A framework for the probabilistic analysis of meteotsunamis

This paper is not subject to U.S. copyright. The definitive version was published in Natural Hazards 74 (2014): 123-142, doi:10.1007/s11069-014-1294-1.A probabilistic technique is developed to assess the hazard from meteotsunamis. Meteotsunamis are unusual sea-level events, generated when the speed of an atmospheric pressure or wind disturbance is comparable to the phase speed of long waves in the ocean. A general aggregation equation is proposed for the probabilistic analysis, based on previous frameworks established for both tsunamis and storm surges, incorporating different sources and source parameters of meteotsunamis. Parameterization of atmospheric disturbances and numerical modeling is performed for the computation of maximum meteotsunami wave amplitudes near the coast. A historical record of pressure disturbances is used to establish a continuous analytic distribution of each parameter as well as the overall Poisson rate of occurrence. A demonstration study is presented for the northeast U.S. in which only isolated atmospheric pressure disturbances from squall lines and derechos are considered. For this study, Automated Surface Observing System stations are used to determine the historical parameters of squall lines from 2000 to 2013. The probabilistic equations are implemented using a Monte Carlo scheme, where a synthetic catalog of squall lines is compiled by sampling the parameter distributions. For each entry in the catalog, ocean wave amplitudes are computed using a numerical hydrodynamic model. Aggregation of the results from the Monte Carlo scheme results in a meteotsunami hazard curve that plots the annualized rate of exceedance with respect to maximum event amplitude for a particular location along the coast. Results from using multiple synthetic catalogs, resampled from the parent parameter distributions, yield mean and quantile hazard curves. Further refinements and improvements for probabilistic analysis of meteotsunamis are discussed

Hygiene, Sanitation, and Water: Forgotten Foundations of Health

As the first article in a four-part PLoS Medicine series on water and sanitation, Jamie Bartram and Sandy Cairncross argue that the massive burden of ill health associated with poor hygiene, sanitation, and water supply demands more attention from health professionals and policymakers

Mapping quantitative trait loci (QTL) in sheep. I. A new male framework linkage map and QTL for growth rate and body weight

A male sheep linkage map comprising 191 microsatellites was generated from a single family of 510 Awassi-Merino backcross progeny. Except for ovine chromosomes 1, 2, 10 and 17, all other chromosomes yielded a LOD score difference greater than 3.0 between the best and second-best map order. The map is on average 11% longer than the Sheep Linkage Map v4.7 male-specific map. This map was employed in quantitative trait loci (QTL) analyses on body-weight and growth-rate traits between birth and 98 weeks of age. A custom maximum likelihood program was developed to map QTL in half-sib families for non-inbred strains (QTL-MLE) and is freely available on request. The new analysis package offers the advantage of enabling QTL × fixed effect interactions to be included in the model. Fifty-four putative QTL were identified on nine chromosomes. Significant QTL with sex-specific effects (i.e. QTL × sex interaction) in the range of 0.4 to 0.7 SD were found on ovine chromosomes 1, 3, 6, 11, 21, 23, 24 and 26

Desire and Dread from the Nucleus Accumbens: Cortical Glutamate and Subcortical GABA Differentially Generate Motivation and Hedonic Impact in the Rat

Background: GABAergic signals to the nucleus accumbens (NAc) shell arise from predominantly subcortical sources whereas glutamatergic signals arise mainly from cortical-related sources. Here we contrasted GABAergic and glutamatergic generation of hedonics versus motivation processes, as a proxy for comparing subcortical and cortical controls of emotion. Local disruptions of either signals in medial shell of NAc generate intense motivated behaviors corresponding to desire and/or dread, along a rostrocaudal gradient. GABA or glutamate disruptions in rostral shell generate appetitive motivation whereas disruptions in caudal shell elicit fearful motivation. However, GABA and glutamate signals in NAc differ in important ways, despite the similarity of their rostrocaudal motivation gradients. Methodology/Principal Findings: Microinjections of a GABAA agonist (muscimol), or of a glutamate AMPA antagonist (DNQX) in medial shell of rats were assessed for generation of hedonic ‘‘liking’ ’ or ‘‘disliking’ ’ by measuring orofacial affective reactions to sucrose-quinine taste. Motivation generation was independently assessed measuring effects on eating versus natural defensive behaviors. For GABAergic microinjections, we found that the desire-dread motivation gradient was mirrored by an equivalent hedonic gradient that amplified affective taste ‘‘liking’ ’ (at rostral sites) versus ‘‘disliking’ ’ (at caudal sites). However, manipulation of glutamatergic signals completely failed to alter pleasure-displeasure reactions to sensory hedonic impact, despite producing a strong rostrocaudal gradient of motivation

Protein kinase C and cardiac dysfunction: a review

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure

HIV infection and HERV expression: a review

The human genome contains multiple copies of retrovirus genomes known as endogenous retroviruses (ERVs) that have entered the germ-line at some point in evolution. Several of these proviruses have retained (partial) coding capacity, so that a number of viral proteins or even virus particles are expressed under various conditions. Human ERVs (HERVs) belong to the beta-, gamma-, or spuma- retrovirus groups. Endogenous delta- and lenti- viruses are notably absent in humans, although endogenous lentivirus genomes have been found in lower primates. Exogenous retroviruses that currently form a health threat to humans intriguingly belong to those absent groups. The best studied of the two infectious human retroviruses is the lentivirus human immunodeficiency virus (HIV) which has an overwhelming influence on its host by infecting cells of the immune system. One HIV-induced change is the induction of HERV transcription, often leading to induced HERV protein expression. This review will discuss the potential HIV-HERV interactions

Visuospatial Integration: Paleoanthropological and Archaeological Perspectives

The visuospatial system integrates inner and outer functional processes, organizing spatial, temporal, and social interactions between the brain, body, and environment. These processes involve sensorimotor networks like the eye–hand circuit, which is especially important to primates, given their reliance on vision and touch as primary sensory modalities and the use of the hands in social and environmental interactions. At the same time, visuospatial cognition is intimately connected with memory, self-awareness, and simulation capacity. In the present article, we review issues associated with investigating visuospatial integration in extinct human groups through the use of anatomical and behavioral data gleaned from the paleontological and archaeological records. In modern humans, paleoneurological analyses have demonstrated noticeable and unique morphological changes in the parietal cortex, a region crucial to visuospatial management. Archaeological data provides information on hand–tool interaction, the spatial behavior of past populations, and their interaction with the environment. Visuospatial integration may represent a critical bridge between extended cognition, self-awareness, and social perception. As such, visuospatial functions are relevant to the hypothesis that human evolution is characterized by changes in brain–body–environment interactions and relations, which enhance integration between internal and external cognitive components through neural plasticity and the development of a specialized embodiment capacity. We therefore advocate the investigation of visuospatial functions in past populations through the paleoneurological study of anatomical elements and archaeological analysis of visuospatial behaviors

Parkinson’s disease mouse models in translational research

Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson’s disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research

Spotlight on Differentially Expressed Genes in Urinary Bladder Cancer

INTRODUCTION: We previously identified common differentially expressed (DE) genes in bladder cancer (BC). In the present study we analyzed in depth, the expression of several groups of these DE genes. MATERIALS AND METHODS: Samples from 30 human BCs and their adjacent normal tissues were analyzed by whole genome cDNA microarrays, qRT-PCR and Western blotting. Our attention was focused on cell-cycle control and DNA damage repair genes, genes related to apoptosis, signal transduction, angiogenesis, as well as cellular proliferation, invasion and metastasis. Four publicly available GEO Datasets were further analyzed, and the expression data of the genes of interest (GOIs) were compared to those of the present study. The relationship among the GOI was also investigated. GO and KEGG molecular pathway analysis was performed to identify possible enrichment of genes with specific biological themes. RESULTS: Unsupervised cluster analysis of DNA microarray data revealed a clear distinction in BC vs. control samples and low vs. high grade tumors. Genes with at least 2-fold differential expression in BC vs. controls, as well as in non-muscle invasive vs. muscle invasive tumors and in low vs. high grade tumors, were identified and ranked. Specific attention was paid to the changes in osteopontin (OPN, SPP1) expression, due to its multiple biological functions. Similarly, genes exhibiting equal or low expression in BC vs. the controls were scored. Significant pair-wise correlations in gene expression were scored. GO analysis revealed the multi-facet character of the GOIs, since they participate in a variety of mechanisms, including cell proliferation, cell death, metabolism, cell shape, and cytoskeletal re-organization. KEGG analysis revealed that the most significant pathway was that of Bladder Cancer (p = 1.5×10(-31)). CONCLUSIONS: The present work adds to the current knowledge on molecular signature identification of BC. Such works should progress in order to gain more insight into disease molecular mechanisms