WorldWideScience

Sample records for human variation application

  1. Size variation in Middle Pleistocene humans.

    Science.gov (United States)

    Arsuaga, J L; Carretero, J M; Lorenzo, C; Gracia, A; Martínez, I; Bermúdez de Castro, J M; Carbonell, E

    1997-08-22

    It has been suggested that European Middle Pleistocene humans, Neandertals, and prehistoric modern humans had a greater sexual dimorphism than modern humans. Analysis of body size variation and cranial capacity variation in the large sample from the Sima de los Huesos site in Spain showed instead that the sexual dimorphism is comparable in Middle Pleistocene and modern populations.

  2. HGVA: the Human Genome Variation Archive

    OpenAIRE

    Lopez, Javier; Coll, Jacobo; Haimel, Matthias; Kandasamy, Swaathi; Tarraga, Joaquin; Furio-Tari, Pedro; Bari, Wasim; Bleda, Marta; Rueda, Antonio; Gr?f, Stefan; Rendon, Augusto; Dopazo, Joaquin; Medina, Ignacio

    2017-01-01

    Abstract High-profile genomic variation projects like the 1000 Genomes project or the Exome Aggregation Consortium, are generating a wealth of human genomic variation knowledge which can be used as an essential reference for identifying disease-causing genotypes. However, accessing these data, contrasting the various studies and integrating those data in downstream analyses remains cumbersome. The Human Genome Variation Archive (HGVA) tackles these challenges and facilitates access to genomic...

  3. Understanding human DNA sequence variation.

    Science.gov (United States)

    Kidd, K K; Pakstis, A J; Speed, W C; Kidd, J R

    2004-01-01

    Over the past century researchers have identified normal genetic variation and studied that variation in diverse human populations to determine the amounts and distributions of that variation. That information is being used to develop an understanding of the demographic histories of the different populations and the species as a whole, among other studies. With the advent of DNA-based markers in the last quarter century, these studies have accelerated. One of the challenges for the next century is to understand that variation. One component of that understanding will be population genetics. We present here examples of many of the ways these new data can be analyzed from a population perspective using results from our laboratory on multiple individual DNA-based polymorphisms, many clustered in haplotypes, studied in multiple populations representing all major geographic regions of the world. These data support an "out of Africa" hypothesis for human dispersal around the world and begin to refine the understanding of population structures and genetic relationships. We are also developing baseline information against which we can compare findings at different loci to aid in the identification of loci subject, now and in the past, to selection (directional or balancing). We do not yet have a comprehensive understanding of the extensive variation in the human genome, but some of that understanding is coming from population genetics.

  4. The offspring quantity–quality trade-off and human fertility variation

    Science.gov (United States)

    Lawson, David W.; Borgerhoff Mulder, Monique

    2016-01-01

    The idea that trade-offs between offspring quantity and quality shape reproductive behaviour has long been central to economic perspectives on fertility. It also has a parallel and richer theoretical foundation in evolutionary ecology. We review the application of the quantity–quality trade-off concept to human reproduction, emphasizing distinctions between clutch size and lifetime fertility, and the wider set of forces contributing to fertility variation in iteroparous and sexually reproducing species like our own. We then argue that in settings approximating human evolutionary history, several factors limit costly sibling competition. Consequently, while the optimization of quantity–quality trade-offs undoubtedly shaped the evolution of human physiology setting the upper limits of reproduction, we argue it plays a modest role in accounting for socio-ecological and individual variation in fertility. Only upon entering the demographic transition can fertility limitation be clearly interpreted as strategically orientated to advancing offspring quality via increased parental investment per child, with low fertility increasing descendant socio-economic success, although not reproductive success. We conclude that existing economic and evolutionary literature has often overemphasized the centrality of quantity–quality trade-offs to human fertility variation and advocate for the development of more holistic frameworks encompassing alternative life-history trade-offs and the evolved mechanisms guiding their resolution. PMID:27022072

  5. Anatomy, Medical Education, and Human Ancestral Variation

    Science.gov (United States)

    Strkalj, Goran; Spocter, Muhammad A.; Wilkinson, A. Tracey

    2011-01-01

    It is argued in this article that the human body both in health and disease cannot be fully understood without adequately accounting for the different levels of human variation. The article focuses on variation due to ancestry, arguing that the inclusion of information pertaining to ancestry in human anatomy teaching materials and courses should…

  6. Genomic variation landscape of the human gut microbiome

    DEFF Research Database (Denmark)

    Schloissnig, Siegfried; Arumugam, Manimozhiyan; Sunagawa, Shinichi

    2013-01-01

    Whereas large-scale efforts have rapidly advanced the understanding and practical impact of human genomic variation, the practical impact of variation is largely unexplored in the human microbiome. We therefore developed a framework for metagenomic variation analysis and applied it to 252 faecal...... polymorphism rates of 0.11 was more variable between gut microbial species than across human hosts. Subjects sampled at varying time intervals exhibited individuality and temporal stability of SNP variation patterns, despite considerable composition changes of their gut microbiota. This indicates...

  7. DNA methylation-based variation between human populations.

    Science.gov (United States)

    Kader, Farzeen; Ghai, Meenu

    2017-02-01

    Several studies have proved that DNA methylation affects regulation of gene expression and development. Epigenome-wide studies have reported variation in methylation patterns between populations, including Caucasians, non-Caucasians (Blacks), Hispanics, Arabs, and numerous populations of the African continent. Not only has DNA methylation differences shown to impact externally visible characteristics, but is also a potential biomarker for underlying racial health disparities between human populations. Ethnicity-related methylation differences set their mark during early embryonic development. Genetic variations, such as single-nucleotide polymorphisms and environmental factors, such as age, dietary folate, socioeconomic status, and smoking, impacts DNA methylation levels, which reciprocally impacts expression of phenotypes. Studies show that it is necessary to address these external influences when attempting to differentiate between populations since the relative impacts of these factors on the human methylome remain uncertain. The present review summarises several reported attempts to establish the contribution of differential DNA methylation to natural human variation, and shows that DNA methylation could represent new opportunities for risk stratification and prevention of several diseases amongst populations world-wide. Variation of methylation patterns between human populations is an exciting prospect which inspires further valuable research to apply the concept in routine medical and forensic casework. However, trans-generational inheritance needs to be quantified to decipher the proportion of variation contributed by DNA methylation. The future holds thorough evaluation of the epigenome to understand quantification, heritability, and the effect of DNA methylation on phenotypes. In addition, methylation profiling of the same ethnic groups across geographical locations will shed light on conserved methylation differences in populations.

  8. Big Data Analysis of Human Genome Variations

    KAUST Repository

    Gojobori, Takashi

    2016-01-25

    Since the human genome draft sequence was in public for the first time in 2000, genomic analyses have been intensively extended to the population level. The following three international projects are good examples for large-scale studies of human genome variations: 1) HapMap Data (1,417 individuals) (http://hapmap.ncbi.nlm.nih.gov/downloads/genotypes/2010-08_phaseII+III/forward/), 2) HGDP (Human Genome Diversity Project) Data (940 individuals) (http://www.hagsc.org/hgdp/files.html), 3) 1000 genomes Data (2,504 individuals) http://ftp.1000genomes.ebi.ac.uk/vol1/ftp/release/20130502/ If we can integrate all three data into a single volume of data, we should be able to conduct a more detailed analysis of human genome variations for a total number of 4,861 individuals (= 1,417+940+2,504 individuals). In fact, we successfully integrated these three data sets by use of information on the reference human genome sequence, and we conducted the big data analysis. In particular, we constructed a phylogenetic tree of about 5,000 human individuals at the genome level. As a result, we were able to identify clusters of ethnic groups, with detectable admixture, that were not possible by an analysis of each of the three data sets. Here, we report the outcome of this kind of big data analyses and discuss evolutionary significance of human genomic variations. Note that the present study was conducted in collaboration with Katsuhiko Mineta and Kosuke Goto at KAUST.

  9. Host genetic variation impacts microbiome composition across human body sites.

    Science.gov (United States)

    Blekhman, Ran; Goodrich, Julia K; Huang, Katherine; Sun, Qi; Bukowski, Robert; Bell, Jordana T; Spector, Timothy D; Keinan, Alon; Ley, Ruth E; Gevers, Dirk; Clark, Andrew G

    2015-09-15

    The composition of bacteria in and on the human body varies widely across human individuals, and has been associated with multiple health conditions. While microbial communities are influenced by environmental factors, some degree of genetic influence of the host on the microbiome is also expected. This study is part of an expanding effort to comprehensively profile the interactions between human genetic variation and the composition of this microbial ecosystem on a genome- and microbiome-wide scale. Here, we jointly analyze the composition of the human microbiome and host genetic variation. By mining the shotgun metagenomic data from the Human Microbiome Project for host DNA reads, we gathered information on host genetic variation for 93 individuals for whom bacterial abundance data are also available. Using this dataset, we identify significant associations between host genetic variation and microbiome composition in 10 of the 15 body sites tested. These associations are driven by host genetic variation in immunity-related pathways, and are especially enriched in host genes that have been previously associated with microbiome-related complex diseases, such as inflammatory bowel disease and obesity-related disorders. Lastly, we show that host genomic regions associated with the microbiome have high levels of genetic differentiation among human populations, possibly indicating host genomic adaptation to environment-specific microbiomes. Our results highlight the role of host genetic variation in shaping the composition of the human microbiome, and provide a starting point toward understanding the complex interaction between human genetics and the microbiome in the context of human evolution and disease.

  10. Genomic Sequence Variation Markup Language (GSVML).

    Science.gov (United States)

    Nakaya, Jun; Kimura, Michio; Hiroi, Kaei; Ido, Keisuke; Yang, Woosung; Tanaka, Hiroshi

    2010-02-01

    With the aim of making good use of internationally accumulated genomic sequence variation data, which is increasing rapidly due to the explosive amount of genomic research at present, the development of an interoperable data exchange format and its international standardization are necessary. Genomic Sequence Variation Markup Language (GSVML) will focus on genomic sequence variation data and human health applications, such as gene based medicine or pharmacogenomics. We developed GSVML through eight steps, based on case analysis and domain investigations. By focusing on the design scope to human health applications and genomic sequence variation, we attempted to eliminate ambiguity and to ensure practicability. We intended to satisfy the requirements derived from the use case analysis of human-based clinical genomic applications. Based on database investigations, we attempted to minimize the redundancy of the data format, while maximizing the data covering range. We also attempted to ensure communication and interface ability with other Markup Languages, for exchange of omics data among various omics researchers or facilities. The interface ability with developing clinical standards, such as the Health Level Seven Genotype Information model, was analyzed. We developed the human health-oriented GSVML comprising variation data, direct annotation, and indirect annotation categories; the variation data category is required, while the direct and indirect annotation categories are optional. The annotation categories contain omics and clinical information, and have internal relationships. For designing, we examined 6 cases for three criteria as human health application and 15 data elements for three criteria as data formats for genomic sequence variation data exchange. The data format of five international SNP databases and six Markup Languages and the interface ability to the Health Level Seven Genotype Model in terms of 317 items were investigated. GSVML was developed as

  11. Understanding human genetic variation in the era of high-throughput sequencing

    OpenAIRE

    Knight, Julian C.

    2010-01-01

    The EMBO/EMBL symposium ‘Human Variation: Cause and Consequence' highlighted advances in understanding the molecular basis of human genetic variation and its myriad implications for biology, human origins and disease.

  12. Application of low background liquid scintillation counting method to pharmacy. Variation of endogenous 14C in human urine

    International Nuclear Information System (INIS)

    Horie, Masanobu; Yanagi, Mashiho; Baba, Shigeo; Kato, Yuka; Yoshimura, Tomoyuki

    2010-01-01

    The intra-day, inter-day and individual variations in endogenous 14 C radioactivity of human urine were studied by use of 5 mL urine. The endogenous 14 C radioactivity of human urine is relatively constant (approximately 1.5 dpm/mL urine). In order to eliminate the effect of endogenous 40 K it is of the greatest importance to count 14 C signal with the optimal window. Since these variations are relatively small, we can estimate correctly the net 14 C activity from the BG value of the same time zone of the day before dosing. (author)

  13. Estimating mobility using sparse data: Application to human genetic variation.

    Science.gov (United States)

    Loog, Liisa; Mirazón Lahr, Marta; Kovacevic, Mirna; Manica, Andrea; Eriksson, Anders; Thomas, Mark G

    2017-11-14

    Mobility is one of the most important processes shaping spatiotemporal patterns of variation in genetic, morphological, and cultural traits. However, current approaches for inferring past migration episodes in the fields of archaeology and population genetics lack either temporal resolution or formal quantification of the underlying mobility, are poorly suited to spatially and temporally sparsely sampled data, and permit only limited systematic comparison between different time periods or geographic regions. Here we present an estimator of past mobility that addresses these issues by explicitly linking trait differentiation in space and time. We demonstrate the efficacy of this estimator using spatiotemporally explicit simulations and apply it to a large set of ancient genomic data from Western Eurasia. We identify a sequence of changes in human mobility from the Late Pleistocene to the Iron Age. We find that mobility among European Holocene farmers was significantly higher than among European hunter-gatherers both pre- and postdating the Last Glacial Maximum. We also infer that this Holocene rise in mobility occurred in at least three distinct stages: the first centering on the well-known population expansion at the beginning of the Neolithic, and the second and third centering on the beginning of the Bronze Age and the late Iron Age, respectively. These findings suggest a strong link between technological change and human mobility in Holocene Western Eurasia and demonstrate the utility of this framework for exploring changes in mobility through space and time. Copyright © 2017 the Author(s). Published by PNAS.

  14. Seasonal variation in human reproduction: environmental factors.

    Science.gov (United States)

    Bronson, F H

    1995-06-01

    Almost all human populations exhibit seasonal variation in births, owing mostly to seasonal variation in the frequency of conception. This review focuses on the degree to which environmental factors like nutrition, temperature and photoperiod contribute to these seasonal patterns by acting directly on the reproductive axis. The reproductive strategy of humans is basically that of the apes: Humans have the capacity to reproduce continuously, albeit slowly, unless inhibited by environmental influences. Two, and perhaps three, environmental factors probably act routinely as seasonal inhibitors in some human populations. First, it seems likely that ovulation is regulated seasonally in populations experiencing seasonal variation in food availability. More specifically, it seems likely that inadequate food intake or the increased energy expenditure required to obtain food, or both, can delay menarche, suppress the frequency of ovulation in the nonlactating adult, and prolong lactational amenorrhea in these populations on a seasonal basis. This action is most easily seen in tropical subsistence societies where food availability often varies greatly owing to seasonal variation in rainfall; hence births in these populations often correlate with rainfall. Second, it seems likely that seasonally high temperatures suppress spermatogenesis enough to influence the incidence of fertilization in hotter latitudes, but possibly only in males wearing clothing that diminishes scrotal cooling. Since most of our knowledge about this phenomenon comes from temperate latitudes, the sensitivity of spermatogenesis in both human and nonhuman primates to heat in the tropics needs further study. It is quite possible that high temperatures suppress ovulation and early embryo survival seasonally in some of these same populations. Since we know less than desired about the effect of heat stress on ovulation and early pregnancy in nonhuman mammals, and nothing at all about it in humans or any of the

  15. Child Development and Structural Variation in the Human Genome

    Science.gov (United States)

    Zhang, Ying; Haraksingh, Rajini; Grubert, Fabian; Abyzov, Alexej; Gerstein, Mark; Weissman, Sherman; Urban, Alexander E.

    2013-01-01

    Structural variation of the human genome sequence is the insertion, deletion, or rearrangement of stretches of DNA sequence sized from around 1,000 to millions of base pairs. Over the past few years, structural variation has been shown to be far more common in human genomes than previously thought. Very little is currently known about the effects…

  16. Variational continuum multiphase poroelasticity theory and applications

    CERN Document Server

    Serpieri, Roberto

    2017-01-01

    This book collects the theoretical derivation of a recently presented general variational macroscopic continuum theory of multiphase poroelasticity (VMTPM), together with its applications to consolidation and stress partitioning problems of interest in several applicative engineering contexts, such as in geomechanics and biomechanics. The theory is derived based on a purely-variational deduction, rooted in the least-Action principle, by considering a minimal set of kinematic descriptors. The treatment herein considered keeps a specific focus on the derivation of most general medium-independent governing equations. It is shown that VMTPM recovers paradigms of consolidated use in multiphase poroelasticity such as Terzaghi's stress partitioning principle and Biot's equations for wave propagation. In particular, the variational treatment permits the derivation of a general medium-independent stress partitioning law, and the proposed variational theory predicts that the external stress, the fluid pressure, and the...

  17. Extensive Variation in Chromatin States Across Humans

    KAUST Repository

    Kasowski, M.

    2013-10-17

    The majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.

  18. Extensive Variation in Chromatin States Across Humans

    KAUST Repository

    Kasowski, M.; Kyriazopoulou-Panagiotopoulou, S.; Grubert, F.; Zaugg, J. B.; Kundaje, A.; Liu, Y.; Boyle, A. P.; Zhang, Q. C.; Zakharia, F.; Spacek, D. V.; Li, J.; Xie, D.; Olarerin-George, A.; Steinmetz, L. M.; Hogenesch, J. B.; Kellis, M.; Batzoglou, S.; Snyder, M.

    2013-01-01

    The majority of disease-associated variants lie outside protein-coding regions, suggesting a link between variation in regulatory regions and disease predisposition. We studied differences in chromatin states using five histone modifications, cohesin, and CTCF in lymphoblastoid lines from 19 individuals of diverse ancestry. We found extensive signal variation in regulatory regions, which often switch between active and repressed states across individuals. Enhancer activity is particularly diverse among individuals, whereas gene expression remains relatively stable. Chromatin variability shows genetic inheritance in trios, correlates with genetic variation and population divergence, and is associated with disruptions of transcription factor binding motifs. Overall, our results provide insights into chromatin variation among humans.

  19. Functional characterization of genetic enzyme variations in human lipoxygenases

    Directory of Open Access Journals (Sweden)

    Thomas Horn

    2013-01-01

    Full Text Available Mammalian lipoxygenases play a role in normal cell development and differentiation but they have also been implicated in the pathogenesis of cardiovascular, hyperproliferative and neurodegenerative diseases. As lipid peroxidizing enzymes they are involved in the regulation of cellular redox homeostasis since they produce lipid hydroperoxides, which serve as an efficient source for free radicals. There are various epidemiological correlation studies relating naturally occurring variations in the six human lipoxygenase genes (SNPs or rare mutations to the frequency for various diseases in these individuals, but for most of the described variations no functional data are available. Employing a combined bioinformatical and enzymological strategy, which included structural modeling and experimental site-directed mutagenesis, we systematically explored the structural and functional consequences of non-synonymous genetic variations in four different human lipoxygenase genes (ALOX5, ALOX12, ALOX15, and ALOX15B that have been identified in the human 1000 genome project. Due to a lack of a functional expression system we resigned to analyze the functionality of genetic variations in the hALOX12B and hALOXE3 gene. We found that most of the frequent non-synonymous coding SNPs are located at the enzyme surface and hardly alter the enzyme functionality. In contrast, genetic variations which affect functional important amino acid residues or lead to truncated enzyme variations (nonsense mutations are usually rare with a global allele frequency<0.1%. This data suggest that there appears to be an evolutionary pressure on the coding regions of the lipoxygenase genes preventing the accumulation of loss-of-function variations in the human population.

  20. Characterization and potential functional significance of human-chimpanzee large INDEL variation

    Directory of Open Access Journals (Sweden)

    Polavarapu Nalini

    2011-10-01

    Full Text Available Abstract Background Although humans and chimpanzees have accumulated significant differences in a number of phenotypic traits since diverging from a common ancestor about six million years ago, their genomes are more than 98.5% identical at protein-coding loci. This modest degree of nucleotide divergence is not sufficient to explain the extensive phenotypic differences between the two species. It has been hypothesized that the genetic basis of the phenotypic differences lies at the level of gene regulation and is associated with the extensive insertion and deletion (INDEL variation between the two species. To test the hypothesis that large INDELs (80 to 12,000 bp may have contributed significantly to differences in gene regulation between the two species, we categorized human-chimpanzee INDEL variation mapping in or around genes and determined whether this variation is significantly correlated with previously determined differences in gene expression. Results Extensive, large INDEL variation exists between the human and chimpanzee genomes. This variation is primarily attributable to retrotransposon insertions within the human lineage. There is a significant correlation between differences in gene expression and large human-chimpanzee INDEL variation mapping in genes or in proximity to them. Conclusions The results presented herein are consistent with the hypothesis that large INDELs, particularly those associated with retrotransposons, have played a significant role in human-chimpanzee regulatory evolution.

  1. Inter-chromosomal variation in the pattern of human population genetic structure

    Directory of Open Access Journals (Sweden)

    Baye Tesfaye M

    2011-05-01

    application of complementary statistical and functional network analysis in human genetic variation studies.

  2. HGVA: the Human Genome Variation Archive.

    Science.gov (United States)

    Lopez, Javier; Coll, Jacobo; Haimel, Matthias; Kandasamy, Swaathi; Tarraga, Joaquin; Furio-Tari, Pedro; Bari, Wasim; Bleda, Marta; Rueda, Antonio; Gräf, Stefan; Rendon, Augusto; Dopazo, Joaquin; Medina, Ignacio

    2017-07-03

    High-profile genomic variation projects like the 1000 Genomes project or the Exome Aggregation Consortium, are generating a wealth of human genomic variation knowledge which can be used as an essential reference for identifying disease-causing genotypes. However, accessing these data, contrasting the various studies and integrating those data in downstream analyses remains cumbersome. The Human Genome Variation Archive (HGVA) tackles these challenges and facilitates access to genomic data for key reference projects in a clean, fast and integrated fashion. HGVA provides an efficient and intuitive web-interface for easy data mining, a comprehensive RESTful API and client libraries in Python, Java and JavaScript for fast programmatic access to its knowledge base. HGVA calculates population frequencies for these projects and enriches their data with variant annotation provided by CellBase, a rich and fast annotation solution. HGVA serves as a proof-of-concept of the genome analysis developments being carried out by the University of Cambridge together with UK's 100 000 genomes project and the National Institute for Health Research BioResource Rare-Diseases, in particular, deploying open-source for Computational Biology (OpenCB) software platform for storing and analyzing massive genomic datasets. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Anatomical-clinical investigations of variations of the human coronary arteries

    OpenAIRE

    Aida Hasanović; Faruk Dilberović; Fehim Ovčina

    2003-01-01

    Variations of the human coronary arteries have always attracted the attention of many researchers. A review of the literature shows that variations can cause ischemic heart disease or sudden cardiac death. The aim of the investigations was to examine the existence and clinical significance of variations of the human coronary arteries. Special attention has been focused on myocardial bridging of the coronary arteries and coronary arteriovenous fistula. Our investigations were carried out on th...

  4. Genetic variation in an individual human exome.

    Directory of Open Access Journals (Sweden)

    Pauline C Ng

    2008-08-01

    Full Text Available There is much interest in characterizing the variation in a human individual, because this may elucidate what contributes significantly to a person's phenotype, thereby enabling personalized genomics. We focus here on the variants in a person's 'exome,' which is the set of exons in a genome, because the exome is believed to harbor much of the functional variation. We provide an analysis of the approximately 12,500 variants that affect the protein coding portion of an individual's genome. We identified approximately 10,400 nonsynonymous single nucleotide polymorphisms (nsSNPs in this individual, of which approximately 15-20% are rare in the human population. We predict approximately 1,500 nsSNPs affect protein function and these tend be heterozygous, rare, or novel. Of the approximately 700 coding indels, approximately half tend to have lengths that are a multiple of three, which causes insertions/deletions of amino acids in the corresponding protein, rather than introducing frameshifts. Coding indels also occur frequently at the termini of genes, so even if an indel causes a frameshift, an alternative start or stop site in the gene can still be used to make a functional protein. In summary, we reduced the set of approximately 12,500 nonsilent coding variants by approximately 8-fold to a set of variants that are most likely to have major effects on their proteins' functions. This is our first glimpse of an individual's exome and a snapshot of the current state of personalized genomics. The majority of coding variants in this individual are common and appear to be functionally neutral. Our results also indicate that some variants can be used to improve the current NCBI human reference genome. As more genomes are sequenced, many rare variants and non-SNP variants will be discovered. We present an approach to analyze the coding variation in humans by proposing multiple bioinformatic methods to hone in on possible functional variation.

  5. A global reference for human genetic variation

    DEFF Research Database (Denmark)

    Auton, Adam; Abecasis, Goncalo R.; M. Altshuler, David

    2015-01-01

    The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals ...

  6. Human footprint variation while performing load bearing tasks.

    Directory of Open Access Journals (Sweden)

    Cara M Wall-Scheffler

    Full Text Available Human footprint fossils have provided essential evidence about the evolution of human bipedalism as well as the social dynamics of the footprint makers, including estimates of speed, sex and group composition. Generally such estimates are made by comparing footprint evidence with modern controls; however, previous studies have not accounted for the variation in footprint dimensions coming from load bearing activities. It is likely that a portion of the hominins who created these fossil footprints were carrying a significant load, such as offspring or foraging loads, which caused variation in the footprint which could extend to variation in any estimations concerning the footprint's maker. To identify significant variation in footprints due to load-bearing tasks, we had participants (N = 30, 15 males and 15 females walk at a series of speeds carrying a 20kg pack on their back, side and front. Paint was applied to the bare feet of each participant to create footprints that were compared in terms of foot length, foot width and foot area. Female foot length and width increased during multiple loaded conditions. An appreciation of footprint variability associated with carrying loads adds an additional layer to our understanding of the behavior and morphology of extinct hominin populations.

  7. Midsagittal Brain Variation among Non-Human Primates: Insights into Evolutionary Expansion of the Human Precuneus.

    Science.gov (United States)

    Pereira-Pedro, Ana Sofia; Rilling, James K; Chen, Xu; Preuss, Todd M; Bruner, Emiliano

    2017-01-01

    The precuneus is a major element of the superior parietal lobule, positioned on the medial side of the hemisphere and reaching the dorsal surface of the brain. It is a crucial functional region for visuospatial integration, visual imagery, and body coordination. Previously, we argued that the precuneus expanded in recent human evolution, based on a combination of paleontological, comparative, and intraspecific evidence from fossil and modern human endocasts as well as from human and chimpanzee brains. The longitudinal proportions of this region are a major source of anatomical variation among adult humans and, being much larger in Homo sapiens, is the main characteristic differentiating human midsagittal brain morphology from that of our closest living primate relative, the chimpanzee. In the current shape analysis, we examine precuneus variation in non-human primates through landmark-based models, to evaluate the general pattern of variability in non-human primates, and to test whether precuneus proportions are influenced by allometric effects of brain size. Results show that precuneus proportions do not covary with brain size, and that the main difference between monkeys and apes involves a vertical expansion of the frontal and occipital regions in apes. Such differences might reflect differences in brain proportions or differences in cranial architecture. In this sample, precuneus variation is apparently not influenced by phylogenetic or allometric factors, but does vary consistently within species, at least in chimpanzees and macaques. This result further supports the hypothesis that precuneus expansion in modern humans is not merely a consequence of increasing brain size or of allometric scaling, but rather represents a species-specific morphological change in our lineage. © 2017 S. Karger AG, Basel.

  8. Intrapopulational body size variation and cranial capacity variation in Middle Pleistocene humans: the Sima de los Huesos sample (Sierra de Atapuerca, Spain).

    Science.gov (United States)

    Lorenzo, C; Carretero, J M; Arsuaga, J L; Gracia, A; Martínez, I

    1998-05-01

    A sexual dimorphism more marked than in living humans has been claimed for European Middle Pleistocene humans, Neandertals and prehistoric modern humans. In this paper, body size and cranial capacity variation are studied in the Sima de los Huesos Middle Pleistocene sample. This is the largest sample of non-modern humans found to date from one single site, and with all skeletal elements represented. Since the techniques available to estimate the degree of sexual dimorphism in small palaeontological samples are all unsatisfactory, we have used the bootstraping method to asses the magnitude of the variation in the Sima de los Huesos sample compared to modern human intrapopulational variation. We analyze size variation without attempting to sex the specimens a priori. Anatomical regions investigated are scapular glenoid fossa; acetabulum; humeral proximal and distal epiphyses; ulnar proximal epiphysis; radial neck; proximal femur; humeral, femoral, ulnar and tibial shaft; lumbosacral joint; patella; calcaneum; and talar trochlea. In the Sima de los Huesos sample only the humeral midshaft perimeter shows an unusual high variation (only when it is expressed by the maximum ratio, not by the coefficient of variation). In spite of that the cranial capacity range at Sima de los Huesos almost spans the rest of the European and African Middle Pleistocene range. The maximum ratio is in the central part of the distribution of modern human samples. Thus, the hypothesis of a greater sexual dimorphism in Middle Pleistocene populations than in modern populations is not supported by either cranial or postcranial evidence from Sima de los Huesos.

  9. Variation in human recombination rates and its genetic determinants.

    Directory of Open Access Journals (Sweden)

    Adi Fledel-Alon

    Full Text Available Despite the fundamental role of crossing-over in the pairing and segregation of chromosomes during human meiosis, the rates and placements of events vary markedly among individuals. Characterizing this variation and identifying its determinants are essential steps in our understanding of the human recombination process and its evolution.Using three large sets of European-American pedigrees, we examined variation in five recombination phenotypes that capture distinct aspects of crossing-over patterns. We found that the mean recombination rate in males and females and the historical hotspot usage are significantly heritable and are uncorrelated with one another. We then conducted a genome-wide association study in order to identify loci that influence them. We replicated associations of RNF212 with the mean rate in males and in females as well as the association of Inversion 17q21.31 with the female mean rate. We also replicated the association of PRDM9 with historical hotspot usage, finding that it explains most of the genetic variance in this phenotype. In addition, we identified a set of new candidate regions for further validation.These findings suggest that variation at broad and fine scales is largely separable and that, beyond three known loci, there is no evidence for common variation with large effects on recombination phenotypes.

  10. Application of Method of Variation to Analyze and Predict Human Induced Modifications of Water Resource Systems

    Science.gov (United States)

    Dessu, S. B.; Melesse, A. M.; Mahadev, B.; McClain, M.

    2010-12-01

    Water resource systems have often used gravitational surface and subsurface flows because of their practicality in hydrological modeling and prediction. Activities such as inter/intra-basin water transfer, the use of small pumps and the construction of micro-ponds challenge the tradition of natural rivers as water resource management unit. On the contrary, precipitation is barely affected by topography and plot harvesting in wet regions can be more manageable than diverting from rivers. Therefore, it is indicative to attend to systems where precipitation drives the dynamics while the internal mechanics constitutes spectrum of human activity and decision in a network of plots. The trade-in volume and path of harvested precipitation depends on water balance, energy balance and the kinematics of supply and demand. Method of variation can be used to understand and predict the implication of local excess precipitation harvest and exchange on the natural water system. A system model was developed using the variational form of Euler-Bernoulli’s equation for the Kenyan Mara River basin. Satellite derived digital elevation models, precipitation estimates, and surface properties such as fractional impervious surface area, are used to estimate the available water resource. Four management conditions are imposed in the model: gravitational flow, open water extraction and high water use investment at upstream and downstream respectively. According to the model, the first management maintains the basin status quo while the open source management could induce externality. The high water market at the upstream in the third management offers more than 50% of the basin-wide total revenue to the upper third section of the basin thus may promote more harvesting. The open source and upstream exploitation suggest potential drop of water availability to downstream. The model exposed the latent potential of economic gradient to reconfigure the flow network along the direction where the

  11. Anatomical variation of human thoracic rib in dry bone.

    Directory of Open Access Journals (Sweden)

    Dr. Nalini Konkani

    2017-12-01

    Full Text Available Introduction: The Ribs are essential structure of osseous thorax and provide information that aids in the interpretation of radiologic images. The purpose of this study to investigate variations in thoracic rib and its morphological & clinical importance. So, In present study attempted to find out additional intercostal spaces due to bifurcation of ribs, less intercostal space due to fusion of ribs, variation of the normal ribs like, gap in the rib, fusion of one rib to another at a shaft of rib. Congenital abnormalities of the ribs are usually asymptomatic, often discovered incidentally on chest X-ray. Effects of this neuroskeletal anomaly can include respiratory difficulties and neurological limitations.Material & Method: The study was carried out in Bone Store of Department of Anatomy, B. J. Medical College, Ahmedabad, Gujarat. Study was carried out on 500 human dried ribs. And the variations in the ribs are studied. We got variation in the human ribs and studied. Result : Variations were seen like out of 500 ribs, Bifid rib having two ends 9(1.8%, rib having bifid space 2(0.4%, fusion rib at the level of shaft 1(0.2%, fusion of first rib and second rib 1(0.2%,first rib having two ends 1(0.2%. Conclusion: Bifid rib is an anatomical variant where the sternal end of the rib is cleaved into two. So we can rule out mesodermal abnormalities, parenchymal lung disease, chest wall tumor or costal fracture.

  12. Pharmacomicrobiomics: the impact of human microbiome variations on systems pharmacology and personalized therapeutics.

    Science.gov (United States)

    ElRakaiby, Marwa; Dutilh, Bas E; Rizkallah, Mariam R; Boleij, Annemarie; Cole, Jason N; Aziz, Ramy K

    2014-07-01

    The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome influence human health, immunity, and different disease states. In this review article, we summarize the key findings and applications of the HMP that may impact pharmacology and personalized therapeutics. We propose a microbiome cloud model, reflecting the temporal and spatial uncertainty of defining an individual's microbiome composition, with examples of how intra-individual variations (such as age and mode of delivery) shape the microbiome structure. Additionally, we discuss how this microbiome cloud concept explains the difficulty to define a core human microbiome and to classify individuals according to their biome types. Detailed examples are presented on microbiome changes related to colorectal cancer, antibiotic administration, and pharmacomicrobiomics, or drug-microbiome interactions, highlighting how an improved understanding of the human microbiome, and alterations thereof, may lead to the development of novel therapeutic agents, the modification of antibiotic policies and implementation, and improved health outcomes. Finally, the prospects of a collaborative computational microbiome research initiative in Africa are discussed.

  13. Genome-wide associations of gene expression variation in humans.

    Directory of Open Access Journals (Sweden)

    Barbara E Stranger

    2005-12-01

    Full Text Available The exploration of quantitative variation in human populations has become one of the major priorities for medical genetics. The successful identification of variants that contribute to complex traits is highly dependent on reliable assays and genetic maps. We have performed a genome-wide quantitative trait analysis of 630 genes in 60 unrelated Utah residents with ancestry from Northern and Western Europe using the publicly available phase I data of the International HapMap project. The genes are located in regions of the human genome with elevated functional annotation and disease interest including the ENCODE regions spanning 1% of the genome, Chromosome 21 and Chromosome 20q12-13.2. We apply three different methods of multiple test correction, including Bonferroni, false discovery rate, and permutations. For the 374 expressed genes, we find many regions with statistically significant association of single nucleotide polymorphisms (SNPs with expression variation in lymphoblastoid cell lines after correcting for multiple tests. Based on our analyses, the signal proximal (cis- to the genes of interest is more abundant and more stable than distal and trans across statistical methodologies. Our results suggest that regulatory polymorphism is widespread in the human genome and show that the 5-kb (phase I HapMap has sufficient density to enable linkage disequilibrium mapping in humans. Such studies will significantly enhance our ability to annotate the non-coding part of the genome and interpret functional variation. In addition, we demonstrate that the HapMap cell lines themselves may serve as a useful resource for quantitative measurements at the cellular level.

  14. Genome-Wide Associations of Gene Expression Variation in Humans.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available The exploration of quantitative variation in human populations has become one of the major priorities for medical genetics. The successful identification of variants that contribute to complex traits is highly dependent on reliable assays and genetic maps. We have performed a genome-wide quantitative trait analysis of 630 genes in 60 unrelated Utah residents with ancestry from Northern and Western Europe using the publicly available phase I data of the International HapMap project. The genes are located in regions of the human genome with elevated functional annotation and disease interest including the ENCODE regions spanning 1% of the genome, Chromosome 21 and Chromosome 20q12-13.2. We apply three different methods of multiple test correction, including Bonferroni, false discovery rate, and permutations. For the 374 expressed genes, we find many regions with statistically significant association of single nucleotide polymorphisms (SNPs with expression variation in lymphoblastoid cell lines after correcting for multiple tests. Based on our analyses, the signal proximal (cis- to the genes of interest is more abundant and more stable than distal and trans across statistical methodologies. Our results suggest that regulatory polymorphism is widespread in the human genome and show that the 5-kb (phase I HapMap has sufficient density to enable linkage disequilibrium mapping in humans. Such studies will significantly enhance our ability to annotate the non-coding part of the genome and interpret functional variation. In addition, we demonstrate that the HapMap cell lines themselves may serve as a useful resource for quantitative measurements at the cellular level.

  15. Feedforward Object-Vision Models Only Tolerate Small Image Variations Compared to Human

    Directory of Open Access Journals (Sweden)

    Masoud eGhodrati

    2014-07-01

    Full Text Available Invariant object recognition is a remarkable ability of primates' visual system that its underlying mechanism has constantly been under intense investigations. Computational modelling is a valuable tool toward understanding the processes involved in invariant object recognition. Although recent computational models have shown outstanding performances on challenging image databases, they fail to perform well when images with more complex variations of the same object are applied to them. Studies have shown that making sparse representation of objects by extracting more informative visual features through a feedforward sweep can lead to higher recognition performances. Here, however, we show that when the complexity of image variations is high, even this approach results in poor performance compared to humans. To assess the performance of models and humans in invariant object recognition tasks, we built a parametrically controlled image database consisting of several object categories varied in different dimensions and levels, rendered from 3D planes. Comparing the performance of several object recognition models with human observers shows that only in low-level image variations the models perform similar to humans in categorization tasks. Furthermore, the results of our behavioral experiments demonstrate that, even under difficult experimental conditions (i.e. briefly presented masked stimuli with complex image variations, human observers performed outstandingly well, suggesting that the models are still far from resembling humans in invariant object recognition. Taken together, we suggest that learning sparse informative visual features, although desirable, is not a complete solution for future progresses in object-vision modelling. We show that this approach is not of significant help in solving the computational crux of object recognition (that is invariant object recognition when the identity-preserving image variations become more complex.

  16. Evaluating variation in human gut microbiota profiles due to DNA extraction method and inter-subject differences.

    Science.gov (United States)

    Wagner Mackenzie, Brett; Waite, David W; Taylor, Michael W

    2015-01-01

    The human gut contains dense and diverse microbial communities which have profound influences on human health. Gaining meaningful insights into these communities requires provision of high quality microbial nucleic acids from human fecal samples, as well as an understanding of the sources of variation and their impacts on the experimental model. We present here a systematic analysis of commonly used microbial DNA extraction methods, and identify significant sources of variation. Five extraction methods (Human Microbiome Project protocol, MoBio PowerSoil DNA Isolation Kit, QIAamp DNA Stool Mini Kit, ZR Fecal DNA MiniPrep, phenol:chloroform-based DNA isolation) were evaluated based on the following criteria: DNA yield, quality and integrity, and microbial community structure based on Illumina amplicon sequencing of the V4 region of bacterial and archaeal 16S rRNA genes. Our results indicate that the largest portion of variation within the model was attributed to differences between subjects (biological variation), with a smaller proportion of variation associated with DNA extraction method (technical variation) and intra-subject variation. A comprehensive understanding of the potential impact of technical variation on the human gut microbiota will help limit preventable bias, enabling more accurate diversity estimates.

  17. Evaluating variation in human gut microbiota profiles due to DNA extraction method and inter-subject differences

    Directory of Open Access Journals (Sweden)

    Brett eWagner Mackenzie

    2015-02-01

    Full Text Available The human gut contains dense and diverse microbial communities which have profound influences on human health. Gaining meaningful insights into these communities requires provision of high quality microbial nucleic acids from human fecal samples, as well as an understanding of the sources of variation and their impacts on the experimental model. We present here a systematic analysis of commonly used microbial DNA extraction methods, and identify significant sources of variation. Five extraction methods (Human Microbiome Project protocol, MoBio PowerSoil DNA Isolation Kit, QIAamp DNA Stool Mini Kit, ZR Fecal DNA MiniPrep, phenol:chloroform-based DNA isolation were evaluated based on the following criteria: DNA yield, quality and integrity, and microbial community structure based on Illumina amplicon sequencing of the V4 region of bacterial and archaeal 16S rRNA genes. Our results indicate that the largest portion of variation within the model was attributed to differences between subjects (biological variation, with a smaller proportion of variation associated with DNA extraction method (technical variation and intra-subject variation. A comprehensive understanding of the potential impact of technical variation on the human gut microbiota will help limit preventable bias, enabling more accurate diversity estimates.

  18. Non-codingRNA sequence variations in human chronic lymphocytic leukemia and colorectal cancer.

    Science.gov (United States)

    Wojcik, Sylwia E; Rossi, Simona; Shimizu, Masayoshi; Nicoloso, Milena S; Cimmino, Amelia; Alder, Hansjuerg; Herlea, Vlad; Rassenti, Laura Z; Rai, Kanti R; Kipps, Thomas J; Keating, Michael J; Croce, Carlo M; Calin, George A

    2010-02-01

    Cancer is a genetic disease in which the interplay between alterations in protein-coding genes and non-coding RNAs (ncRNAs) plays a fundamental role. In recent years, the full coding component of the human genome was sequenced in various cancers, whereas such attempts related to ncRNAs are still fragmentary. We screened genomic DNAs for sequence variations in 148 microRNAs (miRNAs) and ultraconserved regions (UCRs) loci in patients with chronic lymphocytic leukemia (CLL) or colorectal cancer (CRC) by Sanger technique and further tried to elucidate the functional consequences of some of these variations. We found sequence variations in miRNAs in both sporadic and familial CLL cases, mutations of UCRs in CLLs and CRCs and, in certain instances, detected functional effects of these variations. Furthermore, by integrating our data with previously published data on miRNA sequence variations, we have created a catalog of DNA sequence variations in miRNAs/ultraconserved genes in human cancers. These findings argue that ncRNAs are targeted by both germ line and somatic mutations as well as by single-nucleotide polymorphisms with functional significance for human tumorigenesis. Sequence variations in ncRNA loci are frequent and some have functional and biological significance. Such information can be exploited to further investigate on a genome-wide scale the frequency of genetic variations in ncRNAs and their functional meaning, as well as for the development of new diagnostic and prognostic markers for leukemias and carcinomas.

  19. Meiotic gene-conversion rate and tract length variation in the human genome.

    Science.gov (United States)

    Padhukasahasram, Badri; Rannala, Bruce

    2013-02-27

    Meiotic recombination occurs in the form of two different mechanisms called crossing-over and gene-conversion and both processes have an important role in shaping genetic variation in populations. Although variation in crossing-over rates has been studied extensively using sperm-typing experiments, pedigree studies and population genetic approaches, our knowledge of variation in gene-conversion parameters (ie, rates and mean tract lengths) remains far from complete. To explore variability in population gene-conversion rates and its relationship to crossing-over rate variation patterns, we have developed and validated using coalescent simulations a comprehensive Bayesian full-likelihood method that can jointly infer crossing-over and gene-conversion rates as well as tract lengths from population genomic data under general variable rate models with recombination hotspots. Here, we apply this new method to SNP data from multiple human populations and attempt to characterize for the first time the fine-scale variation in gene-conversion parameters along the human genome. We find that the estimated ratio of gene-conversion to crossing-over rates varies considerably across genomic regions as well as between populations. However, there is a great degree of uncertainty associated with such estimates. We also find substantial evidence for variation in the mean conversion tract length. The estimated tract lengths did not show any negative relationship with the local heterozygosity levels in our analysis.European Journal of Human Genetics advance online publication, 27 February 2013; doi:10.1038/ejhg.2013.30.

  20. Systematic documentation and analysis of human genetic variation using the microattribution approach

    Science.gov (United States)

    Giardine, Belinda; Borg, Joseph; Higgs, Douglas R.; Peterson, Kenneth R.; Maglott, Donna; Basak, A. Nazli; Clark, Barnaby; Faustino, Paula; Felice, Alex E.; Francina, Alain; Gallivan, Monica V. E.; Georgitsi, Marianthi; Gibbons, Richard J.; Giordano, Piero C.; Harteveld, Cornelis L.; Joly, Philippe; Kanavakis, Emmanuel; Kollia, Panagoula; Menzel, Stephan; Miller, Webb; Moradkhani, Kamran; Old, John; Papachatzopoulou, Adamantia; Papadakis, Manoussos N.; Papadopoulos, Petros; Pavlovic, Sonja; Philipsen, Sjaak; Radmilovic, Milena; Riemer, Cathy; Schrijver, Iris; Stojiljkovic, Maja; Thein, Swee Lay; Traeger-Synodinos, Jan; Tully, Ray; Wada, Takahito; Waye, John; Wiemann, Claudia; Zukic, Branka; Chui, David H. K.; Wajcman, Henri; Hardison, Ross C.; Patrinos, George P.

    2013-01-01

    We developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to these disorders, and then implemented microattribution to encourage submission of unpublished observations of genetic variation to these public repositories 1. A total of 1,941 unique genetic variants in 37 genes, encoding globins (HBA2, HBA1, HBG2, HBG1, HBD, HBB) and other erythroid proteins (ALOX5AP, AQP9, ARG2, ASS1, ATRX, BCL11A, CNTNAP2, CSNK2A1, EPAS1, ERCC2, FLT1, GATA1, GPM6B, HAO2, HBS1L, KDR, KL, KLF1, MAP2K1, MAP3K5, MAP3K7, MYB, NOS1, NOS2, NOS3, NOX3, NUP133, PDE7B, SMAD3, SMAD6, and TOX) are currently documented in these databases with reciprocal attribution of microcitations to data contributors. Our project provides the first example of implementing microattribution to incentivise submission of all known genetic variation in a defined system. It has demonstrably increased the reporting of human variants and now provides a comprehensive online resource for systematically describing human genetic variation in the globin genes and other genes contributing to hemoglobinopathies and thalassemias. The large repository of previously reported data, together with more recent data, acquired by microattribution, demonstrates how the comprehensive documentation of human variation will provide key insights into normal biological processes and how these are perturbed in human genetic disease. Using the microattribution process set out here, datasets which took decades to accumulate for the globin genes could be assembled rapidly for other genes and disease systems. The principles established here for the globin gene system will serve as a model for other systems and the analysis of other common and/or complex human genetic diseases. PMID:21423179

  1. Association of common genetic variants with human skin color variation in Indian populations.

    Science.gov (United States)

    Sarkar, Anujit; Nandineni, Madhusudan R

    2018-01-01

    Human skin color is one of the most conspicuously variable physical traits that has attracted the attention of physical anthropologists, social scientists and human geneticists. Although several studies have established the underlying genes and their variants affecting human skin color, they were mostly confined to Europeans and Africans and similar studies in Indian populations have been scanty. Studying the association between candidate genetic variants and skin color will help to validate previous findings and to better understand the molecular mechanism of skin color variation. In this study, 22 candidate SNPs from 12 genes were tested for association with skin color in 299 unrelated samples sourced from nine geographical locations in India. Our study establishes the association of 9 SNPs with the phenotype in Indian populations and could explain ∼31% of the variance in skin color. Haplotype analysis of chromosome 15 revealed a significant association of alleles G, A and C of SNPs rs1426654, rs11070627, and rs12913316, respectively, to the phenotype, and accounted for 17% of the variance. Latitude of the sampling location was also a significant factor, contributing to ∼19% of the variation observed in the samples. These observations support the findings that rs1426654 and rs4775730 located in SLC24A5, and rs11070627 and rs12913316 located in MYEF2 and CTXN2 genes respectively, are major contributors toward skin pigmentation and would aid in further unraveling the genotype-phenotype association in Indian populations. These findings can be utilized in forensic DNA applications for criminal investigations. © 2017 Wiley Periodicals, Inc.

  2. Human feeding biomechanics: performance, variation, and functional constraints

    Science.gov (United States)

    Dechow, Paul C.; Wang, Qian; Gharpure, Poorva H.; Baab, Karen L.; Smith, Amanda L.; Weber, Gerhard W.; Grosse, Ian R.; Ross, Callum F.; Richmond, Brian G.; Wright, Barth W.; Byron, Craig; Wroe, Stephen; Strait, David S.

    2016-01-01

    The evolution of the modern human (Homo sapiens) cranium is characterized by a reduction in the size of the feeding system, including reductions in the size of the facial skeleton, postcanine teeth, and the muscles involved in biting and chewing. The conventional view hypothesizes that gracilization of the human feeding system is related to a shift toward eating foods that were less mechanically challenging to consume and/or foods that were processed using tools before being ingested. This hypothesis predicts that human feeding systems should not be well-configured to produce forceful bites and that the cranium should be structurally weak. An alternate hypothesis, based on the observation that humans have mechanically efficient jaw adductors, states that the modern human face is adapted to generate and withstand high biting forces. We used finite element analysis (FEA) to test two opposing mechanical hypotheses: that compared to our closest living relative, chimpanzees (Pan troglodytes), the modern human craniofacial skeleton is (1) less well configured, or (2) better configured to generate and withstand high magnitude bite forces. We considered intraspecific variation in our examination of human feeding biomechanics by examining a sample of geographically diverse crania that differed notably in shape. We found that our biomechanical models of human crania had broadly similar mechanical behavior despite their shape variation and were, on average, less structurally stiff than the crania of chimpanzees during unilateral biting when loaded with physiologically-scaled muscle loads. Our results also show that modern humans are efficient producers of bite force, consistent with previous analyses. However, highly tensile reaction forces were generated at the working (biting) side jaw joint during unilateral molar bites in which the chewing muscles were recruited with bilateral symmetry. In life, such a configuration would have increased the risk of joint dislocation and

  3. Human feeding biomechanics: performance, variation, and functional constraints

    Directory of Open Access Journals (Sweden)

    Justin A. Ledogar

    2016-07-01

    Full Text Available The evolution of the modern human (Homo sapiens cranium is characterized by a reduction in the size of the feeding system, including reductions in the size of the facial skeleton, postcanine teeth, and the muscles involved in biting and chewing. The conventional view hypothesizes that gracilization of the human feeding system is related to a shift toward eating foods that were less mechanically challenging to consume and/or foods that were processed using tools before being ingested. This hypothesis predicts that human feeding systems should not be well-configured to produce forceful bites and that the cranium should be structurally weak. An alternate hypothesis, based on the observation that humans have mechanically efficient jaw adductors, states that the modern human face is adapted to generate and withstand high biting forces. We used finite element analysis (FEA to test two opposing mechanical hypotheses: that compared to our closest living relative, chimpanzees (Pan troglodytes, the modern human craniofacial skeleton is (1 less well configured, or (2 better configured to generate and withstand high magnitude bite forces. We considered intraspecific variation in our examination of human feeding biomechanics by examining a sample of geographically diverse crania that differed notably in shape. We found that our biomechanical models of human crania had broadly similar mechanical behavior despite their shape variation and were, on average, less structurally stiff than the crania of chimpanzees during unilateral biting when loaded with physiologically-scaled muscle loads. Our results also show that modern humans are efficient producers of bite force, consistent with previous analyses. However, highly tensile reaction forces were generated at the working (biting side jaw joint during unilateral molar bites in which the chewing muscles were recruited with bilateral symmetry. In life, such a configuration would have increased the risk of joint

  4. Integrating common and rare genetic variation in diverse human populations.

    Science.gov (United States)

    Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Altshuler, David M; Gibbs, Richard A; Peltonen, Leena; Dermitzakis, Emmanouil; Schaffner, Stephen F; Yu, Fuli; Peltonen, Leena; Dermitzakis, Emmanouil; Bonnen, Penelope E; Altshuler, David M; Gibbs, Richard A; de Bakker, Paul I W; Deloukas, Panos; Gabriel, Stacey B; Gwilliam, Rhian; Hunt, Sarah; Inouye, Michael; Jia, Xiaoming; Palotie, Aarno; Parkin, Melissa; Whittaker, Pamela; Yu, Fuli; Chang, Kyle; Hawes, Alicia; Lewis, Lora R; Ren, Yanru; Wheeler, David; Gibbs, Richard A; Muzny, Donna Marie; Barnes, Chris; Darvishi, Katayoon; Hurles, Matthew; Korn, Joshua M; Kristiansson, Kati; Lee, Charles; McCarrol, Steven A; Nemesh, James; Dermitzakis, Emmanouil; Keinan, Alon; Montgomery, Stephen B; Pollack, Samuela; Price, Alkes L; Soranzo, Nicole; Bonnen, Penelope E; Gibbs, Richard A; Gonzaga-Jauregui, Claudia; Keinan, Alon; Price, Alkes L; Yu, Fuli; Anttila, Verneri; Brodeur, Wendy; Daly, Mark J; Leslie, Stephen; McVean, Gil; Moutsianas, Loukas; Nguyen, Huy; Schaffner, Stephen F; Zhang, Qingrun; Ghori, Mohammed J R; McGinnis, Ralph; McLaren, William; Pollack, Samuela; Price, Alkes L; Schaffner, Stephen F; Takeuchi, Fumihiko; Grossman, Sharon R; Shlyakhter, Ilya; Hostetter, Elizabeth B; Sabeti, Pardis C; Adebamowo, Clement A; Foster, Morris W; Gordon, Deborah R; Licinio, Julio; Manca, Maria Cristina; Marshall, Patricia A; Matsuda, Ichiro; Ngare, Duncan; Wang, Vivian Ota; Reddy, Deepa; Rotimi, Charles N; Royal, Charmaine D; Sharp, Richard R; Zeng, Changqing; Brooks, Lisa D; McEwen, Jean E

    2010-09-02

    Despite great progress in identifying genetic variants that influence human disease, most inherited risk remains unexplained. A more complete understanding requires genome-wide studies that fully examine less common alleles in populations with a wide range of ancestry. To inform the design and interpretation of such studies, we genotyped 1.6 million common single nucleotide polymorphisms (SNPs) in 1,184 reference individuals from 11 global populations, and sequenced ten 100-kilobase regions in 692 of these individuals. This integrated data set of common and rare alleles, called 'HapMap 3', includes both SNPs and copy number polymorphisms (CNPs). We characterized population-specific differences among low-frequency variants, measured the improvement in imputation accuracy afforded by the larger reference panel, especially in imputing SNPs with a minor allele frequency of variation and its role in human disease, and serves as a step towards a high-resolution map of the landscape of human genetic variation.

  5. The study of human Y chromosome variation through ancient DNA.

    Science.gov (United States)

    Kivisild, Toomas

    2017-05-01

    High throughput sequencing methods have completely transformed the study of human Y chromosome variation by offering a genome-scale view on genetic variation retrieved from ancient human remains in context of a growing number of high coverage whole Y chromosome sequence data from living populations from across the world. The ancient Y chromosome sequences are providing us the first exciting glimpses into the past variation of male-specific compartment of the genome and the opportunity to evaluate models based on previously made inferences from patterns of genetic variation in living populations. Analyses of the ancient Y chromosome sequences are challenging not only because of issues generally related to ancient DNA work, such as DNA damage-induced mutations and low content of endogenous DNA in most human remains, but also because of specific properties of the Y chromosome, such as its highly repetitive nature and high homology with the X chromosome. Shotgun sequencing of uniquely mapping regions of the Y chromosomes to sufficiently high coverage is still challenging and costly in poorly preserved samples. To increase the coverage of specific target SNPs capture-based methods have been developed and used in recent years to generate Y chromosome sequence data from hundreds of prehistoric skeletal remains. Besides the prospects of testing directly as how much genetic change in a given time period has accompanied changes in material culture the sequencing of ancient Y chromosomes allows us also to better understand the rate at which mutations accumulate and get fixed over time. This review considers genome-scale evidence on ancient Y chromosome diversity that has recently started to accumulate in geographic areas favourable to DNA preservation. More specifically the review focuses on examples of regional continuity and change of the Y chromosome haplogroups in North Eurasia and in the New World.

  6. Application of magnets with azimuthal field variation in charged particle optics

    International Nuclear Information System (INIS)

    Dojnikov, N.I.; Lamzin, E.A.; Malitskij, N.D.

    1989-01-01

    Examples of concrete application of magnets with azimuthal field variation are presented. Magnetic mirror and bending-focusing device representing a single magnet with azimuthal field variation, providing achromatic beam bending, are used in the LUEh-40m therapeutic acceleration. A single magnet with azimuthal field variation is also used in magnetic mirror. Achromatic magnet for the Elektronika U-003 10 MeV accelerator is fabricated and examined. 2 refs.; 5 figs

  7. Comparison of inter- and intraspecies variation in humans and fruit flies

    Directory of Open Access Journals (Sweden)

    Juliann Shih

    2015-03-01

    Full Text Available Variation is essential to species survival and adaptation during evolution. This variation is conferred by the imperfection of biochemical processes, such as mutations and alterations in DNA sequences, and can also be seen within genomes through processes such as the generation of antibodies. Recent sequencing projects have produced multiple versions of the genomes of humans and fruit flies (Drosophila melanogaster. These give us a chance to study how individual gene sequences vary within and between species. Here we arranged human and fly genes in orthologous pairs and compared such within-species variability with their degree of conservation between flies and humans. We observed that a significant number of proteins associated with mRNA translation are highly conserved between species and yet are highly variable within each species. The fact that we observe this in two species whose lineages separated more than 700 million years ago suggests that this is the result of a very ancient process. We hypothesize that this effect might be attributed to a positive selection for variability of virus-interacting proteins that confers a general resistance to viral hijacking of the mRNA translation machinery within populations. Our analysis points to this and to other processes resulting in positive selection for gene variation.

  8. Application of New Variational Homotopy Perturbation Method For ...

    African Journals Online (AJOL)

    This paper discusses the application of the New Variational Homotopy Perturbation Method (NVHPM) for solving integro-differential equations. The advantage of the new Scheme is that it does not require discretization, linearization or any restrictive assumption of any form be fore it is applied. Several test problems are ...

  9. Genetic Variation and Adaptation in Africa: Implications for Human Evolution and Disease

    Science.gov (United States)

    Gomez, Felicia; Hirbo, Jibril; Tishkoff, Sarah A.

    2014-01-01

    Because modern humans originated in Africa and have adapted to diverse environments, African populations have high levels of genetic and phenotypic diversity. Thus, genomic studies of diverse African ethnic groups are essential for understanding human evolutionary history and how this leads to differential disease risk in all humans. Comparative studies of genetic diversity within and between African ethnic groups creates an opportunity to reconstruct some of the earliest events in human population history and are useful for identifying patterns of genetic variation that have been influenced by recent natural selection. Here we describe what is currently known about genetic variation and evolutionary history of diverse African ethnic groups. We also describe examples of recent natural selection in African genomes and how these data are informative for understanding the frequency of many genetic traits, including those that cause disease susceptibility in African populations and populations of recent African descent. PMID:24984772

  10. Sea level and climate variations

    NARCIS (Netherlands)

    Oerlemans, J.

    1985-01-01

    Review paper, ESA Symposium on Application of Satellite Data to Climate Modelling. Alpbach (Austria) Sea level is an essential component of the climate system, on which many human activities in the coastal zone depend. Climate variations leading to changes in relative sea level are

  11. Loss of variation of state detected in soybean metabolic and human myelomonocytic leukaemia cell transcriptional networks under external stimuli

    KAUST Repository

    Sakata, Katsumi

    2016-10-24

    Soybean (Glycine max) is sensitive to flooding stress, and flood damage at the seedling stage is a barrier to growth. We constructed two mathematical models of the soybean metabolic network, a control model and a flooded model, from metabolic profiles in soybean plants. We simulated the metabolic profiles with perturbations before and after the flooding stimulus using the two models. We measured the variation of state that the system could maintain from a state–space description of the simulated profiles. The results showed a loss of variation of state during the flooding response in the soybean plants. Loss of variation of state was also observed in a human myelomonocytic leukaemia cell transcriptional network in response to a phorbol-ester stimulus. Thus, we detected a loss of variation of state under external stimuli in two biological systems, regardless of the regulation and stimulus types. Our results suggest that a loss of robustness may occur concurrently with the loss of variation of state in biological systems. We describe the possible applications of the quantity of variation of state in plant genetic engineering and cell biology. Finally, we present a hypothetical “external stimulus-induced information loss” model of biological systems.

  12. Loss of variation of state detected in soybean metabolic and human myelomonocytic leukaemia cell transcriptional networks under external stimuli

    KAUST Repository

    Sakata, Katsumi; Saito, Toshiyuki; Ohyanagi, Hajime; Okumura, Jun; Ishige, Kentaro; Suzuki, Harukazu; Nakamura, Takuji; Komatsu, Setsuko

    2016-01-01

    Soybean (Glycine max) is sensitive to flooding stress, and flood damage at the seedling stage is a barrier to growth. We constructed two mathematical models of the soybean metabolic network, a control model and a flooded model, from metabolic profiles in soybean plants. We simulated the metabolic profiles with perturbations before and after the flooding stimulus using the two models. We measured the variation of state that the system could maintain from a state–space description of the simulated profiles. The results showed a loss of variation of state during the flooding response in the soybean plants. Loss of variation of state was also observed in a human myelomonocytic leukaemia cell transcriptional network in response to a phorbol-ester stimulus. Thus, we detected a loss of variation of state under external stimuli in two biological systems, regardless of the regulation and stimulus types. Our results suggest that a loss of robustness may occur concurrently with the loss of variation of state in biological systems. We describe the possible applications of the quantity of variation of state in plant genetic engineering and cell biology. Finally, we present a hypothetical “external stimulus-induced information loss” model of biological systems.

  13. Analysis of indel variations in the human disease-associated genes ...

    Indian Academy of Sciences (India)

    Keywords. insertion–deletion variations; haematological disease; tumours; human genetics. Journal of Genetics ... domly selected healthy Korean individuals using a blood genomic DNA ... Bioinformatics annotation and 3-D protein structure analysis. In this study ..... 2009 A genome-wide meta-analysis identifies. Journal of ...

  14. Patterns of genic intolerance of rare copy number variation in 59,898 human exomes

    Science.gov (United States)

    Ruderfer, Douglas M.; Hamamsy, Tymor; Lek, Monkol; Karczewski, Konrad J.; Kavanagh, David; Samocha, Kaitlin E.; Daly, Mark J.; MacArthur, Daniel G.; Fromer, Menachem; Purcell, Shaun M.

    2016-01-01

    Copy number variation (CNV) impacting protein-coding genes contributes significantly to human diversity and disease. Here we characterized the rates and properties of rare genic CNV (intolerance to CNVs that demonstrated moderate correlation with measures of genic constraint based on single-nucleotide variation (SNV) and was independently correlated with measures of evolutionary conservation. For individuals with schizophrenia, genes impacted by CNVs were more intolerant than in controls. ExAC CNV data constitutes a critical component of an integrated database spanning the spectrum of human genetic variation, aiding the interpretation of personal genomes as well as population-based disease studies. These data are freely available for download and visualization online. PMID:27533299

  15. Humans and Deep Networks Largely Agree on Which Kinds of Variation Make Object Recognition Harder.

    Science.gov (United States)

    Kheradpisheh, Saeed R; Ghodrati, Masoud; Ganjtabesh, Mohammad; Masquelier, Timothée

    2016-01-01

    View-invariant object recognition is a challenging problem that has attracted much attention among the psychology, neuroscience, and computer vision communities. Humans are notoriously good at it, even if some variations are presumably more difficult to handle than others (e.g., 3D rotations). Humans are thought to solve the problem through hierarchical processing along the ventral stream, which progressively extracts more and more invariant visual features. This feed-forward architecture has inspired a new generation of bio-inspired computer vision systems called deep convolutional neural networks (DCNN), which are currently the best models for object recognition in natural images. Here, for the first time, we systematically compared human feed-forward vision and DCNNs at view-invariant object recognition task using the same set of images and controlling the kinds of transformation (position, scale, rotation in plane, and rotation in depth) as well as their magnitude, which we call "variation level." We used four object categories: car, ship, motorcycle, and animal. In total, 89 human subjects participated in 10 experiments in which they had to discriminate between two or four categories after rapid presentation with backward masking. We also tested two recent DCNNs (proposed respectively by Hinton's group and Zisserman's group) on the same tasks. We found that humans and DCNNs largely agreed on the relative difficulties of each kind of variation: rotation in depth is by far the hardest transformation to handle, followed by scale, then rotation in plane, and finally position (much easier). This suggests that DCNNs would be reasonable models of human feed-forward vision. In addition, our results show that the variation levels in rotation in depth and scale strongly modulate both humans' and DCNNs' recognition performances. We thus argue that these variations should be controlled in the image datasets used in vision research.

  16. Humans and deep networks largely agree on which kinds of variation make object recognition harder

    Directory of Open Access Journals (Sweden)

    Saeed Reza Kheradpisheh

    2016-08-01

    Full Text Available View-invariant object recognition is a challenging problem that has attracted much attention among the psychology, neuroscience, and computer vision communities. Humans are notoriously good at it, even if some variations are presumably more difficult to handle than others (e.g. 3D rotations. Humans are thought to solve the problem through hierarchical processing along the ventral stream, which progressively extracts more and more invariant visual features. This feed-forward architecture has inspired a new generation of bio-inspired computer vision systems called deep convolutional neural networks (DCNN, which are currently the best models for object recognition in natural images. Here, for the first time, we systematically compared human feed-forward vision and DCNNs at view-invariant object recognition task using the same set of images and controlling the kinds of transformation (position, scale, rotation in plane, and rotation in depth as well as their magnitude, which we call variation level. We used four object categories: car, ship, motorcycle, and animal. In total, 89 human subjects participated in 10 experiments in which they had to discriminate between two or four categories after rapid presentation with backward masking. We also tested two recent DCNNs (proposed respectively by Hinton's group and Zisserman's group on the same tasks. We found that humans and DCNNs largely agreed on the relative difficulties of each kind of variation: rotation in depth is by far the hardest transformation to handle, followed by scale, then rotation in plane, and finally position (much easier. This suggests that DCNNs would be reasonable models of human feed-forward vision. In addition, our results show that the variation levels in rotation in depth and scale strongly modulate both humans' and DCNNs' recognition performances. We thus argue that these variations should be controlled in the image datasets used in vision research.

  17. Size variation in early human mandibles and molars from Klasies River, South Africa: comparison with other middle and late Pleistocene assemblages and with modern humans.

    Science.gov (United States)

    Royer, Danielle F; Lockwood, Charles A; Scott, Jeremiah E; Grine, Frederick E

    2009-10-01

    Previous studies of the Middle Stone Age human remains from Klasies River have concluded that they exhibited more sexual dimorphism than extant populations, but these claims have not been assessed statistically. We evaluate these claims by comparing size variation in the best-represented elements at the site, namely the mandibular corpora and M(2)s, to that in samples from three recent human populations using resampling methods. We also examine size variation in these same elements from seven additional middle and late Pleistocene sites: Skhūl, Dolní Vestonice, Sima de los Huesos, Arago, Krapina, Shanidar, and Vindija. Our results demonstrate that size variation in the Klasies assemblage was greater than in recent humans, consistent with arguments that the Klasies people were more dimorphic than living humans. Variation in the Skhūl, Dolní Vestonice, and Sima de los Huesos mandibular samples is also higher than in the recent human samples, indicating that the Klasies sample was not unusual among middle and late Pleistocene hominins. In contrast, the Neandertal samples (Krapina, Shanidar, and Vindija) do not evince relatively high mandibular and molar variation, which may indicate that the level of dimorphism in Neandertals was similar to that observed in extant humans. These results suggest that the reduced levels of dimorphism in Neandertals and living humans may have developed independently, though larger fossil samples are needed to test this hypothesis.

  18. The Body as a Substrate of Differentiation. Shifting the Focus from Race Science to Life Scientists' Research on Human Variation

    OpenAIRE

    Lipphardt, Veronika

    2017-01-01

    Abstract This article suggests to focus on the history of human variation instead of focussing on the history of race science. It views the latter as a subset of the former, hence views race science as embedded into the larger field of life scientists' investigations into human variation. This paper explores why human variation is such an attractive and productive object particularly for the life sciences. It proposes that knowledge about human variation is incomplete in a promising way, and ...

  19. Human mobility: Models and applications

    Science.gov (United States)

    Barbosa, Hugo; Barthelemy, Marc; Ghoshal, Gourab; James, Charlotte R.; Lenormand, Maxime; Louail, Thomas; Menezes, Ronaldo; Ramasco, José J.; Simini, Filippo; Tomasini, Marcello

    2018-03-01

    Recent years have witnessed an explosion of extensive geolocated datasets related to human movement, enabling scientists to quantitatively study individual and collective mobility patterns, and to generate models that can capture and reproduce the spatiotemporal structures and regularities in human trajectories. The study of human mobility is especially important for applications such as estimating migratory flows, traffic forecasting, urban planning, and epidemic modeling. In this survey, we review the approaches developed to reproduce various mobility patterns, with the main focus on recent developments. This review can be used both as an introduction to the fundamental modeling principles of human mobility, and as a collection of technical methods applicable to specific mobility-related problems. The review organizes the subject by differentiating between individual and population mobility and also between short-range and long-range mobility. Throughout the text the description of the theory is intertwined with real-world applications.

  20. Genetic variation in a member of the laminin gene family affects variation in body composition in Drosophila and humans

    Directory of Open Access Journals (Sweden)

    Hunter Gary R

    2008-08-01

    Full Text Available Abstract Background The objective of the present study was to map candidate loci influencing naturally occurring variation in triacylglycerol (TAG storage using quantitative complementation procedures in Drosophila melanogaster. Based on our results from Drosophila, we performed a human population-based association study to investigate the effect of natural variation in LAMA5 gene on body composition in humans. Results We identified four candidate genes that contributed to differences in TAG storage between two strains of D. melanogaster, including Laminin A (LanA, which is a member of the α subfamily of laminin chains. We confirmed the effects of this gene using a viable LanA mutant and showed that female flies homozygous for the mutation had significantly lower TAG storage, body weight, and total protein content than control flies. Drosophila LanA is closely related to human LAMA5 gene, which maps to the well-replicated obesity-linkage region on chromosome 20q13.2-q13.3. We tested for association between three common single nucleotide polymorphisms (SNPs in the human LAMA5 gene and variation in body composition and lipid profile traits in a cohort of unrelated women of European American (EA and African American (AA descent. In both ethnic groups, we found that SNP rs659822 was associated with weight (EA: P = 0.008; AA: P = 0.05 and lean mass (EA: P= 0.003; AA: P = 0.03. We also found this SNP to be associated with height (P = 0.01, total fat mass (P = 0.01, and HDL-cholesterol (P = 0.003 but only in EA women. Finally, significant associations of SNP rs944895 with serum TAG levels (P = 0.02 and HDL-cholesterol (P = 0.03 were observed in AA women. Conclusion Our results suggest an evolutionarily conserved role of a member of the laminin gene family in contributing to variation in weight and body composition.

  1. Cultural variation is part of human nature : Literary universals, context-sensitivity, and "shakespeare in the bush".

    Science.gov (United States)

    Sugiyama, Michelle Scalise

    2003-12-01

    In 1966, Laura Bohannan wrote her classic essay challenging the supposition that great literary works speak to universal human concerns and conditions and, by extension, that human nature is the same everywhere. Her evidence: the Tiv of West Africa interpret Hamlet differently from Westerners. While Bohannan's essay implies that cognitive universality and cultural variation are mutually exclusive phenomena, adaptationist theory suggests otherwise. Adaptive problems ("the human condition") and cognitive adaptations ("human nature") are constant across cultures. What differs between cultures is habitat: owing to environmental variation, the means and information relevant to solving adaptive problems differ from place to place. Thus, we find differences between cultures not because human minds differ in design but largely because human habitats differ in resources and history. On this view, we would expect world literature to express both human universals and cultural particularities. Specifically, we should expect to find literary universality at the macro level (e.g., adaptive problems, cognitive adaptations) and literary variation at the micro level (e.g., local solutions to adaptive problems).

  2. Landscape and variation of RNA secondary structure across the human transcriptome.

    OpenAIRE

    Wan, Y; Qu, K; Zhang, QC; Flynn, RA; Manor, O; Ouyang, Z; Zhang, J; Spitale, RC; Snyder, MP; Segal, E; Chang, HY

    2014-01-01

    In parallel to the genetic code for protein synthesis, a second layer of information is embedded in all RNA transcripts in the form of RNA structure. RNA structure influences practically every step in the gene expression program. However, the nature of most RNA structures or effects of sequence variation on structure are not known. Here we report the initial landscape and variation of RNA secondary structures (RSSs) in a human family trio (mother, father and their child). This provides a comp...

  3. Is variation in human radiosensitivity real or artifactual?

    International Nuclear Information System (INIS)

    Nakamura, Nori; Kushiro, Jun-ichi; Sposto, R.; Akiyama, Mitoshi.

    1989-12-01

    Two methods of producing human T-lymphocyte colonies in vitro are described, as well as dose-survival experiments using these methods for the investigation of possible differential radiosensitivity among individuals. In one method, the cloning efficiency (CE) of nonirradiated lymphocytes was between 10 % and 40 % (method 1), whereas subsequent improvement in assay conditions (method 2) resulted in a CE greater than 30 %. In vitro X-irradiation of colonies produced using method 1 revealed that the dose required to kill 90 % of the cells (D 10 ) was 2.87±0.28 Gy (mean ±SD, n = 18) for repeated examinations of lymphocytes from one reference individual. Using method 2, the D 10 values were greater, viz., 3.66±0.21 Gy for 28 repeated tests of the same reference individual and 3.58±0.19 Gy for 31 different individuals. Analysis of variance to compare the data from repeated examinations of one person versus data from single examinations of different persons showed that variation in the D 10 value was not significantly greater in the latter group. These results support the hypothesis that individual variation in human radiosensitivity is quite small, if it exists at all, as far as can be determined by the loss of colony-forming ability of irradiated G 0 lymphocytes. (author)

  4. Understanding variation in human fertility: what can we learn from evolutionary demography?

    Science.gov (United States)

    Sear, Rebecca; Lawson, David W; Kaplan, Hillard; Shenk, Mary K

    2016-04-19

    Decades of research on human fertility has presented a clear picture of how fertility varies, including its dramatic decline over the last two centuries in most parts of the world. Why fertility varies, both between and within populations, is not nearly so well understood. Fertility is a complex phenomenon, partly physiologically and partly behaviourally determined, thus an interdisciplinary approach is required to understand it. Evolutionary demographers have focused on human fertility since the 1980s. The first wave of evolutionary demographic research made major theoretical and empirical advances, investigating variation in fertility primarily in terms of fitness maximization. Research focused particularly on variation within high-fertility populations and small-scale subsistence societies and also yielded a number of hypotheses for why fitness maximization seems to break down as fertility declines during the demographic transition. A second wave of evolutionary demography research on fertility is now underway, paying much more attention to the cultural and psychological mechanisms underpinning fertility. It is also engaging with the complex, multi-causal nature of fertility variation, and with understanding fertility in complex modern and transitioning societies. Here, we summarize the history of evolutionary demographic work on human fertility, describe the current state of the field, and suggest future directions. © 2016 The Author(s).

  5. Global and disease-associated genetic variation in the human Fanconi anemia gene family.

    Science.gov (United States)

    Rogers, Kai J; Fu, Wenqing; Akey, Joshua M; Monnat, Raymond J

    2014-12-20

    Fanconi anemia (FA) is a human recessive genetic disease resulting from inactivating mutations in any of 16 FANC (Fanconi) genes. Individuals with FA are at high risk of developmental abnormalities, early bone marrow failure and leukemia. These are followed in the second and subsequent decades by a very high risk of carcinomas of the head and neck and anogenital region, and a small continuing risk of leukemia. In order to characterize base pair-level disease-associated (DA) and population genetic variation in FANC genes and the segregation of this variation in the human population, we identified 2948 unique FANC gene variants including 493 FA DA variants across 57,240 potential base pair variation sites in the 16 FANC genes. We then analyzed the segregation of this variation in the 7578 subjects included in the Exome Sequencing Project (ESP) and the 1000 Genomes Project (1KGP). There was a remarkably high frequency of FA DA variants in ESP/1KGP subjects: at least 1 FA DA variant was identified in 78.5% (5950 of 7578) individuals included in these two studies. Six widely used functional prediction algorithms correctly identified only a third of the known, DA FANC missense variants. We also identified FA DA variants that may be good candidates for different types of mutation-specific therapies. Our results demonstrate the power of direct DNA sequencing to detect, estimate the frequency of and follow the segregation of deleterious genetic variation in human populations. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Analysis of temporal variation in human masticatory cycles during gum chewing.

    Science.gov (United States)

    Crane, Elizabeth A; Rothman, Edward D; Childers, David; Gerstner, Geoffrey E

    2013-10-01

    The study investigated modulation of fast and slow opening (FO, SO) and closing (FC, SC) chewing cycle phases using gum-chewing sequences in humans. Twenty-two healthy adult subjects participated by chewing gum for at least 20s on the right side and at least 20s on the left side while jaw movements were tracked with a 3D motion analysis system. Jaw movement data were digitized, and chewing cycle phases were identified and analysed for all chewing cycles in a complete sequence. All four chewing cycle phase durations were more variant than total cycle durations, a result found in other non-human primates. Significant negative correlations existed between the opening phases, SO and FO, and between the closing phases, SC and FC; however, there was less consistency in terms of which phases were negatively correlated both between subjects, and between chewing sides within subjects, compared with results reported in other species. The coordination of intra-cycle phases appears to be flexible and to follow complex rules during gum-chewing in humans. Alternatively, the observed intra-cycle phase relationships could simply reflect: (1) variation in jaw kinematics due to variation in how gum was handled by the tongue on a chew-by-chew basis in our experimental design or (2) by variation due to data sampling noise and/or how phases were defined and identified. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Qualitative and quantitative estimations of the effect of geomagnetic field variations on human brain functional state

    International Nuclear Information System (INIS)

    Belisheva, N.K.; Popov, A.N.; Petukhova, N.V.; Pavlova, L.P.; Osipov, K.S.; Tkachenko, S.Eh.; Baranova, T.I.

    1995-01-01

    The comparison of functional dynamics of human brain with reference to qualitative and quantitative characteristics of local geomagnetic field (GMF) variations was conducted. Steady and unsteady states of human brain can be determined: by geomagnetic disturbances before the observation period; by structure and doses of GMF variations; by different combinations of qualitative and quantitative characteristics of GMF variations. Decrease of optimal GMF activity level and the appearance of aperiodic disturbances of GMF can be a reason of unsteady brain's state. 18 refs.; 3 figs

  8. Geography, Ethnicity or Subsistence-Specific Variations in Human Microbiome Composition and Diversity

    Directory of Open Access Journals (Sweden)

    Vinod K. Gupta

    2017-06-01

    Full Text Available One of the fundamental issues in the microbiome research is characterization of the healthy human microbiota. Recent studies have elucidated substantial divergences in the microbiome structure between healthy individuals from different race and ethnicity. This review provides a comprehensive account of such geography, ethnicity or life-style-specific variations in healthy microbiome at five major body habitats—Gut, Oral-cavity, Respiratory Tract, Skin, and Urogenital Tract (UGT. The review focuses on the general trend in the human microbiome evolution—a gradual transition in the gross compositional structure along with a continual decrease in diversity of the microbiome, especially of the gut microbiome, as the human populations passed through three stages of subsistence like foraging, rural farming and industrialized urban western life. In general, gut microbiome of the hunter-gatherer populations is highly abundant with Prevotella, Proteobacteria, Spirochaetes, Clostridiales, Ruminobacter etc., while those of the urban communities are often enriched in Bacteroides, Bifidobacterium, and Firmicutes. The oral and skin microbiome are the next most diverse among different populations, while respiratory tract and UGT microbiome show lesser variations. Higher microbiome diversity is observed for oral-cavity in hunter-gatherer group with higher prevalence of Haemophilus than agricultural group. In case of skin microbiome, rural and urban Chinese populations show variation in abundance of Trabulsiella and Propionibacterium. On the basis of published data, we have characterized the core microbiota—the set of genera commonly found in all populations, irrespective of their geographic locations, ethnicity or mode of subsistence. We have also identified the major factors responsible for geography-based alterations in microbiota; though it is not yet clear which factor plays a dominant role in shaping the microbiome—nature or nurture, host genetics

  9. Application of human volunteer studies in setting exposure limits

    International Nuclear Information System (INIS)

    Bailey, M.R.

    1989-01-01

    Human volunteer studies can provide many of the quantitative data on human radionuclide biokinetics needed to relate organ doses to intakes. They are best suited to characterising parameters that apply to a wide range of compounds, e.g. particle deposition in the respiratory tract, and the retention and excretion of elements after injection into the blood. Their application to quantifying particle clearance from the respiratory tract is discussed, with particular reference to recent findings and the NRPB's programme of volunteer investigations. Evidence to support the view that particle clearance rates are similar for different materials is summarised. Rates of particle clearance from the human lung to the GI tract are calculated from the results of two recent studies. The fraction of the remaining lung content cleared per day is estimated to decrease from ∼ 3 x 10 -3 d -1 at 25 days to ∼ 5 x 10 -4 d -1 at 350 days. There is a large degree of inter-subject variation, with most results conforming to a log-normal distribution with σ g of 1.6. There remains considerable uncertainty about subsequent clearance, and about sites of long-term lung retention. (author)

  10. Genome Architecture and Its Roles in Human Copy Number Variation

    Directory of Open Access Journals (Sweden)

    Lu Chen

    2014-12-01

    Full Text Available Besides single-nucleotide variants in the human genome, large-scale genomic variants, such as copy number variations (CNVs, are being increasingly discovered as a genetic source of human diversity and the pathogenic factors of diseases. Recent experimental findings have shed light on the links between different genome architectures and CNV mutagenesis. In this review, we summarize various genomic features and discuss their contributions to CNV formation. Genomic repeats, including both low-copy and high-copy repeats, play important roles in CNV instability, which was initially known as DNA recombination events. Furthermore, it has been found that human genomic repeats can also induce DNA replication errors and consequently result in CNV mutations. Some recent studies showed that DNA replication timing, which reflects the high-order information of genomic organization, is involved in human CNV mutations. Our review highlights that genome architecture, from DNA sequence to high-order genomic organization, is an important molecular factor in CNV mutagenesis and human genomic instability.

  11. An integrated map of genetic variation from 1.092 human genomes

    DEFF Research Database (Denmark)

    Abecasis, Goncalo R.; Auton, Adam; Brooks, Lisa D.

    2012-01-01

    By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination ...

  12. Evaluation of the interindividual human variation in bioactivation of methyleugenol using physiologically based kinetic modeling and Monte Carlo simulations

    International Nuclear Information System (INIS)

    Al-Subeihi, Ala' A.A.; Alhusainy, Wasma; Kiwamoto, Reiko; Spenkelink, Bert; Bladeren, Peter J. van; Rietjens, Ivonne M.C.M.; Punt, Ans

    2015-01-01

    The present study aims at predicting the level of formation of the ultimate carcinogenic metabolite of methyleugenol, 1′-sulfooxymethyleugenol, in the human population by taking variability in key bioactivation and detoxification reactions into account using Monte Carlo simulations. Depending on the metabolic route, variation was simulated based on kinetic constants obtained from incubations with a range of individual human liver fractions or by combining kinetic constants obtained for specific isoenzymes with literature reported human variation in the activity of these enzymes. The results of the study indicate that formation of 1′-sulfooxymethyleugenol is predominantly affected by variation in i) P450 1A2-catalyzed bioactivation of methyleugenol to 1′-hydroxymethyleugenol, ii) P450 2B6-catalyzed epoxidation of methyleugenol, iii) the apparent kinetic constants for oxidation of 1′-hydroxymethyleugenol, and iv) the apparent kinetic constants for sulfation of 1′-hydroxymethyleugenol. Based on the Monte Carlo simulations a so-called chemical-specific adjustment factor (CSAF) for intraspecies variation could be derived by dividing different percentiles by the 50th percentile of the predicted population distribution for 1′-sulfooxymethyleugenol formation. The obtained CSAF value at the 90th percentile was 3.2, indicating that the default uncertainty factor of 3.16 for human variability in kinetics may adequately cover the variation within 90% of the population. Covering 99% of the population requires a larger uncertainty factor of 6.4. In conclusion, the results showed that adequate predictions on interindividual human variation can be made with Monte Carlo-based PBK modeling. For methyleugenol this variation was observed to be in line with the default variation generally assumed in risk assessment. - Highlights: • Interindividual human differences in methyleugenol bioactivation were simulated. • This was done using in vitro incubations, PBK modeling

  13. Evaluation of the interindividual human variation in bioactivation of methyleugenol using physiologically based kinetic modeling and Monte Carlo simulations

    Energy Technology Data Exchange (ETDEWEB)

    Al-Subeihi, Ala' A.A., E-mail: subeihi@yahoo.com [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands); BEN-HAYYAN-Aqaba International Laboratories, Aqaba Special Economic Zone Authority (ASEZA), P. O. Box 2565, Aqaba 77110 (Jordan); Alhusainy, Wasma; Kiwamoto, Reiko; Spenkelink, Bert [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands); Bladeren, Peter J. van [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands); Nestec S.A., Avenue Nestlé 55, 1800 Vevey (Switzerland); Rietjens, Ivonne M.C.M.; Punt, Ans [Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen (Netherlands)

    2015-03-01

    The present study aims at predicting the level of formation of the ultimate carcinogenic metabolite of methyleugenol, 1′-sulfooxymethyleugenol, in the human population by taking variability in key bioactivation and detoxification reactions into account using Monte Carlo simulations. Depending on the metabolic route, variation was simulated based on kinetic constants obtained from incubations with a range of individual human liver fractions or by combining kinetic constants obtained for specific isoenzymes with literature reported human variation in the activity of these enzymes. The results of the study indicate that formation of 1′-sulfooxymethyleugenol is predominantly affected by variation in i) P450 1A2-catalyzed bioactivation of methyleugenol to 1′-hydroxymethyleugenol, ii) P450 2B6-catalyzed epoxidation of methyleugenol, iii) the apparent kinetic constants for oxidation of 1′-hydroxymethyleugenol, and iv) the apparent kinetic constants for sulfation of 1′-hydroxymethyleugenol. Based on the Monte Carlo simulations a so-called chemical-specific adjustment factor (CSAF) for intraspecies variation could be derived by dividing different percentiles by the 50th percentile of the predicted population distribution for 1′-sulfooxymethyleugenol formation. The obtained CSAF value at the 90th percentile was 3.2, indicating that the default uncertainty factor of 3.16 for human variability in kinetics may adequately cover the variation within 90% of the population. Covering 99% of the population requires a larger uncertainty factor of 6.4. In conclusion, the results showed that adequate predictions on interindividual human variation can be made with Monte Carlo-based PBK modeling. For methyleugenol this variation was observed to be in line with the default variation generally assumed in risk assessment. - Highlights: • Interindividual human differences in methyleugenol bioactivation were simulated. • This was done using in vitro incubations, PBK modeling

  14. NDVI-Based analysis on the influence of human activities on vegetation variation on Hainan Island

    Science.gov (United States)

    Luo, Hongxia; Dai, Shengpei; Xie, Zhenghui; Fang, Jihua

    2018-02-01

    Using the Moderate Resolution Imaging Spectroradiometer-normalized difference vegetation index (NDVI) dataset, we analyzed the predicted NDVI values variation and the influence of human activities on vegetation on Hainan Island during 2001-2015. We investigated the roles of human activities in vegetation variation, particularly from 2002 when implemented the Grain-for-Greenprogram on Hainan Island. The trend analysis, linear regression model and residual analysis were used to analyze the data. The results of the study showed that (1) The predicted vegetation on Hainan Island showed an general upward trend with a linear growth rate of 0.0025/10y (phuman activities. (3) In general, human activities had played a positive role in the vegetation increase on Hainan Island, and the residual NDVI trend of this region showed positive outcomes for vegetation variation after implementing ecological engineering projects. However, it indicated a growing risk of vegetation degradation in the coastal region of Hainan Island as a result of rapid urbanization, land reclamation.

  15. Orion: Detecting regions of the human non-coding genome that are intolerant to variation using population genetics.

    Science.gov (United States)

    Gussow, Ayal B; Copeland, Brett R; Dhindsa, Ryan S; Wang, Quanli; Petrovski, Slavé; Majoros, William H; Allen, Andrew S; Goldstein, David B

    2017-01-01

    There is broad agreement that genetic mutations occurring outside of the protein-coding regions play a key role in human disease. Despite this consensus, we are not yet capable of discerning which portions of non-coding sequence are important in the context of human disease. Here, we present Orion, an approach that detects regions of the non-coding genome that are depleted of variation, suggesting that the regions are intolerant of mutations and subject to purifying selection in the human lineage. We show that Orion is highly correlated with known intolerant regions as well as regions that harbor putatively pathogenic variation. This approach provides a mechanism to identify pathogenic variation in the human non-coding genome and will have immediate utility in the diagnostic interpretation of patient genomes and in large case control studies using whole-genome sequences.

  16. Genetic variation in lipid desaturases and its impact on the development of human disease.

    Science.gov (United States)

    Merino, Diana M; Ma, David W L; Mutch, David M

    2010-06-18

    Perturbations in lipid metabolism characterize many of the chronic diseases currently plaguing our society, such as obesity, diabetes, and cardiovascular disease. Thus interventions that target plasma lipid levels remain a primary goal to manage these diseases. The determinants of plasma lipid levels are multi-factorial, consisting of both genetic and lifestyle components. Recent evidence indicates that fatty acid desaturases have an important role in defining plasma and tissue lipid profiles. This review will highlight the current state-of-knowledge regarding three desaturases (Scd-1, Fads1 and Fads2) and their potential roles in disease onset and development. Although research in rodent models has provided invaluable insight into the regulation and functions of these desaturases, the extent to which murine research can be translated to humans remains unclear. Evidence emerging from human-based research demonstrates that genetic variation in human desaturase genes affects enzyme activity and, consequently, disease risk factors. Moreover, this genetic variation may have a trans-generational effect via breastfeeding. Therefore inter-individual variation in desaturase function is attributed to both genetic and lifestyle components. As such, population-based research regarding the role of desaturases on disease risk is challenged by this complex gene-lifestyle paradigm. Unravelling the contribution of each component is paramount for understanding the inter-individual variation that exists in plasma lipid profiles, and will provide crucial information to develop personalized strategies to improve health management.

  17. PRDM9 variation strongly influences recombination hot-spot activity and meiotic instability in humans.

    Science.gov (United States)

    Berg, Ingrid L; Neumann, Rita; Lam, Kwan-Wood G; Sarbajna, Shriparna; Odenthal-Hesse, Linda; May, Celia A; Jeffreys, Alec J

    2010-10-01

    PRDM9 has recently been identified as a likely trans regulator of meiotic recombination hot spots in humans and mice. PRDM9 contains a zinc finger array that, in humans, can recognize a short sequence motif associated with hot spots, with binding to this motif possibly triggering hot-spot activity via chromatin remodeling. We now report that human genetic variation at the PRDM9 locus has a strong effect on sperm hot-spot activity, even at hot spots lacking the sequence motif. Subtle changes within the zinc finger array can create hot-spot nonactivating or enhancing variants and can even trigger the appearance of a new hot spot, suggesting that PRDM9 is a major global regulator of hot spots in humans. Variation at the PRDM9 locus also influences aspects of genome instability-specifically, a megabase-scale rearrangement underlying two genomic disorders as well as minisatellite instability-implicating PRDM9 as a risk factor for some pathological genome rearrangements.

  18. A map of human genome variation from population-scale sequencing.

    Science.gov (United States)

    Abecasis, Gonçalo R; Altshuler, David; Auton, Adam; Brooks, Lisa D; Durbin, Richard M; Gibbs, Richard A; Hurles, Matt E; McVean, Gil A

    2010-10-28

    The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10(-8) per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.

  19. Landscape and variation of RNA secondary structure across the human transcriptome.

    Science.gov (United States)

    Wan, Yue; Qu, Kun; Zhang, Qiangfeng Cliff; Flynn, Ryan A; Manor, Ohad; Ouyang, Zhengqing; Zhang, Jiajing; Spitale, Robert C; Snyder, Michael P; Segal, Eran; Chang, Howard Y

    2014-01-30

    In parallel to the genetic code for protein synthesis, a second layer of information is embedded in all RNA transcripts in the form of RNA structure. RNA structure influences practically every step in the gene expression program. However, the nature of most RNA structures or effects of sequence variation on structure are not known. Here we report the initial landscape and variation of RNA secondary structures (RSSs) in a human family trio (mother, father and their child). This provides a comprehensive RSS map of human coding and non-coding RNAs. We identify unique RSS signatures that demarcate open reading frames and splicing junctions, and define authentic microRNA-binding sites. Comparison of native deproteinized RNA isolated from cells versus refolded purified RNA suggests that the majority of the RSS information is encoded within RNA sequence. Over 1,900 transcribed single nucleotide variants (approximately 15% of all transcribed single nucleotide variants) alter local RNA structure. We discover simple sequence and spacing rules that determine the ability of point mutations to impact RSSs. Selective depletion of 'riboSNitches' versus structurally synonymous variants at precise locations suggests selection for specific RNA shapes at thousands of sites, including 3' untranslated regions, binding sites of microRNAs and RNA-binding proteins genome-wide. These results highlight the potentially broad contribution of RNA structure and its variation to gene regulation.

  20. Variational analysis of regular mappings theory and applications

    CERN Document Server

    Ioffe, Alexander D

    2017-01-01

    This monograph offers the first systematic account of (metric) regularity theory in variational analysis. It presents new developments alongside classical results and demonstrates the power of the theory through applications to various problems in analysis and optimization theory. The origins of metric regularity theory can be traced back to a series of fundamental ideas and results of nonlinear functional analysis and global analysis centered around problems of existence and stability of solutions of nonlinear equations. In variational analysis, regularity theory goes far beyond the classical setting and is also concerned with non-differentiable and multi-valued operators. The present volume explores all basic aspects of the theory, from the most general problems for mappings between metric spaces to those connected with fairly concrete and important classes of operators acting in Banach and finite dimensional spaces. Written by a leading expert in the field, the book covers new and powerful techniques, whic...

  1. Demographic and spatio-temporal variation in human plague at a persistent focus in Tanzania

    DEFF Research Database (Denmark)

    Davis, S; Makundi, R H; Machang'u, R S

    2006-01-01

    Human plague in the Western Usambara Mountains in Tanzania has been a public health problem since the first outbreak in 1980. The wildlife reservoir is unknown and eradication measures that have proved effective elsewhere in Tanzania appear to fail in this region. We use census data from 2002...... and hospital records kept since 1986 to describe the temporal, spatial and demographic variation in human plague. A seasonal peak in cases occurs from December to February with the numbers of cases during this peak varying between 0 and 1150. Variation in incidence, calculated for each village as the mean...... number of cases per thousand inhabitants per year, indicates that human plague is concentrated around a group of three neighbouring, relatively isolated, high-altitude villages; Nywelo, Madala and Gologolo. However, there was no evidence that these villages were acting as a source of infection...

  2. APPLICATION OF LEARNING CYCLE MODEL (5E LEARNING WITH CHART VARIATION TOWARDSTUDENTS’ CREATIVITY

    Directory of Open Access Journals (Sweden)

    Suciati -

    2015-04-01

    Full Text Available This study aims to determine the differences in the application of the model LC (5E with a technique variation (interrelationship diagram / ID and affinity diagrams / AD of two classes of different school (XIPA-8 class of SMAN 3 Surakarta and class XIPA-6 of SMAN 3 Boyolali, toward the increase of students’ creativity. This research is a qualitative descriptive study. The results of this study, we can conclude that the application of the model LC (5E with a technique variation at two schools can improve students' creativity despite different levels of improvement.

  3. Advances in variational and hemivariational inequalities theory, numerical analysis, and applications

    CERN Document Server

    Migórski, Stanisław; Sofonea, Mircea

    2015-01-01

    Highlighting recent advances in variational and hemivariational inequalities with an emphasis on theory, numerical analysis and applications, this volume serves as an indispensable resource to graduate students and researchers interested in the latest results from recognized scholars in this relatively young and rapidly-growing field. Particularly, readers will find that the volume’s results and analysis present valuable insights into the fields of pure and applied mathematics, as well as civil, aeronautical, and mechanical engineering. Researchers and students will find new results on well posedness to stationary and evolutionary inequalities and their rigorous proofs. In addition to results on modeling and abstract problems, the book contains new results on the numerical methods for variational and hemivariational inequalities. Finally, the applications presented illustrate the use of these results in the study of miscellaneous mathematical models which describe the contact between deformable bodies and a...

  4. Integrative analysis of RNA, translation, and protein levels reveals distinct regulatory variation across humans.

    Science.gov (United States)

    Cenik, Can; Cenik, Elif Sarinay; Byeon, Gun W; Grubert, Fabian; Candille, Sophie I; Spacek, Damek; Alsallakh, Bilal; Tilgner, Hagen; Araya, Carlos L; Tang, Hua; Ricci, Emiliano; Snyder, Michael P

    2015-11-01

    Elucidating the consequences of genetic differences between humans is essential for understanding phenotypic diversity and personalized medicine. Although variation in RNA levels, transcription factor binding, and chromatin have been explored, little is known about global variation in translation and its genetic determinants. We used ribosome profiling, RNA sequencing, and mass spectrometry to perform an integrated analysis in lymphoblastoid cell lines from a diverse group of individuals. We find significant differences in RNA, translation, and protein levels suggesting diverse mechanisms of personalized gene expression control. Combined analysis of RNA expression and ribosome occupancy improves the identification of individual protein level differences. Finally, we identify genetic differences that specifically modulate ribosome occupancy--many of these differences lie close to start codons and upstream ORFs. Our results reveal a new level of gene expression variation among humans and indicate that genetic variants can cause changes in protein levels through effects on translation. © 2015 Cenik et al.; Published by Cold Spring Harbor Laboratory Press.

  5. Balancing selection on a regulatory region exhibiting ancient variation that predates human-neandertal divergence.

    Directory of Open Access Journals (Sweden)

    Omer Gokcumen

    2013-04-01

    Full Text Available Ancient population structure shaping contemporary genetic variation has been recently appreciated and has important implications regarding our understanding of the structure of modern human genomes. We identified a ∼36-kb DNA segment in the human genome that displays an ancient substructure. The variation at this locus exists primarily as two highly divergent haplogroups. One of these haplogroups (the NE1 haplogroup aligns with the Neandertal haplotype and contains a 4.6-kb deletion polymorphism in perfect linkage disequilibrium with 12 single nucleotide polymorphisms (SNPs across diverse populations. The other haplogroup, which does not contain the 4.6-kb deletion, aligns with the chimpanzee haplotype and is likely ancestral. Africans have higher overall pairwise differences with the Neandertal haplotype than Eurasians do for this NE1 locus (p<10⁻¹⁵. Moreover, the nucleotide diversity at this locus is higher in Eurasians than in Africans. These results mimic signatures of recent Neandertal admixture contributing to this locus. However, an in-depth assessment of the variation in this region across multiple populations reveals that African NE1 haplotypes, albeit rare, harbor more sequence variation than NE1 haplotypes found in Europeans, indicating an ancient African origin of this haplogroup and refuting recent Neandertal admixture. Population genetic analyses of the SNPs within each of these haplogroups, along with genome-wide comparisons revealed significant FST (p = 0.00003 and positive Tajima's D (p = 0.00285 statistics, pointing to non-neutral evolution of this locus. The NE1 locus harbors no protein-coding genes, but contains transcribed sequences as well as sequences with putative regulatory function based on bioinformatic predictions and in vitro experiments. We postulate that the variation observed at this locus predates Human-Neandertal divergence and is evolving under balancing selection, especially among European

  6. Brief communication: human cranial variation fits iterative founder effect model with African origin.

    Science.gov (United States)

    von Cramon-Taubadel, Noreen; Lycett, Stephen J

    2008-05-01

    Recent studies comparing craniometric and neutral genetic affinity matrices have concluded that, on average, human cranial variation fits a model of neutral expectation. While human craniometric and genetic data fit a model of isolation by geographic distance, it is not yet clear whether this is due to geographically mediated gene flow or human dispersal events. Recently, human genetic data have been shown to fit an iterative founder effect model of dispersal with an African origin, in line with the out-of-Africa replacement model for modern human origins, and Manica et al. (Nature 448 (2007) 346-349) have demonstrated that human craniometric data also fit this model. However, in contrast with the neutral model of cranial evolution suggested by previous studies, Manica et al. (2007) made the a priori assumption that cranial form has been subject to climatically driven natural selection and therefore correct for climate prior to conducting their analyses. Here we employ a modified theoretical and methodological approach to test whether human cranial variability fits the iterative founder effect model. In contrast with Manica et al. (2007) we employ size-adjusted craniometric variables, since climatic factors such as temperature have been shown to correlate with aspects of cranial size. Despite these differences, we obtain similar results to those of Manica et al. (2007), with up to 26% of global within-population craniometric variation being explained by geographic distance from sub-Saharan Africa. Comparative analyses using non-African origins do not yield significant results. The implications of these results are discussed in the light of the modern human origins debate. (c) 2007 Wiley-Liss, Inc.

  7. Patterns of cis regulatory variation in diverse human populations.

    Directory of Open Access Journals (Sweden)

    Barbara E Stranger

    Full Text Available The genetic basis of gene expression variation has long been studied with the aim to understand the landscape of regulatory variants, but also more recently to assist in the interpretation and elucidation of disease signals. To date, many studies have looked in specific tissues and population-based samples, but there has been limited assessment of the degree of inter-population variability in regulatory variation. We analyzed genome-wide gene expression in lymphoblastoid cell lines from a total of 726 individuals from 8 global populations from the HapMap3 project and correlated gene expression levels with HapMap3 SNPs located in cis to the genes. We describe the influence of ancestry on gene expression levels within and between these diverse human populations and uncover a non-negligible impact on global patterns of gene expression. We further dissect the specific functional pathways differentiated between populations. We also identify 5,691 expression quantitative trait loci (eQTLs after controlling for both non-genetic factors and population admixture and observe that half of the cis-eQTLs are replicated in one or more of the populations. We highlight patterns of eQTL-sharing between populations, which are partially determined by population genetic relatedness, and discover significant sharing of eQTL effects between Asians, European-admixed, and African subpopulations. Specifically, we observe that both the effect size and the direction of effect for eQTLs are highly conserved across populations. We observe an increasing proximity of eQTLs toward the transcription start site as sharing of eQTLs among populations increases, highlighting that variants close to TSS have stronger effects and therefore are more likely to be detected across a wider panel of populations. Together these results offer a unique picture and resource of the degree of differentiation among human populations in functional regulatory variation and provide an estimate for

  8. Applications of exterior difference systems to variations in discrete mechanics

    International Nuclear Information System (INIS)

    Xie Zheng; Li Hongbo

    2008-01-01

    In discrete mechanics, difference equations describe the fundamental physical laws and exhibit many geometric properties. Can these equations be obtained in a geometric way? Using some techniques in exterior difference systems, we investigate the discrete variational problem. As an application, we give a positive answer to the above question for the discrete Newton's, Euler-Lagrange, and Hamilton's equations

  9. Effects of major geometric variations between intracavitary applications on pear-shaped isodose dimension in cancer of the cervix

    International Nuclear Information System (INIS)

    Kim, R. Y.

    1996-01-01

    PURPOSE: The basic principal of intracavitary brachytherapy for cancer of the cervix is based on specific loading rules to achieve a pear-shaped isodose distribution centered around the cervix. Recently, ICRU Report 38 recommends a dose reference volume for reporting. Our previous studies have confirmed that there is considerable variations of geometry between applications. This study is to evaluate the effect of major geometric variations on pear-shaped isodose dimension in manual afterloading low-dose-rate system. MATERIAL AND METHODS: One hundred orthogonal films of 50 patients with cancer of the cervix (2 applications/patient) were reviewed for comparative measurements of geometric variations between applications. Major geometric variations were found for 13 patients in lengths of tandem, 7 patients in colpostats separation and 16 patients in vaginal packing. The direct measurement of these geometric variations were compared with the three-dimensional measurement of the pear-shaped isodose enclosed by the point A between the two applications. RESULTS: The geometric variations in the width of colpostats separation and length of tandem were directly related to the width and height of the pear-shaped isodose dimension. The geometric relationship between the colpostats and distal tandem had an important effect on the thickness of the pear-shape. In optimization of poor geometry for rectum or bladder wall, high dose volume centered around the cervix is reduced without changing the overall pear-shaped volume due to changing configuration of the pear-shaped isodose. In our selected patients with two applications, variations in vaginal packing had no direct effect on the width and thickness of the pear-shape due to other variables. CONCLUSION: Major geometric variations between applications greatly affect the dimension of the pear-shaped isodose distribution. Optimization of poor geometry is quite limited without compromising the high-dose volume centered around the

  10. Variation of topical application to skin under good clinical practice (GCP)

    DEFF Research Database (Denmark)

    Vind-Kezunovic, Dina; Serup, Jørgen Vedelskov

    2016-01-01

    INTRODUCTION: Application of topical products by individuals is inherently variable and accurate dosing can be difficult to control. Variation of the dose used under optimal conditions in drug trials is unknown. METHODS: This trial was part of a double-blind, randomized, placebo-controlled good...

  11. Transcriptome variations among human embryonic stem cell lines are associated with their differentiation propensity.

    Directory of Open Access Journals (Sweden)

    Changbin Sun

    Full Text Available Human embryonic stem cells (hESCs have the potential to form any cell type in the body, making them attractive cell sources in drug screening, regenerative medicine, disease and developmental processes modeling. However, not all hESC lines have the equal potency to generate desired cell types in vitro. Significant variations have been observed for the differentiation efficiency of various human ESC lines. The precise underpinning molecular mechanisms are still unclear. In this work, we compared transcriptome variations of four hESC lines H7, HUES1, HUES8 and HUES9. We found that hESC lines have different gene expression profiles, and these differentially expressed genes (DEGs are significantly enriched in developmental processes, such as ectodermal, mesodermal and endodermal development. The enrichment difference between hESC lines was consistent with its lineage bias. Among these DEGs, some pluripotency factors and genes involved in signaling transduction showed great variations as well. The pleiotropic functions of these genes in controlling hESC identity and early lineage specification, implicated that different hESC lines may utilize distinct balance mechanisms to maintain pluripotent state. When the balance is broken in a certain environment, gene expression variation between them could impact on their different lineage specification behavior.

  12. Microgeographic variation in locomotor traits among lizards in a human-built environment

    Directory of Open Access Journals (Sweden)

    Colin Donihue

    2016-03-01

    Full Text Available Microgeographic variation in fitness-relevant traits may be more common than previously appreciated. The fitness of many vertebrates is directly related to their locomotor capacity, a whole-organism trait integrating behavior, morphology, and physiology. Because locomotion is inextricably related to context, I hypothesized that it might vary with habitat structure in a wide-ranging lizard, Podarcis erhardii, found in the Greek Cyclade Islands. I compared lizard populations living on human-built rock walls, a novel habitat with complex vertical structure, with nearby lizard populations that are naive to human-built infrastructure and live in flat, loose-substrate habitat. I tested for differences in morphology, behavior, and performance. Lizards from built sites were larger and had significantly (and relatively longer forelimbs and hindlimbs. The differences in hindlimb morphology were especially pronounced for distal components—the foot and longest toe. These morphologies facilitated a significant behavioral shift in jumping propensity across a rocky experimental substrate. I found no difference in maximum velocity between these populations; however, females originating from wall sites potentially accelerated faster over the rocky experimental substrate. The variation between these closely neighboring populations suggests that the lizards inhabiting walls have experienced a suite of trait changes enabling them to take advantage of the novel habitat structure created by humans.

  13. Premolar root and canal variation in extant non-human hominoidea.

    Science.gov (United States)

    Moore, N Collin; Hublin, Jean-Jacques; Skinner, Matthew M

    2015-08-11

    The premolar sub-cervical region in four non-human extant ape genera are examined to: 1) define a classification scheme for the premolar root system in order to rigorously characterize, quantify and document variation in root and canal, form, number and configuration; 2) compare this variation within and between genera; and 3) test the hypotheses that sex and size (i.e., the "size/number continuum," Shields, ) of the premolar are determinants of root/canal form and/or number. Microtomography and 3D visualization software are utilized to examine a large sample of Hylobates, Pan, Gorilla, and Pongo (n = 951 teeth). Each premolar root system is examined to ascertain the expected level of variability for each taxon. Cervical surface area (mm 2 ) serves as a metric proxy for tooth size. A Chi-square test of independence is used to assess for variability differences between and within each taxon, and Mann-Whitney U tests are employed to assess the predicted relationship between tooth size and variation within each taxon. Our findings indicate that root and canal configurations, non-metric root traits and tooth size can distinguish between extant ape genera. Within the four ape taxa, premolar size variation is generally, but not always, correlated with canal/root number. Our results indicate that males and females within genera differ in tooth size but not in canal/root form and number. We report previously undocumented variation in the study taxa. Our results are discussed within the context of Miocene Apes as well as the developmental and systematic implications. Am J Phys Anthropol, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  14. Accounting for regional variation in both natural environment and human disturbance to improve performance of multimetric indices of lotic benthic diatoms.

    Science.gov (United States)

    Tang, Tao; Stevenson, R Jan; Infante, Dana M

    2016-10-15

    Regional variation in both natural environment and human disturbance can influence performance of ecological assessments. In this study we calculated 5 types of benthic diatom multimetric indices (MMIs) with 3 different approaches to account for variation in ecological assessments. We used: site groups defined by ecoregions or diatom typologies; the same or different sets of metrics among site groups; and unmodeled or modeled MMIs, where models accounted for natural variation in metrics within site groups by calculating an expected reference condition for each metric and each site. We used data from the USEPA's National Rivers and Streams Assessment to calculate the MMIs and evaluate changes in MMI performance. MMI performance was evaluated with indices of precision, bias, responsiveness, sensitivity and relevancy which were respectively measured as MMI variation among reference sites, effects of natural variables on MMIs, difference between MMIs at reference and highly disturbed sites, percent of highly disturbed sites properly classified, and relation of MMIs to human disturbance and stressors. All 5 types of MMIs showed considerable discrimination ability. Using different metrics among ecoregions sometimes reduced precision, but it consistently increased responsiveness, sensitivity, and relevancy. Site specific metric modeling reduced bias and increased responsiveness. Combined use of different metrics among site groups and site specific modeling significantly improved MMI performance irrespective of site grouping approach. Compared to ecoregion site classification, grouping sites based on diatom typologies improved precision, but did not improve overall performance of MMIs if we accounted for natural variation in metrics with site specific models. We conclude that using different metrics among ecoregions and site specific metric modeling improve MMI performance, particularly when used together. Applications of these MMI approaches in ecological assessments

  15. Human midsagittal brain shape variation: patterns, allometry and integration

    Science.gov (United States)

    Bruner, Emiliano; Martin-Loeches, Manuel; Colom, Roberto

    2010-01-01

    Midsagittal cerebral morphology provides a homologous geometrical reference for brain shape and cortical vs. subcortical spatial relationships. In this study, midsagittal brain shape variation is investigated in a sample of 102 humans, in order to describe and quantify the major patterns of correlation between morphological features, the effect of size and sex on general anatomy, and the degree of integration between different cortical and subcortical areas. The only evident pattern of covariation was associated with fronto-parietal cortical bulging. The allometric component was weak for the cortical profile, but more robust for the posterior subcortical areas. Apparent sex differences were evidenced in size but not in brain shape. Cortical and subcortical elements displayed scarcely integrated changes, suggesting a modular separation between these two areas. However, a certain correlation was found between posterior subcortical and parietal cortical variations. These results should be directly integrated with information ranging from functional craniology to wiring organization, and with hypotheses linking brain shape and the mechanical properties of neurons during morphogenesis. PMID:20345859

  16. Bridging two scholarly islands enriches both: COI DNA barcodes for species identification versus human mitochondrial variation for the study of migrations and pathologies.

    Science.gov (United States)

    Thaler, David S; Stoeckle, Mark Y

    2016-10-01

    DNA barcodes for species identification and the analysis of human mitochondrial variation have developed as independent fields even though both are based on sequences from animal mitochondria. This study finds questions within each field that can be addressed by reference to the other. DNA barcodes are based on a 648-bp segment of the mitochondrially encoded cytochrome oxidase I. From most species, this segment is the only sequence available. It is impossible to know whether it fairly represents overall mitochondrial variation. For modern humans, the entire mitochondrial genome is available from thousands of healthy individuals. SNPs in the human mitochondrial genome are evenly distributed across all protein-encoding regions arguing that COI DNA barcode is representative. Barcode variation among related species is largely based on synonymous codons. Data on human mitochondrial variation support the interpretation that most - possibly all - synonymous substitutions in mitochondria are selectively neutral. DNA barcodes confirm reports of a low variance in modern humans compared to nonhuman primates. In addition, DNA barcodes allow the comparison of modern human variance to many other extant animal species. Birds are a well-curated group in which DNA barcodes are coupled with census and geographic data. Putting modern human variation in the context of intraspecies variation among birds shows humans to be a single breeding population of average variance.

  17. Variation in heterozygosity predicts variation in human substitution rates between populations, individuals and genomic regions.

    Directory of Open Access Journals (Sweden)

    William Amos

    Full Text Available The "heterozygote instability" (HI hypothesis suggests that gene conversion events focused on heterozygous sites during meiosis locally increase the mutation rate, but this hypothesis remains largely untested. As humans left Africa they lost variability, which, if HI operates, should have reduced the mutation rate in non-Africans. Relative substitution rates were quantified in diverse humans using aligned whole genome sequences from the 1,000 genomes project. Substitution rate is consistently greater in Africans than in non-Africans, but only in diploid regions of the genome, consistent with a role for heterozygosity. Analysing the same data partitioned into a series of non-overlapping 2 Mb windows reveals a strong, non-linear correlation between the amount of heterozygosity lost "out of Africa" and the difference in substitution rate between Africans and non-Africans. Putative recent mutations, derived variants that occur only once among the 80 human chromosomes sampled, occur preferentially at the centre of 2 Kb windows that have elevated heterozygosity compared both with the same region in a closely related population and with an immediately adjacent region in the same population. More than half of all substitutions appear attributable to variation in heterozygosity. This observation provides strong support for HI with implications for many branches of evolutionary biology.

  18. Prediction of Human Pharmacokinetic Profile After Transdermal Drug Application Using Excised Human Skin.

    Science.gov (United States)

    Yamamoto, Syunsuke; Karashima, Masatoshi; Arai, Yuta; Tohyama, Kimio; Amano, Nobuyuki

    2017-09-01

    Although several mathematical models have been reported for the estimation of human plasma concentration profiles of drug substances after dermal application, the successful cases that can predict human pharmacokinetic profiles are limited. Therefore, the aim of this study is to investigate the prediction of human plasma concentrations after dermal application using in vitro permeation parameters obtained from excised human skin. The in vitro skin permeability of 7 marketed drug products was evaluated. The plasma concentration-time profiles of the drug substances in humans after their dermal application were simulated using compartment models and the clinical pharmacokinetic parameters. The transdermal process was simulated using the in vitro skin permeation rate and lag time assuming a zero-order absorption. These simulated plasma concentration profiles were compared with the clinical data. The result revealed that the steady-state plasma concentration of diclofenac and the maximum concentrations of nicotine, bisoprolol, rivastigmine, and lidocaine after topical application were within 2-fold of the clinical data. Furthermore, the simulated concentration profiles of bisoprolol, nicotine, and rivastigmine reproduced the decrease in absorption due to drug depletion from the formulation. In conclusion, this simple compartment model using in vitro human skin permeation parameters as zero-order absorption predicted the human plasma concentrations accurately. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  19. Frequency variations of discrete cranial traits in major human populations. III. Hyperostotic variations.

    Science.gov (United States)

    Hanihara, T; Ishida, H

    2001-09-01

    Seven discrete cranial traits usually categorised as hyperostotic characters, the medial palatine canal, hypoglossal canal bridging, precondylar tubercle, condylus tertius, jugular foramen bridging, auditory exostosis, and mylohyoid bridging were investigated in 81 major human population samples from around the world. Significant asymmetric occurrences of the bilateral traits were detected in the medial palatine canal and jugular foramen bridging in several samples. Significant intertrait associations were found between some pairs of the traits, but not consistently across the large geographical samples. The auditory exostosis showed a predominant occurrence in males. With the exception of the auditory exostosis and mylohyoid bridging in a few samples, significant sex differences were slight. The frequency distributions of the traits (except for the auditory exostosis) showed some interregional clinality and intraregional discontinuity, suggesting that genetic drift could have contributed to the observed pattern of variation.

  20. Variation simulation for compliant sheet metal assemblies with applications

    Science.gov (United States)

    Long, Yufeng

    Sheet metals are widely used in discrete products, such as automobiles, aircraft, furniture and electronics appliances, due to their good manufacturability and low cost. A typical automotive body assembly consists of more than 300 parts welded together in more than 200 assembly fixture stations. Such an assembly system is usually quite complex, and takes a long time to develop. As the automotive customer demands products of increasing quality in a shorter time, engineers in automotive industry turn to computer-aided engineering (CAE) tools for help. Computers are an invaluable resource for engineers, not only to simplify and automate the design process, but also to share design specifications with manufacturing groups so that production systems can be tooled up quickly and efficiently. Therefore, it is beneficial to develop computerized simulation and evaluation tools for development of automotive body assembly systems. It is a well-known fact that assembly architectures (joints, fixtures, and assembly lines) have a profound impact on dimensional quality of compliant sheet metal assemblies. To evaluate sheet metal assembly architectures, a special dimensional analysis tool need be developed for predicting dimensional variation of the assembly. Then, the corresponding systematic tools can be established to help engineers select the assembly architectures. In this dissertation, a unified variation model is developed to predict variation in compliant sheet metal assemblies by considering fixture-induced rigid-body motion, deformation and springback. Based on the unified variation model, variation propagation models in multiple assembly stations with various configurations are established. To evaluate the dimensional capability of assembly architectures, quantitative indices are proposed based on the sensitivity matrix, which are independent of the variation level of the process. Examples are given to demonstrate their applications in selecting robust assembly

  1. Benchmark Applications of Variations of Multireference Equation of Motion Coupled-Cluster Theory

    Czech Academy of Sciences Publication Activity Database

    Huntington, L. M.; Demel, Ondřej; Nooijen, M.

    2016-01-01

    Roč. 12, č. 1 (2016), s. 114-132 ISSN 1549-9618 R&D Projects: GA ČR GJ15-00058Y Institutional support: RVO:61388955 Keywords : MR-EOM * Benchmark applications * variations Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 5.245, year: 2016

  2. Human Variome Project Quality Assessment Criteria for Variation Databases.

    Science.gov (United States)

    Vihinen, Mauno; Hancock, John M; Maglott, Donna R; Landrum, Melissa J; Schaafsma, Gerard C P; Taschner, Peter

    2016-06-01

    Numerous databases containing information about DNA, RNA, and protein variations are available. Gene-specific variant databases (locus-specific variation databases, LSDBs) are typically curated and maintained for single genes or groups of genes for a certain disease(s). These databases are widely considered as the most reliable information source for a particular gene/protein/disease, but it should also be made clear they may have widely varying contents, infrastructure, and quality. Quality is very important to evaluate because these databases may affect health decision-making, research, and clinical practice. The Human Variome Project (HVP) established a Working Group for Variant Database Quality Assessment. The basic principle was to develop a simple system that nevertheless provides a good overview of the quality of a database. The HVP quality evaluation criteria that resulted are divided into four main components: data quality, technical quality, accessibility, and timeliness. This report elaborates on the developed quality criteria and how implementation of the quality scheme can be achieved. Examples are provided for the current status of the quality items in two different databases, BTKbase, an LSDB, and ClinVar, a central archive of submissions about variants and their clinical significance. © 2016 WILEY PERIODICALS, INC.

  3. Population genetic inference from personal genome data: impact of ancestry and admixture on human genomic variation.

    Science.gov (United States)

    Kidd, Jeffrey M; Gravel, Simon; Byrnes, Jake; Moreno-Estrada, Andres; Musharoff, Shaila; Bryc, Katarzyna; Degenhardt, Jeremiah D; Brisbin, Abra; Sheth, Vrunda; Chen, Rong; McLaughlin, Stephen F; Peckham, Heather E; Omberg, Larsson; Bormann Chung, Christina A; Stanley, Sarah; Pearlstein, Kevin; Levandowsky, Elizabeth; Acevedo-Acevedo, Suehelay; Auton, Adam; Keinan, Alon; Acuña-Alonzo, Victor; Barquera-Lozano, Rodrigo; Canizales-Quinteros, Samuel; Eng, Celeste; Burchard, Esteban G; Russell, Archie; Reynolds, Andy; Clark, Andrew G; Reese, Martin G; Lincoln, Stephen E; Butte, Atul J; De La Vega, Francisco M; Bustamante, Carlos D

    2012-10-05

    Full sequencing of individual human genomes has greatly expanded our understanding of human genetic variation and population history. Here, we present a systematic analysis of 50 human genomes from 11 diverse global populations sequenced at high coverage. Our sample includes 12 individuals who have admixed ancestry and who have varying degrees of recent (within the last 500 years) African, Native American, and European ancestry. We found over 21 million single-nucleotide variants that contribute to a 1.75-fold range in nucleotide heterozygosity across diverse human genomes. This heterozygosity ranged from a high of one heterozygous site per kilobase in west African genomes to a low of 0.57 heterozygous sites per kilobase in segments inferred to have diploid Native American ancestry from the genomes of Mexican and Puerto Rican individuals. We show evidence of all three continental ancestries in the genomes of Mexican, Puerto Rican, and African American populations, and the genome-wide statistics are highly consistent across individuals from a population once ancestry proportions have been accounted for. Using a generalized linear model, we identified subtle variations across populations in the proportion of neutral versus deleterious variation and found that genome-wide statistics vary in admixed populations even once ancestry proportions have been factored in. We further infer that multiple periods of gene flow shaped the diversity of admixed populations in the Americas-70% of the European ancestry in today's African Americans dates back to European gene flow happening only 7-8 generations ago. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  4. Topographic variation in redifferentiation capacity of chondrocytes in the adult human knee joint.

    Science.gov (United States)

    Stenhamre, H; Slynarski, K; Petrén, C; Tallheden, T; Lindahl, A

    2008-11-01

    The aim of this study was to investigate the topographic variation in matrix production and cell density in the adult human knee joint. Additionally, we have examined the redifferentiation potential of chondrocytes expanded in vitro from the different locations. Full thickness cartilage-bone biopsies were harvested from seven separate anatomical locations of healthy knee joints from deceased adult human donors. Chondrocytes were isolated, expanded in vitro and redifferentiated in a pellet mass culture. Biochemical analysis of total collagen, proteoglycans and cellular content as well as histology and immunohistochemistry were performed on biopsies and pellets. In the biochemical analysis of the biopsies, we found lower proteoglycan to collagen (GAG/HP) ratio in the non-weight bearing (NWB) areas compared to the weight bearing (WB) areas. The chondrocytes harvested from different locations in femur showed a significantly better attachment and proliferation ability as well as good post-expansion chondrogenic capacity in pellet mass culture compared with the cells harvested from tibia. These results demonstrate that there are differences in extra cellular content within the adult human knee in respect to GAG/HP ratio. Additionally, the data show that clear differences between chondrocytes harvested from femur and tibia from healthy human knee joints exist and that the differences are not completely abolished during the process of de- and redifferentiation. These findings emphasize the importance of the understanding of topographic variation in articular cartilage biology when approaching new cartilage repair strategies.

  5. Quantitative variation in obesity-related traits and insulin precursors linked to the OB gene region on human chromosome 7

    Energy Technology Data Exchange (ETDEWEB)

    Duggirala, R.; Stern, M.P.; Reinhart, L.J. [Univ. of Texas Health Science Center, San Antonio, TX (United States)] [and others

    1996-09-01

    Despite the evidence that human obesity has strong genetic determinants, efforts at identifying specific genes that influence human obesity have largely been unsuccessful. Using the sibship data obtained from 32 low-income Mexican American pedigrees ascertained on a type II diabetic proband and a multipoint variance-components method, we tested for linkage between various obesity-related traits plus associated metabolic traits and 15 markers on human chromosome 7. We found evidence for linkage between markers in the OB gene region and various traits, as follows: D7S514 and extremity skinfolds (LOD = 3.1), human carboxypeptidase A1 (HCPA1) and 32,33-split proinsulin level (LOD = 4.2), and HCPA1 and proinsulin level (LOD = 3.2). A putative susceptibility locus linked to the marker D7S514 explained 56% of the total phenotypic variation in extremity skinfolds. Variation at the HCPA1 locus explained 64% of phenotypic variation in proinsulin level and {approximately}73% of phenotypic variation in split proinsulin concentration, respectively. Weaker evidence for linkage to several other obesity-related traits (e.g., waist circumference, body-mass index, fat mass by bioimpedance, etc.) was observed for a genetic location, which is {approximately}15 cM telomeric to OB. In conclusion, our study reveals that the OB region plays a significant role in determining the phenotypic variation of both insulin precursors and obesity-related traits, at least in Mexican Americans. 66 refs., 3 figs., 4 tabs.

  6. Multidimensional structure-function relationships in human β-cardiac myosin from population-scale genetic variation

    NARCIS (Netherlands)

    Homburger, J.R. (Julian R.); Green, E.M. (Eric M.); Caleshu, C. (Colleen); Sunitha, M.S. (Margaret S.); Taylor, R.E. (Rebecca E.); Ruppel, K.M. (Kathleen M.); Metpally, R.P.R. (Raghu Prasad Rao); S.D. Colan (Steven); M. Michels (Michelle); Day, S.M. (Sharlene M.); I. Olivotto (Iacopo); Bustamante, C.D. (Carlos D.); Dewey, F.E. (Frederick E.); Ho, C.Y. (Carolyn Y.); Spudich, J.A. (James A.); Ashley, E.A. (Euan A.)

    2016-01-01

    textabstractMyosin motors are the fundamental force-generating elements of muscle contraction. Variation in the human β-cardiac myosin heavy chain gene (MYH7) can lead to hypertrophic cardiomyopathy (HCM), a heritable disease characterized by cardiac hypertrophy, heart failure, and sudden cardiac

  7. Introduction and application of the multiscale coefficient of variation analysis.

    Science.gov (United States)

    Abney, Drew H; Kello, Christopher T; Balasubramaniam, Ramesh

    2017-10-01

    Quantifying how patterns of behavior relate across multiple levels of measurement typically requires long time series for reliable parameter estimation. We describe a novel analysis that estimates patterns of variability across multiple scales of analysis suitable for time series of short duration. The multiscale coefficient of variation (MSCV) measures the distance between local coefficient of variation estimates within particular time windows and the overall coefficient of variation across all time samples. We first describe the MSCV analysis and provide an example analytical protocol with corresponding MATLAB implementation and code. Next, we present a simulation study testing the new analysis using time series generated by ARFIMA models that span white noise, short-term and long-term correlations. The MSCV analysis was observed to be sensitive to specific parameters of ARFIMA models varying in the type of temporal structure and time series length. We then apply the MSCV analysis to short time series of speech phrases and musical themes to show commonalities in multiscale structure. The simulation and application studies provide evidence that the MSCV analysis can discriminate between time series varying in multiscale structure and length.

  8. Human fertility variation, size-related obstetrical performance and the evolution of sexual stature dimorphism

    OpenAIRE

    Guégan, Jean-François; Teriokhin, A.T.; Thomas, F.

    2000-01-01

    In several animal species, change in sexual size dimorphism is a correlated response to selection on fecundity. In humans, different hypotheses have been proposed to explain the variation of sexual dimorphism in stature, but no consensus has yet emerged. In this paper, we evaluate from a theoretical and an empirical point of view the hypothesis that the extent of sexual dimorphism in human populations results from the interaction between fertility and size-related obstetric complications. We ...

  9. Genomic Features That Predict Allelic Imbalance in Humans Suggest Patterns of Constraint on Gene Expression Variation

    Science.gov (United States)

    Fédrigo, Olivier; Haygood, Ralph; Mukherjee, Sayan; Wray, Gregory A.

    2009-01-01

    Variation in gene expression is an important contributor to phenotypic diversity within and between species. Although this variation often has a genetic component, identification of the genetic variants driving this relationship remains challenging. In particular, measurements of gene expression usually do not reveal whether the genetic basis for any observed variation lies in cis or in trans to the gene, a distinction that has direct relevance to the physical location of the underlying genetic variant, and which may also impact its evolutionary trajectory. Allelic imbalance measurements identify cis-acting genetic effects by assaying the relative contribution of the two alleles of a cis-regulatory region to gene expression within individuals. Identification of patterns that predict commonly imbalanced genes could therefore serve as a useful tool and also shed light on the evolution of cis-regulatory variation itself. Here, we show that sequence motifs, polymorphism levels, and divergence levels around a gene can be used to predict commonly imbalanced genes in a human data set. Reduction of this feature set to four factors revealed that only one factor significantly differentiated between commonly imbalanced and nonimbalanced genes. We demonstrate that these results are consistent between the original data set and a second published data set in humans obtained using different technical and statistical methods. Finally, we show that variation in the single allelic imbalance-associated factor is partially explained by the density of genes in the region of a target gene (allelic imbalance is less probable for genes in gene-dense regions), and, to a lesser extent, the evenness of expression of the gene across tissues and the magnitude of negative selection on putative regulatory regions of the gene. These results suggest that the genomic distribution of functional cis-regulatory variants in the human genome is nonrandom, perhaps due to local differences in evolutionary

  10. Intracultural variation of knowledge about wild plant uses in the Biosphere Reserve Grosses Walsertal (Austria

    Directory of Open Access Journals (Sweden)

    Schunko Christoph

    2012-07-01

    Full Text Available Abstract Background Leading scholars in ethnobiology and ethnomedicine continuously stress the need for moving beyond the bare description of local knowledge and to additionally analyse and theorise about the characteristics and dynamics of human interactions with plants and related local knowledge. Analyses of the variation of local knowledge are thereby perceived as minimal standard. In this study we investigate the distribution and variation of wild plant knowledge in five domains: food, drinks, human medicine, veterinary medicine and customs. We assess relations between the wild plant knowledge of informants and their socio-demographic as well as geographic background. Method Research was conducted in the Biosphere Reserve Grosses Walsertal, Austria. Structured questionnaires were used to inquire wild plant knowledge from 433 informants with varying socio-demographic and geographic background. Children assisted in the data collection. Data was analysed using descriptive statistics and generalized linear models. Results and discussion A majority of respondents is familiar with wild plant uses, however to varying degrees. Knowledge variations depend on the socio-demographic and geographic background of the informants as well as on the domains of knowledge under investigation: women, older informants and homegardeners report more human medicinal applications and applications in drinks than men, younger informants and non-homegardeners; farmers know a greater variety of veterinary medicinal applications than non-farmers; the place of residence relates significantly to food and veterinary uses. Customs are difficult to investigate in standardized matrices. The household-related distribution of work and the general socio-cultural context are especially helpful in order to explain intracultural variation of knowledge in the Grosses Walsertal. Conclusions Research on the intracultural variation of local knowledge exposes cultural characteristics and

  11. Metabolism of styrene in the human liver in vitro: interindividual variation and enantioselectivity

    NARCIS (Netherlands)

    Wenker, M. A.; Kezić, S.; Monster, A. C.; de Wolff, F. A.

    2001-01-01

    1. The interindividual variation and enantioselectivity of the in vitro styrene oxidation by cytochrome P450 have been investigated in 20 human microsomal liver samples. Liver samples were genotyped for the CYP2E1*6 and CYP2E1*5B alleles. 2. Kinetic analysis indicated the presence of at least two

  12. On-chip active gate bias circuit for MMIC amplifier applications with 100% threshold voltage variation compensation

    NARCIS (Netherlands)

    Hek, A.P. de; Busking, E.B.

    2006-01-01

    In this paper the design and performance of an on-chip active gate bias circuit for application in MMIC amplifiers, which gives 100% compensation for threshold variation and at the same time is insensitive to supply voltage variations, is discussed. Design equations have been given. In addition, the

  13. Variational symplectic algorithm for guiding center dynamics and its application in tokamak geometry

    International Nuclear Information System (INIS)

    Qin Hong; Guan Xiaoyin; Tang, William M.

    2009-01-01

    A variational symplectic integrator for the guiding center motion of charged particles in general magnetic fields is developed to enable accurate long-time simulation studies of magnetized plasmas. Instead of discretizing the differential equations of the guiding center motion, the action of the guiding center motion is discretized and minimized to obtain the iteration rules for advancing the dynamics. The variational symplectic integrator conserves exactly a discrete Lagrangian symplectic structure and globally bounds the numerical error in energy by a small number for all simulation time steps. Compared with standard integrators, such as the fourth order Runge-Kutta method, the variational symplectic integrator has superior numerical properties over long integration time. For example, in a two-dimensional tokamak geometry, the variational symplectic integrator is able to guarantee the accuracy for both the trapped and transit particle orbits for arbitrarily long simulation time. This is important for modern large-scale simulation studies of fusion plasmas where it is critical to use algorithms with long-term accuracy and fidelity. The variational symplectic integrator is expected to have a wide range of applications.

  14. Applications of low lift to drag ratio aerobrakes using angle of attack variation for control

    Science.gov (United States)

    Mulqueen, J. A.

    1991-01-01

    Several applications of low lift to drag ratio aerobrakes are investigated which use angle of attack variation for control. The applications are: return from geosynchronous or lunar orbit to low Earth orbit; and planetary aerocapture at Earth and Mars. A number of aerobrake design considerations are reviewed. It was found that the flow impingement behind the aerobrake and the aerodynamic heating loads are the primary factors that control the sizing of an aerobrake. The heating loads and other loads, such as maximum acceleration, are determined by the vehicle ballistic coefficient, the atmosphere entry conditions, and the trajectory design. Several formulations for defining an optimum trajectory are reviewed, and the various performance indices that can be used are evaluated. The 'nearly grazing' optimal trajectory was found to provide the best compromise between the often conflicting goals of minimizing the vehicle propulsive requirements and minimizing vehicle loads. The relationship between vehicle and trajectory design is investigated further using the results of numerical simulations of trajectories for each aerobrake application. The data show the sensitivity of the trajectories to several vehicle parameters and atmospheric density variations. The results of the trajectory analysis show that low lift to drag ratio aerobrakes, which use angle of attack variation for control, can potentially be used for a wide range of aerobrake applications.

  15. Regional variations of cell surface carbohydrates in human oral stratified epithelium

    DEFF Research Database (Denmark)

    Vedtofte, P; Dabelsteen, Erik; Hakomori, S

    1984-01-01

    The distribution of blood group carbohydrate chains with antigen A, B, H type 2 chain (A and B precursor), and N-acetyllactosamine (H type 2 precursor) specificity was studied in human oral epithelium from different anatomical regions. These represented various epithelial differentiation patterns...... epithelium from nine blood group A, two blood group B, and nine blood group O individuals. The blood group carbohydrate chains were examined in tissue sections by immunofluorescence microscopy. The A and B blood group antigens were detected by human blood group sera, and antigen H type 2 chains and N...... antigen H type 2 chains in metaplastically keratinized buccal epithelium was found to differ significantly from that seen in normal non-keratinized buccal epithelium. The regional variations demonstrated in cell surface carbohydrates are suggested to reflect differences in tissue differentiation....

  16. Stable isotopic variation in tropical forest plants for applications in primatology.

    Science.gov (United States)

    Blumenthal, Scott A; Rothman, Jessica M; Chritz, Kendra L; Cerling, Thure E

    2016-10-01

    Stable isotope analysis is a promising tool for investigating primate ecology although nuanced ecological applications remain challenging, in part due to the complex nature of isotopic variability in plant-animal systems. The aim of this study is to investigate sources of carbon and nitrogen isotopic variation at the base of primate food webs that reflect aspects of primate ecology. The majority of primates inhabit tropical forest ecosystems, which are dominated by C3 vegetation. We used stable isotope ratios in plants from Kibale National Park, Uganda, a well-studied closed-canopy tropical forest, to investigate sources of isotopic variation among C3 plants related to canopy stratification, leaf age, and plant part. Unpredictably, our results demonstrate that vertical stratification within the canopy does not explain carbon or nitrogen isotopic variation in leaves. Leaf age can be a significant source of isotopic variation, although the direction and magnitude of this difference is not consistent across tree species. Some plant parts are clearly differentiated in carbon and nitrogen isotopic composition, particularly leaves compared to non-photosynthetic parts such as reproductive parts and woody stem parts. Overall, variation in the isotopic composition of floral communities, plant species, and plant parts demonstrates that stable isotope studies must include analysis of local plant species and parts consumed by the primates under study from within the study area. Am. J. Primatol. 78:1041-1054, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  17. Application of postured human model for SAR measurements

    Science.gov (United States)

    Vuchkovikj, M.; Munteanu, I.; Weiland, T.

    2013-07-01

    In the last two decades, the increasing number of electronic devices used in day-to-day life led to a growing interest in the study of the electromagnetic field interaction with biological tissues. The design of medical devices and wireless communication devices such as mobile phones benefits a lot from the bio-electromagnetic simulations in which digital human models are used. The digital human models currently available have an upright position which limits the research activities in realistic scenarios, where postured human bodies must be considered. For this reason, a software application called "BodyFlex for CST STUDIO SUITE" was developed. In its current version, this application can deform the voxel-based human model named HUGO (Dipp GmbH, 2010) to allow the generation of common postures that people use in normal life, ensuring the continuity of tissues and conserving the mass to an acceptable level. This paper describes the enhancement of the "BodyFlex" application, which is related to the movements of the forearm and the wrist of a digital human model. One of the electromagnetic applications in which the forearm and the wrist movement of a voxel based human model has a significant meaning is the measurement of the specific absorption rate (SAR) when a model is exposed to a radio frequency electromagnetic field produced by a mobile phone. Current SAR measurements of the exposure from mobile phones are performed with the SAM (Specific Anthropomorphic Mannequin) phantom which is filled with a dispersive but homogeneous material. We are interested what happens with the SAR values if a realistic inhomogeneous human model is used. To this aim, two human models, a homogeneous and an inhomogeneous one, in two simulation scenarios are used, in order to examine and observe the differences in the results for the SAR values.

  18. Applicability of Pulse Pressure Variation during Unstable Hemodynamic Events in the Intensive Care Unit: A Five-Day Prospective Multicenter Study

    Directory of Open Access Journals (Sweden)

    Bertrand Delannoy

    2016-01-01

    Full Text Available Pulse pressure variation can predict fluid responsiveness in strict applicability conditions. The purpose of this study was to describe the clinical applicability of pulse pressure variation during episodes of patient hemodynamic instability in the intensive care unit. We conducted a five-day, seven-center prospective study that included patients presenting with an unstable hemodynamic event. The six predefined inclusion criteria for pulse pressure variation applicability were as follows: mechanical ventilation, tidal volume >7 mL/kg, sinus rhythm, no spontaneous breath, heart rate/respiratory rate ratio >3.6, absence of right ventricular dysfunction, or severe valvulopathy. Seventy-three patients presented at least one unstable hemodynamic event, with a total of 163 unstable hemodynamic events. The six predefined criteria for the applicability of pulse pressure variation were completely present in only 7% of these. This data indicates that PPV should only be used alongside a strong understanding of the relevant physiology and applicability criteria. Although these exclusion criteria appear to be profound, they likely represent an absolute contraindication of use for only a minority of critical care patients.

  19. Comparison of organ doses in human phantoms: variations due to body size and posture

    International Nuclear Information System (INIS)

    Feng, Xu; Xiang-Hong, Jia; Xue-Jun, Yu; Zhan-Chun, Pan; Qian, Liu; Chun-Xin, Yang

    2017-01-01

    Organ dose calculations performed using human phantoms can provide estimates of astronauts' health risks due to cosmic radiation. However, the characteristics of such phantoms strongly affect the estimation precision. To investigate organ dose variations with body size and posture in human phantoms, a non-uniform rational B-spline boundary surfaces model was constructed based on cryo-section images. This model was used to establish four phantoms with different body size and posture parameters, whose organs parameters were changed simultaneously and which were voxelised with 4x4x4 mm"3 resolution. Then, using Monte Carlo transport code, the organ doses caused by ≤500 MeV isotropic incident protons were calculated. The dose variations due to body size differences within a certain range were negligible, and the doses received in crouching and standing-up postures were similar. Therefore, a standard Chinese phantom could be established, and posture changes cannot effectively protect astronauts during solar particle events. (authors)

  20. Precision wildlife medicine: applications of the human-centred precision medicine revolution to species conservation.

    Science.gov (United States)

    Whilde, Jenny; Martindale, Mark Q; Duffy, David J

    2017-05-01

    The current species extinction crisis is being exacerbated by an increased rate of emergence of epizootic disease. Human-induced factors including habitat degradation, loss of biodiversity and wildlife population reductions resulting in reduced genetic variation are accelerating disease emergence. Novel, efficient and effective approaches are required to combat these epizootic events. Here, we present the case for the application of human precision medicine approaches to wildlife medicine in order to enhance species conservation efforts. We consider how the precision medicine revolution, coupled with the advances made in genomics, may provide a powerful and feasible approach to identifying and treating wildlife diseases in a targeted, effective and streamlined manner. A number of case studies of threatened species are presented which demonstrate the applicability of precision medicine to wildlife conservation, including sea turtles, amphibians and Tasmanian devils. These examples show how species conservation could be improved by using precision medicine techniques to determine novel treatments and management strategies for the specific medical conditions hampering efforts to restore population levels. Additionally, a precision medicine approach to wildlife health has in turn the potential to provide deeper insights into human health and the possibility of stemming and alleviating the impacts of zoonotic diseases. The integration of the currently emerging Precision Medicine Initiative with the concepts of EcoHealth (aiming for sustainable health of people, animals and ecosystems through transdisciplinary action research) and One Health (recognizing the intimate connection of humans, animal and ecosystem health and addressing a wide range of risks at the animal-human-ecosystem interface through a coordinated, collaborative, interdisciplinary approach) has great potential to deliver a deeper and broader interdisciplinary-based understanding of both wildlife and human

  1. Camera systems in human motion analysis for biomedical applications

    Science.gov (United States)

    Chin, Lim Chee; Basah, Shafriza Nisha; Yaacob, Sazali; Juan, Yeap Ewe; Kadir, Aida Khairunnisaa Ab.

    2015-05-01

    Human Motion Analysis (HMA) system has been one of the major interests among researchers in the field of computer vision, artificial intelligence and biomedical engineering and sciences. This is due to its wide and promising biomedical applications, namely, bio-instrumentation for human computer interfacing and surveillance system for monitoring human behaviour as well as analysis of biomedical signal and image processing for diagnosis and rehabilitation applications. This paper provides an extensive review of the camera system of HMA, its taxonomy, including camera types, camera calibration and camera configuration. The review focused on evaluating the camera system consideration of the HMA system specifically for biomedical applications. This review is important as it provides guidelines and recommendation for researchers and practitioners in selecting a camera system of the HMA system for biomedical applications.

  2. Variational Transition State Theory

    Energy Technology Data Exchange (ETDEWEB)

    Truhlar, Donald G. [Univ. of Minnesota, Minneapolis, MN (United States)

    2016-09-29

    This is the final report on a project involving the development and applications of variational transition state theory. This project involved the development of variational transition state theory for gas-phase reactions, including optimized multidimensional tunneling contributions and the application of this theory to gas-phase reactions with a special emphasis on developing reaction rate theory in directions that are important for applications to combustion. The development of variational transition state theory with optimized multidimensional tunneling as a useful computational tool for combustion kinetics involved eight objectives.

  3. Preanalytical and analytical variation of surface-enhanced laser desorption-ionization time-of-flight mass spectrometry of human serum

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Bøgebo, Rikke; Olsen, Jesper

    2006-01-01

    BACKGROUND: Surface-enhanced laser desorption-ionization time-of-flight (SELDI-TOF) mass spectrometry of human serum is a potential diagnostic tool in human diseases. In the present study, the preanalytical and analytical variation of SELDI-TOF mass spectrometry of serum was assessed in healthy...... was 18% (6%-34%, n=4) for 16 peaks, and inter-individual CV was 38% (16%-56%, n=16) for 20 peaks. CONCLUSIONS: The pre-analytical and analytical conditions of SELDI-TOF mass spectrometry of serum have a significant impact on the protein peaks, with the number of peaks low and the assay variation high...

  4. Identification of species and genetic variation in Taenia isolates from human and swine of North India.

    Science.gov (United States)

    Singh, Satyendra K; Prasad, Kashi N; Singh, Aloukick K; Gupta, Kamlesh K; Chauhan, Ranjeet S; Singh, Amrita; Singh, Avinash; Rai, Ravi P; Pati, Binod K

    2016-10-01

    Taenia solium is the major cause of taeniasis and cysticercosis/neurocysticercosis (NCC) in the developing countries including India, but the existence of other Taenia species and genetic variation have not been studied in India. So, we studied the existence of different Taenia species, and sequence variation in Taenia isolates from human (proglottids and cysticerci) and swine (cysticerci) in North India. Amplification of cytochrome c oxidase subunit 1 gene (cox1) was done by polymerase chain reaction (PCR) followed by sequencing and phylogenetic analysis. We identified two species of Taenia i.e. T. solium and Taenia asiatica in our isolates. T. solium isolates showed similarity with Asian genotype and nucleotide variations from 0.25 to 1.01 %, whereas T. asiatica displayed nucleotide variations ranged from 0.25 to 0.5 %. These findings displayed the minimal genetic variations in North Indian isolates of T. solium and T. asiatica.

  5. Laplace transform overcoming principle drawbacks in application of the variational iteration method to fractional heat equations

    Directory of Open Access Journals (Sweden)

    Wu Guo-Cheng

    2012-01-01

    Full Text Available This note presents a Laplace transform approach in the determination of the Lagrange multiplier when the variational iteration method is applied to time fractional heat diffusion equation. The presented approach is more straightforward and allows some simplification in application of the variational iteration method to fractional differential equations, thus improving the convergence of the successive iterations.

  6. The rhesus macaque is three times as diverse but more closely equivalent in damaging coding variation as compared to the human

    Directory of Open Access Journals (Sweden)

    Yuan Qiaoping

    2012-06-01

    Full Text Available Abstract Background As a model organism in biomedicine, the rhesus macaque (Macaca mulatta is the most widely used nonhuman primate. Although a draft genome sequence was completed in 2007, there has been no systematic genome-wide comparison of genetic variation of this species to humans. Comparative analysis of functional and nonfunctional diversity in this highly abundant and adaptable non-human primate could inform its use as a model for human biology, and could reveal how variation in population history and size alters patterns and levels of sequence variation in primates. Results We sequenced the mRNA transcriptome and H3K4me3-marked DNA regions in hippocampus from 14 humans and 14 rhesus macaques. Using equivalent methodology and sampling spaces, we identified 462,802 macaque SNPs, most of which were novel and disproportionately located in the functionally important genomic regions we had targeted in the sequencing. At least one SNP was identified in each of 16,797 annotated macaque genes. Accuracy of macaque SNP identification was conservatively estimated to be >90%. Comparative analyses using SNPs equivalently identified in the two species revealed that rhesus macaque has approximately three times higher SNP density and average nucleotide diversity as compared to the human. Based on this level of diversity, the effective population size of the rhesus macaque is approximately 80,000 which contrasts with an effective population size of less than 10,000 for humans. Across five categories of genomic regions, intergenic regions had the highest SNP density and average nucleotide diversity and CDS (coding sequences the lowest, in both humans and macaques. Although there are more coding SNPs (cSNPs per individual in macaques than in humans, the ratio of dN/dS is significantly lower in the macaque. Furthermore, the number of damaging nonsynonymous cSNPs (have damaging effects on protein functions from PolyPhen-2 prediction in the macaque is more

  7. Copy number variation of human AMY1 is a minor contributor to variation in salivary amylase expression and activity.

    Science.gov (United States)

    Carpenter, Danielle; Mitchell, Laura M; Armour, John A L

    2017-02-20

    Salivary amylase in humans is encoded by the copy variable gene AMY1 in the amylase gene cluster on chromosome 1. Although the role of salivary amylase is well established, the consequences of the copy number variation (CNV) at AMY1 on salivary amylase protein production are less well understood. The amylase gene cluster is highly structured with a fundamental difference between odd and even AMY1 copy number haplotypes. In this study, we aimed to explore, in samples from 119 unrelated individuals, not only the effects of AMY1 CNV on salivary amylase protein expression and amylase enzyme activity but also whether there is any evidence for underlying difference between the common haplotypes containing odd numbers of AMY1 and even copy number haplotypes. AMY1 copy number was significantly correlated with the variation observed in salivary amylase production (11.7% of variance, P structure may affect expression, but this was not significant in our data.

  8. Quantum variational calculus

    CERN Document Server

    Malinowska, Agnieszka B

    2014-01-01

    This Brief puts together two subjects, quantum and variational calculi by considering variational problems involving Hahn quantum operators. The main advantage of its results is that they are able to deal with nondifferentiable (even discontinuous) functions, which are important in applications. Possible applications in economics are discussed. Economists model time as continuous or discrete. Although individual economic decisions are generally made at discrete time intervals, they may well be less than perfectly synchronized in ways discrete models postulate. On the other hand, the usual assumption that economic activity takes place continuously, is nothing else than a convenient abstraction that in many applications is far from reality. The Hahn quantum calculus helps to bridge the gap between the two families of models: continuous and discrete. Quantum Variational Calculus is self-contained and unified in presentation. It provides an opportunity for an introduction to the quantum calculus of variations fo...

  9. The variation field of the radiosensitivity in the human population: hypersensitivity and hypo sensitivity

    International Nuclear Information System (INIS)

    Bouffler, S.

    2009-01-01

    It is generally admitted in the radiotherapy practice that 5% of patients will present serious reactions of normal tissues. Studies made on human population confirm it exists variations of cell radiosensitivity and genetic factors contribute in a significant manner to the observed variations. The researches of markers able to predict the reactions of normal tissues to the therapy focussed on the identification of sensitive sub-group. It is however obvious that exists also a part of the population relatively hypo sensitive. It would be interesting to make studies on the genome to find genes associated to serious reactions of normal tissues to radiotherapy. (N.C.)

  10. ALDH1A2 (RALDH2 genetic variation in human congenital heart disease

    Directory of Open Access Journals (Sweden)

    Mesquita Sonia MF

    2009-11-01

    ALDH1A2 genetic variation is present in TOF patients, suggesting a possible causal role for this gene in rare cases of human CHD, but does not support the hypothesis that variation at the ALDH1A2 locus is a significant modifier of the risk for CHD in humans.

  11. Blood flow variation in human muscle during electrically stimulated exercise bouts.

    Science.gov (United States)

    Vanderthommen, Marc; Depresseux, Jean-Claude; Dauchat, Luc; Degueldre, Christian; Croisier, Jean-Louis; Crielaard, Jean-Michel

    2002-07-01

    To evaluate, with a high spatial resolution, the blood flow variations in human skeletal muscle during neuromuscular electric stimulation (NMES) and hence to gain better understanding of the mechanisms of muscle spatial recruitment during NMES. One thigh was submitted to 3 stimulation bouts of different durations (S1=4min, S2=8min, S3=12min) with a workload corresponding to 10% of quadriceps maximal isometric voluntary torque. A cyclotron research center at a Belgian university. Ten healthy male volunteers. Not applicable. Participants were studied with positron emission tomography and H(2)(15)O. Tissue blood flow was evaluated during the last 4 minutes of each stimulation bout in multiple regions of interest (ROIs) selected in the transverse section of the stimulated thigh. Mean tissue blood flow was significantly lower during S1 (5.9+/-1.3mL. min(-1). 100g(-1)) than during S2 (10.6+/-3.4mL. min(-1). 100g(-1)) and S3 (11.6+/-3.7mL. min(-1). 100g(-1)) (Precruited ROIs were preferentially located far from the electrode. During NMES, new muscular regions situated far from the stimulation site are recruited. These recruitment mechanisms are particular and contrast with the recruitment of motor units seen during voluntary contraction. Copyright 2002 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation

  12. New Regions of the Human Genome Linked to Skin Color Variation in Some African Populations

    Science.gov (United States)

    In the first study of its kind, an international team of genomics researchers has identified new regions of the human genome that are associated with skin color variation in some African populations, opening new avenues for research on skin diseases and cancer in all populations.

  13. Lack of influence of GTP cyclohydrolase gene (GCH1 variations on pain sensitivity in humans

    Directory of Open Access Journals (Sweden)

    Dionne Raymond A

    2007-03-01

    Full Text Available Abstract Objectives To assess the effect of variations in GTP cyclohydrolase gene (GCH1 on pain sensitivity in humans. Methods Thermal and cold pain sensitivity were evaluated in a cohort of 735 healthy volunteers. Among this cohort, the clinical pain responses of 221 subjects after the surgical removal of impacted third molars were evaluated. Genotyping was done for 38 single nucleotide polymorphisms (SNPs whose heterozygosity > 0.2 in GCH1. Influence of the genetic variations including SNPs and haplotypes on pain sensitivity were analyzed. Results Minor allele frequencies and linkage disequilibrium show significant differences in European Americans, African Americans, Hispanic Americans and Asian Americans. Association analyses in European Americans do not replicate the previously reported important influence of GCH1 variations on pain sensitivity. Conclusion Considering population stratification, previously reported associations between GCH1 genetic variations and pain sensitivity appear weak or negligible in this well characterized model of pain.

  14. Non-synonymous variations in cancer and their effects on the human proteome: workflow for NGS data biocuration and proteome-wide analysis of TCGA data.

    Science.gov (United States)

    Cole, Charles; Krampis, Konstantinos; Karagiannis, Konstantinos; Almeida, Jonas S; Faison, William J; Motwani, Mona; Wan, Quan; Golikov, Anton; Pan, Yang; Simonyan, Vahan; Mazumder, Raja

    2014-01-27

    Next-generation sequencing (NGS) technologies have resulted in petabytes of scattered data, decentralized in archives, databases and sometimes in isolated hard-disks which are inaccessible for browsing and analysis. It is expected that curated secondary databases will help organize some of this Big Data thereby allowing users better navigate, search and compute on it. To address the above challenge, we have implemented a NGS biocuration workflow and are analyzing short read sequences and associated metadata from cancer patients to better understand the human variome. Curation of variation and other related information from control (normal tissue) and case (tumor) samples will provide comprehensive background information that can be used in genomic medicine research and application studies. Our approach includes a CloudBioLinux Virtual Machine which is used upstream of an integrated High-performance Integrated Virtual Environment (HIVE) that encapsulates Curated Short Read archive (CSR) and a proteome-wide variation effect analysis tool (SNVDis). As a proof-of-concept, we have curated and analyzed control and case breast cancer datasets from the NCI cancer genomics program - The Cancer Genome Atlas (TCGA). Our efforts include reviewing and recording in CSR available clinical information on patients, mapping of the reads to the reference followed by identification of non-synonymous Single Nucleotide Variations (nsSNVs) and integrating the data with tools that allow analysis of effect nsSNVs on the human proteome. Furthermore, we have also developed a novel phylogenetic analysis algorithm that uses SNV positions and can be used to classify the patient population. The workflow described here lays the foundation for analysis of short read sequence data to identify rare and novel SNVs that are not present in dbSNP and therefore provides a more comprehensive understanding of the human variome. Variation results for single genes as well as the entire study are available

  15. Natural selection affects multiple aspects of genetic variation at putatively neutral sites across the human genome.

    Science.gov (United States)

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui; Kim, Su Yeon; Korneliussen, Thorfinn; Vinckenbosch, Nicolas; Tian, Geng; Huerta-Sanchez, Emilia; Feder, Alison F; Grarup, Niels; Jørgensen, Torben; Jiang, Tao; Witte, Daniel R; Sandbæk, Annelli; Hellmann, Ines; Lauritzen, Torsten; Hansen, Torben; Pedersen, Oluf; Wang, Jun; Nielsen, Rasmus

    2011-10-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries of genetic variation, like allele frequencies, are also correlated with recombination rate and whether these correlations can be explained solely by negative selection against deleterious mutations or whether positive selection acting on favorable alleles is also required. Here we attempt to address these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations. However, models with strong positive selection on nonsynonymous mutations and little negative selection predict a stronger negative correlation between neutral diversity and nonsynonymous divergence than observed in the actual data, supporting the importance of negative, rather than positive, selection throughout the genome. Further, we show that the widespread presence of weakly deleterious alleles, rather than a small number of strongly positively selected mutations, is responsible for the correlation between neutral genetic diversity and recombination rate. This work suggests that natural selection has affected multiple aspects of linked neutral variation throughout the human genome and that positive selection is not required to explain these observations.

  16. Genetic determination of human facial morphology: links between cleft-lips and normal variation.

    Science.gov (United States)

    Boehringer, Stefan; van der Lijn, Fedde; Liu, Fan; Günther, Manuel; Sinigerova, Stella; Nowak, Stefanie; Ludwig, Kerstin U; Herberz, Ruth; Klein, Stefan; Hofman, Albert; Uitterlinden, Andre G; Niessen, Wiro J; Breteler, Monique M B; van der Lugt, Aad; Würtz, Rolf P; Nöthen, Markus M; Horsthemke, Bernhard; Wieczorek, Dagmar; Mangold, Elisabeth; Kayser, Manfred

    2011-11-01

    Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with non-syndromic cleft lip with or without cleft palate (NSCL/P), and other previous studies showed distinctly differing facial distance measurements when comparing unaffected relatives of NSCL/P patients with normal controls. Here, we test the hypothesis that genetic loci involved in NSCL/P also influence normal variation in facial morphology. We tested 11 SNPs from 10 genomic regions previously showing replicated evidence of association with NSCL/P for association with normal variation of nose width and bizygomatic distance in two cohorts from Germany (N=529) and the Netherlands (N=2497). The two most significant associations found were between nose width and SNP rs1258763 near the GREM1 gene in the German cohort (P=6 × 10(-4)), and between bizygomatic distance and SNP rs987525 at 8q24.21 near the CCDC26 gene (P=0.017) in the Dutch sample. A genetic prediction model explained 2% of phenotype variation in nose width in the German and 0.5% of bizygomatic distance variation in the Dutch cohort. Although preliminary, our data provide a first link between genetic loci involved in a pathological facial trait such as NSCL/P and variation of normal facial morphology. Moreover, we present a first approach for understanding the genetic basis of human facial appearance, a highly intriguing trait with implications on clinical practice, clinical genetics, forensic intelligence, social interactions and personal identity.

  17. Diffusion tensor imaging of the human calf : Variation of inter- and intramuscle-specific diffusion parameters

    NARCIS (Netherlands)

    Schlaffke, Lara; Rehmann, Robert; Froeling, Martijn; Kley, Rudolf; Tegenthoff, Martin; Vorgerd, Matthias; Schmidt-Wilcke, Tobias

    2017-01-01

    Purpose: To investigate to what extent inter- and intramuscular variations of diffusion parameters of human calf muscles can be explained by age, gender, muscle location, and body mass index (BMI) in a specific age group (20-35 years). Materials and Methods: Whole calf muscles of 18 healthy

  18. Human Genome Sequencing in Health and Disease

    Science.gov (United States)

    Gonzaga-Jauregui, Claudia; Lupski, James R.; Gibbs, Richard A.

    2013-01-01

    Following the “finished,” euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better understanding of variation in the human genome. We have consequently begun to appreciate the vastness of individual genetic variation from single nucleotide to structural variants. Translation of genome-scale variation into medically useful information is, however, in its infancy. This review summarizes the initial steps undertaken in clinical implementation of personal genome information, and describes the application of whole-genome and exome sequencing to identify the cause of genetic diseases and to suggest adjuvant therapies. Better analysis tools and a deeper understanding of the biology of our genome are necessary in order to decipher, interpret, and optimize clinical utility of what the variation in the human genome can teach us. Personal genome sequencing may eventually become an instrument of common medical practice, providing information that assists in the formulation of a differential diagnosis. We outline herein some of the remaining challenges. PMID:22248320

  19. Integrative Annotation of Variants from 1092 Humans: Application to Cancer Genomics

    DEFF Research Database (Denmark)

    Khurana, Ekta; Fu, Yao; Colonna, Vincenza

    2013-01-01

    Identifying Important Identifiers Each of us has millions of sequence variations in our genomes. Signatures of purifying or negative selection should help identify which of those variations is functionally important. Khurana et al. (1235587) used sequence polymorphisms from 1092 humans across 14...... sites tended to occur in network hub promoters. Many recurrent somatic cancer variants occurred in noncoding regulatory regions and thus might indicate mutations that drive cancer....

  20. Influence resistance on human health

    Science.gov (United States)

    Abdul Harits, M.; Bahtiar, Yusuf; Achdan, M. Syahdani; Sunarno, .

    2010-05-01

    Health is an important part of human life. Every person in this world want healthy body, in other words free of any disease. When seeing the pattern of human life today is high activity, always eat instant foods and lack of exercise makes a very bad human health from year to year. Therefore, there is need for the health revolution that can keep human health in order to remain in the condition is always healthy. Eat healthy foods four plus five perfect diligent exercise is the real solution to maintain health. In addition also advisable to always check each month to the doctor so that our health can be controlled. Most people underestimate it, especially the routine checks once a month to the doctor, therefore I created a simple research that aims to get people to mengonytrol health at any time without having to check into the doctor. By utilizing the resistance in the human body's health so we can be controlled. By using a simple tool to measure human resistance by using the concept of the bridge. Bridge circuit used to convert impedance variations into voltage variations. One advantage of this circuit is the voltage produced can vary around 0. This means strengthening can be used to raise the voltage level so as sensitivity to variations in impedance also increases. Another application is the impedance measurement accuracy. The bridge is the simplest and most widely used is the Wheatstone bridge circuit. This circuit is used for signal conditioning applications where a sensor can change the resistance value when the process variable is changed.

  1. Calculus of variations

    CERN Document Server

    Elsgolc, L E; Stark, M

    1961-01-01

    Calculus of Variations aims to provide an understanding of the basic notions and standard methods of the calculus of variations, including the direct methods of solution of the variational problems. The wide variety of applications of variational methods to different fields of mechanics and technology has made it essential for engineers to learn the fundamentals of the calculus of variations. The book begins with a discussion of the method of variation in problems with fixed boundaries. Subsequent chapters cover variational problems with movable boundaries and some other problems; sufficiency

  2. Nonlinear Variation of Parameters Formula for Impulsive Differential Equations with Initial Time Difference and Application

    Directory of Open Access Journals (Sweden)

    Peiguang Wang

    2014-01-01

    Full Text Available This paper establishes variation of parameters formula for impulsive differential equations with initial time difference. As an application, one of the results is used to investigate stability properties of solutions.

  3. Pharmacomicrobiomics: The Impact of Human Microbiome Variations on Systems Pharmacology and Personalized Therapeutics

    OpenAIRE

    ElRakaiby, Marwa; Dutilh, Bas E.; Rizkallah, Mariam R.; Boleij, Annemarie; Cole, Jason N.; Aziz, Ramy K.

    2014-01-01

    The Human Microbiome Project (HMP) is a global initiative undertaken to identify and characterize the collection of human-associated microorganisms at multiple anatomic sites (skin, mouth, nose, colon, vagina), and to determine how intra-individual and inter-individual alterations in the microbiome influence human health, immunity, and different disease states. In this review article, we summarize the key findings and applications of the HMP that may impact pharmacology and personalized thera...

  4. Estimation of time-dependent Hurst exponents with variational smoothing and application to forecasting foreign exchange rates

    Science.gov (United States)

    Garcin, Matthieu

    2017-10-01

    Hurst exponents depict the long memory of a time series. For human-dependent phenomena, as in finance, this feature may vary in the time. It justifies modelling dynamics by multifractional Brownian motions, which are consistent with time-dependent Hurst exponents. We improve the existing literature on estimating time-dependent Hurst exponents by proposing a smooth estimate obtained by variational calculus. This method is very general and not restricted to the sole Hurst framework. It is globally more accurate and easier than other existing non-parametric estimation techniques. Besides, in the field of Hurst exponents, it makes it possible to make forecasts based on the estimated multifractional Brownian motion. The application to high-frequency foreign exchange markets (GBP, CHF, SEK, USD, CAD, AUD, JPY, CNY and SGD, all against EUR) shows significantly good forecasts. When the Hurst exponent is higher than 0.5, what depicts a long-memory feature, the accuracy is higher.

  5. [The human variome project and its progress].

    Science.gov (United States)

    Gao, Shan; Zhang, Ning; Zhang, Lei; Duan, Guang-You; Zhang, Tao

    2010-11-01

    The main goal of post genomics is to explain how the genome, the map of which has been constructed in the Human Genome Project, affacts activities of life. This leads to generate multiple "omics": structural genomics, functional genomics, proteomics, metabonomics, et al. In Jun. 2006, Melbourne, Australia, Human Genome Variation Society (HGVS) initiated the Human Variome Project (HVP) to collect all the sequence variation and polymorphism data worldwidely. HVP is to search and determine those mutations related with human diseases by association study between genetype and phenotype on the scale of genome level and other methods. Those results will be translated into clinical application. Considering the potential effects of this project on human health, this paper introduced its origin and main content in detail and discussed its meaning and prospect.

  6. Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome

    NARCIS (Netherlands)

    Collins, Ryan L; Brand, Harrison; Redin, Claire E.; Hanscom, Carrie; Antolik, Caroline; Stone, Matthew R; Glessner, Joseph T.; Mason, Tamara; Pregno, Giulia; Dorrani, Naghmeh; Mandrile, Giorgia; Giachino, Daniela; Perrin, Danielle; Walsh, Cole; Cipicchio, Michelle; Costello, Maura; Stortchevoi, Alexei; An, Joon Yong; Currall, Benjamin B; Seabra, Catarina M; Ragavendran, Ashok; Margolin, Lauren; Martinez-Agosto, Julian A.; Lucente, Diane; Levy, Brynn; Sanders, Jan-Stephan; Wapner, Ronald J.; Quintero-Rivera, Fabiola; Kloosterman, Wigard; Talkowski, Michael E.

    2017-01-01

    Background: Structural variation (SV) influences genome organization and contributes to human disease. However, the complete mutational spectrum of SV has not been routinely captured in disease association studies. Results: We sequenced 689 participants with autism spectrum disorder (ASD) and other

  7. Modeling Individual Cyclic Variation in Human Behavior.

    Science.gov (United States)

    Pierson, Emma; Althoff, Tim; Leskovec, Jure

    2018-04-01

    Cycles are fundamental to human health and behavior. Examples include mood cycles, circadian rhythms, and the menstrual cycle. However, modeling cycles in time series data is challenging because in most cases the cycles are not labeled or directly observed and need to be inferred from multidimensional measurements taken over time. Here, we present Cyclic Hidden Markov Models (CyH-MMs) for detecting and modeling cycles in a collection of multidimensional heterogeneous time series data. In contrast to previous cycle modeling methods, CyHMMs deal with a number of challenges encountered in modeling real-world cycles: they can model multivariate data with both discrete and continuous dimensions; they explicitly model and are robust to missing data; and they can share information across individuals to accommodate variation both within and between individual time series. Experiments on synthetic and real-world health-tracking data demonstrate that CyHMMs infer cycle lengths more accurately than existing methods, with 58% lower error on simulated data and 63% lower error on real-world data compared to the best-performing baseline. CyHMMs can also perform functions which baselines cannot: they can model the progression of individual features/symptoms over the course of the cycle, identify the most variable features, and cluster individual time series into groups with distinct characteristics. Applying CyHMMs to two real-world health-tracking datasets-of human menstrual cycle symptoms and physical activity tracking data-yields important insights including which symptoms to expect at each point during the cycle. We also find that people fall into several groups with distinct cycle patterns, and that these groups differ along dimensions not provided to the model. For example, by modeling missing data in the menstrual cycles dataset, we are able to discover a medically relevant group of birth control users even though information on birth control is not given to the model.

  8. Genome Variation Map: a data repository of genome variations in BIG Data Center.

    Science.gov (United States)

    Song, Shuhui; Tian, Dongmei; Li, Cuiping; Tang, Bixia; Dong, Lili; Xiao, Jingfa; Bao, Yiming; Zhao, Wenming; He, Hang; Zhang, Zhang

    2018-01-04

    The Genome Variation Map (GVM; http://bigd.big.ac.cn/gvm/) is a public data repository of genome variations. As a core resource in the BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, GVM dedicates to collect, integrate and visualize genome variations for a wide range of species, accepts submissions of different types of genome variations from all over the world and provides free open access to all publicly available data in support of worldwide research activities. Unlike existing related databases, GVM features integration of a large number of genome variations for a broad diversity of species including human, cultivated plants and domesticated animals. Specifically, the current implementation of GVM not only houses a total of ∼4.9 billion variants for 19 species including chicken, dog, goat, human, poplar, rice and tomato, but also incorporates 8669 individual genotypes and 13 262 manually curated high-quality genotype-to-phenotype associations for non-human species. In addition, GVM provides friendly intuitive web interfaces for data submission, browse, search and visualization. Collectively, GVM serves as an important resource for archiving genomic variation data, helpful for better understanding population genetic diversity and deciphering complex mechanisms associated with different phenotypes. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Genome Variation Map: a data repository of genome variations in BIG Data Center

    Science.gov (United States)

    Tian, Dongmei; Li, Cuiping; Tang, Bixia; Dong, Lili; Xiao, Jingfa; Bao, Yiming; Zhao, Wenming; He, Hang

    2018-01-01

    Abstract The Genome Variation Map (GVM; http://bigd.big.ac.cn/gvm/) is a public data repository of genome variations. As a core resource in the BIG Data Center, Beijing Institute of Genomics, Chinese Academy of Sciences, GVM dedicates to collect, integrate and visualize genome variations for a wide range of species, accepts submissions of different types of genome variations from all over the world and provides free open access to all publicly available data in support of worldwide research activities. Unlike existing related databases, GVM features integration of a large number of genome variations for a broad diversity of species including human, cultivated plants and domesticated animals. Specifically, the current implementation of GVM not only houses a total of ∼4.9 billion variants for 19 species including chicken, dog, goat, human, poplar, rice and tomato, but also incorporates 8669 individual genotypes and 13 262 manually curated high-quality genotype-to-phenotype associations for non-human species. In addition, GVM provides friendly intuitive web interfaces for data submission, browse, search and visualization. Collectively, GVM serves as an important resource for archiving genomic variation data, helpful for better understanding population genetic diversity and deciphering complex mechanisms associated with different phenotypes. PMID:29069473

  10. Analysis of Long-Term Temperature Variations in the Human Body.

    Science.gov (United States)

    Dakappa, Pradeepa Hoskeri; Mahabala, Chakrapani

    2015-01-01

    Body temperature is a continuous physiological variable. In normal healthy adults, oral temperature is estimated to vary between 36.1°C and 37.2°C. Fever is a complex host response to many external and internal agents and is a potential contributor to many clinical conditions. Despite being one of the foremost vital signs, temperature and its analysis and variations during many pathological conditions has yet to be examined in detail using mathematical techniques. Classical fever patterns based on recordings obtained every 8-12 h have been developed. However, such patterns do not provide meaningful information in diagnosing diseases. Because fever is a host response, it is likely that there could be a unique response to specific etiologies. Continuous long-term temperature monitoring and pattern analysis using specific analytical methods developed in engineering and physics could aid in revealing unique fever responses of hosts and in different clinical conditions. Furthermore, such analysis can potentially be used as a novel diagnostic tool and to study the effect of pharmaceutical agents and other therapeutic protocols. Thus, the goal of our article is to present a comprehensive review of the recent relevant literature and analyze the current state of research regarding temperature variations in the human body.

  11. Effect of speech-intrinsic variations on human and automatic recognition of spoken phonemes.

    Science.gov (United States)

    Meyer, Bernd T; Brand, Thomas; Kollmeier, Birger

    2011-01-01

    The aim of this study is to quantify the gap between the recognition performance of human listeners and an automatic speech recognition (ASR) system with special focus on intrinsic variations of speech, such as speaking rate and effort, altered pitch, and the presence of dialect and accent. Second, it is investigated if the most common ASR features contain all information required to recognize speech in noisy environments by using resynthesized ASR features in listening experiments. For the phoneme recognition task, the ASR system achieved the human performance level only when the signal-to-noise ratio (SNR) was increased by 15 dB, which is an estimate for the human-machine gap in terms of the SNR. The major part of this gap is attributed to the feature extraction stage, since human listeners achieve comparable recognition scores when the SNR difference between unaltered and resynthesized utterances is 10 dB. Intrinsic variabilities result in strong increases of error rates, both in human speech recognition (HSR) and ASR (with a relative increase of up to 120%). An analysis of phoneme duration and recognition rates indicates that human listeners are better able to identify temporal cues than the machine at low SNRs, which suggests incorporating information about the temporal dynamics of speech into ASR systems.

  12. Inter-individual and inter-cell type variation in residual DNA damage after in vivo irradiation of human skin

    International Nuclear Information System (INIS)

    Chua, Melvin Lee Kiang; Somaiah, Navita; Bourne, Sara; Daley, Frances; A'Hern, Roger; Nuta, Otilia; Davies, Sue; Herskind, Carsten; Pearson, Ann; Warrington, Jim; Helyer, Sarah; Owen, Roger; Yarnold, John; Rothkamm, Kai

    2011-01-01

    Purpose: The aim of this study was to compare inter-individual and inter-cell type variation in DNA double-strand break (DSB) repair following in vivo irradiation of human skin. Materials and methods: Duplicate 4 mm core biopsies of irradiated and unirradiated skin were collected from 35 patients 24 h after 4 Gy exposure using 6 MeV electrons. Residual DSB were quantified by scoring 53BP1 foci in dermal fibroblasts, endothelial cells, superficial keratinocytes and basal epidermal cells. Results: Coefficients of inter-individual variation for levels of residual foci 24 h after in vivo irradiation of skin were 39.9% in dermal fibroblasts, 44.3% in endothelial cells, 32.9% in superficial keratinocytes and 46.4% in basal epidermal cells (p < 0.001, ANOVA). In contrast, the coefficient of inter-cell type variation for residual foci levels was only 11.3% in human skin between the different epidermal and dermal cells (p = 0.034, ANOVA). Foci levels between the different skin cell types were correlated (Pearson's R = 0.855-0.955, p < 0.001). Conclusions: Patient-specific factors appear to be more important than cell type-specific factors in determining residual foci levels following in vivo irradiation of human skin.

  13. Mechanism and modelling of source/drain asymmetry variation in 65 nm CMOS devices for SRAM and logic applications

    International Nuclear Information System (INIS)

    Lee, T H; Fang, Y K; Chiang, Y T; Lin, C T; Chen, M S; Cheng, O

    2008-01-01

    The source/drain asymmetry variation of 65 nm CMOS devices for SRAM and logic applications has been investigated in detail. For the first time, we observe that the asymmetry variation is proportional to the inverse of the root square of the device area. In other words, the asymmetry variation should become worse for future advanced CMOS technologies. Fortunately, through the T-CAD simulations and experiments, we find the variation can be improved significantly with the optimization of the poly-gate grain size, extra laser annealing and using a vertical profile poly-gate. Furthermore, the improvement in asymmetry variation leads to a better static noise margin of SRAM

  14. An improvement of the applicability of human factors guidelines for coping with human factors issues in nuclear power plants

    International Nuclear Information System (INIS)

    Lee, Y. H.; Lee, J. Y.

    2003-01-01

    Human factors have been well known as one of the key factors to the system effectiveness as well as the efficiency and safety of nuclear power plants(NPPs). Human factors engineering(HFE) are included in periodic safety review(PSR) on the existing NPPs and the formal safety assessment for the new ones. However, HFE for NPPs is still neither popular in practice nor concrete in methodology. Especially, the human factors guidelines, which are the most frequent form of human factors engineering in practice, reveal the limitations in their applications. We discuss the limitations and their casual factors found in human factors guidelines in order to lesson the workload of HFE practitioners and to improve the applicability of human factors guidelines. According to the purposes and the phases of HFE for NPPs, more selective items and specified criteria should be prepared carefully in the human factors guidelines for the each HFE applications in practice. These finding on the human factors guidelines can be transferred to the other HFE application field, such as military, aviation, telecommunication, HCI, and product safety

  15. Severity of infection and seasonal variation of non-typhoid Salmonelle occurence in humans

    DEFF Research Database (Denmark)

    Gradel, K.O.; Dethlefsen, Claus; Schønheyder, H.C.

    2007-01-01

    Non-typhoid Salmonella infections may present as severe gastroenteritis necessitatinghospitalization and some patients become septic with bacteraemia. We hypothesized that theseasonal variation of non-typhoid Salmonella occurrence in humans diminishes with increasedseverity of infection. We...... examined the seasonal variation of non-typhoid Salmonella infections inthree patient groups with differing severity of infection: outpatients treated for gastroenteritis(n=1490); in-patients treated for gastroenteritis (n=492); and in-patients treated for bacteraemia(n=113). The study was population......-based and included all non-typhoid Salmonella patients ina Danish county from 1994 to 2003. A periodic regression model was used to compute thepeak-to-trough ratio for the three patient groups. The peak-to-trough ratios were 4·3 [95%confidence interval (CI) 3·6–5.0] for outpatients with gastroenteritis, 3·2 (95% CI...

  16. Application of Sequence-based Methods in Human MicrobialEcology

    Energy Technology Data Exchange (ETDEWEB)

    Weng, Li; Rubin, Edward M.; Bristow, James

    2005-08-29

    Ecologists studying microbial life in the environment have recognized the enormous complexity of microbial diversity for many years, and the development of a variety of culture-independent methods, many of them coupled with high-throughput DNA sequencing, has allowed this diversity to be explored in ever greater detail. Despite the widespread application of these new techniques to the characterization of uncultivated microbes and microbial communities in the environment, their application to human health and disease has lagged behind. Because DNA based-techniques for defining uncultured microbes allow not only cataloging of microbial diversity, but also insight into microbial functions, investigators are beginning to apply these tools to the microbial communities that abound on and within us, in what has aptly been called the second Human Genome Project. In this review we discuss the sequence-based methods for microbial analysis that are currently available and their application to identify novel human pathogens, improve diagnosis of known infectious diseases, and to advance understanding of our relationship with microbial communities that normally reside in and on the human body.

  17. Population-genetic nature of copy number variations in the human genome.

    Science.gov (United States)

    Kato, Mamoru; Kawaguchi, Takahisa; Ishikawa, Shumpei; Umeda, Takayoshi; Nakamichi, Reiichiro; Shapero, Michael H; Jones, Keith W; Nakamura, Yusuke; Aburatani, Hiroyuki; Tsunoda, Tatsuhiko

    2010-03-01

    Copy number variations (CNVs) are universal genetic variations, and their association with disease has been increasingly recognized. We designed high-density microarrays for CNVs, and detected 3000-4000 CNVs (4-6% of the genomic sequence) per population that included CNVs previously missed because of smaller sizes and residing in segmental duplications. The patterns of CNVs across individuals were surprisingly simple at the kilo-base scale, suggesting the applicability of a simple genetic analysis for these genetic loci. We utilized the probabilistic theory to determine integer copy numbers of CNVs and employed a recently developed phasing tool to estimate the population frequencies of integer copy number alleles and CNV-SNP haplotypes. The results showed a tendency toward a lower frequency of CNV alleles and that most of our CNVs were explained only by zero-, one- and two-copy alleles. Using the estimated population frequencies, we found several CNV regions with exceptionally high population differentiation. Investigation of CNV-SNP linkage disequilibrium (LD) for 500-900 bi- and multi-allelic CNVs per population revealed that previous conflicting reports on bi-allelic LD were unexpectedly consistent and explained by an LD increase correlated with deletion-allele frequencies. Typically, the bi-allelic LD was lower than SNP-SNP LD, whereas the multi-allelic LD was somewhat stronger than the bi-allelic LD. After further investigation of tag SNPs for CNVs, we conclude that the customary tagging strategy for disease association studies can be applicable for common deletion CNVs, but direct interrogation is needed for other types of CNVs.

  18. STUDY ON NORTHERN AND SOUTHERN INDIA VARIATIONS OF HUMAN SKULL- A SECONDARY RESEARCH

    Directory of Open Access Journals (Sweden)

    Jameskutty Baby Jacob Kaithackal

    2016-12-01

    Full Text Available BACKGROUND Identity of a human being with regard to sex, race, age etc. can be revealed if the skull is suitably examined. The general concept of ethnic and geographic variations being reflected in the body as variations in size, shape, etc. can be checked for in the case of skeleton also. This article is formed out of a term paper study submitted by myself in 2016 to the Yenepoya University, Mangalore, Karnataka, as part of the postgraduate diploma course in Forensic Anthropology. The research was based on a question whether there is a significant difference between human skulls from North and South India. The aims/objectives were bi-fold: to analyse the difference in male and female skull from North Indian and South Indian regions from review of scholarly literature and to explore the possibility identification of individuals from cranial features unique to North and South India. MATERIALS AND METHODS The original articles available on this type of work were extensively reviewed to recognise any traits that differentiated the skulls with regard to their regional variation. RESULTS At the end of the scrutiny of such papers, a summary of the features that distinguished skulls as belonging to northern or southern parts of India was tried. The Indian cranial series, though varied widely in shape, the absence of any statistically significant difference between them made it unreliable to predict skull as male or female by morphometric estimation. The studies by different scholars did not propose for a uniform distinctiveness between north and south Indian skulls. CONCLUSION It was concluded that analysing a single specimen to be of a distinct geographic origin should be done more cautiously when compared to a setting of series analysis where variability might be there of course.

  19. Religious influences on human capital variations in imperial Russia

    Directory of Open Access Journals (Sweden)

    Tomila Lankina

    2012-01-01

    Full Text Available Historical legacies, particularly imperial tutelage and religion, have featured prominently in recent scholarship on political regime variations in post-communist settings, challenging earlier temporally proximate explanations. The overlap between tutelage, geography, and religion has complicated the uncovering of the spatially uneven effects of the various legacies. The author addresses this challenge by conducting sub-national analysis of religious influences within one imperial domain, Russia. In particular, the paper traces how European settlement in imperial Russia has had a bearing on human development in the imperial periphery. The causal mechanism that the paper proposes to account for this influence is the Western communities’ impact on literacy, which is in turn linked in the analysis to the Western Christian, particularly Protestant, roots, of settler populations. The author makes this case by constructing an original dataset based on sub-national data from the hitherto underutilised first imperial census of 1897.

  20. Genetic variation in the Cytb gene of human cerebral Taenia solium cysticerci recovered from clinically and radiologically heterogeneous patients with neurocysticercosis

    Directory of Open Access Journals (Sweden)

    Hector Palafox-Fonseca

    2013-11-01

    Full Text Available Neurocysticercosis (NC is a clinically and radiologically heterogeneous parasitic disease caused by the establishment of larval Taenia solium in the human central nervous system. Host and/or parasite variations may be related to this observed heterogeneity. Genetic differences between pig and human-derived T. solium cysticerci have been reported previously. In this study, 28 cysticerci were surgically removed from 12 human NC patients, the mitochondrial gene that encodes cytochrome b was amplified from the cysticerci and genetic variations that may be related to NC heterogeneity were characterised. Nine different haplotypes (Ht, which were clustered in four haplogroups (Hg, were identified. Hg 3 and 4 exhibited a tendency to associate with age and gender, respectively. However, no significant associations were found between NC heterogeneity and the different T. solium cysticerci Ht or Hg. Parasite variants obtained from patients with similar NC clinical or radiological features were genetically closer than those found in groups of patients with a different NC profile when using the Mantel test. Overall, this study establishes the presence of genetic differences in the Cytb gene of T. solium isolated from human cysticerci and suggests that parasite variation could contribute to NC heterogeneity.

  1. Perfect Form: Variational Principles, Methods, and Applications in Elementary Physics

    International Nuclear Information System (INIS)

    Isenberg, C

    1997-01-01

    This short book is concerned with the physical applications of variational principles of the calculus. It is intended for undergraduate students who have taken some introductory lectures on the subject and have been exposed to Lagrangian and Hamiltonian mechanics. Throughout the book the author emphasizes the historical background to the subject and provides numerous problems, mainly from the fields of mechanics and optics. Some of these problems are provided with an answer, while others, regretfully, are not. It would have been an added help to the undergraduate reader if complete solutions could have been provided in an appendix. The introductory chapter is concerned with Fermat's Principle and image formation. This is followed by the derivation of the Euler - Lagrange equation. The third chapter returns to the subject of optical paths without making the link with a mechanical variational principle - that comes later. Chapters on the subjects of minimum potential energy, least action and Hamilton's principle follow. This volume provides an 'easy read' for a student keen to learn more about the subject. It is well illustrated and will make a useful addition to all undergraduate physics libraries. (book review)

  2. VarioML framework for comprehensive variation data representation and exchange.

    Science.gov (United States)

    Byrne, Myles; Fokkema, Ivo Fac; Lancaster, Owen; Adamusiak, Tomasz; Ahonen-Bishopp, Anni; Atlan, David; Béroud, Christophe; Cornell, Michael; Dalgleish, Raymond; Devereau, Andrew; Patrinos, George P; Swertz, Morris A; Taschner, Peter Em; Thorisson, Gudmundur A; Vihinen, Mauno; Brookes, Anthony J; Muilu, Juha

    2012-10-03

    Sharing of data about variation and the associated phenotypes is a critical need, yet variant information can be arbitrarily complex, making a single standard vocabulary elusive and re-formatting difficult. Complex standards have proven too time-consuming to implement. The GEN2PHEN project addressed these difficulties by developing a comprehensive data model for capturing biomedical observations, Observ-OM, and building the VarioML format around it. VarioML pairs a simplified open specification for describing variants, with a toolkit for adapting the specification into one's own research workflow. Straightforward variant data can be captured, federated, and exchanged with no overhead; more complex data can be described, without loss of compatibility. The open specification enables push-button submission to gene variant databases (LSDBs) e.g., the Leiden Open Variation Database, using the Cafe Variome data publishing service, while VarioML bidirectionally transforms data between XML and web-application code formats, opening up new possibilities for open source web applications building on shared data. A Java implementation toolkit makes VarioML easily integrated into biomedical applications. VarioML is designed primarily for LSDB data submission and transfer scenarios, but can also be used as a standard variation data format for JSON and XML document databases and user interface components. VarioML is a set of tools and practices improving the availability, quality, and comprehensibility of human variation information. It enables researchers, diagnostic laboratories, and clinics to share that information with ease, clarity, and without ambiguity.

  3. Human applications of the INEL patient treatment planning system

    International Nuclear Information System (INIS)

    Wheeler, F.; Wessol, D.; Atkinson, C.; Nigg, D.

    1995-01-01

    During the past few years, murine and large animal research, as well as human studies have provided data to the point where human clinical trials have been initiated at the BMRR using BPA-F for gliomas and at the Massachusetts Institute of Technology Reactor (MITR) using BPA for melanomas of the extremeties. It is expected that glioma trials using BSH will proceed soon at the Petten High Flux Reactor (HFR) in the Netherlands. The first human glioma epithermal boron neutron capture therapy application was performed at the BMRR in the fall of 1994. This was a collaborative effort by BNL, Beth Israel Manhattan hospital, and INEL. The INEL planning system was chosen to perform dose predictions for this application

  4. Plasmodium falciparum CS protein - prime malaria vaccine candidate: definition of the human CTL domain and analysis of its variation

    Directory of Open Access Journals (Sweden)

    Denise L. Doolan

    1992-01-01

    Full Text Available Studies in mice have shown that immunity to malaria sporozoites is mediated primarily by citotoxic T lymphocytes (CTL specific for epitopes within the circumsporozoite (CS protein. Humans, had never been shown to generate CTL against any malaria or other parasite protein. The design of a sub-unit vaccine for humans ralies on the epitopes recognized by CTL being identified and polymorphisms therein being defined. We have developed a novel technique using an entire series of overlapping synthetic peptides to define the epitopes of the Plasmodium falciparum CS protein recognized by human CTL and have analyzed the sequence variation of the protein with respect to the identified CTL epitopic domain. We have demonstrated that some humans can indeed generate CTL. against the P. falciparum CS protein. Furthermore, the extent of variation observed for the CTL recognition domain is finite and the combination of peptides necessary for inclusion in a polyvalent vaccine may be small. If ways can be found to increase immune responsiveness, then a vaccine designed to stimulate CS protein-specific CTL activity may prevent malaria.

  5. Human-Induced Pluripotent Stem Cell Technology and Cardiomyocyte Generation: Progress and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Angela Di Baldassarre

    2018-05-01

    Full Text Available Human-induced pluripotent stem cells (hiPSCs are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs recapitulate phenotypic differences caused by genetic variations, making them attractive human disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as sources of cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs; the methods used to improve scalability of throughput assays for functional screening and drug testing in vitro; the phenotypic characteristics of hiPSCs-derived CMs and their ability to rescue injured CMs through paracrine effects; we also cover the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their immunological features and the potential use in biomedical applications.

  6. Human-Induced Pluripotent Stem Cell Technology and Cardiomyocyte Generation: Progress and Clinical Applications.

    Science.gov (United States)

    Di Baldassarre, Angela; Cimetta, Elisa; Bollini, Sveva; Gaggi, Giulia; Ghinassi, Barbara

    2018-05-25

    Human-induced pluripotent stem cells (hiPSCs) are reprogrammed cells that have hallmarks similar to embryonic stem cells including the capacity of self-renewal and differentiation into cardiac myocytes. The improvements in reprogramming and differentiating methods achieved in the past 10 years widened the use of hiPSCs, especially in cardiac research. hiPSC-derived cardiac myocytes (CMs) recapitulate phenotypic differences caused by genetic variations, making them attractive human disease models and useful tools for drug discovery and toxicology testing. In addition, hiPSCs can be used as sources of cells for cardiac regeneration in animal models. Here, we review the advances in the genetic and epigenetic control of cardiomyogenesis that underlies the significant improvement of the induced reprogramming of somatic cells to CMs; the methods used to improve scalability of throughput assays for functional screening and drug testing in vitro; the phenotypic characteristics of hiPSCs-derived CMs and their ability to rescue injured CMs through paracrine effects; we also cover the novel approaches in tissue engineering for hiPSC-derived cardiac tissue generation, and finally, their immunological features and the potential use in biomedical applications.

  7. Unleashing the power of human genetic variation knowledge: New Zealand stakeholder perspectives.

    Science.gov (United States)

    Gu, Yulong; Warren, James Roy; Day, Karen Jean

    2011-01-01

    This study aimed to characterize the challenges in using genetic information in health care and to identify opportunities for improvement. Taking a grounded theory approach, semistructured interviews were conducted with 48 participants to collect multiple stakeholder perspectives on genetic services in New Zealand. Three themes emerged from the data: (1) four service delivery models were identified in operation, including both those expected models involving genetic counselors and variations that do not route through the formal genetic service program; (2) multiple barriers to sharing and using genetic information were perceived, including technological, organizational, institutional, legal, ethical, and social issues; and (3) impediments to wider use of genetic testing technology, including variable understanding of genetic test utilities among clinicians and the limited capacity of clinical genetic services. Targeting these problems, information technologies and knowledge management tools have the potential to support key tasks in genetic services delivery, improve knowledge processes, and enhance knowledge networks. Because of the effect of issues in genetic information and knowledge management, the potential of human genetic variation knowledge to enhance health care delivery has been put on a "leash."

  8. Initial studies on the variations of load-displacement curves of in vivo human healthy heel pads

    DEFF Research Database (Denmark)

    Matteoli, Sara; Wilhjelm, Jens E.; Virga, Antonio

    2011-01-01

    The aim of this study was to quantify on the measurement variation of in vivo load-displacement curves by using a group of human healthy heel pads. The recordings were done with a compression device measuring force and displacement. Twenty three heel pads, one from each of 23 subjects aged 20...

  9. Variation in tissue outcome of ovine and human engineered heart valve constructs : relevance for tissue engineering

    NARCIS (Netherlands)

    Geemen, van D.; Driessen - Mol, A.; Grootzwagers, L.G.M.; Soekhradj - Soechit, R.S.; Riem Vis, P.W.; Baaijens, F.P.T.; Bouten, C.V.C.

    AIM: Clinical application of tissue engineered heart valves requires precise control of the tissue culture process to predict tissue composition and mechanical properties prior to implantation, and to understand the variation in tissue outcome. To this end we investigated cellular phenotype and

  10. Mechanisms of Surface Antigenic Variation in the Human Pathogenic Fungus Pneumocystis jirovecii.

    Science.gov (United States)

    Schmid-Siegert, Emanuel; Richard, Sophie; Luraschi, Amanda; Mühlethaler, Konrad; Pagni, Marco; Hauser, Philippe M

    2017-11-07

    Microbial pathogens commonly escape the human immune system by varying surface proteins. We investigated the mechanisms used for that purpose by Pneumocystis jirovecii This uncultivable fungus is an obligate pulmonary pathogen that in immunocompromised individuals causes pneumonia, a major life-threatening infection. Long-read PacBio sequencing was used to assemble a core of subtelomeres of a single P. jirovecii strain from a bronchoalveolar lavage fluid specimen from a single patient. A total of 113 genes encoding surface proteins were identified, including 28 pseudogenes. These genes formed a subtelomeric gene superfamily, which included five families encoding adhesive glycosylphosphatidylinositol (GPI)-anchored glycoproteins and one family encoding excreted glycoproteins. Numerical analyses suggested that diversification of the glycoproteins relies on mosaic genes created by ectopic recombination and occurs only within each family. DNA motifs suggested that all genes are expressed independently, except those of the family encoding the most abundant surface glycoproteins, which are subject to mutually exclusive expression. PCR analyses showed that exchange of the expressed gene of the latter family occurs frequently, possibly favored by the location of the genes proximal to the telomere because this allows concomitant telomere exchange. Our observations suggest that (i) the P. jirovecii cell surface is made of a complex mixture of different surface proteins, with a majority of a single isoform of the most abundant glycoprotein, (ii) genetic mosaicism within each family ensures variation of the glycoproteins, and (iii) the strategy of the fungus consists of the continuous production of new subpopulations composed of cells that are antigenically different. IMPORTANCE Pneumocystis jirovecii is a fungus causing severe pneumonia in immunocompromised individuals. It is the second most frequent life-threatening invasive fungal infection. We have studied the mechanisms

  11. Genetics in endocrinology: genetic variation in deiodinases: a systematic review of potential clinical effects in humans.

    Science.gov (United States)

    Verloop, Herman; Dekkers, Olaf M; Peeters, Robin P; Schoones, Jan W; Smit, Johannes W A

    2014-09-01

    Iodothyronine deiodinases represent a family of selenoproteins involved in peripheral and local homeostasis of thyroid hormone action. Deiodinases are expressed in multiple organs and thyroid hormone affects numerous biological systems, thus genetic variation in deiodinases may affect multiple clinical endpoints. Interest in clinical effects of genetic variation in deiodinases has clearly increased. We aimed to provide an overview for the role of deiodinase polymorphisms in human physiology and morbidity. In this systematic review, studies evaluating the relationship between deiodinase polymorphisms and clinical parameters in humans were eligible. No restrictions on publication date were imposed. The following databases were searched up to August 2013: Pubmed, EMBASE (OVID-version), Web of Science, COCHRANE Library, CINAHL (EbscoHOST-version), Academic Search Premier (EbscoHOST-version), and ScienceDirect. Deiodinase physiology at molecular and tissue level is described, and finally the role of these polymorphisms in pathophysiological conditions is reviewed. Deiodinase type 1 (D1) polymorphisms particularly show moderate-to-strong relationships with thyroid hormone parameters, IGF1 production, and risk for depression. D2 variants correlate with thyroid hormone levels, insulin resistance, bipolar mood disorder, psychological well-being, mental retardation, hypertension, and risk for osteoarthritis. D3 polymorphisms showed no relationship with inter-individual variation in serum thyroid hormone parameters. One D3 polymorphism was associated with risk for osteoarthritis. Genetic deiodinase profiles only explain a small proportion of inter-individual variations in serum thyroid hormone levels. Evidence suggests a role of genetic deiodinase variants in certain pathophysiological conditions. The value for determination of deiodinase polymorphism in clinical practice needs further investigation. © 2014 European Society of Endocrinology.

  12. Variation in ovarian follicle density during human fetal development.

    Science.gov (United States)

    Geber, Selmo; Megale, Rodrigo; Vale, Fabiene; Lanna, Ana Maria Arruda; Cabral, Antônio Carlos Vieira

    2012-09-01

    To obtain a precise estimate of ovarian follicle density and variation in the number of follicles at several gestational ages during human fetal development. Twelve necropsied ovaries from 9 fetuses (gestational age: 24 to 36 weeks) and 3 neonates (who died within the first hours of life) were studied. Ovaries were fixed with 4 % formaldehyde and embedded in paraffin. Serial, 7 mm thick sections of the ovaries were cut and evaluated at every 50 cuts. Follicles were counted in 10 regions (each measuring 625 μm(2)) of the ovarian cortex and the number of follicles per mm³ was calculated. The number of follicles per 0.25 mm² ranged from 10.9 (± 4.8) in a neonate to 34.7 (± 10.6) also in a neonate. Among fetuses, follicle density was lowest at 36 weeks of gestation (11.1 ± 6.2) and highest at 26 weeks (32 ± 8.9). The total number of follicles ranged from 500,000 at the age of 22 weeks to > 1,000,000 at the age of 39 weeks. Our results show a peak in the number of follicles during intrauterine life at approximately 26 weeks, followed by a rapid reduction in this number before birth, providing a step forward towards the understanding of primordial follicular assembly in humans and, ultimately, the identification of the determinants of reproductive capacity.

  13. Frequency variations of discrete cranial traits in major human populations. I. Supernumerary ossicle variations.

    Science.gov (United States)

    Hanihara, T; Ishida, H

    2001-06-01

    Four supernumerary ossicle variations-the ossicle at the lambda, the parietal notch bone, the asterionic bone, and the occipitomastoid bone-were examined for laterality differences, intertrait correlations, sex differences, and between group variations in the samples from around the world. Significant laterality differences were not detected in almost all samples. In some pairs of traits, significant association of occurrence were found. Several geographic samples were sexually dimorphic with respect to the asterionic bone and to a lesser extent for the parietal notch bone. East/Northeast Asians including the Arctic populations in general had lower frequencies of the 4 accessory ossicles. Australians, Melanesians and the majority of the New World peoples, on the other hand, generally had high frequencies. In the western hemisphere of the Old World, Subsaharan Africans had relatively high frequencies. Except for the ossicle at the lambda, the distribution pattern in incidence showed clinal variation from south to north. Any identifiable adaptive value related to environmental or subsistence factors may be expressed in such clinal variation. This may allow us to hypothesise that not only mechanical factors but a founder effect, genetic drift, and population structure could have been the underlying causes for interregional variation and possible clines in the incidences of the accessory ossicles.

  14. Techniques and applications for binaural sound manipulation in human-machine interfaces

    Science.gov (United States)

    Begault, Durand R.; Wenzel, Elizabeth M.

    1992-01-01

    The implementation of binaural sound to speech and auditory sound cues (auditory icons) is addressed from both an applications and technical standpoint. Techniques overviewed include processing by means of filtering with head-related transfer functions. Application to advanced cockpit human interface systems is discussed, although the techniques are extendable to any human-machine interface. Research issues pertaining to three-dimensional sound displays under investigation at the Aerospace Human Factors Division at NASA Ames Research Center are described.

  15. Circadian variation of EEG power spectra in NREM and REM sleep in humans: dissociation from body temperature

    Science.gov (United States)

    Dijk, D. J.

    1999-01-01

    In humans, EEG power spectra in REM and NREM sleep, as well as characteristics of sleep spindles such as their duration, amplitude, frequency and incidence, vary with circadian phase. Recently it has been hypothesized that circadian variations in EEG spectra in humans are caused by variations in brain or body temperature and may not represent phenomena relevant to sleep regulatory processes. To test this directly, a further analysis of EEG power spectra - collected in a forced desynchrony protocol in which sleep episodes were scheduled to a 28-h period while the rhythms of body temperature and plasma melatonin were oscillating at their near 24-h period - was carried out. EEG power spectra were computed for NREM and REM sleep occurring between 90-120 and 270-300 degrees of the circadian melatonin rhythm, i.e. just after the clearance of melatonin from plasma in the 'morning' and just after the 'evening' increase in melatonin secretion. Average body temperatures during scheduled sleep at these two circadian phases were identical (36.72 degrees C). Despite identical body temperatures, the power spectra in NREM sleep were very different at these two circadian phases. EEG activity in the low frequency spindle range was significantly and markedly enhanced after the evening increase in plasma melatonin as compared to the morning phase. For REM sleep, significant differences in power spectra during these two circadian phases, in particular in the alpha range, were also observed. The results confirm that EEG power spectra in NREM and REM sleep vary with circadian phase, suggesting that the direct contribution of temperature to the circadian variation in EEG power spectra is absent or only minor, and are at variance with the hypothesis that circadian variations in EEG power spectra are caused by variations in temperature.

  16. Age variations in the properties of human tibial trabecular bone

    DEFF Research Database (Denmark)

    Ding, Ming; Dalstra, M; Danielsen, CC

    1997-01-01

    We tested in compression specimens of human proximal tibial trabecular bone from 31 normal donors aged from 16 to 83 years and determined the mechanical properties, density and mineral and collagen content. Young's modulus and ultimate stress were highest between 40 and 50 years, whereas ultimate...... strain and failure energy showed maxima at younger ages. These age-related variations (except for failure energy) were non-linear. Tissue density and mineral concentration were constant throughout life, whereas apparent density (the amount of bone) varied with ultimate stress. Collagen density (the...... amount of collagen) varied with failure energy. Collagen concentration was maximal at younger ages but varied little with age. Our results suggest that the decrease in mechanical properties of trabecular bone such as Young's modulus and ultimate stress is mainly a consequence of the loss of trabecular...

  17. The application of human engineering in control room of HFETR

    International Nuclear Information System (INIS)

    Yang Shuchun; Shan Songlin

    2003-01-01

    The human-machine system for improving the working environment in the control room of HFETR is described. The reliability of the equipment, instruments and operation by human engineering is increased. The relations between human engineering and lowering human failure in HFETR are also discussed. It is concluded that the further application of human engineering can increase interaction of the human and machine in the control room and provide assurances for the safe and reliable operation of reactor. (authors)

  18. The application of human engineering in control room of HFETR

    Energy Technology Data Exchange (ETDEWEB)

    Shuchun, Yang; Songlin, Shan [Nuclear Power Inst. of China, Chengdu (China)

    2003-07-01

    The human-machine system for improving the working environment in the control room of HFETR is described. The reliability of the equipment, instruments and operation by human engineering is increased. The relations between human engineering and lowering human failure in HFETR are also discussed. It is concluded that the further application of human engineering can increase interaction of the human and machine in the control room and provide assurances for the safe and reliable operation of reactor. (authors)

  19. Intra-individual metameric variation expressed at the enamel-dentine junction of lower post-canine dentition of South African fossil hominins and modern humans.

    Science.gov (United States)

    Pan, Lei; Thackeray, John Francis; Dumoncel, Jean; Zanolli, Clément; Oettlé, Anna; de Beer, Frikkie; Hoffman, Jakobus; Duployer, Benjamin; Tenailleau, Christophe; Braga, José

    2017-08-01

    The aim of this study is to compare the degree and patterning of inter- and intra-individual metameric variation in South African australopiths, early Homo and modern humans. Metameric variation likely reflects developmental and taxonomical issues, and could also be used to infer ecological and functional adaptations. However, its patterning along the early hominin postcanine dentition, particularly among South African fossil hominins, remains unexplored. Using microfocus X-ray computed tomography (µXCT) and geometric morphometric tools, we studied the enamel-dentine junction (EDJ) morphology and we investigated the intra- and inter-individual EDJ metameric variation among eight australopiths and two early Homo specimens from South Africa, as well as 32 modern humans. Along post-canine dentition, shape changes between metameres represented by relative positions and height of dentine horns, outlines of the EDJ occlusal table are reported in modern and fossil taxa. Comparisons of EDJ mean shapes and multivariate analyses reveal substantial variation in the direction and magnitude of metameric shape changes among taxa, but some common trends can be found. In modern humans, both the direction and magnitude of metameric shape change show increased variability in M 2 -M 3 compared to M 1 -M 2 . Fossil specimens are clustered together showing similar magnitudes of shape change. Along M 2 -M 3 , the lengths of their metameric vectors are not as variable as those of modern humans, but they display considerable variability in the direction of shape change. The distalward increase of metameric variation along the modern human molar row is consistent with the odontogenetic models of molar row structure (inhibitory cascade model). Though much remains to be tested, the variable trends and magnitudes in metamerism in fossil hominins reported here, together with differences in the scale of shape change between modern humans and fossil hominins may provide valuable information

  20. VarioML framework for comprehensive variation data representation and exchange

    Directory of Open Access Journals (Sweden)

    Byrne Myles

    2012-10-01

    Full Text Available Abstract Background Sharing of data about variation and the associated phenotypes is a critical need, yet variant information can be arbitrarily complex, making a single standard vocabulary elusive and re-formatting difficult. Complex standards have proven too time-consuming to implement. Results The GEN2PHEN project addressed these difficulties by developing a comprehensive data model for capturing biomedical observations, Observ-OM, and building the VarioML format around it. VarioML pairs a simplified open specification for describing variants, with a toolkit for adapting the specification into one's own research workflow. Straightforward variant data can be captured, federated, and exchanged with no overhead; more complex data can be described, without loss of compatibility. The open specification enables push-button submission to gene variant databases (LSDBs e.g., the Leiden Open Variation Database, using the Cafe Variome data publishing service, while VarioML bidirectionally transforms data between XML and web-application code formats, opening up new possibilities for open source web applications building on shared data. A Java implementation toolkit makes VarioML easily integrated into biomedical applications. VarioML is designed primarily for LSDB data submission and transfer scenarios, but can also be used as a standard variation data format for JSON and XML document databases and user interface components. Conclusions VarioML is a set of tools and practices improving the availability, quality, and comprehensibility of human variation information. It enables researchers, diagnostic laboratories, and clinics to share that information with ease, clarity, and without ambiguity.

  1. Evolution and variation of multigene families

    CERN Document Server

    Ohta, Tomoko

    1980-01-01

    During the last decade and a half, studies of evolution and variation have been revolutionized by the introduction of the methods and concepts of molecular genetics. We can now construct reliable phylogenetic trees, even when fossil records are missing, by compara­ tive studies of protein or mRNA sequences. If, in addition, paleon­ tological information is available, we can estimate the rate at which genes are substituted in the species in the course of evolution. Through the application of electrophoretic methods, it has become possible to study intraspecific variation in molecular terms. We now know that an immense genetic variability exists in a sexually repro­ ducing species, and our human species is no exception. The mathematical theory of population genetics (particularly its stochastic aspects) in conjunction with these new developments led us to formulate the "neutral theory" of molecular evolution, pointing out that chance, in the form of random gene frequency drift, is playing a much more importa...

  2. Learning-based stochastic object models for characterizing anatomical variations

    Science.gov (United States)

    Dolly, Steven R.; Lou, Yang; Anastasio, Mark A.; Li, Hua

    2018-03-01

    It is widely known that the optimization of imaging systems based on objective, task-based measures of image quality via computer-simulation requires the use of a stochastic object model (SOM). However, the development of computationally tractable SOMs that can accurately model the statistical variations in human anatomy within a specified ensemble of patients remains a challenging task. Previously reported numerical anatomic models lack the ability to accurately model inter-patient and inter-organ variations in human anatomy among a broad patient population, mainly because they are established on image data corresponding to a few of patients and individual anatomic organs. This may introduce phantom-specific bias into computer-simulation studies, where the study result is heavily dependent on which phantom is used. In certain applications, however, databases of high-quality volumetric images and organ contours are available that can facilitate this SOM development. In this work, a novel and tractable methodology for learning a SOM and generating numerical phantoms from a set of volumetric training images is developed. The proposed methodology learns geometric attribute distributions (GAD) of human anatomic organs from a broad patient population, which characterize both centroid relationships between neighboring organs and anatomic shape similarity of individual organs among patients. By randomly sampling the learned centroid and shape GADs with the constraints of the respective principal attribute variations learned from the training data, an ensemble of stochastic objects can be created. The randomness in organ shape and position reflects the learned variability of human anatomy. To demonstrate the methodology, a SOM of an adult male pelvis is computed and examples of corresponding numerical phantoms are created.

  3. Natural selection affects multiple aspects of genetic variation at putatively peutral sites across the human genome

    DEFF Research Database (Denmark)

    Lohmueller, Kirk E; Albrechtsen, Anders; Li, Yingrui

    2011-01-01

    A major question in evolutionary biology is how natural selection has shaped patterns of genetic variation across the human genome. Previous work has documented a reduction in genetic diversity in regions of the genome with low recombination rates. However, it is unclear whether other summaries...... these questions by analyzing three different genome-wide resequencing datasets from European individuals. We document several significant correlations between different genomic features. In particular, we find that average minor allele frequency and diversity are reduced in regions of low recombination...... and that human diversity, human-chimp divergence, and average minor allele frequency are reduced near genes. Population genetic simulations show that either positive natural selection acting on favorable mutations or negative natural selection acting against deleterious mutations can explain these correlations...

  4. Application of focus-variation Technique in Measurements of Ultrasonic Vibrations of Grinding pins

    Directory of Open Access Journals (Sweden)

    Wdowik Roman

    2015-01-01

    Full Text Available The paper presents the application of focus-variation technique in measurements of ultrasonic vibrations of grinding pins. Ultrasonic vibrations of tools are applied in ultrasonic assisted grinding. Their measurements are significant for development of this hybrid machining process. Alumina and zirconia ceramic materials in the final fired state were machined in experiments which are known as scratch tests. Diamond grinding pin was used as a tool to machine scratches. Marks of diamond grains, left on the surface of workpieces after machining process, were investigated using The Infinite Focus Real 3D optical microscope. Focus-variation is the principle of operation of this microscope. Investigations concerned possibilities of measurements of an amplitude of axial and radial vibrations in the case of two ceramic materials. Results of performed measurements are presented and discussed for selected machining parameters.

  5. A combination of PhP typing and β-d-glucuronidase gene sequence variation analysis for differentiation of Escherichia coli from humans and animals.

    Science.gov (United States)

    Masters, N; Christie, M; Katouli, M; Stratton, H

    2015-06-01

    We investigated the usefulness of the β-d-glucuronidase gene variance in Escherichia coli as a microbial source tracking tool using a novel algorithm for comparison of sequences from a prescreened set of host-specific isolates using a high-resolution PhP typing method. A total of 65 common biochemical phenotypes belonging to 318 E. coli strains isolated from humans and domestic and wild animals were analysed for nucleotide variations at 10 loci along a 518 bp fragment of the 1812 bp β-d-glucuronidase gene. Neighbour-joining analysis of loci variations revealed 86 (76.8%) human isolates and 91.2% of animal isolates were correctly identified. Pairwise hierarchical clustering improved assignment; where 92 (82.1%) human and 204 (99%) animal strains were assigned to their respective cluster. Our data show that initial typing of isolates and selection of common types from different hosts prior to analysis of the β-d-glucuronidase gene sequence improves source identification. We also concluded that numerical profiling of the nucleotide variations can be used as a valuable approach to differentiate human from animal E. coli. This study signifies the usefulness of the β-d-glucuronidase gene as a marker for differentiating human faecal pollution from animal sources.

  6. Application of variational principles and adjoint integrating factors for constructing numerical GFD models

    Science.gov (United States)

    Penenko, Vladimir; Tsvetova, Elena; Penenko, Alexey

    2015-04-01

    direction on a time step. In each direction, they have tridiagonal structure. They are solved by the sweep method. An important advantage of the discrete-analytical schemes is that the values of derivatives at the boundaries of finite volume are calculated together with the values of the unknown functions. This technique is particularly attractive for problems with dominant convection, as it does not require artificial monotonization and limiters. The same idea of integrating factors is applied in temporal dimension to the stiff systems of equations describing chemical transformation models [2]. The proposed method is applicable for the problems involving convection-diffusion-reaction operators. The work has been partially supported by the Presidium of RAS under Program 43, and by the RFBR grants 14-01-00125 and 14-01-31482. References: 1. V.V. Penenko, E.A. Tsvetova, A.V. Penenko. Variational approach and Euler's integrating factors for environmental studies// Computers and Mathematics with Applications, (2014) V.67, Issue 12, P. 2240-2256. 2. V.V.Penenko, E.A.Tsvetova. Variational methods of constructing monotone approximations for atmospheric chemistry models // Numerical analysis and applications, 2013, V. 6, Issue 3, pp 210-220.

  7. A general product measurability theorem with applications to variational inequalities

    Directory of Open Access Journals (Sweden)

    Kenneth L. Kuttler

    2016-03-01

    Full Text Available This work establishes the existence of measurable weak solutions to evolution problems with randomness by proving and applying a novel theorem on product measurability of limits of sequences of functions. The measurability theorem is used to show that many important existence theorems within the abstract theory of evolution inclusions or equations have straightforward generalizations to settings that include random processes or coefficients. Moreover, the convex set where the solutions are sought is not fixed but may depend on the random variables. The importance of adding randomness lies in the fact that real world processes invariably involve randomness and variability. Thus, this work expands substantially the range of applications of models with variational inequalities and differential set-inclusions.

  8. HSP90 Shapes the Consequences of Human Genetic Variation.

    Science.gov (United States)

    Karras, Georgios I; Yi, Song; Sahni, Nidhi; Fischer, Máté; Xie, Jenny; Vidal, Marc; D'Andrea, Alan D; Whitesell, Luke; Lindquist, Susan

    2017-02-23

    HSP90 acts as a protein-folding buffer that shapes the manifestations of genetic variation in model organisms. Whether HSP90 influences the consequences of mutations in humans, potentially modifying the clinical course of genetic diseases, remains unknown. By mining data for >1,500 disease-causing mutants, we found a strong correlation between reduced phenotypic severity and a dominant (HSP90 ≥ HSP70) increase in mutant engagement by HSP90. Examining the cancer predisposition syndrome Fanconi anemia in depth revealed that mutant FANCA proteins engaged predominantly by HSP70 had severely compromised function. In contrast, the function of less severe mutants was preserved by a dominant increase in HSP90 binding. Reducing HSP90's buffering capacity with inhibitors or febrile temperatures destabilized HSP90-buffered mutants, exacerbating FA-related chemosensitivities. Strikingly, a compensatory FANCA somatic mutation from an "experiment of nature" in monozygotic twins both prevented anemia and reduced HSP90 binding. These findings provide one plausible mechanism for the variable expressivity and environmental sensitivity of genetic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Current trend of annotating single nucleotide variation in humans--A case study on SNVrap.

    Science.gov (United States)

    Li, Mulin Jun; Wang, Junwen

    2015-06-01

    As high throughput methods, such as whole genome genotyping arrays, whole exome sequencing (WES) and whole genome sequencing (WGS), have detected huge amounts of genetic variants associated with human diseases, function annotation of these variants is an indispensable step in understanding disease etiology. Large-scale functional genomics projects, such as The ENCODE Project and Roadmap Epigenomics Project, provide genome-wide profiling of functional elements across different human cell types and tissues. With the urgent demands for identification of disease-causal variants, comprehensive and easy-to-use annotation tool is highly in demand. Here we review and discuss current progress and trend of the variant annotation field. Furthermore, we introduce a comprehensive web portal for annotating human genetic variants. We use gene-based features and the latest functional genomics datasets to annotate single nucleotide variation (SNVs) in human, at whole genome scale. We further apply several function prediction algorithms to annotate SNVs that might affect different biological processes, including transcriptional gene regulation, alternative splicing, post-transcriptional regulation, translation and post-translational modifications. The SNVrap web portal is freely available at http://jjwanglab.org/snvrap. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. A survey on vision-based human action recognition

    NARCIS (Netherlands)

    Poppe, Ronald Walter

    Vision-based human action recognition is the process of labeling image sequences with action labels. Robust solutions to this problem have applications in domains such as visual surveillance, video retrieval and human–computer interaction. The task is challenging due to variations in motion

  11. Genetic Variation in Cardiomyopathy and Cardiovascular Disorders.

    Science.gov (United States)

    McNally, Elizabeth M; Puckelwartz, Megan J

    2015-01-01

    With the wider deployment of massively-parallel, next-generation sequencing, it is now possible to survey human genome data for research and clinical purposes. The reduced cost of producing short-read sequencing has now shifted the burden to data analysis. Analysis of genome sequencing remains challenged by the complexity of the human genome, including redundancy and the repetitive nature of genome elements and the large amount of variation in individual genomes. Public databases of human genome sequences greatly facilitate interpretation of common and rare genetic variation, although linking database sequence information to detailed clinical information is limited by privacy and practical issues. Genetic variation is a rich source of knowledge for cardiovascular disease because many, if not all, cardiovascular disorders are highly heritable. The role of rare genetic variation in predicting risk and complications of cardiovascular diseases has been well established for hypertrophic and dilated cardiomyopathy, where the number of genes that are linked to these disorders is growing. Bolstered by family data, where genetic variants segregate with disease, rare variation can be linked to specific genetic variation that offers profound diagnostic information. Understanding genetic variation in cardiomyopathy is likely to help stratify forms of heart failure and guide therapy. Ultimately, genetic variation may be amenable to gene correction and gene editing strategies.

  12. Human-computer interface incorporating personal and application domains

    Science.gov (United States)

    Anderson, Thomas G [Albuquerque, NM

    2011-03-29

    The present invention provides a human-computer interface. The interface includes provision of an application domain, for example corresponding to a three-dimensional application. The user is allowed to navigate and interact with the application domain. The interface also includes a personal domain, offering the user controls and interaction distinct from the application domain. The separation into two domains allows the most suitable interface methods in each: for example, three-dimensional navigation in the application domain, and two- or three-dimensional controls in the personal domain. Transitions between the application domain and the personal domain are under control of the user, and the transition method is substantially independent of the navigation in the application domain. For example, the user can fly through a three-dimensional application domain, and always move to the personal domain by moving a cursor near one extreme of the display.

  13. Human walking in virtual environments perception, technology, and applications

    CERN Document Server

    Visell, Yon; Campos, Jennifer; Lécuyer, Anatole

    2013-01-01

    This book presents a survey of past and recent developments on human walking in virtual environments with an emphasis on human self-motion perception, the multisensory nature of experiences of walking, conceptual design approaches, current technologies, and applications. The use of virtual reality and movement simulation systems is becoming increasingly popular and more accessible to a wide variety of research fields and applications. While, in the past, simulation technologies have focused on developing realistic, interactive visual environments, it is becoming increasingly obvious that our everyday interactions are highly multisensory. Therefore, investigators are beginning to understand the critical importance of developing and validating locomotor interfaces that can allow for realistic, natural behaviours. The book aims to present an overview of what is currently understood about human perception and performance when moving in virtual environments and to situate it relative to the broader scientific and ...

  14. A new differential calculus on a complex banach space with application to variational problems of quantum theory

    International Nuclear Information System (INIS)

    Sharma, C.S.; Rebelo, I.

    1975-01-01

    It is proved that a semilinear function on a complex banach space is not differentiable according to the usual definition of differentiability in the calculus on banch spaces. It is shown that this result makes the calculus largely inapplicable to the solution od variational problems of quantum mechanics. A new concept of differentiability called semidifferentiability is defined. This generalizes the standard concept of differentiability in a banach space and the resulting calculus is particularly suitable for optimizing real-value functions on a complex banach space and is directly applicable to the solution of quantum mechanical variational problems. As an example of such application a rigorous proof of a generalized version of a result due to Sharma (J. Phys. A; 2:413 (1969)) is given. In the course of this work a new concept of prelinearity is defined and some standard results in the calculus in banach spaces are extended and generalized into more powerful ones applicable directly to prelinear functions and hence yielding the standard results for linear function as particular cases. (author)

  15. Positional variation of applicators during low dose rate intracavitary brachytherapy for cervical cancer: a prospective study

    Directory of Open Access Journals (Sweden)

    Arul Ponni

    2010-10-01

    Full Text Available Purpose: In order to know the effect of variation in position of applicators to the dose received by the tumor volume, critical organs such as rectum and bladder and the correlation of variation on the clinical outcome.Material and methods: 36 patients with histologically proven cervical cancer, undergoing intracavitary brachythe - rapy (ICBT from October 2005 to December 2006 were the subjects of the study. Two pairs of orthogonal X-ray films were taken: one prior to loading of sources and the other after removal of sources. These patients were followed up as per the RTOG criteria.Results: The median duration of insertion was 25 hours with a median follow up period of 6.7 months. The translational variation of the applicator position for all patients was 3 mm and 1 mm (2 SD, respectively, in the patient’s lateral and antero-posterior direction. The rotational variation was 3 and 4 degrees (2 SD in the patient’s transverse and sagittal planes. Detailed analysis of source movement showed following changes in median dose: point A: 14%, point B: 2%, point P: 1%, Rectum 1: 3.5%, Rectum 2: 4% and Bladder: 9.1%. The incidence of rectal toxicity was 6/36(16.7% and that of bladder was 1/36 (2.8%. When the variables were grouped to evaluate the relationship, our study showed statistically significant relationship between: R2 and rectal toxicity (p value: 0.002, point A and rectal toxicity (Pearson: 0.792, lateral displacement/anteroposterior displacement and rectal toxicity (p value: 0.012/0.003, beta angle and R2 (p value: 0.002.Conclusions: The geometric relationships between the ICBT applicators and the critical structures vary during the course of low dose rate brachytherapy. Source movement does result in significant dose alterations in terms of increased rate of complications, but its impact on cure rates needs to be studied in the future.

  16. Human platelet lysate: Replacing fetal bovine serum as a gold standard for human cell propagation?

    Science.gov (United States)

    Burnouf, Thierry; Strunk, Dirk; Koh, Mickey B C; Schallmoser, Katharina

    2016-01-01

    The essential physiological role of platelets in wound healing and tissue repair builds the rationale for the use of human platelet derivatives in regenerative medicine. Abundant growth factors and cytokines stored in platelet granules can be naturally released by thrombin activation and clotting or artificially by freeze/thaw-mediated platelet lysis, sonication or chemical treatment. Human platelet lysate prepared by the various release strategies has been established as a suitable alternative to fetal bovine serum as culture medium supplement, enabling efficient propagation of human cells under animal serum-free conditions for a multiplicity of applications in advanced somatic cell therapy and tissue engineering. The rapidly increasing number of studies using platelet derived products for inducing human cell proliferation and differentiation has also uncovered a considerable variability of human platelet lysate preparations which limits comparability of results. The main variations discussed herein encompass aspects of donor selection, preparation of the starting material, the possibility for pooling in plasma or additive solution, the implementation of pathogen inactivation and consideration of ABO blood groups, all of which can influence applicability. This review outlines the current knowledge about human platelet lysate as a powerful additive for human cell propagation and highlights its role as a prevailing supplement for human cell culture capable to replace animal serum in a growing spectrum of applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. HLA DNA sequence variation among human populations: molecular signatures of demographic and selective events.

    Directory of Open Access Journals (Sweden)

    Stéphane Buhler

    2011-02-01

    Full Text Available Molecular differences between HLA alleles vary up to 57 nucleotides within the peptide binding coding region of human Major Histocompatibility Complex (MHC genes, but it is still unclear whether this variation results from a stochastic process or from selective constraints related to functional differences among HLA molecules. Although HLA alleles are generally treated as equidistant molecular units in population genetic studies, DNA sequence diversity among populations is also crucial to interpret the observed HLA polymorphism. In this study, we used a large dataset of 2,062 DNA sequences defined for the different HLA alleles to analyze nucleotide diversity of seven HLA genes in 23,500 individuals of about 200 populations spread worldwide. We first analyzed the HLA molecular structure and diversity of these populations in relation to geographic variation and we further investigated possible departures from selective neutrality through Tajima's tests and mismatch distributions. All results were compared to those obtained by classical approaches applied to HLA allele frequencies.Our study shows that the global patterns of HLA nucleotide diversity among populations are significantly correlated to geography, although in some specific cases the molecular information reveals unexpected genetic relationships. At all loci except HLA-DPB1, populations have accumulated a high proportion of very divergent alleles, suggesting an advantage of heterozygotes expressing molecularly distant HLA molecules (asymmetric overdominant selection model. However, both different intensities of selection and unequal levels of gene conversion may explain the heterogeneous mismatch distributions observed among the loci. Also, distinctive patterns of sequence divergence observed at the HLA-DPB1 locus suggest current neutrality but old selective pressures on this gene. We conclude that HLA DNA sequences advantageously complement HLA allele frequencies as a source of data used

  18. Anatomical Variations of the Circulus Arteriosus in Cadaveric Human Brains

    Science.gov (United States)

    Gunnal, S. A.; Farooqui, M. S.; Wabale, R. N.

    2014-01-01

    Objective. Circulus arteriosus/circle of Willis (CW) is a polygonal anastomotic channel at the base of the brain which unites the internal carotid and vertebrobasilar system. It maintains the steady and constant supply to the brain. The variations of CW are seen often. The Aim of the present work is to find out the percentage of normal pattern of CW, and the frequency of variations of the CW and to study the morphological and morphometric aspects of all components of CW. Methods. Circulus arteriosus of 150 formalin preserved brains were dissected. Dimensions of all the components forming circles were measured. Variations of all the segments were noted and well photographed. The variations such as aplasia, hypoplasia, duplication, fenestrations, and difference in dimensions with opposite segments were noted. The data collected in the study was analyzed. Results. Twenty-one different types of CW were found in the present study. Normal and complete CW was found in 60%. CW with gross morphological variations was seen in 40%. Maximum variations were seen in the PCoA followed by the ACoA in 50% and 40%, respectively. Conclusion. As it confirms high percentage of variations, all surgical interventions should be preceded by angiography. Awareness of these anatomical variations is important in neurovascular procedures. PMID:24891951

  19. Variation in macronutrients in human bank milk: Influencing factors and implications for human milk banking

    DEFF Research Database (Denmark)

    Michaelsen, K F; Skafte, Ester Lis; Badsberg, Jens Henrik

    1990-01-01

    . There was a large variation in the concentration of energy-yielding macronutrients. The contents of P, F, C, and E in the samples with the highest values (97.5 percentile) were 2.3-, 4.8-, 1.2-, and 2.3-fold, respectively, above the contents in the samples with the lowest values (2.5 percentile). The P content...... decreased exponentially during the 1st 8 months, followed by an increase during the following months. The F content decreased during the 1st 4 months, followed by an almost linear increase. The possible influence of different maternal characteristics on the macronutrient content of the milk was examined...... with a high P content, we have developed a "high-protein" milk with a P content of about 12 g/L (true protein) and an E content of about 725 kcal/L. Thus, by continuous monitoring of macronutrient content in human bank milk it is possible to develop a "high-protein" milk with sufficient P and E content...

  20. Applications of human factors engineering to LNG release prevention and control

    Energy Technology Data Exchange (ETDEWEB)

    Shikiar, R.; Rankin, W.L.; Rideout, T.B.

    1982-06-01

    The results of an investigation of human factors engineering and human reliability applications to LNG release prevention and control are reported. The report includes a discussion of possible human error contributions to previous LNG accidents and incidents, and a discussion of generic HF considerations for peakshaving plants. More specific recommendations for improving HF practices at peakshaving plants are offered based on visits to six facilities. The HF aspects of the recently promulgated DOT regulations are reviewed, and recommendations are made concerning how these regulations can be implemented utilizing standard HF practices. Finally, the integration of HF considerations into overall system safety is illustrated by a presentation of human error probabilities applicable to LNG operations and by an expanded fault tree analysis which explicitly recognizes man-machine interfaces.

  1. Characterising the variations in ethnic skin colours: a new calibrated data base for human skin.

    Science.gov (United States)

    Xiao, K; Yates, J M; Zardawi, F; Sueeprasan, S; Liao, N; Gill, L; Li, C; Wuerger, S

    2017-02-01

    Accurate skin colour measurements are important for numerous medical applications including the diagnosis and treatment of cutaneous disorders and the provision of maxillofacial soft tissue prostheses. In this study, we obtained accurate skin colour measurements from four different ethnic groups (Caucasian, Chinese, Kurdish, Thai) and at four different body locations (Forehead, cheek, inner arm, back of hand) with a view of establishing a new skin colour database for medical and cosmetic applications. Skin colours are measured using a spectrophotometer and converted to a device-independent standard colour appearance space (CIELAB) where skin colour is expressed as values along the three dimensions: Lightness L*, Redness a* and Yellowness b*. Skin colour differences and variation are then evaluated as a function of ethnicity and body location. We report three main results: (1) When plotted in a standard colour appearance space (CIELAB), skin colour distributions for the four ethnic groups overlap significantly, although there are systematic mean differences. Between ethnicities, the most significant skin colour differences occur along the yellowness dimension, with Thai skin exhibiting the highest yellowness (b*) value and Caucasian skin the lowest value. Facial redness (a*) is invariant across the four ethnic groups. (2) Between different body locations, there are significant variations in redness (a*), with the forehead showing the highest redness value and the inner arm the lowest. (3) The colour gamut is smallest in the Chinese sample and largest in the Caucasian sample, with the Chinese gamut lying entirely the Caucasian gamut. Similarly, the largest variability in skin tones is found in the Caucasian group, and the smallest in the Chinese group. Broadly speaking, skin colour variation can be explained by two main factors: individual differences in lightness and yellowness are mostly due to ethnicity, whereas differences in redness are primarily due to

  2. Mutation Rate Variation is a Primary Determinant of the Distribution of Allele Frequencies in Humans.

    Directory of Open Access Journals (Sweden)

    Arbel Harpak

    2016-12-01

    Full Text Available The site frequency spectrum (SFS has long been used to study demographic history and natural selection. Here, we extend this summary by examining the SFS conditional on the alleles found at the same site in other species. We refer to this extension as the "phylogenetically-conditioned SFS" or cSFS. Using recent large-sample data from the Exome Aggregation Consortium (ExAC, combined with primate genome sequences, we find that human variants that occurred independently in closely related primate lineages are at higher frequencies in humans than variants with parallel substitutions in more distant primates. We show that this effect is largely due to sites with elevated mutation rates causing significant departures from the widely-used infinite sites mutation model. Our analysis also suggests substantial variation in mutation rates even among mutations involving the same nucleotide changes. In summary, we show that variable mutation rates are key determinants of the SFS in humans.

  3. Inter- and Intraspecific Variations in the Pectoral Muscles of Common Chimpanzees (Pan troglodytes), Bonobos (Pan paniscus), and Humans (Homo sapiens)

    OpenAIRE

    Potau, J. M.; Arias-Martorell, J.; Bello-Hellegouarch, G.; Casado, A.; Pastor, J. F.; de Paz, F.; Diogo, R.

    2018-01-01

    We have analyzed anatomic variations in the pectoralis major and pectoralis minor muscles of common chimpanzees (Pan\\ud troglodytes) and bonobos(Pan paniscus) and compared them to anatomic variations in these muscles in humans(Homo sapiens). We\\ud have macroscopically dissected these muscles in six adult Pan troglodytes, five Pan paniscus of ages ranging from fetus to adult, and\\ud five adult Homo sapiens. Although Pan troglodytes are thought to lack a separate pectoralis abdominis muscle, we...

  4. Geographic variation in nasal cavity form among three human groups from the Japanese Archipelago: Ecogeographic and functional implications.

    Science.gov (United States)

    Fukase, Hitoshi; Ito, Tsuyoshi; Ishida, Hajime

    2016-05-01

    Geographic variation in human nasal form has often been interpreted as a climatic adaptation, owing to the nasal air-conditioning function. The aim of this study was to further address morphofunctional issues of the nasal cavity, using three human groups from subarctic, temperate, and subtropical regions of the Japanese Archipelago: prehistoric Okhotsk, early-modern Honshu and Okinawa groups. Using three-dimensional coordinates of craniometric landmarks surrounding the nasal cavity, we compared linear measurements regarding nasal cavity form among the three groups and also conducted 3D geometric morphometrics. Both linear measurements and morphometric analyses corroborate the previously reported covariation pattern of nasal cavity shape with climate, where humans from a cold/dry climate tend to possess a relatively tall, narrow, and deep nasal cavity compared with those from a warm/humid environment. The northern Okhotsk group had overall larger cranial airways, which may be attributable to their large facial skeleton. However, the ratio of nasal/bimaxillary breadth was significantly lower in the Okhotsk group, indicating that maxillary size does not necessarily constrain the nasal breadth. In addition, despite the presence of obvious geographic clines in anterior nasal shape, posterior choanal shape lacked the north-south geographic cline. This suggests a certain level of morphofunctional independence between the anterior and posterior nasal openings. The observed geographic variations must, however, be partly considered as a reflection of different ancestral traits and population histories of the three groups. Nevertheless, the results indicate that intergroup variations in nasal cavity morphology can be largely explained by climatic conditions. Am. J. Hum. Biol. 28:343-351, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

  5. On the sum of squared η-μ random variates with application to the performance of wireless communication systems

    KAUST Repository

    Ansari, Imran Shafique; Yilmaz, Ferkan; Alouini, Mohamed-Slim

    2013-01-01

    The probability density function (PDF) and cumulative distribution function of the sum of L independent but not necessarily identically distributed squared η-μ variates, applicable to the output statistics of maximal ratio combining (MRC) receiver

  6. Mechanistic understanding of human-wildlife conflict through a novel application of dynamic occupancy models.

    Science.gov (United States)

    Goswami, Varun R; Medhi, Kamal; Nichols, James D; Oli, Madan K

    2015-08-01

    Crop and livestock depredation by wildlife is a primary driver of human-wildlife conflict, a problem that threatens the coexistence of people and wildlife globally. Understanding mechanisms that underlie depredation patterns holds the key to mitigating conflicts across time and space. However, most studies do not consider imperfect detection and reporting of conflicts, which may lead to incorrect inference regarding its spatiotemporal drivers. We applied dynamic occupancy models to elephant crop depredation data from India between 2005 and 2011 to estimate crop depredation occurrence and model its underlying dynamics as a function of spatiotemporal covariates while accounting for imperfect detection of conflicts. The probability of detecting conflicts was consistently year). The probability of crop depredation occurrence ranged from 0.29 (SE 0.09) to 0.96 (SE 0.04). The probability that sites raided by elephants in primary period t would not be raided in primary period t + 1 varied with elevation gradient in different seasons and was influenced negatively by mean rainfall and village density and positively by distance to forests. Negative effects of rainfall variation and distance to forests best explained variation in the probability that sites not raided by elephants in primary period t would be raided in primary period t + 1. With our novel application of occupancy models, we teased apart the spatiotemporal drivers of conflicts from factors that influence how they are observed, thereby allowing more reliable inference on mechanisms underlying observed conflict patterns. We found that factors associated with increased crop accessibility and availability (e.g., distance to forests and rainfall patterns) were key drivers of elephant crop depredation dynamics. Such an understanding is essential for rigorous prediction of future conflicts, a critical requirement for effective conflict management in the context of increasing human-wildlife interactions. © 2015

  7. Functional analysis and applied optimization in Banach spaces applications to non-convex variational models

    CERN Document Server

    Botelho, Fabio

    2014-01-01

    This book introduces the basic concepts of real and functional analysis. It presents the fundamentals of the calculus of variations, convex analysis, duality, and optimization that are necessary to develop applications to physics and engineering problems. The book includes introductory and advanced concepts in measure and integration, as well as an introduction to Sobolev spaces. The problems presented are nonlinear, with non-convex variational formulation. Notably, the primal global minima may not be attained in some situations, in which cases the solution of the dual problem corresponds to an appropriate weak cluster point of minimizing sequences for the primal one. Indeed, the dual approach more readily facilitates numerical computations for some of the selected models. While intended primarily for applied mathematicians, the text will also be of interest to engineers, physicists, and other researchers in related fields.

  8. Simultaneous inference of selection and population growth from patterns of variation in the human genome

    DEFF Research Database (Denmark)

    Williamson, Scott H.; Hernandez, Ryan; Fledel-Alon, Adi

    2005-01-01

    Natural selection and demographic forces can have similar effects on patterns of DNA polymorphism. Therefore, to infer selection from samples of DNA sequences, one must simultaneously account for demographic effects. Here we take a model-based approach to this problem by developing predictions fo......-specific methods, and (iii) strong evidence for very recent population growth....... for patterns of polymorphism in the presence of both population size change and natural selection. If data are available from different functional classes of variation, and a priori information suggests that mutations in one of those classes are selectively neutral, then the putatively neutral class can...... this method to a large polymorphism data set from 301 human genes and find (i) widespread negative selection acting on standing nonsynonymous variation, (ii) that the fitness effects of nonsynonymous mutations are well predicted by several measures of amino acid exchangeability, especially site...

  9. Land cover variation and West Nile virus prevalence: Patterns, processes, and implications for disease control

    Science.gov (United States)

    Ezenwa, V.O.; Milheim, L.E.; Coffey, M.F.; Godsey, M.S.; King, R.J.; Guptill, S.C.

    2007-01-01

    Identifying links between environmental variables and infectious disease risk is essential to understanding how human-induced environmental changes will effect the dynamics of human and wildlife diseases. Although land cover change has often been tied to spatial variation in disease occurrence, the underlying factors driving the correlations are often unknown, limiting the applicability of these results for disease prevention and control. In this study, we described associations between land cover composition and West Nile virus (WNV) infection prevalence, and investigated three potential processes accounting for observed patterns: (1) variation in vector density; (2) variation in amplification host abundance; and (3) variation in host community composition. Interestingly, we found that WNV infection rates among Culex mosquitoes declined with increasing wetland cover, but wetland area was not significantly associated with either vector density or amplification host abundance. By contrast, wetland area was strongly correlated with host community composition, and model comparisons suggested that this factor accounted, at least partially, for the observed effect of wetland area on WNV infection risk. Our results suggest that preserving large wetland areas, and by extension, intact wetland bird communities, may represent a valuable ecosystem-based approach for controlling WNV outbreaks. ?? Mary Ann Liebert, Inc.

  10. Variational integrators in plasma physics

    International Nuclear Information System (INIS)

    Kraus, Michael

    2013-01-01

    To a large extent, research in plasma physics is concerned with the description and analysis of energy and momentum transfer between different scales and different kinds of waves. In the numerical modelling of such phenomena it appears to be crucial to describe the transfer processes preserving the underlying conservation laws in order to prevent physically spurious solutions. In this work, special numerical methods, so called variational integrators, are developed for several models of plasma physics. Special attention is given to conservation properties like conservation of energy and momentum. By design, variational integrators are applicable to all systems that have a Lagrangian formulation. Usually, equations of motion are derived by Hamilton's action principle and then discretised. In the application of the variational integrator theory, the order of these steps is reversed. At first, the Lagrangian and the accompanying variational principle are discretised, such that discrete equations of motion can be obtained directly by applying the discrete variational principle to the discrete Lagrangian. The advantage of this approach is that the resulting discretisation automatically retains the conservation properties of the continuous system. Following an overview of the geometric formulation of classical mechanics and field theory, which forms the basis of the variational integrator theory, variational integrators are introduced in a framework adapted to problems from plasma physics. The applicability of variational integrators is explored for several important models of plasma physics: particle dynamics (guiding centre dynamics), kinetic theory (the Vlasov-Poisson system) and fluid theory (magnetohydrodynamics). These systems, with the exception of guiding centre dynamics, do not possess a Lagrangian formulation to which the variational integrator methodology is directly applicable. Therefore the theory is extended by linking it to Ibragimov's theory of

  11. Process error rates in general research applications to the Human ...

    African Journals Online (AJOL)

    Objective. To examine process error rates in applications for ethics clearance of health research. Methods. Minutes of 586 general research applications made to a human health research ethics committee (HREC) from April 2008 to March 2009 were examined. Rates of approval were calculated and reasons for requiring ...

  12. Human-Induced Climate Variations Linked to Urbanization: From Observations to Modeling

    Science.gov (United States)

    Shepherd, J. Marshall; Jin, Menglin

    2004-01-01

    The goal of this session is to bring together scientists from interdisciplinary backgrounds to discuss the data, scientific approaches and recent results focusing on the impact of urbanization on the climate. The discussion will highlight current observational and modeling capabilities being employed for investigating the urban environment and its linkage to the change in the Earth's climate system. The goal of the session is to identify our current stand and the future direction on the topic. Urbanization is one of the extreme cases of land use change. Most of population of the world has moved to urban areas. By 1995, more than 70% of population of North America and Europe were living in cities. By 2025, the United Nations estimates that 60% of the worlds population will live in cities. Although currently only 1.2% of the land is urban, better understanding of how the atmosphere-ocean-land-biosphere components interact as a coupled system and the influence of human activities on this system is critical. Our understanding of urbanization effect is incomplete, partly because human activities induce new changes on climate in addition to the original natural variations, and partly because previously few data available for study urban effect globally. Urban construction changes surface roughness, albedo, heat capacity and vegetation coverage. Traffic and industry increase atmospheric aerosol. It is suggested that urbanization may modify rainfall processes through aerosol-cloud interactions or dynamic feedbacks. Because urbanization effect on climate is determined by many factors including land cover, the city's microscale features, population density, and human lifestyle patterns, it is necessary to study urban areas over globe.

  13. Experiences in the application of human factors engineering to human-system interface modernization

    International Nuclear Information System (INIS)

    Trueba Alonso, Pedro; Illobre, Luis Fernandez; Ortega Pascual, Fernando

    2014-01-01

    Almost all the existing Nuclear Power Plants (NPPs) include plans to modernize their existing Instrumentation and Control (I and C) systems and associated Human System Interfaces (HSIs), due to obsolescence problems. Tecnatom, S.A. has been participating in modernization programs in NPPs to help them to plan, specify, design and implement the modernization of control rooms and associated I and C and HSIs. The application of Human Factors Engineering (HFE) in modernization programs is nowadays unavoidable. This is because is becoming a regulatory requirement, and also because it is needed to ensure that any plant modification, involving the modernization of I and C and HSI, is well designed to improve overall plant operations, reliability, and safety. This paper shows some experiences obtained during the application of HFE to the modernization of these HSIs. The experience applying HFE in modernizations and design modifications show a positive effect, improving the associated HSIs, with the acceptability of the final user. (authors)

  14. Experiences in the application of human factors engineering to human-system interface modernization

    International Nuclear Information System (INIS)

    Trueba Alonso, Pedro; Fernandez Illobre, Luis; Ortega Pascual, Fernando

    2015-01-01

    Almost all the existing Nuclear Power Plants (NPPs) include plans to modernize their existing Instrumentation and Control (I and C) systems and associated Human System Interfaces (HSIs), due to obsolescence problems. Tecnatom, S.A. has been participating in modernization programs in NPPs to help them to plan, specify, design and implement the modernization of control rooms and associated I and C and HSIs. The application of Human Factors Engineering (HFE) in modernization programs is nowadays unavoidable. This is because is becoming a regulatory requirement, and also because it is needed to ensure that any plant modification, involving the modernization of I and C and HSI, is well designed to improve overall plant operations, reliability, and safety. This paper shows some experiences obtained during the application of HFE to the modernization of these HSIs. The experience applying HFE in modernizations and design modifications show a positive effect, improving the associated HSIs, with the acceptability of the final user.

  15. Experiences in the application of human factors engineering to human-system interface modernization

    Energy Technology Data Exchange (ETDEWEB)

    Trueba Alonso, Pedro; Fernandez Illobre, Luis; Ortega Pascual, Fernando [Tecnatom S.A., San Sebastian de los Reyes (Spain). Simulation and Control Rooms Div.

    2015-07-15

    Almost all the existing Nuclear Power Plants (NPPs) include plans to modernize their existing Instrumentation and Control (I and C) systems and associated Human System Interfaces (HSIs), due to obsolescence problems. Tecnatom, S.A. has been participating in modernization programs in NPPs to help them to plan, specify, design and implement the modernization of control rooms and associated I and C and HSIs. The application of Human Factors Engineering (HFE) in modernization programs is nowadays unavoidable. This is because is becoming a regulatory requirement, and also because it is needed to ensure that any plant modification, involving the modernization of I and C and HSI, is well designed to improve overall plant operations, reliability, and safety. This paper shows some experiences obtained during the application of HFE to the modernization of these HSIs. The experience applying HFE in modernizations and design modifications show a positive effect, improving the associated HSIs, with the acceptability of the final user.

  16. Inter- and Intraspecific Variations in the Pectoral Muscles of Common Chimpanzees (Pan troglodytes), Bonobos (Pan paniscus), and Humans (Homo sapiens).

    Science.gov (United States)

    Potau, J M; Arias-Martorell, J; Bello-Hellegouarch, G; Casado, A; Pastor, J F; de Paz, F; Diogo, R

    2018-01-01

    We have analyzed anatomic variations in the pectoralis major and pectoralis minor muscles of common chimpanzees (Pan troglodytes) and bonobos (Pan paniscus) and compared them to anatomic variations in these muscles in humans (Homo sapiens) . We have macroscopically dissected these muscles in six adult Pan troglodytes , five Pan paniscus of ages ranging from fetus to adult, and five adult Homo sapiens . Although Pan troglodytes are thought to lack a separate pectoralis abdominis muscle, we have identified this muscle in three of the Pan troglodytes ; none of the Pan paniscus , however, had this muscle. We have also found deep supernumerary fascicles in the pectoralis major of two Pan troglodytes and all five Pan paniscus . In all six Pan troglodytes , the pectoralis minor was inserted at the supraspinatus tendon, while, in Pan paniscus and Homo sapiens , it was inserted at the coracoid process of the scapula. Some of the anatomic features and variations of these muscles in common chimpanzees and bonobos are similar to those found in humans, therefore enhancing our knowledge of primate comparative anatomy and evolution and also shedding light on several clinical issues.

  17. Inter- and Intraspecific Variations in the Pectoral Muscles of Common Chimpanzees (Pan troglodytes, Bonobos (Pan paniscus, and Humans (Homo sapiens

    Directory of Open Access Journals (Sweden)

    J. M. Potau

    2018-01-01

    Full Text Available We have analyzed anatomic variations in the pectoralis major and pectoralis minor muscles of common chimpanzees (Pan troglodytes and bonobos (Pan paniscus and compared them to anatomic variations in these muscles in humans (Homo sapiens. We have macroscopically dissected these muscles in six adult Pan troglodytes, five Pan paniscus of ages ranging from fetus to adult, and five adult Homo sapiens. Although Pan troglodytes are thought to lack a separate pectoralis abdominis muscle, we have identified this muscle in three of the Pan troglodytes; none of the Pan paniscus, however, had this muscle. We have also found deep supernumerary fascicles in the pectoralis major of two Pan troglodytes and all five Pan paniscus. In all six Pan troglodytes, the pectoralis minor was inserted at the supraspinatus tendon, while, in Pan paniscus and Homo sapiens, it was inserted at the coracoid process of the scapula. Some of the anatomic features and variations of these muscles in common chimpanzees and bonobos are similar to those found in humans, therefore enhancing our knowledge of primate comparative anatomy and evolution and also shedding light on several clinical issues.

  18. Application of the Human Activity Assistive Technology model for occupational therapy research.

    Science.gov (United States)

    Giesbrecht, Ed

    2013-08-01

    Theoretical models provide a framework for describing practice and integrating evidence into systematic research. There are few models that relate specifically to the provision of assistive technology in occupational therapy practice. The Human Activity Assistive Technology model is an enduring example that has continued to develop by integrating a social model of disability, concepts from occupational therapy theory and principles of assistive technology adoption and abandonment. This study first describes the core concepts of the Human Activity Assistive Technology model and reviews its development over three successive published versions. A review of the research literature reflects application of the model to clinical practice, study design, outcome measure selection and interpretation of results, particularly among occupational therapists. An evaluative framework is used to critique the adequacy of the Human Activity Assistive Technology model for practice and research, exploring attributes of clarity, simplicity, generality, accessibility and importance. Finally, recommendations are proposed for continued development of the model and research applications. Most of the existing research literature employs the Human Activity Assistive Technology model for background and study design; there is emerging evidence to support the core concepts as predictive factors. Although the concepts are generally simple, clear and applicable to occupational therapy practice and research, evolving terminology and outcomes become more complex with the conflation of integrated theories. The development of the Human Activity Assistive Technology model offers enhanced access and application for occupational therapists, but poses challenges to clarity among concepts. Suggestions are made for further development and applications of the model. © 2013 Occupational Therapy Australia.

  19. Meta-analysis of genome-wide association studies identifies 8 novel loci involved in shape variation of human head hair

    Science.gov (United States)

    Liu, Fan; Chen, Yan; Zhu, Gu; Hysi, Pirro G; Wu, Sijie; Adhikari, Kaustubh; Breslin, Krystal; Pośpiech, Ewelina; Hamer, Merel A; Peng, Fuduan; Muralidharan, Charanya; Acuna-Alonzo, Victor; Canizales-Quinteros, Samuel; Bedoya, Gabriel; Gallo, Carla; Poletti, Giovanni; Rothhammer, Francisco; Bortolini, Maria Catira; Gonzalez-Jose, Rolando; Zeng, Changqing; Xu, Shuhua; Jin, Li; Uitterlinden, André G; Ikram, M Arfan; van Duijn, Cornelia M; Nijsten, Tamar; Walsh, Susan; Branicki, Wojciech; Wang, Sijia; Ruiz-Linares, Andrés; Spector, Timothy D; Martin, Nicholas G; Medland, Sarah E; Kayser, Manfred

    2018-01-01

    Abstract Shape variation of human head hair shows striking variation within and between human populations, while its genetic basis is far from being understood. We performed a series of genome-wide association studies (GWASs) and replication studies in a total of 28 964 subjects from 9 cohorts from multiple geographic origins. A meta-analysis of three European GWASs identified 8 novel loci (1p36.23 ERRFI1/SLC45A1, 1p36.22 PEX14, 1p36.13 PADI3, 2p13.3 TGFA, 11p14.1 LGR4, 12q13.13 HOXC13, 17q21.2 KRTAP, and 20q13.33 PTK6), and confirmed 4 previously known ones (1q21.3 TCHH/TCHHL1/LCE3E, 2q35 WNT10A, 4q21.21 FRAS1, and 10p14 LINC00708/GATA3), all showing genome-wide significant association with hair shape (P < 5e-8). All except one (1p36.22 PEX14) were replicated with nominal significance in at least one of the 6 additional cohorts of European, Native American and East Asian origins. Three additional previously known genes (EDAR, OFCC1, and PRSS53) were confirmed at the nominal significance level. A multivariable regression model revealed that 14 SNPs from different genes significantly and independently contribute to hair shape variation, reaching a cross-validated AUC value of 0.66 (95% CI: 0.62–0.70) and an AUC value of 0.64 in an independent validation cohort, providing an improved accuracy compared with a previous model. Prediction outcomes of 2504 individuals from a multiethnic sample were largely consistent with general knowledge on the global distribution of hair shape variation. Our study thus delivers target genes and DNA variants for future functional studies to further evaluate the molecular basis of hair shape in humans. PMID:29220522

  20. Meta-analysis of genome-wide association studies identifies 8 novel loci involved in shape variation of human head hair.

    Science.gov (United States)

    Liu, Fan; Chen, Yan; Zhu, Gu; Hysi, Pirro G; Wu, Sijie; Adhikari, Kaustubh; Breslin, Krystal; Pospiech, Ewelina; Hamer, Merel A; Peng, Fuduan; Muralidharan, Charanya; Acuna-Alonzo, Victor; Canizales-Quinteros, Samuel; Bedoya, Gabriel; Gallo, Carla; Poletti, Giovanni; Rothhammer, Francisco; Bortolini, Maria Catira; Gonzalez-Jose, Rolando; Zeng, Changqing; Xu, Shuhua; Jin, Li; Uitterlinden, André G; Ikram, M Arfan; van Duijn, Cornelia M; Nijsten, Tamar; Walsh, Susan; Branicki, Wojciech; Wang, Sijia; Ruiz-Linares, Andrés; Spector, Timothy D; Martin, Nicholas G; Medland, Sarah E; Kayser, Manfred

    2018-02-01

    Shape variation of human head hair shows striking variation within and between human populations, while its genetic basis is far from being understood. We performed a series of genome-wide association studies (GWASs) and replication studies in a total of 28 964 subjects from 9 cohorts from multiple geographic origins. A meta-analysis of three European GWASs identified 8 novel loci (1p36.23 ERRFI1/SLC45A1, 1p36.22 PEX14, 1p36.13 PADI3, 2p13.3 TGFA, 11p14.1 LGR4, 12q13.13 HOXC13, 17q21.2 KRTAP, and 20q13.33 PTK6), and confirmed 4 previously known ones (1q21.3 TCHH/TCHHL1/LCE3E, 2q35 WNT10A, 4q21.21 FRAS1, and 10p14 LINC00708/GATA3), all showing genome-wide significant association with hair shape (P 5e-8). All except one (1p36.22 PEX14) were replicated with nominal significance in at least one of the 6 additional cohorts of European, Native American and East Asian origins. Three additional previously known genes (EDAR, OFCC1, and PRSS53) were confirmed at the nominal significance level. A multivariable regression model revealed that 14 SNPs from different genes significantly and independently contribute to hair shape variation, reaching a cross-validated AUC value of 0.66 (95% CI: 0.62-0.70) and an AUC value of 0.64 in an independent validation cohort, providing an improved accuracy compared with a previous model. Prediction outcomes of 2504 individuals from a multiethnic sample were largely consistent with general knowledge on the global distribution of hair shape variation. Our study thus delivers target genes and DNA variants for future functional studies to further evaluate the molecular basis of hair shape in humans. © The Author(s) 2017. Published by Oxford University Press.

  1. Experimental evaluation of multimodal human computer interface for tactical audio applications

    NARCIS (Netherlands)

    Obrenovic, Z.; Starcevic, D.; Jovanov, E.; Oy, S.

    2002-01-01

    Mission critical and information overwhelming applications require careful design of the human computer interface. Typical applications include night vision or low visibility mission navigation, guidance through a hostile territory, and flight navigation and orientation. Additional channels of

  2. Development of a Combined In Vitro Physiologically Based Kinetic (PBK) and Monte Carlo Modelling Approach to Predict Interindividual Human Variation in Phenol-Induced Developmental Toxicity.

    Science.gov (United States)

    Strikwold, Marije; Spenkelink, Bert; Woutersen, Ruud A; Rietjens, Ivonne M C M; Punt, Ans

    2017-06-01

    With our recently developed in vitro physiologically based kinetic (PBK) modelling approach, we could extrapolate in vitro toxicity data to human toxicity values applying PBK-based reverse dosimetry. Ideally information on kinetic differences among human individuals within a population should be considered. In the present study, we demonstrated a modelling approach that integrated in vitro toxicity data, PBK modelling and Monte Carlo simulations to obtain insight in interindividual human kinetic variation and derive chemical specific adjustment factors (CSAFs) for phenol-induced developmental toxicity. The present study revealed that UGT1A6 is the primary enzyme responsible for the glucuronidation of phenol in humans followed by UGT1A9. Monte Carlo simulations were performed taking into account interindividual variation in glucuronidation by these specific UGTs and in the oral absorption coefficient. Linking Monte Carlo simulations with PBK modelling, population variability in the maximum plasma concentration of phenol for the human population could be predicted. This approach provided a CSAF for interindividual variation of 2.0 which covers the 99th percentile of the population, which is lower than the default safety factor of 3.16 for interindividual human kinetic differences. Dividing the dose-response curve data obtained with in vitro PBK-based reverse dosimetry, with the CSAF provided a dose-response curve that reflects the consequences of the interindividual variability in phenol kinetics for the developmental toxicity of phenol. The strength of the presented approach is that it provides insight in the effect of interindividual variation in kinetics for phenol-induced developmental toxicity, based on only in vitro and in silico testing. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

    KAUST Repository

    Cui, Peng; Ding, Feng; Lin, Qiang; Zhang, Lingfang; Li, Ang; Zhang, Zhang; Hu, Songnian; Yu, Jun

    2012-01-01

    Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

  4. Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

    KAUST Repository

    Cui, Peng

    2012-03-23

    Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

  5. Application of four anti-human interferon-alpha monoclonal antibodies for immunoassay and comparative analysis of natural interferon-alpha mixtures

    International Nuclear Information System (INIS)

    Andersson, G.; Lundgren, E.; Ekre, H.P.

    1991-01-01

    Four different mouse monoclonal antibodies to human interferon-alpha (IFN-alpha) were evaluated for application in quantitative and comparative analysis of natural IFN-alpha mixtures. Binding to IFN-alpha subtypes in solution revealed individual reactivity patterns. These patterns changed if the IFN-alpha molecules were immobilized either passively to a surface or bound by another antibody. Also, substitution of a single amino acid in IFN-alpha 2 affected the binding, apparently by altering the conformation. Isoelectric focusing of three natural IFN-alpha preparations from different sources, followed by immunoblotting, resulted in individual patterns with each of the four mAbs and also demonstrated variation in the composition of the IFN-alpha preparations. None of the mAbs was subtype specific, but by combining the different mAbs, and also applying polyclonal anti-human IFN-alpha antibodies, it was possible to design sensitive sandwich ELISAs with broad or more limited IFN-alpha subtype specificity

  6. Cyclic Variations in Sustained Human Performance

    Science.gov (United States)

    Aue, William R.; Arruda, James E.; Kass, Steven J.; Stanny, Claudia J.

    2009-01-01

    Biological rhythms play a prominent role in the modulation of human physiology and behavior. [Smith, K., Valentino, D., & Arruda, J. (2003). "Rhythmic oscillations in the performance of a sustained attention task." "Journal of Clinical and Experimental Neuropsychology," 25, 561-570] suggested that sustained human performance may systematically…

  7. Evolutionary perspectives on human height variation

    NARCIS (Netherlands)

    Stulp, Gert; Barrett, Louise

    Human height is a highly variable trait, both within and between populations, has a high heritability, and influences the manner in which people behave and are treated in society. Although we know much about human height, this information has rarely been brought together in a comprehensive,

  8. Reference free phasing and representation of complex variation

    DEFF Research Database (Denmark)

    Jensen, Jacob Malte

    2017-01-01

    High throughput sequencing has revolutionized our ability to interrogate genomes and entire human genomes are sequenced daily across the world. Mapping of short reads to a reference genome has enhanced our ability to detect genetic variation and is currently the most widely used technology....... Therefore, new methods for detecting variation that reduce reference bias are needed including ways of representing genomes that account for the variability within and between populations. The major histocompatibility complex (MHC) region is one of the most diverse and complex regions of the human genome...... to detect and call variation in humans. However, it has become evident that mapping of short reads to a single reference genome is subject to ascertainment bias (reference bias). This bias is especially pronounced in complex regions of the genome and particularly hampers detection of structural variation...

  9. A Rare Variation of the Human Median Nerve Direction

    Directory of Open Access Journals (Sweden)

    Barfi

    2016-04-01

    Full Text Available Introduction The brachial plexus, a complex network of nerves, innervates to the upper limbs. Variation in the course of the nerves in the upper limb is common. Case Presentation This paper describes two cases of upper limb variations in a cadaver dissected at Lorestan University of Medical Sciences. In the first variation, the median nerve in the arm has a different route, so that the median moves deep into the brachialis muscle. In the latter case, after piercing the coracobrachialis muscle a musculocutaneous nerve exists between the brachialis and biceps and goes to the lateral region of the forearm. This is known as the lateral cutaneous nerve of the forearm nerve, and innervates the skin of the lateral part of the forearm and the dorsal part of the hand. Conclusions Because of the possibility of damage to the brachial plexus branches is high in upper limb injuries and surgeries, full knowledge of normal anatomy and variations of these branches is essential for orthopedic specialists, neurosurgeons, radiologists, and anatomists.

  10. Human-specific HERV-K insertion causes genomic variations in the human genome.

    Directory of Open Access Journals (Sweden)

    Wonseok Shin

    Full Text Available Human endogenous retroviruses (HERV sequences account for about 8% of the human genome. Through comparative genomics and literature mining, we identified a total of 29 human-specific HERV-K insertions. We characterized them focusing on their structure and flanking sequence. The results showed that four of the human-specific HERV-K insertions deleted human genomic sequences via non-classical insertion mechanisms. Interestingly, two of the human-specific HERV-K insertion loci contained two HERV-K internals and three LTR elements, a pattern which could be explained by LTR-LTR ectopic recombination or template switching. In addition, we conducted a polymorphic test and observed that twelve out of the 29 elements are polymorphic in the human population. In conclusion, human-specific HERV-K elements have inserted into human genome since the divergence of human and chimpanzee, causing human genomic changes. Thus, we believe that human-specific HERV-K activity has contributed to the genomic divergence between humans and chimpanzees, as well as within the human population.

  11. Variation tolerant SoC design

    Science.gov (United States)

    Kozhikkottu, Vivek J.

    The scaling of integrated circuits into the nanometer regime has led to variations emerging as a primary concern for designers of integrated circuits. Variations are an inevitable consequence of the semiconductor manufacturing process, and also arise due to the side-effects of operation of integrated circuits (voltage, temperature, and aging). Conventional design approaches, which are based on design corners or worst-case scenarios, leave designers with an undesirable choice between the considerable overheads associated with over-design and significantly reduced manufacturing yield. Techniques for variation-tolerant design at the logic, circuit and layout levels of the design process have been developed and are in commercial use. However, with the incessant increase in variations due to technology scaling and design trends such as near-threshold computing, these techniques are no longer sufficient to contain the effects of variations, and there is a need to address variations at all stages of design. This thesis addresses the problem of variation-tolerant design at the earliest stages of the design process, where the system-level design decisions that are made can have a very significant impact. There are two key aspects to making system-level design variation-aware. First, analysis techniques must be developed to project the impact of variations on system-level metrics such as application performance and energy. Second, variation-tolerant design techniques need to be developed to absorb the residual impact of variations (that cannot be contained through lower-level techniques). In this thesis, we address both these facets by developing robust and scalable variation-aware analysis and variation mitigation techniques at the system level. The first contribution of this thesis is a variation-aware system-level performance analysis framework. We address the key challenge of translating the per-component clock frequency distributions into a system-level application

  12. A sample application of nuclear power human resources model

    International Nuclear Information System (INIS)

    Gurgen, A.; Ergun, S.

    2016-01-01

    One of the most important issues for a new comer country initializing the nuclear power plant projects is to have both quantitative and qualitative models for the human resources development. For the quantitative model of human resources development for Turkey, “Nuclear Power Human Resources (NPHR) Model” developed by the Los Alamos National Laboratory was used to determine the number of people that will be required from different professional or occupational fields in the planning of human resources for Akkuyu, Sinop and the third nuclear power plant projects. The number of people required for different professions for the Nuclear Energy Project Implementation Department, the regulatory authority, project companies, construction, nuclear power plants and the academy were calculated. In this study, a sample application of the human resources model is presented. The results of the first tries to calculate the human resources needs of Turkey were obtained. Keywords: Human Resources Development, New Comer Country, NPHR Model

  13. Apparent Transition in the Human Height Distribution Caused by Age-Dependent Variation during Puberty Period

    Science.gov (United States)

    Iwata, Takaki; Yamazaki, Yoshihiro; Kuninaka, Hiroto

    2013-08-01

    In this study, we examine the validity of the transition of the human height distribution from the log-normal distribution to the normal distribution during puberty, as suggested in an earlier study [Kuninaka et al.: J. Phys. Soc. Jpn. 78 (2009) 125001]. Our data analysis reveals that, in late puberty, the variation in height decreases as children grow. Thus, the classification of a height dataset by age at this stage leads us to analyze a mixture of distributions with larger means and smaller variations. This mixture distribution has a negative skewness and is consequently closer to the normal distribution than to the log-normal distribution. The opposite case occurs in early puberty and the mixture distribution is positively skewed, which resembles the log-normal distribution rather than the normal distribution. Thus, this scenario mimics the transition during puberty. Additionally, our scenario is realized through a numerical simulation based on a statistical model. The present study does not support the transition suggested by the earlier study.

  14. Prebiotics from marine macroalgae for human and animal health applications.

    LENUS (Irish Health Repository)

    O'Sullivan, Laurie

    2010-01-01

    The marine environment is an untapped source of bioactive compounds. Specifically, marine macroalgae (seaweeds) are rich in polysaccharides that could potentially be exploited as prebiotic functional ingredients for both human and animal health applications. Prebiotics are non-digestible, selectively fermented compounds that stimulate the growth and\\/or activity of beneficial gut microbiota which, in turn, confer health benefits on the host. This review will introduce the concept and potential applications of prebiotics, followed by an outline of the chemistry of seaweed polysaccharides. Their potential for use as prebiotics for both humans and animals will be highlighted by reviewing data from both in vitro and in vivo studies conducted to date.

  15. Variation in population exposure in China as a result of differing human activities

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Z.Q. [China Atomic Energy Authority, Beijing (China). Bureau of Safety, Protection and Health; Guo, M.Q. [China Nuclear Industry Huaqing Company, Beijing (China)

    1995-08-01

    The necessity of studying the variations in radiation levels dispassionately is discussed. Human activities may increase, but can also decrease, radiation dose to the population. Travel by air may cause a rise in population collective dose by 3.6 x 10 man.Sv, and travel by ship, train and vehicle may lead to a drop of 5.36 x 10{sup 2} man.Sv. Dwellings of coal cinder brick may increase collective dose by 3.5 x 10{sup 3} man.Sv, and buildings of reinforced concrete may decrease collective dose by 3.7 x 10{sup 3} man.Sv. It is inadequate to study only those activities which may increase radiation levels. (author).

  16. The biological effects of quadripolar radiofrequency sequential application: a human experimental study.

    Science.gov (United States)

    Nicoletti, Giovanni; Cornaglia, Antonia Icaro; Faga, Angela; Scevola, Silvia

    2014-10-01

    An experimental study was conducted to assess the effectiveness and safety of an innovative quadripolar variable electrode configuration radiofrequency device with objective measurements in an ex vivo and in vivo human experimental model. Nonablative radiofrequency applications are well-established anti-ageing procedures for cosmetic skin tightening. The study was performed in two steps: ex vivo and in vivo assessments. In the ex vivo assessments the radiofrequency applications were performed on human full-thickness skin and subcutaneous tissue specimens harvested during surgery for body contouring. In the in vivo assessments the applications were performed on two volunteer patients scheduled for body contouring surgery at the end of the study. The assessment methods were: clinical examination and medical photography, temperature measurement with thermal imaging scan, and light microscopy histological examination. The ex vivo assessments allowed for identification of the effective safety range for human application. The in vivo assessments allowed for demonstration of the biological effects of sequential radiofrequency applications. After a course of radiofrequency applications, the collagen fibers underwent an immediate heat-induced rearrangement and were partially denaturated and progressively metabolized by the macrophages. An overall thickening and spatial rearrangement was appreciated both in the collagen and elastic fibers, the latter displaying a juvenile reticular pattern. A late onset in the macrophage activation after sequential radiofrequency applications was appreciated. Our data confirm the effectiveness of sequential radiofrequency applications in obtaining attenuation of the skin wrinkles by an overall skin tightening.

  17. Rethinking the starch digestion hypothesis for AMY1 copy number variation in humans.

    Science.gov (United States)

    Fernández, Catalina I; Wiley, Andrea S

    2017-08-01

    Alpha-amylase exists across taxonomic kingdoms with a deep evolutionary history of gene duplications that resulted in several α-amylase paralogs. Copy number variation (CNV) in the salivary α-amylase gene (AMY1) exists in many taxa, but among primates, humans appear to have higher average AMY1 copies than nonhuman primates. Additionally, AMY1 CNV in humans has been associated with starch content of diets, and one known function of α-amylase is its involvement in starch digestion. Thus high AMY1 CNV is considered to result from selection favoring more efficient starch digestion in the Homo lineage. Here, we present several lines of evidence that challenge the hypothesis that increased AMY1 CNV is an adaptation to starch consumption. We observe that α- amylase plays a very limited role in starch digestion, with additional steps required for starch digestion and glucose metabolism. Specifically, we note that α-amylase hydrolysis only produces a minute amount of free glucose with further enzymatic digestion and glucose absorption being rate-limiting steps for glucose availability. Indeed α-amylase is nonessential for starch digestion since sucrase-isomaltase and maltase-glucoamylase can hydrolyze whole starch granules while releasing glucose. While higher AMY1 CN and CNV among human populations may result from natural selection, existing evidence does not support starch digestion as the major selective force. We report that in humans α-amylase is expressed in several other tissues where it may have potential roles of evolutionary significance. © 2017 Wiley Periodicals, Inc.

  18. Novel association strategy with copy number variation for identifying new risk Loci of human diseases.

    Directory of Open Access Journals (Sweden)

    Xianfeng Chen

    2010-08-01

    Full Text Available Copy number variations (CNV are important causal genetic variations for human disease; however, the lack of a statistical model has impeded the systematic testing of CNVs associated with disease in large-scale cohort.Here, we developed a novel integrated strategy to test CNV-association in genome-wide case-control studies. We converted the single-nucleotide polymorphism (SNP signal to copy number states using a well-trained hidden Markov model. We mapped the susceptible CNV-loci through SNP site-specific testing to cope with the physiological complexity of CNVs. We also ensured the credibility of the associated CNVs through further window-based CNV-pattern clustering. Genome-wide data with seven diseases were used to test our strategy and, in total, we identified 36 new susceptible loci that are associated with CNVs for the seven diseases: 5 with bipolar disorder, 4 with coronary artery disease, 1 with Crohn's disease, 7 with hypertension, 9 with rheumatoid arthritis, 7 with type 1 diabetes and 3 with type 2 diabetes. Fifteen of these identified loci were validated through genotype-association and physiological function from previous studies, which provide further confidence for our results. Notably, the genes associated with bipolar disorder converged in the phosphoinositide/calcium signaling, a well-known affected pathway in bipolar disorder, which further supports that CNVs have impact on bipolar disorder.Our results demonstrated the effectiveness and robustness of our CNV-association analysis and provided an alternative avenue for discovering new associated loci of human diseases.

  19. Variational integrators in plasma physics

    Energy Technology Data Exchange (ETDEWEB)

    Kraus, Michael

    2013-07-01

    To a large extent, research in plasma physics is concerned with the description and analysis of energy and momentum transfer between different scales and different kinds of waves. In the numerical modelling of such phenomena it appears to be crucial to describe the transfer processes preserving the underlying conservation laws in order to prevent physically spurious solutions. In this work, special numerical methods, so called variational integrators, are developed for several models of plasma physics. Special attention is given to conservation properties like conservation of energy and momentum. By design, variational integrators are applicable to all systems that have a Lagrangian formulation. Usually, equations of motion are derived by Hamilton's action principle and then discretised. In the application of the variational integrator theory, the order of these steps is reversed. At first, the Lagrangian and the accompanying variational principle are discretised, such that discrete equations of motion can be obtained directly by applying the discrete variational principle to the discrete Lagrangian. The advantage of this approach is that the resulting discretisation automatically retains the conservation properties of the continuous system. Following an overview of the geometric formulation of classical mechanics and field theory, which forms the basis of the variational integrator theory, variational integrators are introduced in a framework adapted to problems from plasma physics. The applicability of variational integrators is explored for several important models of plasma physics: particle dynamics (guiding centre dynamics), kinetic theory (the Vlasov-Poisson system) and fluid theory (magnetohydrodynamics). These systems, with the exception of guiding centre dynamics, do not possess a Lagrangian formulation to which the variational integrator methodology is directly applicable. Therefore the theory is extended by linking it to Ibragimov's theory of

  20. Variations of the candidate SEZ6L2 gene on Chromosome 16p11.2 in patients with autism spectrum disorders and in human populations.

    Directory of Open Access Journals (Sweden)

    Marina Konyukh

    Full Text Available BACKGROUND: Autism spectrum disorders (ASD are a group of severe childhood neurodevelopmental disorders with still unknown etiology. One of the most frequently reported associations is the presence of recurrent de novo or inherited microdeletions and microduplications on chromosome 16p11.2. The analysis of rare variations of 8 candidate genes among the 27 genes located in this region suggested SEZ6L2 as a compelling candidate. METHODOLOGY/PRINCIPAL FINDINGS: We further explored the role of SEZ6L2 variations by screening its coding part in a group of 452 individuals, including 170 patients with ASD and 282 individuals from different ethnic backgrounds of the Human Genome Diversity Panel (HGDP, complementing the previously reported screening. We detected 7 previously unidentified non-synonymous variations of SEZ6L2 in ASD patients. We also identified 6 non-synonymous variations present only in HGDP. When we merged our results with the previously published, no enrichment of non-synonymous variation in SEZ6L2 was observed in the ASD group compared with controls. CONCLUSIONS/SIGNIFICANCE: Our results provide an extensive ascertainment of the genetic variability of SEZ6L2 in human populations and do not support a major role for SEZ6L2 sequence variations in the susceptibility to ASD.

  1. Marine Enzymes: Production and Applications for Human Health.

    Science.gov (United States)

    Rao, T Eswara; Imchen, M; Kumavath, R

    Marine microbial enzymes have wide applications in bioindustries. Selection of microorganisms for enzyme production at the industrial level requires good yield and high production rate. A number of enzymes such as amylase, caseinase, lipase, gelatinase, and DNases have been discovered from microbes isolated from extreme marine environments. Such enzymes are thermostable, tolerant to a varied range of pH and other harsh conditions required in industrial applications. Novelty in their structure and characteristics has shown promising scope to the researchers in academia and industry. In this chapter, we present a bird's eye view on recent research works in the field of enzyme production from marine origin as well as their potential biological applications relevant to human health. © 2017 Elsevier Inc. All rights reserved.

  2. Variational principles of continuum mechanics II applications

    CERN Document Server

    Berdichevsky, Victor L

    2009-01-01

    This concise and understandable book about variational principles of continuum mechanics presents the classical models. The book is accessible to applied mathematicians, physicists and engineers who have an interest in continuum mechanics.

  3. Prebiotics from Marine Macroalgae for Human and Animal Health Applications

    Science.gov (United States)

    O’Sullivan, Laurie; Murphy, Brian; McLoughlin, Peter; Duggan, Patrick; Lawlor, Peadar G.; Hughes, Helen; Gardiner, Gillian E.

    2010-01-01

    The marine environment is an untapped source of bioactive compounds. Specifically, marine macroalgae (seaweeds) are rich in polysaccharides that could potentially be exploited as prebiotic functional ingredients for both human and animal health applications. Prebiotics are non-digestible, selectively fermented compounds that stimulate the growth and/or activity of beneficial gut microbiota which, in turn, confer health benefits on the host. This review will introduce the concept and potential applications of prebiotics, followed by an outline of the chemistry of seaweed polysaccharides. Their potential for use as prebiotics for both humans and animals will be highlighted by reviewing data from both in vitro and in vivo studies conducted to date. PMID:20714423

  4. Techniques and applications of the human reliability analysis in nuclear facilities

    International Nuclear Information System (INIS)

    Pinto, Fausto C.

    1995-01-01

    The analysis and prediction of the man-machine interaction are the objectives of human reliability analysis. In this work is presented in a manner that could be used by experts in the field of Probabilistic Safety Assessment, considering primarily the aspects of human errors. The Technique of Human Error Rate Prediction (THERP) is used in large scale to obtain data on human error. Applications of this technique are presented, as well as aspects of the state-of-art and of research and development of this particular field of work, where the construction of a reliable data bank is considered essential. In this work is also developed an application of the THERP for the TRIGA Mark 1 IPR R-1 Reactor of the Centro de Desenvolvimento de Tecnologia Nuclear, Brazilian research institute of nuclear technology. The results indicate that some changes must be made in the emergency procedures of the reactor, in order to achieve a higher level of safety

  5. Rib Geometry Explains Variation in Dynamic Structural Response: Potential Implications for Frontal Impact Fracture Risk.

    Science.gov (United States)

    Murach, Michelle M; Kang, Yun-Seok; Goldman, Samuel D; Schafman, Michelle A; Schlecht, Stephen H; Moorhouse, Kevin; Bolte, John H; Agnew, Amanda M

    2017-09-01

    The human thorax is commonly injured in motor vehicle crashes, and despite advancements in occupant safety rib fractures are highly prevalent. The objective of this study was to quantify the ability of gross and cross-sectional geometry, separately and in combination, to explain variation of human rib structural properties. One hundred and twenty-two whole mid-level ribs from 76 fresh post-mortem human subjects were tested in a dynamic frontal impact scenario. Structural properties (peak force and stiffness) were successfully predicted (p rib cross-sectional geometry obtained via direct histological imaging (total area, cortical area, and section modulus) and were improved further when utilizing a combination of cross-sectional and gross geometry (robusticity, whole bone strength index). Additionally, preliminary application of a novel, adaptive thresholding technique, allowed for total area and robusticity to be measured on a subsample of standard clinical CT scans with varied success. These results can be used to understand variation in individual rib response to frontal loading as well as identify important geometric parameters, which could ultimately improve injury criteria as well as the biofidelity of anthropomorphic test devices (ATDs) and finite element (FE) models of the human thorax.

  6. Visualisation of Massive Military Datasets: Human Factors, Applications, and Technologies

    Science.gov (United States)

    2001-05-01

    we have been confronted with data of new kinds at a rate faster than our human brains can manage to turn into information. “Visualisation” means the...because variation of these kinds do not have the qaulities of textons. Figure 2.5 A trivial Icon Map in which there is a data attribute, shown as...information management is to ensure that the right information is available to the right person, at the right time, and shown in such a way that the person

  7. Variational methods in molecular modeling

    CERN Document Server

    2017-01-01

    This book presents tutorial overviews for many applications of variational methods to molecular modeling. Topics discussed include the Gibbs-Bogoliubov-Feynman variational principle, square-gradient models, classical density functional theories, self-consistent-field theories, phase-field methods, Ginzburg-Landau and Helfrich-type phenomenological models, dynamical density functional theory, and variational Monte Carlo methods. Illustrative examples are given to facilitate understanding of the basic concepts and quantitative prediction of the properties and rich behavior of diverse many-body systems ranging from inhomogeneous fluids, electrolytes and ionic liquids in micropores, colloidal dispersions, liquid crystals, polymer blends, lipid membranes, microemulsions, magnetic materials and high-temperature superconductors. All chapters are written by leading experts in the field and illustrated with tutorial examples for their practical applications to specific subjects. With emphasis placed on physical unders...

  8. Genetic analysis of variation in human meiotic recombination.

    Directory of Open Access Journals (Sweden)

    Reshmi Chowdhury

    2009-09-01

    Full Text Available The number of recombination events per meiosis varies extensively among individuals. This recombination phenotype differs between female and male, and also among individuals of each gender. In this study, we used high-density SNP genotypes of over 2,300 individuals and their offspring in two datasets to characterize recombination landscape and to map the genetic variants that contribute to variation in recombination phenotypes. We found six genetic loci that are associated with recombination phenotypes. Two of these (RNF212 and an inversion on chromosome 17q21.31 were previously reported in the Icelandic population, and this is the first replication in any other population. Of the four newly identified loci (KIAA1462, PDZK1, UGCG, NUB1, results from expression studies provide support for their roles in meiosis. Each of the variants that we identified explains only a small fraction of the individual variation in recombination. Notably, we found different sequence variants associated with female and male recombination phenotypes, suggesting that they are regulated by different genes. Characterization of genetic variants that influence natural variation in meiotic recombination will lead to a better understanding of normal meiotic events as well as of non-disjunction, the primary cause of pregnancy loss.

  9. Applications of human error analysis to aviation and space operations

    International Nuclear Information System (INIS)

    Nelson, W.R.

    1998-01-01

    For the past several years at the Idaho National Engineering and Environmental Laboratory (INEEL) we have been working to apply methods of human error analysis to the design of complex systems. We have focused on adapting human reliability analysis (HRA) methods that were developed for Probabilistic Safety Assessment (PSA) for application to system design. We are developing methods so that human errors can be systematically identified during system design, the potential consequences of each error can be assessed, and potential corrective actions (e.g. changes to system design or procedures) can be identified. These applications lead to different requirements when compared with HR.As performed as part of a PSA. For example, because the analysis will begin early during the design stage, the methods must be usable when only partial design information is available. In addition, the ability to perform numerous ''what if'' analyses to identify and compare multiple design alternatives is essential. Finally, since the goals of such human error analyses focus on proactive design changes rather than the estimate of failure probabilities for PRA, there is more emphasis on qualitative evaluations of error relationships and causal factors than on quantitative estimates of error frequency. The primary vehicle we have used to develop and apply these methods has been a series of prqjects sponsored by the National Aeronautics and Space Administration (NASA) to apply human error analysis to aviation operations. The first NASA-sponsored project had the goal to evaluate human errors caused by advanced cockpit automation. Our next aviation project focused on the development of methods and tools to apply human error analysis to the design of commercial aircraft. This project was performed by a consortium comprised of INEEL, NASA, and Boeing Commercial Airplane Group. The focus of the project was aircraft design and procedures that could lead to human errors during airplane maintenance

  10. Circadian Macronutrients Variations over the First 7 Weeks of Human Milk Feeding of Preterm Infants.

    Science.gov (United States)

    Moran-Lev, Hadar; Mimouni, Francis B; Ovental, Amit; Mangel, Laurence; Mandel, Dror; Lubetzky, Ronit

    2015-09-01

    Little is known about circadian variations of macronutrients content of expressed preterm human milk (HM). This study evaluated diurnal variations of macronutrients and energy content of preterm HM over the first 7 weeks of lactation and tested the hypothesis that values obtained during a morning sample are predictive of those obtained from an evening sample. Expressed HM was obtained from 32 mothers of preterm infants (26-33 weeks in gestational age), who routinely expressed all their milk every 3 hours from the beginning of the second to the seventh week after delivery. One aliquot was obtained from the first morning expression and the second from the evening expression. Energy and macronutrients contents were measured using an HM analyzer. Mean fat and energy contents of all samples obtained during the whole period were significantly higher in evening samples (p < 0.0001). There were no significant differences between morning and evening carbohydrates and protein contents. Concentrations of protein, carbohydrates, and fat from morning samples were predictive of evening concentrations to different extents (R(2) = 0.720, R(2) = 0.663, and R(2) = 0.20, respectively; p < 0.02). The predictability of evening values by morning values was not influenced by the week of lactation at sampling or by individual patients. In repeated-measures analysis of variance performed on 11 patients who completed the whole 7-week period, over time, there was a significant decrease in fat, energy, and protein contents, whereas carbohydrates content remained unchanged. Day-night differences remained significant only for fat content. Circadian variations in fat and energy concentrations of HM are consistent over the first 7 weeks of lactation. There are no consistent circadian variations in HM protein and carbohydrates. Over a given day, there are little variations in protein and carbohydrates content, but fat concentrations are more variable, and evening values are less well predicted by

  11. Applications of Pharmacogenetics in Revealing Variations in ...

    African Journals Online (AJOL)

    acer

    taking place in molecular biology techniques. Drug action is now more ... the latest findings of genetic variations in pharmacological targets related to disorders of major .... Similarly, Gly 9 allele. (Ser9Gly) of the dopamine D3 receptor gene.

  12. Accelerating cross-validation with total variation and its application to super-resolution imaging.

    Directory of Open Access Journals (Sweden)

    Tomoyuki Obuchi

    Full Text Available We develop an approximation formula for the cross-validation error (CVE of a sparse linear regression penalized by ℓ1-norm and total variation terms, which is based on a perturbative expansion utilizing the largeness of both the data dimensionality and the model. The developed formula allows us to reduce the necessary computational cost of the CVE evaluation significantly. The practicality of the formula is tested through application to simulated black-hole image reconstruction on the event-horizon scale with super resolution. The results demonstrate that our approximation reproduces the CVE values obtained via literally conducted cross-validation with reasonably good precision.

  13. Humanized mouse models: Application to human diseases.

    Science.gov (United States)

    Ito, Ryoji; Takahashi, Takeshi; Ito, Mamoru

    2018-05-01

    Humanized mice are superior to rodents for preclinical evaluation of the efficacy and safety of drug candidates using human cells or tissues. During the past decade, humanized mouse technology has been greatly advanced by the establishment of novel platforms of genetically modified immunodeficient mice. Several human diseases can be recapitulated using humanized mice due to the improved engraftment and differentiation capacity of human cells or tissues. In this review, we discuss current advanced humanized mouse models that recapitulate human diseases including cancer, allergy, and graft-versus-host disease. © 2017 Wiley Periodicals, Inc.

  14. On the applicability of brain reading for predictive human-machine interfaces in robotics.

    Science.gov (United States)

    Kirchner, Elsa Andrea; Kim, Su Kyoung; Straube, Sirko; Seeland, Anett; Wöhrle, Hendrik; Krell, Mario Michael; Tabie, Marc; Fahle, Manfred

    2013-01-01

    The ability of today's robots to autonomously support humans in their daily activities is still limited. To improve this, predictive human-machine interfaces (HMIs) can be applied to better support future interaction between human and machine. To infer upcoming context-based behavior relevant brain states of the human have to be detected. This is achieved by brain reading (BR), a passive approach for single trial EEG analysis that makes use of supervised machine learning (ML) methods. In this work we propose that BR is able to detect concrete states of the interacting human. To support this, we show that BR detects patterns in the electroencephalogram (EEG) that can be related to event-related activity in the EEG like the P300, which are indicators of concrete states or brain processes like target recognition processes. Further, we improve the robustness and applicability of BR in application-oriented scenarios by identifying and combining most relevant training data for single trial classification and by applying classifier transfer. We show that training and testing, i.e., application of the classifier, can be carried out on different classes, if the samples of both classes miss a relevant pattern. Classifier transfer is important for the usage of BR in application scenarios, where only small amounts of training examples are available. Finally, we demonstrate a dual BR application in an experimental setup that requires similar behavior as performed during the teleoperation of a robotic arm. Here, target recognition processes and movement preparation processes are detected simultaneously. In summary, our findings contribute to the development of robust and stable predictive HMIs that enable the simultaneous support of different interaction behaviors.

  15. On the applicability of brain reading for predictive human-machine interfaces in robotics.

    Directory of Open Access Journals (Sweden)

    Elsa Andrea Kirchner

    Full Text Available The ability of today's robots to autonomously support humans in their daily activities is still limited. To improve this, predictive human-machine interfaces (HMIs can be applied to better support future interaction between human and machine. To infer upcoming context-based behavior relevant brain states of the human have to be detected. This is achieved by brain reading (BR, a passive approach for single trial EEG analysis that makes use of supervised machine learning (ML methods. In this work we propose that BR is able to detect concrete states of the interacting human. To support this, we show that BR detects patterns in the electroencephalogram (EEG that can be related to event-related activity in the EEG like the P300, which are indicators of concrete states or brain processes like target recognition processes. Further, we improve the robustness and applicability of BR in application-oriented scenarios by identifying and combining most relevant training data for single trial classification and by applying classifier transfer. We show that training and testing, i.e., application of the classifier, can be carried out on different classes, if the samples of both classes miss a relevant pattern. Classifier transfer is important for the usage of BR in application scenarios, where only small amounts of training examples are available. Finally, we demonstrate a dual BR application in an experimental setup that requires similar behavior as performed during the teleoperation of a robotic arm. Here, target recognition processes and movement preparation processes are detected simultaneously. In summary, our findings contribute to the development of robust and stable predictive HMIs that enable the simultaneous support of different interaction behaviors.

  16. The application of human error prevention tool in Tianwan nuclear power station

    International Nuclear Information System (INIS)

    Qiao Zhiguo

    2013-01-01

    This paper mainly discusses the application and popularization of human error prevention tool in Tianwan nuclear power station, including the study on project implementation background, main contents and innovation, performance management, innovation practice and development, and performance of innovation application. (authors)

  17. Variation-aware advanced CMOS devices and SRAM

    CERN Document Server

    Shin, Changhwan

    2016-01-01

    This book provides a comprehensive overview of contemporary issues in complementary metal-oxide semiconductor (CMOS) device design, describing how to overcome process-induced random variations such as line-edge-roughness, random-dopant-fluctuation, and work-function variation, and the applications of novel CMOS devices to cache memory (or Static Random Access Memory, SRAM). The author places emphasis on the physical understanding of process-induced random variation as well as the introduction of novel CMOS device structures and their application to SRAM. The book outlines the technical predicament facing state-of-the-art CMOS technology development, due to the effect of ever-increasing process-induced random/intrinsic variation in transistor performance at the sub-30-nm technology nodes. Therefore, the physical understanding of process-induced random/intrinsic variations and the technical solutions to address these issues plays a key role in new CMOS technology development. This book aims to provide the reade...

  18. Applications of Pharmacogenetics in Revealing Variations in ...

    African Journals Online (AJOL)

    This review article presents the latest findings of genetic variations in pharmacological targets related to disorders of major systems such as central nervous system, cardiovascular system, and the respiratory system especially in relation to asthma and the HLA antigen genotype in hypersensitivity reactions. East and Central ...

  19. Body size and allometric variation in facial shape in children.

    Science.gov (United States)

    Larson, Jacinda R; Manyama, Mange F; Cole, Joanne B; Gonzalez, Paula N; Percival, Christopher J; Liberton, Denise K; Ferrara, Tracey M; Riccardi, Sheri L; Kimwaga, Emmanuel A; Mathayo, Joshua; Spitzmacher, Jared A; Rolian, Campbell; Jamniczky, Heather A; Weinberg, Seth M; Roseman, Charles C; Klein, Ophir; Lukowiak, Ken; Spritz, Richard A; Hallgrimsson, Benedikt

    2018-02-01

    Morphological integration, or the tendency for covariation, is commonly seen in complex traits such as the human face. The effects of growth on shape, or allometry, represent a ubiquitous but poorly understood axis of integration. We address the question of to what extent age and measures of size converge on a single pattern of allometry for human facial shape. Our study is based on two large cross-sectional cohorts of children, one from Tanzania and the other from the United States (N = 7,173). We employ 3D facial imaging and geometric morphometrics to relate facial shape to age and anthropometric measures. The two populations differ significantly in facial shape, but the magnitude of this difference is small relative to the variation within each group. Allometric variation for facial shape is similar in both populations, representing a small but significant proportion of total variation in facial shape. Different measures of size are associated with overlapping but statistically distinct aspects of shape variation. Only half of the size-related variation in facial shape can be explained by the first principal component of four size measures and age while the remainder associates distinctly with individual measures. Allometric variation in the human face is complex and should not be regarded as a singular effect. This finding has important implications for how size is treated in studies of human facial shape and for the developmental basis for allometric variation more generally. © 2017 Wiley Periodicals, Inc.

  20. Big Data Analysis of Human Genome Variations

    KAUST Repository

    Gojobori, Takashi

    2016-01-01

    Since the human genome draft sequence was in public for the first time in 2000, genomic analyses have been intensively extended to the population level. The following three international projects are good examples for large-scale studies of human

  1. Challenges for coexistence of machine to machine and human to human applications in mobile network

    DEFF Research Database (Denmark)

    Sanyal, R.; Cianca, E.; Prasad, Ramjee

    2012-01-01

    A key factor for the evolution of the mobile networks towards 4G is to bring to fruition high bandwidth per mobile node. Eventually, due to the advent of a new class of applications, namely, Machine-to-Machine, we foresee new challenges where bandwidth per user is no more the primal driver...... be evolved to address various nuances of the mobile devices used by man and machines. The bigger question is as follows. Is the state-of-the-art mobile network designed optimally to cater both the Human-to-Human and Machine-to-Machine applications? This paper presents the primary challenges....... As an immediate impact of the high penetration of M2M devices, we envisage a surge in the signaling messages for mobility and location management. The cell size will shrivel due to high tele-density resulting in even more signaling messages related to handoff and location updates. The mobile network should...

  2. VariVis: a visualisation toolkit for variation databases

    Directory of Open Access Journals (Sweden)

    Smith Timothy D

    2008-04-01

    Full Text Available Abstract Background With the completion of the Human Genome Project and recent advancements in mutation detection technologies, the volume of data available on genetic variations has risen considerably. These data are stored in online variation databases and provide important clues to the cause of diseases and potential side effects or resistance to drugs. However, the data presentation techniques employed by most of these databases make them difficult to use and understand. Results Here we present a visualisation toolkit that can be employed by online variation databases to generate graphical models of gene sequence with corresponding variations and their consequences. The VariVis software package can run on any web server capable of executing Perl CGI scripts and can interface with numerous Database Management Systems and "flat-file" data files. VariVis produces two easily understandable graphical depictions of any gene sequence and matches these with variant data. While developed with the goal of improving the utility of human variation databases, the VariVis package can be used in any variation database to enhance utilisation of, and access to, critical information.

  3. Quantitative historical analysis uncovers a single dimension of complexity that structures global variation in human social organization

    Science.gov (United States)

    Turchin, Peter; Currie, Thomas E.; Whitehouse, Harvey; François, Pieter; Feeney, Kevin; Mullins, Daniel; Hoyer, Daniel; Collins, Christina; Grohmann, Stephanie; Mendel-Gleason, Gavin; Turner, Edward; Dupeyron, Agathe; Cioni, Enrico; Reddish, Jenny; Levine, Jill; Jordan, Greine; Brandl, Eva; Williams, Alice; Cesaretti, Rudolf; Krueger, Marta; Ceccarelli, Alessandro; Figliulo-Rosswurm, Joe; Tuan, Po-Ju; Peregrine, Peter; Marciniak, Arkadiusz; Preiser-Kapeller, Johannes; Kradin, Nikolay; Korotayev, Andrey; Palmisano, Alessio; Baker, David; Bidmead, Julye; Bol, Peter; Christian, David; Cook, Connie; Covey, Alan; Feinman, Gary; Júlíusson, Árni Daníel; Kristinsson, Axel; Miksic, John; Mostern, Ruth; Petrie, Cameron; Rudiak-Gould, Peter; ter Haar, Barend; Wallace, Vesna; Mair, Victor; Xie, Liye; Baines, John; Bridges, Elizabeth; Manning, Joseph; Lockhart, Bruce; Bogaard, Amy; Spencer, Charles

    2018-01-01

    Do human societies from around the world exhibit similarities in the way that they are structured, and show commonalities in the ways that they have evolved? These are long-standing questions that have proven difficult to answer. To test between competing hypotheses, we constructed a massive repository of historical and archaeological information known as “Seshat: Global History Databank.” We systematically coded data on 414 societies from 30 regions around the world spanning the last 10,000 years. We were able to capture information on 51 variables reflecting nine characteristics of human societies, such as social scale, economy, features of governance, and information systems. Our analyses revealed that these different characteristics show strong relationships with each other and that a single principal component captures around three-quarters of the observed variation. Furthermore, we found that different characteristics of social complexity are highly predictable across different world regions. These results suggest that key aspects of social organization are functionally related and do indeed coevolve in predictable ways. Our findings highlight the power of the sciences and humanities working together to rigorously test hypotheses about general rules that may have shaped human history. PMID:29269395

  4. High-confidence assessment of functional impact of human mitochondrial non-synonymous genome variations by APOGEE.

    Directory of Open Access Journals (Sweden)

    Stefano Castellana

    2017-06-01

    Full Text Available 24,189 are all the possible non-synonymous amino acid changes potentially affecting the human mitochondrial DNA. Only a tiny subset was functionally evaluated with certainty so far, while the pathogenicity of the vast majority was only assessed in-silico by software predictors. Since these tools proved to be rather incongruent, we have designed and implemented APOGEE, a machine-learning algorithm that outperforms all existing prediction methods in estimating the harmfulness of mitochondrial non-synonymous genome variations. We provide a detailed description of the underlying algorithm, of the selected and manually curated training and test sets of variants, as well as of its classification ability.

  5. Variations in the formation of the human caudal spinal cord.

    Science.gov (United States)

    Saraga-Babić, M; Sapunar, D; Wartiovaara, J

    1995-01-01

    Collection of 15 human embryos between 4-8 developmental weeks was used to histologically investigate variations in the development of the caudal part of the spinal cord and the neighboring axial organs (notochord and vertebral column). In the 4-week embryo, two types of neurulation were parallelly observed along the anteroposterior body axis: primary in the areas cranial to the neuroporus caudalis and secondary in the more caudal tail regions. In the 5-week embryos, both parts of the neural tube fused, forming only one continuous lumen in the developing spinal cord. In the three examined embryos we found anomalous pattern of spinal cord formation. Caudal parts of these spinal cords displayed division of their central canal into two or three separate lumina, each surrounded by neuroepithelial layer. In the caudal area of the spinal cord, derived by secondary neurulation, formation of separate lumina was neither connected to any anomalous notochord or vertebral column formation, nor the appearance of any major axial disturbances. We suggest that development of the caudal part of the spinal cord differs from its cranial region not only in the type of neurulation, but also in the destiny of its derivatives and possible modes of abnormality formation.

  6. Strongly nonlinear parabolic variational inequalities.

    Science.gov (United States)

    Browder, F E; Brézis, H

    1980-02-01

    An existence and uniqueness result is established for a general class of variational inequalities for parabolic partial differential equations of the form partial differentialu/ partial differentialt + A(u) + g(u) = f with g nondecreasing but satisfying no growth condition. The proof is based upon a type of compactness result for solutions of variational inequalities that should find a variety of other applications.

  7. Application of monoclonal antibodies for diagnosis and treatment of human digestive cancer

    International Nuclear Information System (INIS)

    Otsuji, Eigo

    2007-01-01

    Radioimmunoscintigraphic applications of monoclonal antibodies (Mabs) for noninvasive detection and visualization of target tumors have grown immensely, and it suggests that Mabs can reach specifically to the targeted tumors in the human body. Radionuclides, cytotoxic drugs and anti-cancer drugs can be coupled to these specific MAbs to detect the extent of disease and/or to treat the tumors. Many of such immunoconjugates were studied for targeting therapy for cancer in animal experiments and some of them have applied to human. In this paper, we described the existing status of application of Mabs for diagnosis and immunotargeting therapy of digestive cancers. (author)

  8. Variation of Human Salivary O-Glycome.

    Directory of Open Access Journals (Sweden)

    Radoslaw P Kozak

    Full Text Available The study of saliva O-glycosylation is receiving increasing attention due to the potential of glycans for disease biomarkers, but also due to easy access and non-invasive collection of saliva as biological fluid. Saliva is rich in glycoproteins which are secreted from the bloodstream or produced by salivary glands. Mucins, which are highly O-glycosylated proteins, are particularly abundant in human saliva. Their glycosylation is associated with blood group and secretor status, and represents a reservoir of potential disease biomarkers. This study aims to analyse and compare O-glycans released from whole human mouth saliva collected 3 times a day from a healthy individual over a 5 days period. O-linked glycans were released by hydrazinolysis, labelled with procainamide and analysed by ultra-high performance liquid chromatography with fluorescence detection (UHPLC-FLR coupled to electrospray ionization mass spectrometry (ESI-MS/MS. The sample preparation method showed excellent reproducibility and can therefore be used for biomarker discovery. Our data demonstrates that the O-glycosylation in human saliva changes significantly during the day. These changes may be related to changes in the salivary concentrations of specific proteins.

  9. The effects of local control station design variation on plant risk

    International Nuclear Information System (INIS)

    O'Hara, J.

    1989-01-01

    The existence of human engineering deficiencies at local control stations (LCSs) was addressed in a study (NUREG/CR-3696) conducted by the Pacific Northwest Laboratory (PNL). PNL concluded that the existence of these human factors deficiencies at safety significant LCSs increases the potential for operator errors that could be detrimental to plant and public safety. However, PNL did not specific analysis to evaluate the effects of LCS design variations on human performance, on plant risk, or on the cost benefit feasibility of upgrading LCSs. The purpose of the present investigation was to conduct such an analysis. The specific objectives of the research were (1) to further define important local control stations, human factors related LCS design variations, and typical human engineering deficiencies (HEDs) at LCSs; (2) to determine the effect of LCS design variations on human performance, i.e., on risk-significant human errors (HEs); (3) to determine the effect of LCS-induced human performance variation on plant risk as measured by core melt frequency (CMF); and (4) to determine whether LCS improvements (upgrades in LCS design to mitigate HEDs) are feasible in a scoping-type value-impact analysis. The results can be summarized as follows. There was an overall effect of LCS variations on human performance. The transition from the worst LCS configuration to the best resulted in an absolute reduction or improvement of 0.82 in mean HEP (reduction by a factor of 20). The transition from low to high levels of FC was associated with a 0.46 (86%) reduction in mean HEP. The majority of the effect was accounted for in the transition from the low to medium levels. The Panel Design dimension also had an effect on human performance although not as large as functional centralization. Upgrading from a low to high panel design resulted in a 0.29 (69%) reduction in mean HEP

  10. Stochastic variation in telomere shortening rate causes heterogeneity of human fibroblast replicative life span.

    Science.gov (United States)

    Martin-Ruiz, Carmen; Saretzki, Gabriele; Petrie, Joanne; Ladhoff, Juliane; Jeyapalan, Jessie; Wei, Wenyi; Sedivy, John; von Zglinicki, Thomas

    2004-04-23

    The replicative life span of human fibroblasts is heterogeneous, with a fraction of cells senescing at every population doubling. To find out whether this heterogeneity is due to premature senescence, i.e. driven by a nontelomeric mechanism, fibroblasts with a senescent phenotype were isolated from growing cultures and clones by flow cytometry. These senescent cells had shorter telomeres than their cycling counterparts at all population doubling levels and both in mass cultures and in individual subclones, indicating heterogeneity in the rate of telomere shortening. Ectopic expression of telomerase stabilized telomere length in the majority of cells and rescued them from early senescence, suggesting a causal role of telomere shortening. Under standard cell culture conditions, there was a minor fraction of cells that showed a senescent phenotype and short telomeres despite active telomerase. This fraction increased under chronic mild oxidative stress, which is known to accelerate telomere shortening. It is possible that even high telomerase activity cannot fully compensate for telomere shortening in all cells. The data show that heterogeneity of the human fibroblast replicative life span can be caused by significant stochastic cell-to-cell variation in telomere shortening.

  11. Human Y chromosome copy number variation in the next generation sequencing era and beyond.

    Science.gov (United States)

    Massaia, Andrea; Xue, Yali

    2017-05-01

    The human Y chromosome provides a fertile ground for structural rearrangements owing to its haploidy and high content of repeated sequences. The methodologies used for copy number variation (CNV) studies have developed over the years. Low-throughput techniques based on direct observation of rearrangements were developed early on, and are still used, often to complement array-based or sequencing approaches which have limited power in regions with high repeat content and specifically in the presence of long, identical repeats, such as those found in human sex chromosomes. Some specific rearrangements have been investigated for decades; because of their effects on fertility, or their outstanding evolutionary features, the interest in these has not diminished. However, following the flourishing of large-scale genomics, several studies have investigated CNVs across the whole chromosome. These studies sometimes employ data generated within large genomic projects such as the DDD study or the 1000 Genomes Project, and often survey large samples of healthy individuals without any prior selection. Novel technologies based on sequencing long molecules and combinations of technologies, promise to stimulate the study of Y-CNVs in the immediate future.

  12. Human-computer interaction handbook fundamentals, evolving technologies and emerging applications

    CERN Document Server

    Sears, Andrew

    2007-01-01

    This second edition of The Human-Computer Interaction Handbook provides an updated, comprehensive overview of the most important research in the field, including insights that are directly applicable throughout the process of developing effective interactive information technologies. It features cutting-edge advances to the scientific knowledge base, as well as visionary perspectives and developments that fundamentally transform the way in which researchers and practitioners view the discipline. As the seminal volume of HCI research and practice, The Human-Computer Interaction Handbook feature

  13. Biotechnological Patents Applications of the Deuterium Oxide in Human Health.

    Science.gov (United States)

    da S Mariano, Reysla M; Bila, Wendell C; Trindade, Maria Jaciara F; Lamounier, Joel A; Galdino, Alexsandro S

    2017-01-01

    Deuterium oxide is a molecule that has been used for decades in several studies related to human health. Currently, studies on D2O have mobilized a "Race for Patenting" worldwide. Several patents have been registered from biomedical and technological studies of D2O showing the potential of this stable isotope in industry and health care ecosystems. Most of the patents related to the applications of the deuterium oxide in human health have been summarized in this review. The following patents databases were consulted: European Patent Office (Espacenet), the United States Patent and Trademark Office (USPTO), the United States Latin America Patents (LATIPAT), Patent scope -Search International and National Patent Collections (WIPO), Google Patents and Free Patents Online. With this review, the information was collected on recent publications including 22 patents related to deuterium oxide and its applications in different areas. This review showed that deuterium oxide is a promising component in different areas, including biotechnology, chemistry and medicine. In addition, the knowledge of this compound was covered, reinforcing its importance in the field of biotechnology and human health. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Variation in decision making

    NARCIS (Netherlands)

    Dall, Sasha R. X.; Gosling, Samuel; Gordon D.A., Brown,; Dingemanse, Niels; Ido, Erev,; Martin, Kocher,; Laura, Schulz,; Todd, Peter M; Weissing, Franz; Wolf, Max; Hammerstein, Peter; Stevens, Jeffrey R.

    2012-01-01

    Variation in how organisms allocate their behavior over their lifetimes is key to determining Darwinian fitness., and thus the evolution of human and nonhuman decision making. This chapter explores how decision making varies across biologically and societally significant scales and what role such

  15. Investigating the sex-related geometric variation of the human cranium.

    Science.gov (United States)

    Bertsatos, Andreas; Papageorgopoulou, Christina; Valakos, Efstratios; Chovalopoulou, Maria-Eleni

    2018-01-29

    Accurate sexing methods are of great importance in forensic anthropology since sex assessment is among the principal tasks when examining human skeletal remains. The present study explores a novel approach in assessing the most accurate metric traits of the human cranium for sex estimation based on 80 ectocranial landmarks from 176 modern individuals of known age and sex from the Athens Collection. The purpose of the study is to identify those distance and angle measurements that can be most effectively used in sex assessment. Three-dimensional landmark coordinates were digitized with a Microscribe 3DX and analyzed in GNU Octave. An iterative linear discriminant analysis of all possible combinations of landmarks was performed for each unique set of the 3160 distances and 246,480 angles. Cross-validated correct classification as well as multivariate DFA on top performing variables reported 13 craniometric distances with over 85% classification accuracy, 7 angles over 78%, as well as certain multivariate combinations yielding over 95%. Linear regression of these variables with the centroid size was used to assess their relation to the size of the cranium. In contrast to the use of generalized procrustes analysis (GPA) and principal component analysis (PCA), which constitute the common analytical work flow for such data, our method, although computational intensive, produced easily applicable discriminant functions of high accuracy, while at the same time explored the maximum of cranial variability.

  16. Application of human engineering to design of central control room and evaluation

    International Nuclear Information System (INIS)

    Tani, Mamoru

    1986-01-01

    The central control room of a nuclear power station is the center of the operation control, monitoring and management of the plant, therefore, the design by the application of human engineering has been performed on the basis of the experience and achievement in thermal power stations and other industries. In this report, the application of human engineering to the development of the new control boards for PWRs and the evaluation are described. In a nuclear power station, the number of the machinery and equipment composing it is large, and the interrelation among them is complex, accordingly, in the information processing system for operation monitoring and control, the man-machine interface works with high density. The concept of multiple protection design requires to show numerous plant parameters on a central control board, and this also complicates the man-machine interface. The introduction of human engineering was seriously studied after the TMI accident. In order to increase the safety and reliability of a plant, the new central control and monitoring system aims at facilitating operation and monitoring, and lightening burden and preventing mistakes in handling and judgement. The operational sequence diagram and mock-up varification, the application of human engineering and the evaluation, the synthetic real-time verification at the time of abnormality and accident, and the evaluation of the reliability improvement of men are reported. (Kako, I.)

  17. Noninvasive monitoring local variations of fever and edema on human: potential for point-of-care inflammation assessment

    Science.gov (United States)

    Li, Zebin; Li, Xianglin; Li, Ting

    2018-02-01

    Tissue inflammation is often accompanied by fever and edema, which are common and troublesome problems that probably trigger disability, lymphangitis, cosmetic deformity and cellulitis. Here we developed a device, which can measure concentration and temperature variations of water in local human body by extended near infrared spectroscopy in 900 1000 nm wavelength range. An experiment of four steps incremental cycling exercise was designed to change tissue water concentration and temperature of subjects. Body temperature was also estimated by tympanic thermometer and surface thermometer as comparisons during the experiment. In the stage of recovery after exercise, the signal detected by custom device is similar to tympanic thermometer at the beginning, but it is closer to the temperature of surface later. In particular, this signal shows a better linearity, and a significant change when the exercise was suspended. This study demonstrated the potential of optical touch-sensing for inflammation severity monitoring by measuring water concentration and temperature variations in local lesions.

  18. Effect of variation of geometric parameters on the flow within a synthetic models of lower human airways

    Science.gov (United States)

    Espinosa Moreno, Andres Santiago; Duque Daza, Carlos Alberto

    2017-11-01

    The effects of variation of two geometric parameters, such as bifurcation angle and carina rounding radius, during the respiratory inhalation process, are studied numerically using two synthetic models of lower human airways. Laminar flow simulations were performed for six angles and three rounding radius, for 500, 1000, 1500 and 2000 for Reynolds numbers. Numerical results showed the existence of a direct relationship between the deformation of the velocity profiles (effect produced by the bifurcation) and the vortical structures observed through the secondary flow patterns. It is observed that the location of the vortices (and their related saddle point) is associated with the displacement of the velocity peak. On the other hand, increasing the angle and the rounding radius seems to bring about a growth of the pressure drop, which in turn displaces the distribution and peaks of the maximum shear stresses of the carina, that is, of the bifurcation point. Some physiological effects associated with the phenomena produced by these geometric variations are also discussed.

  19. Human upper limb manipulator mass center motion and mass moments of inertia variation

    Directory of Open Access Journals (Sweden)

    Nikolova Gergana

    2018-01-01

    Full Text Available Motion control is complicated for people having traumas or neurological diseases. An underlying assumption in our work is that the motion of healthy people is optimal with respect to positioning accuracy, movement response, and energy expenditure. In this paper, a new approach for determination of the human upper limb mass-inertial characteristics is presented by using the 3D geometrical mathematical modeling analysis approach. Two examples will be given to illustrate the main features and advantages of the proposed design concepts. The objective of the work presented in this paper is a determination of the mass properties of a two joints human upper limb manipulator. Results are aimed to have application in an exoskeleton design, the design of manipulation system and external manipulation system, serving people with some motion difficulties, as well as in sport and rehabilitation.

  20. Variations of intracavitary applicator geometry during multiple HDR brachytherapy insertions in carcinoma cervix and its influence on reporting as per ICRU report 38

    International Nuclear Information System (INIS)

    Datta, Niloy Ranjan; Kumar, Shaleen; Das, Koilpillai Joseph Maria; Pandey, Chandra Mani; Halder, Shikha; Ayyagari, Sunder

    2001-01-01

    Purpose: This paper examines the extent of variation in the applicator geometry during multiple high dose rate (HDR) intracavitary brachytherapy (ICBT) applications and its impact on reporting as per ICRU report 38. Materials and methods: Eighty orthogonal radiographs from 20 consecutive patients of carcinoma cervix (FIGO stages, IIA-IIIB) having four HDR ICBT applications of 6 Gy each at weekly intervals following teletherapy were evaluated. The applicator consisted of a flexible intrauterine tandem (IUT) independent of the ovoid assembly. The applicator geometry was evaluated in terms of: α angle, β angle, intrauterine length (IUTL), interovoid (IOV), os to right ovoid (ORT) and os to left ovoid (OLT) distances along with vertical (VDL) and anteroposterior displacements (ADL) of the os with respect to the ovoids. The Cartesian co-ordinates (X, Y, and Z) of the IUT tip, centre of both ovoids and os were also measured. Doses to right point A (ARD), left point A (ALD), along with a reference volume of 6 Gy for ICRU height (IRH), width (IRW), thickness (IRT) and volume (IRV) were estimated for each application. Results: Highly significant differences (P<0.001) between four insertions in any given patient across 20 patients for α angle, β angle, IUTL, IOV, ORT, VDL, co-ordinates of the IUT, ovoids and os were observed, except for ADL (P=0.041) and OLT (P=0.247). As a consequence, variations were observed in ARD (P=0.027), ALD (P=0.017); IRH, IRW, IRT and IRV (all P<0.001). Applicator factors which influenced the various dose specification parameters were: β angle and ORT for both ARD and ALD; UTLN, VDL and ORT for IRH; UTLN and IOV for IRW; UTLN for IRT and VDL for the 6 Gy IRV. Conclusions: A significant variation of the applicator geometry and its movement was observed in patients undergoing multiple HDR ICBT. This could have implications for reporting dose and volume specifications as required by ICRU report 38

  1. Application of human reliability analysis methodology of second generation

    International Nuclear Information System (INIS)

    Ruiz S, T. de J.; Nelson E, P. F.

    2009-10-01

    The human reliability analysis (HRA) is a very important part of probabilistic safety analysis. The main contribution of HRA in nuclear power plants is the identification and characterization of the issues that are brought together for an error occurring in the human tasks that occur under normal operation conditions and those made after abnormal event. Additionally, the analysis of various accidents in history, it was found that the human component has been a contributing factor in the cause. Because of need to understand the forms and probability of human error in the 60 decade begins with the collection of generic data that result in the development of the first generation of HRA methodologies. Subsequently develop methods to include in their models additional performance shaping factors and the interaction between them. So by the 90 mid, comes what is considered the second generation methodologies. Among these is the methodology A Technique for Human Event Analysis (ATHEANA). The application of this method in a generic human failure event, it is interesting because it includes in its modeling commission error, the additional deviations quantification to nominal scenario considered in the accident sequence of probabilistic safety analysis and, for this event the dependency actions evaluation. That is, the generic human failure event was required first independent evaluation of the two related human failure events . So the gathering of the new human error probabilities involves the nominal scenario quantification and cases of significant deviations considered by the potential impact on analyzed human failure events. Like probabilistic safety analysis, with the analysis of the sequences were extracted factors more specific with the highest contribution in the human error probabilities. (Author)

  2. Errors in data interpretation from genetic variation of human analytes

    OpenAIRE

    Howie, Heather L.; Delaney, Meghan; Wang, Xiaohong; Er, Lay See; Kapp, Linda; Lebedev, Jenna N.; Zimring, James C.

    2017-01-01

    In recent years, the extent of our vulnerability to misinterpretation due to poorly characterized reagents has become an issue of great concern. Antibody reagents have been identified as a major source of error, contributing to the ?reproducibility crisis.? In the current report, we define an additional dimension of the crisis; in particular, we define variation of the targets being analyzed. We report that natural variation in the immunoglobulin ?constant? region alters the reactivity with c...

  3. An Analytic Equation Partitioning Climate Variation and Human Impacts on River Sediment Load

    Science.gov (United States)

    Zhang, J.; Gao, G.; Fu, B.

    2017-12-01

    Spatial or temporal patterns and process-based equations could co-exist in hydrologic model. Yet, existing approaches quantifying the impacts of those variables on river sediment load (RSL) changes are found to be severely limited, and new ways to evaluate the contribution of these variables are thus needed. Actually, the Newtonian modeling is hardly achievable for this process due to the limitation of both observations and knowledge of mechanisms, whereas laws based on the Darwinian approach could provide one component of a developed hydrologic model. Since that streamflow is the carrier of suspended sediment, sediment load changes are documented in changes of streamflow and suspended sediment concentration (SSC) - water discharge relationships. Consequently, an analytic equation for river sediment load changes are proposed to explicitly quantify the relative contributions of climate variation and direct human impacts on river sediment load changes. Initially, the sediment rating curve, which is of great significance in RSL changes analysis, was decomposed as probability distribution of streamflow and the corresponding SSC - water discharge relationships at equally spaced discharge classes. Furthermore, a proposed segmentation algorithm based on the fractal theory was used to decompose RSL changes attributed to these two portions. Additionally, the water balance framework was utilized and the corresponding elastic parameters were calculated. Finally, changes in climate variables (i.e. precipitation and potential evapotranspiration) and direct human impacts on river sediment load could be figured out. By data simulation, the efficiency of the segmentation algorithm was verified. The analytic equation provides a superior Darwinian approach partitioning climate and human impacts on RSL changes, as only data series of precipitation, potential evapotranspiration and SSC - water discharge are demanded.

  4. Variational study of fermionic and bosonic systems with non-Gaussian states: Theory and applications

    Science.gov (United States)

    Shi, Tao; Demler, Eugene; Ignacio Cirac, J.

    2018-03-01

    We present a new variational method for investigating the ground state and out of equilibrium dynamics of quantum many-body bosonic and fermionic systems. Our approach is based on constructing variational wavefunctions which extend Gaussian states by including generalized canonical transformations between the fields. The key advantage of such states compared to simple Gaussian states is presence of non-factorizable correlations and the possibility of describing states with strong entanglement between particles. In contrast to the commonly used canonical transformations, such as the polaron or Lang-Firsov transformations, we allow parameters of the transformations to be time dependent, which extends their regions of applicability. We derive equations of motion for the parameters characterizing the states both in real and imaginary time using the differential structure of the variational manifold. The ground state can be found by following the imaginary time evolution until it converges to a steady state. Collective excitations in the system can be obtained by linearizing the real-time equations of motion in the vicinity of the imaginary time steady-state solution. Our formalism allows us not only to determine the energy spectrum of quasiparticles and their lifetime, but to obtain the complete spectral functions and to explore far out of equilibrium dynamics such as coherent evolution following a quantum quench. We illustrate and benchmark this framework with several examples: a single polaron in the Holstein and Su-Schrieffer-Heeger models, non-equilibrium dynamics in the spin-boson and Kondo models, the superconducting to charge density wave phase transitions in the Holstein model.

  5. 1H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    International Nuclear Information System (INIS)

    Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D.

    2011-01-01

    The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in 1 H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

  6. Task demands and individual variation in referring expressions

    NARCIS (Netherlands)

    Baltaretu, Adriana-Alexandra; Castro Ferreira, Thiago

    Aiming to improve the human-likeness of natural language generation systems, this study investigates different sources of variation that might influence the production of referring expressions (REs), namely the effect of task demands and inter- intra- individual variation. We collected REs using a

  7. Human biological rhythm in traditional Chinese medicine

    Directory of Open Access Journals (Sweden)

    Tianxing Zhang

    2016-10-01

    Full Text Available Traditional Chinese medicine (TCM has a comprehensive and thorough understanding of biological rhythm. Biological rhythm is an inherent connotation of “harmony between human and nature”, one of the thoughts in TCM. TCM discusses emphatically circadian rhythm, syzygial rhythm and seasonal rhythm, and particularly circadian and seasonal rhythms. Theories of Yin Yang and Five Elements are the principles and methods, with which TCM understands biological rhythms. Based on theories in TCM, biological rhythm in essence is a continuous variation of the human body state synchronized with natural rhythms, and theories of Yin Yang and Five Elements are both language tools to describe this continuous variation and theoretical tools for its investigation and application. The understandings of biological rhythm in TCM can be applied to etiology, health care, disease control and treatment. Many understandings in TCM have been confirmed by modern research and clinical reports, but there are still some pending issues. TCM is distinguished for its holistic viewpoint on biological rhythms.

  8. Experimental and analytical variation in human urine in 1H NMR spectroscopy-based metabolic phenotyping studies.

    Science.gov (United States)

    Maher, Anthony D; Zirah, Séverine F M; Holmes, Elaine; Nicholson, Jeremy K

    2007-07-15

    1H NMR spectroscopy potentially provides a robust approach for high-throughput metabolic screening of biofluids such as urine and plasma, but sample handling and preparation need careful optimization to ensure that spectra accurately report biological status or disease state. We have investigated the effects of storage temperature and time on the 1H NMR spectral profiles of human urine from two participants, collected three times a day on four different days. These were analyzed using modern chemometric methods. Analytical and preparation variation (tested between -40 degrees C and room temperature) and time of storage (to 24 h) were found to be much less influential than biological variation in sample classification. Statistical total correlation spectroscopy and discriminant function methods were used to identify the specific metabolites that were hypervariable due to preparation and biology. Significant intraindividual variation in metabolite profiles were observed even for urine collected on the same day and after at least 6 h fasting. The effect of long-term storage at different temperatures was also investigated, showing urine is stable if frozen for at least 3 months and that storage at room temperature for long periods (1-3 months) results in a metabolic profile explained by bacterial activity. Presampling (e.g., previous day) intake of food and medicine can also strongly influence the urinary metabolic profiles indicating that collective detailed participant historical meta data are important for interpretation of metabolic phenotypes and for avoiding false biomarker discovery.

  9. Striatal dopamine release and genetic variation of the serotonin 2C receptor in humans.

    Science.gov (United States)

    Mickey, Brian J; Sanford, Benjamin J; Love, Tiffany M; Shen, Pei-Hong; Hodgkinson, Colin A; Stohler, Christian S; Goldman, David; Zubieta, Jon-Kar

    2012-07-04

    Mesoaccumbal and nigrostriatal projections are sensitive to stress, and heightened stress sensitivity is thought to confer risk for neuropsychiatric disorders. Serotonin 2C (5-HT(2C)) receptors mediate the inhibitory effects of serotonin on dopaminergic circuitry in experimental animals, and preclinical findings have implicated 5-HT(2C) receptors in motivated behaviors and psychotropic drug mechanisms. In humans, a common missense single-nucleotide change (rs6318, Cys23Ser) in the 5-HT(2C) receptor gene (HTR2C) has been associated with altered activity in vitro and with clinical mood disorders. We hypothesized that dopaminergic circuitry would be more sensitive to stress in humans carrying the Ser23 variant. To test this hypothesis, we studied 54 healthy humans using positron emission tomography and the displaceable D(2)/D(3) receptor radiotracer [(11)C]raclopride. Binding potential (BP(ND)) was quantified before and after a standardized stress challenge consisting of 20 min of moderate deep muscular pain, and reduction in BP(ND) served as an index of dopamine release. The Cys23Ser variant was genotyped on a custom array, and ancestry informative markers were used to control for population stratification. We found greater dopamine release in the nucleus accumbens, caudate nucleus, and putamen among Ser23 carriers, after controlling for sex, age, and ancestry. Genotype accounted for 12% of the variance in dopamine release in the nucleus accumbens. There was no association of Cys23Ser with baseline BP(ND). These findings indicate that a putatively functional HTR2C variant (Ser23) is associated with greater striatal dopamine release during pain in healthy humans. Mesoaccumbal stress sensitivity may mediate the effects of HTR2C variation on risk of neuropsychiatric disorders.

  10. Splines and variational methods

    CERN Document Server

    Prenter, P M

    2008-01-01

    One of the clearest available introductions to variational methods, this text requires only a minimal background in calculus and linear algebra. Its self-contained treatment explains the application of theoretic notions to the kinds of physical problems that engineers regularly encounter. The text's first half concerns approximation theoretic notions, exploring the theory and computation of one- and two-dimensional polynomial and other spline functions. Later chapters examine variational methods in the solution of operator equations, focusing on boundary value problems in one and two dimension

  11. Variation in sister chromatid exchange frequencies between human and pig whole blood, plasma leukocyte, and mononuclear leukocyte cultures

    International Nuclear Information System (INIS)

    Larramendy, M.L.; Reigosa, M.A.

    1986-01-01

    Sister chromatid exchange (SCE) induction by ultraviolet (UV) light was studied in both human and pig whole blood cultures (WBC) and plasma leukocyte cultures (PLC). No variation in SCE frequency was observed between pig WBC and PLC in control as well as in treated cells. Conversely, SCE frequencies of human PLC were consistently higher than those of WBC in control and UV-exposed cells. Thus, red blood cells (RBCs) do not influence the sensitivity of lymphocytes to UV LIGHT exposure, and there must be some different culture condition(s) in the inducation of SCEs between human WBC and PLC but not in swine lymphocyte cultures. Since the BrdUrd/lymphocyte ratio of WBC was halved in PLC, the effect of BrdUrd concentration in inducing the SCE baseline frequency of PLC may be ruled out. Neither the cell separation technique nor polymorphonuclear leukocytes had a significant role in the elevated SCE frequency of human PLC or MLC. Experiments where human RBCs were titrated into human PLC showed that the induction of an elevated SCE frequency of PLC was suppressed in a dose-dependent manner by the presence of RBCs in the culture medium. Since the incorporation of pig or human RBCs into human PLC as well as into MLC reduced the SCE frequency to that of WBC, a common component and/or function existing in these cells is suggested. Analysis of different RBC components showed that RBCs, specifically RBC ghosts, release a diffusible but not dialyzable corrective factor into culture medium that is able to reduce the SCE frequencies of PLC

  12. Accelerated Simulation of Kinetic Transport Using Variational Principles and Sparsity

    Energy Technology Data Exchange (ETDEWEB)

    Caflisch, Russel [Univ. of California, Los Angeles, CA (United States)

    2017-06-30

    This project is centered on the development and application of techniques of sparsity and compressed sensing for variational principles, PDEs and physics problems, in particular for kinetic transport. This included derivation of sparse modes for elliptic and parabolic problems coming from variational principles. The research results of this project are on methods for sparsity in differential equations and their applications and on application of sparsity ideas to kinetic transport of plasmas.

  13. Victims of ‘private’ crimes and application of human rights in interpersonal relations

    Directory of Open Access Journals (Sweden)

    Reiter Axelle

    2013-01-01

    Full Text Available International human rights law has been challenged because of its alleged inability to safeguard the rights of the most vulnerable victims of violence. Whereas in real life they are often marginalized and effectively left without adequate protection, this is not to be attributed to the absence of an appropriate normative framework but rather to the contempt, lack of enforcement and systemic neglect of their claims. This paper proposes to find a ‘cure’ inside international human rights law, by strengthening the mechanisms that permit a horizontal application of human rights standards in private relations. The paper is divided in four sections. The first section describes the problematic at hand, focusing in particular on violence against women and children. The three subsequent sections then analyze the avenues open to victims in order to claim a ‘third-party’ application of human rights treaties against non-state actors who have violated their fundamental rights.

  14. Enzymatic modification of phospholipids forfunctional applications and human nutrition

    DEFF Research Database (Denmark)

    Guo, Zheng; Vikbjerg, Anders / Falk; Xu, Xuebing

    2005-01-01

    analogs based on the latest understanding of pivotal role of phospholipids in manifold biological processes, exploration of remarkable application potentials of phospholipids in meliorating human health, as well as development of new chemical and biotechnological approaches applied to the modification...... design. This will of course provide fundamental bases also for the development of enzymatic technology to produce structured or modified phospholipids....

  15. Cosmic ray variations of solar origin in relation to human physiological state during the December 2006 solar extreme events

    Science.gov (United States)

    Papailiou, M.; Mavromichalaki, H.; Vassilaki, A.; Kelesidis, K. M.; Mertzanos, G. A.; Petropoulos, B.

    2009-02-01

    There is an increasing amount of evidence linking biological effects to solar and geomagnetic disturbances. A series of studies is published referring to the changes in human physiological responses at different levels of geomagnetic activity. In this study, the possible relation between the daily variations of cosmic ray intensity, measured by the Neutron Monitor at the Cosmic Ray Station of the University of Athens (http://cosray.phys.uoa.gr) and the average daily and hourly heart rate variations of persons, with no symptoms or hospital admission, monitored by Holter electrocardiogram, is considered. This work refers to a group of persons admitted to the cardiological clinic of the KAT Hospital in Athens during the time period from 4th to 24th December 2006 that is characterized by extreme solar and geomagnetic activity. A series of Forbush decreases started on 6th December and lasted until the end of the month and a great solar proton event causing a Ground Level Enhancement (GLE) of the cosmic ray intensity on 13th December occurred. A sudden decrease of the cosmic ray intensity on 15th December, when a geomagnetic storm was registered, was also recorded in Athens Neutron Monitor station (cut-off rigidity 8.53 GV) with amplitude of 4%. It is noticed that during geomagnetically quiet days the heart rate and the cosmic ray intensity variations are positively correlated. When intense cosmic ray variations, like Forbush decreases and relativistic proton events produced by strong solar phenomena occur, cosmic ray intensity and heart rate get minimum values and their variations, also, coincide. During these events the correlation coefficient of these two parameters changes and follows the behavior of the cosmic ray intensity variations. This is only a small part of an extended investigation, which has begun using data from the year 2002 and is still in progress.

  16. Characterization of PDMS samples with variation of its synthesis parameters for tunable optics applications

    Science.gov (United States)

    Marquez-Garcia, Josimar; Cruz-Félix, Angel S.; Santiago-Alvarado, Agustin; González-García, Jorge

    2017-09-01

    Nowadays the elastomer known as polydimethylsiloxane (PDMS, Sylgard 184), due to its physical properties, low cost and easy handle, have become a frequently used material for the elaboration of optical components such as: variable focal length liquid lenses, optical waveguides, solid elastic lenses, etc. In recent years, we have been working in the characterization of this material for applications in visual sciences; in this work, we describe the elaboration of PDMSmade samples, also, we present physical and optical properties of the samples by varying its synthesis parameters such as base: curing agent ratio, and both, curing time and temperature. In the case of mechanical properties, tensile and compression tests were carried out through a universal testing machine to obtain the respective stress-strain curves, and to obtain information regarding its optical properties, UV-vis spectroscopy is applied to the samples to obtain transmittance and absorbance curves. Index of refraction variation was obtained through an Abbe refractometer. Results from the characterization will determine the proper synthesis parameters for the elaboration of tunable refractive surfaces for potential applications in robotics.

  17. Variational principles for dissipative waves

    Science.gov (United States)

    Dodin, I. Y.; Ruiz, D. E.

    2016-10-01

    Variational methods are a powerful tool in plasma theory. However, their applications are typically restricted to conservative systems or require doubling of variables, which often contradicts the purpose of the variational approach altogether. We show that these restrictions can be relaxed for some classes of dynamical systems that are of practical interest in plasma physics, particularly including dissipative plasma waves. Applications will be discussed to calculating dispersion relations and modulational dynamics of individual plasma waves and wave ensembles. The work was supported by the NNSA SSAA Program through DOE Research Grant No. DE-NA0002948, by the U.S. DOE through Contract No. DE-AC02-09CH11466, and by the U.S. DOD NDSEG Fellowship through Contract No. 32-CFR-168a.

  18. Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory

    Directory of Open Access Journals (Sweden)

    Adriana eBarman

    2014-04-01

    Full Text Available The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT and the logical memory section of the Wechsler Memory Scale (WMS. Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e. the myopia risk allele showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point towards pleitropic effects of RASGRF1 genetic variations on complex neural function in humans.

  19. Variations in Glycogen Synthesis in Human Pluripotent Stem Cells with Altered Pluripotent States

    Science.gov (United States)

    Chen, Richard J.; Zhang, Guofeng; Garfield, Susan H.; Shi, Yi-Jun; Chen, Kevin G.; Robey, Pamela G.; Leapman, Richard D.

    2015-01-01

    Human pluripotent stem cells (hPSCs) represent very promising resources for cell-based regenerative medicine. It is essential to determine the biological implications of some fundamental physiological processes (such as glycogen metabolism) in these stem cells. In this report, we employ electron, immunofluorescence microscopy, and biochemical methods to study glycogen synthesis in hPSCs. Our results indicate that there is a high level of glycogen synthesis (0.28 to 0.62 μg/μg proteins) in undifferentiated human embryonic stem cells (hESCs) compared with the glycogen levels (0 to 0.25 μg/μg proteins) reported in human cancer cell lines. Moreover, we found that glycogen synthesis was regulated by bone morphogenetic protein 4 (BMP-4) and the glycogen synthase kinase 3 (GSK-3) pathway. Our observation of glycogen bodies and sustained expression of the pluripotent factor Oct-4 mediated by the potent GSK-3 inhibitor CHIR-99021 reveals an altered pluripotent state in hPSC culture. We further confirmed glycogen variations under different naïve pluripotent cell growth conditions based on the addition of the GSK-3 inhibitor BIO. Our data suggest that primed hPSCs treated with naïve growth conditions acquire altered pluripotent states, similar to those naïve-like hPSCs, with increased glycogen synthesis. Furthermore, we found that suppression of phosphorylated glycogen synthase was an underlying mechanism responsible for altered glycogen synthesis. Thus, our novel findings regarding the dynamic changes in glycogen metabolism provide new markers to assess the energetic and various pluripotent states in hPSCs. The components of glycogen metabolic pathways offer new assays to delineate previously unrecognized properties of hPSCs under different growth conditions. PMID:26565809

  20. Medicare Geographic Variation - Public Use File

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Medicare Geographic Variation Public Use File provides the ability to view demographic, utilization and quality indicators at the state level (including...

  1. From genomic variation to personalized medicine

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Schmiegelow, Kjeld

    Genomic variation is the basis of interindividual differences in observable traits and disease susceptibility. Genetic studies are the driving force of personalized medicine, as many of the differences in treatment efficacy can be attributed to our genomic background. The rapid development...... a considerable amount of the phenotype variability, hence the major difficulty of interpretation lies in the complexity of molecular interactions. This PhD thesis describes the state-of-art of the functional human variation research (Chapter 1) and introduces childhood acute lymphoblastic leukaemia (ALL...... the thesis and includes some final remarks on the perspectives of genomic variation research and personalized medicine. In summary, this thesis demonstrates the feasibility of integrative analyses of genomic variations and introduces large-scale hypothesis-driven SNP exploration studies as an emerging...

  2. Exploring subdomain variation in biomedical language

    Directory of Open Access Journals (Sweden)

    Séaghdha Diarmuid Ó

    2011-05-01

    Full Text Available Abstract Background Applications of Natural Language Processing (NLP technology to biomedical texts have generated significant interest in recent years. In this paper we identify and investigate the phenomenon of linguistic subdomain variation within the biomedical domain, i.e., the extent to which different subject areas of biomedicine are characterised by different linguistic behaviour. While variation at a coarser domain level such as between newswire and biomedical text is well-studied and known to affect the portability of NLP systems, we are the first to conduct an extensive investigation into more fine-grained levels of variation. Results Using the large OpenPMC text corpus, which spans the many subdomains of biomedicine, we investigate variation across a number of lexical, syntactic, semantic and discourse-related dimensions. These dimensions are chosen for their relevance to the performance of NLP systems. We use clustering techniques to analyse commonalities and distinctions among the subdomains. Conclusions We find that while patterns of inter-subdomain variation differ somewhat from one feature set to another, robust clusters can be identified that correspond to intuitive distinctions such as that between clinical and laboratory subjects. In particular, subdomains relating to genetics and molecular biology, which are the most common sources of material for training and evaluating biomedical NLP tools, are not representative of all biomedical subdomains. We conclude that an awareness of subdomain variation is important when considering the practical use of language processing applications by biomedical researchers.

  3. Human skin volatiles: a review.

    Science.gov (United States)

    Dormont, Laurent; Bessière, Jean-Marie; Cohuet, Anna

    2013-05-01

    Odors emitted by human skin are of great interest to biologists in many fields; applications range from forensic studies to diagnostic tools, the design of perfumes and deodorants, and the ecology of blood-sucking insect vectors of human disease. Numerous studies have investigated the chemical composition of skin odors, and various sampling methods have been used for this purpose. The literature shows that the chemical profile of skin volatiles varies greatly among studies, and the use of different sampling procedures is probably responsible for some of these variations. To our knowledge, this is the first review focused on human skin volatile compounds. We detail the different sampling techniques, each with its own set of advantages and disadvantages, which have been used for the collection of skin odors from different parts of the human body. We present the main skin volatile compounds found in these studies, with particular emphasis on the most frequently studied body regions, axillae, hands, and feet. We propose future directions for promising experimental studies on odors from human skin, particularly in relation to the chemical ecology of blood-sucking insects.

  4. Regularization by Functions of Bounded Variation and Applications to Image Enhancement

    International Nuclear Information System (INIS)

    Casas, E.; Kunisch, K.; Pola, C.

    1999-01-01

    Optimization problems regularized by bounded variation seminorms are analyzed. The optimality system is obtained and finite-dimensional approximations of bounded variation function spaces as well as of the optimization problems are studied. It is demonstrated that the choice of the vector norm in the definition of the bounded variation seminorm is of special importance for approximating subspaces consisting of piecewise constant functions. Algorithms based on a primal-dual framework that exploit the structure of these nondifferentiable optimization problems are proposed. Numerical examples are given for denoising of blocky images with very high noise

  5. Local variations in {sup 14}C - How is bomb-pulse dating of human tissues and cells affected?

    Energy Technology Data Exchange (ETDEWEB)

    Stenstroem, Kristina, E-mail: Kristina.Stenstrom@nuclear.lu.s [Lund University, Department of Physics, Division of Nuclear Physics, Box 118, SE-221 00 Lund (Sweden); Skog, Goeran [Lund University, GeoBiosphere Science Centre, Geocentrum II, Soelvegatan 12, SE-223 672 Lund (Sweden); Nilsson, Carl Magnus [Lund University, Department of Physics, Division of Nuclear Physics, Box 118, SE-221 00 Lund (Sweden); Lund University, Department of Medical Radiation Physics, Malmoe University Hospital, SE-205 02 Malmoe (Sweden); Hellborg, Ragnar [Lund University, Department of Physics, Division of Nuclear Physics, Box 118, SE-221 00 Lund (Sweden); Svegborn, Sigrid Leide [Lund University, Department of Medical Radiation Physics, Malmoe University Hospital, SE-205 02 Malmoe (Sweden); Georgiadou, Elisavet [Lund University, Department of Physics, Division of Nuclear Physics, Box 118, SE-221 00 Lund (Sweden); Mattsson, Soeren [Lund University, Department of Medical Radiation Physics, Malmoe University Hospital, SE-205 02 Malmoe (Sweden)

    2010-04-15

    Atmospheric nuclear weapons testing in the late 1950s and early 1960s almost doubled the amount of {sup 14}C in the atmosphere. The resulting {sup 14}C 'bomb-pulse' has been shown to provide useful age information in e.g. forensic and environmental sciences, biology and the geosciences. The technique is also currently being used for retrospective cell dating in man, in order to provide insight into the rate of formation of new cells in the human body. Bomb-pulse dating relies on precise measurements of the declining {sup 14}C concentration in atmospheric CO{sub 2} collected at clean-air sites. However, it is not always recognized that the calculations can be complicated in some cases by significant local variations in the specific activity of {sup 14}C in carbon in the air and foodstuff. This paper presents investigations of local {sup 14}C variations in the vicinities of nuclear installations and laboratories using {sup 14}C. Levels of {sup 14}C in workers using this radioisotope are also discussed.

  6. Radio sterilized human ligaments and their clinical application

    International Nuclear Information System (INIS)

    Luna Z, D.; Reyes F, M. L.; Diaz M, I.; Hernandez R, G.

    2009-10-01

    The ligaments are human tissues that are used in the transplantation area. A ligament is an anatomical structure in band form, composed by resistant fibers that connect the tissues that unite the bones with the articulations. In an articulation, the ligaments allow and facilitate the movement inside the natural anatomical directions, while it restricts those movements that are anatomically abnormal, impeding lesions that could arise of this type of movements. The kneecap ligament is a very important tissue in the knee mobility and of walking in the human beings. This ligament can injure it because of automobile accidents, for sport lesions or illnesses, and in many cases the only form of recovering the knee movement is carried out a transplant with the purpose of replacing the damage ligament by allo gen kneecap ligament processed in specialized Tissue Banks where the tissue is sterilized with gamma radiation of 60 Co at very low temperatures, obtaining high quality ligaments for clinical application in injured patients. The kneecap ligaments are processed in the Tissue Banks with a segment of kneecap bone, a segment of tibial bone, the contained ligament between both bones and in some cases a fraction of the quadriceps tendon. In this work is given a description of the selection method of the tissue that includes the donor's serologic control, the kneecap ligament processing in the Radio Sterilized Tissues Bank, its sterilization with gamma radiation of 60 Co, also it is indicated like the clinical application of the allo gen ligament was realized in a hasty patient and whose previous crossed ligament was injured. Finally the results are presented from the tissue obtaining until the clinical application of it is, and in this case is observed a favorable initial evolution of the transplantation patient. (Author)

  7. 34 CFR 97.118 - Applications and proposals lacking definite plans for involvement of human subjects.

    Science.gov (United States)

    2010-07-01

    ... Education PROTECTION OF HUMAN SUBJECTS Federal Policy for the Protection of Human Subjects (Basic ED Policy for Protection of Human Research Subjects) § 97.118 Applications and proposals lacking definite plans..., or contracts are submitted to departments or agencies with the knowledge that subjects may be...

  8. Mathematical human phantoms and their application to radiation protection

    International Nuclear Information System (INIS)

    Yamaguchi, Yasuhiro

    1998-01-01

    This review described the characteristics of mathematical phantoms, their history over 30 years and their application. Mathematical phantoms are classified into two models of formula and voxel types. In the former, human body and organs are described by 2- and/or 3-D mathematical formula and can be seen as a combination of solid bodies like spheres, cubes and ovals. The phantom is composed from three tissue components (bone, lung and soft tissue) and made on data on Reference Man in ICRP Publ. 23. The latter voxel (volume pixel) phantom consists from a number of small cubes based on CT and MRI images of a certain man. For instance, the phantom CHILD, 1.54 x 1.54 x 8.00 mm 3 in size, is based on a 7-year old child, which consisting from about one million voxels. The mathematical phantom was first made in Oak Ridge National Laboratory in the middle of the nineteen-sixties, which have undergone various improvements to reach MIRD-5 phantom. Thereafter, many similitude phantoms have been made as a variation of MIRD-5, depending on age and sex (e.g., ADAM and EVA). Voxel phantom was made in the middle of nineteen-eighties and have undergone improvements which are continued even currently in Japan, U.S. etc. The mathematical phantoms are used for calculation of radiation transport program by Monte Carlo method in the field of radiation protection. Also in the field of medicine, the phantom is used for calculation of internal and external exposure doses, of correction constants of externally measuring instruments, of doses for neutron capture therapy and of A-bomb exposure doses in Hiroshima and Nagasaki for reevaluation. Recently, the development of phantom is in the current from formula phantom to voxel one due to the purpose of precision and standardization. (K.H.)

  9. Circle of willis and its variations; morphometric study in adult human cadavers

    Directory of Open Access Journals (Sweden)

    Raghavendra, Shirol VS, Daksha Dixit, Anil Kumar Reddy Y, Desai SP

    2014-04-01

    Full Text Available Background and Objectives: Circle of Willis plays a vital role in collateral circulation and redistribution of blood to all areas of the brain. Variation in circle of Willis is known to cause grave disorders like cerebrovascular disorders, subarachnoid haemorrhage, cerebral aneurysm and schizophrenia. The objectives of the present study are to study the formation and branching pattern of circle of Willis and also to study the distribution of variations. MATERIALS & Methods: The study was conducted on 50 adult brain specimens. Each brain was removed in one piece by dissection and the circle of Willis was observed for its formation, pattern and variations. Results: Among the 50 specimens studied, 28 cases (56% had a normal pattern of circle of Willis and variations were observed in the remaining 22 cases (44%. More number of variations was observed on the right side than on the left side. The most common variation observed was hypoplastic posterior communicating artery (7 cases, 31.8%. Posterior communicating artery was found to be the most variable vessel while middle cerebral artery was the least variable vessel. Interpretation and Conclusion: The results with respect to the circle of Willis and all its component arteries were consistent with the results in the available literature. The only exception was the increased incidence of absence of both the anterior and posterior communicating arteries. This finding is of clinical significance to neurologists and neurosurgeons in this geographical location of north Karnataka. A higher incidence of variations in the communicating arteries is likely to manifest as a higher incidence in disorders like migraine, schizophrenia and cerebrovascular disorders due to compromised collateral circulation and poor redistribution of blood.

  10. Using spectral element method to solve variational inequalities with applications in finance

    International Nuclear Information System (INIS)

    Moradipour, M.; Yousefi, S.A.

    2015-01-01

    Under the Black–Scholes model, the value of an American option solves a time dependent variational inequality problem (VIP). In this paper, first we discretize the variational inequality of American option in temporal direction by applying the Rannacher time stepping and achieve a sequence of elliptic variational inequalities. Second we discretize the spatial domain of variational inequalities by using spectral element methods with high order Lagrangian polynomials introduced on Gauss–Legendre–Lobatto points. Also by computing integrals by the Gauss–Legendre–Lobatto quadrature rule we derive a sequence of the linear complementarity problems (LCPs) having a positive definite sparse coefficient matrix. To find the unique solutions of the LCPs, we use the projected successive over-relaxation (PSOR) algorithm. Furthermore we present some existence and uniqueness theorems for the variational inequalities and LCPs. Finally, theoretical results are verified on the relevant numerical examples.

  11. Geographic Variation in Medicare Spending Dashboard

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Geographic Variation Dashboards present Medicare fee-for-service per-capita spending at the state and county level in an interactive format. We calculated the...

  12. Improved physiologically based pharmacokinetic model for oral exposures to chromium in mice, rats, and humans to address temporal variation and sensitive populations.

    Science.gov (United States)

    Kirman, C R; Suh, M; Proctor, D M; Hays, S M

    2017-06-15

    A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding of the toxicokinetics of the gastrointestinal tract following oral exposures. Improvements were made to: (1) the reduction model, which describes the pH-dependent reduction of Cr(VI) to Cr(III) in the gastrointestinal tract under both fasted and fed states; (2) drinking water pattern simulations, to better describe dosimetry in rodents under the conditions of the NTP cancer bioassay; and (3) parameterize the model to characterize potentially sensitive human populations. Important species differences, sources of non-linear toxicokinetics, and human variation are identified and discussed within the context of human health risk assessment. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Using recruitment source timing and diagnosticity to enhance applicants' occupation-specific human capital.

    Science.gov (United States)

    Campion, Michael C; Ployhart, Robert E; Campion, Michael A

    2017-05-01

    [Correction Notice: An Erratum for this article was reported in Vol 102(5) of Journal of Applied Psychology (see record 2017-14296-001). In the article, the following headings were inadvertently set at the wrong level: Method, Participants and Procedure, Measures, Occupation specific human capital, Symbolic jobs, Relevant majors, Occupation-specific capital hotspots, Source timing, Source diagnosticity, Results, and Discussion. All versions of this article have been corrected.] This study proposes that reaching applicants through more diagnostic recruitment sources earlier in their educational development (e.g., in high school) can lead them to invest more in their occupation-specific human capital (OSHC), thereby making them higher quality candidates. Using a sample of 78,157 applicants applying for jobs within a desirable professional occupation in the public sector, results indicate that applicants who report hearing about the occupation earlier, and applicants who report hearing about the occupation through more diagnostic sources, have higher levels of OSHC upon application. Additionally, source timing and diagnosticity affect the likelihood of candidates applying for jobs symbolic of the occupation, selecting relevant majors, and attending educational institutions with top programs related to the occupation. These findings suggest a firm's recruiting efforts may influence applicants' OSHC investment strategies. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  14. Generalized bi-quasi-variational inequalities for quasi-semi-monotone and bi-quasi-semi-monotone operators with applications in non-compact settings and minimization problems

    Directory of Open Access Journals (Sweden)

    Chowdhury Molhammad SR

    2000-01-01

    Full Text Available Results are obtained on existence theorems of generalized bi-quasi-variational inequalities for quasi-semi-monotone and bi-quasi-semi-monotone operators in both compact and non-compact settings. We shall use the concept of escaping sequences introduced by Border (Fixed Point Theorem with Applications to Economics and Game Theory, Cambridge University Press, Cambridge, 1985 to obtain results in non-compact settings. Existence theorems on non-compact generalized bi-complementarity problems for quasi-semi-monotone and bi-quasi-semi-monotone operators are also obtained. Moreover, as applications of some results of this paper on generalized bi-quasi-variational inequalities, we shall obtain existence of solutions for some kind of minimization problems with quasi- semi-monotone and bi-quasi-semi-monotone operators.

  15. Variational techniques in non-perturbative QCD

    CERN Document Server

    Kovner, Alex; Kovner, Alex

    2004-01-01

    We review attempts to apply the variational principle to understand the vacuum of non-abelian gauge theories. In particular, we focus on the method explored by Ian Kogan and collaborators, which imposes exact gauge invariance on the trial Gaussian wave functional prior to the minimization of energy. We describe the application of the method to a toy model -- confining compact QED in 2+1 dimensions -- where it works wonderfully and reproduces all known non-trivial results. We then follow its applications to pure Yang-Mills theory in 3+1 dimensions at zero and finite temperature. Among the results of the variational calculation are dynamical mass generation and the analytic description of the deconfinement phase transition.

  16. Potential Applications for Radioisotope Power Systems in Support of Human Exploration Missions

    Science.gov (United States)

    Cataldo, Robert L.; Colozza, Anthony J.; Schmitz, Paul C.

    2013-01-01

    Radioisotope power systems (RPS) for space applications have powered over 27 U.S. space systems, starting with Transit 4A and 4B in 1961, and more recently with the successful landing of the Mars Science Laboratory rover Curiosity in August 2012. RPS enable missions with destinations far from the Sun with faint solar flux, on planetary surfaces with dense or dusty atmospheres, and at places with long eclipse periods where solar array sizes and energy storage mass become impractical. RPS could also provide an enabling capability in support of human exploration activities. It is envisioned that with the higher power needs of most human mission concepts, a high efficiency thermal-to-electric technology would be required such as the Advanced Stirling Radioisotope generator (ASRG). The ASRG should be capable of a four-fold improvement in efficiency over traditional thermoelectric RPS. While it may be impractical to use RPS as a main power source, many other applications could be considered, such as crewed pressurized rovers, in-situ resource production of propellants, back-up habitat power, drilling, any mobile or remote activity from the main base habitat, etc. This paper will identify potential applications and provide concepts that could be a practical extension of the current ASRG design in providing for robust and flexible use of RPS on human exploration missions.

  17. Establishment and clinical application of immunoradiometric assay for human growth hormone in serum

    International Nuclear Information System (INIS)

    Ji Jinfeng; Wu Congyuan; Niu Zhanpo; Zhang Kui; Song Ailing; Deng Jieying; Shi Mifan

    1992-01-01

    An immunoradiometric assay (IRMA) for human growth hormone (hGH) in serum is developed based on two high specific monoclonal antibodies against hGh. It can specifically detect the levels of serum bioactive hGh and had no cross-reaction with human prolactin (hPRL) and hGh oligmeric forms. The sensitivity was 0.2 ng/ml and the recovery for different concentrations of hGh was 92.0% ∼ 103.2%. The coefficients of variation for intra and inter-assay were<9.1% and <14.2%, respectively. Integral analysis of the results of RIA and IRMA with the patients' clinical manifestations revealed that hGh IRMA is better than hGh RIA in reflecting the clinical states of different acromegalic patients

  18. Common Variation in the DOPA Decarboxylase (DDC) Gene and Human Striatal DDC Activity In Vivo.

    Science.gov (United States)

    Eisenberg, Daniel P; Kohn, Philip D; Hegarty, Catherine E; Ianni, Angela M; Kolachana, Bhaskar; Gregory, Michael D; Masdeu, Joseph C; Berman, Karen F

    2016-08-01

    The synthesis of multiple amine neurotransmitters, such as dopamine, norepinephrine, serotonin, and trace amines, relies in part on DOPA decarboxylase (DDC, AADC), an enzyme that is required for normative neural operations. Because rare, loss-of-function mutations in the DDC gene result in severe enzymatic deficiency and devastating autonomic, motor, and cognitive impairment, DDC common genetic polymorphisms have been proposed as a source of more moderate, but clinically important, alterations in DDC function that may contribute to risk, course, or treatment response in complex, heritable neuropsychiatric illnesses. However, a direct link between common genetic variation in DDC and DDC activity in the living human brain has never been established. We therefore tested for this association by conducting extensive genotyping across the DDC gene in a large cohort of 120 healthy individuals, for whom DDC activity was then quantified with [(18)F]-FDOPA positron emission tomography (PET). The specific uptake constant, Ki, a measure of DDC activity, was estimated for striatal regions of interest and found to be predicted by one of five tested haplotypes, particularly in the ventral striatum. These data provide evidence for cis-acting, functional common polymorphisms in the DDC gene and support future work to determine whether such variation might meaningfully contribute to DDC-mediated neural processes relevant to neuropsychiatric illness and treatment.

  19. Ureaplasma Species Multiple Banded Antigen (MBA) Variation Is Associated with the Severity of Inflammation In vivo and In vitro in Human Placentae.

    Science.gov (United States)

    Sweeney, Emma L; Kallapur, Suhas G; Meawad, Simone; Gisslen, Tate; Stephenson, Sally-Anne; Jobe, Alan H; Knox, Christine L

    2017-01-01

    Background: The multiple banded antigen (MBA), a surface-exposed lipoprotein, is a proposed virulence factor of Ureaplasma spp. We previously demonstrated that the number of Ureaplasma parvum MBA size variants in amniotic fluid was inversely proportional to the severity of chorioamnionitis in experimentally infected pregnant sheep. However, the effect of ureaplasma MBA size variation on inflammation in human pregnancies has not been reported. Methods: Ureaplasmas isolated from the chorioamnion of pregnant women from a previous study ( n = 42) were speciated/serotyped and MBA size variation was demonstrated by PCR and western blot. Results were correlated with the severity of chorioamnionitis and cord blood cytokines. In vitro , THP-1-derived macrophages were exposed to recombinant-MBA proteins of differing sizes and NF-κB activation and cytokine responses were determined. Results: MBA size variation was identified in 21/32 (65.6%) clinical isolates (in 10 clinical isolates MBA size variation was unable to be determined). Any size variation (increase/decrease) of the MBA (regardless of Ureaplasma species or serovar) was associated with mild or absent chorioamnionitis ( P = 0.023) and lower concentrations of cord blood cytokines IL-8 ( P = 0.04) and G-CSF ( P = 0.008). In vitro , recombinant-MBA variants elicited different cytokine responses and altered expression of NF-κB p65. Conclusion: This study demonstrates that size variation of the ureaplasma MBA protein modulates the host immune response in vivo and in vitro .

  20. Structure of the human vitreoretinal border region

    DEFF Research Database (Denmark)

    Heegaard, Steffen

    1994-01-01

    Øjenpatologi, vitreoretinal border region, inner limiting membrane, retina, topographical variation, human......Øjenpatologi, vitreoretinal border region, inner limiting membrane, retina, topographical variation, human...

  1. Human reliability impact on in-service inspection

    International Nuclear Information System (INIS)

    Spanner, J.C. Sr.

    1986-01-01

    This paper describes a study conducted to identify, characterize, and evaluate the human reliability aspects of ultrasonic testing/inservice inspection (UT/ISI). Recent measurements of UT/ISI system effectiveness have revealed wide variations in performance; suggesting that insufficient emphasis is being placed on the human reliability aspects of nondestructive examination. It appears that NDE performance can be improved through application of the human factors principles relating to the task, training, procedure, environmental, and individual difference variables. These variables are collectively referred to as performance-shaping factors. A man-machine systems model was developed to describe the UT/ISI process using functional task descriptors. The relative operating characteristic (ROC) analysis method, which is derived from signal detection theory, offers unique attributes for analyzing NDT performance. The results of a limited human factors evaluation conducted in conjunction with a mini-round robin test are also described

  2. Experimental evaluation of a system for human life detection under debris

    Science.gov (United States)

    Joju, Reshma; Konica, Pimplapure Ramya T.; Alex, Zachariah C.

    2017-11-01

    It is difficult to for the human beings to be found under debris or behind the walls in case of military applications. Due to which several rescue techniques such as robotic systems, optical devices, and acoustic devices were used. But if victim was unconscious then these rescue system failed. We conducted an experimental analysis on whether the microwaves could detect heart beat and breathing signals of human beings trapped under collapsed debris. For our analysis we used RADAR based on by Doppler shift effect. We calculated the minimum speed that the RADAR could detect. We checked the frequency variation by placing the RADAR at a fixed position and placing the object in motion at different distances. We checked the frequency variation by using objects of different materials as debris behind which the motion was made. The graphs of different analysis were plotted.

  3. Application of human induced pluripotent stem cells to model fibrodysplasia ossificans progressiva.

    Science.gov (United States)

    Barruet, Emilie; Hsiao, Edward C

    2018-04-01

    Fibrodysplasia ossificans progressiva (FOP) is a genetic condition characterized by massive heterotopic ossification. FOP patients have mutations in the Activin A type I receptor (ACVR1), a bone morphogenetic protein (BMP) receptor. FOP is a progressive and debilitating disease characterized by bone formation flares that often occur after trauma. Since it is often difficult or impossible to obtain large amounts of tissue from human donors due to the risks of inciting more heterotopic bone formation, human induced pluripotent stem cells (hiPSCs) provide an attractive source for establishing in vitro disease models and for applications in drug screening. hiPSCs have the ability to self-renew, allowing researchers to obtain large amounts of starting material. hiPSCs also have the potential to differentiate into any cell type in the body. In this review, we discuss how the application of hiPSC technology to studying FOP has changed our perspectives on FOP disease pathogenesis. We also consider ongoing challenges and emerging opportunities for the use of human iPSCs in drug discovery and regenerative medicine. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Time-Depending Parametric Variational Approach for an Economic General Equilibrium Problem of Pure Exchange with Application

    International Nuclear Information System (INIS)

    Scaramuzzino, F.

    2009-01-01

    This paper considers a qualitative analysis of the solution of a pure exchange general economic equilibrium problem according to two independent parameters. Some recently results obtained by the author in the static and the dynamic case have been collected. Such results have been applied in a particular parametric case: it has been focused the attention on a numerical application for which the existence of the solution of time-depending parametric variational inequality that describes the equilibrium conditions has been proved by means of the direct method. By using MatLab computation after a linear interpolation, the curves of equilibrium have been visualized.

  5. A function space framework for structural total variation regularization with applications in inverse problems

    Science.gov (United States)

    Hintermüller, Michael; Holler, Martin; Papafitsoros, Kostas

    2018-06-01

    In this work, we introduce a function space setting for a wide class of structural/weighted total variation (TV) regularization methods motivated by their applications in inverse problems. In particular, we consider a regularizer that is the appropriate lower semi-continuous envelope (relaxation) of a suitable TV type functional initially defined for sufficiently smooth functions. We study examples where this relaxation can be expressed explicitly, and we also provide refinements for weighted TV for a wide range of weights. Since an integral characterization of the relaxation in function space is, in general, not always available, we show that, for a rather general linear inverse problems setting, instead of the classical Tikhonov regularization problem, one can equivalently solve a saddle-point problem where no a priori knowledge of an explicit formulation of the structural TV functional is needed. In particular, motivated by concrete applications, we deduce corresponding results for linear inverse problems with norm and Poisson log-likelihood data discrepancy terms. Finally, we provide proof-of-concept numerical examples where we solve the saddle-point problem for weighted TV denoising as well as for MR guided PET image reconstruction.

  6. MitoLSDB: a comprehensive resource to study genotype to phenotype correlations in human mitochondrial DNA variations.

    Directory of Open Access Journals (Sweden)

    Shamnamole K

    Full Text Available Human mitochondrial DNA (mtDNA encodes a set of 37 genes which are essential structural and functional components of the electron transport chain. Variations in these genes have been implicated in a broad spectrum of diseases and are extensively reported in literature and various databases. In this study, we describe MitoLSDB, an integrated platform to catalogue disease association studies on mtDNA (http://mitolsdb.igib.res.in. The main goal of MitoLSDB is to provide a central platform for direct submissions of novel variants that can be curated by the Mitochondrial Research Community. MitoLSDB provides access to standardized and annotated data from literature and databases encompassing information from 5231 individuals, 675 populations and 27 phenotypes. This platform is developed using the Leiden Open (source Variation Database (LOVD software. MitoLSDB houses information on all 37 genes in each population amounting to 132397 variants, 5147 unique variants. For each variant its genomic location as per the Revised Cambridge Reference Sequence, codon and amino acid change for variations in protein-coding regions, frequency, disease/phenotype, population, reference and remarks are also listed. MitoLSDB curators have also reported errors documented in literature which includes 94 phantom mutations, 10 NUMTs, six documentation errors and one artefactual recombination. MitoLSDB is the largest repository of mtDNA variants systematically standardized and presented using the LOVD platform. We believe that this is a good starting resource to curate mtDNA variants and will facilitate direct submissions enhancing data coverage, annotation in context of pathogenesis and quality control by ensuring non-redundancy in reporting novel disease associated variants.

  7. Genome-Wide Fine-Scale Recombination Rate Variation in Drosophila melanogaster

    Science.gov (United States)

    Song, Yun S.

    2012-01-01

    Estimating fine-scale recombination maps of Drosophila from population genomic data is a challenging problem, in particular because of the high background recombination rate. In this paper, a new computational method is developed to address this challenge. Through an extensive simulation study, it is demonstrated that the method allows more accurate inference, and exhibits greater robustness to the effects of natural selection and noise, compared to a well-used previous method developed for studying fine-scale recombination rate variation in the human genome. As an application, a genome-wide analysis of genetic variation data is performed for two Drosophila melanogaster populations, one from North America (Raleigh, USA) and the other from Africa (Gikongoro, Rwanda). It is shown that fine-scale recombination rate variation is widespread throughout the D. melanogaster genome, across all chromosomes and in both populations. At the fine-scale, a conservative, systematic search for evidence of recombination hotspots suggests the existence of a handful of putative hotspots each with at least a tenfold increase in intensity over the background rate. A wavelet analysis is carried out to compare the estimated recombination maps in the two populations and to quantify the extent to which recombination rates are conserved. In general, similarity is observed at very broad scales, but substantial differences are seen at fine scales. The average recombination rate of the X chromosome appears to be higher than that of the autosomes in both populations, and this pattern is much more pronounced in the African population than the North American population. The correlation between various genomic features—including recombination rates, diversity, divergence, GC content, gene content, and sequence quality—is examined using the wavelet analysis, and it is shown that the most notable difference between D. melanogaster and humans is in the correlation between recombination and

  8. Hybrid Iterative Scheme for Triple Hierarchical Variational Inequalities with Mixed Equilibrium, Variational Inclusion, and Minimization Constraints

    Directory of Open Access Journals (Sweden)

    Lu-Chuan Ceng

    2014-01-01

    Full Text Available We introduce and analyze a hybrid iterative algorithm by combining Korpelevich's extragradient method, the hybrid steepest-descent method, and the averaged mapping approach to the gradient-projection algorithm. It is proven that, under appropriate assumptions, the proposed algorithm converges strongly to a common element of the fixed point set of finitely many nonexpansive mappings, the solution set of a generalized mixed equilibrium problem (GMEP, the solution set of finitely many variational inclusions, and the solution set of a convex minimization problem (CMP, which is also a unique solution of a triple hierarchical variational inequality (THVI in a real Hilbert space. In addition, we also consider the application of the proposed algorithm to solving a hierarchical variational inequality problem with constraints of the GMEP, the CMP, and finitely many variational inclusions.

  9. Applicability of non-invasively collected matrices for human biomonitoring

    Directory of Open Access Journals (Sweden)

    Nickmilder Marc

    2009-03-01

    Full Text Available Abstract With its inclusion under Action 3 in the Environment and Health Action Plan 2004–2010 of the European Commission, human biomonitoring is currently receiving an increasing amount of attention from the scientific community as a tool to better quantify human exposure to, and health effects of, environmental stressors. Despite the policy support, however, there are still several issues that restrict the routine application of human biomonitoring data in environmental health impact assessment. One of the main issues is the obvious need to routinely collect human samples for large-scale surveys. Particularly the collection of invasive samples from susceptible populations may suffer from ethical and practical limitations. Children, pregnant women, elderly, or chronically-ill people are among those that would benefit the most from non-invasive, repeated or routine sampling. Therefore, the use of non-invasively collected matrices for human biomonitoring should be promoted as an ethically appropriate, cost-efficient and toxicologically relevant alternative for many biomarkers that are currently determined in invasively collected matrices. This review illustrates that several non-invasively collected matrices are widely used that can be an valuable addition to, or alternative for, invasively collected matrices such as peripheral blood sampling. Moreover, a well-informed choice of matrix can provide an added value for human biomonitoring, as different non-invasively collected matrices can offer opportunities to study additional aspects of exposure to and effects from environmental contaminants, such as repeated sampling, historical overview of exposure, mother-child transfer of substances, or monitoring of substances with short biological half-lives.

  10. Diurnal Variations of Human Circulating Cell-Free Micro-RNA.

    Directory of Open Access Journals (Sweden)

    Niels H H Heegaard

    Full Text Available A 24-hour light and dark cycle-dependent rhythmicity pervades physiological processes in virtually all living organisms including humans. These regular oscillations are caused by external cues to endogenous, independent biological time-keeping systems (clocks. The rhythm is reflected by gene expression that varies in a circadian and specific fashion in different organs and tissues and is regulated largely by dynamic epigenetic and post-transcriptional mechanisms. This leads to well-documented oscillations of specific electrolytes, hormones, metabolites, and plasma proteins in blood samples. An emerging, important class of gene regulators is short single-stranded RNA (micro-RNA, miRNA that interferes post-transcriptionally with gene expression and thus may play a role in the circadian variation of gene expression. MiRNAs are promising biomarkers by virtue of their disease-specific tissue expression and because of their presence as stable entities in the circulation. However, no studies have addressed the putative circadian rhythmicity of circulating, cell-free miRNAs. This question is important both for using miRNAs as biological markers and for clues to miRNA function in the regulation of circadian gene expression. Here, we investigate 92 miRNAs in plasma samples from 24 young male, healthy volunteers repeatedly sampled 9 times during a 24-hour stay in a regulated environment. We demonstrate that a third (26/79 of the measurable plasma miRNAs (using RT-qPCR on a microfluidic system exhibit a rhythmic behavior and are distributed in two main phase patterns. Some of these miRNAs weakly target known clock genes and many have strong targets in intracellular MAPK signaling pathways. These novel findings highlight the importance of considering bio-oscillations in miRNA biomarker studies and suggest the further study of a set of specific circulating miRNAs in the regulation and functioning of biological clocks.

  11. {sup 1}H NMR-based metabolic profiling reveals inherent biological variation in yeast and nematode model systems

    Energy Technology Data Exchange (ETDEWEB)

    Szeto, Samuel S. W.; Reinke, Stacey N.; Lemire, Bernard D., E-mail: bernard.lemire@ualberta.ca [University of Alberta, Department of Biochemistry, School of Molecular and Systems Medicine (Canada)

    2011-04-15

    The application of metabolomics to human and animal model systems is poised to provide great insight into our understanding of disease etiology and the metabolic changes that are associated with these conditions. However, metabolomic studies have also revealed that there is significant, inherent biological variation in human samples and even in samples from animal model systems where the animals are housed under carefully controlled conditions. This inherent biological variability is an important consideration for all metabolomics analyses. In this study, we examined the biological variation in {sup 1}H NMR-based metabolic profiling of two model systems, the yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans. Using relative standard deviations (RSD) as a measure of variability, our results reveal that both model systems have significant amounts of biological variation. The C. elegans metabolome possesses greater metabolic variance with average RSD values of 29 and 39%, depending on the food source that was used. The S. cerevisiae exometabolome RSD values ranged from 8% to 12% for the four strains examined. We also determined whether biological variation occurs between pairs of phenotypically identical yeast strains. Multivariate statistical analysis allowed us to discriminate between pair members based on their metabolic phenotypes. Our results highlight the variability of the metabolome that exists even for less complex model systems cultured under defined conditions. We also highlight the efficacy of metabolic profiling for defining these subtle metabolic alterations.

  12. Elastic scattering of positronium: Application of the confined variational method

    KAUST Repository

    Zhang, Junyi

    2012-08-01

    We demonstrate for the first time that the phase shift in elastic positronium-atom scattering can be precisely determined by the confined variational method, in spite of the fact that the Hamiltonian includes an unphysical confining potential acting on the center of mass of the positron and one of the atomic electrons. As an example, we study the S-wave elastic scattering for the positronium-hydrogen scattering system, where the existing 4% discrepancy between the Kohn variational calculation and the R-matrix calculation is resolved. © Copyright EPLA, 2012.

  13. Elastic scattering of positronium: Application of the confined variational method

    KAUST Repository

    Zhang, Junyi; Yan, Zong-Chao; Schwingenschlö gl, Udo

    2012-01-01

    We demonstrate for the first time that the phase shift in elastic positronium-atom scattering can be precisely determined by the confined variational method, in spite of the fact that the Hamiltonian includes an unphysical confining potential acting on the center of mass of the positron and one of the atomic electrons. As an example, we study the S-wave elastic scattering for the positronium-hydrogen scattering system, where the existing 4% discrepancy between the Kohn variational calculation and the R-matrix calculation is resolved. © Copyright EPLA, 2012.

  14. Human hair follicle organ culture: theory, application and perspectives.

    Science.gov (United States)

    Langan, Ewan A; Philpott, Michael P; Kloepper, Jennifer E; Paus, Ralf

    2015-12-01

    For almost a quarter of a century, ex vivo studies of human scalp hair follicles (HFs) have permitted major advances in hair research, spanning diverse fields such as chronobiology, endocrinology, immunology, metabolism, mitochondrial biology, neurobiology, pharmacology, pigmentation and stem cell biology. Despite this, a comprehensive methodological guide to serum-free human HF organ culture (HFOC) that facilitates the selection and analysis of standard HF biological parameters and points out both research opportunities and pitfalls to newcomers to the field is still lacking. The current methods review aims to close an important gap in the literature and attempts to promote standardisation of human HFOC. We provide basic information outlining the establishment of HFOC through to detailed descriptions of the analysis of standard read-out parameters alongside practical examples. The guide closes by pointing out how serum-free HFOC can be utilised optimally to obtain previously inaccessible insights into human HF biology and pathology that are of interest to experimental dermatologists, geneticists, developmental biologists and (neuro-) endocrinologists alike and by highlighting novel applications of the model, including gene silencing and gene expression profiling of defined, laser capture-microdissected HF compartments. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Using the Screened Coulomb Potential to Illustrate the Variational Method

    Science.gov (United States)

    Zuniga, Jose; Bastida, Adolfo; Requena, Alberto

    2012-01-01

    The screened Coulomb potential, or Yukawa potential, is used to illustrate the application of the single and linear variational methods. The trial variational functions are expressed in terms of Slater-type functions, for which the integrals needed to carry out the variational calculations are easily evaluated in closed form. The variational…

  16. Applications and safety considerations of Lactobacillus salivarius as a probiotic in animal and human health.

    Science.gov (United States)

    Chaves, B D; Brashears, M M; Nightingale, K K

    2017-03-03

    The goals of this review are to summarize the current knowledge on the application of Lactobacillus salivarius as a probiotic in animals and humans, and to address safety concerns with its use on live hosts. Overall, several strains of L. salivarius are well established probiotics with multiple applications in animal health, particularly to reduce colonization by gastrointestinal pathogens, and to a lesser extent, as a production and quality aid. In humans, L. salivarius has been used to prevent and treat a variety of chronic diseases, including asthma, cancer, atopic dermatitis and halitosis, and to a much limited extent, to prevent or treat infections. Based on the results from primary research evidence, it seems that L. salivarius does not pose a health risk to animals or humans in the doses currently used for a variety of applications; however, there is a systematic lack of studies assuring the safety of many of the strains intended for clinical use. This review provides researchers in the field with up-to-date information regarding applications and safety of L. salivarius. Furthermore, it helps researchers identify knowledge gaps and potential opportunities for microbiological and clinical research. © 2017 The Society for Applied Microbiology.

  17. Discrete variational methods and their application to electronic structures

    International Nuclear Information System (INIS)

    Ellis, D.E.

    1987-01-01

    Some general concepts concerning Discrete Variational methods are developed and applied to problems of determination of eletronic spectra, charge densities and bonding of free molecules, surface-chemisorbed species and bulk solids. (M.W.O.) [pt

  18. Assessing the impacts of human activities and climate variations on grassland productivity by partial least squares structural equation modeling (PLS-SEM)

    Institute of Scientific and Technical Information of China (English)

    SHA Zongyao; XIE Yichun; TAN Xicheng; BAI Yongfei; LI Jonathan; LIU Xuefeng

    2017-01-01

    The cause-effect associations between geographical phenomena are an important focus in ecological research.Recent studies in structural equation modeling (SEM) demonstrated the potential for analyzing such associations.We applied the variance-based partial least squares SEM (PLS-SEM) and geographically-weighted regression (GWR) modeling to assess the human-climate impact on grassland productivity represented by above-ground biomass (AGB).The human and climate factors and their interaction were taken to explain the AGB variance by a PLS-SEM developed for the grassland ecosystem in Inner Mongolia,China.Results indicated that 65.5% of the AGB variance could be explained by the human and climate factors and their interaction.The case study showed that the human and climate factors imposed a significant and negative impact on the AGB and that their interaction alleviated to some extent the threat from the intensified human-climate pressure.The alleviation may be attributable to vegetation adaptation to high human-climate stresses,to human adaptation to climate conditions or/and to recent vegetation restoration programs in the highly degraded areas.Furthermore,the AGB response to the human and climate factors modeled by GWR exhibited significant spatial variations.This study demonstrated that the combination of PLS-SEM and GWR model is feasible to investigate the cause-effect relation in socio-ecological systems.

  19. The variational nodal method: history and recent accomplishments

    International Nuclear Information System (INIS)

    Lewis, E.E.

    2004-01-01

    The variational nodal method combines spherical harmonics expansions in angle with hybrid finite element techniques is space to obtain multigroup transport response matrix algorithms applicable to both deep penetration and reactor core physics problems. This survey briefly recounts the method's history and reviews its capabilities. The variational basis for the approach is presented and two methods for obtaining discretized equations in the form of response matrices are detailed. The first is that contained the widely used VARIANT code, while the second incorporates newly developed integral transport techniques into the variational nodal framework. The two approaches are combined with a finite sub element formulation to treat heterogeneous nodes. Applications are presented for both a deep penetration problem and to an OECD benchmark consisting of LWR MOX fuel assemblies. Ongoing work is discussed. (Author)

  20. A Study of Variations of the Branching Patterns of right Upper Lobar Bronchus by Corrosive Cast Method

    Directory of Open Access Journals (Sweden)

    SV Solanki

    2015-06-01

    Full Text Available Introduction: Respiratory system is the basic prerequisite for living organisms. So precise knowledge of normal anatomy and various dimensions of human respiratory tract is inevitable. The right upper lobe bronchus is prevailingly trifurcates into apical, anterior and posterior segmental bronchi. Material and Methods: The present study was done on 28 tracheo-bronchial casts prepared by corrosive cast method in the anatomy department of B. J. medical college of Ahmedabad, Gujarat, India from 2011 to 2013. Result and Observation: In 16 specimens (57% normal trifurcate branching pattern was seen in right upper lobar bronchus. Most common variation observed was bifurcate pattern in right upper lobar bronchus in 36% of specimens. In 7% specimens quadrivial pattern was seen in right upper lobar bronchus in which it divided into four bronchi. Conclusion: The knowledge of anatomy and variation in branching pattern of the tracheo-bronchial tree enables the physicians to recognize clinical picture and pathology of human lungs, as well as the application of therapeutic and diagnostic methods like tracheal intubation, bronchoscopy, bronchography and postural drainage etc.

  1. Sparse Variational Bayesian SAGE Algorithm With Application to the Estimation of Multipath Wireless Channels

    DEFF Research Database (Denmark)

    Shutin, Dmitriy; Fleury, Bernard Henri

    2011-01-01

    In this paper, we develop a sparse variational Bayesian (VB) extension of the space-alternating generalized expectation-maximization (SAGE) algorithm for the high resolution estimation of the parameters of relevant multipath components in the response of frequency and spatially selective wireless...... channels. The application context of the algorithm considered in this contribution is parameter estimation from channel sounding measurements for radio channel modeling purpose. The new sparse VB-SAGE algorithm extends the classical SAGE algorithm in two respects: i) by monotonically minimizing...... parametric sparsity priors for the weights of the multipath components. We revisit the Gaussian sparsity priors within the sparse VB-SAGE framework and extend the results by considering Laplace priors. The structure of the VB-SAGE algorithm allows for an analytical stability analysis of the update expression...

  2. The German VR Simulation Realism Scale--psychometric construction for virtual reality applications with virtual humans.

    Science.gov (United States)

    Poeschl, Sandra; Doering, Nicola

    2013-01-01

    Virtual training applications with high levels of immersion or fidelity (for example for social phobia treatment) produce high levels of presence and therefore belong to the most successful Virtual Reality developments. Whereas display and interaction fidelity (as sub-dimensions of immersion) and their influence on presence are well researched, realism of the displayed simulation depends on the specific application and is therefore difficult to measure. We propose to measure simulation realism by using a self-report questionnaire. The German VR Simulation Realism Scale for VR training applications was developed based on a translation of scene realism items from the Witmer-Singer-Presence Questionnaire. Items for realism of virtual humans (for example for social phobia training applications) were supplemented. A sample of N = 151 students rated simulation realism of a Fear of Public Speaking application. Four factors were derived by item- and principle component analysis (Varimax rotation), representing Scene Realism, Audience Behavior, Audience Appearance and Sound Realism. The scale developed can be used as a starting point for future research and measurement of simulation realism for applications including virtual humans.

  3. Relevance of phenotypic variation in risk assessment: The scientific viewpoint

    International Nuclear Information System (INIS)

    Setlow, R.B.

    1986-01-01

    A number of examples are presented indicating the types of variation that may be expected in the responses of the human population to deleterious agents of an endogeneous or exogenous nature. If one assumes that the variations in repair in the normal population are reflected in large variations in carcinogenic risk per unit of exposure, then the dose-response curves at low doses cannot be extrapolated from high doeses without knowing the distribution of sensitivities among humans. The probability of determining this range by ecpidemiological studies on a random population by small. On the other hand, the probability of determining the range by careful genetic and molecular studies appears high enough so that such experiments now are being carried out. They cannot be carried out on real populations, using chronic exposures. Hence, the ability to estimate dose-response relations in the low dose region on human populations can only be by making theoretical constructs that, in turn, are dependent on fundamental research. 12 refs., 2 tabs

  4. Investigation of Interfraction Variations of MammoSite Balloon Applicator in High-Dose-Rate Brachytherapy of Partial Breast Irradiation

    International Nuclear Information System (INIS)

    Kim, Yongbok; Johnson, Mark M.S.; Trombetta, Mark G.; Parda, David S.; Miften, Moyed

    2008-01-01

    Purpose: To measure the interfraction changes of the MammoSite applicator and evaluate their dosimetric effect on target coverage and sparing of organs at risk. Methods and Materials: A retrospective evaluation of the data from 19 patients who received 10 fractions (34 Gy) of high-dose-rate partial breast irradiation was performed. A computed tomography-based treatment plan was generated for Fraction 1, and a computed tomography scan was acquired just before the delivery of each fraction to ensure a consistent shape of the balloon. The eccentricity, asymmetry, and planning target volume (PTV) for plan evaluation purposes (PTV E VAL), as well as trapped air gaps, were measured for all patients. Furthermore, 169 computed tomography-based treatment plans were retrospectively generated for Fractions 2-10. Interfraction dosimetric variations were evaluated using the %PTV E VAL coverage, target dose homogeneity index, target dose conformal index, and maximum doses to the organs at risks. Results: The average variation of eccentricity and asymmetry from Fraction 1 values of 3.5% and 1.1 mm was -0.4% ± 1.6% and -0.1 ± 0.6 mm. The average trapped air gap volume was dramatically reduced from before treatment (3.7 cm 3 ) to Fraction 1 (0.8 cm 3 ). The PTV E VAL volume change was insignificant. The average variation for the %PTV E VAL, target dose homogeneity, and target dose conformal index from Fraction 1 values of 94.7%, 0.64, and 0.85 was 0.15% ± 2.4%, -0.35 ± 2.4%, and -0.34 ± 4.9%, respectively. The average Fraction 1 maximum skin and ipsilateral lung dose of 3.2 Gy and 2.0 Gy varied by 0.08 ± 0.47 and -0.16 ± 0.29 Gy, respectively. Conclusion: The interfraction variations were patient specific and fraction dependent. Although the average interfraction dose variations for the target and organs at risk were not clinically significant, the maximum variations could be clinically significant

  5. Modeling Per Capita State Health Expenditure Variat...

    Data.gov (United States)

    U.S. Department of Health & Human Services — Modeling Per Capita State Health Expenditure Variation State-Level Characteristics Matter, published in Volume 3, Issue 4, of the Medicare and Medicaid Research...

  6. Within-Host Variations of Human Papillomavirus Reveal APOBEC-Signature Mutagenesis in the Viral Genome.

    Science.gov (United States)

    Hirose, Yusuke; Onuki, Mamiko; Tenjimbayashi, Yuri; Mori, Seiichiro; Ishii, Yoshiyuki; Takeuchi, Takamasa; Tasaka, Nobutaka; Satoh, Toyomi; Morisada, Tohru; Iwata, Takashi; Miyamoto, Shingo; Matsumoto, Koji; Sekizawa, Akihiko; Kukimoto, Iwao

    2018-03-28

    Persistent infection with oncogenic human papillomaviruses (HPVs) causes cervical cancer, accompanied with the accumulation of somatic mutations into the host genome. There are concomitant genetic changes in the HPV genome during viral infection; however, their relevance to cervical carcinogenesis is poorly understood. Here we explored within-host genetic diversity of HPV by performing deep sequencing analyses of viral whole-genome sequences in clinical specimens. The whole genomes of HPV types 16, 52 and 58 were amplified by type-specific PCR from total cellular DNA of cervical exfoliated cells collected from patients with cervical intraepithelial neoplasia (CIN) and invasive cervical cancer (ICC), and were deep-sequenced. After constructing a reference vial genome sequence for each specimen, nucleotide positions showing changes with > 0.5% frequencies compared to the reference sequence were determined for individual samples. In total, 1,052 positions of nucleotide variations were detected in HPV genomes from 151 samples (CIN1, n = 56; CIN2/3, n = 68; ICC, n = 27), with varying numbers per sample. Overall, C-to-T and C-to-A substitutions were the dominant changes observed across all histological grades. While C-to-T transitions were predominantly detected in CIN1, their prevalence was decreased in CIN2/3 and fell below that of C-to-A transversions in ICC. Analysis of the tri-nucleotides context encompassing substituted bases revealed that Tp C pN, a preferred target sequence for cellular APOBEC cytosine deaminases, was a primary site for C-to-T substitutions in the HPV genome. These results strongly imply that the APOBEC proteins are drivers of HPV genome mutation, particularly in CIN1 lesions. IMPORTANCE HPVs exhibit surprisingly high levels of genetic diversity, including a large repertoire of minor genomic variants in each viral genotype. Here, by conducting deep sequencing analyses, we show for the first time a comprehensive snapshot of the "within

  7. Neural Differentiation of Human Pluripotent Stem Cells for Nontherapeutic Applications: Toxicology, Pharmacology, and In Vitro Disease Modeling

    Directory of Open Access Journals (Sweden)

    May Shin Yap

    2015-01-01

    Full Text Available Human pluripotent stem cells (hPSCs derived from either blastocyst stage embryos (hESCs or reprogrammed somatic cells (iPSCs can provide an abundant source of human neuronal lineages that were previously sourced from human cadavers, abortuses, and discarded surgical waste. In addition to the well-known potential therapeutic application of these cells in regenerative medicine, these are also various promising nontherapeutic applications in toxicological and pharmacological screening of neuroactive compounds, as well as for in vitro modeling of neurodegenerative and neurodevelopmental disorders. Compared to alternative research models based on laboratory animals and immortalized cancer-derived human neural cell lines, neuronal cells differentiated from hPSCs possess the advantages of species specificity together with genetic and physiological normality, which could more closely recapitulate in vivo conditions within the human central nervous system. This review critically examines the various potential nontherapeutic applications of hPSC-derived neuronal lineages and gives a brief overview of differentiation protocols utilized to generate these cells from hESCs and iPSCs.

  8. Evolutionary developmental pathology and anthropology: A new field linking development, comparative anatomy, human evolution, morphological variations and defects, and medicine.

    Science.gov (United States)

    Diogo, Rui; Smith, Christopher M; Ziermann, Janine M

    2015-11-01

    We introduce a new subfield of the recently created field of Evolutionary-Developmental-Anthropology (Evo-Devo-Anth): Evolutionary-Developmental-Pathology-and-Anthropology (Evo-Devo-P'Anth). This subfield combines experimental and developmental studies of nonhuman model organisms, biological anthropology, chordate comparative anatomy and evolution, and the study of normal and pathological human development. Instead of focusing on other organisms to try to better understand human development, evolution, anatomy, and pathology, it places humans as the central case study, i.e., as truly model organism themselves. We summarize the results of our recent Evo-Devo-P'Anth studies and discuss long-standing questions in each of the broader biological fields combined in this subfield, paying special attention to the links between: (1) Human anomalies and variations, nonpentadactyly, homeotic transformations, and "nearest neighbor" vs. "find and seek" muscle-skeleton associations in limb+facial muscles vs. other head muscles; (2) Developmental constraints, the notion of "phylotypic stage," internalism vs. externalism, and the "logic of monsters" vs. "lack of homeostasis" views about human birth defects; (3) Human evolution, reversions, atavisms, paedomorphosis, and peromorphosis; (4) Scala naturae, Haeckelian recapitulation, von Baer's laws, and parallelism between phylogeny and development, here formally defined as "Phylo-Devo parallelism"; and (5) Patau, Edwards, and Down syndrome (trisomies 13, 18, 21), atavisms, apoptosis, heart malformations, and medical implications. © 2015 Wiley Periodicals, Inc.

  9. Human Genetic Variation and Yellow Fever Mortality during 19th Century U.S. Epidemics

    Science.gov (United States)

    2014-01-01

    ABSTRACT We calculated the incidence, mortality, and case fatality rates for Caucasians and non-Caucasians during 19th century yellow fever (YF) epidemics in the United States and determined statistical significance for differences in the rates in different populations. We evaluated nongenetic host factors, including socioeconomic, environmental, cultural, demographic, and acquired immunity status that could have influenced these differences. While differences in incidence rates were not significant between Caucasians and non-Caucasians, differences in mortality and case fatality rates were statistically significant for all epidemics tested (P < 0.01). Caucasians diagnosed with YF were 6.8 times more likely to succumb than non-Caucasians with the disease. No other major causes of death during the 19th century demonstrated a similar mortality skew toward Caucasians. Nongenetic host factors were examined and could not explain these large differences. We propose that the remarkably lower case mortality rates for individuals of non-Caucasian ancestry is the result of human genetic variation in loci encoding innate immune mediators. PMID:24895309

  10. A human error taxonomy and its application to an automatic method accident analysis

    International Nuclear Information System (INIS)

    Matthews, R.H.; Winter, P.W.

    1983-01-01

    Commentary is provided on the quantification aspects of human factors analysis in risk assessment. Methods for quantifying human error in a plant environment are discussed and their application to system quantification explored. Such a programme entails consideration of the data base and a taxonomy of factors contributing to human error. A multi-levelled approach to system quantification is proposed, each level being treated differently drawing on the advantages of different techniques within the fault/event tree framework. Management, as controller of organization, planning and procedure, is assigned a dominant role. (author)

  11. The application of cognitive models to the evaluation and prediction of human reliability

    International Nuclear Information System (INIS)

    Embrey, D.E.; Reason, J.T.

    1986-01-01

    The first section of the paper provides a brief overview of a number of important principles relevant to human reliability modeling that have emerged from cognitive models, and presents a synthesis of these approaches in the form of a Generic Error Modeling System (GEMS). The next section illustrates the application of GEMS to some well known nuclear power plant (NPP) incidents in which human error was a major contributor. The way in which design recommendations can emerge from analyses of this type is illustrated. The third section describes the use of cognitive models in the classification of human errors for prediction and data collection purposes. The final section addresses the predictive modeling of human error as part of human reliability assessment in Probabilistic Risk Assessment

  12. an investigation into the applicability of natural load variation

    African Journals Online (AJOL)

    Rev. Anoliefo

    Keywords – impedance matching,energy yield,natural load variation,maximum power ... Wind speed of 1 m/s and absolute air mass of 1.5 are also ... Unfortunately, solar modules operate under ..... thin-film photovoltaic plants by using physical.

  13. Human dental pulp stem cells: Applications in future regenerative medicine

    Science.gov (United States)

    Potdar, Pravin D; Jethmalani, Yogita D

    2015-01-01

    Stem cells are pluripotent cells, having a property of differentiating into various types of cells of human body. Several studies have developed mesenchymal stem cells (MSCs) from various human tissues, peripheral blood and body fluids. These cells are then characterized by cellular and molecular markers to understand their specific phenotypes. Dental pulp stem cells (DPSCs) are having a MSCs phenotype and they are differentiated into neuron, cardiomyocytes, chondrocytes, osteoblasts, liver cells and β cells of islet of pancreas. Thus, DPSCs have shown great potentiality to use in regenerative medicine for treatment of various human diseases including dental related problems. These cells can also be developed into induced pluripotent stem cells by incorporation of pluripotency markers and use for regenerative therapies of various diseases. The DPSCs are derived from various dental tissues such as human exfoliated deciduous teeth, apical papilla, periodontal ligament and dental follicle tissue. This review will overview the information about isolation, cellular and molecular characterization and differentiation of DPSCs into various types of human cells and thus these cells have important applications in regenerative therapies for various diseases. This review will be most useful for postgraduate dental students as well as scientists working in the field of oral pathology and oral medicine. PMID:26131314

  14. Improved physiologically based pharmacokinetic model for oral exposures to chromium in mice, rats, and humans to address temporal variation and sensitive populations

    Energy Technology Data Exchange (ETDEWEB)

    Kirman, C.R., E-mail: ckirman@summittoxicology.com [Summit Toxicology, PO Box 3209, Bozeman, MT 59715 (United States); Suh, M.; Proctor, D.M. [ToxStrategies, Mission Viejo, CA (United States); Hays, S.M. [Summit Toxicology, PO Box 3209, Bozeman, MT 59715 (United States)

    2017-06-15

    A physiologically based pharmacokinetic (PBPK) model for hexavalent chromium [Cr(VI)] in mice, rats, and humans developed previously (Kirman et al., 2012, 2013), was updated to reflect an improved understanding of the toxicokinetics of the gastrointestinal tract following oral exposures. Improvements were made to: (1) the reduction model, which describes the pH-dependent reduction of Cr(VI) to Cr(III) in the gastrointestinal tract under both fasted and fed states; (2) drinking water pattern simulations, to better describe dosimetry in rodents under the conditions of the NTP cancer bioassay; and (3) parameterize the model to characterize potentially sensitive human populations. Important species differences, sources of non-linear toxicokinetics, and human variation are identified and discussed within the context of human health risk assessment. - Highlights: • An improved version of the PBPK model for Cr(VI) toxicokinetics was developed. • The model incorporates data collected to fill important data gaps. • Model predictions for specific age groups and sensitive subpopulations are provided. • Implications to human health risk assessment are discussed.

  15. Variation Principles and Applications in the Study of Cell Structure and Aging

    Science.gov (United States)

    Economos, Angelos C.; Miquel, Jaime; Ballard, Ralph C.; Johnson, John E., Jr.

    1981-01-01

    In this report we have attempted to show that "some reality lies concealed in biological variation". This "reality" has its principles, laws, mechanisms, and rules, only a few of which we have sketched. A related idea we pursued was that important information may be lost in the process of ignoring frequency distributions of physiological variables (as is customary in experimental physiology and gerontology). We suggested that it may be advantageous to expand one's "statistical field of vision" beyond simple averages +/- standard deviations. Indeed, frequency distribution analysis may make visible some hidden information not evident from a simple qualitative analysis, particularly when the effect of some external factor or condition (e.g., aging, dietary chemicals) is being investigated. This was clearly illustrated by the application of distribution analysis in the study of variation in mouse liver cellular and fine structure, and may be true of fine structural studies in general. In living systems, structure and function interact in a dynamic way; they are "inseparable," unlike in technological systems or machines. Changes in fine structure therefore reflect changes in function. If such changes do not exceed a certain physiologic range, a quantitative analysis of structure will provide valuable information on quantitative changes in function that may not be possible or easy to measure directly. Because there is a large inherent variation in fine structure of cells in a given organ of an individual and among individuals, changes in fine structure can be analyzed only by studying frequency distribution curves of various structural characteristics (dimensions). Simple averages +/- S.D. do not in general reveal all information on the effect of a certain factor, because often this effect is not uniform; on the contrary, this will be apparent from distribution analysis because the form of the curves will be affected. We have also attempted to show in this chapter that

  16. alpha-Lactalbumin species variation, HAMLET formation, and tumor cell death.

    Science.gov (United States)

    Pettersson, Jenny; Mossberg, Ann-Kristin; Svanborg, Catharina

    2006-06-23

    HAMLET (human alpha-lactalbumin made lethal to tumor cells) is a tumoricidal complex of apo alpha-lactalbumin and oleic acid, formed in casein after low pH treatment of human milk. This study examined if HAMLET-like complexes are present in casein from different species and if isolated alpha-lactalbumin from those species can form such complexes with oleic acid. Casein from human, bovine, equine, and porcine milk was separated by ion exchange chromatography and active complexes were only found in human casein. This was not explained by alpha-lactalbumin sequence variation, as purified bovine, equine, porcine, and caprine alpha-lactalbumins formed complexes with oleic acid with biological activity similar to HAMLET. We conclude that structural variation of alpha-lactalbumins does not preclude the formation of HAMLET-like complexes and that natural HAMLET formation in casein was unique to human milk, which also showed the highest oleic acid content.

  17. Understanding 3D human torso shape via manifold clustering

    Science.gov (United States)

    Li, Sheng; Li, Peng; Fu, Yun

    2013-05-01

    Discovering the variations in human torso shape plays a key role in many design-oriented applications, such as suit designing. With recent advances in 3D surface imaging technologies, people can obtain 3D human torso data that provide more information than traditional measurements. However, how to find different human shapes from 3D torso data is still an open problem. In this paper, we propose to use spectral clustering approach on torso manifold to address this problem. We first represent high-dimensional torso data in a low-dimensional space using manifold learning algorithm. Then the spectral clustering method is performed to get several disjoint clusters. Experimental results show that the clusters discovered by our approach can describe the discrepancies in both genders and human shapes, and our approach achieves better performance than the compared clustering method.

  18. Human – Computer Systems Interaction Backgrounds and Applications 2 Part 1

    CERN Document Server

    Kulikowski, Juliusz; Mroczek, Teresa

    2012-01-01

    The main contemporary human-system interaction (H-SI) problems consist in design and/or improvement of the tools for effective exchange of information between individual humans or human groups and technical systems created for humans aiding in reaching their vital goals. This book is a second issue in a series devoted to the novel in H-SI results and contributions reached for the last years by many research groups in European and extra-European countries. The preliminary (usually shortened) versions of the chapters  were presented as conference papers at the 3rd International Conference on H-SI held in Rzeszow, Poland, in 2010. A  large number of valuable papers  selected for publication caused a necessity to publish the book in two volumes. The given, 1st Volume  consists of sections devoted to: I. Decision Supporting Systems, II. Distributed Knowledge Bases and WEB Systems and III. Impaired Persons  Aiding Systems. The decision supporting systems concern various application areas, like enterprises mana...

  19. Variations in soil-to-red pepper transfer factors of radionuclides with time of their application and fruit harvest

    International Nuclear Information System (INIS)

    Choi, Yong Ho; Lee, Won Yun; Lim, Kwang Muk; Park, Soo Won; Lee, Myung Ho; Lee, Chang Woo; Lee, Hyun Duk; Lee, Jeong Ho

    1997-01-01

    A mixed solution of 54 Mn, 60 Co, 85 Sr and 137 Cs was applied to the soil of culture boxes in a greenhouse 2 days before transplanting red pepper and at 3 different times during its growth for investigating transfer factors (m 2 /kg-dry) for its green and red fruits. Transfer factors varied with radionuclide, application time and harvest time by factors of about 20-100. They decreased mostly radionuclide, application time and harvest time by factors of about 20-100. They decreased mostly in the order of 85 Sr> 54 Mn> 60 Co> 137 Cs while 54 Mn and 60 Co was higher than 85 Sr when time lapse between application and harvest was short. Transfer factors of 85 Sr and 137 Cs at the last application were lower than those at the previous one by factors of 3-20 depending on harvest time. Variations in 54 Mn and 60 Co transfer factors with application time after transplanting were comparatively low. Transfer factors of 54 Mn, 60 Co and 85 Sr mixed with topsoil before transplanting were up to 3-9 times higher than those for the application onto soil surface 2 days after transplanting root-uptake concentrations of the radionuclides in red pepper fruit and taking proper measures for its harvest and consumption at the event of an accidental release during the growing season of red pepper

  20. Generalized variational formulations for extended exponentially fractional integral

    Directory of Open Access Journals (Sweden)

    Zuo-Jun Wang

    2016-01-01

    Full Text Available Recently, the fractional variational principles as well as their applications yield a special attention. For a fractional variational problem based on different types of fractional integral and derivatives operators, corresponding fractional Lagrangian and Hamiltonian formulation and relevant Euler–Lagrange type equations are already presented by scholars. The formulations of fractional variational principles still can be developed more. We make an attempt to generalize the formulations for fractional variational principles. As a result we obtain generalized and complementary fractional variational formulations for extended exponentially fractional integral for example and corresponding Euler–Lagrange equations. Two illustrative examples are presented. It is observed that the formulations are in exact agreement with the Euler–Lagrange equations.

  1. Isolation of human foetal myoblasts and its application for microencapsulation

    Science.gov (United States)

    Li, Anna Aihua; Bourgeois, Jacqueline; Potter, Murray; Chang, Patricia L

    2008-01-01

    Abstract Foetal cells secrete more growth factors, generate less immune response, grow and proliferate better than adult cells. These characteristics make them desirable for recombinant modification and use in microencapsulated cellular gene therapeutics. We have established a system in vitro to obtain a pure population of primary human foetal myoblasts under several rounds of selection with non-collagen coated plates and identified by desmin staining. These primary myoblasts presented good proliferation ability and better differentiation characteristics in monolayer and after microencapsulation compared to murine myoblast C2C12 cells based on creatine phosphokinase (CPK), major histocompatibility complex (MHC) and multi-nucleated myotubule determination. The lifespan of primary myoblasts was 70 population doublings before entering into senescent state, with a population time of 18–24 hrs. Hence, we have developed a protocol for isolating human foetal primary myoblasts with excellent differentiation potential and robust growth and longevity. They should be useful for cell-based therapy in human clinical applications with microencapsulation technology. PMID:18366454

  2. Variational principles for Ginzburg-Landau equation by He's semi-inverse method

    International Nuclear Information System (INIS)

    Liu, W.Y.; Yu, Y.J.; Chen, L.D.

    2007-01-01

    Via the semi-inverse method of establishing variational principles proposed by He, a generalized variational principle is established for Ginzburg-Landau equation. The present theory provides a quite straightforward tool to the search for various variational principles for physical problems. This paper aims at providing a more complete theoretical basis for applications using finite element and other direct variational methods

  3. Current applications of human pluripotent stem cells: possibilities and challenges.

    Science.gov (United States)

    Ho, Pai-Jiun; Yen, Men-Luh; Yet, Shaw-Fang; Yen, B Linju

    2012-01-01

    Stem cells are self-renewable cells with the differentiation capacity to develop into somatic cells with biological functions. This ability to sustain a renewable source of multi- and/or pluripotential differentiation has brought new hope to the field of regenerative medicine in terms of cell therapy and tissue engineering. Moreover, stem cells are invaluable tools as in vitro models for studying diverse fields, from basic scientific questions such as developmental processes and lineage commitment, to practical application including drug screening and testing. The stem cells with widest differentiation potential are pluripotent stem cells (PSCs), which are rare cells with the ability to generate somatic cells from all three germ layers. PSCs are considered the most optimal choice for therapeutic potential of stem cells, bringing new impetus to the field of regenerative medicine. In this article, we discuss the therapeutic potential of human PSCs (hPSCs) including human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), reviewing the current preclinical and clinical data using these stem cells. We describe the classification of different sources of hPSCs, ongoing research, and currently encountered clinical obstacles of these novel and versatile human stem cells.

  4. Human activities as a driver of spatial variation in the trophic structure of fish communities on Pacific coral reefs.

    Science.gov (United States)

    Ruppert, Jonathan L W; Vigliola, Laurent; Kulbicki, Michel; Labrosse, Pierre; Fortin, Marie-Josée; Meekan, Mark G

    2018-01-01

    Anthropogenic activities such as land-use change, pollution and fishing impact the trophic structure of coral reef fishes, which can influence ecosystem health and function. Although these impacts may be ubiquitous, they are not consistent across the tropical Pacific Ocean. Using an extensive database of fish biomass sampled using underwater visual transects on coral reefs, we modelled the impact of human activities on food webs at Pacific-wide and regional (1,000s-10,000s km) scales. We found significantly lower biomass of sharks and carnivores, where there were higher densities of human populations (hereafter referred to as human activity); however, these patterns were not spatially consistent as there were significant differences in the trophic structures of fishes among biogeographic regions. Additionally, we found significant changes in the benthic structure of reef environments, notably a decline in coral cover where there was more human activity. Direct human impacts were the strongest in the upper part of the food web, where we found that in a majority of the Pacific, the biomass of reef sharks and carnivores were significantly and negatively associated with human activity. Finally, although human-induced stressors varied in strength and significance throughout the coral reef food web across the Pacific, socioeconomic variables explained more variation in reef fish trophic structure than habitat variables in a majority of the biogeographic regions. Notably, economic development (measured as GDP per capita) did not guarantee healthy reef ecosystems (high coral cover and greater fish biomass). Our results indicate that human activities are significantly shaping patterns of trophic structure of reef fishes in a spatially nonuniform manner across the Pacific Ocean, by altering processes that organize communities in both "top-down" (fishing of predators) and "bottom-up" (degradation of benthic communities) contexts. © 2017 John Wiley & Sons Ltd.

  5. Genetic variations in the DNA replication origins of human papillomavirus family correlate with their oncogenic potential.

    Science.gov (United States)

    Yilmaz, Gulden; Biswas-Fiss, Esther E; Biswas, Subhasis B

    2018-04-01

    Human papillomaviruses (HPVs) encompass a large family of viruses that range from benign to highly carcinogenic. The crucial differences between benign and carcinogenic types of HPV remain unknown, except that the two HPV types differ in the frequency of DNA replication. We have systematically analyzed the mechanism of HPV DNA replication initiation in low-risk and high-risk HPVs. Our results demonstrate that HPV-encoded E2 initiator protein and its four binding sites in the replication origin play pivotal roles in determining the destiny of the HPV-infected cell. We have identified strain-specific single nucleotide variations in E2 binding sites found only in the high-risk HPVs. We have demonstrated that these variations result in attenuated formation of the E2-DNA complex. E2 binding to these sites is linked to the activation of the DNA replication origin as well as initiation of DNA replication. Both electrophoretic mobility shift assay and atomic force microscopy studies demonstrated that binding of E2 from either low- or high-risk HPVs with variant binding sequences lacked multimeric E2-DNA complex formation in vitro. These results provided a molecular basis of differential DNA replication in the two types of HPVs and pointed to a correlation with the development of cancer. Copyright © 2017. Published by Elsevier B.V.

  6. Variational transition state theory

    International Nuclear Information System (INIS)

    Truhlar, D.G.

    1986-01-01

    This project is concerned with the development and applications of generalized transition state theory and multidimensional tunneling approximations to chemical reaction rates. They have developed and implemented several practical versions of variational transition state theory (VTST), namely canonical variational theory (CVT), improved canonical variational theory (ICVT), and microcanonical variational theory (μVT). They have also developed and implemented several accurate multidimensional semiclassical tunneling approximations, the most accurate of which are the small-curvature semiclassical adiabatic (SCSA), large-curvature version-3 (LC3), and least-action (LA) approximations. They have applied the methods to thermal rate constants, using transmission coefficients based on ground-state tunneling, and they have also presented and applied adiabatic and diabatic extensions to calculated rate constants for vibrationally excited reactants. Their general goal is to develop accurate methods for calculating chemical reaction rate constants that remain practical even for reasonably complicated molecules. The approximations mentioned above yield rate constants for systems whose potential energy surface is known or assumed. Thus a second, equally important aspect of their work is the determination or modeling, semi-empirically and/or from electronic structure calculations, of potential energy surfaces

  7. Human resource development progress to sustain nuclear science and technology applications in Cameroon

    International Nuclear Information System (INIS)

    Simo, A.; Nyobe, J.B.

    2004-01-01

    Full text: Cameroon as a Member of the International Atomic Energy Agency (IAEA) has made full use of the Agency's Technical Co-operation Programme in his effort to promote peaceful applications of nuclear science and technology at national level. This paper presents the progress made in the development of reliable human resources. Results obtained have been achieved through national and regional technical co-operation projects. Over the past twenty years, the development of human resources in nuclear science and technology has focused on the training of national scientists and engineers in various fields such as crop and animal production, human and animal nutrition, human health applications, medical physics, non-destructive testing in industry, groundwater management, maintenance of medical and scientific equipment, radiation protection and radioactive waste management. Efforts made also involve the development of graduate teaching in nuclear sciences at the national universities. However, the lack of adequate training facilities remains a major concern. The development of new training/learning methods is being considered at national level through network linking of national training centres with existing international training institutions, and the use of Information Communication Technologies (ICT) which offer great flexibility with regard to the number of trainees and the actual needs. (author)

  8. Human resource development progress to sustain nuclear science and technology applications in Cameroon

    International Nuclear Information System (INIS)

    Simo, A.; Nyobe, J.B.

    2004-01-01

    Cameroon as a Member of the International Atomic Energy Agency (IAEA) has made full use of the Agency's Technical Co-operation Programme in his effort to promote peaceful applications of nuclear science and technology at national level. This paper presents the progress made in the development of reliable human resources. Results obtained have been achieved through national and regional technical co-operation projects. Over the past twenty years, the development of human resources in nuclear science and technology has focussed on the training of national scientists and engineers in various fields such as crop and animal production, human and animal nutrition, human health applications, medical physics, non destructive testing in industry, groundwater management, maintenance of medical and scientific equipment, radiation protection and radioactive waste management. Efforts made also involve the development of graduate teaching in nuclear sciences at the national universities. However, the lack of adequate training facilities remains a major concern. The development of new training/learning methods is being considered at national level through network linking of national training centres with existing international training institutions, and the use of Information Communication Technologies (ICT) which offer great flexibility with regard to the number of trainees and the actual needs. (author)

  9. Learning through the Variation Theory: A Case Study

    Science.gov (United States)

    Cheng, Eddie W. L.

    2016-01-01

    The variation theory stems from the concept of phenomenography. Although some applications of the theory can be found, the theory is not well known in the field of education, especially with respect to the teaching of business and management subjects. The aim of this paper is to explore the use of the variation theory for teaching management…

  10. Analysis of substructural variation in families of enzymatic proteins with applications to protein function prediction

    Directory of Open Access Journals (Sweden)

    Fofanov Viacheslav Y

    2010-05-01

    Full Text Available Abstract Background Structural variations caused by a wide range of physico-chemical and biological sources directly influence the function of a protein. For enzymatic proteins, the structure and chemistry of the catalytic binding site residues can be loosely defined as a substructure of the protein. Comparative analysis of drug-receptor substructures across and within species has been used for lead evaluation. Substructure-level similarity between the binding sites of functionally similar proteins has also been used to identify instances of convergent evolution among proteins. In functionally homologous protein families, shared chemistry and geometry at catalytic sites provide a common, local point of comparison among proteins that may differ significantly at the sequence, fold, or domain topology levels. Results This paper describes two key results that can be used separately or in combination for protein function analysis. The Family-wise Analysis of SubStructural Templates (FASST method uses all-against-all substructure comparison to determine Substructural Clusters (SCs. SCs characterize the binding site substructural variation within a protein family. In this paper we focus on examples of automatically determined SCs that can be linked to phylogenetic distance between family members, segregation by conformation, and organization by homology among convergent protein lineages. The Motif Ensemble Statistical Hypothesis (MESH framework constructs a representative motif for each protein cluster among the SCs determined by FASST to build motif ensembles that are shown through a series of function prediction experiments to improve the function prediction power of existing motifs. Conclusions FASST contributes a critical feedback and assessment step to existing binding site substructure identification methods and can be used for the thorough investigation of structure-function relationships. The application of MESH allows for an automated

  11. Variational model for one-dimensional quantum magnets

    Science.gov (United States)

    Kudasov, Yu. B.; Kozabaranov, R. V.

    2018-04-01

    A new variational technique for investigation of the ground state and correlation functions in 1D quantum magnets is proposed. A spin Hamiltonian is reduced to a fermionic representation by the Jordan-Wigner transformation. The ground state is described by a new non-local trial wave function, and the total energy is calculated in an analytic form as a function of two variational parameters. This approach is demonstrated with an example of the XXZ-chain of spin-1/2 under a staggered magnetic field. Generalizations and applications of the variational technique for low-dimensional magnetic systems are discussed.

  12. Gyarmati’s Variational Principle of Dissipative Processes

    Directory of Open Access Journals (Sweden)

    József Verhás

    2014-04-01

    Full Text Available Like in mechanics and electrodynamics, the fundamental laws of the thermodynamics of dissipative processes can be compressed into Gyarmati’s variational principle. This variational principle both in its differential (local and in integral (global forms was formulated by Gyarmati in 1965. The consistent application of both the local and the global forms of Gyarmati’s principle provides all the advantages throughout explicating the theory of irreversible thermodynamics that are provided in the study of mechanics and electrodynamics by the corresponding classical variational principles, e.g., Gauss’ differential principle of least constraint or Hamilton’s integral principle.

  13. The Prediction of Length-of-day Variations Based on Gaussian Processes

    Science.gov (United States)

    Lei, Y.; Zhao, D. N.; Gao, Y. P.; Cai, H. B.

    2015-01-01

    Due to the complicated time-varying characteristics of the length-of-day (LOD) variations, the accuracies of traditional strategies for the prediction of the LOD variations such as the least squares extrapolation model, the time-series analysis model, and so on, have not met the requirements for real-time and high-precision applications. In this paper, a new machine learning algorithm --- the Gaussian process (GP) model is employed to forecast the LOD variations. Its prediction precisions are analyzed and compared with those of the back propagation neural networks (BPNN), general regression neural networks (GRNN) models, and the Earth Orientation Parameters Prediction Comparison Campaign (EOP PCC). The results demonstrate that the application of the GP model to the prediction of the LOD variations is efficient and feasible.

  14. On the Use of Biomineral Oxygen Isotope Data to Identify Human Migrants in the Archaeological Record: Intra-Sample Variation, Statistical Methods and Geographical Considerations.

    Directory of Open Access Journals (Sweden)

    Emma Lightfoot

    Full Text Available Oxygen isotope analysis of archaeological skeletal remains is an increasingly popular tool to study past human migrations. It is based on the assumption that human body chemistry preserves the δ18O of precipitation in such a way as to be a useful technique for identifying migrants and, potentially, their homelands. In this study, the first such global survey, we draw on published human tooth enamel and bone bioapatite data to explore the validity of using oxygen isotope analyses to identify migrants in the archaeological record. We use human δ18O results to show that there are large variations in human oxygen isotope values within a population sample. This may relate to physiological factors influencing the preservation of the primary isotope signal, or due to human activities (such as brewing, boiling, stewing, differential access to water sources and so on causing variation in ingested water and food isotope values. We compare the number of outliers identified using various statistical methods. We determine that the most appropriate method for identifying migrants is dependent on the data but is likely to be the IQR or median absolute deviation from the median under most archaeological circumstances. Finally, through a spatial assessment of the dataset, we show that the degree of overlap in human isotope values from different locations across Europe is such that identifying individuals' homelands on the basis of oxygen isotope analysis alone is not possible for the regions analysed to date. Oxygen isotope analysis is a valid method for identifying first-generation migrants from an archaeological site when used appropriately, however it is difficult to identify migrants using statistical methods for a sample size of less than c. 25 individuals. In the absence of local previous analyses, each sample should be treated as an individual dataset and statistical techniques can be used to identify migrants, but in most cases pinpointing a specific

  15. Computational Modeling of Human Metabolism and Its Application to Systems Biomedicine.

    Science.gov (United States)

    Aurich, Maike K; Thiele, Ines

    2016-01-01

    Modern high-throughput techniques offer immense opportunities to investigate whole-systems behavior, such as those underlying human diseases. However, the complexity of the data presents challenges in interpretation, and new avenues are needed to address the complexity of both diseases and data. Constraint-based modeling is one formalism applied in systems biology. It relies on a genome-scale reconstruction that captures extensive biochemical knowledge regarding an organism. The human genome-scale metabolic reconstruction is increasingly used to understand normal cellular and disease states because metabolism is an important factor in many human diseases. The application of human genome-scale reconstruction ranges from mere querying of the model as a knowledge base to studies that take advantage of the model's topology and, most notably, to functional predictions based on cell- and condition-specific metabolic models built based on omics data.An increasing number and diversity of biomedical questions are being addressed using constraint-based modeling and metabolic models. One of the most successful biomedical applications to date is cancer metabolism, but constraint-based modeling also holds great potential for inborn errors of metabolism or obesity. In addition, it offers great prospects for individualized approaches to diagnostics and the design of disease prevention and intervention strategies. Metabolic models support this endeavor by providing easy access to complex high-throughput datasets. Personalized metabolic models have been introduced. Finally, constraint-based modeling can be used to model whole-body metabolism, which will enable the elucidation of metabolic interactions between organs and disturbances of these interactions as either causes or consequence of metabolic diseases. This chapter introduces constraint-based modeling and describes some of its contributions to systems biomedicine.

  16. Rare and common regulatory variation in population-scale sequenced human genomes.

    Directory of Open Access Journals (Sweden)

    Stephen B Montgomery

    2011-07-01

    Full Text Available Population-scale genome sequencing allows the characterization of functional effects of a broad spectrum of genetic variants underlying human phenotypic variation. Here, we investigate the influence of rare and common genetic variants on gene expression patterns, using variants identified from sequencing data from the 1000 genomes project in an African and European population sample and gene expression data from lymphoblastoid cell lines. We detect comparable numbers of expression quantitative trait loci (eQTLs when compared to genotypes obtained from HapMap 3, but as many as 80% of the top expression quantitative trait variants (eQTVs discovered from 1000 genomes data are novel. The properties of the newly discovered variants suggest that mapping common causal regulatory variants is challenging even with full resequencing data; however, we observe significant enrichment of regulatory effects in splice-site and nonsense variants. Using RNA sequencing data, we show that 46.2% of nonsynonymous variants are differentially expressed in at least one individual in our sample, creating widespread potential for interactions between functional protein-coding and regulatory variants. We also use allele-specific expression to identify putative rare causal regulatory variants. Furthermore, we demonstrate that outlier expression values can be due to rare variant effects, and we approximate the number of such effects harboured in an individual by effect size. Our results demonstrate that integration of genomic and RNA sequencing analyses allows for the joint assessment of genome sequence and genome function.

  17. Impact of seasonal variation, age and smoking status on human semen parameters: The Massachusetts General Hospital experience

    Science.gov (United States)

    Chen, Zuying; Godfrey-Bailey, Linda; Schiff, Isaac; Hauser, Russ

    2004-01-01

    Background To investigate the relationship of human semen parameters with season, age and smoking status. Methods The present study used data from subjects recruited into an ongoing cross-sectional study on the relationship between environmental agents and semen characteristics. Our population consisted of 306 patients who presented to the Vincent Memorial Andrology Laboratory of Massachusetts General Hospital for semen evaluation. Sperm concentration and motility were measured with computer aided sperm analysis (CASA). Sperm morphology was scored using Tygerberg Kruger strict criteria. Regression analyses were used to investigate the relationships between semen parameters and season, age and smoking status, adjusting for abstinence interval. Results Sperm concentration in the spring was significantly higher than in winter, fall and summer (p seasons. There were no statistically significant relationships between semen parameters and smoking status, though current smokers tended to have lower sperm concentration. We also did not find a statistically significant relationship between age and semen parameters. Conclusions We found seasonal variations in sperm concentration and suggestive evidence of seasonal variation in sperm motility and percent sperm with normal morphology. Although smoking status was not a significant predictor of semen parameters, this may have been due to the small number of current smokers in the study. PMID:15507127

  18. Review on present state of human model researches in nuclear engineering and the prospect for their industrial applications

    International Nuclear Information System (INIS)

    Yoshikawa, Hidekazu; Furuta, Kazuo; Nakagawa, Tsuneo; Yoshimura, Seiichi; Yoshida, Kazuo; Naito, Norio

    1999-01-01

    Reviews have been made on the researches and developments for human models in the field of nuclear engineering. Until now, the related works have been made mainly for the modeling of plant operator and operator crew in the control room, but also there arise new tendencies of extending the modeling works for maintenance field as well as for personnel training purposes. The whole range of human model research is divided into the five areas of (a) modeling for machine system, (b) measurement and analysis of human information behavior, (c) modeling of human internal information process, (d) modeling of human interaction with machine system, and (e) that of between human themselves. The real examples of the human model developments as well as their methods, applications, and the model validations are described, and then, the further subjects and efforts are pointed out which would be needed for the broader industrial application of the human modeling. (author)

  19. Iterative ensemble variational methods for nonlinear data assimilation: Application to transport and atmospheric chemistry

    International Nuclear Information System (INIS)

    Haussaire, Jean-Matthieu

    2017-01-01

    Data assimilation methods are constantly evolving to adapt to the various application domains. In atmospheric sciences, each new algorithm has first been implemented on numerical weather prediction models before being ported to atmospheric chemistry models. It has been the case for 4D variational methods and ensemble Kalman filters for instance. The new 4D ensemble variational methods (4D EnVar) are no exception. They were developed to take advantage of both variational and ensemble approaches and they are starting to be used in operational weather prediction centers, but have yet to be tested on operational atmospheric chemistry models. The validation of new data assimilation methods on these models is indeed difficult because of the complexity of such models. It is hence necessary to have at our disposal low-order models capable of synthetically reproducing key physical phenomena from operational models while limiting some of their hardships. Such a model, called L95-GRS, has therefore been developed. Il combines the simple meteorology from the Lorenz-95 model to a tropospheric ozone chemistry module with 7 chemical species. Even though it is of low dimension, it reproduces some of the physical and chemical phenomena observable in real situations. A data assimilation method, the iterative ensemble Kalman smoother (IEnKS), has been applied to this model. It is an iterative 4D EnVar method which solves the full non-linear variational problem. This application validates 4D EnVar methods in the context of non-linear atmospheric chemistry, but also raises the first limits of such methods, most noticeably when they are applied to weakly coupled stable models. After this experiment, results have been extended to a realistic atmospheric pollution prediction model. 4D EnVar methods, via the IEnKS, have once again shown their potential to take into account the non-linearity of the chemistry model in a controlled environment, with synthetic observations. However, the

  20. Variation in the human lymphocyte sister chromatid exchange frequency as a function of time: results of daily and twice-weekly sampling

    Energy Technology Data Exchange (ETDEWEB)

    Tucker, J.D.; Christensen, M.L.; Strout, C.L.; McGee, K.A.; Carrano, A.V.

    1987-01-01

    The variation in lymphocyte sister chromatid exchange (SCE) frequency was investigated in healthy nonsmokers who were not taking any medication. Two separate studies were undertaken. In the first, blood was drawn from four women twice a week for 8 weeks. These donors recorded the onset and termination of menstruation and times of illness. In the second study, blood was obtained from two women and two men for 5 consecutive days on two separate occasions initiated 14 days apart. Analysis of the mean SCE frequencies in each study indicated that significant temporal variation occurred in each donor, and that more variation occurred in the longer study. Some of the variation was found to be associated with the menstrual cycle. In the daily study, most of the variation appeared to be random, but occasional day-to-day changes occurred that were greater than those expected by chance. To determine how well a single SCE sample estimated the pooled mean for each donor in each study, the authors calculated the number of samples that encompassed that donor's pooled mean within 1 or more standard errors. For both studies, about 75% of the samples encompassed the pooled mean within 2 standard errors. An analysis of high-frequency cells (HFCs) was also undertaken. The results for each study indicate that the proportion of HFCs, compared with the use of Fisher's Exact test, is significantly more constant than the means, which were compared by using the t-test. These results coupled with our previous work suggest that HFC analysis may be the method of choice when analyzing data from human population studies.

  1. Cracking the Code of Human Diseases Using Next-Generation Sequencing: Applications, Challenges, and Perspectives

    Directory of Open Access Journals (Sweden)

    Vincenza Precone

    2015-01-01

    Full Text Available Next-generation sequencing (NGS technologies have greatly impacted on every field of molecular research mainly because they reduce costs and increase throughput of DNA sequencing. These features, together with the technology’s flexibility, have opened the way to a variety of applications including the study of the molecular basis of human diseases. Several analytical approaches have been developed to selectively enrich regions of interest from the whole genome in order to identify germinal and/or somatic sequence variants and to study DNA methylation. These approaches are now widely used in research, and they are already being used in routine molecular diagnostics. However, some issues are still controversial, namely, standardization of methods, data analysis and storage, and ethical aspects. Besides providing an overview of the NGS-based approaches most frequently used to study the molecular basis of human diseases at DNA level, we discuss the principal challenges and applications of NGS in the field of human genomics.

  2. Significance of functional disease-causal/susceptible variants identified by whole-genome analyses for the understanding of human diseases.

    Science.gov (United States)

    Hitomi, Yuki; Tokunaga, Katsushi

    2017-01-01

    Human genome variation may cause differences in traits and disease risks. Disease-causal/susceptible genes and variants for both common and rare diseases can be detected by comprehensive whole-genome analyses, such as whole-genome sequencing (WGS), using next-generation sequencing (NGS) technology and genome-wide association studies (GWAS). Here, in addition to the application of an NGS as a whole-genome analysis method, we summarize approaches for the identification of functional disease-causal/susceptible variants from abundant genetic variants in the human genome and methods for evaluating their functional effects in human diseases, using an NGS and in silico and in vitro functional analyses. We also discuss the clinical applications of the functional disease causal/susceptible variants to personalized medicine.

  3. Human Induced Pluripotent Stem Cells from Basic Research to Potential Clinical Applications in Cancer

    Directory of Open Access Journals (Sweden)

    Teresa de Souza Fernandez

    2013-01-01

    Full Text Available The human induced pluripotent stem cells (hiPSCs are derived from a direct reprogramming of human somatic cells to a pluripotent stage through ectopic expression of specific transcription factors. These cells have two important properties, which are the self-renewal capacity and the ability to differentiate into any cell type of the human body. So, the discovery of hiPSCs opens new opportunities in biomedical sciences, since these cells may be useful for understanding the mechanisms of diseases in the production of new diseases models, in drug development/drug toxicity tests, gene therapies, and cell replacement therapies. However, the hiPSCs technology has limitations including the potential for the development of genetic and epigenetic abnormalities leading to tumorigenicity. Nowadays, basic research in the hiPSCs field has made progress in the application of new strategies with the aim to enable an efficient production of high-quality of hiPSCs for safety and efficacy, necessary to the future application for clinical practice. In this review, we show the recent advances in hiPSCs’ basic research and some potential clinical applications focusing on cancer. We also present the importance of the use of statistical methods to evaluate the possible validation for the hiPSCs for future therapeutic use toward personalized cell therapies.

  4. Human iPSC for Therapeutic Approaches to the Nervous System: Present and Future Applications

    Directory of Open Access Journals (Sweden)

    Maria Giuseppina Cefalo

    2016-01-01

    Full Text Available Many central nervous system (CNS diseases including stroke, spinal cord injury (SCI, and brain tumors are a significant cause of worldwide morbidity/mortality and yet do not have satisfying treatments. Cell-based therapy to restore lost function or to carry new therapeutic genes is a promising new therapeutic approach, particularly after human iPSCs became available. However, efficient generation of footprint-free and xeno-free human iPSC is a prerequisite for their clinical use. In this paper, we will first summarize the current methodology to obtain footprint- and xeno-free human iPSC. We will then review the current iPSC applications in therapeutic approaches for CNS regeneration and their use as vectors to carry proapoptotic genes for brain tumors and review their applications for modelling of neurological diseases and formulating new therapeutic approaches. Available results will be summarized and compared. Finally, we will discuss current limitations precluding iPSC from being used on large scale for clinical applications and provide an overview of future areas of improvement. In conclusion, significant progress has occurred in deriving iPSC suitable for clinical use in the field of neurological diseases. Current efforts to overcome technical challenges, including reducing labour and cost, will hopefully expedite the integration of this technology in the clinical setting.

  5. Circle of willis and its variations; morphometric study in adult human cadavers

    OpenAIRE

    Raghavendra, Shirol VS, Daksha Dixit, Anil Kumar Reddy Y, Desai SP

    2014-01-01

    Background and Objectives: Circle of Willis plays a vital role in collateral circulation and redistribution of blood to all areas of the brain. Variation in circle of Willis is known to cause grave disorders like cerebrovascular disorders, subarachnoid haemorrhage, cerebral aneurysm and schizophrenia. The objectives of the present study are to study the formation and branching pattern of circle of Willis and also to study the distribution of variations. MATERIALS & Methods: The study was cond...

  6. Bounded variation and around

    CERN Document Server

    Appell, Jürgen; Merentes Díaz, Nelson José

    2013-01-01

    This monographis a self-contained exposition of the definition and properties of functionsof bounded variation and their various generalizations; the analytical properties of nonlinear composition operators in spaces of such functions; applications to Fourier analysis, nonlinear integral equations, and boundary value problems. The book is written for non-specialists. Every chapter closes with a list of exercises and open problems.

  7. In-plant application of industry experience to enhance human reliability

    International Nuclear Information System (INIS)

    Hannaman, G.W.; Singh, A.

    1993-01-01

    This paper describes the way that modern data-base computer tools can enhance the ability to collect, organize, evaluate, and use industry experience. By combining the computer tools with knowledge from human reliability assessment tools, data, and frameworks, the data base can become a tool for collecting and assessing the lessons learned from past events. By integrating the data-base system with plant risk models, engineers can focus on those activities that can enhance over-all system reliability. The evaluation helps identify technology and tools to reduce human errors during operations and maintenance. Learning from both in-plant and industry experience can help enhance safety and reduce the cost of plant operations. Utility engineers currently assess events that occur in nuclear plants throughout the world for in-plant applicability. Established computer information networks, documents, bulletins, and other information sources provide a large number of event descriptions to help individual plants benefit from this industry experience. The activities for coordinating reviews of event descriptions from other plants for in-plant applications require substantial engineering time to collect, organize, evaluate, and apply. Data-base tools can help engineers efficiently handle and sort the data so that they can concentrate on understanding the importance of the event, developing cost-effective interventions, and communicating implementation plans for plant improvement. An Electric Power Research Institute human reliability project has developed a classification system with modern data-base software to help engineers efficiently process, assess, and apply information contained in the events to enhance plant operation. Plant-specific classification of industry experience provides a practical method for efficiently taking into account industry when planning maintenance activities and reviewing plant safety

  8. Architecture and functional ecology of the human gastrocnemius muscle-tendon unit.

    Science.gov (United States)

    Butler, Erin E; Dominy, Nathaniel J

    2016-04-01

    The gastrocnemius muscle-tendon unit (MTU) is central to human locomotion. Structural variation in the human gastrocnemius MTU is predicted to affect the efficiency of locomotion, a concept most often explored in the context of performance activities. For example, stiffness of the Achilles tendon varies among individuals with different histories of competitive running. Such a finding highlights the functional variation of individuals and raises the possibility of similar variation between populations, perhaps in response to specific ecological or environmental demands. Researchers often assume minimal variation in human populations, or that industrialized populations represent the human species as well as any other. Yet rainforest hunter-gatherers, which often express the human pygmy phenotype, contradict such assumptions. Indeed, the human pygmy phenotype is a potential model system for exploring the range of ecomorphological variation in the architecture of human hindlimb muscles, a concept we review here. © 2015 Anatomical Society.

  9. Metabolomics in plants and humans: applications in the prevention and diagnosis of diseases.

    Science.gov (United States)

    Gomez-Casati, Diego F; Zanor, Maria I; Busi, María V

    2013-01-01

    In the recent years, there has been an increase in the number of metabolomic approaches used, in parallel with proteomic and functional genomic studies. The wide variety of chemical types of metabolites available has also accelerated the use of different techniques in the investigation of the metabolome. At present, metabolomics is applied to investigate several human diseases, to improve their diagnosis and prevention, and to design better therapeutic strategies. In addition, metabolomic studies are also being carried out in areas such as toxicology and pharmacology, crop breeding, and plant biotechnology. In this review, we emphasize the use and application of metabolomics in human diseases and plant research to improve human health.

  10. Eliminating Unpredictable Variation through Iterated Learning

    Science.gov (United States)

    Smith, Kenny; Wonnacott, Elizabeth

    2010-01-01

    Human languages may be shaped not only by the (individual psychological) processes of language acquisition, but also by population-level processes arising from repeated language learning and use. One prevalent feature of natural languages is that they avoid unpredictable variation. The current work explores whether linguistic predictability might…

  11. Applications for Electrical Impedance Tomography (EIT) and Electrical Properties of the Human Body.

    Science.gov (United States)

    Lymperopoulos, Georgios; Lymperopoulos, Panagiotis; Alikari, Victoria; Dafogianni, Chrisoula; Zyga, Sofia; Margari, Nikoletta

    2017-01-01

    Electrical Impedance Tomography (EIT) is a promising application that displays changes in conductivity within a body. The basic principle of the method is the repeated measurement of surface voltages of a body, which are a result of rolling injection of known and small-volume sinusoidal AC current to the body through the electrodes attached to its surface. This method finds application in biomedicine, biology and geology. The objective of this paper is to present the applications of Electrical Impedance Tomography, along with the method's capabilities and limitations due to the electrical properties of the human body. For this purpose, investigation of existing literature has been conducted, using electronic databases, PubMed, Google Scholar and IEEE Xplore. In addition, there was a secondary research phase, using paper citations found during the first research phase. It should be noted that Electrical Impedance Tomography finds use in a plethora of medical applications, as the different tissues of the body have different conductivities and dielectric constants. Main applications of EIT include imaging of lung function, diagnosis of pulmonary embolism, detection of tumors in the chest area and diagnosis and distinction of ischemic and hemorrhagic stroke. EIT advantages include portability, low cost and safety, which the method provide, since it is a noninvasive imaging method that does not cause damage to the body. The main disadvantage of the method, which blocks its wider spread, appears in the image composition from the voltage measurements, which are conducted by electrodes placed on the periphery of the body, because the injected currents are affected nonlinearly by the general distribution of the electrical properties of the body. Furthermore, the complex impedance of the skin-electrode interface can be modelled by using a capacitor and two resistor, as a result of skin properties. In conclusion, Electrical Impedance Tomography is a promising method for the

  12. Variational derivatives in locally Lagrangian field theories and Noether-Bessel-Hagen currents

    NARCIS (Netherlands)

    Cattafi, Francesco; Palese, Marcella; Winterroth, Ekkehart

    2016-01-01

    The variational Lie derivative of classes of forms in the Krupka's variational sequence is defined as a variational Cartan formula at any degree, in particular for degrees lesser than the dimension of the basis manifold. As an example of application, we determine the condition for a

  13. Variational principles for particles and fields in Heisenberg matrix mechanics

    International Nuclear Information System (INIS)

    Klein, A.; Li, C.T.; Vassanji, M.

    1980-01-01

    For many years we have advocated a form of quantum mechanics based on the application of sum rule methods (completeness) to the equations of motion and to the commutation relations, i.e., to Heisenberg matrix mechanics. Sporadically we have discussed or alluded to a variational foundation for this method. In this paper we present a series of variational principles applicable to a range of systems from one-dimensional quantum mechanics to quantum fields. The common thread is that the stationary quantity is the trace of the Hamiltonian over Hilbert space (or over a subspace of interest in an approximation) expressed as a functional of matrix elements of the elementary operators of the theory. These parameters are constrained by the kinematical relations of the theory introduced by the method of Lagrange multipliers. For the field theories, variational principles in which matrix elements of the density operators are chosen as fundamental are also developed. A qualitative discussion of applications is presented

  14. In silico detection of sequence variations modifying transcriptional regulation.

    Directory of Open Access Journals (Sweden)

    Malin C Andersen

    2008-01-01

    Full Text Available Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the regulation of the gene, the in silico binding site prediction improves the selection of candidate regulatory polymorphisms for further analyses. The bioinformatics software generated for the analysis has been implemented as a Web-based application system entitled RAVEN (regulatory analysis of variation in enhancers. The RAVEN system is available at http://www.cisreg.ca for all researchers interested in the detection and characterization of regulatory sequence variation.

  15. In Silico Detection of Sequence Variations Modifying Transcriptional Regulation

    Science.gov (United States)

    Andersen, Malin C; Engström, Pär G; Lithwick, Stuart; Arenillas, David; Eriksson, Per; Lenhard, Boris; Wasserman, Wyeth W; Odeberg, Jacob

    2008-01-01

    Identification of functional genetic variation associated with increased susceptibility to complex diseases can elucidate genes and underlying biochemical mechanisms linked to disease onset and progression. For genes linked to genetic diseases, most identified causal mutations alter an encoded protein sequence. Technological advances for measuring RNA abundance suggest that a significant number of undiscovered causal mutations may alter the regulation of gene transcription. However, it remains a challenge to separate causal genetic variations from linked neutral variations. Here we present an in silico driven approach to identify possible genetic variation in regulatory sequences. The approach combines phylogenetic footprinting and transcription factor binding site prediction to identify variation in candidate cis-regulatory elements. The bioinformatics approach has been tested on a set of SNPs that are reported to have a regulatory function, as well as background SNPs. In the absence of additional information about an analyzed gene, the poor specificity of binding site prediction is prohibitive to its application. However, when additional data is available that can give guidance on which transcription factor is involved in the regulation of the gene, the in silico binding site prediction improves the selection of candidate regulatory polymorphisms for further analyses. The bioinformatics software generated for the analysis has been implemented as a Web-based application system entitled RAVEN (regulatory analysis of variation in enhancers). The RAVEN system is available at http://www.cisreg.ca for all researchers interested in the detection and characterization of regulatory sequence variation. PMID:18208319

  16. Variation in the human ribs geometrical properties and mechanical response based on X-ray computed tomography images resolution.

    Science.gov (United States)

    Perz, Rafał; Toczyski, Jacek; Subit, Damien

    2015-01-01

    Computational models of the human body are commonly used for injury prediction in automobile safety research. To create these models, the geometry of the human body is typically obtained from segmentation of medical images such as computed tomography (CT) images that have a resolution between 0.2 and 1mm/pixel. While the accuracy of the geometrical and structural information obtained from these images depend greatly on their resolution, the effect of image resolution on the estimation of the ribs geometrical properties has yet to be established. To do so, each of the thirty-four sections of ribs obtained from a Post Mortem Human Surrogate (PMHS) was imaged using three different CT modalities: standard clinical CT (clinCT), high resolution clinical CT (HRclinCT), and microCT. The images were processed to estimate the rib cross-section geometry and mechanical properties, and the results were compared to those obtained from the microCT images by computing the 'deviation factor', a metric that quantifies the relative difference between results obtained from clinCT and HRclinCT to those obtained from microCT. Overall, clinCT images gave a deviation greater than 100%, and were therefore deemed inadequate for the purpose of this study. HRclinCT overestimated the rib cross-sectional area by 7.6%, the moments of inertia by about 50%, and the cortical shell area by 40.2%, while underestimating the trabecular area by 14.7%. Next, a parametric analysis was performed to quantify how the variations in the estimate of the geometrical properties affected the rib predicted mechanical response under antero-posterior loading. A variation of up to 45% for the predicted peak force and up to 50% for the predicted stiffness was observed. These results provide a quantitative estimate of the sensitivity of the response of the FE model to the resolution of the images used to generate it. They also suggest that a correction factor could be derived from the comparison between microCT and

  17. The architecture of gene regulatory variation across multiple human tissues: the MuTHER study.

    Directory of Open Access Journals (Sweden)

    Alexandra C Nica

    2011-02-01

    Full Text Available While there have been studies exploring regulatory variation in one or more tissues, the complexity of tissue-specificity in multiple primary tissues is not yet well understood. We explore in depth the role of cis-regulatory variation in three human tissues: lymphoblastoid cell lines (LCL, skin, and fat. The samples (156 LCL, 160 skin, 166 fat were derived simultaneously from a subset of well-phenotyped healthy female twins of the MuTHER resource. We discover an abundance of cis-eQTLs in each tissue similar to previous estimates (858 or 4.7% of genes. In addition, we apply factor analysis (FA to remove effects of latent variables, thus more than doubling the number of our discoveries (1,822 eQTL genes. The unique study design (Matched Co-Twin Analysis--MCTA permits immediate replication of eQTLs using co-twins (93%-98% and validation of the considerable gain in eQTL discovery after FA correction. We highlight the challenges of comparing eQTLs between tissues. After verifying previous significance threshold-based estimates of tissue-specificity, we show their limitations given their dependency on statistical power. We propose that continuous estimates of the proportion of tissue-shared signals and direct comparison of the magnitude of effect on the fold change in expression are essential properties that jointly provide a biologically realistic view of tissue-specificity. Under this framework we demonstrate that 30% of eQTLs are shared among the three tissues studied, while another 29% appear exclusively tissue-specific. However, even among the shared eQTLs, a substantial proportion (10%-20% have significant differences in the magnitude of fold change between genotypic classes across tissues. Our results underline the need to account for the complexity of eQTL tissue-specificity in an effort to assess consequences of such variants for complex traits.

  18. Dental size variation in the Atapuerca-SH Middle Pleistocene hominids.

    Science.gov (United States)

    Bermúdez de Castro, J M; Sarmiento, S; Cunha, E; Rosas, A; Bastir, M

    2001-09-01

    The Middle Pleistocene Atapuerca-Sima de los Huesos (SH) site in Spain has yielded the largest sample of fossil hominids so far found from a single site and belonging to the same biological population. The SH dental sample includes a total of 452 permanent and deciduous teeth, representing a minimum of 27 individuals. We present a study of the dental size variation in these hominids, based on the analysis of the mandibular permanent dentition: lateral incisors, n=29; canines, n=27; third premolars, n=30; fourth premolars, n=34; first molars, n=38; second molars, n=38. We have obtained the buccolingual diameter and the crown area (measured on occlusal photographs) of these teeth, and used the bootstrap method to assess the amount of variation in the SH sample compared with the variation of a modern human sample from the Museu Antropologico of the Universidade of Coimbra (Portugal). The SH hominids have, in general terms, a dental size variation higher than that of the modern human sample. The analysis is especially conclusive for the canines. Furthermore, we have estimated the degree of sexual dimorphism of the SH sample by obtaining male and female dental subsamples by means of sexing the large sample of SH mandibular specimens. We obtained the index of sexual dimorphism (ISD=male mean/female mean) and the values were compared with those obtained from the sexed modern human sample from Coimbra, and with data found in the literature concerning several recent human populations. In all tooth classes the ISD of the SH hominids was higher than that of modern humans, but the differences were generally modest, except for the canines, thus suggesting that canine size sexual dimorphism in Homo heidelbergensis was probably greater than that of modern humans. Since the approach of sexing fossil specimens has some obvious limitations, these results should be assessed with caution. Additional data from SH and other European Middle Pleistocene sites would be necessary to test

  19. Quantitative Susceptibility Mapping of Human Brain Reflects Spatial Variation in Tissue Composition

    Science.gov (United States)

    Li, Wei; Wu, Bing; Liu, Chunlei

    2011-01-01

    Image phase from gradient echo MRI provides a unique contrast that reflects brain tissue composition variations, such as iron and myelin distribution. Phase imaging is emerging as a powerful tool for the investigation of functional brain anatomy and disease diagnosis. However, the quantitative value of phase is compromised by its nonlocal and orientation dependent properties. There is an increasing need for reliable quantification of magnetic susceptibility, the intrinsic property of tissue. In this study, we developed a novel and accurate susceptibility mapping method that is also phase-wrap insensitive. The proposed susceptibility mapping method utilized two complementary equations: (1) the Fourier relationship of phase and magnetic susceptibility; and (2) the first-order partial derivative of the first equation in the spatial frequency domain. In numerical simulation, this method reconstructed the susceptibility map almost free of streaking artifact. Further, the iterative implementation of this method allowed for high quality reconstruction of susceptibility maps of human brain in vivo. The reconstructed susceptibility map provided excellent contrast of iron-rich deep nuclei and white matter bundles from surrounding tissues. Further, it also revealed anisotropic magnetic susceptibility in brain white matter. Hence, the proposed susceptibility mapping method may provide a powerful tool for the study of brain physiology and pathophysiology. Further elucidation of anisotropic magnetic susceptibility in vivo may allow us to gain more insight into the white matter microarchitectures. PMID:21224002

  20. A Review on the Applications of Crowdsourcing in Human Pathology

    Science.gov (United States)

    Alialy, Roshanak; Tavakkol, Sasan; Tavakkol, Elham; Ghorbani-Aghbologhi, Amir; Ghaffarieh, Alireza; Kim, Seon Ho; Shahabi, Cyrus

    2018-01-01

    The advent of the digital pathology has introduced new avenues of diagnostic medicine. Among them, crowdsourcing has attracted researchers’ attention in the recent years, allowing them to engage thousands of untrained individuals in research and diagnosis. While there exist several articles in this regard, prior works have not collectively documented them. We, therefore, aim to review the applications of crowdsourcing in human pathology in a semi-systematic manner. We first, introduce a novel method to do a systematic search of the literature. Utilizing this method, we, then, collect hundreds of articles and screen them against a predefined set of criteria. Furthermore, we crowdsource part of the screening process, to examine another potential application of crowdsourcing. Finally, we review the selected articles and characterize the prior uses of crowdsourcing in pathology. PMID:29531847

  1. A review on the applications of crowdsourcing in human pathology

    Directory of Open Access Journals (Sweden)

    Roshanak Alialy

    2018-01-01

    Full Text Available The advent of the digital pathology has introduced new avenues of diagnostic medicine. Among them, crowdsourcing has attracted researchers' attention in the recent years, allowing them to engage thousands of untrained individuals in research and diagnosis. While there exist several articles in this regard, prior works have not collectively documented them. We, therefore, aim to review the applications of crowdsourcing in human pathology in a semi-systematic manner. We first, introduce a novel method to do a systematic search of the literature. Utilizing this method, we, then, collect hundreds of articles and screen them against a predefined set of criteria. Furthermore, we crowdsource part of the screening process, to examine another potential application of crowdsourcing. Finally, we review the selected articles and characterize the prior uses of crowdsourcing in pathology.

  2. Variational inequalities and flow in porous media

    International Nuclear Information System (INIS)

    Chipot, M.

    1984-01-01

    This book is concerned with regularity theory for obstacle problems, and with the dam problem, which, in the rectangular case, is one of the most interesting applications of variational inequalities with an obstacle

  3. A novel system for transcutaneous application of carbon dioxide causing an "artificial Bohr effect" in the human body.

    Directory of Open Access Journals (Sweden)

    Yoshitada Sakai

    Full Text Available BACKGROUND: Carbon dioxide (CO(2 therapy refers to the transcutaneous administration of CO(2 for therapeutic purposes. This effect has been explained by an increase in the pressure of O(2 in tissues known as the Bohr effect. However, there have been no reports investigating the oxygen dissociation of haemoglobin (Hb during transcutaneous application of CO(2in vivo. In this study, we investigate whether the Bohr effect is caused by transcutaneous application of CO2 in human living body. METHODS: We used a novel system for transcutaneous application of CO(2 using pure CO(2 gas, hydrogel, and a plastic adaptor. The validity of the CO(2 hydrogel was confirmed in vitro using a measuring device for transcutaneous CO(2 absorption using rat skin. Next, we measured the pH change in the human triceps surae muscle during transcutaneous application of CO(2 using phosphorus-31 magnetic resonance spectroscopy ((31P-MRS in vivo. In addition, oxy- and deoxy-Hb concentrations were measured with near-infrared spectroscopy in the human arm with occulted blood flow to investigate O2 dissociation from Hb caused by transcutaneous application of CO(2. RESULTS: The rat skin experiment showed that CO(2 hydrogel enhanced CO(2 gas permeation through the rat skin. The intracellular pH of the triceps surae muscle decreased significantly 10 min. after transcutaneous application of CO(2. The NIRS data show the oxy-Hb concentration decreased significantly 4 min. after CO(2 application, and deoxy-Hb concentration increased significantly 2 min. after CO(2 application in the CO(2-applied group compared to the control group. Oxy-Hb concentration significantly decreased while deoxy-Hb concentration significantly increased after transcutaneous CO(2 application. CONCLUSIONS: Our novel transcutaneous CO(2 application facilitated an O(2 dissociation from Hb in the human body, thus providing evidence of the Bohr effect in vivo.

  4. Sources of variation in hair cortisol in wild and captive non-human primates.

    Science.gov (United States)

    Fourie, Nicolaas H; Brown, Janine L; Jolly, Clifford J; Phillips-Conroy, Jane E; Rogers, Jeffrey; Bernstein, Robin M

    2016-04-01

    Hair cortisol analysis is a potentially powerful tool for evaluating adrenal function and chronic stress. However, the technique has only recently been applied widely to studies of wildlife, including primates, and there are numerous practical and technical factors that should be considered to ensure good quality data and the validity of results and conclusions. Here we report on various intrinsic and extrinsic sources of variation in hair cortisol measurements in wild and captive primates. Hair samples from both wild and captive primates revealed that age and sex can affect hair cortisol concentrations; these effects need to be controlled for when making comparisons between individual animals or populations. Hair growth rates also showed considerable inter-specific variation among a number of primate species. We describe technical limitations of hair analyses and variation in cortisol concentrations as a function of asynchronous hair growth, anatomical site of collection, and the amount and numbers of hair/s used for cortisol extraction. We discuss these sources of variation and their implications for proper study design and interpretation of results. Published by Elsevier GmbH.

  5. Variation in calculated human exposure. Comparison of calculations with seven European human exposure models

    NARCIS (Netherlands)

    Swartjes F; ECO

    2003-01-01

    Twenty scenarios, differing with respect to land use, soil type and contaminant, formed the basis for calculating human exposure from soil contaminants with the use of models contributed by seven European countries (one model per country). Here, the human exposures to children and children

  6. A formalism for the calculus of variations with spinors

    Energy Technology Data Exchange (ETDEWEB)

    Bäckdahl, Thomas, E-mail: thobac@chalmers.se [The School of Mathematics, University of Edinburgh, JCMB 6228, Peter Guthrie Tait Road, Edinburgh EH9 3FD, United Kingdom and Mathematical Sciences - Chalmers University of Technology and University of Gothenburg - SE-412 96 Gothenburg (Sweden); Valiente Kroon, Juan A., E-mail: j.a.valiente-kroon@qmul.ac.uk [School of Mathematical Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS (United Kingdom)

    2016-02-15

    We develop a frame and dyad gauge-independent formalism for the calculus of variations of functionals involving spinorial objects. As a part of this formalism, we define a modified variation operator which absorbs frame and spin dyad gauge terms. This formalism is applicable to both the standard spacetime (i.e., SL(2, ℂ)) 2-spinors as well as to space (i.e., SU(2, ℂ)) 2-spinors. We compute expressions for the variations of the connection and the curvature spinors.

  7. A formalism for the calculus of variations with spinors

    International Nuclear Information System (INIS)

    Bäckdahl, Thomas; Valiente Kroon, Juan A.

    2016-01-01

    We develop a frame and dyad gauge-independent formalism for the calculus of variations of functionals involving spinorial objects. As a part of this formalism, we define a modified variation operator which absorbs frame and spin dyad gauge terms. This formalism is applicable to both the standard spacetime (i.e., SL(2, ℂ)) 2-spinors as well as to space (i.e., SU(2, ℂ)) 2-spinors. We compute expressions for the variations of the connection and the curvature spinors

  8. Variations in riboflavin binding by human plasma: identification of immunoglobulins as the major proteins responsible

    International Nuclear Information System (INIS)

    Innis, W.S.; McCormick, D.B.; Merrill, A.H. Jr.

    1985-01-01

    Riboflavin binding by plasma proteins from healthy human subjects was examined by equilibrium dialysis using a physiological concentration of [2-14C]riboflavin (0.04 microM). Binding ranged from 0.080 to 0.917 pmole of riboflavin/mg of protein (with a mean +/- SD of 0.274 +/- 0.206), which corresponded to 4.14 to 49.4 pmole/ml of plasma (15.5 +/- 11.0) (N = 34). Males and females yielded similar results. Upon fractionation of plasma by gel filtration, the major riboflavin-binding components eluted with albumin and gamma-globulins. Albumin was purified and found to bind riboflavin only very weakly (Kd = 3.8 to 10.4 mM), although FMN and photochemical degradation products (e.g., lumiflavine and lumichrome) were more tightly bound. Binding in the gamma-globulin fraction was attributed to IgG and IGA because the binding protein(s) and immunoglobulins copurified using various methods were removed by treatment of plasma with protein A-agarose, and were coincident upon immunoelectrophoresis followed by autoradiography to detect [2-14C]riboflavin. Differences among the plasma samples correlated with the binding recovered with the immunoglobulins. Binding was not directly related to the total IgG or IgA levels of subjects. Hence, it appears that the binding is due to a subfraction of these proteins. These findings suggest that riboflavin-binding immunoglobulins are a major cause of variations in riboflavin binding in human circulation, and may therefore affect the utilization of this micronutrient

  9. Testing the Processing Hypothesis of word order variation using a probabilistic language model

    NARCIS (Netherlands)

    Bloem, J.

    2016-01-01

    This work investigates the application of a measure of surprisal to modeling a grammatical variation phenomenon between near-synonymous constructions. We investigate a particular variation phenomenon, word order variation in Dutch two-verb clusters, where it has been established that word order

  10. Human behavior understanding in networked sensing theory and applications of networks of sensors

    CERN Document Server

    Spagnolo, Paolo; Distante, Cosimo

    2014-01-01

    This unique text/reference provides a broad overview of both the technical challenges in sensor network development, and the real-world applications of distributed sensing. Important aspects of distributed computing in large-scale networked sensor systems are analyzed in the context of human behavior understanding, including such topics as systems design tools and techniques, in-network signals, and information processing. Additionally, the book examines a varied range of application scenarios, covering surveillance, indexing and retrieval, patient care, industrial safety, social and ambient

  11. Analysis of genetic variation and potential applications in genome-scale metabolic modeling

    DEFF Research Database (Denmark)

    Cardoso, Joao; Andersen, Mikael Rørdam; Herrgard, Markus

    2015-01-01

    scale and resolution by re-sequencing thousands of strains systematically. In this article, we review challenges in the integration and analysis of large-scale re-sequencing data, present an extensive overview of bioinformatics methods for predicting the effects of genetic variants on protein function......Genetic variation is the motor of evolution and allows organisms to overcome the environmental challenges they encounter. It can be both beneficial and harmful in the process of engineering cell factories for the production of proteins and chemicals. Throughout the history of biotechnology......, there have been efforts to exploit genetic variation in our favor to create strains with favorable phenotypes. Genetic variation can either be present in natural populations or it can be artificially created by mutagenesis and selection or adaptive laboratory evolution. On the other hand, unintended genetic...

  12. Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects

    Science.gov (United States)

    Meier-Ewert, H. K.; Ridker, P. M.; Rifai, N.; Price, N.; Dinges, D. F.; Mullington, J. M.

    2001-01-01

    BACKGROUND: The concentration of C-reactive protein (CRP) in otherwise healthy subjects has been shown to predict future risk of myocardial infarction and stroke. CRP is synthesized by the liver in response to interleukin-6, the serum concentration of which is subject to diurnal variation. METHODS: To examine the existence of a time-of-day effect for baseline CRP values, we determined CRP concentrations in hourly blood samples drawn from healthy subjects (10 males, 3 females; age range, 21-35 years) during a baseline day in a controlled environment (8 h of nighttime sleep). RESULTS: Overall CRP concentrations were low, with only three subjects having CRP concentrations >2 mg/L. Comparison of raw data showed stability of CRP concentrations throughout the 24 h studied. When compared with cutoff values of CRP quintile derived from population-based studies, misclassification of greater than one quintile did not occur as a result of diurnal variation in any of the subjects studied. Nonparametric ANOVA comparing different time points showed no significant differences for both raw and z-transformed data. Analysis for rhythmic diurnal variation using a method fitting a cosine curve to the group data was negative. CONCLUSIONS: Our data show that baseline CRP concentrations are not subject to time-of-day variation and thus help to explain why CRP concentrations are a better predictor of vascular risk than interleukin-6. Determination of CRP for cardiovascular risk prediction may be performed without concern for diurnal variation.

  13. Solutions to variational inequalities of parabolic type

    Science.gov (United States)

    Zhu, Yuanguo

    2006-09-01

    The existence of strong solutions to a kind of variational inequality of parabolic type is investigated by the theory of semigroups of linear operators. As an application, an abstract semi permeable media problem is studied.

  14. Big Data and Intelligence: Applications, Human Capital, and Education

    Directory of Open Access Journals (Sweden)

    Michael Landon-Murray

    2016-06-01

    Full Text Available The potential for big data to contribute to the US intelligence mission goes beyond bulk collection, social media and counterterrorism. Applications will speak to a range of issues of major concern to intelligence agencies, from military operations to climate change to cyber security. There are challenges too: procurement lags, data stovepiping, separating signal from noise, sources and methods, a range of normative issues, and central to managing these challenges, human capital. These potential applications and challenges are discussed and a closer look at what data scientists do in the Intelligence Community (IC is offered. Effectively filling the ranks of the IC’s data science workforce will depend on the provision of well-trained data scientists from the higher education system. Program offerings at America’s top fifty universities will thus be surveyed (just a few years ago there were reportedly no degrees in data science. One Master’s program that has melded data science with intelligence is examined as well as a university big data research center focused on security and intelligence. This discussion goes a long way to clarify the prospective uses of data science in intelligence while probing perhaps the key challenge to optimal application of big data in the IC.

  15. Chondrocyte heterogeneity: immunohistologically defined variation of integrin expression at different sites in human fetal knees.

    Science.gov (United States)

    Salter, D M; Godolphin, J L; Gourlay, M S

    1995-04-01

    During development and at maturity different forms of cartilage vary in morphology and macromolecular content. This reflects heterogeneity of chondrocyte activity, in part involving differential interactions with the adjacent extracellular matrix via specialized cell surface receptors such as integrins. We undertook an immunohistological study on a series of human fetal knee joints to assess variation in the expression of integrins by chondrocytes and potential matrix ligands in articular, epiphyseal, growth plate, and meniscal cartilage. The results show that articular chondrocytes (beta 1+, beta 5 alpha V+, alpha 1+, alpha 2+/-, alpha 5+, weakly alpha 6+, alpha V+) differed from epiphyseal (beta 1+, beta 5 alpha V+, alpha 1+/-, alpha 2+/-, alpha 5+, alpha 6+, alpha V+) growth plate (beta 1+, beta 5 alpha V+, alpha 1-, alpha 2-, alpha 5+, alpha 6+, alpha V+), and meniscal cells (beta 1+, beta 5 alpha V+, alpha 1+, strongly alpha 2+, alpha 5+, alpha 6+, alpha V+ in expression of integrin subunits. There was no expression of beta 3, beta 4, beta 6, or alpha 3 by chondrocytes. These results differ from previous reports on the expression of integrins by adult articular cartilage, where alpha 2 and alpha 6 are not seen. Variation in distribution of matrix ligands was also seen. Fibronectin, laminin and Type VI collagen were expressed in all cartilages but there was restricted expression of tenascin, ED-A and ED-B fibronectin isoforms (articular cartilage and meniscus), and vitronectin (absent from growth plate cartilage). Regulated expression of integrins by chondrocytes, associated with changes in the pericellular matrix composition, is of potential importance in control of cartilage differentiation and function in health and disease.

  16. Note: Dynamic Conjectural Variations in a Lanchester Oligopoly

    OpenAIRE

    Gary M. Erickson

    1997-01-01

    An approach based on dynamic conjectural variations is advanced for developing dynamic advertising strategies in a Lanchester oligopoly differential game. The approach allows competitors to anticipate rival reactions to market-share state variables, and maintains the computational advantage of open-loop Nash equilibrium strategies. In an empirical application to the ready-to-eat cereal industry, it is shown that advertising strategies based on dynamic conjectural variations can better explain...

  17. Genetic effects on gene expression across human tissues

    NARCIS (Netherlands)

    Battle, Alexis; Brown, Christopher D.; Engelhardt, Barbara E.; Montgomery, Stephen B.; Aguet, François; Ardlie, Kristin G.; Cummings, Beryl B.; Gelfand, Ellen T.; Getz, Gad; Hadley, Kane; Handsaker, Robert E.; Huang, Katherine H.; Kashin, Seva; Karczewski, Konrad J.; Lek, Monkol; Li, Xiao; MacArthur, Daniel G.; Nedzel, Jared L.; Nguyen, Duyen T.; Noble, Michael S.; Segrè, Ayellet V.; Trowbridge, Casandra A.; Tukiainen, Taru; Abell, Nathan S.; Balliu, Brunilda; Barshir, Ruth; Basha, Omer; Bogu, Gireesh K.; Brown, Andrew; Castel, Stephane E.; Chen, Lin S.; Chiang, Colby; Conrad, Donald F.; Cox, Nancy J.; Damani, Farhan N.; Davis, Joe R.; Delaneau, Olivier; Dermitzakis, Emmanouil T.; Eskin, Eleazar; Ferreira, Pedro G.; Frésard, Laure; Gamazon, Eric R.; Garrido-Martín, Diego; Gewirtz, Ariel D. H.; Gliner, Genna; Gloudemans, Michael J.; Guigo, Roderic; Hall, Ira M.; Han, Buhm; He, Yuan

    2017-01-01

    Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression

  18. Identification of stiffness variations in supporting substances of a human canine tooth with a bracket-beam-piezoelectric sensor and its electromechanical impedance

    Directory of Open Access Journals (Sweden)

    Hector A. Tinoco

    2017-06-01

    Full Text Available In this paper, an experimental method is described to identify the stiffness variations produced by drillings done in different supporting substances of a human canine tooth. To measure the supporting substances parameters through of a canine, a sensor-actuator system was developed. The sensor-actuator device was composed of a stainless steel bracket bonded to a steel wire attached to two piezoelectric transducers, with a concentrated mass attached to the end of the wire. To excite the device, high frequency voltage (between 5 and 10 KHz was applied through the piezo-transducers, which affects the tooth by means of the vibration of the wire. High frequency mechanical vibrations allowed the appraisal of the mechanical response from the supporting substances. Mechanical responses associated with the stiffness of the support were quantified with the electrical impedance of the piezo-transducers. The device was coupled to the crown of a canine tooth simulating a condition of fixing as in the bone, the tooth was fastened by the root portion inside the supporting substance. Four supporting substances were characterized for the tests. After establishing base values of the stiffness of each supporting substance, the stiffness variations were assessed in two stages (two drillings; these were made perpendicularly to the longitudinal axis of the tooth, Results show that it is possible to assess stiffness variations with the proposed methodology as well as to quantify the stiffness differences, by means of variation indexes.

  19. Systematic documentation and analysis of human genetic variation in hemoglobinopathies using the microattribution approach

    NARCIS (Netherlands)

    B. Giardine (Belinda); J. Borg (Joseph); D.R. Higgs (Douglas); K.R. Peterson (Kenneth R.); J.N.J. Philipsen (Sjaak); D. Maglott (Donna); B.K. Singleton (Belinda K.); D.J. Anstee (David J.); A.N. Basak (Nazli); B.H. Clark (Bruce); F.C. Costa (Flavia C.); P. Faustino (Paula); H. Fedosyuk (Halyna); A.E. Felice (Alex); A. Francina (Alain); R. Galanello (Renzo); M.V.E. Gallivan (Monica V. E.); M. Georgitsi (Marianthi); R.J. Gibbons (Richard J.); P.C. Giordano (Piero Carlo); C.L. Harteveld (Cornelis); J.D. Hoyer (James D.); M. Jarvis (Martin); P. Joly (Philippe); E. Kanavakis (Emmanuel); P. Kollia (Panagoula); S. Menzel (Stephan); W.G. Miller (William); K. Moradkhani (Kamran); J. Old (John); A. Papachatzpoulou (Adamantia); M.N. Papadakis (Manoussos); P. Papadopoulos (Petros); S. Pavlovic (Sonja); L. Perseu (Lucia); M. Radmilovic (Milena); C. Riemer (Cathy); S. Satta (Stefania); I.A. Schrijver (Ingrid); M. Stojiljkovic (Maja); S.L. Thein; J. Traeger-Synodinos (Joanne); R. Tully (Ray); T. Wada (Takahito); J.S. Waye (John); C. Wiemann (Claudia); B. Zukic (Branka); D.H.K. Chui (David H. K.); H. Wajcman (Henri); R. Hardison (Ross); G.P. Patrinos (George)

    2011-01-01

    textabstractWe developed a series of interrelated locus-specific databases to store all published and unpublished genetic variation related to hemoglobinopathies and thalassemia and implemented microattribution to encourage submission of unpublished observations of genetic variation to these public

  20. Variational regularization of 3D data experiments with Matlab

    CERN Document Server

    Montegranario, Hebert

    2014-01-01

    Variational Regularization of 3D Data provides an introduction to variational methods for data modelling and its application in computer vision. In this book, the authors identify interpolation as an inverse problem that can be solved by Tikhonov regularization. The proposed solutions are generalizations of one-dimensional splines, applicable to n-dimensional data and the central idea is that these splines can be obtained by regularization theory using a trade-off between the fidelity of the data and smoothness properties.As a foundation, the authors present a comprehensive guide to the necessary fundamentals of functional analysis and variational calculus, as well as splines. The implementation and numerical experiments are illustrated using MATLAB®. The book also includes the necessary theoretical background for approximation methods and some details of the computer implementation of the algorithms. A working knowledge of multivariable calculus and basic vector and matrix methods should serve as an adequat...

  1. The ecological importance of intraspecific variation.

    Science.gov (United States)

    Des Roches, Simone; Post, David M; Turley, Nash E; Bailey, Joseph K; Hendry, Andrew P; Kinnison, Michael T; Schweitzer, Jennifer A; Palkovacs, Eric P

    2018-01-01

    Human activity is causing wild populations to experience rapid trait change and local extirpation. The resulting effects on intraspecific variation could have substantial consequences for ecological processes and ecosystem services. Although researchers have long acknowledged that variation among species influences the surrounding environment, only recently has evidence accumulated for the ecological importance of variation within species. We conducted a meta-analysis comparing the ecological effects of variation within a species (intraspecific effects) with the effects of replacement or removal of that species (species effects). We evaluated direct and indirect ecological responses, including changes in abundance (or biomass), rates of ecological processes and changes in community composition. Our results show that intraspecific effects are often comparable to, and sometimes stronger than, species effects. Species effects tend to be larger for direct ecological responses (for example, through consumption), whereas intraspecific effects and species effects tend to be similar for indirect responses (for example, through trophic cascades). Intraspecific effects are especially strong when indirect interactions alter community composition. Our results summarize data from the first generation of studies examining the relative ecological effects of intraspecific variation. Our conclusions can help inform the design of future experiments and the formulation of strategies to quantify and conserve biodiversity.

  2. Solid mechanics a variational approach

    CERN Document Server

    Dym, Clive L

    2013-01-01

    Solid Mechanics: A Variational Approach, Augmented Edition presents a lucid and thoroughly developed approach to solid mechanics for students engaged in the study of elastic structures not seen in other texts currently on the market. This work offers a clear and carefully prepared exposition of variational techniques as they are applied to solid mechanics. Unlike other books in this field, Dym and Shames treat all the necessary theory needed for the study of solid mechanics and include extensive applications. Of particular note is the variational approach used in developing consistent structural theories and in obtaining exact and approximate solutions for many problems.  Based on both semester and year-long courses taught to undergraduate seniors and graduate students, this text is geared for programs in aeronautical, civil, and mechanical engineering, and in engineering science. The authors’ objective is two-fold: first, to introduce the student to the theory of structures (one- and two-dimensional) as ...

  3. A New Result Concerning the Solvability of a Class of General Systems of Variational Equations with Nonmonotone Operators: Applications to Dirichlet and Neumann Nonlinear Problems

    Directory of Open Access Journals (Sweden)

    Luisa Toscano

    2016-01-01

    Full Text Available A new result of solvability for a wide class of systems of variational equations depending on parameters and governed by nonmonotone operators is found in a Banach real and reflexive space with applications to Dirichlet and Neumann problems related to nonlinear elliptic systems.

  4. Defining the diverse spectrum of inversions, complex structural variation, and chromothripsis in the morbid human genome.

    Science.gov (United States)

    Collins, Ryan L; Brand, Harrison; Redin, Claire E; Hanscom, Carrie; Antolik, Caroline; Stone, Matthew R; Glessner, Joseph T; Mason, Tamara; Pregno, Giulia; Dorrani, Naghmeh; Mandrile, Giorgia; Giachino, Daniela; Perrin, Danielle; Walsh, Cole; Cipicchio, Michelle; Costello, Maura; Stortchevoi, Alexei; An, Joon-Yong; Currall, Benjamin B; Seabra, Catarina M; Ragavendran, Ashok; Margolin, Lauren; Martinez-Agosto, Julian A; Lucente, Diane; Levy, Brynn; Sanders, Stephan J; Wapner, Ronald J; Quintero-Rivera, Fabiola; Kloosterman, Wigard; Talkowski, Michael E

    2017-03-06

    Structural variation (SV) influences genome organization and contributes to human disease. However, the complete mutational spectrum of SV has not been routinely captured in disease association studies. We sequenced 689 participants with autism spectrum disorder (ASD) and other developmental abnormalities to construct a genome-wide map of large SV. Using long-insert jumping libraries at 105X mean physical coverage and linked-read whole-genome sequencing from 10X Genomics, we document seven major SV classes at ~5 kb SV resolution. Our results encompass 11,735 distinct large SV sites, 38.1% of which are novel and 16.8% of which are balanced or complex. We characterize 16 recurrent subclasses of complex SV (cxSV), revealing that: (1) cxSV are larger and rarer than canonical SV; (2) each genome harbors 14 large cxSV on average; (3) 84.4% of large cxSVs involve inversion; and (4) most large cxSV (93.8%) have not been delineated in previous studies. Rare SVs are more likely to disrupt coding and regulatory non-coding loci, particularly when truncating constrained and disease-associated genes. We also identify multiple cases of catastrophic chromosomal rearrangements known as chromoanagenesis, including somatic chromoanasynthesis, and extreme balanced germline chromothripsis events involving up to 65 breakpoints and 60.6 Mb across four chromosomes, further defining rare categories of extreme cxSV. These data provide a foundational map of large SV in the morbid human genome and demonstrate a previously underappreciated abundance and diversity of cxSV that should be considered in genomic studies of human disease.

  5. Sphingosine-1-Phosphate Signaling Regulates Myogenic Responsiveness in Human Resistance Arteries.

    Directory of Open Access Journals (Sweden)

    Sonya Hui

    Full Text Available We recently identified sphingosine-1-phosphate (S1P signaling and the cystic fibrosis transmembrane conductance regulator (CFTR as prominent regulators of myogenic responsiveness in rodent resistance arteries. However, since rodent models frequently exhibit limitations with respect to human applicability, translation is necessary to validate the relevance of this signaling network for clinical application. We therefore investigated the significance of these regulatory elements in human mesenteric and skeletal muscle resistance arteries. Mesenteric and skeletal muscle resistance arteries were isolated from patient tissue specimens collected during colonic or cardiac bypass surgery. Pressure myography assessments confirmed endothelial integrity, as well as stable phenylephrine and myogenic responses. Both human mesenteric and skeletal muscle resistance arteries (i express critical S1P signaling elements, (ii constrict in response to S1P and (iii lose myogenic responsiveness following S1P receptor antagonism (JTE013. However, while human mesenteric arteries express CFTR, human skeletal muscle resistance arteries do not express detectable levels of CFTR protein. Consequently, modulating CFTR activity enhances myogenic responsiveness only in human mesenteric resistance arteries. We conclude that human mesenteric and skeletal muscle resistance arteries are a reliable and consistent model for translational studies. We demonstrate that the core elements of an S1P-dependent signaling network translate to human mesenteric resistance arteries. Clear species and vascular bed variations are evident, reinforcing the critical need for further translational study.

  6. Gauging Variational Inference

    Energy Technology Data Exchange (ETDEWEB)

    Chertkov, Michael [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Ahn, Sungsoo [Korea Advanced Inst. Science and Technology (KAIST), Daejeon (Korea, Republic of); Shin, Jinwoo [Korea Advanced Inst. Science and Technology (KAIST), Daejeon (Korea, Republic of)

    2017-05-25

    Computing partition function is the most important statistical inference task arising in applications of Graphical Models (GM). Since it is computationally intractable, approximate methods have been used to resolve the issue in practice, where meanfield (MF) and belief propagation (BP) are arguably the most popular and successful approaches of a variational type. In this paper, we propose two new variational schemes, coined Gauged-MF (G-MF) and Gauged-BP (G-BP), improving MF and BP, respectively. Both provide lower bounds for the partition function by utilizing the so-called gauge transformation which modifies factors of GM while keeping the partition function invariant. Moreover, we prove that both G-MF and G-BP are exact for GMs with a single loop of a special structure, even though the bare MF and BP perform badly in this case. Our extensive experiments, on complete GMs of relatively small size and on large GM (up-to 300 variables) confirm that the newly proposed algorithms outperform and generalize MF and BP.

  7. Reflectance diffuse optical tomography. Its application to human brain mapping

    International Nuclear Information System (INIS)

    Ueda, Yukio; Yamanaka, Takeshi; Yamashita, Daisuke; Suzuki, Toshihiko; Ohmae, Etsuko; Oda, Motoki; Yamashita, Yutaka

    2005-01-01

    We report the successful application of reflectance diffuse optical tomography (DOT) using near-infrared light with the new reconstruction algorithm that we developed to the observation of regional hemodynamic changes in the brain under specific mental tasks. Our results reveal the heterogeneous distribution of oxyhemoglobin and deoxyhemoglobin in the brain, showing complementary images of oxyhemoglobin and deoxyhemoglobin changes in certain regions. We conclude that our reflectance DOT has practical potential for human brain mapping, as well as in the diagnostic imaging of brain diseases. (author)

  8. The first Malay database toward the ethnic-specific target molecular variation.

    Science.gov (United States)

    Halim-Fikri, Hashim; Etemad, Ali; Abdul Latif, Ahmad Zubaidi; Merican, Amir Feisal; Baig, Atif Amin; Annuar, Azlina Ahmad; Ismail, Endom; Salahshourifar, Iman; Liza-Sharmini, Ahmad Tajudin; Ramli, Marini; Shah, Mohamed Irwan; Johan, Muhammad Farid; Hassan, Nik Norliza Nik; Abdul-Aziz, Noraishah Mydin; Mohd Noor, Noor Haslina; Nur-Shafawati, Ab Rajab; Hassan, Rosline; Bahar, Rosnah; Zain, Rosnah Binti; Yusoff, Shafini Mohamed; Yusoff, Surini; Tan, Soon Guan; Thong, Meow-Keong; Wan-Isa, Hatin; Abdullah, Wan Zaidah; Mohamed, Zahurin; Abdul Latiff, Zarina; Zilfalil, Bin Alwi

    2015-04-30

    The Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9(th) October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb). Currently, MyHVPDb provides only information about the genetic variations and mutations found in the Malays. In the near future, it will expand for the other Malaysian ethnics as well. The data sets are specified based on diseases or genetic mutation types which have three main subcategories: Single Nucleotide Polymorphism (SNP), Copy Number Variation (CNV) followed by the mutations which code for the common diseases among Malaysians. MyHVPDb has been open to the local researchers, academicians and students through the registration at the portal of MyHVP ( http://hvpmalaysia.kk.usm.my/mhgvc/index.php?id=register ). This database would be useful for clinicians and researchers who are interested in doing a study on genomics population and genetic diseases in order to obtain up-to-date and accurate information regarding the population-specific variations and also useful for those in countries with similar ethnic background.

  9. Mobile Applications for Patient-centered Care Coordination: A Review of Human Factors Methods Applied to their Design, Development, and Evaluation.

    Science.gov (United States)

    Baysari, M T; Westbrook, J I

    2015-08-13

    To examine if human factors methods were applied in the design, development, and evaluation of mobile applications developed to facilitate aspects of patient-centered care coordination. We searched MEDLINE and EMBASE (2013-2014) for studies describing the design or the evaluation of a mobile health application that aimed to support patients' active involvement in the coordination of their care. 34 papers met the inclusion criteria. Applications ranged from tools that supported self-management of specific conditions (e.g. asthma) to tools that provided coaching or education. Twelve of the 15 papers describing the design or development of an app reported the use of a human factors approach. The most frequently used methods were interviews and surveys, which often included an exploration of participants' current use of information technology. Sixteen papers described the evaluation of a patient application in practice. All of them adopted a human factors approach, typically an examination of the use of app features and/or surveys or interviews which enquired about patients' views of the effects of using the app on their behaviors (e.g. medication adherence), knowledge, and relationships with healthcare providers. No study in our review assessed the impact of mobile applications on health outcomes. The potential of mobile health applications to assist patients to more actively engage in the management of their care has resulted in a large number of applications being developed. Our review showed that human factors approaches are nearly always adopted to some extent in the design, development, and evaluation of mobile applications.

  10. Copy number variation in the bovine genome

    DEFF Research Database (Denmark)

    Fadista, João; Thomsen, Bo; Holm, Lars-Erik

    2010-01-01

    to genetic variation in cattle. Results We designed and used a set of NimbleGen CGH arrays that tile across the assayable portion of the cattle genome with approximately 6.3 million probes, at a median probe spacing of 301 bp. This study reports the highest resolution map of copy number variation...... in the cattle genome, with 304 CNV regions (CNVRs) being identified among the genomes of 20 bovine samples from 4 dairy and beef breeds. The CNVRs identified covered 0.68% (22 Mb) of the genome, and ranged in size from 1.7 to 2,031 kb (median size 16.7 kb). About 20% of the CNVs co-localized with segmental...... duplications, while 30% encompass genes, of which the majority is involved in environmental response. About 10% of the human orthologous of these genes are associated with human disease susceptibility and, hence, may have important phenotypic consequences. Conclusions Together, this analysis provides a useful...

  11. Control Variates for Monte Carlo Valuation of American Options

    DEFF Research Database (Denmark)

    Rasmussen, Nicki S.

    2005-01-01

    This paper considers two applications of control variates to the Monte Carlo valuation of American options. The main contribution of the paper lies in the particular choice of a control variate for American or Bermudan options. It is shown that for any martingale process used as a control variate...... technique is used for improving the least-squares Monte Carlo (LSM) approach for determining exercise strategies. The suggestions made allow for more efficient estimation of the continuation value, used in determining the strategy. An additional suggestion is made in order to improve the stability...

  12. Human body heat for powering wearable devices: From thermal energy to application

    International Nuclear Information System (INIS)

    Thielen, Moritz; Sigrist, Lukas; Magno, Michele; Hierold, Christofer; Benini, Luca

    2017-01-01

    Highlights: • A complete system optimization for wearable thermal harvesting from body heat to the application is proposed. • State-of-the-art thermal harvesters and DC-DC converters are compared and classified. • Extensive simulation and experiments are carried out to characterize the harvesting performance. • A case study demonstrates the feasibility to supply a multi-sensor wearables only from body heat. - Abstract: Energy harvesting is the key technology to enable self-sustained wearable devices for the Internet of Things and medical applications. Among various types of harvesting sources such as light, vibration and radio frequency, thermoelectric generators (TEG) are a promising option due to their independence of light conditions or the activity of the wearer. This work investigates scavenging of human body heat and the optimization of the power conversion efficiency from body core to the application. We focus on the critical interaction between thermal harvester and power conditioning circuitry and compare two approaches: (1) a high output voltage, low thermal resistance μTEG combined with a high efficiency actively controlled single inductor DC-DC converter, and (2) a high thermal resistance, low electric resistance mTEG in combination with a low-input voltage coupled inductors based DC-DC converter. The mTEG approach delivers up to 65% higher output power per area in a lab setup and 1–15% in a real-world experiment on the human body depending on physical activity and environmental conditions. Using off-the-shelf and low-cost components, we achieve an average power of 260 μW (μTEG) to 280 μW (mTEG) and power densities of 13 μW cm"−"2 (μTEG) to 14 μW cm"−"2 (mTEG) for systems worn on the human wrist. With the small and lightweight harvesters optimized for wearability, 16% (mTEG) to 24% (μTEG) of the theoretical maximum efficiency is achieved in a worst-case scenario. This efficiency highly depends on the application specific conditions

  13. Annotating the biomedical literature for the human variome.

    Science.gov (United States)

    Verspoor, Karin; Jimeno Yepes, Antonio; Cavedon, Lawrence; McIntosh, Tara; Herten-Crabb, Asha; Thomas, Zoë; Plazzer, John-Paul

    2013-01-01

    This article introduces the Variome Annotation Schema, a schema that aims to capture the core concepts and relations relevant to cataloguing and interpreting human genetic variation and its relationship to disease, as described in the published literature. The schema was inspired by the needs of the database curators of the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) database, but is intended to have application to genetic variation information in a range of diseases. The schema has been applied to a small corpus of full text journal publications on the subject of inherited colorectal cancer. We show that the inter-annotator agreement on annotation of this corpus ranges from 0.78 to 0.95 F-score across different entity types when exact matching is measured, and improves to a minimum F-score of 0.87 when boundary matching is relaxed. Relations show more variability in agreement, but several are reliable, with the highest, cohort-has-size, reaching 0.90 F-score. We also explore the relevance of the schema to the InSiGHT database curation process. The schema and the corpus represent an important new resource for the development of text mining solutions that address relationships among patient cohorts, disease and genetic variation, and therefore, we also discuss the role text mining might play in the curation of information related to the human variome. The corpus is available at http://opennicta.com/home/health/variome.

  14. Human Reliability Analysis. Applicability of the HRA-concept in maintenance shutdown

    International Nuclear Information System (INIS)

    Obenius, Aino

    2007-08-01

    work tasks. Errors and mistakes during this plant operating state may have severe consequences, both on the immediate work, as well as on the future power production. The human influence on the technical system is of great importance when analysing the LPSD condition. This should also affect the basis and performance of the analysis, to make as a realistic analysis as possible. When analysing human operation during LPSD, a holistic perspective should be used. A way to take the human abilities and performance variability into consideration is important. The study of performed analysis of human reliability for the LPSD condition shows, that the normative and/or descriptive approach and the linear cause-effect model are used. The main objective of HRAs performed within SPSAs is the quantification of human interaction and error frequency. Modelling of human behaviour in complex, sociotechnical systems differs in theory and practice. A reason may be that models as the one for functional resonance, not yet are applicable for practising analysts, due to a lack of well tried methods and the fact that analysis of the LPSD condition is performed in the PSA concept, which defines the type of results sought from the HRA, i.e. probabilities for human error. LPSD analysis methods need to be further evaluated, validated and developed. The basis for the analysis should, instead of PSA, be a holistic analysis according to how Man, Technology and Organization affect the system and plant safety. To achieve this, further activities could be to perform an in-depth study of existing analysis of the LPSD condition, to develop specifications of requirement for LPSD analysis, to further validate the HRA work process as well as to further develop practically applicable methods for human performance and variability analysis in sociotechnical systems

  15. From phenotypic to molecular polymorphisms involved in naturally occurring variation for plant development

    NARCIS (Netherlands)

    Alonso-Blanco, C.; Mendez-Vigo, B.; Koornneef, M.

    2005-01-01

    An enormous amount of naturally occurring genetic variation affecting development is found within wild and domesticated plant species. This diversity is presumably involved in plant adaptation to different natural environments or in human preferences. In addition, such intraspecific variation

  16. An interactive web application for the dissemination of human systems immunology data.

    Science.gov (United States)

    Speake, Cate; Presnell, Scott; Domico, Kelly; Zeitner, Brad; Bjork, Anna; Anderson, David; Mason, Michael J; Whalen, Elizabeth; Vargas, Olivia; Popov, Dimitry; Rinchai, Darawan; Jourde-Chiche, Noemie; Chiche, Laurent; Quinn, Charlie; Chaussabel, Damien

    2015-06-19

    Systems immunology approaches have proven invaluable in translational research settings. The current rate at which large-scale datasets are generated presents unique challenges and opportunities. Mining aggregates of these datasets could accelerate the pace of discovery, but new solutions are needed to integrate the heterogeneous data types with the contextual information that is necessary for interpretation. In addition, enabling tools and technologies facilitating investigators' interaction with large-scale datasets must be developed in order to promote insight and foster knowledge discovery. State of the art application programming was employed to develop an interactive web application for browsing and visualizing large and complex datasets. A collection of human immune transcriptome datasets were loaded alongside contextual information about the samples. We provide a resource enabling interactive query and navigation of transcriptome datasets relevant to human immunology research. Detailed information about studies and samples are displayed dynamically; if desired the associated data can be downloaded. Custom interactive visualizations of the data can be shared via email or social media. This application can be used to browse context-rich systems-scale data within and across systems immunology studies. This resource is publicly available online at [Gene Expression Browser Landing Page ( https://gxb.benaroyaresearch.org/dm3/landing.gsp )]. The source code is also available openly [Gene Expression Browser Source Code ( https://github.com/BenaroyaResearch/gxbrowser )]. We have developed a data browsing and visualization application capable of navigating increasingly large and complex datasets generated in the context of immunological studies. This intuitive tool ensures that, whether taken individually or as a whole, such datasets generated at great effort and expense remain interpretable and a ready source of insight for years to come.

  17. Promise and Capability of NASA's Earth Observing System to Monitor Human-Induced Climate Variations

    Science.gov (United States)

    King, M. D.

    2003-01-01

    The Earth Observing System (EOS) is a space-based observing system comprised of a series of satellite sensors by which scientists can monitor the Earth, a Data and Information System (EOSDIS) enabling researchers worldwide to access the satellite data, and an interdisciplinary science research program to interpret the satellite data. The Moderate Resolution Imaging Spectroradiometer (MODIS), developed as part of the Earth Observing System (EOS) and launched on Terra in December 1999 and Aqua in May 2002, is designed to meet the scientific needs for satellite remote sensing of clouds, aerosols, water vapor, and land and ocean surface properties. This sensor and multi-platform observing system is especially well suited to observing detailed interdisciplinary components of the Earth s surface and atmosphere in and around urban environments, including aerosol optical properties, cloud optical and microphysical properties of both liquid water and ice clouds, land surface reflectance, fire occurrence, and many other properties that influence the urban environment and are influenced by them. In this presentation I will summarize the current capabilities of MODIS and other EOS sensors currently in orbit to study human-induced climate variations.

  18. APPLICABILITY OF A HUMAN LACTOFERRIN IN PEDIATRIC PRACTICE

    Directory of Open Access Journals (Sweden)

    T. E. Borovik

    2014-01-01

    Full Text Available Modern data on efficiency and safety of a recombinant human lactoferrin (hLf and prospects of its use in pediatric practice are presented in the review of literary data. The unique anti-infectious properties of biologically active protein of the hLf, its high antimicrobic, antiviral, antifungal and anti-parasitic activity are noted. Ability to stimulate natural immunity, to interact with other antimicrobic peptides, in particular, with lysozyme and secretory leukocyte protease inhibitor is analysed. In this regard it is indicated prospects of application of the hLf in treatment of prematurely born and hypotrophic children, patients with chronic nutritional deficiency for the purpose of prevention of infectious diseases and correction of inflammatory changes in the organism of a child, includingacute respiratory virus and enteric infections in children. It is expedient to apply hLf in surgical practice for reduction of a degree of manifestation of the acute pro-inflammatory response, and also for prevention of infectious complications, especially after abdominal operations, in complex treatment of children with a severe generalized infection and multi-organ failure, for prevention of intrahospital nosocomial infections in children hospitals.Key words: children, prematurely born, nutritional deficiency, infections, lactoferrin, recombinant human lactoferrin.

  19. Measuring Accurate Body Parameters of Dressed Humans with Large-Scale Motion Using a Kinect Sensor

    Directory of Open Access Journals (Sweden)

    Sidan Du

    2013-08-01

    Full Text Available Non-contact human body measurement plays an important role in surveillance, physical healthcare, on-line business and virtual fitting. Current methods for measuring the human body without physical contact usually cannot handle humans wearing clothes, which limits their applicability in public environments. In this paper, we propose an effective solution that can measure accurate parameters of the human body with large-scale motion from a Kinect sensor, assuming that the people are wearing clothes. Because motion can drive clothes attached to the human body loosely or tightly, we adopt a space-time analysis to mine the information across the posture variations. Using this information, we recover the human body, regardless of the effect of clothes, and measure the human body parameters accurately. Experimental results show that our system can perform more accurate parameter estimation on the human body than state-of-the-art methods.

  20. Maslow's Theory of Human Motivation and its Deep Roots in Individualism: Interrogating Maslow's Applicability in Africa

    OpenAIRE

    Mawere, Munyaradzi; Mubaya, Tapuwa R.; van Reisen, Mirjam; Stam, van, Gertjan; Mawere, Munyaradzi; Nhemachena, Artwell

    2016-01-01

    Since the postulation of Abraham Maslow's theory of human motivation, the theory has been celebrated as the determining factor to account for and explain human wants and needs. While the theory has its genealogy from an individualistic society, the United States of America, where it was crafted and propelled to take a stand as a universal theory determining human wants and needs across the world, little has been done to critically examine its seemingly perceived universality and applicability...

  1. Principal component analysis to evaluate the spatial variation of ...

    African Journals Online (AJOL)

    Discretisation of the particle sizes is highlighted as both a challenge and an opportunity and it is recommended that it be used as a tuning parameter in gauging kaolin variations across samples and in validating new predictive modeling applications. Successful applications will depend on how clay and data scientists keep ...

  2. Assessing vegetation response to climatic variations and human activities: spatiotemporal NDVI variations in the Hexi Corridor and surrounding areas from 2000 to 2010

    Science.gov (United States)

    Guan, Qingyu; Yang, Liqin; Guan, Wenqian; Wang, Feifei; Liu, Zeyu; Xu, Chuanqi

    2018-03-01

    Vegetation cover is a commonly used indicator for evaluating terrestrial environmental conditions, and for revealing environmental evolution and transitions. Spatiotemporal variations in the vegetation cover of the Hexi Corridor and surrounding areas from 2000 to 2010 were investigated using MODIS NDVI data, and the causes of vegetation cover changes were analyzed, considering both climatic variability and human activities. The vegetation cover of the study area increased during 2000-2010. The greenness of the vegetation showed a significant increase from the northwest to the southeast, which was similar to the spatial distribution of the annual precipitation. Variations in vegetation have a close relationship with those in precipitation within the Qilian Mountains region, but the NDVI is negatively correlated with precipitation in oasis areas. Increasing temperatures led to drought, inhibiting vegetation growth in summer; however, increasing temperatures may have also advanced and prolonged the growing periods in spring and autumn. The NDVI showed a slight degradation in March and July, primarily in the Qilian Mountains, and especially the Wushao Mountains. In March, due to low temperatures, the metabolism rate of vegetation was too slow to enable strong plant growth in high elevations of the Qilian Mountains. In July, increasing temperatures enhanced the intensity of transpiration and decreasing precipitation reduced the moisture available to plants, producing a slight degradation of vegetation in the Qilian Mountains. In May and August, the NDVI showed a significant improvement, primarily in the artificial oases and the Qilian Mountains. Abundant precipitation provided the necessary water for plant growth, and suitable temperatures increased the efficiency of photosynthesis, resulting in a significant improvement of vegetation in the Qilian Mountains. The improvement of production technologies, especially in irrigation, has been beneficial to the growth of

  3. Morphometric and Statistical Analysis of the Palmaris Longus Muscle in Human and Non-Human Primates

    Science.gov (United States)

    Aversi-Ferreira, Roqueline A. G. M. F.; Bretas, Rafael Vieira; Maior, Rafael Souto; Davaasuren, Munkhzul; Paraguassú-Chaves, Carlos Alberto; Nishijo, Hisao; Aversi-Ferreira, Tales Alexandre

    2014-01-01

    The palmaris longus is considered a phylogenetic degenerate metacarpophalangeal joint flexor muscle in humans, a small vestigial forearm muscle; it is the most variable muscle in humans, showing variation in position, duplication, slips and could be reverted. It is frequently studied in papers about human anatomical variations in cadavers and in vivo, its variation has importance in medical clinic, surgery, radiological analysis, in studies about high-performance athletes, in genetics and anthropologic studies. Most studies about palmaris longus in humans are associated to frequency or case studies, but comparative anatomy in primates and comparative morphometry were not found in scientific literature. Comparative anatomy associated to morphometry of palmaris longus could explain the degeneration observed in this muscle in two of three of the great apes. Hypothetically, the comparison of the relative length of tendons and belly could indicate the pathway of the degeneration of this muscle, that is, the degeneration could be associated to increased tendon length and decreased belly from more primitive primates to those most derivate, that is, great apes to modern humans. In conclusion, in primates, the tendon of the palmaris longus increase from Lemuriformes to modern humans, that is, from arboreal to terrestrial primates and the muscle became weaker and tending to be missing. PMID:24860810

  4. Morphometric and Statistical Analysis of the Palmaris Longus Muscle in Human and Non-Human Primates

    Directory of Open Access Journals (Sweden)

    Roqueline A. G. M. F. Aversi-Ferreira

    2014-01-01

    Full Text Available The palmaris longus is considered a phylogenetic degenerate metacarpophalangeal joint flexor muscle in humans, a small vestigial forearm muscle; it is the most variable muscle in humans, showing variation in position, duplication, slips and could be reverted. It is frequently studied in papers about human anatomical variations in cadavers and in vivo, its variation has importance in medical clinic, surgery, radiological analysis, in studies about high-performance athletes, in genetics and anthropologic studies. Most studies about palmaris longus in humans are associated to frequency or case studies, but comparative anatomy in primates and comparative morphometry were not found in scientific literature. Comparative anatomy associated to morphometry of palmaris longus could explain the degeneration observed in this muscle in two of three of the great apes. Hypothetically, the comparison of the relative length of tendons and belly could indicate the pathway of the degeneration of this muscle, that is, the degeneration could be associated to increased tendon length and decreased belly from more primitive primates to those most derivate, that is, great apes to modern humans. In conclusion, in primates, the tendon of the palmaris longus increase from Lemuriformes to modern humans, that is, from arboreal to terrestrial primates and the muscle became weaker and tending to be missing.

  5. PGG: An Online Pattern Based Approach for Stream Variation Management

    Institute of Scientific and Technical Information of China (English)

    Lu-An Tang; Bin Cui; Hong-Yan Li; Gao-Shan Miao; Dong-Qing Yang; Xin-Biao Zhou

    2008-01-01

    Many database applications require efficient processing of data streams with value variations and fiuctuant sampling frequency. The variations typically imply fundamental features of the stream and important domain knowledge of underlying objects. In some data streams, successive events seem to recur in a certain time interval, but the data indeed evolves with tiny differences as time elapses. This feature, so called pseudo periodicity, poses a new challenge to stream variation management. This study focuses on the online management for variations over such streams. The idea can be applied to many scenarios such as patient vital signal monitoring in medical applications. This paper proposes a new method named Pattern Growth Graph (PGG) to detect and manage variations over evolving streams with following features: 1) adopts the wave-pattern to capture the major information of data evolution and represent them compactly;2) detects the variations in a single pass over the stream with the help of wave-pattern matching algorithm; 3) only stores different segments of the pattern for incoming stream, and hence substantially compresses the data without losing important information; 4) distinguishes meaningful data changes from noise and reconstructs the stream with acceptable accuracy.Extensive experiments on real datasets containing millions of data items, as well as a prototype system, are carried out to demonstrate the feasibility and effectiveness of the proposed scheme.

  6. Human performance improvement in organizations: Potential application for the nuclear industry

    International Nuclear Information System (INIS)

    2005-11-01

    This publication is primarily intended for managers and specialists in nuclear facility operating organizations working in the area of human performance improvement. It is intended to provide them with practical information they can use to improve human performance in their organizations. While some of the information provided in this publication is based upon the experience of nuclear facility operating organizations, most of it comes from human performance improvement initiatives in non-nuclear organizations and industries. The nuclear industry has a long tradition of sharing good management practices in order to foster continuous improvement. However, it is not always realized that many of the practices that are now well established initially came from non-nuclear industries and were subsequently adapted for application to nuclear power plant operating organizations. There is, therefore, good reason to periodically review non-nuclear industry practices for ideas that might have direct or indirect application to the nuclear industry in order to potentially gain benefits such as the following: new approaches to certain problem areas, insights into new or impending challenges, improvements in existing practices, benchmarking of opportunities, development of learning organizations and avoidance of collective blind spots. The preparation of this report was an activity of the project on Effective Training to Achieve Excellence in the Performance of NPP Personnel. The objective of this project is to enhance the capability of Member States to utilize proven practices developed and transferred by the IAEA for improving personnel performance. The expected outcome from this project is the increased use by organizations in Members States of proven engineering and management practices and methodologies developed and transferred by the IAEA to improve personnel performance

  7. Smart sensor systems for human health breath monitoring applications.

    Science.gov (United States)

    Hunter, G W; Xu, J C; Biaggi-Labiosa, A M; Laskowski, D; Dutta, P K; Mondal, S P; Ward, B J; Makel, D B; Liu, C C; Chang, C W; Dweik, R A

    2011-09-01

    Breath analysis techniques offer a potential revolution in health care diagnostics, especially if these techniques can be brought into standard use in the clinic and at home. The advent of microsensors combined with smart sensor system technology enables a new generation of sensor systems with significantly enhanced capabilities and minimal size, weight and power consumption. This paper discusses the microsensor/smart sensor system approach and provides a summary of efforts to migrate this technology into human health breath monitoring applications. First, the basic capability of this approach to measure exhaled breath associated with exercise physiology is demonstrated. Building from this foundation, the development of a system for a portable asthma home health care system is described. A solid-state nitric oxide (NO) sensor for asthma monitoring has been identified, and efforts are underway to miniaturize this NO sensor technology and integrate it into a smart sensor system. It is concluded that base platform microsensor technology combined with smart sensor systems can address the needs of a range of breath monitoring applications and enable new capabilities for healthcare.

  8. Variation of serum and urine cotinine in passive and active smokers and applicability in preconceptional smoking cessation counseling

    International Nuclear Information System (INIS)

    Weerd, Sabina de; Thomas, Chris M.G.; Kuster, Josien E.T.G.; Cikot, Rolf J.L.M.; Steegers, Eric A.P.

    2002-01-01

    This study assessed the applicability of serum and urine cotinine as a biochemical marker of self-reported smoking habits for use in a preconception smoking cessation program. The variation of serum and urine cotinine over the course of the day was investigated in a sample of 21 smokers and 8 passive smokers who reported their smoking habits and exposure to smoke daily in a questionnaire for 10 consecutive days. Blood and urine samples were collected on two sampling days, 1 week apart. Both serum and urine cotinine assay could distinguish between passive and active smokers, but not between higher categories of smokers (1019 and ≥20 cigarettes per ay) due to significant intersubject overlap. In serum, no significant differences were found between morning and afternoon cotinine concentrations in either day, in contrast to urine cotinine (with lower excretions observed n the morning). An overall coefficient of variation of 22- was observed for both specimens in smokers. Because serum cotinine is subject to lower variability over the course of the day, it is more practical for use in a clinical setting where appointments are scheduled throughout the day in order o confirm smoking status

  9. Human-Computer Interaction Handbook Fundamentals, Evolving Technologies, and Emerging Applications

    CERN Document Server

    Jacko, Julie A

    2012-01-01

    The third edition of a groundbreaking reference, The Human--Computer Interaction Handbook: Fundamentals, Evolving Technologies, and Emerging Applications raises the bar for handbooks in this field. It is the largest, most complete compilation of HCI theories, principles, advances, case studies, and more that exist within a single volume. The book captures the current and emerging sub-disciplines within HCI related to research, development, and practice that continue to advance at an astonishing rate. It features cutting-edge advances to the scientific knowledge base as well as visionary perspe

  10. Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol.

    Science.gov (United States)

    Alvarez, Monica I; Glover, Luke C; Luo, Peter; Wang, Liuyang; Theusch, Elizabeth; Oehlers, Stefan H; Walton, Eric M; Tram, Trinh Thi Bich; Kuang, Yu-Lin; Rotter, Jerome I; McClean, Colleen M; Chinh, Nguyen Tran; Medina, Marisa W; Tobin, David M; Dunstan, Sarah J; Ko, Dennis C

    2017-09-12

    Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi ( S Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches.

  11. Rhythmic dynamics and synchronization via dimensionality reduction: application to human gait.

    Directory of Open Access Journals (Sweden)

    Jie Zhang

    Full Text Available Reliable characterization of locomotor dynamics of human walking is vital to understanding the neuromuscular control of human locomotion and disease diagnosis. However, the inherent oscillation and ubiquity of noise in such non-strictly periodic signals pose great challenges to current methodologies. To this end, we exploit the state-of-the-art technology in pattern recognition and, specifically, dimensionality reduction techniques, and propose to reconstruct and characterize the dynamics accurately on the cycle scale of the signal. This is achieved by deriving a low-dimensional representation of the cycles through global optimization, which effectively preserves the topology of the cycles that are embedded in a high-dimensional Euclidian space. Our approach demonstrates a clear advantage in capturing the intrinsic dynamics and probing the subtle synchronization patterns from uni/bivariate oscillatory signals over traditional methods. Application to human gait data for healthy subjects and diabetics reveals a significant difference in the dynamics of ankle movements and ankle-knee coordination, but not in knee movements. These results indicate that the impaired sensory feedback from the feet due to diabetes does not influence the knee movement in general, and that normal human walking is not critically dependent on the feedback from the peripheral nervous system.

  12. Diffusion tensor imaging of the human calf: Variation of inter- and intramuscle-specific diffusion parameters.

    Science.gov (United States)

    Schlaffke, Lara; Rehmann, Robert; Froeling, Martijn; Kley, Rudolf; Tegenthoff, Martin; Vorgerd, Matthias; Schmidt-Wilcke, Tobias

    2017-10-01

    To investigate to what extent inter- and intramuscular variations of diffusion parameters of human calf muscles can be explained by age, gender, muscle location, and body mass index (BMI) in a specific age group (20-35 years). Whole calf muscles of 18 healthy volunteers were evaluated. Magnetic resonance imaging (MRI) was performed using a 3T scanner and a 16-channel Torso XL coil. Diffusion-weighted images were acquired to perform fiber tractography and diffusion tensor imaging (DTI) analysis for each muscle of both legs. Fiber tractography was used to separate seven lower leg muscles. Associations between DTI parameters and confounds were evaluated. All muscles were additionally separated in seven identical segments along the z-axis to evaluate intramuscular differences in diffusion parameters. Fractional anisotropy (FA) and mean diffusivity (MD) were obtained for each muscle with low standard deviations (SDs) (SD FA : 0.01-0.02; SD MD : 0.07-0.14(10 -3 )). We found significant differences in FA values of the tibialis anterior muscle (AT) and extensor digitorum longus (EDL) muscles between men and women for whole muscle FA (two-sample t-tests; AT: P = 0.0014; EDL: P = 0.0004). We showed significant intramuscular differences in diffusion parameters between adjacent segments in most calf muscles (P < 0.001). Whereas muscle insertions showed higher (SD 0.03-0.06) than muscle bellies (SD 0.01-0.03), no relationships between FA or MD with age or BMI were found. Inter- and intramuscular variations in diffusion parameters of the calf were shown, which are not related to age or BMI in this age group. Differences between muscle belly and insertion should be considered when interpreting datasets not including whole muscles. 3 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1137-1148. © 2017 International Society for Magnetic Resonance in Medicine.

  13. A variational principle for Newton-Cartan theory

    International Nuclear Information System (INIS)

    Goenner, H.F.M.

    1984-01-01

    In the framework of a space-time theory of gravitation a variational principle is set up for the gravitational field equations and the equations of motion of matter. The general framework leads to Newton's equations of motion with an unspecified force term and, for irrotational motion, to a restriction on the propagation of the shear tensor along the streamlines of matter. The field equations obtained from the variation are weaker than the standard field equations of Newton-Cartan theory. An application to fluids with shear and bulk viscosity is given. (author)

  14. Design and Generation of Humanized Single-chain Fv Derived from Mouse Hybridoma for Potential Targeting Application.

    Science.gov (United States)

    Khantasup, Kannika; Chantima, Warangkana; Sangma, Chak; Poomputsa, Kanokwan; Dharakul, Tararaj

    2015-12-01

    Single-chain variable antibody fragments (scFvs) are attractive candidates for targeted immunotherapy in several human diseases. In this study, a concise humanization strategy combined with an optimized production method for humanizing scFvs was successfully employed. Two antibody clones, one directed against the hemagglutinin of H5N1 influenza virus, the other against EpCAM, a cancer biomarker, were used to demonstrate the validity of the method. Heavy chain (VH) and light chain (VL) variable regions of immunoglobulin genes from mouse hybridoma cells were sequenced and subjected to the construction of mouse scFv 3-D structure. Based on in silico modeling, the humanized version of the scFv was designed via complementarity-determining region (CDR) grafting with the retention of mouse framework region (FR) residues identified by primary sequence analysis. Root-mean-square deviation (RMSD) value between mouse and humanized scFv structures was calculated to evaluate the preservation of CDR conformation. Mouse and humanized scFv genes were then constructed and expressed in Escherichia coli. Using this method, we successfully generated humanized scFvs that retained the targeting activity of their respective mouse scFv counterparts. In addition, the humanized scFvs were engineered with a C-terminal cysteine residue (hscFv-C) for site-directed conjugation for use in future targeting applications. The hscFv-C expression was extensively optimized to improve protein production yield. The protocol yielded a 20-fold increase in production of hscFv-Cs in E. coli periplasm. The strategy described in this study may be applicable in the humanization of other antibodies derived from mouse hybridoma.

  15. Application of bacteriophages in post-harvest control of human pathogenic and food spoiling bacteria.

    Science.gov (United States)

    Pérez Pulido, Rubén; Grande Burgos, Maria José; Gálvez, Antonio; Lucas López, Rosario

    2016-10-01

    Bacteriophages have attracted great attention for application in food biopreservation. Lytic bacteriophages specific for human pathogenic bacteria can be isolated from natural sources such as animal feces or industrial wastes where the target bacteria inhabit. Lytic bacteriophages have been tested in different food systems for inactivation of main food-borne pathogens including Listeria monocytogenes, Staphylococcus aureus, Escherichia coli O157:H7, Salmonella enterica, Shigella spp., Campylobacter jejuni and Cronobacter sakazkii, and also for control of spoilage bacteria. Application of lytic bacteriophages could selectively control host populations of concern without interfering with the remaining food microbiota. Bacteriophages could also be applied for inactivation of bacteria attached to food contact surfaces or grown as biofilms. Bacteriophages may receive a generally recognized as safe status based on their lack of toxicity and other detrimental effects to human health. Phage preparations specific for L. monocytogenes, E. coli O157:H7 and S. enterica serotypes have been commercialized and approved for application in foods or as part of surface decontamination protocols. Phage endolysins have a broader host specificity compared to lytic bacteriophages. Cloned endolysins could be used as natural preservatives, singly or in combination with other antimicrobials such as bacteriocins.

  16. Variation in alternative splicing across human tissues

    OpenAIRE

    Yeo, Gene; Holste, Dirk; Kreiman, Gabriel; Burge, Christopher B

    2004-01-01

    Background: Alternative pre-mRNA splicing (AS) is widely used by higher eukaryotes to generate different protein isoforms in specific cell or tissue types. To compare AS events across human tissues, we analyzed the splicing patterns of genomically aligned expressed sequence tags (ESTs) derived from libraries of cDNAs from different tissues. Results: Controlling for differences in EST coverage among tissues, we found that the brain and testis had the highest levels of exon skipping. The most p...

  17. Environmental variation and population responses to global change

    NARCIS (Netherlands)

    Lawson, Callum R.; Vindenes, Yngvild; Bailey, Liam; van de Pol, Martijn

    2015-01-01

    Species' responses to environmental changes such as global warming are affected not only by trends in mean conditions, but also by natural and human-induced environmental fluctuations. Methods are needed to predict how such environmental variation affects ecological and evolutionary processes, in

  18. Study on human physiological parameters for monitoring of mental works in the nuclear power plant

    International Nuclear Information System (INIS)

    Takano, Ken-ichi; Yoshino, Kenji; Ishii, Keiichiro; Nakasa, Hiroyasu; Shigeta, Sadayoshi.

    1982-01-01

    To prevent outbreaks of the wrong operation and judgement in the nuclear power plant, human conditions of body and mind should be taken into consideration particularly for the mental works such as inspection and monitoring. To estimate human conditions quantitatively by the measurement of human physiological parameters, this paper presents the following experimental results. (1) Physiological parameters are estimated from both sides of biological meanings and the applicability to field works. (2) Time variation of the parameters is investigated in mental simulation tests in order to select a good indicator of mental fatigue. (3) Correlation analysis between mental fatigue indexes and physiological parameters shows that the heart rate is a best indicator. (author)

  19. Planning the Human Variome Project: The Spain Report†

    Science.gov (United States)

    Kaput, Jim; Cotton, Richard G. H.; Hardman, Lauren; Al Aqeel, Aida I.; Al-Aama, Jumana Y.; Al-Mulla, Fahd; Aretz, Stefan; Auerbach, Arleen D.; Axton, Myles; Bapat, Bharati; Bernstein, Inge T.; Bhak, Jong; Bleoo, Stacey L.; Blöcker, Helmut; Brenner, Steven E.; Burn, John; Bustamante, Mariona; Calzone, Rita; Cambon-Thomsen, Anne; Cargill, Michele; Carrera, Paola; Cavedon, Lawrence; Cho, Yoon Shin; Chung, Yeun-Jun; Claustres, Mireille; Cutting, Garry; Dalgleish, Raymond; den Dunnen, Johan T.; Díaz, Carlos; Dobrowolski, Steven; dos Santos, M. Rosário N.; Ekong, Rosemary; Flanagan, Simon B.; Flicek, Paul; Furukawa, Yoichi; Genuardi, Maurizio; Ghang, Ho; Golubenko, Maria V.; Greenblatt, Marc S.; Hamosh, Ada; Hancock, John M.; Hardison, Ross; Harrison, Terence M.; Hoffmann, Robert; Horaitis, Rania; Howard, Heather J.; Barash, Carol Isaacson; Izagirre, Neskuts; Jung, Jongsun; Kojima, Toshio; Laradi, Sandrine; Lee, Yeon-Su; Lee, Jong-Young; Gil-da-Silva-Lopes, Vera L.; Macrae, Finlay A.; Maglott, Donna; Marafie, Makia J.; Marsh, Steven G.E.; Matsubara, Yoichi; Messiaen, Ludwine M.; Möslein, Gabriela; Netea, Mihai G.; Norton, Melissa L.; Oefner, Peter J.; Oetting, William S.; O’Leary, James C.; de Ramirez, Ana Maria Oller; Paalman, Mark H.; Parboosingh, Jillian; Patrinos, George P.; Perozzi, Giuditta; Phillips, Ian R.; Povey, Sue; Prasad, Suyash; Qi, Ming; Quin, David J.; Ramesar, Rajkumar S.; Richards, C. Sue; Savige, Judith; Scheible, Dagmar G.; Scott, Rodney J.; Seminara, Daniela; Shephard, Elizabeth A.; Sijmons, Rolf H.; Smith, Timothy D.; Sobrido, María-Jesús; Tanaka, Toshihiro; Tavtigian, Sean V.; Taylor, Graham R.; Teague, Jon; Töpel, Thoralf; Ullman-Cullere, Mollie; Utsunomiya, Joji; van Kranen, Henk J.; Vihinen, Mauno; Watson, Michael; Webb, Elizabeth; Weber, Thomas K.; Yeager, Meredith; Yeom, Young I.; Yim, Seon-Hee; Yoo, Hyang-Sook

    2018-01-01

    The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Since variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008. PMID:19306394

  20. Exploring the current application of professional competencies in human resource management in the South African context

    Directory of Open Access Journals (Sweden)

    Nico Schutte

    2015-11-01

    Full Text Available Orientation: Human research (HR practitioners have an important role to play in the sustainability and competitiveness of organisations. Yet their strategic contribution and the value they add remain unrecognised. Research purpose: The main objective of this research was to explore the extent to which HR practitioners are currently allowed to display HR competencies in the workplace, and whether any significant differences exist between perceived HR competencies, based on the respondents’ demographic characteristics. Motivation for the study: Limited empirical research exists on the extent to which HR practitioners are allowed to display key competencies in the South African workplace. Research approach, design, and method: A quantitative research approach was followed. A Human Resource Management Professional Competence Questionnaire was administered to HR practitioners and managers (N = 481. Main findings: The results showed that HR competencies are poorly applied in selected South African workplaces. The competencies that were indicated as having the poorest application were talent management, HR metrics, HR business knowledge, and innovation. The white ethic group experienced a poorer application of all human research management (HRM competencies compared to the black African ethnic group. Practical/managerial implications: The findings of the research highlighted the need for management to evaluate the current application of HR practices in the workplace and also the extent to which HR professionals are involved as strategic business partners. Contribution/value-add: This research highlights the need for the current application of HR competencies in South African workplaces to be improved.

  1. A discrete variational identity on semi-direct sums of Lie algebras

    Energy Technology Data Exchange (ETDEWEB)

    M, Wenxiu [Department of Mathematics and Statistics, University of South Florida, Tampa, FL 33620-5700 (United States)

    2007-12-14

    The discrete variational identity under general bilinear forms on semi-direct sums of Lie algebras is established. The constant {gamma} involved in the variational identity is determined through the corresponding solution to the stationary discrete zero-curvature equation. An application of the resulting variational identity to a class of semi-direct sums of Lie algebras in the Volterra lattice case furnishes Hamiltonian structures for the associated integrable couplings of the Volterra lattice hierarchy.

  2. A discrete variational identity on semi-direct sums of Lie algebras

    International Nuclear Information System (INIS)

    M, Wenxiu

    2007-01-01

    The discrete variational identity under general bilinear forms on semi-direct sums of Lie algebras is established. The constant γ involved in the variational identity is determined through the corresponding solution to the stationary discrete zero-curvature equation. An application of the resulting variational identity to a class of semi-direct sums of Lie algebras in the Volterra lattice case furnishes Hamiltonian structures for the associated integrable couplings of the Volterra lattice hierarchy

  3. Variational principles for locally variational forms

    International Nuclear Information System (INIS)

    Brajercik, J.; Krupka, D.

    2005-01-01

    We present the theory of higher order local variational principles in fibered manifolds, in which the fundamental global concept is a locally variational dynamical form. Any two Lepage forms, defining a local variational principle for this form, differ on intersection of their domains, by a variationally trivial form. In this sense, but in a different geometric setting, the local variational principles satisfy analogous properties as the variational functionals of the Chern-Simons type. The resulting theory of extremals and symmetries extends the first order theories of the Lagrange-Souriau form, presented by Grigore and Popp, and closed equivalents of the first order Euler-Lagrange forms of Hakova and Krupkova. Conceptually, our approach differs from Prieto, who uses the Poincare-Cartan forms, which do not have higher order global analogues

  4. Non-commuting variations in mathematics and physics a survey

    CERN Document Server

    Preston, Serge

    2016-01-01

    This text presents and studies the method of so –called noncommuting variations in Variational Calculus. This method was pioneered by Vito Volterra who noticed that the conventional Euler-Lagrange (EL-) equations are not applicable in Non-Holonomic Mechanics and suggested to modify the basic rule used in Variational Calculus. This book presents a survey of Variational Calculus with non-commutative variations and shows that most basic properties of conventional Euler-Lagrange Equations are, with some modifications, preserved for EL-equations with K-twisted (defined by K)-variations. Most of the book can be understood by readers without strong mathematical preparation (some knowledge of Differential Geometry is necessary). In order to make the text more accessible the definitions and several necessary results in Geometry are presented separately in Appendices I and II Furthermore in Appendix III a short presentation of the Noether Theorem describing the relation between the symmetries of the differential equa...

  5. Genetic variation in natural honeybee populations, Apis mellifera capensis

    Science.gov (United States)

    Hepburn, Randall; Neumann, Peter; Radloff, Sarah E.

    2004-09-01

    Genetic variation in honeybee, Apis mellifera, populations can be considerably influenced by breeding and commercial introductions, especially in areas with abundant beekeeping. However, in southern Africa apiculture is based on the capture of wild swarms, and queen rearing is virtually absent. Moreover, the introduction of European subspecies constantly failed in the Cape region. We therefore hypothesize a low human impact on genetic variation in populations of Cape honeybees, Apis mellifera capensis. A novel solution to studying genetic variation in honeybee populations based on thelytokous worker reproduction is applied to test this hypothesis. Environmental effects on metrical morphological characters of the phenotype are separated to obtain a genetic residual component. The genetic residuals are then re-calculated as coefficients of genetic variation. Characters measured included hair length on the abdomen, width and length of wax plate, and three wing angles. The data show for the first time that genetic variation in Cape honeybee populations is independent of beekeeping density and probably reflects naturally occurring processes such as gene flow due to topographic and climatic variation on a microscale.

  6. A statistical model for measurement error that incorporates variation over time in the target measure, with application to nutritional epidemiology.

    Science.gov (United States)

    Freedman, Laurence S; Midthune, Douglas; Dodd, Kevin W; Carroll, Raymond J; Kipnis, Victor

    2015-11-30

    Most statistical methods that adjust analyses for measurement error assume that the target exposure T is a fixed quantity for each individual. However, in many applications, the value of T for an individual varies with time. We develop a model that accounts for such variation, describing the model within the framework of a meta-analysis of validation studies of dietary self-report instruments, where the reference instruments are biomarkers. We demonstrate that in this application, the estimates of the attenuation factor and correlation with true intake, key parameters quantifying the accuracy of the self-report instrument, are sometimes substantially modified under the time-varying exposure model compared with estimates obtained under a traditional fixed-exposure model. We conclude that accounting for the time element in measurement error problems is potentially important. Copyright © 2015 John Wiley & Sons, Ltd.

  7. Original article Temperamental variation in learned irrelevance in humans

    Directory of Open Access Journals (Sweden)

    Aleksandra Gruszka

    2015-07-01

    Full Text Available Background Learned irrelevance (LIRR represents one of the mechanisms of attentional set-shifting and refers to the inability to attend to, or to learn about, any aspect of a stimulus previously experienced as irrelevant. Although it has been extensively studied in the context of clinical populations, not much is known about LIRR effects in relation to normal variation in individual differences. The present study was designed to assess how temperamental factors may modulate LIRR. Participants and procedures Sixty-eight healthy volunteers performed a visual discrimination learning task modelled after Wisconsin Card Sorting Test. To test the susceptibility to learned irrelevance, participants were expected to shift their attention either to a dimension that prior to the extra-dimensional shift was completely irrelevant, or to a dimension that was previously partly correlated with reinforcement. Temperamental traits were assessed using the Formal Characteristics of Behaviour-Temperament Inventory (Zawadzki & Strelau, 1997. Intelligence level was stratified according to Raven’s Advanced Progressive Matrices (Raven, Raven, & Court, 2003. Results Low level of Briskness and high level of Perseverance were related to enhanced susceptibility to LIRR. High levels of Activity and Emotional Reactivity were related to the poorer performance on the extra-dimensional set-shifting. No effects of other temperament characteristics or intelligence on LIRR were observed. Conclusions The results confirm a strong variation in LIRR related to individual differences in temperament, which appears to be unrelated to DA function. Our results highlight the importance of considering individual differences in studies on cognitive control.

  8. Application of fuzzy synthetic assessment to assess human factors design level on reactor control panel

    International Nuclear Information System (INIS)

    Peng Xuecheng

    1999-01-01

    Reactor control panel design level on human factors must be considered by designer. The author evaluated the human factor design level of arrangement and combinations including the switch buttons, meter dials and indication lamps on Minjiang Reactor and High-Flux Engineer Test Reactor (HFETR) critical device by application of fuzzy synthetic assessment method in mathematics. From the assessment results, the advantages and shortcomings are fount, and some modification suggestions have also been proposed

  9. Spanwise drag variation on low Re wings -- revisited

    Science.gov (United States)

    Yang, Shanling; Spedding, Geoffrey

    2011-11-01

    Aerodynamic performance measurement and prediction of airfoils and wings at chord Reynolds numbers below 105 is both difficult and increasingly important in application to small-scale aircraft. Not only are the aerodynamics strongly affected by the dynamics of the unstable laminar boundary layer but the flow is decreasingly likely to be two-dimensional as Re decreases. The spanwise variation of the flow along a two-dimensional geometry is often held to be responsible for the large variations in measured profile drag coefficient. Here we measure local two-dimensional drag coefficients along a finite wing using non-intrusive PIV methods. Variations in Cd (y) can be related to local flow variations on the wing itself. Integrated values can be compared with force balance data, and the proper description of drag components at low Re will be discussed.

  10. Peer-review study of the draft handbook for human-reliability analysis with emphasis on nuclear-power-plant applications, NUREG/CR-1278

    Energy Technology Data Exchange (ETDEWEB)

    Brune, R. L.; Weinstein, M.; Fitzwater, M. E.

    1983-01-01

    This report describes a peer review of the draft Handbook for Human Reliability Analysis with Emphasis on Nuclear Power Plant Applications, NUREG/CR-1278. The purpose of the study was to determine to what extent peers agree with the human behavior models and estimates of human error probabilities (HEPs) contained in the Handbook. Twenty-nine human factors experts participated in the study. Twenty of the participants were Americans; nine were from other countries. The peers performed human reliability analyses of a variety of human performance scenarios describing operator activities in nuclear power plant settings. They also answered questionnaires pertaining to the contents and application of the Handbook. An analysis of peer solutions to the human reliability analysis problems and peer responses to the questionnaire was performed. Recommendations regarding the format and contents of the Handbook were developed from the study findings.

  11. Serial Analysis of Gene Expression: Applications in Human Studies

    Directory of Open Access Journals (Sweden)

    Tuteja Renu

    2004-01-01

    Full Text Available Serial analysis of gene expression (SAGE is a powerful tool, which provides quantitative and comprehensive expression profile of genes in a given cell population. It works by isolating short fragments of genetic information from the expressed genes that are present in the cell being studied. These short sequences, called SAGE tags, are linked together for efficient sequencing. The frequency of each SAGE tag in the cloned multimers directly reflects the transcript abundance. Therefore, SAGE results in an accurate picture of gene expression at both the qualitative and the quantitative levels. It does not require a hybridization probe for each transcript and allows new genes to be discovered. This technique has been applied widely in human studies and various SAGE tags/SAGE libraries have been generated from different cells/tissues such as dendritic cells, lung fibroblast cells, oocytes, thyroid tissue, B-cell lymphoma, cultured keratinocytes, muscles, brain tissues, sciatic nerve, cultured Schwann cells, cord blood-derived mast cells, retina, macula, retinal pigment epithelial cells, skin cells, and so forth. In this review we present the updated information on the applications of SAGE technology mainly to human studies.

  12. Designing human centered GeoVisualization application--the SanaViz--for telehealth users: a case study.

    Science.gov (United States)

    Joshi, Ashish; de Araujo Novaes, Magdala; Machiavelli, Josiane; Iyengar, Sriram; Vogler, Robert; Johnson, Craig; Zhang, Jiajie; Hsu, Chiehwen E

    2012-01-01

    Public health data is typically organized by geospatial unit. GeoVisualization (GeoVis) allows users to see information visually on a map. Examine telehealth users' perceptions towards existing public health GeoVis applications and obtains users' feedback about features important for the design and development of Human Centered GeoVis application "the SanaViz". We employed a cross sectional study design using mixed methods approach for this pilot study. Twenty users involved with the NUTES telehealth center at Federal University of Pernambuco (UFPE), Recife, Brazil were enrolled. Open and closed ended questionnaires were used to gather data. We performed audio recording for the interviews. Information gathered included socio-demographics, prior spatial skills and perception towards use of GeoVis to evaluate telehealth services. Card sorting and sketching methods were employed. Univariate analysis was performed for the continuous and categorical variables. Qualitative analysis was performed for open ended questions. Existing Public Health GeoVis applications were difficult to use. Results found interaction features zooming, linking and brushing and representation features Google maps, tables and bar chart as most preferred GeoVis features. Early involvement of users is essential to identify features necessary to be part of the human centered GeoVis application "the SanaViz".

  13. Empirical Mode Decomposition on the sphere: application to the spatial scales of surface temperature variations

    Directory of Open Access Journals (Sweden)

    N. Fauchereau

    2008-06-01

    Full Text Available Empirical Mode Decomposition (EMD is applied here in two dimensions over the sphere to demonstrate its potential as a data-adaptive method of separating the different scales of spatial variability in a geophysical (climatological/meteorological field. After a brief description of the basics of the EMD in 1 then 2 dimensions, the principles of its application on the sphere are explained, in particular via the use of a zonal equal area partitioning. EMD is first applied to an artificial dataset, demonstrating its capability in extracting the different (known scales embedded in the field. The decomposition is then applied to a global mean surface temperature dataset, and we show qualitatively that it extracts successively larger scales of temperature variations related, for example, to topographic and large-scale, solar radiation forcing. We propose that EMD can be used as a global data-adaptive filter, which will be useful in analysing geophysical phenomena that arise as the result of forcings at multiple spatial scales.

  14. Variational integrators for reduced magnetohydrodynamics

    Energy Technology Data Exchange (ETDEWEB)

    Kraus, Michael, E-mail: michael.kraus@ipp.mpg.de [Max-Planck-Institut für Plasmaphysik, Boltzmannstraße 2, 85748 Garching (Germany); Technische Universität München, Zentrum Mathematik, Boltzmannstraße 3, 85748 Garching (Germany); Tassi, Emanuele, E-mail: tassi@cpt.univ-mrs.fr [Aix-Marseille Université, Université de Toulon, CNRS, CPT, UMR 7332, 163 avenue de Luminy, case 907, 13288 cedex 9 Marseille (France); Grasso, Daniela, E-mail: daniela.grasso@infm.polito.it [ISC-CNR and Politecnico di Torino, Dipartimento Energia, C.so Duca degli Abruzzi 24, 10129 Torino (Italy)

    2016-09-15

    Reduced magnetohydrodynamics is a simplified set of magnetohydrodynamics equations with applications to both fusion and astrophysical plasmas, possessing a noncanonical Hamiltonian structure and consequently a number of conserved functionals. We propose a new discretisation strategy for these equations based on a discrete variational principle applied to a formal Lagrangian. The resulting integrator preserves important quantities like the total energy, magnetic helicity and cross helicity exactly (up to machine precision). As the integrator is free of numerical resistivity, spurious reconnection along current sheets is absent in the ideal case. If effects of electron inertia are added, reconnection of magnetic field lines is allowed, although the resulting model still possesses a noncanonical Hamiltonian structure. After reviewing the conservation laws of the model equations, the adopted variational principle with the related conservation laws is described both at the continuous and discrete level. We verify the favourable properties of the variational integrator in particular with respect to the preservation of the invariants of the models under consideration and compare with results from the literature and those of a pseudo-spectral code.

  15. Statistical Shape Analysis of the Human Ear Canal with Application to In-the-Ear Hearing Aid Design

    DEFF Research Database (Denmark)

    Paulsen, Rasmus Reinhold

    2004-01-01

    This thesis is about the statistical shape analysis of the human ear canal with application to the mechanical design of in-the-ear hearing aids. Initially, it is described how a statistical shape model of the human ear canal is built based on a training set of laser-scanned ear impressions. A thin...

  16. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tissue culture media for human ex vivo tissue and cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture...

  17. In-Space Assembly Capability Assessment for Potential Human Exploration and Science Applications

    Science.gov (United States)

    Jefferies, Sharon A.; Jones, Christopher A.; Arney, Dale C.; Stillwagen, Frederic H.; Chai, Patrick R.; Hutchinson, Craig D.; Stafford, Matthew A.; Moses, Robert W.; Dempsey, James A.; Rodgers, Erica M.; hide

    2017-01-01

    Human missions to Mars present several major challenges that must be overcome, including delivering multiple large mass and volume elements, keeping the crew safe and productive, meeting cost constraints, and ensuring a sustainable campaign. Traditional methods for executing human Mars missions minimize or eliminate in-space assembly, which provides a narrow range of options for addressing these challenges and limits the types of missions that can be performed. This paper discusses recent work to evaluate how the inclusion of in-space assembly in space mission architectural concepts could provide novel solutions to address these challenges by increasing operational flexibility, robustness, risk reduction, crew health and safety, and sustainability. A hierarchical framework is presented to characterize assembly strategies, assembly tasks, and the required capabilities to assemble mission systems in space. The framework is used to identify general mission system design considerations and assembly system characteristics by assembly strategy. These general approaches are then applied to identify potential in-space assembly applications to address each challenge. Through this process, several focus areas were identified where applications of in-space assembly could affect multiple challenges. Each focus area was developed to identify functions, potential assembly solutions and operations, key architectural trades, and potential considerations and implications of implementation. This paper helps to identify key areas to investigate were potentially significant gains in addressing the challenges with human missions to Mars may be realized, and creates a foundation on which to further develop and analyze in-space assembly concepts and assembly-based architectures.

  18. Preliminary Data on the Safety of Phytoene- and Phytofluene-Rich Products for Human Use including Topical Application

    Directory of Open Access Journals (Sweden)

    Fabien Havas

    2018-01-01

    Full Text Available The colorless carotenoids phytoene and phytofluene are comparatively understudied compounds found in common foods (e.g., tomatoes and in human plasma, internal tissues, and skin. Being naturally present in common foods, their intake at dietary levels is not expected to present a safety concern. However, since the interest in these compounds in the context of many applications is expanding, it is important to conduct studies aimed at assessing their safety. We present here results of in vitro cytotoxicity and genotoxicity studies, revealing no significant cytotoxic or genotoxic potential and of short- and long-term human in vivo skin compatibility studies with phytoene- and phytofluene-rich tomato and Dunaliella salina alga extracts, showing a lack of irritancy or sensitization reactions. These results support the safe use of phytoene- and phytofluene-rich products in human topical applications.

  19. Development and clinical application of human gastrin radioimmunoassay

    International Nuclear Information System (INIS)

    Ginabreda, M.G.P.; Borghi, V.C.; Bettarello, A.

    1988-08-01

    The determination of human gastrin levels in the blood is very important for diagnosis of gastrointestinal disorders. This work describes the radioimmunoassay of gastrin developed according to Russell et al. and its clinical application measuring fasting levels of this hormone in normal subjects, gastrectomized, chagasics, patients with chronic renal failure (CRF), pernicious anemia (PA) and Zollinger-Ellison syndrome (ZES). Synthetic human gastrin was used for radioiodination and as standard, while the specific antibody was raised in rabbits. Gastrin was radioiodinated by a modification of the chloramine T technique and purified by anion exchange chromatography in QAE-Sephadex A-25 to a specific activity around 200 uCi/ug. The assays were performed by incubation of 125 I-gastrin, standard gastrin (zero to 500 pmol/l) or unknown samples with the antiserum for 4 days at 4 0 C. The antibody bound and free 125 I-gastrin was separated by adsorption of the latter to the charcoal. The basal gastrin values of normal subjects ranged from 2 to 74 pmol/l, being these levels higher in the chagasics (from 6 to 261 pmol/l). Higher levels of gastrin were determined in patients with CRF (from 12 to 350 pmol/l), PA (from 160 to 680 pmol/l) and with ZES(1010 pmol/l), while very low levels were confirmed in gastrectomized (from 1 to 8 pmol/l). (author) [pt

  20. Assessments and applications to enhance human reliability and reduce risk during less-than-full-power operations

    International Nuclear Information System (INIS)

    Hannaman, G.W.; Singh, A.

    1992-01-01

    Study of events, interviews with plant personnel, and applications of risk studies indicate that the risk of a potential accident during less-than-full-power (LTFP) operation is becoming a greater fraction of the risk as improvements are made to the full-power operations. Industry efforts have been increased to reduce risk and the cost of shutdown operations. These efforts consider the development and application of advanced tools to help utilities proactively identify issues and develop contingencies and interventions to enhance reliability and reduce risk of low-power operations at nuclear power plants. The role for human reliability assessments is to help improve utility outage planning to better achieve schedule and risk control objectives. Improvements are expected to include intervention tools to identify and reduce human error, definition of new instructional modules, and prioritization of risk reduction issues for operators. The Electric Power Research Institute is sponsoring a project to address the identification and quantification of factors that affect human reliability during LTFP operation of nuclear power plants. The results of this project are expected to promote the development of proactively applied interventions and contingencies for enhanced human reliability during shutdown operations

  1. The Human Thioredoxin System: Modifications and Clinical Applications

    Directory of Open Access Journals (Sweden)

    Seyed Isaac Hashemy

    2011-03-01

    Full Text Available The thioredoxin system, comprising thioredoxin (Trx, thioredoxin reductase (TrxR and NADPH, is one of the major cellular antioxidant systems, implicated in a large and growing number of biological functions. Trx acts as an oxidoreductase via a highly conserved dithiol/disulfide motif located in the active site (-Trp-Cys-Gly-Pro-Cys-Lys-. Different factors are involved in the regulation of Trx activity, including its expression level, localization, protein-protein interactions, post-translational modifications and some chemical inhibitors. Mammalian TrxRs are selenoproteins which have a –Cys-Val-Asn-Val-Gly-Cys- N-terminal active site, as well as a C-terminal selenium-containing active site. Besides two Cys-residues in the redox-regulatory domain of cytosolic Trx (Trx1, human Trx1 has three additional Cys-residues. Post-translational modifications of human Trx1 which are involved in the regulation of its activity can happen via modification of Cys-residues including thiol oxidation, glutathionylation and S-nitrosylation or via modification of other amino acid residues such as nitration of Tyr-49. Because of the numerous functions of the thioredoxin system, its inhibition (mainly happens via the targeting TrxR can result in major cellular consequences, which are potentially pro-oxidant in nature, leading to cell death via necrosis or apoptosis if overexpression of Trx and other antioxidative enzymes can not recuperate cell response. Considering this feature, several anticancer drugs have been used which can inhibit TrxR. Elevated levels of Trx and/or TrxR have been reported in many different human malignancies, positively correlated with aggressive tumor growth and poor prognosis. Moreover, anti-oxidative and anti-apoptotic effects of Trx are reasons to study its clinical application as a drug.

  2. Application of the variational dynamic of nucleic acids with a prognosis of survival in hematological patients subjected to whole-body irradiation for a bone-marrow transplantation

    International Nuclear Information System (INIS)

    Morera, Lourdes; Garcia, Omar; Proenza, Emma; Carnot, Jose

    1996-01-01

    The main purpose of this work is to study the variational dynamics of nuclei acids in patients either subjected or not of abortive peaks and its prospective application as a prognostic indicator which might contribute to the therapeutic decision making in cases of BMT and irradiation related acute syndromes

  3. Nasal application of HSV encoding human preproenkephalin blocks craniofacial pain in a rat model of traumatic brain injury

    DEFF Research Database (Denmark)

    Sørensen, Jens Christian Hedemann; Meidahl, Anders Christian Nørgaard; Tzabazis

    2017-01-01

    pain using nasal application of a herpes simplex virus (HSV)-based vector expressing human proenkephalin (SHPE) to target the trigeminal ganglia. Mild TBI was induced in rats by the use of a modified fluid percussion model. Two days after mild TBI, following the development of facial mechanical...... lasting at least 45 days. On the other hand, nasal SHPE application 2 days post-TBI attenuated facial allodynia, reaching significance by day 4–7 and maintaining this effect throughout the duration of the experiment. Immunohistochemical examination revealed strong expression of human proenkephalin...

  4. SV-AUTOPILOT: optimized, automated construction of structural variation discovery and benchmarking pipelines

    NARCIS (Netherlands)

    W.Y. Leung; T. Marschall (Tobias); Y. Paudel; L. Falquet; H. Mei (Hailiang); A. Schönhuth (Alexander); T.Y. Maoz

    2015-01-01

    htmlabstractBackground Many tools exist to predict structural variants (SVs), utilizing a variety of algorithms. However, they have largely been developed and tested on human germline or somatic (e.g. cancer) variation. It seems appropriate to exploit this wealth of technology available for humans

  5. Geographical variation and the determinants of domestic endotoxin levels in mattress dust in Europe

    NARCIS (Netherlands)

    Chen, C.M.; Thiering, E.; Doekes, G.; Zock, J.P.; Bakolis, I.; Norbäck, D.; Sunyer, J.; Villani, S.; Verlato, G.; Täubel, M.; Jarvis, D.

    2012-01-01

    Endotoxin exposures have manifold effects on human health. The geographical variation and determinants of domestic endotoxin levels in Europe have not yet been extensively described. To investigate the geographical variation and determinants of domestic endotoxin concentrations in mattress dust in

  6. Systematic review of the concentrations of oligosaccharides in human milk.

    Science.gov (United States)

    Thurl, Stephan; Munzert, Manfred; Boehm, Günther; Matthews, Catherine; Stahl, Bernd

    2017-11-01

    Oligosaccharides are the third largest solid component in human milk. These diverse compounds are thought to have numerous beneficial functions in infants, including protection against infectious diseases. The structures of more than 100 oligosaccharides in human milk have been elucidated so far. The aim of this review was to identify the main factors that affect the concentrations of oligosaccharides in human milk and to determine whether it is possible to calculate representative and reliable mean concentrations. A comprehensive literature search on oligosaccharide concentrations in human milk was performed in 6 electronic databases: BIOSIS, Current Contents Search, Embase, Lancet Titles, MEDLINE and PubMed. The initial search resulted in 1363 hits. After the elimination of duplicates, the literature was screened. The application of strict inclusion criteria resulted in 21 articles selected. Oligosaccharide concentrations, both mean values and single values, reported in the literature were sorted by gestational age, secretor status of mothers, and defined lactation periods. Mean concentrations, including confidence limits, of 33 neutral and acidic oligosaccharides reported could be calculated. Concentrations of oligosaccharides in human milk show variations that are dependent on both the secretor type of the mother and the lactation period as examined by analyses of variance. In addition, large interlaboratory variations in the data were observed. Worldwide interlaboratory quantitative analyses of identical milk samples would be required to identify the most reliable methods of determining concentrations of oligosaccharides in human milk. The data presented here contribute to the current knowledge about the composition and quantities of oligosaccharides in human milk and may foster greater understanding of the biological functions of these compounds. © The Author(s) 2017. Published by Oxford University Press on behalf of the International Life Sciences Institute.

  7. On the sum of squared η-μ random variates with application to the performance of wireless communication systems

    KAUST Repository

    Ansari, Imran Shafique

    2013-06-01

    The probability density function (PDF) and cumulative distribution function of the sum of L independent but not necessarily identically distributed squared η-μ variates, applicable to the output statistics of maximal ratio combining (MRC) receiver operating over η-μ fading channels that includes the Hoyt and the Nakagami-m models as special cases, is presented in closed-form in terms of the Fox\\'s H function. Further analysis, particularly on the bit error rate via PDF-based approach, is also represented in closed form in terms of the extended Fox\\'s H function (H). The proposed new analytical results complement previous results and are illustrated by extensive numerical and Monte Carlo simulation results. © 2013 IEEE.

  8. Diversity of halophilic archaea in fermented foods and human intestines and their application.

    Science.gov (United States)

    Lee, Han-Seung

    2013-12-01

    Archaea are prokaryotic organisms distinct from bacteria in the structural and molecular biological sense, and these microorganisms are known to thrive mostly at extreme environments. In particular, most studies on halophilic archaea have been focused on environmental and ecological researches. However, new species of halophilic archaea are being isolated and identified from high salt-fermented foods consumed by humans, and it has been found that various types of halophilic archaea exist in food products by culture-independent molecular biological methods. In addition, even if the numbers are not quite high, DNAs of various halophilic archaea are being detected in human intestines and much interest is given to their possible roles. This review aims to summarize the types and characteristics of halophilic archaea reported to be present in foods and human intestines and to discuss their application as well.

  9. The Biological Effects of Quadripolar Radiofrequency Sequential Application: A Human Experimental Study

    OpenAIRE

    Nicoletti, Giovanni; Cornaglia, Antonia Icaro; Faga, Angela; Scevola, Silvia

    2014-01-01

    Objective: An experimental study was conducted to assess the effectiveness and safety of an innovative quadripolar variable electrode configuration radiofrequency device with objective measurements in an ex vivo and in vivo human experimental model. Background data: Nonablative radiofrequency applications are well-established anti-ageing procedures for cosmetic skin tightening. Methods: The study was performed in two steps: ex vivo and in vivo assessments. In the ex vivo assessments the radio...

  10. Few single nucleotide variations in exomes of human cord blood induced pluripotent stem cells.

    Directory of Open Access Journals (Sweden)

    Rui-Jun Su

    Full Text Available The effect of the cellular reprogramming process per se on mutation load remains unclear. To address this issue, we performed whole exome sequencing analysis of induced pluripotent stem cells (iPSCs reprogrammed from human cord blood (CB CD34(+ cells. Cells from a single donor and improved lentiviral vectors for high-efficiency (2-14% reprogramming were used to examine the effects of three different combinations of reprogramming factors: OCT4 and SOX2 (OS, OS and ZSCAN4 (OSZ, OS and MYC and KLF4 (OSMK. Five clones from each group were subject to whole exome sequencing analysis. We identified 14, 11, and 9 single nucleotide variations (SNVs, in exomes, including untranslated regions (UTR, in the five clones of OSMK, OS, and OSZ iPSC lines. Only 8, 7, and 4 of these, respectively, were protein-coding mutations. An average of 1.3 coding mutations per CB iPSC line is remarkably lower than previous studies using fibroblasts and low-efficiency reprogramming approaches. These data demonstrate that point nucleotide mutations during cord blood reprogramming are negligible and that the inclusion of genome stabilizers like ZSCAN4 during reprogramming may further decrease reprogramming-associated mutations. Our findings provide evidence that CB is a superior source of cells for iPSC banking.

  11. Hybrid Steepest-Descent Methods for Triple Hierarchical Variational Inequalities

    Directory of Open Access Journals (Sweden)

    L. C. Ceng

    2015-01-01

    Full Text Available We introduce and analyze a relaxed iterative algorithm by combining Korpelevich’s extragradient method, hybrid steepest-descent method, and Mann’s iteration method. We prove that, under appropriate assumptions, the proposed algorithm converges strongly to a common element of the fixed point set of infinitely many nonexpansive mappings, the solution set of finitely many generalized mixed equilibrium problems (GMEPs, the solution set of finitely many variational inclusions, and the solution set of general system of variational inequalities (GSVI, which is just a unique solution of a triple hierarchical variational inequality (THVI in a real Hilbert space. In addition, we also consider the application of the proposed algorithm for solving a hierarchical variational inequality problem with constraints of finitely many GMEPs, finitely many variational inclusions, and the GSVI. The results obtained in this paper improve and extend the corresponding results announced by many others.

  12. Quality standards for DNA sequence variation databases to improve clinical management under development in Australia

    Directory of Open Access Journals (Sweden)

    B. Bennetts

    2014-09-01

    Full Text Available Despite the routine nature of comparing sequence variations identified during clinical testing to database records, few databases meet quality requirements for clinical diagnostics. To address this issue, The Royal College of Pathologists of Australasia (RCPA in collaboration with the Human Genetics Society of Australasia (HGSA, and the Human Variome Project (HVP is developing standards for DNA sequence variation databases intended for use in the Australian clinical environment. The outputs of this project will be promoted to other health systems and accreditation bodies by the Human Variome Project to support the development of similar frameworks in other jurisdictions.

  13. The role of oxytocin in relationships between dogs and humans and potential applications for the treatment of separation anxiety in dogs.

    Science.gov (United States)

    Thielke, Lauren E; Udell, Monique A R

    2017-02-01

    The hormone oxytocin plays an important role in attachment formation and bonding between humans and domestic dogs. Recent research has led to increased interest in potential applications for intranasal oxytocin to aid with the treatment of psychological disorders in humans. While a few studies have explored the effects of intranasally administered oxytocin on social cognition and social bonding in dogs, alternative applications have not yet been explored for the treatment of behavioural problems in this species. One potentially important application for intranasal oxytocin in dogs could be the treatment of separation anxiety, a common attachment disorder in dogs. Here we provide an overview of what is known about the role of oxytocin in the human-dog bond and canine separation anxiety, and discuss considerations for future research looking to integrate oxytocin into behavioural treatment based on recent findings from both the human and dog literature. © 2015 Cambridge Philosophical Society.

  14. The variational nodal method: some history and recent activity

    International Nuclear Information System (INIS)

    Lewis, E.E.; Smith, M.A.; Palmiotti, G.

    2005-01-01

    The variational nodal method combines spherical harmonics expansions in angle with hybrid finite element techniques in space to obtain multigroup transport response matrix algorithms applicable to a wide variety of reactor physics problems. This survey briefly recounts the method's history and reviews its capabilities. Two methods for obtaining discretized equations in the form of response matrices are compared. The first is that contained the widely used VARIANT code, while the second incorporates more recently developed integral transport techniques into the variational nodal framework. The two approaches are combined with a finite sub-element formulation to treat heterogeneous nodes. Results are presented for application to a deep penetration problem and to an OECD benchmark consisting of LWR Mox fuel assemblies. Ongoing work is discussed. (authors)

  15. A Probabilistic Approach to Second Order Variational Inequalities ...

    Indian Academy of Sciences (India)

    . Under certain conditions we show the existence of a unique viscosity solution of these variational inequalities and give a stochastic representation to this solution. As an application, we study a stochastic game with stopping times and show ...

  16. Plants as Factories for Human Pharmaceuticals: Applications and Challenges.

    Science.gov (United States)

    Yao, Jian; Weng, Yunqi; Dickey, Alexia; Wang, Kevin Yueju

    2015-12-02

    Plant molecular farming (PMF), defined as the practice of using plants to produce human therapeutic proteins, has received worldwide interest. PMF has grown and advanced considerably over the past two decades. A number of therapeutic proteins have been produced in plants, some of which have been through pre-clinical or clinical trials and are close to commercialization. Plants have the potential to mass-produce pharmaceutical products with less cost than traditional methods. Tobacco-derived antibodies have been tested and used to combat the Ebola outbreak in Africa. Genetically engineered immunoadhesin (DPP4-Fc) produced in green plants has been shown to be able to bind to MERS-CoV (Middle East Respiratory Syndrome), preventing the virus from infecting lung cells. Biosafety concerns (such as pollen contamination and immunogenicity of plant-specific glycans) and costly downstream extraction and purification requirements, however, have hampered PMF production from moving from the laboratory to industrial application. In this review, the challenges and opportunities of PMF are discussed. Topics addressed include; transformation and expression systems, plant bioreactors, safety concerns, and various opportunities to produce topical applications and health supplements.

  17. Plants as Factories for Human Pharmaceuticals: Applications and Challenges

    Directory of Open Access Journals (Sweden)

    Jian Yao

    2015-12-01

    Full Text Available Plant molecular farming (PMF, defined as the practice of using plants to produce human therapeutic proteins, has received worldwide interest. PMF has grown and advanced considerably over the past two decades. A number of therapeutic proteins have been produced in plants, some of which have been through pre-clinical or clinical trials and are close to commercialization. Plants have the potential to mass-produce pharmaceutical products with less cost than traditional methods. Tobacco-derived antibodies have been tested and used to combat the Ebola outbreak in Africa. Genetically engineered immunoadhesin (DPP4-Fc produced in green plants has been shown to be able to bind to MERS-CoV (Middle East Respiratory Syndrome, preventing the virus from infecting lung cells. Biosafety concerns (such as pollen contamination and immunogenicity of plant-specific glycans and costly downstream extraction and purification requirements, however, have hampered PMF production from moving from the laboratory to industrial application. In this review, the challenges and opportunities of PMF are discussed. Topics addressed include; transformation and expression systems, plant bioreactors, safety concerns, and various opportunities to produce topical applications and health supplements.

  18. Anatomic variations of the cochlea and relations to other temporal bone structures

    Energy Technology Data Exchange (ETDEWEB)

    Dimopoulos, P.; Muren, C. (Akademiska Sjukhuset, Uppsala (Sweden). Dept. of Diagnostic Radiology Sabbatsberg' s Sjukhus, Stockholm (Sweden). Dept. of Diagnostic Radiology)

    1990-09-01

    The size and shape of the human cochlea and the normal ranges of variation of its dimensions were evaluated in 95 plastic casts, prepared from temporal bone specimens. The normal range of variation is fairly small, and is not age-dependent. Obvious digression from this range, associated with pertinent clinical symptoms, indicates an abnormality. (orig./MG).

  19. Psychological scaling of expert estimates of human error probabilities: application to nuclear power plant operation

    International Nuclear Information System (INIS)

    Comer, K.; Gaddy, C.D.; Seaver, D.A.; Stillwell, W.G.

    1985-01-01

    The US Nuclear Regulatory Commission and Sandia National Laboratories sponsored a project to evaluate psychological scaling techniques for use in generating estimates of human error probabilities. The project evaluated two techniques: direct numerical estimation and paired comparisons. Expert estimates were found to be consistent across and within judges. Convergent validity was good, in comparison to estimates in a handbook of human reliability. Predictive validity could not be established because of the lack of actual relative frequencies of error (which will be a difficulty inherent in validation of any procedure used to estimate HEPs). Application of expert estimates in probabilistic risk assessment and in human factors is discussed

  20. Dermal application of nitric oxide releasing acidified nitrite-containing liniments significantly reduces blood pressure in humans.

    Science.gov (United States)

    Opländer, Christian; Volkmar, Christine M; Paunel-Görgülü, Adnana; Fritsch, Thomas; van Faassen, Ernst E; Mürtz, Manfred; Grieb, Gerrit; Bozkurt, Ahmet; Hemmrich, Karsten; Windolf, Joachim; Suschek, Christoph V

    2012-02-15

    Vascular ischemic diseases, hypertension, and other systemic hemodynamic and vascular disorders may be the result of impaired bioavailability of nitric oxide (NO). NO but also its active derivates like nitrite or nitroso compounds are important effector and signal molecules with vasodilating properties. Our previous findings point to a therapeutical potential of cutaneous administration of NO in the treatment of systemic hemodynamic disorders. Unfortunately, no reliable data are available on the mechanisms, kinetics and biological responses of dermal application of nitric oxide in humans in vivo. The aim of the study was to close this gap and to explore the therapeutical potential of dermal nitric oxide application. We characterized with human skin in vitro and in vivo the capacity of NO, applied in a NO-releasing acidified form of nitrite-containing liniments, to penetrate the epidermis and to influence local as well as systemic hemodynamic parameters. We found that dermal application of NO led to a very rapid and significant transepidermal translocation of NO into the underlying tissue. Depending on the size of treated skin area, this translocation manifests itself through a significant systemic increase of the NO derivates nitrite and nitroso compounds, respectively. In parallel, this translocation was accompanied by an increased systemic vasodilatation and blood flow as well as reduced blood pressure. We here give evidence that in humans dermal application of NO has a therapeutic potential for systemic hemodynamic disorders that might arise from local or systemic insufficient availability of NO or its bio-active NO derivates, respectively. Copyright © 2012 Elsevier Inc. All rights reserved.