Publikationen Natur- und Ingenieurwissenschaften 2013

Originalarbeiten in wissenschaftlichen Fachzeitschriften

Originalarbeiten in wissenschaftlichen Fachzeitschriften

Jahre: 2013

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2013

Mischnik M, Boyanova D, ..., Timmer J, Dandekar T
A Boolean view separates platelet activatory and inhibitory signalling as verified by phosphorylation monitoring including threshold behaviour and integrin modulation
2013 MOLECULAR BIOSYSTEMS, Band: 9, Nummer: 6, Seiten: 1326 - 1339
KurzfassungPlatelets are critical for haemostasis and blood clotting. However, since under normal circumstances blood should flow without clotting, its function is regulated via a complex interplay of activating and inhibiting signal transduction pathways. Understanding this network is crucial for treatment of cardiovascular and bleeding diseases. Detailed protein interaction and phosphorylation data are explored to establish a simplified Boolean model of the central platelet cascades. We implemented the model by means of CellNetAnalyzer and showed how different signalling events coalesce into a fully activated system state. Furthermore, we examined the networks’ inherent threshold behaviour using the semi-quantitative modelling software SQUAD. Finally, predictions are verified monitoring phosphorylations which mark different activation phases as modelled. The model can also be applied to simulate different pharmacological conditions as they modify node activity (aspirin, clopidogrel, milrinon, iloprost, combination) and is available for further studies. It agrees well with observations. Activatory pathways are diversified to cope with complex environmental conditions. Platelet activation needs several activation steps to integrate over different network subsets, as they are formed by the interplay of activating kinases, calcium mobilization, and the inhibiting cAMP-PKA system. System stability analysis shows two phases: a sub-threshold behaviour, characterized by integration over different activatory and inhibitory conditions, and a beyond threshold phase, represented by competition and shutting down of counter-regulatory pathways. The integrin network and Akt-protein are critical for stable effector response. Dynamic threshold-analysis reveals a dependency of the relative activating input strength necessary to irreversibly engage the system from the absolute inhibitory signal strength.
Kraus H, Kaiser S, Aumann K, Bonelt P, Salzer U, Vestweber D, M. Erlacher, M. Kunze, M. Burger, K. Pieper, H. Sic, A. Rolink, H. Eibel, M. Rizzi
A Feeder-Free Differentiation System Identifies Autonomously Proliferating B Cell Precursors in Human Bone Marrow.
2013 J Immunol, Band: 192, Nummer: 3, Seiten: 1044 - 1054
Knauer S, Holt A, ..., Laux T
A Protodermal miR394 Signal Defines a Region of Stem Cell Competence in the Arabidopsis Shoot Meristem
2013 DEVELOPMENTAL CELL, Band: 24, Nummer: 2, Seiten: 125 - 132
KurzfassungA long-standing question in plants and animals is how spatial patterns are maintained within stem cell niches despite ongoing cell divisions. Here we address how, during shoot meristem formation in Arabidopsis thaliana, the three apical cell layers acquire stem cell identity. Using a sensitized mutant screen, we identified miR394 as a mobile signal produced by the surface cell layer (the protoderm) that confers stem cell competence to the distal meristem by repressing the F box protein LEAF CURLING RESPONSIVENESS. This repression is required to potentiate signaling from underneath the stem cells by the transcription factor WUSCHEL, maintaining stem cell pluripotency. The interaction of two opposing signaling centers provides a mechanistic framework of how stem cells are localized at the tip of the meristem. Although the constituent cells change, the surface layer provides a stable point of reference in the self-organizing meristem.
Parsons J, Altmann F, Graf M, Stadlmann J, Reski R, Decker E
A gene responsible for prolylhydroxylation of moss-produced recombinant human erythropoietin
2013 SCIENTIFIC REPORTS, Band: 3, Seite: UNSP 3019
KurzfassungRecombinant production of pharmaceutical proteins is crucial, not only for personalized medicine. While most biopharmaceuticals are currently produced in mammalian cell culture, plant-made pharmaceuticals gain momentum. Post-translational modifications in plants are similar to those in humans, however, existing differences may affect quality, safety and efficacy of the products. A frequent modification in higher eukaryotes is prolyl-4-hydroxylase (P4H)-catalysed prolyl-hydroxylation. P4H sequence recognition sites on target proteins differ between humans and plants leading to non-human posttranslational modifications of recombinant human proteins produced in plants. The resulting hydroxyprolines display the anchor for plant-specific O-glycosylation, which bears immunogenic potential for patients. Here we describe the identification of a plant gene responsible for non-human prolyl-hydroxylation of human erythropoietin (hEPO) recombinantly produced in plant (moss) bioreactors. Targeted ablation of this gene abolished undesired prolyl-hydroxylation of hEPO and thus paves the way for plant-made pharmaceuticals humanized via glyco-engineering in moss bioreactors.
Hovener JB, Schwaderlapp N, Lickert T, Duckett SB, Mewis RE, Highton LA, Kenny SM, Green GG, Leibfritz D, Korvink JG, Hennig J, von Elverfeldt D
A hyperpolarized equilibrium for magnetic resonance.
2013 Nat Commun, Band: 4, Seiten: 2946 - 2946
Scarel F, Ehli C, Guldi DM, Mateo-Alonso A
A non-covalent strategy to prepare electron donor-acceptor rotaxanes.
2013 Chem Commun, Band: 49, Nummer: 82, Seiten: 9452 - 9454
Wend S, ..., Palme K, Weber W, Dovzhenko A, Zurbriggen M
A quantitative ratiometric sensor for time-resolved analysis of auxin dynamics
2013 SCIENTIFIC REPORTS, Band: 3, Seite: 2052
KurzfassungTime-resolved quantitative analysis of auxin-mediated processes in plant cells is as of yet limited. By applying a synergistic mammalian and plant synthetic biology approach, we have developed a novel ratiometric luminescent biosensor with wide applicability in the study of auxin metabolism, transport, and signalling. The sensitivity and kinetic properties of our genetically encoded biosensor open new perspectives for the analysis of highly complex auxin dynamics in plant growth and development.
Mueller K, Engesser R, ..., Nagy F, Timmer J, Zubriggen M, Weber W
A red/far-red light-responsive bi-stable toggle switch to control gene expression in mammalian cells
2013 NUCLEIC ACIDS RESEARCH, Band: 41, Nummer: 7, Seite: e77
KurzfassungGrowth and differentiation of multicellular systems is orchestrated by spatially restricted gene expression programs in specialized subpopulations. The targeted manipulation of such processes by synthetic tools with high-spatiotemporal resolution could, therefore, enable a deepened understanding of developmental processes and open new opportunities in tissue engineering. Here, we describe the first red/far-red light-triggered gene switch for mammalian cells for achieving gene expression control in time and space. We show that the system can reversibly be toggled between stable on- and off-states using short light pulses at 660 or 740 nm. Red light-induced gene expression was shown to correlate with the applied photon number and was compatible with different mammalian cell lines, including human primary cells. The light-induced expression kinetics were quantitatively analyzed by a mathematical model. We apply the system for the spatially controlled engineering of angiogenesis in chicken embryos. The system’s performance combined with cell- and tissue-compatible regulating red light will enable unprecedented spatiotemporally controlled molecular interventions in mammalian cells, tissues and organisms.
Abeliovich H, Zarei M, Rigbolt K, Youle R, Dengjel J
A role for mitochondrial dynamics in the segregation of mitochondrial matrix proteins during stationary phase mitophagy
2013 MOLECULAR BIOLOGY OF THE CELL, Band: 24
Schaefer J, Kraft A, Reininger S, Santiso-Quinones G, Himmel D, Trapp N, Gellrich U, Breit B, Krossing I
A systematic investigation of coinage metal carbonyl complexes stabilized by fluorinated alkoxy aluminates.
2013 Chem-eur J, Band: 19, Nummer: 37, Seiten: 12468 - 12485
Verdeny A, Mielke A, Mintert F
Accurate effective Hamiltonians via unitary flow in Floquet space.
2013 Phys Rev Lett, Band: 111, Nummer: 17, Seiten: 175301 - 175301
Schulze M, Bercioux D, Urban D
Adiabatic pumping in the quasi-one-dimensional triangle lattice
2013 PHYSICAL REVIEW B, Band: 87, Nummer: 2, Seite: 024301
KurzfassungWe analyze the properties of the quasi-one-dimensional triangle lattice emphasizing the occurrence of flat bands and band touching via the tuning of the lattice hopping parameters and on-site energies. The spectral properties of the infinite system will be compared with the transmission through a finite piece of the lattice with attached semi-infinite leads. Furthermore, we investigate the adiabatic pumping properties of such a system: Depending on the transmission through the lattice, this results in nonzero integer charge transfers or transfers that increase linearly with the lattice size.
Gossling S
Advancing a clinical transport psychology
2013 TRANSPORTATION RESEARCH PART F-TRAFFIC PSYCHOLOGY AND BEHAVIOUR, Band: 19, Seiten: 11 - 21
KurzfassungThis article argues that mental disorders are a dimension so far largely overlooked in studies of transport behaviour and mobility consumption, even though they may to a considerable degree affect how we understand, value, and use different transport modes. Mental disorders include anxiety-, mood-, substance abuse-, and personality disorders, each of which affects only up to a few per cent of the population in industrialised countries. On an aggregated basis, however, mental illnesses influence large parts of the population. Based on an exploratory research approach, this article discusses how mental disorders affect, and are affected by, mobility consumption, also identifying social, political and/or institutional mechanisms that contribute to or validate mental disorders. It is argued that without a better understanding of these interrelationships, mobility consumption and growth cannot be fully understood. Results are consequently of relevance for transport planning, the prevention of accidents, as well as the design of interventions to develop more sustainable transport systems. (C) 2013 Elsevier Ltd. All rights reserved.
Halbach S, Rigbolt K, Woehrle F, Diedrich B, Gretzmeier C, Brummer T, Dengjel J
Alterations of Gab2 signalling complexes in imatinib and dasatinib treated chronic myeloid leukaemia cells
2013 CELL COMMUNICATION AND SIGNALING, Band: 11
KurzfassungBackground: The Gab2 docking protein acts as an important signal amplifier downstream of various growth factor receptors and Bcr-Abl, the driver of chronic myeloid leukaemia (CML). Despite the success of Bcr-Abl tyrosine kinase inhibitors (TKI) in the therapy of CML, TKI-resistance remains an unsolved problem in the clinic. We have recently shown that Gab2 signalling counteracts the efficacy of four distinct Bcr-Abl inhibitors. In the course of that project, we noticed that two clinically relevant drugs, imatinib and dasatinib, provoke distinct alterations in the electrophoretic mobility of Gab2, its signalling output and protein interactions. As the signalling potential of the docking protein is highly modulated by its phosphorylation status, we set out to obtain more insights into the impact of TKIs on Gab2 phosphorylation. Findings: Using stable isotope labelling by amino acids in cell culture (SILAC)-based quantitative mass spectrometry (MS), we show now that imatinib and dasatinib provoke distinct effects on the phosphorylation status and interactome of Gab2. This study identifies several new phosphorylation sites on Gab2 and confirms many sites previously known from other experimental systems. At equimolar concentrations, dasatinib is more effective in preventing Gab2 tyrosine and serine/threonine phosphorylation than imatinib. It also affects the phosphorylation status of more residues than imatinib. In addition, we also identify novel components of the Gab2 signalling complex, such as casein kinases, stathmins and PIP1 as well as known interaction partners whose association with Gab2 is disrupted by imatinib and/or dasatinib. Conclusions: By using MS-based proteomics, we have identified new and confirmed known phosphorylation sites and interaction partners of Gab2, which may play an important role in the regulation of this docking protein. Given the growing importance of Gab2 in several tumour entities we expect that our results will help to understand the complex regulation of Gab2 and how this docking protein can contribute to malignancy.
Alvarez A, Hime G, Silva J, Marchesin D
Analytic regularization of an inverse filtration problem in porous media
2013 INVERSE PROBLEMS, Band: 29, Nummer: 2
KurzfassungIn Alvarez et al (2006 Inverse Problems 22 69-88), we studied the direct and inverse problem of deep bed filtration for a model proposed by Herzig et al (1970 Indus. Eng. Chem. 65 8-35), which describes particle retention in a porous medium under injection of water with solid inclusions. However, many questions were left unanswered. Here most of these issues are solved for an alternate model of deep bed filtration also from [10]. Both models depend on the filtration function, which must be recovered from experimental data histories by solving an inverse problem. The main issues solved here are: (i) we establish the stability of the inverse problem under adequate conditions, leading to a robust numerical procedure; (ii) we present a numerical method for the direct problem that allows us to solve the inverse problem by parameter estimation in several spatial dimensions. We impose conditions on the experimental data preprocessing that allow us to recover analytic filtration functions with adequate physical behavior.
Dolderer J, Medved F, Haas R, Siegel-Axel D, Schiller S, Schaller H.-E.
Angiogenesis and Vascularisation in Adipose Tissue Engineering
2013 HANDCHIRURGIE MIKROCHIRURGIE PLASTISCHE CHIRURGIE, Band: 45, Nummer: 2, Seiten: 99 - 107
KurzfassungThe current standard for the reconstruction of large soft tissue defects with exposed bone, nerves or blood vessels, for example after extensive tumor resections, complex injuries, severe burns or infections, is the local or free microsurgical tissue transfer. Despite the development of new surgical techniques and many synthetic materials, there are still a large number of limitations and complications at the donor and recipient site. Thus, in a subset of patients either complete treatment is not possible or poses problems. Therefore, there is a great need for the development of new methods and materials allowing for a permanent replacement with body own soft tissue. A promising therapeutic approach is the soft tissue replacement with autologous adipose tissue. Innovative research on the reconstruction of soft tissue by adipose tissue, and clinical and experimental studies on the long-term survival and transplantation of autologous adipose tissue showed that the free fat tissue graft without direct vascular connection come along with disappointing results. Often a loss of volume or a complete resorption of the graft because of insufficient tissue quality by lack of cell differentiation was observed. This fact points to the special role of the maintenance and development of the graft’s blood supply (angiogenesis and vascularization) crucial for maintaining a constant volume of the tissue. The rapidly growing interdisciplinary field of tissue engineering offers alternative solutions to the existing treatment options with the aim to produce autologous adipose tissue, stable in volume in vitro as well as in vivo, which can be transplanted as a permanent tissue replacement to corresponding parts of the body. Numerous studies have demonstrated the important and most critical factor of vascularisation for quality, volume and long-term survival of transplanted newly generated adipose tissue constructs. Although our understanding of the regulatory mechanisms of adipogenesis is still limited, there are clear indications that the complex sequences of cell interactions in the differentiation and proliferation of adipocytes is directly related to angiogenesis.
Kozhummal R, Yang Y, Gueder F, Kuecuekbayrak U, Zacharias M
Antisolvent Crystallization Approach to Construction of CuI Superstructures with Defined Geometries
2013 ACS NANO, Band: 7, Nummer: 3, Seiten: 2820 - 2828
KurzfassungA facile high-yield production of cuprous Iodide (CuI) superstructures is reported by antisolvent crystallization using acetonitrile/water as a solvent/antisolvent couple under ambient conditions. In the presence of trace water, the metastable water droplets act as templates to induce the precipitation of hollow spherical Cul superstructures consisting of orderly aligned building blocks after drop coating. With water in excess in the mixed solution, an instant precipitation of Cul random aggregates takes place due to rapid crystal growth via Ion-by-ion attachment induced by a strong antisolvent effect. However, this uncontrolled process can be modified by adding polymer polyvinyl pyrrolidone (PVP) In water to restrict the size of initially formed Cul crystal nuclei through the effective coordination effect of PVP. As a result, Cul superstructures with a cuboid geometry are constructed by gradual self-assembly of the small Cul crystals via oriented attachment. The precipitated Cul superstructures have been used as competent adsorbents to remove organic dyes from the water due to their mesocrystal feature. Besides, the Cul superstructures have been applied either as a self-sacrificial template or only as a structuring template for the flexible design of other porous materials such as CuO and TiO2. This system provides an ideal platform to simultaneously Investigate the superstructure formation enforced by antisolvent crystallization with and without organic additives.
Bussing A, Hirdes AT, Baumann K, Hvidt NC, Heusser P
Aspects of spirituality in medical doctors and their relation to specific views of illness and dealing with their patients' individual situation.
2013 Evid-based Compl Alt, Band: 2013, Seiten: 734392 - 734392
Loetz C, Mueller J, Frick E, Petersen Y, Hvidt N, Mauer C
Attachment Theory and Spirituality: Two Threads Converging in Palliative Care?
2013 EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
KurzfassungThe aim of this paper is to discuss and explore the interrelation between two concepts, attachment theory and the concept of spirituality, which are important to palliative care and to founding a multivariate understanding of the patient’s needs and challenges. Both concepts have been treated by research in diverse and multiform ways, but little effort has yet been made to integrate them into one theoretical framework in reference to the palliative context. In this paper, we begin an attempt to close this scientific gap theoretically. Following the lines of thought in this paper, we assume that spirituality can be conceptualized as an adequate response of a person’s attachment pattern to the peculiarity of the palliative situation. Spirituality can be seen both as a recourse to securely based relationships and as an attempt to explore the ultimate unknown, the mystery of one’s own death. Thus, spirituality in the palliative context corresponds to the task of attachment behavior: to transcend symbiosis while continuing bonds and thus to explore the unknown environment independently and without fear. Spiritual activity is interpreted as a human attachment behavior option that receives special quality and importance in the terminal stage of life. Implications for clinical practice and research are discussed in the final section of the paper.
Romao S, Gasser N, Becker A, ..., Dengjel J, et al.
Autophagy proteins stabilize pathogen-containing phagosomes for prolonged MHC II antigen processing
2013 JOURNAL OF CELL BIOLOGY, Band: 203, Nummer: 5, Seiten: 757 - 766
KurzfassungAntigen preservation for presentation is a hallmark of potent antigen-presenting cells. In this paper, we report that in human macrophages and dendritic cells, a subset of phagosomes gets coated with Atg8/LC3, a component of the molecular machinery of macroautophagy, and maintains phagocytosed antigens for prolonged presentation on major histocompatibility complex class II molecules. These Atg8/LC3-positive phagosomes are formed around the antigen with TLR2 agonists and require reactive oxygen species production by NOX2 for their generation. A deficiency in the NOX2-dependent formation of these antigen storage phagosomes could contribute to compromise antifungal immune control in chronic granulomatous disease patients.
Schiller S
Biomimetic Systems: The Tethered Bilayer Lipid Membrane
2013 HANDBOOK OF BIOFUNCTIONAL SURFACES, Seiten: 639 - 683
KurzfassungIn this chapter tethered bilayer lipid membranes (tBLMs) will be presented as a model system allowing to mimic important functions of the cell. Due to their complexity and supramolecular architecture, tBLMs touch many other topics of the book, such as self-assembled monolayers (SAMs). After a brief introduction into model membrane systems, the specific components of tBLMs, important for their application, will be addressed, followed by an overview of the different tBLM systems used today, including some examples. Special emphasis will be placed on the question, in which way do the chemical and physical properties of tBLM components determine the membrane properties and quality? A set of necessary components-a toolbox of structures and functions combined with an overview of surface-analytical tools allowing to analyze tBLMs-as well as their properties impacting the biomimetic membrane in the tBLM format will be presented. This chapter intends to constitute a starting point reflecting on some “essentials” illuminating the entry into the wonderful world of biomimetic systems exemplified by tBLMs.
Mader M, Mader W, Sommerlade L, Timmer J, Schelter B
Block-bootstrapping for noisy data
2013 JOURNAL OF NEUROSCIENCE METHODS, Band: 219, Nummer: 2, Seiten: 285 - 291
KurzfassungBackground: Statistical inference of signals is key to understand fundamental processes in the neurosciences. It is essential to distinguish true from random effects. To this end, statistical concepts of confidence intervals, significance levels and hypothesis tests are employed. Bootstrap-based approaches complement the analytical approaches, replacing the latter whenever these are not possible. New method: Block-bootstrap was introduced as an adaption of the ordinary bootstrap for serially correlated data. For block-bootstrap, the signals are cut into independent blocks, yielding independent samples. The key parameter for block-bootstrapping is the block length. In the presence of noise, naive approaches to block-bootstrapping fail. Here, we present an approach based on block-bootstrapping which can cope even with high noise levels. This method naturally leads to an algorithm of block-bootstrapping that is immediately applicable to observed signals. Results: While naive block-bootstrapping easily results in a misestimation of the block length, and therefore in an over-estimation of the confidence bounds by 50%, our new approach provides an optimal determination of these, still keeping the coverage correct. Comparison with existing methods: In several applications bootstrapping replaces analytical statistics. Block-bootstrapping is applied to serially correlated signals. Noise, ubiquitous in the neurosciences, is typically neglected. Our new approach not only explicitly includes the presence of (observational) noise in the statistics but also outperforms conventional methods and reduces the number of false-positive conclusions. Conclusions: The presence of noise has impacts on statistical inference. Our ready-to-apply method enables a rigorous statistical assessment based on block-bootstrapping for noisy serially correlated data. (C) 2013 Elsevier B.V. All rights reserved.
Wangler N, Welsche M, Blazek M, Blessing M, Vervliet-Scheebaum M, Reski R, Mueller C, Reinecke H, Steigert J, Roth G, Zengerle R, Paust N
Bubble Jet agent release cartridge for chemical single cell stimulation
2013 BIOMEDICAL MICRODEVICES, Band: 15, Nummer: 1, Seiten: 1 - 8
KurzfassungWe present a new method for the distinct specific chemical stimulation of single cells and small cell clusters within their natural environment. By single-drop release of chemical agents with droplets in size of typical cell diameters (d < 30 mu m) on-demand micro gradients can be generated for the specific manipulation of single cells. A single channel and a double channel agent release cartridge with integrated fluidic structures and integrated agent reservoirs are shown, tested, and compared in this publication. The single channel setup features a fluidic structure fabricated by anisotropic etching of silicon. To allow for simultaneous release of different agents even though maintaining the same device size, the second type comprises a double channel fluidic structure, fabricated by photolithographic patterning of TMMF. Dispensed droplet volumes are V = 15 pl and V = 10 pl for the silicon and the TMMF based setups, respectively. Utilizing the agent release cartridges, the application in biological assays was demonstrated by hormone-stimulated premature bud formation in Physcomitrella patens and the individual staining of one single L 929 cell within a confluent grown cell culture.
Nystroem A, Velati D, Mittapalli V, Fritsch A, Kern J, Bruckner-Tuderman L
C7 plays a dual role in skin wound healing
2013 JOURNAL OF INVESTIGATIVE DERMATOLOGY, Band: 133, Nummer: 1
Xu H, Huang L, Lai YC, Grebogi C
Chiral Scars in Chaotic Dirac Fermion Systems
2013 PHYSICAL REVIEW LETTERS, Band: 110, Nummer: 6, Seite: 064102
KurzfassungDo relativistic quantum scars in classically chaotic systems possess unique features that are not shared by nonrelativistic quantum scars? We report a class of relativistic quantum scars in massless Dirac fermion systems whose phases return to the original values or acquire a 2 pi change only after circulating twice about some classical unstable periodic orbits. We name such scars chiral scars, the successful identification of which has been facilitated tremendously by our development of an analytic, conformal-mapping-based method to calculate an unprecedentedly large number of eigenstates with high accuracy. Our semiclassical theory indicates that the physical origin of chiral scars can be attributed to a combined effect of chirality intrinsic to massless Dirac fermions and the geometry of the underlying classical orbit. DOI: 10.1103/PhysRevLett.110.064102
Nystroem A, Velati D, Mittapalli V, Fritsch A, Kern J, Bruckner-Tuderman L
Collagen VII plays a dual role in wound healing
2013 JOURNAL OF CLINICAL INVESTIGATION, Band: 123, Nummer: 8, Seiten: 3498 - 3509
KurzfassungAlthough a host of intracellular signals is known to contribute to wound healing, the role of the cell microenvironment in tissue repair remains elusive. Here we employed 2 different mouse models of genetic skin fragility to assess the role of the basement membrane protein collagen VII (COL7A1) in wound healing. COL7A1 secures the attachment of the epidermis to the dermis, and its mutations cause a human skin fragility disorder coined recessive dystrophic epidermolysis bullosa (RDEB) that is associated with a constant wound burden. We show that COL7A1 is instrumental for skin wound closure by 2 interconnected mechanisms. First, COL7A1 was required for re-epithelialization through organization of laminin-332 at the dermal-epidermal junction. Its loss perturbs laminin-332 organization during wound healing, which in turn abrogates strictly polarized expression of integrin alpha 6 beta 4 in basal keratinocytes and negatively impacts the laminin-332/integrin alpha 6 beta 4 signaling axis guiding keratinocyte migration. Second, COL7A1 supported dermal fibroblast migration and regulates their cytokine production in the granulation tissue. These findings, which were validated in human wounds, identify COL7A1 as a critical player in physiological wound healing in humans and mice and may facilitate development of therapeutic strategies not only for RDEB, but also for other chronic wounds.
Feuerstein TJ
Commentary: Gabapentin-lactam and gamma-aminobutyric acid/lactam analogs: the enigma of their mechanism of action.
2013 Int J Oral Max Impl, Band: 28, Nummer: 5, Seiten: e239 - e242
Spiegelhalder K, Regen W, Nanovska S, Baglioni C, Riemann D
Comorbid Sleep Disorders in Neuropsychiatric Disorders Across the Life Cycle
2013 CURRENT PSYCHIATRY REPORTS, Band: 15, Nummer: 6, Seite: 364
KurzfassungThe association between psychopathology and poor sleep has long been recognized. The current review focuses on the association between the most prevalent sleep disorders (insomnia, sleep-related breathing disorders and restless legs syndrome) and four major psychiatric disorders: alcohol dependence, schizophrenia, depression and anxiety disorders. Decreased total sleep time and increased sleep onset latency as measured by polysomnography as well an increase of the prevalence of insomnia has been reported in all of these psychiatric disorders. Furthermore, sleep disturbance is a risk factor for their development. Cognitive-behavioral therapy for insomnia has been shown to have a positive impact on both sleep and symptoms of depression and anxiety. Whether adequate treatment of sleep disorders can prevent the incidence of psychiatric disorders, remains to be investigated.
Spiegelhalder K
Comorbid sleep disorders in neuropsychiatric disorders across the life cycle.
2013 Curr Psychiat Rep, Band: 15, Nummer: 364
Berezovska G, Prada-Gracia D, Rao F
Consensus for the Fip35 folding mechanism?
2013 J Chem Phys, Band: 139, Nummer: 3, Seiten: 035102 - 035102
Sprenger A, Weber S, Zarai M, Engelke R, Nascimento JM, Gretzmeier C, Hilpert M, Boerries M, Has C, Busch H, Bruckner-Tuderman L, Dengjel J
Consistency of the proteome in primary human keratinocytes with respect to gender, age, and skin localization.
2013 Mol Cell Proteomics, Band: 12, Nummer: 9, Seiten: 2509 - 2521
Jahanshahi K, Botiz I, ..., Reiter G
Crystallization of Poly(gamma-benzyl L-glutamate) in Thin Film Solutions: Structure and Pattern Formation
2013 MACROMOLECULES, Band: 46, Nummer: 4, Seiten: 1470 - 1476
KurzfassungWe have investigated the formation of poly(gamma-benzyl L-glutamate) (PBLG) crystals from semidilute thin film solutions. Crystallization was initiated by adding methanol, a nonsolvent. After drying, each PBLG crystal possessed an internal domain structure exhibiting a zigzag pattern consisting of parallel stripes of alternating orientations between domains. X-ray scattering and electron diffraction revealed within these crystals a pseudohexagonal packing of the PBLG alpha-helices with their axis oriented parallel to the plane of the substrate. On the basis of optical anisotropy studies, it could be shown that the orientation of the helix axis was parallel to the stripes. While forming in solution, the objects are assumed to consist of a hexagonal columnar liquid crystalline phase. Upon drying, lateral packing density of the helices increased and resulted in a net dilative strain perpendicular to the columns, which is supposed to cause the formation of zigzag patterns.
Tholen S, Biniossek M, ..., Boerries M, Busch H, Reinheckel T, Schilling O
Deletion of Cysteine Cathepsins B or L Yields Differential Impacts on Murine Skin Proteome and Degradome
2013 MOLECULAR & CELLULAR PROTEOMICS, Band: 12, Nummer: 3, Seiten: 611 - 625
KurzfassungNumerous studies highlight the fact that concerted proteolysis is essential for skin morphology and function. The cysteine protease cathepsin L (Ctsl) has been implicated in epidermal proliferation and desquamation, as well as in hair cycle regulation. In stark contrast, mice deficient in cathepsin B (Ctsb) do not display an overt skin phenotype. To understand the systematic consequences of deleting Ctsb or Ctsl, we determined the protein abundances of > 1300 proteins and proteolytic cleavage events in skin samples of wild-type, Ctsb(-/-), and Ctsl(-/-) mice via mass-spectrometry-based proteomics. Both protease deficiencies revealed distinct quantitative changes in proteome composition. Ctsl(-/-) skin revealed increased levels of the cysteine protease inhibitors cystatin B and cystatin M/E, increased cathepsin D, and an accumulation of the extracellular glycoprotein periostin. Immunohistochemistry located periostin predominantly in the hypodermal connective tissue of Ctsl(-/-) skin. The proteomic identification of proteolytic cleavage sites within skin proteins revealed numerous processing sites that are underrepresented in Ctsl(-/-) or Ctsb(-/-) samples. Notably, few of the affected cleavage sites shared the canonical Ctsl or Ctsb specificity, providing further evidence of a complex proteolytic network in the skin. Novel processing sites in proteins such as dermokine and Notch-1 were detected. Simultaneous analysis of acetylated protein N termini showed prototypical mammalian N-alpha acetylation. These results illustrate an influence of both Ctsb and Ctsl on the murine skin proteome and degradome, with the phenotypic consequences of the absence of either protease differing considerably. Molecular & Cellular Proteomics 12: 10.1074/mcp.M112.017962, 611-625, 2013.
Menzel A, Guebeli R, Gueder F, Weber W, Zacharias M
Detection of real-time dynamics of drug-target interactions by ultralong nanowalls
2013 LAB ON A CHIP, Band: 13, Nummer: 21, Seiten: 4173 - 4179
KurzfassungDetecting drug-target interactions in real-time is a powerful approach for drug discovery and analytics. We show here for the first time the ultra fast electrical real-time detection and quantification of antibiotics using a novel biohybrid nanosensor. The biomolecular sensing is performed on ultralong (mm range) high aspect ratio nanowall (50 nm width) surfaces functionalized with operator DNA tetO which is specifically bound by the sensor protein TetR. This sensor protein is released from the operator DNA in a dose dependent manner by exposing the device functionalized with this bound DNA-protein complex to tetracycline antibiotics. As a result, the electrical conductance is accordingly modulated by these surface net charge changes. The switching mechanism of sensor proteins attached at the functionalized surfaces and releasing them again by antibiotics is demonstrated. With the here presented device the detection limit is below the limits of prevailing detection methods. Moreover, the study is extended to detect antibiotic residues in spiked organic milk from cows far below the maximum residual level of the European Union. In spiked milk samples a detection limit for tetracycline concentrations in the 100 fM level was achieved. The nanowall devices are fabricated by atomic layer deposition-based spacer lithography on full wafer scale which is a simple approach capable for mass production.
Welz A, Cocosco C, ..., Korvink J, Hennig J, Zaitsev M
Development and Characterization of An Unshielded PatLoc Gradient Coil for Human Head Imaging
2013 CONCEPTS IN MAGNETIC RESONANCE PART B-MAGNETIC RESONANCE ENGINEERING, Band: 43, Nummer: 4, Seiten: 111 - 125
KurzfassungA cylindrical head gradient insert for human imaging with non-linear spatial encoding magnetic fields (SEMs) has been designed, optimized and successfully integrated with a modified 3T clinical MR system. This PatLoc (parallel acquisition technique using localized gradients) SEM coil uses SEMs that resemble second-order magnetic shim fields, but with much higher amplitude as well as the possibility for rapid switching. This work describes the optimization of a coil design and measurement methods to characterize its SEMs, induced self-eddy currents and concomitant fields. Magnetic field maps of the SEMs are measured and it is demonstrated that the induced self-eddy current magnetic fields are small and can be compensated. A method to measure concomitant fields is presented and those fields are compared to simulated data. Finally, in vivo human images acquired using the PatLoc system are presented and discussed. (c) 2013 Wiley Periodicals, Inc. Concepts Magn Reson Part B (Magn Reson Engineering) 43B: 111-125, 2013
Hill M, Baron P, ..., Krossing I
Direct Fluorination of Cyclic Carbonates and closo-K-2[B12H12] in a Slug-Flow Ministructured Reactor
2013 CHEMPLUSCHEM, Band: 78, Nummer: 4, Seiten: 292 - 301
KurzfassungA novel minireactor for direct fluorination of organic and inorganic substances was tested. The reactor consists of nickel-coated copper blocks with mechanically machined 1mm channels and is equipped with an active cooling system. The direct fluorination of ethylene carbonate and propylene carbonate is described. For the fluorinated propylene carbonate, the NMR data of various fluorinated isomers were determined. The Gibbs reaction energies for the direct fluorination of ethylene and propylene carbonate were calculated at the reliable G3 level of theory. The excellent decomposition stability of the cyclic carbonates against high fluorine and HF concentrations also qualifies them as good solvents for direct fluorination processes, especially for ionic substrates. In this respect, the direct fluorination of the inorganic salt closo-K2[B12H12] in cyclic carbonates is presented.
Sharaf A, Krieglstein K, Spittau B
Distribution of microglia in the postnatal murine nigrostriatal system
2013 CELL AND TISSUE RESEARCH, Band: 351, Nummer: 3, Seiten: 373 - 382
KurzfassungParkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN) and the subsequent loss of striatal target innervation. Neuroinflammatory responses have been described for virtually all PD cases analysed. Microglia are the resident immune cells of the central nervous system and, thus, are the mediators of neuroinflammation. Approximately 12% of all central nervous system cells are microglia but the distribution and density of microglia differ within distinct brain regions. Interestingly, the SN has been shown to contain more microglia than adjacent structures. We have analysed changes in microglia numbers and in microglial morphology in the postnatal murine nigrostriatal system at various stages ranging from postnatal day 0 (P0) up to 24 months of age. We clearly show that the microglia numbers in the SN and in the striatum dramatically increase from P0 to P15 and significantly decrease in both areas in 18-month-old and 24-month-old animals. Moreover, microglia in the nigrostriatal system of aged mice show signs of dystrophy and degeneration, such as cytoplasmic inclusions, deramification of their processes and membrane blebbing. Our results support the hypothesis of microglial dystrophy during aging in the murine nigrostriatal system, accompanied by subsequent impairment of normal microglial functions. Microglial dysfunction during aging might be a potential risk factor for the development and/or progression of PD.
Mischnik M, Hubertus K, Geiger J, Dandekar T, Timmer J
Dynamical modelling of prostaglandin signalling in platelets reveals individual receptor contributions and feedback properties
2013 MOLECULAR BIOSYSTEMS, Band: 9, Nummer: 10, Seiten: 2520 - 2529
KurzfassungProstaglandins are the key-players in diminishing platelet function. They exert their effects via a variety of surface receptors that are linked to the cAMP/PKA-signalling cascade. However, less is known about the quantitative impact of the individual receptors on the underlying pathway. We present here a comprehensive ordinary differential equation-based model of the platelet cAMP pathway, including the four prostaglandin receptors IP, DP1, EP3 and EP4, the ADP receptor P2Y12, a detailed PKA-module as well as downstream-targets. Parameter estimation along with a comprehensive combination of time-course and dose-response measurements revealed the individual quantitative role of each receptor in elevating or decreasing pathway activity. A comparison of the two inhibiting receptors EP3 and P2Y12 exhibited a greater signalling strength of the EP3 receptor with implications for antithrombotic treatment. Furthermore, analysis of different model topologies revealed a direct influence of PKA on adenylate cyclase, reducing its maximum catalytic speed. Finally, we show here for the first time the dynamic behaviour of VASP-phosphorylation, which is commonly used as a marker for platelet-inhibition. We validate our model by comparing it to further experimental data.
Benk C, Mauch A, ..., Korvink JG, Markl M, Jung B
Effect of cannula position in the thoracic aorta with continuous left ventricular support: four-dimensional flow-sensitive magnetic resonance imaging in an in vitro model
2013 EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, Band: 44, Nummer: 3, Seiten: 551 - 558
KurzfassungLeft ventricular assist devices (LVADs) have become an important treatment option for heart failure patients. However, altered blood flow patterns are suspected to affect perfusion in the aorta or cause structural changes to the aortic root, leading to regurgitation and valve dysfunction or thrombus formation. The purpose of this study was to evaluate flow patterns in a realistic in vitro model system using four-dimensional flow-sensitive magnetic resonance imaging. A magnetic resonance compatible model system was developed consisting of an aorta connected to a VAD simulating the pulsatile flow of the native heart. An LVAD was connected to the aorta model via three different cannula positions. Flow patterns in the entire system as well as flow rates in predefined positions for reduced and zero cardiac output were evaluated. Cannula position influences flow patterns and flow rates in the entire thoracic aorta. For a residual cardiac output, a larger anastomosis and a decreased flow rate of the LAVD result in a higher flow rate and smaller retrograde flow in the ascending aorta when compared with a smaller anastomosis or a cannula position in the descending aorta. Pronounced flow turbulences in the aorta were observed for the cannula position in the descending aorta. In the setting of reduced cardiac output, as commonly observed in patients on LVAD therapy, a large anastomosis to the ascending aorta for the outflow cannula induces the least-adverse flow patterns in the aortic root. Our approach may aid in a better understanding of LVAD-induced flow-pattern changes. Optimization of the cannula position and anastomosis may help to prevent the progression of aortic valve-regurgitation and thrombus formation.
Naik AW, Kangas JD, Langmead CJ, Murphy RF
Efficient modeling and active learning discovery of biological responses.
2013 Plos One, Band: 8, Nummer: 12, Seiten: e83996 - e83996
Spittau B, ..., Krieglstein K
Endogenous transforming growth factor-beta promotes quiescence of primary microglia in vitro
2013 GLIA, Band: 61, Nummer: 2, Seiten: 287 - 300
KurzfassungMicroglia are the immune cells of the central nervous system (CNS) and play important roles under physiological and pathophysiological conditions. Activation of microglia has been reported for a variety of CNS diseases and is believed to be involved in inflammation-mediated neurodegeneration. Loss of TGF beta 1 results in increased microgliosis and neurodegeneration in mice which indicates that TGF beta 1 is an important regulator of microglial functions in vivo. Here, we addressed the role of endogenous TGF beta signaling for microglia in vitro. We clearly demonstrate active TGF beta signaling in primary microglia and further introduce Klf10 as a new TGF beta target gene in microglia. Moreover, we provide evidence that microglia express and release TGF beta 1 that acts in an autocrine manner to activate microglial TGF beta/Smad signaling in vitro. Using microarrays, we identified TGF beta-regulated genes in microglia that are involved in TGF beta 1 processing, its extracellular storage as well as activation of latent TGF beta. Finally, we demonstrate that pharmacological inhibition of microglial TGF beta signaling resulted in upregulation of the proinflammatory markers IL6 and iNOS and downregulation of the alternative activation markers Arg1 and Ym1 in vitro. Together, these data clearly show that endogenous TGF beta 1 and autocrine TGF beta signaling is important for microglial quiescence in vitro and further suggest the upregulation of TGF beta 1 in neurodegenerative diseases as a mechanism to regulate microglia functions and silence neuroinflammation. (c) 2012 Wiley Periodicals, Inc.
Buettner S, Habernig L, ..., Dengjel J, Meisinger C, Sigrist S, Madeo F
Endonuclease G mediates alpha-synuclein cytotoxicity during Parkinson’s disease
2013 EMBO JOURNAL, Band: 32, Nummer: 23, Seiten: 3041 - 3054
KurzfassungMalfunctioning of the protein alpha-synuclein is critically involved in the demise of dopaminergic neurons relevant to Parkinson’s disease. Nonetheless, the precise mechanisms explaining this pathogenic neuronal cell death remain elusive. Endonuclease G (EndoG) is a mitochondrially localized nuclease that triggers DNA degradation and cell death upon translocation from mitochondria to the nucleus. Here, we show that EndoG displays cytotoxic nuclear localization in dopaminergic neurons of human Parkinson-diseased patients, while EndoG depletion largely reduces alpha-synuclein-induced cell death in human neuroblastoma cells. Xenogenic expression of human alpha-synuclein in yeast cells triggers mitochondria-nuclear translocation of EndoG and EndoG-mediated DNA degradation through a mechanism that requires a functional kynurenine pathway and the permeability transition pore. In nematodes and flies, EndoG is essential for the alpha-synuclein-driven degeneration of dopaminergic neurons. Moreover, the locomotion and survival of alpha-synuclein-expressing flies is compromised, but reinstalled by parallel depletion of EndoG. In sum, we unravel a phylogenetically conserved pathway that involves EndoG as a critical downstream executor of alpha-synuclein cytotoxicity.
Tichy M, de Melo F, Kus M, Mintert F, Buchleitner A
Entanglement of identical particles and the detection process
2013 FORTSCHRITTE DER PHYSIK-PROGRESS OF PHYSICS, Band: 61, Nummer: 2-3, SI, Seiten: 225 - 237
KurzfassungWe introduce detector-level entanglement, a unified entanglement concept for identical particles that takes into account the possible deletion of many-particle which-way information through the detection process. The concept implies a measure for the effective indistinguishability of the particles, which is controlled by the measurement setup and which quantifies the extent to which the (anti-)symmetrization of the wave-function impacts on physical observables. Initially indistinguishable particles can gain or loose entanglement on their transition to distinguishability, and their quantum statistical behavior depends on their initial entanglement. Our results show that entanglement cannot be attributed to a state of identical particles alone, but that the detection process has to be incorporated in the analysis. (C) 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Kiritsi D, Pigors M, ..., Bruckner-Tuderman L, Has C
Epidermolysis Bullosa Simplex Ogna Revisited
2013 JOURNAL OF INVESTIGATIVE DERMATOLOGY, Band: 133, Nummer: 1, Seiten: 270 - 273
Tolosa A, Zhou X, Spittau B, Krieglstein K
Establishment of a Survival and Toxic Cellular Model for Parkinson’s Disease from Chicken Mesencephalon
2013 NEUROTOXICITY RESEARCH, Band: 24, Nummer: 2, Seiten: 119 - 129
KurzfassungCellular models for Parkinson’s disease (PD) represent a fast and efficient tool in the screening for drug candidates and factors involved in the disease pathogenesis. The objective of this study was to establish and characterize a survival and toxic cellular model for PD by culturing dopaminergic neurons from embryonic chicken ventral midbrain. We show that as in rodents, the common neurotrophic factors-brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), and fibroblast growth factor 2 (FGF2)-are able to support the survival of chicken midbrain dopaminergic neurons. Furthermore, after treatment with MPP+ or rotenone as in vitro models for PD, the number of tyrosine hydroxylase-positive cells decreased drastically. This effect could be significantly rescued by treatment with BDNF or GDNF. Together, our results indicate that mechanisms of neuroprotection of dopaminergic neurons are conserved between chicken and mammals. This supports the use of primary culture from chicken embryonic midbrain as a suitable tool for the study of neuroprotection in vitro.
Rohe A, Goellner C, Wichapong K, Erdmann F, Al-Mazaideh G, Sippl W, Schmidt M
Evaluation of potential Myt1 kinase inhibitors by TR-FRET based binding assay
2013 EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, Band: 61, Nummer: SI, Seiten: 41 - 48
KurzfassungIn the human cell cycle, the Myt1 kinase is a crucial regulator of the G2/M transition. Because this membrane-associated kinase is hard to obtain and assay, there is a distinct lack of data so far. Here we report the derivatization of a glycoglycerolipid which was shown previously to be active in a Myt1 activity assay. These compounds were tested in a binding assay together with a set of common kinase inhibitors against a full-length Myt1 expressed in a human cell line. Dasatinib exhibited nanomolar affinity whereas broad coverage inhibitors such as sunitinib and staurosporine derivatives did not show any effect. We also carried out docking studies for the most potent compounds allowing further insights into the inhibitor interaction of this kinase. The glycoglycerolipids showed no significant effects in the binding assay, endorsing the idea of a mechanism of action distant from the active site. (C) 2012 Elsevier Masson SAS. All rights reserved.
Bussing A, Wirth AG, Humbroich K, Gerbershagen K, Schimrigk S, Haupts M, Baumann K, Heusser P
Faith as a resource in patients with multiple sclerosis is associated with a positive interpretation of illness and experience of gratitude/awe.
2013 Evid-based Compl Alt, Band: 2013, Seiten: 128575 - 128575
Mendoza M, Succi S, Herrmann H
Flow Through Randomly Curved Manifolds
2013 SCIENTIFIC REPORTS, Band: 3
KurzfassungWe present a computational study of the transport properties of campylotic (intrinsically curved) media. It is found that the relation between the flow through a campylotic media, consisting of randomly located curvature perturbations, and the average Ricci scalar of the system, exhibits two distinct functional expressions, depending on whether the typical spatial extent of the curvature perturbation lies above or below the critical value maximizing the overall scalar of curvature. Furthermore, the flow through such systems as a function of the number of curvature perturbations is found to present a sublinear behavior for large concentrations, due to the interference between curvature perturbations leading to an overall less curved space. We have also characterized the flux through such media as a function of the local Reynolds number and the scale of interaction between impurities. For the purpose of this study, we have also developed and validated a new lattice Boltzmann model.
Preiss U, Steinfeld G, ..., Krossing I
Fluorinated Weakly Coordinating Anions [M(hfip)6] (M = Nb, Ta): Syntheses, Structural Characterizations and Computations
2013 ZEITSCHRIFT FUR ANORGANISCHE UND ALLGEMEINE CHEMIE, Band: 639, Nummer: 5, Seiten: 714 - 721
KurzfassungThe synthesis, spectroscopic and structural characterisation of a series of [M(hfip)6] (M = Nb, Ta; hfip = OC(H)(CF3)2) salts that are the typical starting materials to introduce these weakly coordinating anions by metathesis reactions into a given system is described. The salts Li[Nb(hfip)6] and Li[Ta(hfip)6] formed in 65 to 77% yield from freshly sublimed MCl5 and Li[hfip]. By contrast, several attempts to synthesize Li[Sb(hfip)6] on the similar route (replace NbCl5 by SbCl5) failed to yield a pure product. Upon metathesis of the Li-niobate with AgF in CH2Cl2, the pure Ag[Nb(hfip)6] formed. Mixing Li[Nb(hfip)6] with an equimolar amount of ClCPh3 in CH2Cl2 gave the yellow [CPh3][Nb(hfip)6]. Several of the compounds were characterized by X-ray analysis. Thus, the crystal structures of the Li+- and Ag+-solvates 1, 2-C6H4F2LiNb(hfip)62, [Li(H2O)][Ta(hfip)6], and [Ag(C6H5F)][Nb(hfip)6] as well as that of [CPh3][Nb(hfip)6] were solved and are described in this work.
Lee E, Baumann K
German psychiatrists' observation and interpretation of religiosity/spirituality.
2013 Evid-based Compl Alt, Band: 2013, Seiten: 280168 - 280168
Heermann S, Matlik K, Hinz U, Fey J, Arumae U, Krieglstein K
Glia cell line-derived neurotrophic factor mediates survival of murine sympathetic precursors
2013 JOURNAL OF NEUROSCIENCE RESEARCH, Band: 91, Nummer: 6, Seiten: 780 - 785
KurzfassungDuring embryonic development, neurons are first produced in excess, and final numbers are adjusted by apoptosis at later stages. Crucial to this end is the amount of target-derived growth factor available for the neurons. By this means, the target size correctly matches the innervating neuron number. This target-derived survival has been well studied for sympathetic neurons, and nerve growth factor (NGF) was identified to be the crucial factor for maintaining sympathetic neurons at late embryonic and early postnatal stages, with a virtual complete loss of sympathetic neurons in NGF knockout (KO) mice. This indicates that all sympathetic neurons are dependent on NGF. However, also different glia cell line-derived neurotrophic factor (GDNF) KO mice consistently presented a loss of sympathetic neurons. This was the rationale for investigating the role of GDNF for sympathetic precursor/neuron survival. Here we show that GDNF is capable of promoting survival of 30% sympathetic precursors dissociated at E13. This is in line with data from GDNF KOs in which a comparable sympathetic neuron loss was observed at late embryonic stages, although the onset of the phenotype was unclear. We further present data showing that GDNF ligand and canonical receptors are expressed in sympathetic neurons especially at embryonic stages, raising the possibility of an autocrine/paracrine GDNF action. Finally, we show that GDNF also maintained neonatal sympathetic neurons (40%) cultured for 2 days. However, the GDNF responsiveness was lost at 5 days in vitro. (c) 2013 Wiley Periodicals, Inc.
Sprenger A, Kuttner V, Bruckner-Tuderman L, Dengjel J
Global proteome analyses of SILAC-labeled skin cells.
2013 Methods Mol Biol, Band: 961, Seiten: 179 - 191
Kuttner V, Mack C, Rigbolt KT, Kern JS, Schilling O, Busch H, Bruckner-Tuderman L, Dengjel J
Global remodelling of cellular microenvironment due to loss of collagen VII.
2013 Mol Syst Biol, Band: 9, Seiten: 657 - 657
Dettmann A, Heilig Y, Ludwig S, Schmitt K, Illgen J, Fleissner A, O. Valerius, S. Seiler
HAM-2 and HAM-3 are central for the assembly of the Neurospora STRIPAK complex at the nuclear envelope and regulate nuclear accumulation of the MAP kinase MAK-1 in a MAK-2-dependent manner.
2013 Mol Microbiol, Band: 90, Nummer: 4, Seiten: 796 - 812
Levi F, Mintert F
Hierarchies of Multipartite Entanglement
2013 PHYSICAL REVIEW LETTERS, Band: 110, Nummer: 15, Seite: 052321
KurzfassungWe derive hierarchies of separability criteria that identify the different degrees of entanglement ranging from bipartite to genuine multipartite in mixed quantum states of arbitrary size. DOI: 10.1103/PhysRevLett.110.150402
Hug S, Raue A, Hasenauer J, Bachmann J, Klingmueller U, Timmer J, Theis F
High-dimensional Bayesian parameter estimation: Case study for a model of JAK2/STAT5 signaling
2013 MATHEMATICAL BIOSCIENCES, Band: 246, Nummer: 2, Seiten: 293 - 304
KurzfassungIn this work we present results of a detailed Bayesian parameter estimation for an analysis of ordinary differential equation models. These depend on many unknown parameters that have to be inferred from experimental data. The statistical inference in a high-dimensional parameter space is however conceptually and computationally challenging. To ensure rigorous assessment of model and prediction uncertainties we take advantage of both a profile posterior approach and Markov chain Monte Carlo sampling. We analyzed a dynamical model of the JAK2/STAT5 signal transduction pathway that contains more than one hundred parameters. Using the profile posterior we found that the corresponding posterior distribution is bimodal. To guarantee efficient mixing in the presence of multimodal posterior distributions we applied a multi-chain sampling approach. The Bayesian parameter estimation enables the assessment of prediction uncertainties and the design of additional experiments that enhance the explanatory power of the model. This study represents a proof of principle that detailed statistical analysis for quantitative dynamical modeling used in systems biology is feasible also in high-dimensional parameter spaces. (C) 2013 Elsevier Inc. All rights reserved.
Mendoza M, Herrmann H, Succi S
Hydrodynamic Model for Conductivity in Graphene
2013 SCIENTIFIC REPORTS, Band: 3
KurzfassungBased on the recently developed picture of an electronic ideal relativistic fluid at the Dirac point, we present an analytical model for the conductivity in graphene that is able to describe the linear dependence on the carrier density and the existence of a minimum conductivity. The model treats impurities as submerged rigid obstacles, forming a disordered medium through which graphene electrons flow, in close analogy with classical fluid dynamics. To describe the minimum conductivity, we take into account the additional carrier density induced by the impurities in the sample. The model, which predicts the conductivity as a function of the impurity fraction of the sample, is supported by extensive simulations for different values of e, the dimensionless strength of the electric field, and provides excellent agreement with experimental data.
Amtage F, Feuerstein TJ, Meier S, Prokop T, Piroth T, Pinsker MO
Hypokinesia upon Pallidal Deep Brain Stimulation of Dystonia: Support of a GABAergic Mechanism.
2013 Front Neurol, Band: 4, Seiten: 198 - 198
Bode C, Diedrich B, ..., Baumgarten G
IMMUNOMODULATORY EFFECTS OF ANTIBIOTICS ON THE INNATE IMMUNE RESPONSE DURING SEPSIS
2013 INTENSIVE CARE MEDICINE, Band: 39, Nummer: 2
Meiby E, Zetterberg M, Ohlson S, Hernandez V, Edwards K
Immobilized lipodisks as model membranes in high-throughput HPLC-MS analysis
2013 ANALYTICAL AND BIOANALYTICAL CHEMISTRY, Band: 405, Nummer: 14, Seiten: 4859 - 4869
KurzfassungLipodisks, also referred to as polyethylene glycol (PEG)-stabilized bilayer disks, have previously been demonstrated to hold great potential as model membranes in drug partition studies. In this study, an HPLC-MS system with stably immobilized lipodisks is presented. Functionalized lipodisks were immobilized on two different HPLC support materials either covalently by reductive amination or by streptavidin-biotin binding. An analytical HPLC column with immobilized lipodisks was evaluated by analysis of mixtures containing 15 different drug compounds. The efficiency, reproducibility, and stability of the system were found to be excellent. In situ incorporation of cyclooxygenase-1 (COX-1) in immobilized lipodisks on a column was also achieved. Specific binding of COX-1 to the immobilized lipodisks was validated by interaction studies with QCM-D. These results, taken together, open up the possibility of studying ligand interactions with membrane proteins by weak affinity chromatography.
Deschler F, Riedel D, Ecker B, von Hauff E, Da Como E, MacKenzie R
Increasing organic solar cell efficiency with polymer interlayers
2013 PHYSICAL CHEMISTRY CHEMICAL PHYSICS, Band: 15, Nummer: 3, Seiten: 764 - 769
KurzfassungWe demonstrate how organic solar cell efficiency can be increased by introducing a pure polymer interlayer between the PEDOT:PSS layer and the polymer: fullerene blend. We observe an increase in device efficiency with three different material systems over a number of devices. Using both electrical characterization and numerical modeling we show that the increase in efficiency is caused by optical absorption in the pure polymer layer and hence efficient charge separation at the polymer bulkheterojunction interface.
Yu L, Li X, ..., Stingelin N
Influence of Solid-State Microstructure on the Electronic Performance of 5,11-Bis(triethylsilylethynyl) Anthradithiophene
2013 CHEMISTRY OF MATERIALS, Band: 25, Nummer: 9, Seiten: 1823 - 1828
KurzfassungThe rich phase behavior of 5,11-bis(triethylsilylethynyl) anthradithiophene (TES ADT) - one of the most promising, solution-processable small molecular organic semiconductors - is analyzed, revealing the highest performing polymorph among four solid-state phases, opening pathways toward the reliable fabrication of high-performance it bottom-gate/bottom-contact transistors.
Spiegelhalder K
Insomnia does not appear to be associated with substantial structural brain changes
2013 Sleep, Band: 36, Seiten: 731 - 737
Rejiba S, Frelan M, Hermann A, Arndt K, Hajri A
Interfering Peptides Targeting Transcription Factor AP1 for Pancreatic Cancer Gene Therapy
2013 MOLECULAR THERAPY, Band: 21, Nummer: 1
MacKenzie R, ..., von Hauff E, ..., Nelson J
Interpreting the Density of States Extracted from Organic Solar Cells Using Transient Photocurrent Measurements
2013 JOURNAL OF PHYSICAL CHEMISTRY C, Band: 117, Nummer: 24, Seiten: 12407 - 12414
KurzfassungThe energetic distribution of trapped carrier states (DoS) in organic photovoltaic (OPV) devices is a key device parameter which controls carrier mobility and the recombination rate; as such, it can ultimately limit device efficiency. Recent studies have attempted to measure the DoS from working OPV devices using transient photocurrent methods adapted from the time-of-flight (ToF) method originally developed to measure mobility in thick unipolar devices. While a method to extract the DoS from OPV devices using a simple optoelectronic means would be valuable, analysis is complicated by the presence of both electrons and holes in the bipolar organic solar cells. The presence of both carrier species leads to distortion of the extracted DoS due to (a) recombination losses removing carriers from the photocurrent transient thus changing its shape and (b) both LUMO and HOMO DoS features being observed simultaneously in any measurement. In this paper we use a detailed device model to determine the conditions under which the DoS can safely be extracted from the transient photocurrent from bipolar devices. We show that under conditions of reverse bias it is possible to extract the undistorted DoS from a working OPV device. We apply our method to estimate the DoS in a bulk heterojunction solar cell made of a novel low band gap, diketopyrrolopyrrole-based polymer blended with [6,6]-phenyl-C71-butyric acid methyl ester (PC71BM) and solar cells made of poly(3 hexylthiophene):phenyl-C61-butyric acid methyl ester (P3HT:PCBM) annealed over a range of temperatures.
Abeliovich H, Zarei M, Rigbolt K, Youle R, Dengjel J
Involvement of mitochondrial dynamics in the segregation of mitochondrial matrix proteins during stationary phase mitophagy
2013 Nat Commun, Band: 4, Seite: 2789
Scheidt CE, Waller E, Endorf K, Schmidt S, Konig R, Zeeck A, Joos A, Lacour M
Is brief psychodynamic psychotherapy in primary fibromyalgia syndrome with concurrent depression an effective treatment? A randomized controlled trial.
2013 Gen Hosp Psychiat, Band: 35, Nummer: 2, Seiten: 160 - 167
Raue A, Kreutz C, Theis F, Timmer J
Joining forces of Bayesian and frequentist methodology: a study for inference in the presence of non-identifiability
2013 PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, Band: 371, Nummer: 1984
KurzfassungIncreasingly complex applications involve large datasets in combination with nonlinear and high-dimensional mathematical models. In this context, statistical inference is a challenging issue that calls for pragmatic approaches that take advantage of both Bayesian and frequentist methods. The elegance of Bayesian methodology is founded in the propagation of information content provided by experimental data and prior assumptions to the posterior probability distribution of model predictions. However, for complex applications, experimental data and prior assumptions potentially constrain the posterior probability distribution insufficiently. In these situations, Bayesian Markov chain Monte Carlo sampling can be infeasible. From a frequentist point of view, insufficient experimental data and prior assumptions can be interpreted as non-identifiability. The profile-likelihood approach offers to detect and to resolve non-identifiability by experimental design iteratively. Therefore, it allows one to better constrain the posterior probability distribution until Markov chain Monte Carlo sampling can be used securely. Using an application from cell biology, we compare both methods and show that a successive application of the two methods facilitates a realistic assessment of uncertainty in model predictions. (C) 2012 The Author(s) Published by the Royal Society. All rights
Weber S, Fernandez-Cachon ML, Nascimento JM, Knauer S, Offermann B, Murphy RF, Boerries M, Busch H
Label-free detection of neuronal differentiation in cell populations using
2013 Plos One, Band: 8, Nummer: 2, Seiten: e56690 - e56690
Subannajui K, Menzel A, ..., Zacharias M
Large-Scale Nano Piezo Force Position Arrays as Ultrahigh-Resolution Micro- and Nanoparticle Tracker
2013 ADVANCED FUNCTIONAL MATERIALS, Band: 23, Nummer: 2, Seiten: 191 - 197
KurzfassungDefining the position of an object on a planar substrate by force sensors is a common technology nowadays. Many products are commercialized worldwide, which make use of force sensors, especially, for instance, touchpads. Here advanced lithography processes together with piezoelectric materials are demonstrated to fabricate an extremely high resolution force sensor. The approach combines a large array of nanoscale piezoelectric lines fabricated on Si wafer by phase-shift lithography and atomic-layer-deposition-based spacer lithography techniques. These key lithography methods are utilized to fabricate ultralong (cm range) nanolines on the wafer scale. ZnO and P(VDF-TrFE) are selected here as materials for piezoelectric signal generators. The detection mechanisms are explained and simulations combined with experimental data are demonstrated to prove the concept. The signal generated when an object approaches one single line is in the nanoampere range. The result enables a new and simple path for a device fabrication, which defines the position with micro- and nanometer resolution and can be used, for example, as micro- and nanoparticle trackers.
Moradi N, Greiner A, Rao F, Succi S
Lattice Boltzmann implementation of the three-dimensional Ben-Naim potential for water-like fluids.
2013 J Chem Phys, Band: 138, Nummer: 12, Seiten: 124105 - 124105
Mohseni F, Mendoza M, Succi S, Herrmann H
Lattice Boltzmann model for ultrarelativistic flows
2013 PHYSICAL REVIEW D, Band: 87, Nummer: 8
KurzfassungWe develop a relativistic lattice Boltzmann model capable of describing relativistic fluid dynamics at ultra-high velocities, with Lorentz factors up to gamma similar to 10. To this purpose, we first build a new lattice kinetic scheme by expanding the Maxwell-Juttner distribution function in an orthogonal basis of polynomials and applying an appropriate quadrature, providing the discrete versions of the relativistic Boltzmann equation and the equilibrium distribution. To achieve ultra-high velocities, we include a flux limiter scheme, and introduce the bulk viscosity by a suitable extension of the discrete relativistic Boltzmann equation. The model is validated by performing simulations of shock waves in viscous quark-gluon plasmas and comparing with existing models, finding very good agreement. To the best of our knowledge, we for the first time successfully simulate viscous shock waves in the highly relativistic regime. Moreover, we show that our model can also be used for near-inviscid flows even at very high velocities. Finally, as an astrophysical application, we simulate a relativistic shock wave, generated by, say, a supernova explosion, colliding with a massive interstellar cloud, e. g., molecular gas. DOI: 10.1103/PhysRevD.87.083003
Raue A, Schilling M, ..., Klingmueller U, Timmer J
Lessons Learned from Quantitative Dynamical Modeling in Systems Biology
2013 PLOS ONE, Band: 8, Nummer: 9, Seite: e74335
KurzfassungDue to the high complexity of biological data it is difficult to disentangle cellular processes relying only on intuitive interpretation of measurements. A Systems Biology approach that combines quantitative experimental data with dynamic mathematical modeling promises to yield deeper insights into these processes. Nevertheless, with growing complexity and increasing amount of quantitative experimental data, building realistic and reliable mathematical models can become a challenging task: the quality of experimental data has to be assessed objectively, unknown model parameters need to be estimated from the experimental data, and numerical calculations need to be precise and efficient. Here, we discuss, compare and characterize the performance of computational methods throughout the process of quantitative dynamic modeling using two previously established examples, for which quantitative, dose- and time-resolved experimental data are available. In particular, we present an approach that allows to determine the quality of experimental data in an efficient, objective and automated manner. Using this approach data generated by different measurement techniques and even in single replicates can be reliably used for mathematical modeling. For the estimation of unknown model parameters, the performance of different optimization algorithms was compared systematically. Our results show that deterministic derivative-based optimization employing the sensitivity equations in combination with a multi-start strategy based on latin hypercube sampling outperforms the other methods by orders of magnitude in accuracy and speed. Finally, we investigated transformations that yield a more efficient parameterization of the model and therefore lead to a further enhancement in optimization performance. We provide a freely available open source software package that implements the algorithms and examples compared here.
Tichy M, Mintert F, Buchleitner A
Limits to multipartite entanglement generation with bosons and fermions
2013 PHYSICAL REVIEW A, Band: 87, Nummer: 2
KurzfassungMany-photon interference in linear-optics setups can be exploited to generate and to detect multipartite entanglement. Without recurring to any interparticle interaction, many entangled states have been created experimentally, and a panoply of theoretical schemes for the generation of various classes of entangled states is available. Here, we present a unifying framework that accommodates the present experiments and theoretical protocols for the creation of multiparticle entanglement via interference. A general representation of the states that can be created is provided for bosons and fermions for any particle number and for any dimensionality of the entangled degree of freedom. Using this framework, we derive an upper bound on the generalized Schmidt number of the states that can be generated, and we establish bounds on the dimensionality of the manifold of these states. We show that-at the expense of a smaller success probability-more states can be created with bosons than with fermions and give an intuitive interpretation of the state representation and of the established bounds in terms of superimposed many-particle paths. DOI: 10.1103/PhysRevA.87.022319
Cui J, Amico L, Fan H, Gu M, Hamma A, Vedral V
Local characterization of one-dimensional topologically ordered states
2013 PHYSICAL REVIEW B, Band: 88, Nummer: 12, Seite: 125117
KurzfassungWe consider one-dimensional Hamiltonian systems whose ground states display symmetry-protected topological order. We show that ground states within the topological phase cannot be connected with each other through local operations and classical communication between a bipartition of the system. Our claim is demonstrated by analyzing the entanglement spectrum and Renyi entropies of different physical systems that provide examples for symmetry-protected topological phases. Specifically, we consider the spin-1/2 cluster-Ising model and a class of spin-1 models undergoing quantum phase transitions to the Haldane phase. Our results provide a probe for symmetry-protected topological order. Since the picture holds even at the system’s local scale, our analysis can serve as a local experimental test for topological order.
Albrecht K, Martin-Rodero A, Monreal R, Muehlbacher L, Levy Yeyati A
Long transient dynamics in the Anderson-Holstein model out of equilibrium
2013 PHYSICAL REVIEW B, Band: 87, Nummer: 8
KurzfassungWe calculate the time-dependent nonequilibrium current through a single-level quantum dot strongly coupled to a vibrational mode. The nonequilibrium real-time dynamics caused by an instantaneous coupling of the leads to the quantum dot is discussed using an approximate method. The approach, which is specially designed for the strong polaronic regime, is based on the so-called polaron tunneling approximation. Considering different initial dot occupations, we show that a common steady state is reached after times much larger than the typical electron tunneling times due to a polaron blocking effect in the dot charge. A direct comparison is made with numerically exact data, showing good agreement for the time scales accessible by the diagrammatic Monte Carlo simulation method. DOI: 10.1103/PhysRevB.87.085127
Li L, ..., Tabata O, Li W
Manipulation of DNA origami nanotubes in liquid using programmable tapping-mode atomic force microscopy
2013 MICRO & NANO LETTERS, Band: 8, Nummer: 10, Seiten: 641 - 645
KurzfassungThe nanoscale manipulation of 1D soft and flexible ‘DNA origami nanotubes’ (DONs) that are 6 nm in diameter and 400 nm in length, and placed on a mica substrate in a TE/Mg2+ buffer solution, was executed by an atomic force microscopy (AFM) tip using a programmable tapping-mode manipulation strategy. The AFM’s tip tapping amplitude was controlled to be less than or equal to 10 nm while vibrating in a solution with Mg2+ concentration of 10-20 mM. A series of single-point and one-step manipulation experiments revealed that manipulation can be achieved with an 80% successful rate under the condition that the AFM tip vibration amplitude is 3-4 nm and the Mg2+ concentration is 10 mM. Utilising this optimised condition, multipoint and multistep manipulation based on the programmable tapping-mode AFM process was conducted and nanomanipulation of DONs was successfully demonstrated.
Kauzlaric D, Meier J, Espanol P, Greiner A, Succi S
Markovian equations of motion for non-Markovian coarse-graining and properties for graphene blobs
2013 NEW JOURNAL OF PHYSICS, Band: 15
KurzfassungWe obtain Markovian equations of motion for a many body system of interacting coarse-grained (CG) variables and additional fluxes. The investigated CG variables belong to the special family of linear combinations of atomistic degrees of freedom. The system of Markovian equations of motion approximates Mori’s exact non-Markovian generalized Langevin equation and is easy to solve by computer simulation. All parameters of the equations can be obtained from equilibrium molecular dynamics simulations of the investigated microscopic system. These parameters are either equal to the famous static covariances from Mori’s continued fraction or they represent generalized constant friction matrices. We propose two different ways to compute these friction matrices based on Mori’s continued fraction. Finally, some of the parameters are computed numerically for the special case of centre of mass variables in the graphene lattice and it is found that the CG variables interact with their additional fluxes in a spatially very local way.
Lee P, Li WC, ..., Botiz I, Reiter G, et al.
Massive Enhancement of Photoluminescence through Nanofilm Dewetting
2013 ACS NANO, Band: 7, Nummer: 8, Seiten: 6658 - 6666
KurzfassungDue to the rather low efficiencies of conjugated polymers in solid films, their successful applications are scarce. However, recently several experiments Indicated that a proper control of molecular conformations and stresses acting on the polymers may provide constructive ways to boost efficiency. Here, we report an amazingly large enhancement of photoluminescence as a consequence of strong shear forces acting on the polymer chains during nanofilm dewetting. Such sheared chains exhibited an emission probability many times higher than the nonsheared chains within a nondewetted film. This increase in emission probability Was accompanied by the emergence of an additional blue-shifted emission peak, suggesting reductions in conjugation length induced by the dewetting-driven mass redistribution. Intriguingly, exciton quenching on narrow-band-gap substrates was also reduced, indicating suppression of vibronic interactions of excitons. Dewetting and related shearing processes resulting in enhanced Photoluminescence efficiency are compatible with existing fabrication methods of polymer based diodes and solar cells.
Yalcin A, ..., Klaus G, Timmer J, Luebbert M, Hackanson B
MeDIP coupled with a promoter tiling array as a platform to investigate global DNA methylation patterns in AML cells
2013 LEUKEMIA RESEARCH, Band: 37, Nummer: 1, Seiten: 102 - 111
KurzfassungHypermethylation of CpGs in promoter regions and subsequent changes in gene expression are common features in acute myeloid leukemia (AML). Genome-wide studies of the methylome are not only useful to understand changes in DNA methylation and gene regulation but also to identify potential targets for antileukemic treatment. Here we performed methylated DNA immunoprecipitation (MeDIP) in the AML cell line HL-60 and donor-derived CD34+ cells, followed by hybridization on a human promoter tiling array. The comparative analysis of HL-60 versus CD34+ cells revealed differentially methylated promoter regions including genes that are frequently methylated in AML, such as p15/INK4B, OLIG2, RAR beta 2 and estrogen receptor. Microarray data was validated by quantitative pyrosequencing. We corroborate previous reports that MeDIP, in our study combined with a promoter tiling array (MeDIP-Chip), is a robust method to identify genes that are differentially methylated in AML cells in a genome-wide manner, and is thus useful to identify new epigenetic targets for therapeutic or prognostic research. (C) 2012 Elsevier Ltd. All rights reserved.
Reyes-Romero D, Cubukcu A, Urban G
Measurement and simulation of the frequency response of a thermal flow sensor at different flow speeds
2013 SENSORS AND ACTUATORS A-PHYSICAL, Band: 189, Seiten: 168 - 176
KurzfassungThis contribution presents the complete (amplitude and phase) frequency response of a calorimetric flow sensor in a free, laminar air stream at different flow speeds ranging from 0 to 5 m/s. Given the geometry of the sensor, which features a central thermistor closely surrounded by a heater element, the complexity of the resulting frequency response is reduced by applying a simple transformation. This transformation involves taking the ratio between the temperature oscillations at the surrounding thermistors and the central thermistor. The resulting frequency response shows a second order transfer function of real poles. The parameters of this transfer function are used to analyze the effect of the flow speed on the frequency response. Results show that for air, the position of the first characteristic pole remains constant at the downstream thermistor for flow speeds up to 1 m/s. Experimental and simulated results are consistent, which allows the further study of the sensor’s response by means of numerical simulations in order to determine the effect of the thermal properties of the fluids on the frequency response. The ultimately goal is to achieve fluid independent flow measurement. (C) 2012 Elsevier B.V. All rights reserved.
Campana F
Mihai Metrics with cone singularities along normal crossing divisors and holomorphic tensor fields
2013 Ann. Sci. Éc. Norm. Supér., Band: 46, Nummer: 6, Seiten: 879 - 916
Abeliovich H, Zarei M, Rigbolt K, Youle R, Dengjel J
Mitophagy as a quality control mechanism in Saccharomyces cerevisiae
2013 FASEB JOURNAL, Band: 27
Singh M, Ren F, ..., Palme K
Modification of plant Rac/Rop GTPase signalling using bacterial toxin transgenes
2013 PLANT JOURNAL, Band: 73, Nummer: 2, Seiten: 314 - 324
KurzfassungBacterial protein toxins which modify Rho GTPase are useful for the analysis of Rho signalling in animal cells, but these toxins cannot be taken up by plant cells. We demonstrate in vitro deamidation of Arabidopsis Rop4 by Escherichia coli Cytotoxic Necrotizing Factor 1 (CNF1) and glucosylation by Clostridium difficile toxin B. Expression of the catalytic domain of CNF1 caused modification and activation of co-expressed Arabidopsis Rop4 GTPase in tobacco leaves, resulting in hypersensitive-like cell death. By contrast, the catalytic domain of toxin B modified and inactivated co-expressed constitutively active Rop4, blocking the hypersensitive response caused by over-expression of active Rops. In transgenic Arabidopsis, both CNF1 and toxin B inhibited Rop-dependent polar morphogenesis of leaf epidermal cells. Toxin B expression also inhibited Rop-dependent morphogenesis of root hairs and trichome branching, and resulted in root meristem enlargement and dwarf growth. Our results show that CNF1 and toxin B transgenes are effective tools in Rop GTPase signalling studies.
Fuchs A, Kauzlaric D, Greiner A, Succi S, Korvink J
Molecular Dynamics Simulations of Nanoparticle Interactions with a Planar Wall: Does Shape Matter?
2013 COMMUNICATIONS IN COMPUTATIONAL PHYSICS, Band: 13, Nummer: 3, SI, Seiten: 900 - 915
KurzfassungWe investigate the hydrodynamic interactions of spherical colloidal nano particles and nano tetrahedra near a planar wall by means of molecular dynamics (MD) simulations of rigid particles within an all-atom solvent. For both spherical and nano-tetrahedral particles, we find that the parallel and perpendicular components of the local diffusion coefficient and viscosity, show good agreement with hydrodynamic theory of Faxen and Brenner. This provides further evidence that low perturbations from sphericality of a nanoparticle’s shape has little influence on its local diffusive behaviour, and that for this particular case, the continuum theory fluid dynamics is valid even down to molecular scales.
Boerries M, Grahammer F, Eiselein S, Buck M, Meyer C, Goedel M, Bechtel W, Zschiedrich S, Pfeifer D, Laloe D, Arrondel C, Goncalves S, Kruger M, Harvey SJ, Busch H, Dengjel J, Huber TB
Molecular fingerprinting of the podocyte reveals novel gene and protein regulatory networks.
2013 Kidney Int, Band: 83, Nummer: 6, Seiten: 1052 - 1064
Mueller K, Engesser R, ..., Timmer J, Zurbriggen M, Weber W
Multi-chromatic control of mammalian gene expression and signaling
2013 NUCLEIC ACIDS RESEARCH, Band: 41, Nummer: 12, Seite: e124
KurzfassungThe emergence and future of mammalian synthetic biology depends on technologies for orchestrating and custom tailoring complementary gene expression and signaling processes in a predictable manner. Here, we demonstrate for the first time multi-chromatic expression control in mammalian cells by differentially inducing up to three genes in a single cell culture in response to light of different wavelengths. To this end, we developed an ultraviolet B (UVB)-inducible expression system by designing a UVB-responsive split transcription factor based on the Arabidopsis thaliana UVB receptor UVR8 and the WD40 domain of COP1. The system allowed high (up to 800-fold) UVB-induced gene expression in human, monkey, hamster and mouse cells. Based on a quantitative model, we determined critical system parameters. By combining this UVB-responsive system with blue and red light-inducible gene control technology, we demonstrate multi-chromatic multi-gene control by differentially expressing three genes in a single cell culture in mammalian cells, and we apply this system for the multi-chromatic control of angiogenic signaling processes. This portfolio of optogenetic tools enables the design and implementation of synthetic biological networks showing unmatched spatiotemporal precision for future research and biomedical applications.
Schreiber A, Schiller S
Nanobiotechnology of protein-based compartments: steps toward nanofactories
2013 BIOINSPIRED BIOMIMETIC AND NANOBIOMATERIALS, Band: 2, Nummer: 4, Seiten: 154 - 172
KurzfassungNanobiotechnology of toroids/donuts, yoctowells, tubes, cages, capsids, compartments and organelles based on protein-building blocks allows for the definition of precise reaction spaces in vitro and in vivo. Utilizing a synthetic biology approach, the generation of compartment-forming protein ‘bio-bricks’ points toward new ways to control the assembly of these structures to develop nanofactories in vivo. This is envisioned to be an important step allowing for the precise assembly of novel metabolic cascades within nanoreactors in the future. The ability to site-selectively modify proteins by inserting or replacing selected natural and unnatural amino acids at defined positions, provides the necessary tools to control novel functions via ‘genetic programming’. The protein-building blocks, already embedded in nature’s nanocompartment tool box, will be the focus of this review. The various protein structures forming compartments in vitro and in vivo will be presented together with their current applications.
Engelen J, Khatib M, Abelmann L, Elwenspoek M
Nanopositioner actuator energy cost and performance
2013 SENSORS AND ACTUATORS A-PHYSICAL, Band: 199, Seiten: 353 - 365
KurzfassungWe investigate the energy consumption and seek-time performance of different actuator types for nanopositioners, with emphasis on their use in a parallel-probe-based data-storage system. Analytical models are derived to calculate the energy consumption and performance of electrodynamic (coil and permanent magnet) and comb-drive actuators. The equations are used to simulate the operation of probe-storage devices with these actuator types under a realistic file system load. The electrostatic comb-drive actuators are more energy efficient than the electrodynamic actuators, by an order of magnitude for slow movements and a factor of 2.5 for high-acceleration movements. Overall in a probe-storage device, comb-drive actuation is a factor of 3.3 more energy efficient than electrodynamic actuation, at the same level of performance. The analytical model presented in this work can be used to direct the optimization of nanopositioners and their use, for example, in terms of the data layout on the medium and the ‘shutdown’ policy of probe-storage devices. (C) 2013 Elsevier B.V. All rights reserved.
Al-Ahmad A, Laird D, Zou P, Tomakidi P, Steinberg T, Lienkamp K
Nature-Inspired Antimicrobial Polymers - Assessment of Their Potential for Biomedical Applications
2013 PLOS ONE, Band: 8, Nummer: 9, Seite: e73812
KurzfassungWe explored the potential of poly(oxonorbornene)-based synthetic mimics of antimicrobial peptides (SMAMPs), a promising new class of antimicrobial polymers with cell-selectivity and low resistance development potential, for clinical applications. We evaluated their antimicrobial activity against a panel of seven clinical and regulatory relevant bacteria strains, and tested their toxicity with two different kinds of primary human cells. For the antimicrobial activity, we performed the minimum inhibitory concentration (MIC) assay and determined the minimum bactericidal concentration (MBC) according to the NCCLS guidelines. The results revealed specific problems that may occur when testing the antimicrobial activity of amphiphilic cationic polymers, and confirmed the working hypothesis that the more hydrophilic SMAMP polymers in our portfolio were ‘doubly selective’, i.e. they are not only selective for bacteria over mammalian cells, but also for Gram-positive over Gram-negative bacteria. The data also showed that we could improve the broad-band activity of one SMAMP, and in combination with the results from the cell toxicity experiments, identified this polymer as a promising candidate for further in-vitro and in-vivo testing. Transmission electron studies revealed that the cellular envelopes of both E. coli and S. aureus were severely damaged due to SMAMP action on the bacterial membrane, which strengthened the argument that SMAMPs closely resemble antimicrobial peptides. To test cell toxicity, we used the traditional hemolysis assay with human red blood cells, and the novel xCelligence assay with primary human fibroblasts. The data reported here is the first example in which a hemolysis assay is benchmarked against the xCelligence assay. It revealed that the same trends were obtained using these complementary methods. This establishes the xCelligence assay with primary human cells as a useful tool for SMAMP characterization.
Busch H, Boerries M, Bao J, ..., Rensing S
Network Theory Inspired Analysis of Time-Resolved Expression Data Reveals Key Players Guiding P. patens Stem Cell Development
2013 PLOS ONE, Band: 8, Nummer: 4, Seite: e60494
KurzfassungTranscription factors (TFs) often trigger developmental decisions, yet, their transcripts are often only moderately regulated and thus not easily detected by conventional statistics on expression data. Here we present a method that allows to determine such genes based on trajectory analysis of time-resolved transcriptome data. As a proof of principle, we have analysed apical stem cells of filamentous moss (P. patens) protonemata that develop from leaflets upon their detachment from the plant. By our novel correlation analysis of the post detachment transcriptome kinetics we predict five out of 1,058 TFs to be involved in the signaling leading to the establishment of pluripotency. Among the predicted regulators is the basic helix loop helix TF PpRSL1, which we show to be involved in the establishment of apical stem cells in P. patens. Our methodology is expected to aid analysis of key players of developmental decisions in complex plant and animal systems.
Spiegelhalder K, Regen W, Baglioni C, Riemann D, Winkelman J
Neuroimaging Studies in Insomnia
2013 CURRENT PSYCHIATRY REPORTS, Band: 15, Nummer: 11
KurzfassungChronic insomnia is one of the most prevalent psychiatric disorders and has a significant impact on individual’s health. However, the pathophysiology of the disorder is poorly understood. The current review focuses on neuroimaging findings in insomnia. In summary, the current data suggest the following: (1) insomnia is characterized by corticolimbic overactivity during sleep and wakefulness that interferes with sleep initiation and/or maintenance; (2) insomnia patients’ daytime performance is associated with a hypoactivation of task-related areas; (3) neurochemically, insomnia patients are probably characterized by reduced cortical GABA levels; (4) insomnia may be associated with abnormal brain morphometry in the frontal cortex, hippocampus and/or anterior cingulate cortex. Future investigations should include larger sample sizes or longitudinal within-subject comparisons. Other possible methodological improvements are discussed.
Ra YS, Tichy M, Lim HT, Kwon O, Mintert F, Buchleitner A, Kim YH
Nonmonotonic quantum-to-classical transition in multiparticle interference
2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Band: 110, Nummer: 4, Seiten: 1227 - 1231
KurzfassungQuantum-mechanical wave-particle duality implies that probability distributions for granular detection events exhibit wave-like interference. On the single-particle level, this leads to self-interference-e.g., on transit across a double slit-for photons as well as for large, massive particles, provided that no which-way information is available to any observer, even in principle. When more than one particle enters the game, their specific many-particle quantum features are manifested in correlation functions, provided the particles cannot be distinguished. We are used to believe that interference fades away monotonically with increasing distinguishability-in accord with available experimental evidence on the single- and on the many-particle level. Here, we demonstrate experimentally and theoretically that such monotonicity of the quantum-to-classical transition is the exception rather than the rule whenever more than two particles interfere. As the distinguishability of the particles is continuously increased, different numbers of particles effectively interfere, which leads to interference signals that are, in general, nonmonotonic functions of the distinguishability of the particles. This observation opens perspectives for the experimental characterization of many-particle coherence and sheds light on decoherence processes in many-particle systems.
Kiritsi D, Chmel N, Arnold A, Jakob T, Bruckner-Tuderman L, Has C
Novel and Recurrent AAGAB Mutations: Clinical Variability and Molecular Consequences
2013 JOURNAL OF INVESTIGATIVE DERMATOLOGY, Band: 133, Nummer: 10, Seiten: 2483 - 2486
Ra YS, Tichy M, Lim HT, Kwon O, Mintert F, Buchleitner A, Kim YH
Observation of detection-dependent multi-photon coherence times
2013 NATURE COMMUNICATIONS, Band: 4, Seite: 2451
KurzfassungThe coherence time constitutes one of the most critical parameters that determines whether or not interference is observed in an experiment. For photons, it is traditionally determined by the effective spectral bandwidth of the photon. Here we report on multi-photon interference experiments in which the multi-photon coherence time, defined by the width of the interference signal, depends on the number of interfering photons and on the measurement scheme chosen to detect the particles. A theoretical analysis reveals that all multi-photon interferences with more than two particles feature this dependence, which can be attributed to higher-order effects in the mutual indistinguishability of the particles. As a striking consequence, a single, well-defined many-particle quantum state can exhibit qualitatively different degrees of interference, depending on the chosen observable. Therefore, optimal sensitivity in many-particle quantum interferometry can only be achieved by choosing a suitable detection scheme.
Campana F
On families of Lagrangian tori on hyperkähler manifolds
2013 J Geom Phys, Band: 71, Seiten: 53 - 57
Rejiba S, Bigand C, Parmentier C, Masmoudi A, Hajri A
Oncosuppressive Suicide Gene Virotherapy “PVH1-yCD/5-FC” for Pancreatic Peritoneal Carcinomatosis Treatment: NF kappa B and Akt/PI3K Involvement
2013 PLOS ONE, Band: 8, Nummer: 8
KurzfassungPeritoneal carcinomatosis is common in advanced pancreatic cancer. Despite current standard treatment, patients with this disease until recently were considered incurable. Cancer gene therapy using oncolytic viruses have generated much interest over the past few years. Here, we investigated a new gene directed enzyme prodrug therapy (GDEPT) approach for an oncosuppressive virotherapy strategy using parvovirus H1 (PV-H1) which preferentially replicates and kills malignant cells. Although, PV-H1 is not potent enough to destroy tumors, it represents an attractive vector for cancer gene therapy. We therefore sought to determine whether the suicide gene/prodrug system, yCD/5-FC could be rationally combined to PV-H1 augmenting its intrinsic oncolytic activity for pancreatic cancer prevention and treatment. We showed that the engineered recombinant parvovirus rPVH1-yCD with 5-FC treatment increased significantly the intrinsic cytotoxic effect and resulted in potent induction of apoptosis and tumor growth inhibition in chemosensitive and chemoresistant cells. Additionally, the suicide gene-expressing PV-H1 infection reduced significantly the constitutive activities of NF kappa B and Akt/PI3K. Combination of their pharmacological inhibitors (MG132 and LY294002) with rPVH1-yCD/5-FC resulted in substantial increase of antitumor activity. In vivo, high and sustained expression of NS1 and yCD was observed in the disseminated tumor nodules and absent in normal tissues. Treatment of mice bearing intraperitoneal pancreatic carcinomatosis with rPVH1-yCD/5-FC resulted in a drastic inhibition of tumor cell spreading and subsequent increase in long-term survival. Together, the presented data show the improved oncolytic activity of wPV-H1 by yCD/5-FC and thus provides valuable effective and promising virotherapy strategy for prevention of tumor recurrence and treatment. In the light of this study, the suicide gene parvovirotherapy approach represents a new weapon in the war against pancreatic cancer. Moreover, these preliminary accomplishments are opening new field for future development of new combined targeted therapies to have a meaningful impact on advanced cancer.
Huenefeld C, Mezger M, ..., Bruckner-Tuderman L, et al.
One goal, different strategies - molecular and cellular approaches for the treatment of inherited skin fragility disorders
2013 EXPERIMENTAL DERMATOLOGY, Band: 22, Nummer: 3, Seiten: 162 - 167
KurzfassungEpidermolysis bullosa (EB) is a heterogeneous group of inherited diseases characterized by the formation of blisters in the skin and mucosa. There is no cure or effective treatment for these potentially severe and fatal diseases. Over the past few years, several reports have proposed different molecular strategies as new therapeutic options for the management of EB. From classical vector-based gene therapy to cell-based strategies such as systemic application of bone marrow stem cells or local application of fibroblasts, a broad range of molecular approaches have been explored. This array also includes novel methods, such as protein replacement therapy, gene silencing and the use of induced pluripotent stem cells (iPCs). In this review, we summarize current concepts of how inherited blistering diseases might be treated in the future and discuss the opportunities, promises, concerns and risks of these innovative approaches.
Jia F, Kumar R, Korvink J
Optimal Magnetic Susceptibility Matching in 3D
2013 MAGNETIC RESONANCE IN MEDICINE, Band: 69, Nummer: 4, Seiten: 1146 - 1156
KurzfassungWhen an object is inserted into the strong homogeneous magnetic field of a magnetic resonance magnet, its intrinsic relative susceptibility can cause unwanted local magnetic field inhomogeneities in the space surrounding the object. As is known, this effect can be partially countered by selectively adding material layers with opposing sign in susceptibility to the part. The determination of an optimal magnetic susceptibility distribution is an inverse problem, in which the susceptibility-induced inhomogeneity of the magnetic field inside a region of interest is reduced by redistributing the placement of materials in the design domain. This article proposes an efficient numerical topology optimization method for obtaining an optimal magnetic susceptibility distribution, in particular, for which the induced spatial magnetic field inhomogeneity is minimized. Using a material density function as a design variable, the value of the magnetic field inside a computational domain is determined using a finite element method. The first-order sensitivity of the objective function is calculated using an adjoint equation method. Numerical examples on a variety of design domain geometries illustrate the effectiveness of the optimization method. The method is of specific interest for the design of interventional magnetic resonance devices. It is a particularly useful method if passive shimming of magnetic resonance equipment is aimed for. Magn Reson Med 69:1146-1156, 2013. (C) 2012 Wiley Periodicals, Inc.
Heilig Y, Schmitt K, Seiler S
Phospho-Regulation of the Neurospora crassa Septation Initiation Network.
2013 Plos One, Band: 8, Nummer: 10, Seiten: e79464 - e79464
Kim S, Colpitts C, ..., Reski R, Sterenberg B, Suh DY
Physcomitrella PpORS, Basal to Plant Type III Polyketide Synthases in Phylogenetic Trees, Is a Very Long Chain 2 ‘-Oxoalkylresorcinol Synthase
2013 JOURNAL OF BIOLOGICAL CHEMISTRY, Band: 288, Nummer: 4, Seiten: 2767 - 2777
KurzfassungThe plant type III polyketide synthases (PKSs), which produce diverse secondary metabolites with different biological activities, have successfully co-evolved with land plants. To gain insight into the roles that ancestral type III PKSs played during the early evolution of land plants, we cloned and characterized PpORS from the moss Physcomitrella. PpORS has been proposed to closely resemble the most recent common ancestor of the plant type III PKSs. PpORS condenses a very long chain fatty acyl-CoA with four molecules of malonyl-CoA and catalyzes decarboxylative aldol cyclization to yield the pentaketide 2’-oxoalkylresorcinol. Therefore, PpORS is a 2’-oxoalkylresorcinol synthase. Structure modeling and sequence alignments identified a unique set of amino acid residues (Gln(218), Val(277), and Ala(286)) at the putative PpORS active site. Substitution of the Ala(286) to Phe apparently constricted the active site cavity, and the A286F mutant instead produced triketide alkylpyrones from fatty acyl-CoA substrates with shorter chain lengths. Phylogenetic analysis and comparison of the active sites of PpORS and alkylresorcinol synthases from sorghum and rice suggested that the gramineous enzymes evolved independently from PpORS to have similar functions but with distinct active site architecture. Microarray analysis revealed that PpORS is exclusively expressed in nonprotonemal moss cells. The in planta function of PpORS, therefore, is probably related to a nonprotonemal structure, such as the cuticle.
Eriksson A, Edwards K, Hagfeldt A, Hernandez V
Physicochemical Characterization of Phosphopeptide/Titanium Dioxide Interactions Employing the Quartz Crystal Microbalance Technique
2013 JOURNAL OF PHYSICAL CHEMISTRY B, Band: 117, Nummer: 7, Seiten: 2019 - 2025
KurzfassungThe rapidly growing field of phosphoproteomics has led to a strong demand for procedures enabling fast and reliable isolation and enrichment of phosphorylated proteins and peptides. During the past decade, several novel phosphopeptide enrichment methods based on the affinity of phosphoryl groups for titanium dioxide (TiO2) have been developed and tested. The ultimate goal of obtaining comprehensive phosphoproteomes has, however, been found difficult to achieve and the obtained results often vary, dependent on the enrichment method and protocol used. In the present study, the physical chemistry of the phosphopeptide binding to TiO2 is investigated by means of measurements using a quartz crystal microbalance with dissipation monitoring (QCM-D). Special emphasis is put on the effect of the degree of phosphorylation of the phosphopeptide, the impact of the primary amino acid structure, and the role of electrostatic interactions. The results show that, in general, adsorption of phosphopeptides follows the Langmuir model and that the affinity for the TiO2 surface increases in a nonlinear fashion with increasing degree of phosphorylation. An exception was detected, however, where positive cooperativity between the peptides existed and the Langmuir model no longer applied. The source behind the cooperativity could be traced back to the primary amino acid structure and, more specifically, the presence of positively charged amino acids in positions that enable electrostatic interaction with phosphoryl groups on neighboring peptides. Regardless of the net peptide charge, the TiO2-phosphopeptide interaction was for all phosphopeptides investigated found to be mainly of electrostatic origin. This study highlights and explains some of the most common problems with the TiO2-based enrichment methods used today.
Aureggi V, Ehmke V, ..., Breit B, Diederich F
Potent Inhibitors of Malarial Aspartic Proteases, the Plasmepsins, by Hydroformylation of Substituted 7-Azanorbornenes
2013 CHEMISTRY-A EUROPEAN JOURNAL, Band: 19, Nummer: 1, Seiten: 155 - 164
KurzfassungThe increasing prevalence of multidrug-resistant strains of the malarial parasite Plasmodium falciparum requires the urgent development of new therapeutic agents with novel modes of action. The vacuolar malarial aspartic proteases plasmepsin (PM) I, II, and IV are involved in hemoglobin degradation and play a central role in the growth and maturation of the parasite in the human host. We report the structure-based design, synthesis, and in vitro evaluation of a new generation of PM inhibitors featuring a highly decorated 7-azabicyclo[2.2.1] heptane core. While this protonated central core addresses the catalytic Asp dyad, three substituents bind to the flap, the S1/S3, and the S1’ pockets of the enzymes. A hydroformylation reaction is the key synthetic step for the introduction of the new vector reaching into the S1’ pocket. The configuration of the racemic ligands was confirmed by extensive NMR and X-ray crystallographic analysis. In vitro biological assays revealed high potency of the new inhibitors against the three plasmepsins (IC50 values down to 6 nm) and good selectivity towards the closely related human cathepsins D and E. The occupancy of the S1’ pocket makes an essential contribution to the gain in binding affinity and selectivity, which is particularly large in the case of the PM IV enzyme. Designing non-peptidic ligands for PM II is a valid route to generate compounds that inhibit the entire family of vacuolar plasmepsins.
Song S, Eckerle S, Onichtchouk D, Marrs J, Nitschke R, Driever W
Pou5f1-Dependent EGF Expression Controls E-Cadherin Endocytosis, Cell Adhesion, and Zebrafish Epiboly Movements
2013 DEVELOPMENTAL CELL, Band: 24, Nummer: 5, Seiten: 486 - 501
KurzfassungInitiation of motile cell behavior in embryonic development occurs during late blastula stages when gastrulation begins. At this stage, the strong adhesion of blastomeres has to be modulated to enable dynamic behavior, similar to epithelial-to-mesenchymal transitions. We show that, in zebrafish maternal and zygotic (MZ)spg embryos mutant for the stem cell transcription factor Pou5f1/Oct4, which are severely delayed in the epiboly gastrulation movement, all blastomeres are defective in E-cadherin (E-cad) endosomal trafficking, and E-cad accumulates at the plasma membrane. We find that Pou5f1-dependent control of EGF expression regulates endosomal E-cad trafficking. EGF receptor may act via modulation of p120 activity. Loss of E-cad dynamics reduces cohesion of cells in reaggregation assays. Quantitative analysis of cell behavior indicates that dynamic E-cad endosomal trafficking is required for epiboly cell movements. We hypothesize that dynamic control of E-cad trafficking is essential to effectively generate new adhesion sites when cells move relative to each other.
Spiegelhalder K
Predictability of alcohol relapse by hippocampal volumetry and psychometric variables.
2013 Psychiatry Research: Neuroimaging, Band: 212, Seiten: 14 - 18
Kreutz C, Raue A, Kaschek D, Timmer J
Profile likelihood in systems biology
2013 FEBS JOURNAL, Band: 280, Nummer: 11, Seiten: 2564 - 2571
KurzfassungInferring knowledge about biological processes by a mathematical description is a major characteristic of Systems Biology. To understand and predict system’s behavior the available experimental information is translated into a mathematical model. Since the availability of experimental data is often limited and measurements contain noise, it is essential to appropriately translate experimental uncertainty to model parameters as well as to model predictions. This is especially important in Systems Biology because typically large and complex models are applied and therefore the limited experimental knowledge might yield weakly specified model components. Likelihood profiles have been recently suggested and applied in the Systems Biology for assessing parameter and prediction uncertainty. In this article, the profile likelihood concept is reviewed and the potential of the approach is demonstrated for a model of the erythropoietin (EPO) receptor.
Inhofer A, Bercioux D
Proposal for an on-demand source of polarized electrons into the edges of a topological insulator
2013 PHYSICAL REVIEW B, Band: 88, Nummer: 23
KurzfassungWe propose a device that allows for the emission of pairs of spin-polarized electrons into the edge states of a two-dimensional topological insulator. Charge and spin emission is achieved using a periodically driven quantum dot weakly coupled to the edge states of the host topological insulator. We present calculations of the emitted time-dependent charge and spin currents of such a dynamical scatterer using the Floquet scattering matrix approach. Experimental signatures of spin-polarized two-particle emission can be found in noise measurements. Here a new form of noise suppression, named Z(2) antibunching, is introduced. Additionally, we propose a setup in which entanglement of the emitted electrons is generated. This entanglement is based on a postselection procedure and becomes manifest in a violation of a Clauser-Horne-Shimony-Holt inequality.
Fischer M, Horn S, ..., Dengjel J, Herrmann J, Riemer J
Protein import and oxidative folding in the mitochondrial intermembrane space of intact mammalian cells
2013 MOLECULAR BIOLOGY OF THE CELL, Band: 24, Nummer: 14, Seiten: 2160 - 2170
KurzfassungOxidation of cysteine residues to disulfides drives import of many proteins into the intermembrane space of mitochondria. Recent studies in yeast unraveled the basic principles of mitochondrial protein oxidation, but the kinetics under physiological conditions is unknown. We developed assays to follow protein oxidation in living mammalian cells, which reveal that import and oxidative folding of proteins are kinetically and functionally coupled and depend on the oxidoreductase Mia40, the sulfhydryl oxidase augmenter of liver regeneration (ALR), and the intracellular glutathione pool. Kinetics of substrate oxidation depends on the amount of Mia40 and requires tightly balanced amounts of ALR. Mia40-dependent import of Cox19 in human cells depends on the inner membrane potential. Our observations reveal considerable differences in the velocities of mitochondrial import pathways: whereas preproteins with bipartite targeting sequences are imported within seconds, substrates of Mia40 remain in the cytosol for several minutes and apparently escape premature degradation and oxidation.
Hisch T, Liertzer M, Pogany D, Mintert F, Rotter S
Pump-Controlled Directional Light Emission from Random Lasers
2013 PHYSICAL REVIEW LETTERS, Band: 111, Nummer: 2
KurzfassungThe angular emission pattern of a random laser is typically very irregular and difficult to tune. Here we show by detailed numerical calculations that one can overcome the lack of control over this emission pattern by actively shaping the spatial pump distribution. We demonstrate, in particular, how to obtain customized pump profiles to achieve highly directional emission. Going beyond the regime of strongly scattering media where localized modes with a given directionality can simply be selected by the pump, we present an optimization-based approach which shapes extended lasing modes in the weakly scattering regime according to any predetermined emission pattern.
Spiegelhalder K
Quantitative measurement of sleep quality using cardiopulmonary coupling analysis: A retrospective comparison of individuals with and without primary insomnia.
2013 Sleep Breath, Band: 17, Seiten: 713 - 721
Zarei M, Sprenger A, Gretzmeier C, Dengjel J
Rapid combinatorial ERLIC-SCX solid-phase extraction for in-depth phosphoproteome analysis.
2013 J Proteome Res, Band: 12, Nummer: 12, Seiten: 5989 - 5995
Lenz L, Urban D, Bercioux D
Rashba spin-orbit interaction in graphene armchair nanoribbons
2013 EUROPEAN PHYSICAL JOURNAL B, Band: 86, Nummer: 12
KurzfassungWe study graphene nanoribbons (GNRs) with armchair edges in the presence of Rashba spin-orbit interactions (RSOI). We impose the boundary conditions on the tight binding Hamiltonians for bulk graphene with RSOI by means of a sine transform and study the influence of RSOI on the spectra and the spin polarization in detail. We derive the low energy approximation of the RSOI Hamiltonian for the zeroth and first order in momentum and test their ranges of validity. The choice of a basis appropriate for armchair boundaries is important in the case of mode-coupling effects and leads to results that are easy to work with.
Nystroem A, Buttgereit J, Bader M, ..., Hausser I, Bruckner-Tuderman L, Kern J
Rat Model for Dominant Dystrophic Epidermolysis Bullosa: Glycine Substitution Reduces Collagen VII Stability and Shows Gene-Dosage Effect
2013 PLOS ONE, Band: 8, Nummer: 5, Seite: e64243
KurzfassungDystrophic epidermolysis bullosa, a severely disabling hereditary skin fragility disorder, is caused by mutations in the gene coding for collagen VII, a specialized adhesion component of the dermal-epidermal junction zone. Both recessive and dominant forms are known; the latter account for about 40% of cases. Patients with dominant dystrophic epidermolysis bullosa exhibit a spectrum of symptoms ranging from mild localized to generalized skin manifestations. Individuals with the same mutation can display substantial phenotypic variance, emphasizing the role of modifying genes in this disorder. The etiology of dystrophic epidermolysis bullosa has been known for around two decades; however, important pathogenetic questions such as involvement of modifier genes remain unanswered and a causative therapy has yet to be developed. Much of the failure to make progress in these areas is due to the lack of suitable animal models that capture all aspects of this complex monogenetic disorder. Here, we report the first rat model of dominant dystrophic epidermolysis bullosa. Affected rats carry a spontaneous glycine to aspartic acid substitution, p.G1867D, within the main structural domain of collagen VII. This confers dominant-negative interference of protein folding and decreases the stability of mutant collagen VII molecules and their polymers, the anchoring fibrils. The phenotype comprises fragile and blister-prone skin, scarring and nail dystrophy. The model recapitulates all signs of the human disease with complete penetrance. Homozygous carriers of the mutation are more severely affected than heterozygous ones, demonstrating for the first time a gene-dosage effect of mutated alleles in dystrophic epidermolysis bullosa. This novel viable and workable animal model for dominant dystrophic epidermolysis bullosa will be valuable for addressing molecular disease mechanisms, effects of modifying genes, and development of novel molecular therapies for patients with dominantly transmitted skin disease.
Zimmer A, Lang D, ..., Rensing S, Reski R
Reannotation and extended community resources for the genome of the non-seed plant Physcomitrella patens provide insights into the evolution of plant gene structures and functions
2013 BMC GENOMICS, Band: 14
KurzfassungBackground: The moss Physcomitrella patens as a model species provides an important reference for early-diverging lineages of plants and the release of the genome in 2008 opened the doors to genome-wide studies. The usability of a reference genome greatly depends on the quality of the annotation and the availability of centralized community resources. Therefore, in the light of accumulating evidence for missing genes, fragmentary gene structures, false annotations and a low rate of functional annotations on the original release, we decided to improve the moss genome annotation. Results: Here, we report the complete moss genome re-annotation (designated V1.6) incorporating the increased transcript availability from a multitude of developmental stages and tissue types. We demonstrate the utility of the improved P. patens genome annotation for comparative genomics and new extensions to the cosmoss.org resource as a central repository for this plant “flagship” genome. The structural annotation of 32,275 protein-coding genes results in 8387 additional loci including 1456 loci with known protein domains or homologs in Plantae. This is the first release to include information on transcript isoforms, suggesting alternative splicing events for at least 10.8% of the loci. Furthermore, this release now also provides information on non-protein-coding loci. Functional annotations were improved regarding quality and coverage, resulting in 58% annotated loci (previously: 41%) that comprise also 7200 additional loci with GO annotations. Access and manual curation of the functional and structural genome annotation is provided via the www.cosmoss.org model organism database. Conclusions: Comparative analysis of gene structure evolution along the green plant lineage provides novel insights, such as a comparatively high number of loci with 5’-UTR introns in the moss. Comparative analysis of functional annotations reveals expansions of moss house-keeping and metabolic genes and further possibly adaptive, lineage-specific expansions and gains including at least 13% orphan genes.
Mendoza M, Karlin I, Succi S, Herrmann H
Relativistic lattice Boltzmann model with improved dissipation
2013 PHYSICAL REVIEW D, Band: 87, Nummer: 6
KurzfassungWe develop a relativistic lattice Boltzmann (LB) model, providing a more accurate description of dissipative phenomena in relativistic hydrodynamics than previously available with existing LB schemes. The procedure applies to the ultrarelativistic regime, in which the kinetic energy (temperature) far exceeds the rest mass energy, although the extension to massive particles and/or low temperatures is conceptually straightforward. In order to improve the description of dissipative effects, the Maxwell-Juttner distribution is expanded in a basis of orthonormal polynomials, so as to correctly recover the third-order moment of the distribution function. In addition, a time dilatation is also applied, in order to preserve the compatibility of the scheme with a Cartesian cubic lattice. To the purpose of comparing the present LB model with previous ones, the time transformation is also applied to a lattice model which recovers terms up to second order, namely up to the energy-momentum tensor. The approach is validated through quantitative comparison between the second- and third-order schemes with Boltzmann approach multiparton scattering (the solution of the full relativistic Boltzmann equation) for moderately high viscosity and velocities, and also with previous LB models in the literature. Excellent agreement with BAMPS and more accurate results than previous relativistic lattice Boltzmann models are reported. DOI: 10.1103/PhysRevD.87.065027
Tasca D, Rudnicki L, Gomes R, Toscano F, Walborn S
Reliable Entanglement Detection under Coarse-Grained Measurements
2013 PHYSICAL REVIEW LETTERS, Band: 110, Nummer: 21
KurzfassungWe derive reliable entanglement witnesses for coarse-grained measurements on continuous variable systems. These witnesses never return a “false positive” for identification of entanglement, under any degree of coarse graining. We show that even in the case of Gaussian states, entanglement witnesses based on the Shannon entropy can outperform those based on variances. We apply our results to experimental identification of spatial entanglement of photon pairs.
Dumit V, Kuettner V, Kaeppler J, Piera-Velazquez S, Jimenez S, Bruckner-Tuderman L, Uitto J, Dengjel J
Resemblances between scleroderma and ageing in skin fibroblasts
2013 JOURNAL OF INVESTIGATIVE DERMATOLOGY, Band: 133, Nummer: 1
Jahanshahi K, Botiz I, Reiter R, Scherer H, Reiter G
Reversible Nucleation, Growth, and Dissolution of Poly(gamma-benzyl L-glutamate) Hexagonal Columnar Liquid Crystals by Addition and Removal of a Nonsolvent
2013 CRYSTAL GROWTH & DESIGN, Band: 13, Nummer: 10, Seiten: 4490 - 4494
KurzfassungWe have investigated the process of nucleation and growth and its reversal (i.e., dissolution) of ordered poly(gamma-benzyl L-glutamate) (PBLG) objects in thin film solutions containing a few percent of alpha-helical PBLG dissolved in chloroform Nucleation, growth, and dissolution rate were controlled by adding and removing, respectively, defined amounts of a nonsolvent (methanol), introduced through the vapor phase by regulating its flow rate and vapor pressure. Adding methanol to the isotropic polymer solution allowed for the induction of nucleation and growth, even with polymer solutions of very low concentrations, which were significantly below the solubility limit (equilibrium volume fraction). The variation of the number density of nuclei with the supersaturation ratio was found to fit well the predictions of the classical nucleation theory, for all equilibrium concentrations. For a given supersaturation ratio, fewer objects were nucleated for lower equilibrium concentrations.
Botiz I, Freyberg P, Stingelin N, Yang A, Reiter G
Reversibly Slowing Dewetting of Conjugated Polymers by Light
2013 MACROMOLECULES, Band: 46, Nummer: 6, Seiten: 2352 - 2356
KurzfassungDewetting, i.e., the retraction of a fluid from a surface it “dislikes”, is a macroscopic phenomenon controlled through parameters like viscosity and surface tension on length-scales much larger than the size of the molecules. So far, dewetting was known to proceed in the same manner, independent of the dewetting film being illuminated by light or not, e.g., through an optical microscope. Here, we demonstrate that the velocity of dewetting of conjugated polymers can be reversibly tuned through appropriate exposure to light. We relate this observation to the absorption of photons of suitable energy resulting in the generation of excitons which may partially delocalize along and across polymer chains and so induce changes in polymer chain conformation. Such changes, in turn, may cause stiffening or overlap of polymer chains and thus lead to macroscopically detectable differences in behavior of an ensemble of conjugated molecules expressed via material properties like viscosity.
Rigas S, Ditengou F, ..., Palme K, Hatzopoulos P
Root gravitropism and root hair development constitute coupled developmental responses regulated by auxin homeostasis in the Arabidopsis root apex
2013 NEW PHYTOLOGIST, Band: 197, Nummer: 4, Seiten: 1130 - 1141
KurzfassungActive polar transport establishes directional auxin flow and the generation of local auxin gradients implicated in plant responses and development. Auxin modulates gravitropism at the root tip and root hair morphogenesis at the differentiation zone. Genetic and biochemical analyses provide evidence for defective basipetal auxin transport in trh1 roots. The trh1, pin2, axr2 and aux1 mutants, and transgenic plants overexpressing PIN1, all showing impaired gravity response and root hair development, revealed ectopic PIN1 localization. The auxin antagonist hypaphorine blocked root hair elongation and caused moderate agravitropic root growth, also leading to PIN1 mislocalization. These results suggest that auxin imbalance leads to proximal and distal developmental defects in Arabidopsis root apex, associated with agravitropic root growth and root hair phenotype, respectively, providing evidence that these two auxin-regulated processes are coupled. Cell-specific subcellular localization of TRH1-YFP in stele and epidermis supports TRH1 engagement in auxin transport, and hence impaired function in trh1 causes dual defects of auxin imbalance. The interplay between intrinsic cues determining root epidermal cell fate through the TTG/GL2 pathway and environmental cues including abiotic stresses modulates root hair morphogenesis. As a consequence of auxin imbalance in Arabidopsis root apex, ectopic PIN1 mislocalization could be a risk aversion mechanism to trigger root developmental responses ensuring root growth plasticity.
Palme K, Teale W
Root systems analysis branches out
2013 MOLECULAR SYSTEMS BIOLOGY, Band: 9
Seibaek L, Hounsgaard L, Hvidt N
Secular, Spiritual, and Religious Existential Concerns of Women with Ovarian Cancer during Final Diagnostics and Start of Treatment
2013 EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
KurzfassungIntroduction. This paper deals with secular, spiritual, and religious existential concerns during severe illness. Materials and Methods. Qualitative research interviews were made before and after surgery with women who underwent final diagnostics, surgery, and chemotherapy for ovarian cancer. By applying a phenomenological-hermeneutic text interpretation methodology the findings were systematically identified, placed into meaning structures, interpreted, and critically discussed. Results. The analysis offered insight into the complexity of challenges and personal development over time in being a woman with ovarian cancer during her first treatment period. Although the women experienced their health to be seriously threatened, they also felt hope, will, and courage. The diagnostic procedures and treatment had comprehensive impact on their lives. However, hope and spirituality were important resources of comfort and meaning. Conclusion. Hope and courage to face life represent significant personal resources that are created not only in the interplay between body and mind but also between patients and their healthcare professionals. The women dealt with this in a dialectical manner, so that hope and despair could be present simultaneously. In this process secular, spiritual, and religious existential meaning orientations assisted the women in creating new narratives and obtain new orientations in life.
Lv C, Xue Q, ..., Yan Z
Self-assembly of double helical nanostructures inside carbon nanotubes
2013 NANOSCALE, Band: 5, Nummer: 10, Seiten: 4191 - 4199
KurzfassungWe use molecular dynamics (MD) simulations to show that a DNA-like double helix of two poly(acetylene) (PA) chains can form inside single-walled carbon nanotubes (SWNTs). The computational results indicate that SWNTs can activate and guide the self-assembly of polymer chains, allowing them to adopt a helical configuration in a SWNT through the combined action of the van der Waals potential well and the p-p stacking interaction between the polymer and the inner surface of SWNTs. Meanwhile both the SWNT size and polymer chain stiffness determine the outcome of the nanostructure. Furthermore, we also found that water clusters encourage the self-assembly of PA helical structures in the tube. This molecular model may lead to a better understanding of the formation of a double helix biological molecule inside SWNTs. Alternatively, it could form the basis of a novel nanoscale material by utilizing the ‘empty’ spaces of SWNTs.
Thomas P, Straube A, Timmer J, Fleck C, Grima R
Signatures of nonlinearity in single cell noise-induced oscillations
2013 JOURNAL OF THEORETICAL BIOLOGY, Band: 335, Seiten: 222 - 234
KurzfassungA class of theoretical models seeks to explain rhythmic single cell data by postulating that they are generated by intrinsic noise in biochemical systems whose deterministic models exhibit only damped oscillations. The main features of such noise-induced oscillations are quantified by the power spectrum which measures the dependence of the oscillatory signal’s power with frequency. In this paper we derive an approximate closed-form expression for the power spectrum of any monostable biochemical system close to a Hopf bifurcation, where noise-induced oscillations are most pronounced. Unlike the commonly used linear noise approximation which is valid in the macroscopic limit of large volumes, our theory is valid over a wide range of volumes and hence affords a more suitable description of single cell noise-induced oscillations. Our theory predicts that the spectra have three universal features: (i) a dominant peak at some frequency, (ii) a smaller peak at twice the frequency of the dominant peak and (iii) a peak at zero frequency. Of these, the linear noise approximation predicts only the first feature while the remaining two stem from the combination of intrinsic noise and nonlinearity in the law of mass action. The theoretical expressions are shown to accurately match the power spectra determined from stochastic simulations of mitotic and circadian oscillators. Furthermore it is shown how recently acquired single cell rhythmic fibroblast data displays all the features predicted by our theory and that the experimental spectrum is well described by our theory but not by the conventional linear noise approximation. (C) 2013 Elsevier Ltd. All rights reserved.
Kurek A, Xalter R, Stuerzel M, Muelhaupt R
Silica Nanofoam (NF) Supported Single- and Dual-Site Catalysts for Ethylene Polymerization with Morphology Control and Tailored Bimodal Molar Mass Distributions
2013 MACROMOLECULES, Band: 46, Nummer: 23, Seiten: 9197 - 9201
KurzfassungHighly active single- and dual-site catalysts supported on silica nanofoams (NF) enable the control of both polyethylene (PE) morphology and tailoring of bimodal PE molar mass distribution in catalytic ethylene polymerization. In a templating process, aqueous polystyrene (PS) nano suspensions are mineralized and calcinated at 600 degrees C, thus producing NF with specific surface area of 1200 m(2)/g and average pore diameter varying between 20 and 80 nm. Mineralization of the aqueous PS nano suspensions in a water-in-oil emulsion affords spherical NF with average diameter of 40 mu m and control of pore size. The methylalumoxane- (MAO-) tethered NF immobilizes single-site catalysts such as metallocene (nBuZr), bisiminopyridine iron(II) (Fe) and constrained geometry chinolyl cyclopentadienyl chromium(III) complexes (Cr-1). Immobilization of binary blends of Fe/Cr-1 and nBuZr/Cr-1 affords NF-supported dual-site catalysts. The catalyst activity, PE particle size and molecular weight distribution varies as a function of the NF pore size. Typically, macroporous NF (pore size of 75 nm) are effective supports for Cr-1, producing ultrahigh molecular weight polyethylene (UHMWPE, M-w > 10(6) g/mol). Dual -site catalysts such as nBuZr/Cr-1 on mesoporous NF (pore size of 20 nm) enable tailoring of bimodal PE molar mass distribution with UHMWPE content increasing with increasing Cr-1/nBuZr molar ratio.
Schweitzer J, Loehr H, Bonkowsky J, Huebscher K, Driever W
Sim1a and Arnt2 contribute to hypothalamo-spinal axon guidance by regulating Robo2 activity via a Robo3-dependent mechanism
2013 DEVELOPMENT, Band: 140, Nummer: 1, Seiten: 93 - 106
KurzfassungPrecise spatiotemporal control of axon guidance factor expression is a prerequisite for formation of functional neuronal connections. Although Netrin/Dcc- and Robo/Slit-mediated attractive and repulsive guidance of commissural axons have been extensively studied, little is known about mechanisms controlling mediolateral positioning of longitudinal axons in vertebrates. Here, we use a genetic approach in zebrafish embryos to study pathfinding mechanisms of dopaminergic and neuroendocrine longitudinal axons projecting from the hypothalamus into hindbrain and spinal cord. The transcription factors Sim1a and Arnt2 contribute to differentiation of a defined population of dopaminergic and neuroendocrine neurons. We show that both factors also control aspects of axon guidance: Sim1a or Arnt2 depletion results in displacement of hypothalamo-spinal longitudinal axons towards the midline. This phenotype is suppressed in robo3 guidance receptor mutant embryos. In the absence of Sim1a and Arnt2, expression of the robo3 splice isoform robo3a.1 is increased in the hypothalamus, indicating negative control of robo3a.1 transcription by these factors. We further provide evidence that increased Robo3a.1 levels interfere with Robo2-mediated repulsive axon guidance. Finally, we show that the N-terminal domain unique to Robo3a.1 mediates the block of Robo2 repulsive activity. Therefore, Sim1a and Arnt2 contribute to control of lateral positioning of longitudinal hypothalamic-spinal axons by negative regulation of robo3a.1 expression, which in turn attenuates the repulsive activity of Robo2.
Romero D, Kogan K, Cubukcu A, Urban G
Simultaneous flow and thermal conductivity measurement of gases utilizing a calorimetric flow sensor
2013 SENSORS AND ACTUATORS A-PHYSICAL, Band: 203, Seiten: 225 - 233
KurzfassungThis contribution presents a calorimetric flow sensor that is capable of determining the thermal conductivity of gases (k) under flow conditions. The measuring principle relies on using high frequency heat generation at 200 Hz in order to confine the AC heat transfer into a thin region over the surface of the channel wall, where the flow velocity profile is always close to zero. The thermal conductivity of several common gases and their mixtures is measured for flow rates up to 750 sccm. The sensor takes advantage of DC excitation to measure the flow rate (Q) provided that the volumetric heat capacity (pc(p)) or the thermal diffusivity (alpha =k/(pc(p))) of the gas is known. This paper also presents two analytical models that qualitatively describe the measuring principles. Theoretically predicted functions fit well the experimental results.
Leyva-Castillo J, Hener P, Michea P, Karasuyama H, Chan S, Soumelis V, Li M
Skin thymic stromal lymphopoietin initiates Th2 responses through an orchestrated immune cascade
2013 NATURE COMMUNICATIONS, Band: 4, Seite: UNSP 2847
KurzfassungThymic stromal lymphopoietin (TSLP) has emerged as a key initiator in Th2 immune responses, but the TSLP-driven immune cascade leading to Th2 initiation remains to be delineated. Here, by dissecting the cellular network triggered by mouse skin TSLP in vivo, we uncover that TSLP-promoted IL-4 induction in CD4(+) T cells in skin-draining lymph nodes is driven by an orchestrated ‘DC-T-Baso-T’ cascade, which represents a sequential cooperation of dendritic cells (DCs), CD4(+) T cells and basophils. Moreover, we reveal that TSLP-activated DCs prime naive CD4(+) Tcells to produce IL-3 via OX40L signalling and demonstrate that the OX40L-IL-3 axis has a critical role in mediating basophil recruitment, CD4(+) T-cell expansion and Th2 priming. These findings thus add novel insights into the cellular network and signal axis underlying the initiation of Th2 immune responses.
Bartels B, Mintert F
Smooth optimal control with Floquet theory
2013 PHYSICAL REVIEW A, Band: 88, Nummer: 5, Seite: 052315
KurzfassungThis paper describes an approach to construct temporally shaped control pulses that drive a quantum system toward desired properties. A parametrization in terms of periodic functions with predefined frequencies permits us to realize a smooth, typically simple shape of the pulses; their optimization can be performed based on a variational analysis with Floquet theory. As we show with selected specific examples, this approach permits us to control the dynamics of interacting spins, such that gate operations and entanglement dynamics can be implemented with very high accuracy.
Weiss D, Greiner A, Lienemann J, Korvink J
Sph based optimization of electrowetting-driven digital microfluidics with advanced actuation patterns
2013 INTERNATIONAL JOURNAL OF MODERN PHYSICS C, Band: 24, Nummer: 12, SI
KurzfassungFast and thorough mixing is a crucial operation of digital micro fluidic devices, where discrete and small fluid portions are moved and processed. In this paper, we want to analyze and to optimize the mixing process by substituting conventional motion and superposing oscillatory and translational modes. An accurate multiphase smoothed particle hydrodynamics (SPH) discretization for incompressible flow is instantiated. Different harmonic excitation patterns for the solid-liquid surface energy are applied and their influence on droplet mode shapes, formation of eddies and the Shannon entropy of droplet fluid components are measured. We tailor enhanced actuation patterns which improve mixing grade and reduce mixing time.
Erichsen NB, Buessing A
Spiritual Needs of Elderly Living in Residential/Nursing Homes
2013 EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
KurzfassungWhile the research on spiritual needs of patients with chronic and life-threatening diseases increases, there is limited knowledge about psychosocial and spiritual needs of elderly living in residential/nursing homes. We were interested in which needs were of relevance at all, and how these needs are related to life satisfaction and mood states. For that purpose we enrolled 100 elderly living in residential/nursing homes (mean age 84 +/- 7 years, 82% women) and provided standardized questionnaires, that is, Spiritual Needs Questionnaire (SpNQ), Brief Multidimensional Life Satisfaction Scale (BMLSS), Quality of Life in Elders with Multimorbidity (FLQM) questionnaire, and a mood states scale (ASTS). Religious needs and Existential needs were of low relevance, while inner peace needs were of some and needs for giving/generativity of highest relevance. Regression analyses revealed that the specific needs were predicted best by religious trust and mood states, particularly tiredness. However, life satisfaction and quality of life were not among the significant predictors. Most had the intention to connect with those who will remember them, although they fear that there is limited interest in their concerns. It remains an open issue how these unmet needs can be adequately supported.
Bussing A, Gunther A, Baumann K, Frick E, Jacobs C
Spiritual dryness as a measure of a specific spiritual crisis in catholic priests: associations with symptoms of burnout and distress.
2013 Evid-based Compl Alt, Band: 2013, Seiten: 246797 - 246797
Bussing A, Janko A, Baumann K, Hvidt NC, Kopf A
Spiritual needs among patients with chronic pain diseases and cancer living in a secular society.
2013 Pain Med, Band: 14, Nummer: 9, Seiten: 1362 - 1373
Viftrup D, Hvidt N, Buus N
Spiritually and Religiously Integrated Group Psychotherapy: A Systematic Literature Review
2013 EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
KurzfassungWe systematically reviewed the research literature on spiritually and religiously integrated group psychotherapy to answer the following three questions: first, how are spirituality and religiosity defined; second, how are spiritual and religious factors characterized and integrated into group psychotherapy; and, third, what is the outcome of the group psychotherapies? We searched in two databases: PsycINFO and PubMed. Inclusion and exclusion criteria and checklists from standardized assessment tools were applied to the research literature. Qualitative and quantitative papers were included. In total, 8 articles were considered eligible for the review. Findings from the evaluation suggested that the concepts of spirituality and religiosity were poorly conceptualized and the way in which spiritual and religious factors were integrated into such group psychotherapies, which distinguished it from other types of group psychotherapies, was not fully conceptualized or understood either. However, clear and delimited conceptualization of spiritual and religious factors is crucial in order to be able to conclude the direct influences of spiritual or religious factors on outcomes. Implications for spiritually or religiously integrated group psychotherapy and conducting research in this field are propounded.
Reiter G
Stability of Thin Liquid Films
2013 NANOSCALE LIQUID INTERFACES: WETTING, PATTERNING, AND FORCE MICROSCOPY AT THE MOLECULAR SCALE, Seiten: 155 - 191
KurzfassungAlthough weak but long-ranged intermolecular interactions like dispersion forces are present everywhere, we often do not consider them as important. However, when symmetry is broken at interfaces, the strength of these forces becomes clearly relevant, and due to their long-range nature they may have drastic consequences on the stability of thin films. We demonstrate that a force (per unit area) of less than 1 Pa is capable of inducing morphological changes in up to 100 nm thick fluid films, even if molecules are chemically attached to the substrate. We present experimental results on the temporal evolution of different morphologies of unstable thin liquid polymer films caused by destabilizing intermolecular forces. Four distinct stages of pattern evolution have been identified: (A) amplification of surface fluctuations, (B) breakup of the film and formation of holes, (C) growth and coalescence of holes, and (D) droplet formation and ripening. Besides a linear dependence on film viscosity and surface tension, the time tau for film rupture varied significantly with film thickness h (tau similar to h(5)), as expected by theory. In addition, the influence of the bounding media is investigated by covering such films with different bounding liquids, thus varying the interfacial tension by two orders of magnitude. Clearly, an increase in compatibility between the film and the bounding liquid results in a faster amplification of an instability with a shorter characteristic wavelength. Inversely, based on the characteristic parameters describing the instability, we are able to determine extremely small interfacial tensions with a remarkable accuracy. These results demonstrate the relevance of long-range forces, even at amazingly large separations, with implications in many fields, ranging from physical properties of thin films to biology.
Witt B, Mintert F
Stationary quantum coherence and transport in disordered networks
2013 NEW JOURNAL OF PHYSICS, Band: 15, Seite: 093020
KurzfassungWe examine the excitation transport across quantum networks that are continuously driven by a constant and incoherent source. In particular we investigate the coherence properties of incoherently driven networks by employing recent tools from entanglement theory that enable a rigorous interpretation of coherence in the site basis. With these tools at hand we identify coherent delocalization of excitations over several sites to be a crucial prerequisite for highly efficient transport across networks driven by an incoherent source. These results are set into context with the latest discussion of the occurrence of coherence in molecular complexes that are driven by incoherent sun light.
Menard G, Gilbert T, Hatnean J, Kraft Anne, Krossing I, Stephan D
Stoichiometric Reduction of CO2 to CO by Phosphine/AIX(3)-Based Frustrated Lewis Pairs
2013 ORGANOMETALLICS, Band: 32, Nummer: 15, Seiten: 4416 - 4422
KurzfassungThe reactions of the bulky phosphines Mes(3)P or (otol)(3)P with AlX3 (X = I, Br, Cl) and CO2 are probed and shown to give complexes of the form Mes(3)PC(OAlX3)(2) (X = I (3), Br (4), Cl (S)) and (otol)(3)PC(OAll(3))(2) (6). The former compounds under CO2 are further transformed to Mes(3)PC(OAlX2)(2)OAlX3 (X = I (8), Br (10)) and [Mes(3)PX][AlX4] (X = I (9), Br (11)). These latter reactions are thought to proceed via dissociation of alane, as evidenced by the generation of (otol)(3)PC(OAl(C6F5)(3)) from (otol)(3)PC(OAl(C6F5)(3))(2) (7) and the isolation of (otol)(3)PC(O)OAl(OC(CF3)(3))(3) (15). Subsequent insertion of CO2 into the Al-X bond is evidenced by the characterization of [(C6F5)C(O)OAl(C6F5)(2)](2) (14) from the reaction of Al(C6F5)(3) and CO2. The isolation of Al(C6F5)(3)center dot(2)-(C6H5Br) (16) also suggests dissociation of Al(C6F5)(3) from 7 may be facilitated by interactions with solvent. Kinetics of the formation of 8/9 from 3 show the reaction is first order in 3 and CO2 and the rate-determining step involves an associative process. A mechanism involving dissociation of alane and subsequent insertion of CO2 into the Al-X bond is proposed.
Marek M, Kannan S, , Sippl W, Jung M, et al.
Structural Basis for the Inhibition of Histone Deacetylase 8 (HDAC8), a Key Epigenetic Player in the Blood Fluke Schistosoma mansoni
2013 PLOS PATHOGENS, Band: 9, Nummer: 9
KurzfassungThe treatment of schistosomiasis, a disease caused by blood flukes parasites of the Schistosoma genus, depends on the intensive use of a single drug, praziquantel, which increases the likelihood of the development of drug-resistant parasite strains and renders the search for new drugs a strategic priority. Currently, inhibitors of human epigenetic enzymes are actively investigated as novel anti-cancer drugs and have the potential to be used as new anti-parasitic agents. Here, we report that Schistosoma mansoni histone deacetylase 8 (smHDAC8), the most expressed class I HDAC isotype in this organism, is a functional acetyl-L-lysine deacetylase that plays an important role in parasite infectivity. The crystal structure of smHDAC8 shows that this enzyme adopts a canonical alpha/beta HDAC fold, with specific solvent exposed loops corresponding to insertions in the schistosome HDAC8 sequence. Importantly, structures of smHDAC8 in complex with generic HDAC inhibitors revealed specific structural changes in the smHDAC8 active site that cannot be accommodated by human HDACs. Using a structure-based approach, we identified several small-molecule inhibitors that build on these specificities. These molecules exhibit an inhibitory effect on smHDAC8 but show reduced affinity for human HDACs. Crucially, we show that a newly identified smHDAC8 inhibitor has the capacity to induce apoptosis and mortality in schistosomes. Taken together, our biological and structural findings define the framework for the rational design of small-molecule inhibitors specifically interfering with schistosome epigenetic mechanisms, and further support an anti-parasitic epigenome targeting strategy to treat neglected diseases caused by eukaryotic pathogens.
Mostarda S, Levi F, Prada-Gracia D, Mintert F, Rao F
Structure-dynamics relationship in coherent transport through disordered systems.
2013 Nat Commun, Band: 4, Seiten: 2296 - 2296
Feng L, Benner P, Korvink J
Subspace recycling accelerates the parametric macro-modeling of MEMS
2013 INTERNATIONAL JOURNAL FOR NUMERICAL METHODS IN ENGINEERING, Band: 94, Nummer: 1, Seiten: 84 - 110
KurzfassungA fast computational technique that speeds up the process of parametric macro-model extraction is proposed. An efficient starting point is the technique of parametric model order reduction (PMOR). The key step in PMOR is the computation of a projection matrix V, which requires the computation of multiple moment matrices of the underlying system. In turn, for each moment matrix, a linear system with multiple right-hand sides has to be solved. Usually, a considerable number of linear systems must be solved when the system includes more than two free parameters. If the original system is of very large size, the linear solution step is computationally expensive. In this paper, the subspace recycling algorithm outer generalized conjugate residual method combined with generalized minimal residual method with deflated restarting (GCRO-DR), is considered as a basis to solve the sequence of linear systems. In particular, two more efficient recycling algorithms, G-DRvar1 and G-DRvar2, are proposed. Theoretical analysis and simulation results show that both the GCRO-DR method and its variants G-DRvar1 and G-DRvar2 are very efficient when compared with the standard solvers. Furthermore, the presented algorithms overcome the bottleneck of a recently proposed subspace recycling method the modified Krylov recycling generalized minimal residual method. From these subspace recycling algorithms, a PMOR process for macro-model extraction can be significantly accelerated. Copyright (c) 2013 John Wiley & Sons, Ltd.
Scholz F, Himmel D, Scherer H, Krossing I
Superacidic or Not ...? Synthesis, Characterisation, and Acidity of the Room-Temperature Ionic Liquid [C(CH3)(3)](+)[Al2Br7](-)
2013 CHEMISTRY-A EUROPEAN JOURNAL, Band: 19, Nummer: 1, Seiten: 109 - 116
KurzfassungThe room-temperature ionic liquid (RT-IL) [C(CH3)(3)](+)[Al2Br7](-) (m. p. 2 degrees C) was generated by bromide abstraction from tert-butyl bromide with the Lewis acid aluminum bromide in the absence of solvent. The crystal structure of the tert-butyl cation salt was determined by X-ray diffraction. NMR, IR, and Raman spectroscopy, as well as quantum-chemical and thermo-dynamic calculations, confirm the composition of this RT-IL. Thus, one may consider this RT-IL to be a readily accessible (and on a large scale) cationic Bronsted acid (protonated isobutene) with the potential for further reactivity. Based on the new absolute Bronsted acidity scale, we calculated an absolute pH(abs) value of 171 for liquid bulk [C(CH3)(3)](+)[Al2Br7](-). This value is about as acidic as 100% sulfuric acid (pH(abs) = 171) and, thus, on the edge of superacidity.
Mueller K, Engesser R, Timmer J, Nagy F, Zurbriggen M, Weber W
Synthesis of phycocyanobilin in mammalian cells
2013 CHEMICAL COMMUNICATIONS, Band: 49, Nummer: 79, Seiten: 8970 - 8972
KurzfassungThe chromophore 3-Z phycocyanobilin (PCB, (2R,3Z)-8,12-bis-(2-carboxyethyl)-18-ethyl-3-ethylidene-2,7,13,17-tetram ethyl-2,3-dihydrobilin-1,19(21H,24H)-dione) mediates red and far-red light perception in natural and synthetic biological systems. Here we describe a PCB synthesis strategy in mammalian cells. We optimize the production by co-localizing the biocatalysts to the substrate source, by coordinating the availability of the biocatalysts and by reducing the degradation of the reaction product. We show that the resulting PCB levels of 2 mu M are sufficient to sustain the functionality of red light-responsive optogenetic tools suitable for the light-inducible control of gene expression in mammalian cells.
Kubo M, Imai A, Nishiyama T, Ishikawa M, Sato Y, Kurata T, Hiwatashi Y, Reski R, Hasebe M
System for stable beta-estradiol-inducible gene expression in the moss Physcomitrella patens.
2013 Plos One, Band: 8, Nummer: 9, Seiten: e77356 - e77356
Speck J, Raeuber C, ..., Arndt K, Mueller K
TAT hitchhiker selection expanded to folding helpers, multimeric interactions and combinations with protein fragment complementation
2013 PROTEIN ENGINEERING DESIGN & SELECTION, Band: 26, Nummer: 3, Seiten: 225 - 242
KurzfassungThe twin-arginine translocation (TAT) pathway of the bacterial cytoplasmic membrane mediates translocation only of proteins that accomplished a native-like conformation. We deploy this feature in modular selection systems for directed evolution, in which folding helpers as well as dimeric or oligomeric proteinprotein interactions enable TAT-dependent translocation of the resistance marker TEM -lactamase (L). Specifically, we demonstrate and analyze selection of (i) enhancers for folding by direct TAT translocation selection of a target protein interposed between the TorA signal sequence and L, (ii) dimeric or oligomeric proteinprotein interactions by hitchhiker translocation (HiT) selection of proteins fused to the TorA signal sequence and to the L, respectively and (iii) heterotrimeric proteinprotein interactions by combining HiT with protein fragment complementation selection of proteins fused to two split L fragments and TorA, respectively. The lactamase fragments were additionally engineered for improved activity and stability. Applicability was benchmarked with interaction partners of known affinity and multimerization whereby cellular fitness correlated well with biophysical protein properties. Ultimately, the HiT selection was employed to identify peptides, which specifically bind to leukemia- and melanoma-relevant target proteins (MITF and ETO) by coiled-coil or tetra-helix-bundle formation with high affinity. The various versions of TAT selection led to inhibiting peptides (iPEPs) of disease-promoting interactions and enabled so far difficult to achieve selections.
Lucas F, Mintert F, Buchleitner A
Tailoring many-body entanglement through local control
2013 PHYSICAL REVIEW A, Band: 88, Nummer: 3
KurzfassungWe construct optimal time-local control pulses based on a multipartite entanglement measure as target functional. The underlying control Hamiltonians are derived in a purely algebraic fashion, and the resulting pulses drive a composite quantum system rapidly into that highly entangled state which can be created most efficiently for a given interaction mechanism, and which bears entanglement that is robust against decoherence. Moreover, it is shown that the control scheme is insensitive to experimental imperfections in first order.
Dautzenberg M, Just A
Temporal characteristics of nitric oxide-, prostaglandin-, and EDHF-mediated components of endothelium-dependent vasodilation in the kidney
2013 AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, Band: 305, Nummer: 9, Seiten: R987 - R998
KurzfassungEndothelium-dependent vasodilation is mediated by nitric oxide (NO), prostaglandins (PG), and endothelium-derived hyperpolarizing factor (EDHF). We studied the contributions and temporal characteristics of these components in the renal vasodilator responses to acetylcholine (ACh) and bradykinin (BK) and in the buffering of vasoconstrictor responses to norepinephrine (NE) and angiotensin II (ANG II). Renal blood flow (RBF) and vascular conductance (RVC) were studied in anesthetized rats in response to renal arterial bolus injections before and after inhibition of NO-synthase (N(G-)nitro-L-arginine methyl ester, L-NAME), cyclooxygenase (indomethacin, INDO), or both. ACh increased RVC peaking at maximal time (t(max)) = 29 s. L-NAME (n = 8) diminished the integrated response and made it substantially faster (t(max) = 18 s). The point-by-point difference caused by L-NAME (= NO component) integrated to 74% of control and was much slower (t(max) = 38 s). INDO (n = 9) reduced the response without affecting t(max) (36 vs. 30 s). The difference (= PG) reached 21% of the control with t(max) = 25 s. L-NAME + INDO (n = 17) reduced the response to 18% and markedly accelerated t(max) to 16s (= EDHF). Results were similar for BK with slightly more PG and less NO contribution than for ACh. Constrictor responses to NE and ANG II were augmented and decelerated by L-NAME and L-NAME + INDO. The calculated difference (= buffering by NO or NO + PG) was slower than the constriction. It is concluded that NO, PG, and EDHF contribute > 50%, 20-40%, and <20% to the renal vasodilator effect of ACh and BK, respectively. EDHF acts substantially faster and less sustained (t(max) = 16 s) than NO and PG (t(max) = 30 s). Constrictor buffering by NO and PG is not constant over time, but renders the constriction less sustained.
Kraft A, Possart J, Scherer H, Beck J, Himmel D, Krossing I
The Al(ORF)(3)/H2O/Phosphane [R-F = C(CF3)(3)] System - Protonation of Phosphanes and Absolute BrOnsted Acidity
2013 EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Nummer: 17, Seiten: 3054 - 3062
KurzfassungThe synthesis of the classical, neutral donor-acceptor adducts Ph2MeP-/Ph3P-/Ph3As-Al(ORF)3 and H2O-Al(ORF)3 [1, 2, 3, 4, ORF = OC(CF3)3] is reported. The intermediate H2O-Al(ORF)3 (4) was generated by substitution of PhF in PhF-Al(ORF)3 with H2O and was analyzed in a long-term NMR study over 22 days. This BrOnsted acidic system was used in orienting experiments to protonate phosphanes such as PMePh2, PPh3, PCy3, P(tBu)3, and PCy2[2,4,6-(iPr)3C6H2]. Depending on the use of one or two equivalents of PhF-Al(ORF)3, the new weakly coordinating anions [(RFO)3Al(-OH)Al(ORF)3]- or [HOAl(ORF)3]- were obtained. However, in dependence of the steric bulk of the phosphanes, stable and unreactive R3P-Al(ORF)3 adducts were also observed in the NMR experiments. The absolute acidity of the key H2O-Al(ORF)3 adduct was evaluated by the relaxed COSMO cluster-continuum (rCCC, COSMO = conductor-like screening model) model in fluorobenzene solution. For a 0.001 M solution of H2O-Al(ORF)3, the medium acidity resulted as -986 kJmol-1 or a pHabs value of 173. Long-term hydrolysis of H2O-Al(ORF)3 (4), probably to give HORF and HOAl(ORF)2 followed by trimerization, gave [HOAl(ORF)2]3 (10), which was identified by X-ray diffraction.
Pinosa F, Begheldo M, ..., Palme K
The Arabidopsis thaliana Mob1A gene is required for organ growth and correct tissue patterning of the root tip
2013 ANNALS OF BOTANY, Band: 112, Nummer: 9, Seiten: 1803 - 1814
KurzfassungThe Mob1 family includes a group of kinase regulators conserved throughout eukaryotes. In multicellular organisms, Mob1 is involved in cell proliferation and apoptosis, thus controlling appropriate cell number and organ size. These functions are also of great importance for plants, which employ co-ordinated growth processes to explore the surrounding environment and respond to changing external conditions. Therefore, this study set out to investigate the role of two Arabidopsis thaliana Mob1-like genes, namely Mob1A and Mob1B, in plant development. A detailed spatio-temporal analysis of Mob1A and Mob1B gene expression was performed by means of bioinformatic tools, the generation of expression reporter lines and in situ hybridization of gene-specific probes. To explore the function of the two genes in plant development, knock-out and knock-down mutants were isolated and their phenotype quantitatively characterized. Transcripts of the two genes were detected in specific sets of cells in all plant organs. Mob1A was upregulated by several stress conditions as well as by abscisic acid and salicylic acid. A knock-out mutation in Mob1B did not cause any visible defect in plant development, whereas suppression of Mob1A expression affected organ growth and reproduction. In the primary root, reduced levels of Mob1A expression brought about severe defects in tissue patterning of the stem cell niche and columella and led to a decrease in meristem size. Moreover, loss of Mob1A function resulted in a higher sensitivity of root growth to abscisic acid. Taken together, the results indicate that arabidopsis Mob1A is involved in the co-ordination of tissue patterning and organ growth, similarly to its orthologues in other multicellular eukaryotes. In addition, Mob1A serves a plant-specific function by contributing to growth adjustments in response to stress conditions.
Spiegelhalder K
The Glasgow Sleep Impact Index (GSII): a novel patient-centred measure for assessing sleep-related quality of life impairment in insomnia disorder.
2013 Sleep Med, Band: 14, Seiten: 493 - 501
Demeyer S, Michoel T, Fostier J, Audenaert P, Pickavet M, Demeester P
The Index-Based Subgraph Matching Algorithm (ISMA): Fast Subgraph Enumeration in Large Networks Using Optimized Search Trees
2013 PLOS ONE, Band: 8, Nummer: 4, Seite: e61183
KurzfassungSubgraph matching algorithms are designed to find all instances of predefined subgraphs in a large graph or network and play an important role in the discovery and analysis of so-called network motifs, subgraph patterns which occur more often than expected by chance. We present the index-based subgraph matching algorithm (ISMA), a novel tree-based algorithm. ISMA realizes a speedup compared to existing algorithms by carefully selecting the order in which the nodes of a query subgraph are investigated. In order to achieve this, we developed a number of data structures and maximally exploited symmetry characteristics of the subgraph. We compared ISMA to a naive recursive tree-based algorithm and to a number of well-known subgraph matching algorithms. Our algorithm outperforms the other algorithms, especially on large networks and with large query subgraphs. An implementation of ISMA in Java is freely available at http://sourceforge.net/projects/isma.
Cooper L, Walls R, ..., Reski R, et al.
The Plant Ontology as a Tool for Comparative Plant Anatomy and Genomic Analyses
2013 PLANT AND CELL PHYSIOLOGY, Band: 54, Nummer: 2
KurzfassungThe Plant Ontology (PO; ext-link-type=”uri” xlink:href=”http://www.plantontology.org/” xmlns:xlink=”http://www.w3.org/1999/xlink”>http://www.plantontolog y.org/) is a publicly available, collaborative effort to develop and maintain a controlled, structured vocabulary (’ontology’) of terms to describe plant anatomy, morphology and the stages of plant development. The goals of the PO are to link (annotate) gene expression and phenotype data to plant structures and stages of plant development, using the data model adopted by the Gene Ontology. From its original design covering only rice, maize and Arabidopsis, the scope of the PO has been expanded to include all green plants. The PO was the first multispecies anatomy ontology developed for the annotation of genes and phenotypes. Also, to our knowledge, it was one of the first biological ontologies that provides translations (via synonyms) in non-English languages such as Japanese and Spanish. As of Release #18 (July 2012), there are about 2.2 million annotations linking PO terms to > 110,000 unique data objects representing genes or gene models, proteins, RNAs, germplasm and quantitative trait loci (QTLs) from 22 plant species. In this paper, we focus on the plant anatomical entity branch of the PO, describing the organizing principles, resources available to users and examples of how the PO is integrated into other plant genomics databases and web portals. We also provide two examples of comparative analyses, demonstrating how the ontology structure and PO-annotated data can be used to discover the patterns of expression of the LEAFY (LFY) and terpene synthase (TPS) gene homologs.
Petersen A, Succi S
The Z-index: A geometric representation of productivity and impact which accounts for information in the entire rank-citation profile
2013 JOURNAL OF INFORMETRICS, Band: 7, Nummer: 4, Seiten: 823 - 832
KurzfassungWe present a simple generalization of Hirsch’s h-index, Z = root h(2) + C/root 5, where C is the total number of citations. Z is aimed at correcting the potentially excessive penalty made by h on a scientist’s highly cited papers, because for the majority of scientists analyzed, we find the excess citation fraction (C - h(2))/C to be distributed closely around the value 0.75, meaning that 75% of the author’s impact is neglected. Additionally, Z is less sensitive to local changes in a scientist’s citation profile, namely perturbations which increase h while only marginally affecting C. Using real career data for 476 physicists careers and 488 biologist careers, we analyze both the distribution of Z and the rank stability of Z with respect to the Hirsch index h and the Egghe index g. We analyze careers distributed across a wide range of total impact, including top-cited physicists and biologists for benchmark comparison. In practice, the Z-index requires the same information needed to calculate h and could be effortlessly incorporated within career profile databases, such as Google Scholar and ResearcherID. Because Z incorporates information from the entire publication profile while being more robust than h and g to local perturbations, we argue that Z is better suited for ranking comparisons in academic decision-making scenarios comprising a large number of scientists. (C) 2013 Elsevier Ltd. All rights reserved.
Ramb R, ..., Weiller C, Grebogi C, Schwarzbauer C, Timmer J, Schelter B
The impact of latent confounders in directed network analysis in neuroscience
2013 PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES, Band: 371, Nummer: 1997, SI, Seite: 20110612
KurzfassungIn the analysis of neuroscience data, the identification of task-related causal relationships between various areas of the brain gives insights about the network of physiological pathways that are active during the task. One increasingly used approach to identify causal connectivity uses the concept of Granger causality that exploits predictability of activity in one region by past activity in other regions of the brain. Owing to the complexity of the data, selecting components for the analysis of causality as a preprocessing step has to be performed. This includes predetermined-and often arbitrary-exclusion of information. Therefore, the system is confounded by latent sources. In this paper, the effect of latent confounders is demonstrated, and paths of influence among three components are studied. While methods for analysing Granger causality are commonly based on linear vector autoregressive models, the effects of latent confounders are expected to be present also in nonlinear systems. Therefore, all analyses are also performed for a simulated nonlinear system and discussed with regard to applications in neuroscience.
Hanfland R, Fischer M, Bruetting W, Wuerfel U, MacKenzie R
The physical meaning of charge extraction by linearly increasing voltage transients from organic solar cells
2013 APPLIED PHYSICS LETTERS, Band: 103, Nummer: 6
KurzfassungCarrier mobility in organic solar cells is almost exclusively determined with the Charge Extraction by Linearly Increasing Voltage (CELIV) technique; indeed much of our understanding of the recombination and charge transport mechanisms in organic solar cells is based on CELIV measurements. However, since the conception of the CELIV method, our understanding of organic semiconductors has significantly advanced. In this work, we critically examine the CELIV methods ability to provide accurate material data in the light of recent advances in our understanding of trap states and their influence on mobility in organic semiconductors. We then apply this knowledge to understand the mechanisms responsible for degradation in organic solar cells. (C) 2013 AIP Publishing LLC.
Prada-Gracia D, Shevchuk R, Rao F
The quest for self-consistency in hydrogen bond definitions.
2013 J Chem Phys, Band: 139, Nummer: 8, Seiten: 084501 - 084501
While P, Korvink J, Shah N, Poole M
Theoretical design of gradient coils with minimum power dissipation: Accounting for the discretization of current density into coil windings
2013 JOURNAL OF MAGNETIC RESONANCE, Band: 235, Seiten: 85 - 94
KurzfassungGradient coil windings are typically constructed from either variable width copper tracks or fixed width wires. Excessive power dissipation within these windings during gradient coil operation limits the maximum drive current or duty cycle of the coil. It is common to design gradient coils in terms of a continuous minimum power current density and to perform a discretization to obtain the locations of the coil tracks or wires. However, the existence of finite gaps between these conductors and a maximum conductor width leads to an underestimation of coil resistance when calculated using the continuous current density. Put equivalently, the actual current density within the tracks or wires is higher than that used in the optimization and this departure results in suboptimal coil designs. In this work, a mapping to an effective current density is proposed to account for these effects and provide the correct contribution to the power dissipation. This enables the design of gradient coils that are genuinely optimal in terms of power minimization, post-discretization. The method was applied to the theoretical design of a variety of small x- and z-gradient coils for use in small animal imaging and coils for human head imaging. Computer-driven comparisons were made between coils designed with and without the current density mapping, in terms of simulated power dissipation. For coils to be built using variable width tracks, the method provides slight reductions in power dissipation in most cases and substantial gains only in cases where the minimum separation between track centre-lines is less than twice the gap size. However, for coils to be built using fixed width wires, very considerable reductions in dissipated power are consistently attainable (up to 60%) when compared to standard approaches of coil optimization. (c) 2013 Elsevier Inc. All rights reserved.
Chandrasekaran S, Faiella G, Prado L, Toelle F, Muelhaupt R, Schulte K
Thermally reduced graphene oxide acting as a trap for multiwall carbon nanotubes in bi-filler epoxy composites
2013 COMPOSITES PART A-APPLIED SCIENCE AND MANUFACTURING, Band: 49, Seiten: 51 - 57
KurzfassungThe effect of thermally reduced graphene oxide (TRGO) on the electrical percolation threshold of multi wall carbon nanotube (MWCNT)/epoxy cured composites is studied along with their combined rheological/electrical behavior in their suspension state. In contrast to MWCNT and carbon black (CB) based epoxy composites, there is no prominent percolation threshold for the bi-filler (TRGO-MWCNT/epoxy) composite. Furthermore, the electrical conductivity of the bi-filler composite is two orders of magnitude lower (similar to 1 x 10(-5) S/m) than the pristine MWCNT/epoxy composites (similar to 1 x 10(-3) S/m). This result is primarily due to the strong interaction between TRGO and MWCNTs. Optical micrographs of the suspension and scanning electron micrographs of the cured composites indicate trapping of MWCNTs onto TRGO sheets. A morphological model describing this interaction is presented. (C) 2013 Elsevier Ltd. All rights reserved.
Svetovoy V, Sanders R, Elwenspoek M
Transient nanobubbles in short-time electrolysis
2013 JOURNAL OF PHYSICS-CONDENSED MATTER, Band: 25, Nummer: 18
KurzfassungWater electrolysis in a microsystem is observed and analyzed on a short-time scale of similar to 10 mu s. The very unusual properties of the process are stressed. An extremely high current density is observed because the process is not limited by the diffusion of electroactive species. The high current is accompanied by a high relative supersaturation, S > 1000, that results in homogeneous nucleation of bubbles. On the short-time scale only nanobubbles can be formed. These nanobubbles densely cover the electrodes and aggregate at a later time to microbubbles. The effect is significantly intensified with a small increase of temperature. Application of alternating polarity voltage pulses produces bubbles containing a mixture of hydrogen and oxygen. Spontaneous reaction between gases is observed for stoichiometric bubbles with sizes smaller than similar to 150 nm. Such bubbles disintegrate violently affecting the surfaces of the electrodes.
Mendoza M, Karlin I, Succi S, Herrmann H
Ultrarelativistic transport coefficients in two dimensions
2013 JOURNAL OF STATISTICAL MECHANICS-THEORY AND EXPERIMENT
KurzfassungWe compute the shear and bulk viscosities, as well as the thermal conductivity, of an ultrarelativistic fluid obeying the relativistic Boltzmann equation in 2 + 1 space time dimensions. The relativistic Boltzmann equation is taken in the single relaxation time approximation, based on two approaches, the first due to Marle and using the Eckart decomposition, and the second proposed by Anderson and Witting and using the Landau-Lifshitz decomposition. In both cases, the local equilibrium is given by a Maxwell-Juttner distribution. It is shown that, apart from slightly different numerical prefactors, the two models lead to a different dependence of the transport coefficients on the fluid temperature, quadratic and linear, for the case of Marle and Anderson-Witting, respectively. However, by modifying the Marle model according to the prescriptions given in previous results, it is found that the temperature dependence becomes the same as for the Anderson-Witting model.
Fischer A, Korvink J, Roxhed N, Stemme G, Wallrabe U, Niklaus F
Unconventional applications of wire bonding create opportunities for microsystem integration
2013 JOURNAL OF MICROMECHANICS AND MICROENGINEERING, Band: 23, Nummer: 8
KurzfassungAutomatic wire bonding is a highly mature, cost-efficient and broadly available back-endprocess, intended to create electrical interconnections in semiconductor chip packaging. Modern production wire-bonding tools can bond wires with speeds of up to 30 bonds per second with placement accuracies of better than 2 mu m, and the ability to form each wire individually into a desired shape. These features render wire bonding a versatile tool also for integrating wires in applications other than electrical interconnections. Wire bonding has been adapted and used to implement a variety of innovative microstructures. This paper reviews unconventional uses and applications of wire bonding that have been reported in the literature. The used wire-bonding techniques and materials are discussed, and the implemented applications are presented. They include the realization and integration of coils, transformers, inductors, antennas, electrodes, through silicon vias, plugs, liquid and vacuum seals, plastic fibers, shape memory alloy actuators, energy harvesters and sensors.
Lichtenthaler M, Higelin A, ..., Krossing I
Univalent Gallium Salts of Weakly Coordinating Anions: Effective Initiators/Catalysts for the Synthesis of Highly Reactive Polyisobutylene
2013 ORGANOMETALLICS, Band: 32, Nummer: 22, Seiten: 6725 - 6735
KurzfassungThe scope of the univalent gallium salts [Ga-(C6H5F)(2)](+)[Al(ORF)(4)](-) and the new completely characterized [Ga(1,3,5-Me3C6H3)(2)](+)[Al(ORF)(4)](-) (R-F = C(CF3)(3)) was investigated in terms of initiating or catalyzing the synthesis of highly reactive poly(2-methylpropylene)-highly reactive polyisobutylene (HR-PIB)-in several solvents. A series of polymerization reactions proved the high efficiency and quality of the univalent gallium salts for the polymerization of isobutylene. The best results were obtained using very low concentrations of [Ga(C6H5F)(2)](+)[Al(ORF)(4)](-) (down to 0.007 mol%) while working at reaction temperatures of up to +/- 0 degrees C and in the noncarcinogenic and non-water hazardous solvent toluene. Under these conditions, HR-PIB with an alpha-content of terminal olefinic double bonds up to 91 mol% and a molecular weight of 1000-2000 was obtained in good yields. Upon changing [Ga(C6H5F)(2)](+)[Al(ORF)(4)](-) for the electron richer [Ga(1,3,5-Me3C6H3)(2)](+)[Al-(ORF)(4)](-), polymerization temperatures could be increased to +10 degrees C. The reactivity of the gallium(I) cations therefore seems to be tunable through ligand exchange reactions. Experimental results, density functional theory calculations, and mass spectrometric investigations point toward a coordinative polymerization mechanism.
Thantanapally C, Patill D, Succi S, Ansumali S
Universal mechanism for saturation of vorticity growth in fully developed fluid turbulence
2013 JOURNAL OF FLUID MECHANICS, Band: 728
KurzfassungNumerical results from large-scale, long-time, simulations of decaying homogeneous turbulence are reported, which indicate that blow-up of inviscid flows is tamed by the emergence of collective dynamics of coherent structures. The simulations also suggest that this collective dynamics might lead to universal behaviour during the transient evolution of turbulence. In particular, simulations with three different initial conditions show evidence of a k(-3) log k spectrum in the transient stage, before the Kolmogorov k(-5/3) asymptotic regime is attained. Such a universal transient might serve as a spectral funnel to the time-asymptotic Kolmogorov spectrum, which is invariably observed in the late stage of all three simulations presented in this work. The present work is entirely based on simulation evidence. However, the statistical analysis of the coherent structures suggests an analogy with population dynamics, which might be conducive to new mathematical models of transient decaying turbulence.
Higelin A, Keller S, Gohringer C, Jones C, Krossing I
Unusual tilted carbene coordination in carbene complexes of gallium(I) and indium(I).
2013 Angew Chem Int Edit, Band: 52, Nummer: 18, Seiten: 4941 - 4944
Harb J, Saleh O, Kittemann D, Neuwald D, Frank W, Reski R
Upregulation of polyphenol-related genes prevents ‘skin burning’ of well-colored ‘Cameo’ apples stored under stressful controlled atmosphere conditions
2013 POSTHARVEST BIOLOGY AND TECHNOLOGY, Band: 77, Seiten: 121 - 127
Kurzfassung‘Skin burning’ of ‘Cameo’ apples resulting in poorly colored fruit can occur in storage under high CO2 condition. To elucidate possible reasons for this physiological disorder, we assessed the differential expression of polyphenol-related genes. Poorly colored and well-colored mature ‘Cameo’ apples were stored under either high (3%) or low (0.7%) CO2 levels, both in combination with 1% O-2, and monitored for seven months for ‘skin burning’. Samples were obtained by the end of storage period, and OCR analyses were conducted using gene specific primers. We found expression levels of chalcone synthase (MdCHS), chalcone isomerase (MdCHI), anthocyanidin synthase (MdANS), flavonol synthase (MdFLS), dihydroflavonolreductase (MdDFR), and leucoanthocyanidinreductase (MdIAR1) genes to be substantially higher in well-colored compared to poorly colored apples. The delay in establishing the stressful controlled atmosphere (CA) storage condition (3% CO2 level) led to significantly higher expression levels of MdIAR1, MdCHI, anthocyanidinreductase (MdANR) and flavanone 3-hydroxylase (MdF3H), which may explain the lower incidence of ‘skin burning’ by delayed CA fruit. On the other hand, after seven months in storage, the expression levels of phenylalanine ammonia-lyase (MdPAL), MdCHS, MdCHI, MdDFR, MdFLS, and MdF3H, were significantly higher in poorly colored injured apples, which reflect a feedback mechanism to synthesize more polyphenols to counteract the stressful storage condition. (C) 2012 Elsevier B.V. All rights reserved.
Chia Gomez L, Bollgruen P, Egunov A, Mager D, Malloggi F, Korvink J, Luchnikov V
Vapour processed self-rolled poly(dimethylsiloxane) microcapillaries form microfluidic devices with engineered inner surface
2013 LAB ON A CHIP, Band: 13, Nummer: 19, Seiten: 3827 - 3831
KurzfassungWe propose a microfluidics device whose main functional part consists of a microcapillary produced by the self-rolling of a thin poly(dimethylsiloxane) film. Rolling is caused by inhomogeneous swelling of the film, pre-treated by oxygen plasma, in the vapour of chloroform. The capillaries are integrated with external electrical circuits by co-rolling electrodes and micro-resistors. The local control of temperature in the tubes by Joule heating is illustrated via the rate of an intra-tubular chemiluminescent reaction. The novel tubes with engineered inner structure can find numerous advanced applications such as functional elements of integrated microfluidics circuits.
Schmidt T, Durr J, Keuper M, Blein T, Palme K, Ronneberger O
Variational attenuation correction in two-view confocal microscopy.
2013 Bmc Bioinformatics, Band: 14, Seiten: 366 - 366
Vithanage D, Devizis A, Abramavicius V, Infahsaeng Y, Abramavicius D, MacKenzie R, Keivanidis P, Yartsev A, Hertel D, Nelson J, Sundstrom V, Gulbinas V
Visualizing charge separation in bulk heterojunction organic solar cells
2013 NATURE COMMUNICATIONS, Band: 4
KurzfassungSolar cells based on conjugated polymer and fullerene blends have been developed as a low-cost alternative to silicon. For efficient solar cells, electron-hole pairs must separate into free mobile charges that can be extracted in high yield. We still lack good understanding of how, why and when carriers separate against the Coulomb attraction. Here we visualize the charge separation process in bulk heterojunction solar cells by directly measuring charge carrier drift in a polymer: fullerene blend with ultrafast time resolution. We show that initially only closely separated (<1 nm) charge pairs are created and they separate by several nanometres during the first several picoseconds. Charge pairs overcome Coulomb attraction and form free carriers on a subnanosecond time scale. Numerical simulations complementing the experimental data show that fast three-dimensional charge diffusion within an energetically disordered medium, increasing the entropy of the system, is sufficient to drive the charge separation process.
Moazenzadeh A, Spengler N, Lausecker R, Rezvani A, Mayer M, Korvink J, Wallrabe U
Wire bonded 3D coils render air core microtransformers competitive
2013 JOURNAL OF MICROMECHANICS AND MICROENGINEERING, Band: 23, Nummer: 11
KurzfassungWe present a novel wafer-level fabrication method for 3D solenoidal microtransformers using an automatic wire bonder for chip-scale, very high frequency regime applications. Using standard microelectromechanical systems fabrication processes for the manufacturing of supporting structures, together with ultra-fast wire bonding for the fabrication of solenoids, enables the flexible and repeatable fabrication, at high throughput, of high performance air core microtransformers. The primary and secondary solenoids are wound one on top of the other in the lateral direction, using a 25 mu m thick insulated wire. Besides commonly available gold wire, we also introduce insulated copper wire to our coil winding process. The influence of copper on the transformer properties is explored and compared to gold. A simulation model based on the solenoids’ wire bonding trajectories has been defined using the FastHenry software to accurately predict and optimize the transformer’s inductive properties. The transformer chips are encapsulated in polydimethylsiloxane in order to protect the coils from environmental influences and mechanical damage. Meanwhile, the effect of the increase in the internal capacitance of the chips as a result of the encapsulation is analyzed. A fabricated transformer with 20 windings in both the primary and the secondary coils, and a footprint of 1 mm(2), yields an inductance of 490 nH, a maximum efficiency of 68%, and a coupling factor of 94%. The repeatability of the coil winding process was investigated by comparing the data of 25 identically processed devices. Finally, the microtransformers are benchmarked to underline the potential of the technology in rendering air core transformers competitive.
Ren HP, Baptista M, Grebogi C
Wireless Communication with Chaos
2013 PHYSICAL REVIEW LETTERS, Band: 110, Nummer: 18, Seite: 184101
KurzfassungThe modern world fully relies on wireless communication. Because of intrinsic physical constraints of the wireless physical media (multipath, damping, and filtering), signals carrying information are strongly modified, preventing information from being transmitted with a high bit rate. We show that, though a chaotic signal is strongly modified by the wireless physical media, its Lyapunov exponents remain unaltered, suggesting that the information transmitted is not modified by the channel. For some particular chaotic signals, we have indeed proved that the dynamic description of both the transmitted and the received signals is identical and shown that the capacity of the chaos-based wireless channel is unaffected by the multipath propagation of the physical media. These physical properties of chaotic signals warrant an effective chaos-based wireless communication system.
Schaefer J, Himmel D, Krossing I
[Au(2-C2H4)3]+[Al(ORF)4] a Stable Homoleptic (Ethene)gold Complex
2013 EUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Nummer: 15, Seiten: 2712 - 2717
KurzfassungThe simple metathesis reaction of the silver(I) weakly coordinating anion (WCA) salt Ag[Al(ORF)4] RF = C(CF3)3 with gold(I) chloride and ethene led to the formation of the second isolable tris(ethene)gold(I) complex, the last missing entry in the triad [M(C2H4)3]+[Al(ORF)4] (M = Cu, Ag, Au). The Au atom is coordinated by three ethene ligands in a distorted trigonal-planar manner in a so-called spoke-wheel arrangement. The formation of the tris(ethene) complex instead of the more expected bis(ethene) complex was analyzed by theoretical investigations and by a BornFajansHaber cycle for [Au(C2H4)3]+[Al(ORF)4] as well as the only other known example [Au(C2H4)3]+[SbF6].
Vehlow C, Hasenauer J, ..., Timmer J, et al.
iVUN: interactive Visualization of Uncertain biochemical reaction Networks
2013 BMC BIOINFORMATICS, Band: 14, Nummer: 19
KurzfassungBackground: Mathematical models are nowadays widely used to describe biochemical reaction networks. One of the main reasons for this is that models facilitate the integration of a multitude of different data and data types using parameter estimation. Thereby, models allow for a holistic understanding of biological processes. However, due to measurement noise and the limited amount of data, uncertainties in the model parameters should be considered when conclusions are drawn from estimated model attributes, such as reaction fluxes or transient dynamics of biological species. Methods and results: We developed the visual analytics system iVUN that supports uncertainty-aware analysis of static and dynamic attributes of biochemical reaction networks modeled by ordinary differential equations. The multivariate graph of the network is visualized as a node-link diagram, and statistics of the attributes are mapped to the color of nodes and links of the graph. In addition, the graph view is linked with several views, such as line plots, scatter plots, and correlation matrices, to support locating uncertainties and the analysis of their time dependencies. As demonstration, we use iVUN to quantitatively analyze the dynamics of a model for Epo-induced JAK2/STAT5 signaling. Conclusion: Our case study showed that iVUN can be used to perform an in-depth study of biochemical reaction networks, including attribute uncertainties, correlations between these attributes and their uncertainties as well as the attribute dynamics. In particular, the linking of different visualization options turned out to be highly beneficial for the complex analysis tasks that come with the biological systems as presented here.
Nazio F, Strappazzon F, Antonioli M, ..., Gretzmeier C, Dengjel J, et al.
mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6
2013 NATURE CELL BIOLOGY, Band: 15, Nummer: 4
KurzfassungAutophagy is important in the basal or stress-induced clearance of bulk cytosol, damaged organelles, pathogens and selected proteins by specific vesicles, the autophagosomes. Following mTOR (mammalian target of rapamycin) inhibition, autophagosome formation is primed by the ULK1 and the beclin-1-Vps34-AMBRA1 complexes, which are linked together by a scaffold platform, the exocyst. Although several regulative steps have been described along this pathway, few targets of mTOR are known, and the cross-talk between ULK1 and beclin 1 complexes is still not fully understood. We show that under non-autophagic conditions, mTOR inhibits AMBRA1 by phosphorylation, whereas on autophagy induction, AMBRA1 is dephosphorylated. In this condition, AMBRA1, interacting with the E3-ligase TRAF6, supports ULK1 ubiquitylation by LYS-63-linked chains, and its subsequent stabilization, self-association and function. As ULK1 has been shown to activate AMBRA1 by phosphorylation, the proposed pathway may act as a positive regulation loop, which may be targeted in human disorders linked to impaired autophagy.