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Showing papers by "University of Würzburg published in 2010"



Journal ArticleDOI
Georges Aad1, Brad Abbott1, Jalal Abdallah1, A. A. Abdelalim1  +2582 moreInstitutions (23)
TL;DR: The simulation software for the ATLAS Experiment at the Large Hadron Collider is being used for large-scale production of events on the LHC Computing Grid, including supporting the detector description, interfacing the event generation, and combining the GEANT4 simulation of the response of the individual detectors.
Abstract: The simulation software for the ATLAS Experiment at the Large Hadron Collider is being used for large-scale production of events on the LHC Computing Grid. This simulation requires many components, from the generators that simulate particle collisions, through packages simulating the response of the various detectors and triggers. All of these components come together under the ATLAS simulation infrastructure. In this paper, that infrastructure is discussed, including that supporting the detector description, interfacing the event generation, and combining the GEANT4 simulation of the response of the individual detectors. Also described are the tools allowing the software validation, performance testing, and the validation of the simulated output against known physics processes.

1,514 citations


Journal ArticleDOI
07 Jan 2010-Nature
TL;DR: Findings establish chronic active BCR signalling as a new pathogenetic mechanism in ABC DLBCL, suggesting several therapeutic strategies.
Abstract: A role for B-cell-receptor (BCR) signalling in lymphomagenesis has been inferred by studying immunoglobulin genes in human lymphomas and by engineering mouse models, but genetic and functional evidence for its oncogenic role in human lymphomas is needed. Here we describe a form of 'chronic active' BCR signalling that is required for cell survival in the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). The signalling adaptor CARD11 is required for constitutive NF-kappaB pathway activity and survival in ABC DLBCL. Roughly 10% of ABC DLBCLs have mutant CARD11 isoforms that activate NF-kappaB, but the mechanism that engages wild-type CARD11 in other ABC DLBCLs was unknown. An RNA interference genetic screen revealed that a BCR signalling component, Bruton's tyrosine kinase, is essential for the survival of ABC DLBCLs with wild-type CARD11. In addition, knockdown of proximal BCR subunits (IgM, Ig-kappa, CD79A and CD79B) killed ABC DLBCLs with wild-type CARD11 but not other lymphomas. The BCRs in these ABC DLBCLs formed prominent clusters in the plasma membrane with low diffusion, similarly to BCRs in antigen-stimulated normal B cells. Somatic mutations affecting the immunoreceptor tyrosine-based activation motif (ITAM) signalling modules of CD79B and CD79A were detected frequently in ABC DLBCL biopsy samples but rarely in other DLBCLs and never in Burkitt's lymphoma or mucosa-associated lymphoid tissue lymphoma. In 18% of ABC DLBCLs, one functionally critical residue of CD79B, the first ITAM tyrosine, was mutated. These mutations increased surface BCR expression and attenuated Lyn kinase, a feedback inhibitor of BCR signalling. These findings establish chronic active BCR signalling as a new pathogenetic mechanism in ABC DLBCL, suggesting several therapeutic strategies.

1,463 citations


Journal ArticleDOI
A. A. Abdo1, A. A. Abdo2, Markus Ackermann3, Marco Ajello3  +285 moreInstitutions (39)
TL;DR: The first Fermi-LAT catalog (1FGL) as mentioned in this paper contains 1451 sources detected and characterized in the 100 MeV to 100 GeV range, and the threshold likelihood Test Statistic is 25, corresponding to a significance of just over 4 sigma.
Abstract: We present a catalog of high-energy gamma-ray sources detected by the Large Area Telescope (LAT), the primary science instrument on the Fermi Gamma-ray Space Telescope (Fermi), during the first 11 months of the science phase of the mission, which began on 2008 August 4. The First Fermi-LAT catalog (1FGL) contains 1451 sources detected and characterized in the 100 MeV to 100 GeV range. Source detection was based on the average flux over the 11 month period, and the threshold likelihood Test Statistic is 25, corresponding to a significance of just over 4 sigma. The 1FGL catalog includes source location regions, defined in terms of elliptical fits to the 95% confidence regions and power-law spectral fits as well as flux measurements in five energy bands for each source. In addition, monthly light curves are provided. Using a protocol defined before launch we have tested for several populations of gamma-ray sources among the sources in the catalog. For individual LAT-detected sources we provide firm identifications or plausible associations with sources in other astronomical catalogs. Identifications are based on correlated variability with counterparts at other wavelengths, or on spin or orbital periodicity. For the catalogs and association criteria that we have selected, 630 of the sources are unassociated. Care was taken to characterize the sensitivity of the results to the model of interstellar diffuse gamma-ray emission used to model the bright foreground, with the result that 161 sources at low Galactic latitudes and toward bright local interstellar clouds are flagged as having properties that are strongly dependent on the model or as potentially being due to incorrectly modeled structure in the Galactic diffuse emission.

1,412 citations


Journal ArticleDOI
TL;DR: Using a multiparameter tuning model, this work describes how dimension, density, stiffness, and orientation of the extracellular matrix together with cell determinants—including cell–cell and cell–matrix adhesion, cytoskeletal polarity and stiffness, etc.—interdependently control migration mode and efficiency.
Abstract: Cell migration underlies tissue formation, maintenance, and regeneration as well as pathological conditions such as cancer invasion. Structural and molecular determinants of both tissue environment and cell behavior define whether cells migrate individually (through amoeboid or mesenchymal modes) or collectively. Using a multiparameter tuning model, we describe how dimension, density, stiffness, and orientation of the extracellular matrix together with cell determinants-including cell-cell and cell-matrix adhesion, cytoskeletal polarity and stiffness, and pericellular proteolysis-interdependently control migration mode and efficiency. Motile cells integrate variable inputs to adjust interactions among themselves and with the matrix to dictate the migration mode. The tuning model provides a matrix of parameters that control cell movement as an adaptive and interconvertible process with relevance to different physiological and pathological contexts.

1,239 citations


Journal ArticleDOI
TL;DR: The task-switching paradigm offers enormous possibilities to study cognitive control as well as task interference, and the current review provides an overview of recent research on both topics.
Abstract: The task-switching paradigm offers enormous possibilities to study cognitive control as well as task interference. The current review provides an overview of recent research on both topics. First, we review different experimental approaches to task switching, such as comparing mixed-task blocks with single-task blocks, predictable task-switching and task-cuing paradigms, intermittent instructions, and voluntary task selection. In the 2nd part, we discuss findings on preparatory control mechanisms in task switching and theoretical accounts of task preparation. We consider preparation processes in two-stage models, consider preparation as an all-or-none process, address the question of whether preparation is switch-specific, reflect on preparation as interaction of cue encoding and memory retrieval, and discuss the impact of verbal mediation on preparation. In the 3rd part, we turn to interference phenomena in task switching. We consider proactive interference of tasks and inhibition of recently performed tasks indicated by asymmetrical switch costs and n-2 task-repetition costs. We discuss stimulus-based interference as a result of stimulus-based response activation and stimulus-based task activation, and response-based interference because of applying bivalent rather than univalent responses, response repetition effects, and carryover of response selection and execution. In the 4th and final part, we mention possible future research fields.

1,223 citations


Journal ArticleDOI
TL;DR: An increased number of tumor-associated macrophages was strongly associated with shortened survival in patients with classic Hodgkin's lymphoma and provides a new biomarker for risk stratification.
Abstract: Background Despite advances in treatments for Hodgkin's lymphoma, about 20% of patients still die from progressive disease. Current prognostic models predict the outcome of treatment with imperfect accuracy, and clinically relevant biomarkers have not been established to improve on the International Prognostic Score. Methods Using gene-expression profiling, we analyzed 130 frozen samples obtained from patients with classic Hodgkin's lymphoma during diagnostic lymph-node biopsy to determine which cellular signatures were correlated with treatment outcome. We confirmed our findings in an independent cohort of 166 patients, using immunohistochemical analysis. Results Gene-expression profiling identified a gene signature of tumor-associated macrophages that was significantly associated with primary treatment failure (P=0.02). In an independent cohort of patients, we found that an increased number of CD68+ macrophages was correlated with a shortened progression-free survival (P=0.03) and with an increased like...

1,135 citations


Journal ArticleDOI
TL;DR: Available data from biomonitoring studies clearly indicate that the general population is exposed to BPA and is at risk from internal exposure to unconjugated BPA.
Abstract: BackgroundBisphenol A (BPA) is one of the highest-volume chemicals produced worldwide, and human exposure to BPA is thought to be ubiquitous. Thus, there are concerns that the amount of BPA to whic...

1,124 citations


Journal ArticleDOI
TL;DR: The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered.
Abstract: BACKGROUND: Consensus guidelines on the definition, investigation, and treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) have been previously published in European Journal of Neurology and Journal of the Peripheral Nervous System. OBJECTIVES: To revise these guidelines. METHODS: Disease experts, including a representative of patients, considered references retrieved from MEDLINE and Cochrane Systematic Reviews published between August 2004 and July 2009 and prepared statements that were agreed in an iterative fashion. RECOMMENDATIONS: The Task Force agreed on Good Practice Points to define clinical and electrophysiological diagnostic criteria for CIDP with or without concomitant diseases and investigations to be considered. The principal treatment recommendations were: (i) intravenous immunoglobulin (IVIg) (Recommendation Level A) or corticosteroids (Recommendation Level C) should be considered in sensory and motor CIDP; (ii) IVIg should be considered as the initial treatment in pure motor CIDP (Good Practice Point); (iii) if IVIg and corticosteroids are ineffective, plasma exchange (PE) should be considered (Recommendation Level A); (iv) if the response is inadequate or the maintenance doses of the initial treatment are high, combination treatments or adding an immunosuppressant or immunomodulatory drug should be considered (Good Practice Point); (v) symptomatic treatment and multidisciplinary management should be considered (Good Practice Point).

1,051 citations


Journal ArticleDOI
01 Sep 2010-Pain
TL;DR: Somatosensory profiles with different combinations of loss and gain are shared across the major neuropathic pain syndromes, including thermal and mechanical hyperalgesias, which were most frequent in complex regional pain syndrome and peripheral nerve injury, allodynia in postherpetic neuralgia.
Abstract: Neuropathic pain is accompanied by both positive and negative sensory signs. To explore the spectrum of sensory abnormalities, 1236 patients with a clinical diagnosis of neuropathic pain were assessed by quantitative sensory testing (QST) following the protocol of DFNS (German Research Network on Neuropathic Pain), using both thermal and mechanical nociceptive as well as non-nociceptive stimuli. Data distributions showed a systematic shift to hyperalgesia for nociceptive, and to hypoesthesia for non-nociceptive parameters. Across all parameters, 92% of the patients presented at least one abnormality. Thermosensory or mechanical hypoesthesia (up to 41%) was more frequent than hypoalgesia (up to 18% for mechanical stimuli). Mechanical hyperalgesias occurred more often (blunt pressure: 36%, pinprick: 29%) than thermal hyperalgesias (cold: 19%, heat: 24%), dynamic mechanical allodynia (20%), paradoxical heat sensations (18%) or enhanced wind-up (13%). Hyperesthesia was less than 5%. Every single sensory abnormality occurred in each neurological syndrome, but with different frequencies: thermal and mechanical hyperalgesias were most frequent in complex regional pain syndrome and peripheral nerve injury, allodynia in postherpetic neuralgia. In postherpetic neuralgia and in central pain, subgroups showed either mechanical hyperalgesia or mechanical hypoalgesia. The most frequent combinations of gain and loss were mixed thermal/mechanical loss without hyperalgesia (central pain and polyneuropathy), mixed loss with mechanical hyperalgesia in peripheral neuropathies, mechanical hyperalgesia without any loss in trigeminal neuralgia. Thus, somatosensory profiles with different combinations of loss and gain are shared across the major neuropathic pain syndromes. The characterization of underlying mechanisms will be needed to make a mechanism-based classification feasible.

842 citations


Journal ArticleDOI
15 Jan 2010-Science
TL;DR: Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation.
Abstract: We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents.

Journal ArticleDOI
TL;DR: The Generalized Nash Equilibrium Problem is an important model that has its roots in the economic sciences but is being fruitfully used in many different fields and its main properties and solution algorithms are discussed.
Abstract: The Generalized Nash Equilibrium Problem is an important model that has its roots in the economic sciences but is being fruitfully used in many different fields. In this survey paper we aim at discussing its main properties and solution algorithms, pointing out what could be useful topics for future research in the field.

Journal ArticleDOI
TL;DR: The IQX hypothesis is a strong candidate to be taken into account when deriving relationships between QoE and QoS parameters and is shown to outperform previously published logarithmic functions.
Abstract: Quality of experience ties together user perception, experience, and expectations to application and network performance, typically expressed by quality of service parameters. Quantitative relationships between QoE and QoS are required in order to be able to build effective QoE control mechanisms onto measurable QoS parameters. Against this background, this article proposes a generic formula in which QoE and QoS parameters are connected through an exponential relationship, called IQX hypothesis. The formula relates changes of QoE with respect to QoS to the current level of QoE, is simple to match, and its limit behaviors are straightforward to interpret. It validates the IQX hypothesis for streaming services, where QoE in terms of Mean Opinion Scores is expressed as functions of loss and reordering ratio, the latter of which is caused by jitter. For web surfing as the second application area, matchings provided by the IQX hypothesis are shown to outperform previously published logarithmic functions. We conclude that the IQX hypothesis is a strong candidate to be taken into account when deriving relationships between QoE and QoS parameters.

Journal ArticleDOI
TL;DR: This paper focuses on the prospect of improving the lives of countless disabled individuals through a combination of BCI technology with existing assistive technologies (AT) and identifies four application areas where disabled individuals could greatly benefit from advancements inBCI technology, namely, “Communication and Control”, ‘Motor Substitution’, ”Entertainment” and “Motor Recovery”.
Abstract: In recent years, new research has brought the field of electroencephalogram (EEG)-based brain–computer interfacing (BCI) out of its infancy and into a phase of relative maturity through many demonstrated prototypes such as brain-controlled wheelchairs, keyboards, and computer games. With this proof-of-concept phase in the past, the time is now ripe to focus on the development of practical BCI technologies that can be brought out of the lab and into real-world applications. In particular, we focus on the prospect of improving the lives of countless disabled individuals through a combination of BCI technology with existing assistive technologies (AT). In pursuit of more practical BCIs for use outside of the lab, in this paper, we identify four application areas where disabled individuals could greatly benefit from advancements in BCI technology, namely, “Communication and Control”, “Motor Substitution”, “Entertainment”, and “Motor Recovery”. We review the current state of the art and possible future developments, while discussing the main research issues in these four areas. In particular, we expect the most progress in the development of technologies such as hybrid BCI architectures, user–machine adaptation algorithms, the exploitation of users’ mental states for BCI reliability and confidence measures, the incorporation of principles in human–computer interaction (HCI) to improve BCI usability, and the development of novel BCI technology including better EEG devices.

Journal ArticleDOI
TL;DR: In this paper, the authors study two limiting cases of turbulence forcing in numerical experiments: solenoidal (divergence-free) forcing and compressive (curl-free), and compare their results to observations.
Abstract: Context. Density and velocity fluctuations on virtually all scales observed with modern telescopes show that molecular clouds (MCs) are turbulent. The forcing and structural characteristics of this turbulence are, however, still poorly understood.Aims. To shed light on this subject, we study two limiting cases of turbulence forcing in numerical experiments: solenoidal (divergence-free) forcing and compressive (curl-free) forcing, and compare our results to observations.Methods. We solve the equations of hydrodynamics on grids with up to 10243 cells for purely solenoidal and purely compressive forcing. Eleven lower-resolution models with different forcing mixtures are also analysed.Results. Using Fourier spectra and Δ -variance, we find velocity dispersion-size relations consistent with observations and independent numerical simulations, irrespective of the type of forcing. However, compressive forcing yields stronger compression at the same rms Mach number than solenoidal forcing, resulting in a three times larger standard deviation of volumetric and column density probability distributions (PDFs). We compare our results to different characterisations of several observed regions, and find evidence of different forcing functions. Column density PDFs in the Perseus MC suggest the presence of a mainly compressive forcing agent within a shell, driven by a massive star. Although the PDFs are close to log-normal, they have non-Gaussian skewness and kurtosis caused by intermittency. Centroid velocity increments measured in the Polaris Flare on intermediate scales agree with solenoidal forcing on that scale. However, Δ -variance analysis of the column density in the Polaris Flare suggests that turbulence is driven on large scales, with a significant compressive component on the forcing scale. This indicates that, although likely driven with mostly compressive modes on large scales, turbulence can behave like solenoidal turbulence on smaller scales. Principal component analysis of G216-2.5 and most of the Rosette MC agree with solenoidal forcing, but the interior of an ionised shell within the Rosette MC displays clear signatures of compressive forcing.Conclusions. The strong dependence of the density PDF on the type of forcing must be taken into account in any theory using the PDF to predict properties of star formation. We supply a quantitative description of this dependence. We find that different observed regions show evidence of different mixtures of compressive and solenoidal forcing, with more compressive forcing occurring primarily in swept-up shells. Finally, we emphasise the role of the sonic scale for protostellar core formation, because core formation close to the sonic scale would naturally explain the observed subsonic velocity dispersions of protostellar cores.

Journal ArticleDOI
TL;DR: Among a range of other findings, EC effects were stronger for high than for low contingency awareness, for supraliminal than for subliminal US presentation, for postacquisition than for postextinction effects, and for self-report than for implicit measures.
Abstract: This article presents a meta-analysis of research on evaluative conditioning (EC), defined as a change in the liking of a stimulus (conditioned stimulus; CS) that results from pairing that stimulus with other positive or negative stimuli (unconditioned stimulus; US). Across a total of 214 studies included in the main sample, the mean EC effect was d = .52, with a 95% confidence interval of .466-.582. As estimated from a random-effects model, about 70% of the variance in effect sizes were attributable to true systematic variation rather than sampling error. Moderator analyses were conducted to partially explain this variation, both as a function of concrete aspects of the procedural implementation and as a function of the abstract aspects of the relation between CS and US. Among a range of other findings, EC effects were stronger for high than for low contingency awareness, for supraliminal than for subliminal US presentation, for postacquisition than for postextinction effects, and for self-report than for implicit measures. These findings are discussed with regard to the procedural boundary conditions of EC and theoretical accounts about the mental processes underlying EC.

Journal ArticleDOI
TL;DR: A genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson’s and subclinical disease and healthy controls identified 10 gene sets that were all associated with PD.
Abstract: Parkinson’s disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson’s and subclinical disease and healthy controls. We analyzed 6.8 million raw data points from nine genome-wide expression studies, and 185 laser-captured human dopaminergic neuron and substantia nigra transcriptomes, followed by two-stage replication on three platforms. We found 10 gene sets with previously unknown associations with Parkinson’s disease. These gene sets pinpoint defects in mitochondrial electron transport, glucose utilization, and glucose sensing and reveal that they occur early in disease pathogenesis. Genes controlling cellular bioenergetics that are expressed in response to peroxisome proliferator–activated receptor γ coactivator-1α (PGC-1α) are underexpressed in Parkinson’s disease patients. Activation of PGC-1α results in increased expression of nuclear-encoded subunits of the mitochondrial respiratory chain and blocks the dopaminergic neuron loss induced by mutant α-synuclein or the pesticide rotenone in cellular disease models. Our systems biology analysis of Parkinson’s disease identifies PGC-1α as a potential therapeutic target for early intervention.

Journal ArticleDOI
TL;DR: An overview of the physical function of organic solar cells, their state-of-the-art performance and limitations, as well as novel concepts to achieve a better material stability and higher power conversion efficiencies are presented in this paper.
Abstract: Organic solar cells have the potential to be low-cost and efficient solar energy converters, with a promising energy balance. They are made of carbon-based semiconductors, which exhibit favourable light absorption and charge generation properties, and can be manufactured by low temperature processes such as printing from solvent-based inks, which are compatible with flexible plastic substrates or even paper. In this review, we will present an overview of the physical function of organic solar cells, their state-of-the-art performance and limitations, as well as novel concepts to achieve a better material stability and higher power conversion efficiencies. We will also briefly review processing and cost in view of the market potential.

Journal ArticleDOI
TL;DR: Revision of the guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy, published in 2005, has become appropriate owing to publication of more relevant articles and most of the new studies focused on small fiber neuropathy (SFN).
Abstract: Background: Revision of the guidelines on the use of skin biopsy in the diagnosis of peripheral neuropathy, published in 2005, has become appropriate owing to publication of more relevant articles. Most of the new studies focused on small fiber neuropathy (SFN), a subtype of neuropathy for which the diagnosis was first developed through skin biopsy examination. This revision focuses on the use of this technique to diagnose SFN. Methods: Task force members searched the Medline database from 2005, the year of the publication of the first EFNS guideline, to June 30th, 2009. All pertinent articles were rated according to the EFNS and PNS guidance. After a consensus meeting, the task force members created a manuscript that was subsequently revised by two experts (JML and JVS) in the field of peripheral neuropathy and clinical neurophysiology, who were not previously involved in the use of skin biopsy. Results and Conclusions: Distal leg skin biopsy with quantification of the linear density of intraepidermal nerve fibers (IENF), using generally agreed upon counting rules, is a reliable and efficient technique to assess the diagnosis of SFN (Recommendation Level A). Normative reference values are available for bright-field immunohistochemistry (Recommendation Level A) but not yet for confocal immunofluorescence or the blister technique. The morphometric analysis of IENF density, either performed with bright-field or immunofluorescence microscopy, should always refer to normative values matched for age (Recommendation Level A). Newly established laboratories should undergo adequate training in a well-established skin biopsy laboratory and provide their own stratified for age and gender normative values, intra- and interobserver reliability, and interlaboratory agreement. Quality control of the procedure at all levels is mandatory (Good Practice Point). Procedures to quantify subepidermal nerve fibers and autonomic innervated structures, including erector pili muscles, and skin vessels, are under development but need to be confirmed by further studies. Sweat gland innervation can be examined using an unbiased stereologic technique recently proposed (Recommendation Level B).A reduced IENF density is associated with the risk of developing neuropathic pain (Recommendation Level B), but it does not correlate with its intensity. Serial skin biopsies might be useful for detecting early changes of IENF density, which predict the progression of neuropathy, and to assess degeneration and regeneration of IENF (Recommendation Level C). However, further studies are warranted to confirm its potential usefulness as an outcome measure in clinical practice and research. Skin biopsy has not so far been useful for identifying the etiology of SFN. Finally, we emphasize that 3-mm skin biopsy at the ankle is a safe procedure based on the experience of 10 laboratories reporting absence of serious side effects in approximately 35 000 biopsies and a mere 0.19% incidence of non-serious side effects in about 15 years of practice (Good Practice Point).

Journal ArticleDOI
TL;DR: In index cases from 1,100 German families with gynecological malignancies, the first unambiguous evidence of highly penetrant mutations associated with human cancer in a RAD51 paralog is provided and support the 'common disease, rare allele' hypothesis.
Abstract: Germline mutations in a number of genes involved in the recombinational repair of DNA double-strand breaks are associated with predisposition to breast and ovarian cancer. RAD51C is essential for homologous recombination repair, and a biallelic missense mutation can cause a Fanconi anemia-like phenotype. In index cases from 1,100 German families with gynecological malignancies, we identified six monoallelic pathogenic mutations in RAD51C that confer an increased risk for breast and ovarian cancer. These include two frameshift-causing insertions, two splice-site mutations and two nonfunctional missense mutations. The mutations were found exclusively within 480 pedigrees with the occurrence of both breast and ovarian tumors (BC/OC; 1.3%) and not in 620 pedigrees with breast cancer only or in 2,912 healthy German controls. These results provide the first unambiguous evidence of highly penetrant mutations associated with human cancer in a RAD51 paralog and support the 'common disease, rare allele' hypothesis.

Journal ArticleDOI
TL;DR: The impact of increasing the CT energy-in order to raise the open circuit voltage, but lowering the kinetic excess energy of the CT complexes at the same time-on the charge photogeneration will be discussed.
Abstract: Charge transfer complexes are interfacial charge pairs residing at the donor-acceptor heterointerface in organic solar cell. Experimental evidence shows that it is crucial for the photovoltaic performance, as both photocurrent and open circuit voltage directly depend on it. For charge photogeneration, charge transfer complexes represent the intermediate but essential step between exciton dissotiation and charge extraction. Recombination of free charges to the ground state is via the bound charge transfer state before being lost to the ground state. In terms of the open circuit voltage, its maximum achievable value is determined by the energy of the charge transfer state. An important question is whether or not maximum photocurrent and maximum open circuit voltage can be achieved simultaneously. The impact of increasing the CT energy-in order to raise the open circuit voltage, but lowering the kinetic excess energy of the CT complexes at the same time-on the charge photogeneration will accordingly be discussed. Clearly, the fundamental understanding of the processes involving the charge transfer state is essential for an optimisation of the performance of organic solar cells.

Journal ArticleDOI
TL;DR: In this paper, Zhang et al. gave the full microscopic derivation of the model Hamiltonian for the three-dimensional topological insulators in the Ω(n) family of materials.
Abstract: In this paper we give the full microscopic derivation of the model Hamiltonian for the three-dimensional topological insulators in the ${\mathrm{Bi}}_{2}{\mathrm{Se}}_{3}$ family of materials (${\mathrm{Bi}}_{2}{\mathrm{Se}}_{3}$, ${\mathrm{Bi}}_{2}{\mathrm{Te}}_{3}$ and ${\mathrm{Sb}}_{2}{\mathrm{Te}}_{3}$). We first give a physical picture to understand the electronic structure by analyzing atomic orbitals and applying symmetry principles. Subsequently, we give the full microscopic derivation of the model Hamiltonian introduced by Zhang et al. [Nat. Phys. 5, 438 (2009)] based both on symmetry principles and the $\mathbf{k}\ensuremath{\cdot}\mathbf{p}$ perturbation theory. Two different types of ${k}^{3}$ terms, which break the in-plane full rotation symmetry down to threefold rotation symmetry, are taken into account. An effective Hamiltonian is derived for the topological surface states. Both bulk and surface models are investigated in the presence of an external magnetic field, and the associated Landau level structure is presented. For a more quantitative fitting to the first principle calculations, we also present a model Hamiltonian including eight energy bands.

Journal ArticleDOI
01 Jun 2010-Leukemia
TL;DR: Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of residents of Olmsted County, Minnesota, 50 years of age or older and is characterized by having an M protein <15 g/l, IgG type and a normal free light chain (FLC) ratio.
Abstract: Monoclonal gammopathy of undetermined significance (MGUS) was identified in 3.2% of 21 463 residents of Olmsted County, Minnesota, 50 years of age or older. The risk of progression to multiple myeloma, Waldenstrom's macroglobulinemia, AL amyloidosis or a lymphoproliferative disorder is approximately 1% per year. Low-risk MGUS is characterized by having an M protein <15 g/l, IgG type and a normal free light chain (FLC) ratio. Patients should be followed with serum protein electrophoresis at six months and, if stable, can be followed every 2-3 years or when symptoms suggestive of a plasma cell malignancy arise. Patients with intermediate and high-risk MGUS should be followed in 6 months and then annually for life. The risk of smoldering (asymptomatic) multiple myeloma (SMM) progressing to multiple myeloma or a related disorder is 10% per year for the first 5 years, 3% per year for the next 5 years and 1-2% per year for the next 10 years. Testing should be done 2-3 months after the initial recognition of SMM. If the results are stable, the patient should be followed every 4-6 months for 1 year and, if stable, every 6-12 months.

Journal ArticleDOI
TL;DR: The Biodiversity Exploratories (www.biodiversityexploratories.de ) as mentioned in this paper is a large-scale and long-term project for functional biodiversity, which includes a hierarchical set of standardized field plots in three different regions of Germany covering manifold management types and intensities in grasslands and forests.

Journal ArticleDOI
TL;DR: The fulfilment of universal psychological needs, such as competence, relatedness, popularity, stimulation, meaning, security, or autonomy, is considered to be the major source of positive experience with interactive technologies.

Journal ArticleDOI
TL;DR: An overview of the physical function of organic solar cells, their state-of-the-art performance and limitations, as well as novel concepts to achieve a better material stability and higher power conversion efficiencies are presented in this paper.
Abstract: Organic solar cells have the potential to be low-cost and efficient solar energy converters, with a promising energy balance. They are made from carbon-based semiconductors, which exhibit favourable light absorption and charge generation properties, and can be manufactured by low temperature processes such as printing from solvent-based inks, which are compatible with flexible plastic substrates or even paper. In this review, we will present an overview of the physical function of organic solar cells, their state-of-the-art performance and limitations, as well as novel concepts to achieve a better material stability and higher power conversion efficiencies. We will also briefly review processing and cost in view of the market potential.

Journal ArticleDOI
Georges Aad1, Brad Abbott2, Jalal Abdallah3, A. A. Abdelalim4  +3098 moreInstitutions (192)
TL;DR: In this article, the authors used the ATLAS detector to detect dijet asymmetry in the collisions of lead ions at the Large Hadron Collider and found that the transverse energies of dijets in opposite hemispheres become systematically more unbalanced with increasing event centrality, leading to a large number of events which contain highly asymmetric di jets.
Abstract: By using the ATLAS detector, observations have been made of a centrality-dependent dijet asymmetry in the collisions of lead ions at the Large Hadron Collider. In a sample of lead-lead events with a per-nucleon center of mass energy of 2.76 TeV, selected with a minimum bias trigger, jets are reconstructed in fine-grained, longitudinally segmented electromagnetic and hadronic calorimeters. The transverse energies of dijets in opposite hemispheres are observed to become systematically more unbalanced with increasing event centrality leading to a large number of events which contain highly asymmetric dijets. This is the first observation of an enhancement of events with such large dijet asymmetries, not observed in proton-proton collisions, which may point to an interpretation in terms of strong jet energy loss in a hot, dense medium.

Journal ArticleDOI
TL;DR: A neurophysiological predictor of BCI performance is proposed which can be determined from a two minute recording of a 'relax with eyes open' condition using two Laplacian EEG channels.

Journal ArticleDOI
TL;DR: This review will present examples of probiotic actions from three general modes of actions into which probiotic effects can be classified.

Journal ArticleDOI
26 Mar 2010-Science
TL;DR: In cardiomyocytes from healthy adult rats and mice, spatially confined β2AR-induced cAMP signals are localized exclusively to the deep transverse tubules, whereas functional β1ARs are distributed across the entire cell surface.
Abstract: The β 1 - and β 2 -adrenergic receptors (βARs) on the surface of cardiomyocytes mediate distinct effects on cardiac function and the development of heart failure by regulating production of the second messenger cyclic adenosine monophosphate (cAMP). The spatial localization in cardiomyocytes of these βARs, which are coupled to heterotrimeric guanine nucleotide–binding proteins (G proteins), and the functional implications of their localization have been unclear. We combined nanoscale live-cell scanning ion conductance and fluorescence resonance energy transfer microscopy techniques and found that, in cardiomyocytes from healthy adult rats and mice, spatially confined β 2 AR-induced cAMP signals are localized exclusively to the deep transverse tubules, whereas functional β 1 ARs are distributed across the entire cell surface. In cardiomyocytes derived from a rat model of chronic heart failure, β 2 ARs were redistributed from the transverse tubules to the cell crest, which led to diffuse receptor-mediated cAMP signaling. Thus, the redistribution of β 2 ARs in heart failure changes compartmentation of cAMP and might contribute to the failing myocardial phenotype.