Osmotic Pressure of Water in Nafion~

Mechanical failure modes leading to cracks or breeches in proton exchange membrane fuel cells are driven by mechanical forces associated with swelling from water uptake and shrinkage from dehumidifi-cation. To determine the magnitude of compressive mechanical stress imposed by water swelling in a proton exchange fuel-cell membrane, the osmotic pressure of water in a perfluorosulfonic acid ionomer (Nafion? N 117) membrane was measured using a hydrostatic piston-cylinder device with an in-situ hydrophilic frit. Experiments indicate that hydrostatic stresses greater than 103.5 MPa are created in a membrane when swollen with water at 23℃ suggesting that pressure from water swelling can distort Nafion N 117-based structures as the osmotic pressure is of the same order of magnitude as the flow stress of Nafion N 117.     

Patterns of somatic mutation in human cancer genomes

Cancers arise owing to mutations in a subset of genes that confer growth advantage. The availability of the human genome sequence led us to propose that systematic resequencing of cancer genomes for mutations would lead to the discovery of many additional cancer genes. Here we report more than 1,000 somatic mutations found in 274 megabases (Mb) of DNA corresponding to the coding exons of 518 protein kinase genes in 210 diverse human cancers. There was substantial variation in the number and pattern of mutations in individual cancers reflecting different exposures, DNA repair defects and cellular origins. Most somatic mutations are likely to be 'passengers' that do not contribute to oncogenesis. However, there was evidence for 'driver' mutations contributing to the development of the cancers studied in approximately 120 genes. Systematic sequencing of cancer genomes therefore reveals the evolutionary diversity of cancers and implicates a larger repertoire of cancer genes than previously anticipated.     

Molecular recognition of microbial lipid-based antigens by T cells

The immune system has evolved to protect hosts from pathogens. T cells represent a critical component of the immune system by their engagement in host defence mechanisms against microbial infections. Our knowledge of the molecular recognition by T cells of pathogen-derived peptidic antigens that are presented by the major histocompatibility complex glycoproteins is now well established. However, lipids represent an additional, distinct chemical class of molecules that when presented by the family of CD1 antigen-presenting molecules can serve as antigens, and be recognized by specialized subsets of T cells leading to antigen-specific activation. Over the past decades, numerous CD1-presented self- and bacterial lipid-based antigens have been isolated and characterized. However, our understanding at the molecular level of T cell immunity to CD1 molecules presenting microbial lipid-based antigens is still largely unexplored. Here, we review the insights and the molecular basis underpinning the recognition of microbial lipid-based antigens by T cells.     

Taxonomy and variation of the Lopidea nigridia complex of western North America (Heteroptera: Miridae, Orthotylinae)

External morphological variation in the Lopidea nigridia "complex" of western North America was examined using principal component analysis and showed continuous variation among populations in most characters. External morphology did not parallel paramere structure and did not substantiate previously recognized species. There was little correlation between dorsal coloration and paramere structure. Cluster analysis (UPGMA) using paramere and color characters failed to group populations coded as the same species and also failed to group all specimens of any one population. The variation in structure of the parameres and vesicae among populations of the nigridia complex was no greater than the interpopulational variation of these structures structures in the congeneric species marginata Uhler. Lopidea nigridia Uhler is treated as a polytypic species comprising three subspecies: Lopidea nigridia nigridia Uhler, a fuscous-white form from the sagebrush steppe of the Great Basin and the chaparral of southern California; Lopidea nigridia serica Knight, a solid red form from the eastern slopes of the Rocky Mountains from Alberta to Colorado and east across the Northern Great Plains to southern Manitoba; Lopidea nigridia aculeata Van Duzee, a polymorphic form varying from solid red to fuscous red and white from the Cascade Mountains and eastern slopes of the coastal ranges of British Columbia, Washington, and Oregon, the Blue and Wallawa mountains of Oregon and Washington, and throughout the Coastal and Sierra Nevada ranges of California. The following new synonymies are created: Lopidea nigridia Uhler -- Lopidea raineri Knight, Lopidea scullent Knight, Lopidea rolfsi Knight, and Lopidea wilcoxi Knight; Lopidea nigridia aculeata Van Duzee -- Lopidea nigridia hirta Van Duzee, Lopidea usingeri Van Duzee, Lopidea discreta Van Duzee, Lopidea fallax Knight, Lopidea Yakima Knight, Lopidea audeni Knight, Lopidea eriogoni Knight, Lopidea calcaria Knight, Lopidea chamberlini Knight, Lopidea angustata Knight, Lopidea rubrofusca Knight, and Lopidea flavicostata Knight and Schaffner; Lopidea nigridia serica Knight -- Lopidea medleri Akingbohungbe.     

Bayesian Analysis of Asymmetric Stochastic Conditional Duration Model

This paper proposes Markov chain Monte Carlo methods to estimate the parameters and log durations of the correlated or asymmetric stochastic conditional duration models. Following the literature, instead of fitting the models directly, the observation equation of the models is first subjected to a logarithmic transformation. A correlation is then introduced between the transformed innovation and the latent process in an attempt to improve the statistical fits of the models. In order to perform one‐step‐ahead in‐sample and out‐of‐sample duration forecasts, an auxiliary particle filter is used to approximate the filter distributions of the latent states. Simulation studies and application to the IBM transaction dataset illustrate that our proposed estimation methods work well in terms of parameter and log duration estimation. Copyright © 2014 John Wiley & Sons, Ltd.     

On the Benefits of Equicorrelation for Portfolio Allocation

The importance of modelling correlation has long been recognised in the field of portfolio management, with large‐dimensional multivariate problems increasingly becoming the focus of research. This paper provides a straightforward and commonsense approach toward investigating a number of models used to generate forecasts of the correlation matrix for large‐dimensional problems. We find evidence in favour of assuming equicorrelation across various portfolio sizes, particularly during times of crisis. During periods of market calm, however, the suitability of the constant conditional correlation model cannot be discounted, especially for large portfolios. A portfolio allocation problem is used to compare forecasting methods. The global minimum variance portfolio and Model Confidence Set are used to compare methods, while portfolio weight stability and relative economic value are also considered. Copyright © 2015 John Wiley & Sons, Ltd.     

The Hill equation and the origin of quantitative pharmacology

This review addresses the 100-year-old Hill equation (published in January 22, 1910), the first formula relating the result of a reversible association (e.g., concentration of a complex, magnitude of an effect) to the variable concentration of one of the associating substances (the other being present in a constant and relatively low concentration). In addition, the Hill equation was the first (and is the simplest) quantitative receptor model in pharmacology. Although the Hill equation is an empirical receptor model (its parameters have only physico-chemical meaning for a simple ligand binding reaction), it requires only minor a priori knowledge about the mechanism of action for the investigated agonist to reliably fit concentration-response curve data and to yield useful results (in contrast to most of the advanced receptor models). Thus, the Hill equation has remained an important tool for physiological and pharmacological investigations including drug discovery, moreover it serves as a theoretical basis for the development of new pharmacological models.     

Positron emission tomography after MPTP: observations relating to the cause of Parkinson's disease

The dopa analogue 6-fluorodopa (6-FD) used with positron emission tomography (PET) allows in vivo visualization of dopamine and its metabolites in nigrostriatal nerve endings. We have now found abnormal 6-FD scans in four subjects exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). None had parkinsonism. The results suggest subclinical damage to the nigrostriatal pathway. This is the first direct evidence that dopaminergic impairment can exist without clinical deficits. Here we discuss this finding in the context of the hypothesis that Parkinson's disease may stem from clinically silent damage to the substantia nigra, followed by slow attrition of neurones in this region because of its particular vulnerability to cell loss as a normal consequence of ageing.     

Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells

Myeloid cells are a feature of most tissues. Here we show that during development, retinal myeloid cells (RMCs) produce Wnt ligands to regulate blood vessel branching. In the mouse retina, where angiogenesis occurs postnatally, somatic deletion in RMCs of the Wnt ligand transporter Wntless results in increased angiogenesis in the deeper layers. We also show that mutation of Wnt5a and Wnt11 results in increased angiogenesis and that these ligands elicit RMC responses via a non-canonical Wnt pathway. Using cultured myeloid-like cells and RMC somatic deletion of Flt1, we show that an effector of Wnt-dependent suppression of angiogenesis by RMCs is Flt1, a naturally occurring inhibitor of vascular endothelial growth factor (VEGF). These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching.