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Ice sheet simulations suffer from vast parametric uncertainties, such as the basal sliding boundary condition or geothermal heat flux. Quantifying the resulting uncertainties in predictions is of utmost importance to support judicious decision-making, but high-fidelity simulations are too expensive to embed within uncertainty quantification (UQ) computations. UQ methods typically employ Monte Carlo simulation to estimate statistics of interest, which requires hundreds (or more) of ice sheet simulations. Cheaper low-fidelity models are readily available (e.g., approximated physics, coarser meshes), but replacing the high-fidelity model with a lower fidelity surrogate introduces bias, which means that UQ results generated with a low-fidelity model cannot be rigorously trusted. Multifidelity UQ retains the high-fidelity model but expands the estimator to shift computations to low-fidelity models, while still guaranteeing an unbiased estimate. Through this exploitation of multiple models, multifidelity estimators guarantee a target accuracy at reduced computational cost. This paper presents a comprehensive multifidelity UQ framework for ice sheet simulations. We present three multifidelity UQ approaches—Multifidelity Monte Carlo, Multilevel Monte Carlo, and the Best Linear Unbiased Estimator—that enable tractable UQ for continental-scale ice sheet simulations. We demonstrate the techniques on a model of the Greenland ice sheet to estimate the 2015-2050 ice mass loss, verify their estimates through comparison with Monte Carlo simulations, and give a comparative performance analysis. For a target accuracy equivalent to 1 mm sea level rise contribution at 95 % confidence, the multifidelity estimators achieve computational speedups of two orders of magnitude. [ABSTRACT FROM AUTHOR]

We construct and analyze families of periodic delay orbits for a class of delay differential equations in two dimensions depending on two real-valued functions. These families are parametrized by the delay parameter. It is possible to represent the dependency of these periodic delay orbits on the delay parameter by a curve in the plane, without loss of information. It turns out that the singularities of these curves necessarily are cusps in the non-degenerate case. After discussing degenerate situations in general, we explain how to glue different families of periodic delay orbits at degeneracies in the delay parameter. [ABSTRACT FROM AUTHOR]

Background: The German College of General Practitioners and Family Physicians (DEGAM) issued a COVID-19 guideline with eleven recommendations to support primary care services during the pandemic. Their use in general practices beyond the pandemic can contribute to pandemic preparedness. This study analysed general practitioners' (GPs) interest in applying recommended organisational changes in non-pandemic times. Methods: Data from the German egePan GP survey (n = 516 GPs) - a multi-level clustered randomised web-based survey - were analysed. GPs' interest in the future application of the eleven guideline recommendations was calculated. In addition, each recommendation was evaluated by the GPs using a Net-Promoter-Score (NPS range − 100 to 100). A linear regression model identified GP and practice characteristics associated with a higher interest in applying recommendations in non-pandemic times. Results: 98.5% of the GPs indicated the intention to implement at least one guideline recommendation prospectively: disinfectant dispensers at the entrance (86%), optimised consultation scheduling to reduce waiting times (83%), and glass screens in the reception area (72%), which also received the highest NPS scores. In contrast, lower interest was observed for items such as insurance card readers handled by patients (48%), only selected staff treating infectious patients (44%), and video consultations for patients with infections (26%). A higher interest to implement recommendations in non-pandemic times was associated with a higher crisis leadership score (p < 0.001), using the Corona-Warn-App (p = 0.007), and being a female GP (p = 0.045). In addition, GPs from Western, Northern, and Southern, and those with a higher patient volume per three months, were more interested in future implementation. Conclusions: Overall, GPs demonstrated the readiness to follow the DEGAM COVID-19 guideline outside pandemic periods, establishing them as key contributors to pandemic preparedness in Germany. [ABSTRACT FROM AUTHOR]

Limited healthcare availability impacts population health. Regional disparities in GP density across Germany raise questions about their association with regional socioeconomic characteristics. This longitudinal nationwide ecological German study used regional data at the county level (n = 401) from 2015 to 2019 provided by the Federal Institute for Research on Building, Urban Affairs and Spatial Development (BBSR). The outcome was general practitioners (GPs) density, defined as the number of GPs per 10,000 inhabitants. Univariate Moran's I, cluster analysis (LISA), and spatial lag of X (SLX) models were employed to analyse the spatial distribution of GP density and its correlation with various regional socioeconomic characteristics from a cross-sectional and longitudinal perspective. In contrast to the univariate analysis, rural counties showed the highest GP density the multivariate model. Several counties were identified as embedded in low- or high-GP-density clusters. In 2015 and 2019, larger household size (2015: std. β = −2.31, p = 0.021; 2019: std. β = −4.14, p < 0.001) and higher unemployment rate (2015: std. β = −2.84, p = 0.005; 2019: std. β = −5.47, p < 0.001) were associated with lower GP density. In the longitudinal model, a greater increase in the unemployment rate was related to a greater decrease in GP density (std. β = −2.17, p = 0.030). A higher regional unemployment rate is linked to lower GP availability in Germany, and a greater increase in the unemployment rate was related to a greater decrease in GP availability over time. This necessitates policy intervention to avoid socioeconomic disparities in GP care. [ABSTRACT FROM AUTHOR]

Objective: This article aims to analyze the openness of data in Brazilian federal university libraries, as required by open government initiatives and current Brazilian legislation, using the indicators of the ISO 11620:2014 standard as a reference. Method: The methodology includes quantitative and qualitative analysis of library data available on official portals and application of questionnaires at the 69 federal universities linked to the MEC. Result: The results indicate that the majority of libraries do not have their data included in the University's Open Data Plans, violating the guidelines of the Comptroller General of the Union. Although libraries collect data and produce reports, their participation in open data initiatives still is limited. Conclusions: There is potential for greater engagement in promoting transparency and access to information about the data produced and held by these spaces. [ABSTRACT FROM AUTHOR]

Summary: Recent development of methods to discover and engineer therapeutic T‐cell receptors (TCRs) or antibody mimics of TCRs, and to understand their immunology and pharmacology, lag two decades behind therapeutic antibodies. Yet we have every expectation that TCR‐based agents will be similarly important contributors to the treatment of a variety of medical conditions, especially cancers. TCR engineered cells, soluble TCRs and their derivatives, TCR‐mimic antibodies, and TCR‐based CAR T cells promise the possibility of highly specific drugs that can expand the scope of immunologic agents to recognize intracellular targets, including mutated proteins and undruggable transcription factors, not accessible by traditional antibodies. Hurdles exist regarding discovery, specificity, pharmacokinetics, and best modality of use that will need to be overcome before the full potential of TCR‐based agents is achieved. HLA restriction may limit each agent to patient subpopulations and off‐target reactivities remain important barriers to widespread development and use of these new agents. In this review we discuss the unique opportunities for these new classes of drugs, describe their unique antigenic targets, compare them to traditional antibody therapeutics and CAR T cells, and review the various obstacles that must be overcome before full application of these drugs can be realized. [ABSTRACT FROM AUTHOR]

Integrin adhesion complexes are essential membrane-associated cellular compartments for metazoan life. The formation of initial integrin adhesion complexes is a dynamic process involving focal adhesion proteins assembled at the integrin cytoplasmic tails and the inner leaflet of the plasma membrane. The weak multivalent protein interactions within the complex and with the plasma membrane suggest that liquid-liquid phase separation could play a role in the nascent adhesion assembly. Here, we report that solid-supported lipid membranes supplemented with phosphoinositides induce the phase separation of minimal integrin adhesion condensates composed of integrin β1 tails, kindlin, talin, paxillin, and FAK at physiological ionic strengths and protein concentrations. We show that the presence of phosphoinositides is key to enriching kindlin and talin on the lipid membrane, which is necessary to further induce the phase separation of paxillin and FAK at the membrane. Our data demonstrate that lipid membrane surfaces set the local solvent conditions for steering the membranelocalized phase separation even in a regime where no condensate formation of proteins occurs in bulk solution. [ABSTRACT FROM AUTHOR]

A 60-year-old woman presented with a cutaneous eruption in the right submammary area. She had a history of psoriasis, lichen sclerosus, and previous breast cancer. The clinical differential diagnosis included various conditions such as cutaneous lymphangioma, varicella zoster reactivation, extragenital lichen sclerosus, and angiosarcoma. Bacterial swabs cultured coagulase-negative staphylococcus, while viral swabs were negative. Histopathological findings revealed an atypical vascular lesion (AVL) of the breast. AVLs are distinct lesions that occur after radiation therapy and breast conserving surgery, typically appearing as erythematous papules, plaques, or vesicles. They can have lymphatic or vascular histology and may be a precursor to angiosarcoma, although true cytological atypia and mitotic activity are absent in AVLs. Ancillary testing for amplification of the MYC gene can help distinguish AVLs from angiosarcomas. [Extracted from the article]

Integrin-mediated adhesion is essential for metazoan life. Integrin binding to ligand requires an activation step prior to binding ligand that depends on direct binding of talin and kindlin to the β-integrin cytoplasmic tail and the transmission of force from the actomyosin via talin to the integrin-ligand bonds. However, the affinity of talin for integrin tails is low. It is therefore still unclear how such low-affinity bonds are reinforced to transmit forces up to 10 to 40 pN. In this study, we use single-molecule force spectroscopy by optical tweezers to investigate the mechanical stability of the talin⋅integrin bond in the presence and absence of kindlin. While talin and integrin alone form a weak and highly dynamic slip bond, the addition of kindlin-2 induces a force-independent, ideal talin⋅integrin bond, which relies on the steric proximity of and the intervening amino acid sequences between the talin- and kindlin-binding sites in the β-integrin tail. Our findings show how kindlin cooperates with talin to enable transmission of high forces required to stabilize cell adhesion. [ABSTRACT FROM AUTHOR]

Simple Summary: The malignant growth and therapy resistance of isocitrate dehydrogenase (IDH)-wildtype glioblastoma is thought to be driven by a subpopulation of tumor cells with cancer stem-like cell (CSC) properties. Employing a high-throughput in vitro drug screen, we identified LGK974 and berberine as drugs that impair wingless (WNT) signaling and can thereby sensitize glioblastoma stem-like cells (GSCs) to glucose starvation-induced cell death. The main goal of this study was to characterize the role of the WNT pathway in mediating the survival and metabolic plasticity of GSCs under nutrient-restricted growth conditions. Gas chromatography mass spectrometry (GC-MS) was used to determine WNT-specific alterations of intracellular metabolites in GSCs grown under nutrient restriction, i.e., glucose depletion, or under standard conditions. Metabolic fingerprints hold the promise to complement classic biomarkers, thus potentially aiding the prediction of tumor behavior and patient prognosis. Isocitrate dehydrogenase (IDH)-wildtype glioblastoma is the most common primary malignant brain tumor. It is associated with a particularly poor prognosis, as reflected by an overall median survival of only 15 months in patients who undergo a supramarginal surgical reduction of the tumor mass followed by combined chemoradiotherapy. The highly malignant nature of IDH-wildtype glioblastoma is thought to be driven by glioblastoma stem-like cells (GSCs) that harbor the ability of self-renewal, survival, and adaptability to challenging environmental conditions. The wingless (WNT) signaling pathway is a phylogenetically highly conserved stemness pathway, which promotes metabolic plasticity and adaptation to a nutrient-limited tumor microenvironment. To unravel the reciprocal regulation of the WNT pathway and the nutrient-limited microenvironment, glioblastoma cancer stem-like cells were cultured in a medium with either standard or reduced glucose concentrations for various time points (24, 48, and 72 h). Glucose depletion reduced cell viability and facilitated the survival of a small population of starvation-resistant tumor cells. The surviving cells demonstrated increased clonogenic and invasive properties as well as enhanced chemosensitivity to pharmacological inhibitors of the WNT pathway (LGK974, berberine). Glucose depletion partially led to the upregulation of WNT target genes such as CTNNB1, ZEB1, and AXIN2 at the mRNA and corresponding protein levels. LGK974 treatment alone or in combination with glucose depletion also altered the metabolite concentration in intracellular compartments, suggesting WNT-mediated metabolic regulation. Taken together, our findings suggest that WNT-mediated metabolic plasticity modulates the survival of GSCs under nutrient-restricted environmental conditions. [ABSTRACT FROM AUTHOR]

Isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) is a fast growing and highly heterogeneous tumor, often characterized by the presence of glioblastoma stem cells (GSCs). The plasticity of GSCs results in therapy resistance and impairs anti-tumor immune response by influencing immune cells in the tumor microenvironment (TME). Previously, β-catenin was associated with stemness in GBM as well as with immune escape mechanisms. Here, we investigated the effect of β-catenin on attracting monocytes towards GBM cells. In addition, we evaluated whether CCL2 is involved in β-catenin crosstalk between monocytes and tumor cells. Our analysis revealed that shRNA targeting β-catenin in GBMs reduces monocytes attraction and impacts CCL2 secretion. The addition of recombinant CCL2 restores peripheral blood mononuclear cells (PBMC) migration towards medium (TCM) conditioned by shβ-catenin GBM cells. CCL2 knockdown in GBM cells shows similar effects and reduces monocyte migration to a similar extent as β-catenin knockdown. When investigating the effect of CCL2 on β-catenin activity, we found that CCL2 modulates components of the Wnt/β-catenin pathway and alters the clonogenicity of GBM cells. In addition, the pharmacological β-catenin inhibitor MSAB reduces active β-catenin, downregulates the expression of associated genes and alters CCL2 secretion. Taken together, we showed that β-catenin plays an important role in attracting monocytes towards GBM cells in vitro. We hypothesize that the interactions between β-catenin and CCL2 contribute to maintenance of GSCs via modulating immune cell interaction and promoting GBM growth and recurrence. [ABSTRACT FROM AUTHOR]

Salamanders are often used as a model of early tetrapod locomotion, due to their generalized tetrapod body plan. We imaged five individuals of wandering salamander, Aneides vagrans, during horizontal and vertical locomotion and compared kinematic and gait adjustments made to compensate for each condition. We used ImageJ to calculate duty factor, stride length, stride frequency, contralateral foot spread, heading of climbing, and forward velocity. Like other terrestrial salamanders, A. vagrans use a diagonal couplet, lateral sequence walk on horizontal surfaces. When walking vertically, however, they use a single‐foot gait, taking smaller steps and extending the duty factor compared with level walking. Salamanders adjusted their limbs to have a wider contralateral foot spread between fore‐ and hindfeet when walking downward as compared to walking upward or horizontally. These gait adjustments may minimize the risk of slipping or falling by increasing the number of contact points during the stride cycle, and by bringing their center of mass closer to the surface. We found that salamanders moved at a significantly faster velocity when traveling horizontally compared to vertically. Furthermore, we found no significant difference between upward and downward velocity, despite greater stride lengths in upward locomotion; this was explained by a higher stride frequency in downward locomotion. We estimate travel time up or down an old‐growth redwood tree to be on the scale of hours, a significant time investment that may encourage alternatives when available. These results suggest that, in an ecological context, while salamanders are capable of traveling straight down a redwood tree, they may simply tend to jump. [ABSTRACT FROM AUTHOR]

Introduction. Emergency department (ED) triage regarding infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is challenging. During the coronavirus disease 2019 (COVID-19) outbreak in Germany, the diagnostic outcomes of critically ill patients admitted to the resuscitation room in the ED of our academic 754-bed hospital should be analyzed. Methods. All resuscitation room patients between March 1st and April 15th 2020 were included in this retrospective study. Every patient with suspicion of SARS-CoV-2 infection received a pharyngeal swab for real-time polymerase chain reaction (rt-PCR), divided in the clinical subgroups of "highly suspicious for COVID-19" and "COVID-19 as differential diagnosis." All respiratory and infectious symptoms were included as at least "differential diagnosis" as an expanded suspicion strategy. Results. Ninety-five patients were included (trauma n = 14 , critically ill n = 81). Of 3 highly suspicious patients, 2 had rt-PCR positive pharyngeal swabs. In 39 patients, COVID-19 was defined as differential diagnosis, and 3 were positive for SARS-CoV-2. Of them, pharyngeal swabs were positive in 1 case, while in 2 cases, only tracheal fluid was rt-PCR positive while the pharyngeal swabs were negative. In one of these 2 cases, chest computed tomography (CT) was also negative for ground-glass opacities but showed a pulmonary abscess and pulmonary embolism. Conclusion. We recommend an expanded suspicion strategy for COVID-19 due to unexpected diagnostic outcomes. Personal protective equipment should be used in every resuscitation room operation due to unexpected cases and initial knowledge gaps. Furthermore, tracheal fluid should be tested for SARS-CoV-2 in every intubated patient due to cases with negative pharyngeal swabs and negative chest CT. [ABSTRACT FROM AUTHOR]

In the present work, the analytical model proposed by Van Houtte et al. (1993) is applied to predict geometric earing in cup drawing using a non-circular blank geometry. In order to validate the theoretical results, non-linear finite element simulations were carried out. It is observed that the predictions of the theoretical model are in close agreement with the results of the finite element simulations, even for unusual blank contours. Based on this confidence, the analytical earing model is paired with a simple iterative earing compensation procedure in order to calculate the blank contour which is required to obtain an earing-free cup. These results, in turn, are confronted with those obtained by means of the analytical earing compensation approach proposed by Engler et al. (2011). Very good agreement between both approaches is found. Practical applications of the analytical earing compensation approach involving anisotropic materials demonstrate its very good performance. [ABSTRACT FROM AUTHOR]

Earliest Carboniferous stromatolites were found in the Qianheishan (QHS) Formation in the Dashuigou section, Gansu Province, northwestern China. These stromatolites are exposed in a conglomerate‐dominated succession of about 22.5 m in thickness, which can be traced laterally for more than 200 m in outcrop. They consist mainly of micrite, peloids, oncoids, silt‐sized quartz grains, and sparry calcite with rare fine to coarse quartz grains and bioclasts. The occurrence of marine fossils (e.g., bryozoans) and fenestral structures in the stromatolites suggests that they developed in intertidal environments. Three types of stromatolite laminae were distinguished including micritic laminae, grain‐dominated mixed laminae, and micrite‐dominated mixed laminae. These laminae are separated by thin micritic crusts and form two lamination styles of repetitive lamination and alternating lamination. The development of grain‐rich and micrite‐rich laminae in the stromatolites implies that they were formed by the combination of microbial baffling, binding, and calcification. Facies analysis suggests that growth and demise of the stromatolites were controlled by relative sea‐level changes. They grew during a continuous relative sea‐level rise, indicated by variations in their thickness and morphology. Stromatolites change from thin‐bedded laminar forms in the lower part of the studied interval to medium‐bedded wavy‐laminar forms and thick‐bedded domal forms in the middle and upper parts, respectively. Their demise was triggered by dramatic relative sea‐level fall, evidenced from the sandstone facies overlying the stromatolite interval. The occurrence of the QHS stromatolites provides an excellent example for microbial proliferation and profound changes in the marine biosphere after the end‐Devonian Hangenberg extinction event. [ABSTRACT FROM AUTHOR]

Mitochondria supply virtually all eukaryotic cells with energy through ATP production by oxidative phosphoryplation (OXPHOS). Accordingly, maintenance of mitochondrial function is fundamentally important to sustain cellular health and various diseases have been linked to mitochondrial dysfunction. Biogenesis of OXPHOS complexes crucially depends on mitochondrial DNA (mtDNA) that encodes essential subunits of the respiratory chain and is distributed in multiple copies throughout the mitochondrial network. During cell division, mitochondria, including mtDNA, need to be accurately apportioned to daughter cells. This process requires an intimate and coordinated interplay between the cell cycle, mitochondrial dynamics and the replication and distribution of mtDNA. Recent years have seen exciting advances in the elucidation of the mechanisms that facilitate these processes and essential key players have been identified. Moreover, segregation of qualitatively distinct mitochondria during asymmetric cell division is emerging as an important quality control step, which secures the maintenance of a healthy cell population. [ABSTRACT FROM AUTHOR]

In this paper, we propose a reduced order approach for 3D variational data assimilation governed by parameterized partial differential equations. In contrast to the classical 3D-VAR formulation that penalizes the measurement error directly, we present a modified formulation that penalizes the experimentally observable misfit in the measurement space. Furthermore, we include a model correction term that allows to obtain an improved state estimate. We begin by discussing the influence of the measurement space on the amplification of noise and prove a necessary and sufficient condition for the identification of a "good" measurement space. We then propose a certified reduced basis (RB) method for the estimation of the model correction, the state prediction, the adjoint solution, and the observable misfit with respect to the true state for real-time and many-query applications. A posteriori bounds are proposed for the error in each of these approximations. Finally, we introduce different approaches for the generation of the reduced basis spaces and the stability-based selection of measurement functionals. The 3D-VAR method and the associated certified reduced basis approximation are tested in a parameter and state estimation problem for a steady-state thermal conduction problem with unknown parameters and unknown Neumann boundary conditions. [ABSTRACT FROM AUTHOR]

Background Longitudinal studies on associations between changes in living environment and health are few and focus on movers. Next to causal effects, differences in health can, however, result due to residential mobility. The present study explored changes in living environment related to (changes in) physical health among non-movers. Causality was reinforced by a novel study design. Methods We obtained longitudinal data on both living environment and physical health covering 4601 non-movers aged 18+ with 16 076 health observations from the German Socio-Economic Panel between 1999 and 2014. Changing and stable perceived living environment from three domains (infrastructure, environmental pollution, housing conditions) were included at household level. We performed linear regressions with robust standard errors and generalized estimating equations to predict the physical component summary (PCS) at baseline and changes in PCS over time. Results Stable moderate and worst as well as worsened environmental pollution and infrastructure were associated with worse PCS at baseline, as were stable poor and worsened housing conditions. Stable worst infrastructure was associated with negative changes in PCS for both sexes. Men's changes in PCS were more affected by worsened environmental pollution than women's. Conclusion A suboptimal living environment has short- and long-term negative effects on physical health. Because even short-term changes in the living environment have an immediate influence on an individual's health status and health trajectories, public attention to living environment is essential to fight existing health inequalities. [ABSTRACT FROM AUTHOR]

The "Calcaires à Productus " or "Calcaires à Productus giganteus " on the southern slope of the Montagne Noire (Hérault, France) consist of numerous isolated olistolitic limestone blocks, generally transported by gravitational flows into siliciclastic basinal deposits. The present paper is the first systematic monographic study of gigantoproductids, semiplanids, and some other large-sized productid brachiopods from the upper Viséan to Serpukhovian strata of the Montagne Noire. Gigantoproductids are represented by abundant Datangia semiglobosa and Kansuella spp.; a single Globosoproductus specimen is described. The semiplanids are represented by Latiproductus aff. latissimus , L. latissimus complicatus and L. edelburgensis , and the linoproductids by Balakhonia aff. kokdscharensis. The Montagne Noire productid faunas are found in very different facies including shell beds and microbial mounds. They are most abundant in assemblages from agitated, shallow water environments with a firm substrate where rugose corals are rare or absent. The palaeobiogeographical relations to the other regions in the western Palaeotethys are often limited to taxa with an almost cosmopolitan character. Worth noting is the absence of Gigantoproductus sensu stricto in the Montagne Noire. This genus, and other brachiopod taxa, migrated probably during the late Serpukhovian into southern France. On a larger scale, the presence of Kansuella indicates faunal exchanges with the eastern Palaeotethys (South China) via a westward migration path along North China, the Central Asian Orogenic Belt and south-eastern Laurussia. The studied taxa, even at the genus level, did not migrate into North America even if the Alleghanian Isthmus was still open. [ABSTRACT FROM AUTHOR]

We consider optimal sensor placement for a family of linear Bayesian inverse problems characterized by a deterministic hyper-parameter. The hyper-parameter describes distinct configurations in which measurements can be taken of the observed physical system. To optimally reduce the uncertainty in the system's model with a single set of sensors, the initial sensor placement needs to account for the non-linear state changes of all admissible configurations. We address this requirement through an observability coefficient which links the posteriors' uncertainties directly to the choice of sensors. We propose a greedy sensor selection algorithm to iteratively improve the observability coefficient for all configurations through orthogonal matching pursuit. The algorithm allows explicitly correlated noise models even for large sets of candidate sensors, and remains computationally efficient for high-dimensional forward models through model order reduction. We demonstrate our approach on a large-scale geophysical model of the Perth Basin, and provide numerical studies regarding optimality and scalability with regard to classic optimal experimental design utility functions. • Proposes an efficient, sequential optimal sensor placement algorithm for hyper-parameterized problems with correlated noise. • Chooses sensors based on an observability coefficient, β , requiring only a single full-order model solve per selected sensor. • Analyses β 's sensitivity to model approximations and its relation to the max eigenvalue of the posterior covariance matrix. • Proposes sensor selection algorithm that iteratively improves the observability coefficient over all hyper-parameters. • Tested using a large-scale geophysical model of the Perth Basin. [ABSTRACT FROM AUTHOR]

Highlights • This paper describes the development of in situ test equipment for the study of fundamental processes in production engineering. • An in situ turning device was developed, tested and used to observe the chip formation on the microstructure scale of a steel sample. • Laser beam micro welding was integrated into the LC-SEM to achieve in situ analysis of the welding process of stainless steel. • A heating module was employed for in situ wetting experiments to observe the formation and solidification of the melt of a tin-copper brazing filler on an aluminium cast alloy. Abstract A large-chamber scanning electron microscope (LC-SEM) provides an ideal platform for the installation of large-scale in situ experiments. Our LC-SEM has internal chamber dimensions of 1,2 × 1,3 × 1,4 m3 (W × H × D) (Fig.1) and makes it possible to incorporate novel in situ experimental devices, which are reported on here. The present manuscript describes in detail the development of in situ test equipment for the study of a broad range of processes in production engineering. Direct observation of the materials modification mechanisms provides fundamental insight into the underlying process characteristics. An in situ turning device was developed, tested and used to observe the chip formation on the microstructure scale of a 43CrMo4-sample. Laser beam micro welding was integrated into the LC-SEM to achieve in situ analysis of the welding process on stainless steel 1.4310. A heating module was employed for in situ wetting experiments to observe the formation and solidification of the melt of a tin-copper brazing filler on an aluminium cast alloy. [ABSTRACT FROM AUTHOR]

The Pennsylvanian to lower Permian succession at Madiyi, South China, represents a nearshore mixed siliciclastic‐carbonate system characterized by cyclic sedimentation patterns along a depth gradient from continental siliciclastics to marine open platform carbonates. Various palaeokarst features related to subaerial exposure are widely distributed. Additionally, pedogenesis was pervasive. The identification of twenty‐eight sedimentary cycles grouped into five sequences allows the reconstruction of a relative sea‐level curve. The cycles represent higher frequency changes superimposed on the long‐term evolution. After the initial transgression, the sea level remained relatively low in the late Bashkirian to early Moscovian. Then, it rose stepwise until a major drop occurred in the late Moscovian. Afterwards, the sea level rose again, but marine sedimentation ceased during at least the early Kasimovian. The area was flooded in the late Kasimovian, and the sea level rose until a late Gzhelian sea‐level drop. The subsequent marine sequence contains uppermost Gzhelian to upper Asselian deposits, which are capped by lower Permian continental facies associated with a major regional regression. Shallow to deeper marine sedimentary settings recorded high‐frequency sea‐level changes throughout South China during the late Bashkirian to Asselian. The main transgression–regression cycles are clearly associated with different depositional settings during several time intervals. Furthermore, the good correlations among South China, Ukraine, and the U.S. Mid‐continent are rooted in the impact of Gondwanan glaciations on the global sedimentation patterns. However, not all changes at Madiyi are the result of glacio‐eustatic sea‐level fluctuations; some are related to the local subsidence history and the rise of the Xuefeng Uplift. [ABSTRACT FROM AUTHOR]

Three efficient methods for five-membered ring carbocycle synthesis have been developed from simple starting materials using samarium(II) reagents. A Reformatsky aldol reaction proceeded efficiently with samarium(II) iodide using lithium bromide as an additive. A new intramolecular alkylation of a samarium enolate was realized with a pendant sulfonate ester leaving group. Pinacol cyclization of a simple diketone was also demonstrated giving a diol product in high stereoselectivity. A promising lead result has been established demonstrating enantioselectivity in a chiral ligand controlled Reformatsky aldol reaction. [ABSTRACT FROM AUTHOR]

DC-SIGN is a cell-surface receptor for several pathogenic threats, such as HIV, Ebola virus, or Mycobacterium tuberculosis. Multiple attempts to develop inhibitors of the underlying carbohydrate-protein interactions have been undertaken in the past fifteen years. Still, drug-like DC-SIGN ligands are sparse, which is most likely due to its hydrophilic, solvent-exposed carbohydrate-binding site. Herein, we report on a parallel fragment screening against DC-SIGN applying SPR and a reporter displacement assay, which complements previous screenings using 19F NMR spectroscopy and chemical fragment microarrays. Hit validation by SPR and 1H-15N HSQC NMR spectroscopy revealed that although no fragment bound in the primary carbohydrate site, five secondary sites are available to harbor drug-like molecules. Building on key interactions of the reported fragment hits, these pockets will be targeted in future approaches to accelerate the development of DC-SIGN inhibitors. [ABSTRACT FROM AUTHOR]

Der Oberflächenrezeptor DC ‐ SIGN ermöglicht die Aufnahme von Krankheitserregern wie HIV, Ebolavirus oder Mycobacterium tuberculosis. Daher gab es zahlreiche Versuche, Inhibitoren gegen die Bindung dieses Rezeptors an Kohlenhydratstrukturen dieser Pathogene zu entwickeln. Wegen der hydrophilen und wenig markanten Glykan ‐ Bindestelle kennt man nur wenige Wirkstoff ‐ ähnliche Liganden für DC ‐ SIGN. Parallele Fragment ‐ Screenings mit SPR ‐ Spektroskopie und einem Reporter Displacement Assay ergänzen vorherige Screenings mit 19F ‐ NMR ‐ Spektroskopie und chemischen Mikroarrays. Die Validierung aktiver Substanzen mit SPR ‐ und 1H ‐ 15N ‐ HSQC ‐ NMR ‐ Spektroskopie zeigte, dass kein Fragment in die primäre Kohlenhydrattasche bindet, dafür jedoch fünf sekundäre Bindestellen vorhanden sind, die mit Wirkstoff ‐ ähnlichen Molekülen interagieren können. Mithilfe der Schlüsselinteraktionen der hier gezeigten Fragmente können diese Regionen gezielt erkundet und zukünftige Ansätze zur Entwicklung von DC ‐ SIGN ‐ Inhibitoren beschleunigt werden. Mehrere Bindetaschen: DC ‐ SIGN, seit 15 Jahren bekannt für seine Rolle in der HIV ‐ trans ‐ Infektion von T ‐ Zellen, ist eines der vielversprechendsten Zielproteine aus der Familie der Glykan ‐ bindenden Proteine. Trotzdem sind nur wenige Wirkstoff ‐ ähnliche Effektoren bekannt, was sich möglicherweise mithilfe von sekundären Bindetaschen umgehen lassen könnte, die durch Wirkstoffe adressierbar sind. [ABSTRACT FROM AUTHOR]

Late Viséan brachiopods from the eastern Tafilalt (Morocco), and more precisely from the area comprised between the Jebel Begaa to the southwest, and Gara El Itima to the northeast (close to the Algerian border), are described systematically for the first time. Despite the limited material available, 18 species belonging to 17 genera have been recognized within the limestone beds of the Merdani and Zrigat formations, in which the productides (Productidina) and spiriferides are the most diverse. Representatives of the subfamily Gigantoproductidinae, which are close, if not conspecific, to those present in contemporaneous rocks of the nearby Béchar Basin (Algeria), occur in the late Viséan Zrigat Formation. Additional research based on more abundant material is necessary to investigate thoroughly the relationships existing between the Béchar Basin and the Tafilalt, which may have been part of the former during the Carboniferous. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Many biological processes from infection to tumor immune evasion are controlled by cell surface sialylation. To gather further insight into these processes, methods to alter cell surface sialylation are required. One way to achieve this is inhibiting the key enzyme of sialic acid de novo biosynthesis, the intracellular bifunctional UDP- N-acetylglucosamine epimerase/ N-acetylmannosamine kinase (GNE/MNK). Here, we present low molecular weight inhibitors of MNK activity based on picolinic acid derivatives. They were identified in a fragment screening using 19F NMR and validated in a biochemical inhibition assay followed by a structure-activity relationship analysis and docking. The optimized compound 6-carbamoylpicolinic acid inhibits MNK with a double-digit micromolar affinity. Its low molecular weight (166 Da) renders this picolinic acid derivative an exquisite starting point for the development of high-affinity MNK inhibitors, which may serve as molecular probes or lead candidates in future. [ABSTRACT FROM AUTHOR]

Incorporation of early druggability assessment in the drug discovery process provides a means to prioritize target proteins for high-throughput screening. We present chemical fragment arrays as a method that is capable of determining the druggability of a given target with low protein and compound consumption, enabling rapid decision making during early phases of drug discovery. [ABSTRACT FROM AUTHOR]

The Permocarboniferous siliciclastic formations represent the largest hydrothermal reservoir in the northern Upper Rhine Graben in SW Germany and have so far been investigated in large-scale studies only. The Cenozoic Upper Rhine Graben crosses the Permocarboniferous Saar-Nahe Basin, a Variscan intramontane molasse basin. Due to the subsidence in this graben structure, the top of the up to 2-km-thick Permocarboniferous is located at a depth of 600-2900 m and is overlain by Tertiary and Quaternary sediments. At this depth, the reservoir temperatures exceed 150 °C, which are sufficient for geothermal electricity generation with binary power plants. To further assess the potential of this geothermal reservoir, detailed information on thermophysical and hydraulic properties of the different lithostratigraphical units and their depositional environment is essential. Here, we present an integrated study of outcrop analogues and drill core material. In total, 850 outcrop samples were analyzed, measuring porosity, permeability, thermal conductivity and thermal diffusivity. Furthermore, 62 plugs were taken from drillings that encountered or intersected the Permocarboniferous at depths between 1800 and 2900 m. Petrographic analysis of 155 thin sections of outcrop samples and samples taken from reservoir depth was conducted to quantify the mineral composition, sorting and rounding of grains and the kind of cementation. Its influence on porosity, permeability, the degree of compaction and illitization was quantified. Three parameters influencing the reservoir properties of the Permocarboniferous were detected. The strongest and most destructive influence on reservoir quality is related to late diagenetic processes. An illitic and kaolinitic cementation and impregnation of bitumina document CO- and CH-rich acidic pore water conditions, which are interpreted as fluids that migrated along a hydraulic contact from an underlying Carboniferous hydrocarbon source rock. Migrating oil and acidic waters led to the dissolution of haematite cements in the lower Permocarboniferous formations. During the Eocene, subsidence of the Upper Rhine Graben porosities and permeabilities of the sandstones of these formations were strongly reduced to 2.5 % and 3.2 × 10 m. The second important influence on reservoir quality is the distinct depositional environment and its influence on early diagenetic processes. In early stage diagenesis, the best influence on reservoir properties exhibits a haematite cementation. It typically occurs in eolian sandstones of the Kreuznach Formation (Upper Permocarboniferous) and is characterized by grain covering haematite coatings, which are interpreted to inhibit cementation, compaction and illitization of pore space during burial. Eolian sandstones taken from outcrops and reservoir depths exhibit the highest porosities (16.4; 12.3 %) and permeabilities (2.0 × 10; 8.4 × 10 m). A third important influence on reservoir quality is the general mineral composition and the quartz content which is the highest in the Kreuznach Formation with 73.8 %. Based on the integrated study of depositional environments and diagenetic processes, reservoir properties of the different Permocarboniferous formations within the northern Upper Rhine Graben and their changes with burial depth can be predicted with satisfactory accuracy. This leads to a better understanding of the reservoir quality and enables an appropriate well design for exploration and exploitation of these geothermal resources. [ABSTRACT FROM AUTHOR]

This Article directs scholarly and regulatory attention to an overlooked subcategory within online and mobile entities that offer financial services--big data and social netbanks. Recently, big data companies like Google, Amazon, and Apple, as well as social networks like Facebook and Twitter, have been making forays into the financial services market, capitalizing on their massive troves of user data and social information. Providing the first in-depth study of big data and social netbanks, this Article analyzes these players' entry into the financial services market and surveys the current regulatory framework for those new bank-like entities. Despite the large numbers of technology companies offering financial services and their massive pool of subscribers, regulation of online nonbanks currently consists of a hodgepodge of statutes and regulations. In particular, as this Article shows, existing regulation does not differentiate between this recently emerging form of bank-like services and other online/mobile nonbanks. As big data and social netbanks increasingly eat at the edges of the traditional banking market, this Article makes a key descriptive contribution by presenting a comprehensive analysis of the new entrants. This Article also makes a significant normative contribution by listing the distinctive characteristics of big data and social netbanks and other issues that regulators should be mindful of when designing an appropriate regulatory scheme. These characteristics and issues include consumers' access to financial services, social consequences, competition in the financial market, cybersecurity, privacy, and specific consumers' rights. [ABSTRACT FROM AUTHOR]

Mass spectrometry-based metabolome profiling became the method of choice in systems biology approaches and aims to enhance biological understanding of complex biological systems. Genomics, transcriptomics, and proteomics are well established technologies and are commonly used by many scientists. In comparison, metabolomics is an emerging field and has not reached such high-throughput, routine and coverage than other omics technologies. Nevertheless, substantial improvements were achieved during the last years. Integrated data derived from multi-omics approaches will provide a deeper understanding of entire biological systems. Metabolome profiling is mainly hampered by its diversity, variation of metabolite concentration by several orders of magnitude and biological data interpretation. Thus, multiple approaches are required to cover most of the metabolites. No software tool is capable of comprehensively translating all the data into a biologically meaningful context yet. In this review, we discuss the advantages of metabolome profiling and main obstacles limiting progress in systems biology. [ABSTRACT FROM AUTHOR]

A biography of Edouard Poty, palaeontologist and geologist, is presented. He was born in Searing, Belgium in 1949. He entered the University of Liège, Belgium in 1967 to study geology, which was at that time, Geological and Mineralogical Sciences. He enrolled in civilian service as a mathematics teacher in Algeria.

Biodiversity hotspots are defined as areas of unusually high biological diversity. This definition is less clear for palaeohotspots but the Royseux locality in Southern Belgium is interpreted as such a site because of the large number of coral species that co-occur within a small area and short time interval. Forty-one species (29 genera) of rugose, tabulate and heterocorallia corals are known within a 6 m-thick 4th order parasequence (100 kyr). These numbers increase to 50 species in 30 genera if the entire succession is considered. Consequently, Royseux is regarded as the richest site for late Viséan coral diversity on a global scale. Comparison with other sites from Spain, Morocco, the British Isles, and eastern Australia confirms this view. The diversity of brachiopods (at least 18 species within 16 genera) and other invertebrates is also assessed. The great palaeobiodiversity is tentatively explained by the interplay of several global and local causes, including high late Viséan biodiversity at the global scale associated with tectonically and sedimentarydriven micro-environment differentiation. Conversely, the Royseux locality has yielded few endemic taxa. [ABSTRACT FROM AUTHOR]

The Kulm facies of the Montagne Noire formed in a foreland basin south of the French Massif Central. During the preorogenic phase (Tournaisian -- early late Viséan) two major facies domains can be differentiated in the Montagne Noire. The Mont Peyroux Succession represents more distal environments with an almost continuous stratigraphical record, which displays the development from a deeper-water carbonate platform to a starved basin facies, which is followed by the onset of calciturbidite deposition. The contemporaneous Ecailles Succession, only found in exotic blocks, represents the proximal environments with important stratigraphical gaps. The synorogenic phase of the basin (early late Viséan -- Serpukhovian?) is characterized by flysch deposits, which contain in the later stages large exotic blocks indicating the final collapse of a mixed-siliciclastic carbonate shelf system. Differences in the Kulm sequence of the Carboniferous foreland basin of southern France (Montagne Noire, Mouthoumet Massif and Pyrénées) are due to different local palaeotopographies and distances to platform areas and sediment sources in the preorogenic sedimentation, and the timing of the onset of the synorogenic sedimentation and the migration of the depocentre from east to west. Striking similarities in respect to the overall facies, but also to the development of particular facies during a particular time slice exist to the succession of the Rhenish Kulm Basin, especially its north-western part; e.g. dark shales with phosphatic nodules during the Lower Alum Shale Event or the interruption of the bedded chert deposition by deeper water carbonates during the latest Tournaisian -- earliest Viséan. [ABSTRACT FROM AUTHOR]

Copyright literature has been long familiar with the lack of licensing choices in various creative markets. In the absence of lawful licensing alternatives, consumers of works as well as secondary creators wishing to use protected elements of preexisting works are often left with no choice but to either infringe on the copyright or refrain from the use. As the dearth of licensing impedes further creation, it greatly conflicts with the utilitarian foundation of copyright and its constitutional goal to promote creative progress. Legal scholarship has submitted various recommendations in response to the licensing failure, but none of them has proved to be effective in alleviating copyright's licensing shortage. This article contributes to the ongoing discourse by introducing the subtle incentive theory of copyright licensing. The subtle incentive theory encourages rightholders to engage in licensing by considering the lack of licensing alternatives in the market for a particular work as a mitigating factor in the fair use analysis. Specifically, the subtle incentive theory propounds the mirror image of a test that was already mandated in American Geophysical Union v. Texaco in the mid-1990s, but which has since been used exclusively to deny fair use. By so doing, the subtle incentive theory mends a logical error in fair use reasoning and promotes a better creation market by making a zero-cost doctrinal change to ameliorate copyright licensing shortfalls. While the subtle incentive theory avoids aggressive interference in market dynamics and respects rightholders' proprietorial choices, it does not leave the licensing failure to be repaired exclusively by the market, and adds an important policy statement as to the significance of original and secondary creation alike. [ABSTRACT FROM AUTHOR]

The article reports on a study related to the crystal structure of kindlin-2 which plays a significant role in integrin activation, clustering and signaling. It defines integrins as the family of heterodimeric adhesion molecules which mediate cell matrix adhesion by binding extracellular matrix proteins such as collagens, fibronectin and laminins. It also mentions significance of adhesome in transmitting biochemical signals into the cell and connect integrins to the actin cytoskeleton.

MUTYH-associated polyposis (MAP) is an autosomal recessive adenomatous polyposis caused by biallelic germline mutations of the base-excision-repair gene MUTYH. In MAP patients of European origin, the combined allele frequency of the mutations p.Tyr179Cys and p.Gly396Asp ranges between 50 and 82%, while these mutations have not been identified in Far Eastern Asian populations, supporting the hypothesis that a founder effect has occurred at some point in European history. To investigate the natural history of the two common European MUTYH alleles, we genotyped six gene-flanking microsatellite markers in 80 unrelated Italian and German MAP patients segregating one or both mutations and calculated their age in generations (g) by using DMLE+2.2 software. Three distinct common haplotypes, one for p.Tyr179Cys and two for p.Gly396Asp, were identified. Estimated mutation ages were 305 g (95% CS: 271-418) for p.Tyr179Cys and 350 g (95% CS: 313-435) for p.Gly396Asp. These results provide evidence for strong founder effects and suggest that the p.Tyr179Cys and p.Gly396Asp mutations derive from ancestors who lived between 5-8 thousand years and 6-9 thousand years B.C., respectively. [ABSTRACT FROM AUTHOR]

The Tournaisian and Viséan were formerly considered as series and in Belgium were divided into two (Hastarian and Ivorian) and three stages (Moliniacian, Livian and Warnantian), which are now considered as substages. The Belgian substages are based on conodonts and foraminifers, and incidentally on rugose corals, and are described here. Their boundaries, biostratigraphy and sequence stratigraphy are well detailed and clearly defined. The base of the Hastarian (lower Tournaisian) corresponds to the base of the Tournaisian (base of Carboniferous); the base of the Ivorian (upper Tournaisian) corresponds to the appearance of the conodont Polygnathus communis carina, a little above the last Siphonodella; the base of the Moliniacian (lower Viséan) corresponds to the base of the Viséan stage defined by the first occurrence of the foraminifer Eoparastaffella simplex; the Livian (middle Viséan) corresponds to the foraminiferal MFZ12 Zone and is marked by the appearance of Koskinotextularia and Pojarkovella nibelis; the base of the Warnantian (upper Viséan) is marked by the appearance of Neoarchaediscus, Vissariotaxis, Planospirodiscus, and Palaeotextularia with a bilaminar wall, the index taxa of the MFZ13-Neoarchaediscus Zone. The up-to-date chronostratigraphic subdivision of the Tournaisian and Viséan is not limited to Belgium and the surrounding areas. It can be applied through Eurasia as far as South China. The Belgian units could therefore be the basis for a future international division of the Tournaisian into two parts (Hastarian and Ivorian) and of the Viséan into three parts (Moliniacian, Livian and Warnantian), corresponding to time intervals of c. 5–8 Ma. [ABSTRACT FROM AUTHOR]

Abstract: The present series of papers summarizes the results of a three-year research project on the realistic simulation of sound fields in car passenger compartments using a combined Finite Element (FE) and Geometrical Acoustics (GA) approach. The simulations are conducted for the whole audible frequency range with the loudspeakers of the car audio system as the sound sources. The challenges faced during the project relate to fundamental questions regarding the realistic sound field simulation in small enclosures with strong modal and diffraction effects. While Part I of this series of papers focusses on the determination of the boundary and source conditions for the simulation model of the car compartment, the present paper, denoted here as Part II, presents extensive objective and subjective comparisons of the corresponding room acoustic measurement and simulation results. By applying the FE method to the low frequency part of the room transfer function (RTF) the study aims at the quantification of potential objective and subjective benefits with regard to the simulation quality in small rooms, when compared to a purely geometrical acoustics approach. The main challenges and limitations in the simulation domain are due to the very small volume, the difficult to determine source and boundary conditions and the considerable diffraction effects (especially at the seats) in the car passenger compartments. In order to keep the complexity of the FE simulations at a manageable level, all boundary conditions were described by acoustic surface impedances and no fluid-structural coupling was considered in the FE simulation model. While the results of the study reveal that an overall good agreement regarding the energy distribution in time and frequency domain is generally possible even in such complex enclosures, the results also clearly show the limitations of the impedance boundary approach in the FE domain as well as the strong sensitivity of the simulation results with regard to the uncertainty in the boundary and source conditions in both simulation domains. It can thus be concluded, that possible fields of application of the FE extension in room acoustic simulations lie in the prediction of the modally dominated low frequency part of the RTF of well defined rooms and in the prediction of sound fields that are strongly affected by near-field or diffraction effects as in the car passenger compartment. However, due to the considerable problems in the determination of realistic boundary conditions for the FE model, improved measurement techniques are urgently needed to further improve the overall simulation quality. [Copyright &y& Elsevier]

Abstract: The present series of papers summarizes the results of a three-year research project on the realistic simulation of car audio sound in car passenger compartments using a combined Finite Element (FE) and Geometrical Acoustics (GA) approach. The simulations are conducted for the whole audible frequency range with the loudspeakers of the car audio system as the sound sources. The challenges faced during the project relate to fundamental questions regarding the realistic sound field simulation in small enclosures with strong modal and diffraction effects. The paper denoted here as Part I focuses on boundary and source representations in the FE and GA domain and suggests guidelines for a best-possible acquisition of the required data. Since a straight-forward determination of the boundary and source characteristics is mostly hampered by the immense complexity and inhomogeneity of the materials and loudspeaker configurations inside a car compartment, different measurement and calculation methods have been applied to determine the required data and quantify the corresponding uncertainty. The paper clearly points out the strength and weaknesses of the applied methods depending on the considered frequency range and material characteristics. In order to keep the complexity of the FE simulations at a manageable level, all passive boundaries were considered as locally reacting with impedance conditions. Part II of the study applies the obtained data in combined FE-GA room acoustic simulations and compares the simulated room impulse responses (RIR) with corresponding measurement results. In a final step the observed differences in the RIRs are related to the uncertainty and inherent errors in the boundary and source representation. [Copyright &y& Elsevier]

The article focuses on the importance of the public choice on the copyright law making. Topics discussed include public choice theory, impact of the public choice theory on the lawmaking and Stop Online Piracy Act (SOPA). It also discusses the Preventing Real Online Threats to Economic Creativity and Theft of Intellectual Property Act (PIPA).

Mapping of proteins involved in normal eye functions is a prerequisite to identify pathological changes during eye disease processes. We therefore analysed the proteome of human vitreous by applying in-depth proteomic screening technologies. For ethical reasons human vitreous samples were obtained by vitrectomy from "surrogate normal patients" with epiretinal gliosis that is considered to constitute only negligible pathological vitreoretinal changes. We applied different protein prefractionation strategies including liquid phase isoelectric focussing, 1D SDS gel electrophoresis and a combination of both and compared the number of identified proteins obtained by the respective method. Liquid phase isoelectric focussing followed by SDS gel electrophoresis increased the number of identified proteins by a factor of five compared to the analysis of crude unseparated human vitreous. Depending on the prefractionation method proteins were subjected to trypsin digestion either in-gel or in solution and the resulting peptides were analysed on a UPLC system coupled online to an LTQ Orbitrap XL mass spectrometer. The obtained mass spectra were searched against the SwissProt database using the Mascot search engine. Bioinformatics tools were used to annotate known biological functions to the detected proteins. Following this strategy we examined the vitreous proteomes of three individuals and identified 1111 unique proteins. Besides structural, transport and binding proteins, we detected 261 proteins with known enzymatic activity, 51 proteases, 35 protease inhibitors, 35 members of complement and coagulation cascades, 15 peptide hormones, 5 growth factors, 11 cytokines, 47 receptors, 30 proteins of visual perception, 91 proteins involved in apoptosis regulation and 265 proteins with signalling activity. This highly complex mixture strikingly differs from the human plasma proteome. Thus human vitreous fluid seems to be a unique body fluid. 262 unique proteins were detected which are present in all three patient samples indicating that these might represent the constitutive protein pattern of human vitreous. The presented catalogue of human vitreous proteins will enhance our understanding of physiological processes in the eye and provides the groundwork for future studies on pathological vitreous proteome changes. [ABSTRACT FROM AUTHOR]

Abstract: Two new yield functions for orthotropic sheet metals are proposed. The first one, called Yld2011-18p, provides 18 parameters that may be calibrated to experimental data. The second one, called Yld2011-27p, is a straightforward extension and provides 27 parameters. Both yield functions are unconditionally convex. Their formulations are based on the established concept of multiple linear transformations of the stress deviator. Furthermore, they are able to account for planar as well as for three-dimensional stress states. The proposed yield functions are applied to describe complex plastic anisotropies of different alloys. The ability of accurately predicting earing in cup-drawing is demonstrated by means of a non-linear finite element analysis. [Copyright &y& Elsevier]

The article presents a clinical utility gene card for adenomatous polyposis coli with autosomal recessive indications. It notes that a diagnostic approach of high frequency is needed in large deletions for gene dosage analysis. It mentions that intronic sequences on genomic DNA will need direct sequencing of exons.

The article discusses the highlights of the XIth International Symposium on Fossil Cnidaria and Porifera that was held in Liège, Belgium from August 19-29, 2011. The event was attended by 103 participants from 27 countries and 101 abstracts were presented. The first day of the post-symposium field-trip was devoted to the Strunian coral-stromatoporoid biostromes and the Devonian-Carboniferous transition.