Science.gov

Sample records for limited human studies

  1. Born to run. Studying the limits of human performance

    PubMed Central

    2012-01-01

    It is recognised that regular physical activity and a high level of fitness are powerful predictors of positive health outcomes. There is a long and rich history of significant feats of human endurance with some, for example, the death of the first marathon runner, Pheidippides, associated with negative health outcomes. Early studies on endurance running used X-ray and interview techniques to evaluate competitors and comment on performance. Since then, comparatively few studies have looked at runners competing in distances longer than a marathon. Those that have, tend to show significant musculoskeletal injuries and a remarkable level of adaptation to this endurance load. The TransEurope Footrace Project followed ultra-endurance runners aiming to complete 4,500 Km of running in 64 days across Europe. This pioneering study will assess the impact of extreme endurance on human physiology; analysing musculoskeletal and other tissue/organ injuries, and the body's potential ability to adapt to extreme physiological stress. The results will be of interest not only to endurance runners, but to anyone interested in the limits of human performance. Please see related article: http://www.biomedcentral.com/1741-7015/10/78 PMID:22812408

  2. Studying the lower limit of human vision with a single-photon source

    NASA Astrophysics Data System (ADS)

    Holmes, Rebecca; Christensen, Bradley; Street, Whitney; Wang, Ranxiao; Kwiat, Paul

    2015-05-01

    Humans can detect a visual stimulus of just a few photons. Exactly how few is not known--psychological and physiological research have suggested that the detection threshold may be as low as one photon, but the question has never been directly tested. Using a source of heralded single photons based on spontaneous parametric downconversion, we can directly characterize the lower limit of vision. This system can also be used to study temporal and spatial integration in the visual system, and to study visual attention with EEG. We may eventually even be able to investigate how human observers perceive quantum effects such as superposition and entanglement. Our progress and some preliminary results will be discussed.

  3. Limits of resolution of genetic linkage studies: Implications for the positional cloning of human disease genes

    SciTech Connect

    Boehnke, M. )

    1994-08-01

    Positional cloning studies to identify disease genes are being carried out for many human genetic diseases. Such studies often include a genome-scan linkage analysis to identify the rough chromosomal location of a disease gene, fine structure genetic mapping to define and narrow the chromosomal interval in which the disease gene may be located, and physical mapping and gene identification in the genetically defined interval to clone the disease gene. During the planning of a positional cloning study, it is important to know that, if linkage is found, the genetic interval identified is likely to be sufficiently narrow to be dissected efficiently by methods of physical mapping and gene identification. Thus, one wishes to know the limits of resolution of a genetic linkage study. In this paper, the author determines for Mendelian diseases the distributions and moments of three measures of linkage resolution: (1) in a set of N chromosomes, the distance between the nearest crossovers that flank a disease locus, (2) the distance between the nearest genetic markers that flank the pair of flanking crossovers after a genome scan, and (3) the distance between the nearest flanking markers after additional randomly placed markers are generated and typed in an identified interval. These results provide explicit sample-size guidelines for future positional cloning studies of Mendelian diseases and make possible a more objective evaluation of whether a proposed positional cloning study is likely to be successful. The author also briefly discusses the more difficult problem of linkage resolution for complex genetic diseases. 14 refs., 1 fig., 6 tabs.

  4. Overcoming Current Limitations in Humanized Mouse Research

    PubMed Central

    Brehm, Michael A.; Shultz, Leonard D.; Luban, Jeremy; Greiner, Dale L.

    2013-01-01

    Immunodeficient mice engrafted with human cells and tissues have provided an exciting alternative to in vitro studies with human tissues and nonhuman primates for the study of human immunobiology. A major breakthrough in the early 2000s was the introduction of a targeted mutation in the interleukin 2 (IL-2) receptor common gamma chain (IL2rgnull) into mice that were already deficient in T and B cells. Among other immune defects, natural killer (NK) cells are disrupted in these mice, permitting efficient engraftment with human hematopoietic cells that generate a functional human immune system. These humanized mouse models are becoming increasingly important for preclinical studies of human immunity, hematopoiesis, tissue regeneration, cancer, and infectious diseases. In particular, humanized mice have enabled studies of the pathogenesis of human-specific pathogens, including human immunodeficiency virus type 1, Epstein Barr virus, and Salmonella typhi. However, there are a number of limitations in the currently available humanized mouse models. Investigators are continuing to identify molecular mechanisms underlying the remaining defects in the engrafted human immune system and are generating “next generation” models to overcome these final deficiencies. This article provides an overview of some of the emerging models of humanized mice, their use in the study of infectious diseases, and some of the remaining limitations that are currently being addressed. PMID:24151318

  5. Overcoming current limitations in humanized mouse research.

    PubMed

    Brehm, Michael A; Shultz, Leonard D; Luban, Jeremy; Greiner, Dale L

    2013-11-01

    Immunodeficient mice engrafted with human cells and tissues have provided an exciting alternative to in vitro studies with human tissues and nonhuman primates for the study of human immunobiology. A major breakthrough in the early 2000s was the introduction of a targeted mutation in the interleukin 2 (IL-2) receptor common gamma chain (IL2rg(null)) into mice that were already deficient in T and B cells. Among other immune defects, natural killer (NK) cells are disrupted in these mice, permitting efficient engraftment with human hematopoietic cells that generate a functional human immune system. These humanized mouse models are becoming increasingly important for preclinical studies of human immunity, hematopoiesis, tissue regeneration, cancer, and infectious diseases. In particular, humanized mice have enabled studies of the pathogenesis of human-specific pathogens, including human immunodeficiency virus type 1, Epstein Barr virus, and Salmonella typhi. However, there are a number of limitations in the currently available humanized mouse models. Investigators are continuing to identify molecular mechanisms underlying the remaining defects in the engrafted human immune system and are generating "next generation" models to overcome these final deficiencies. This article provides an overview of some of the emerging models of humanized mice, their use in the study of infectious diseases, and some of the remaining limitations that are currently being addressed. PMID:24151318

  6. Limits of predictability in human mobility.

    PubMed

    Song, Chaoming; Qu, Zehui; Blumm, Nicholas; Barabsi, Albert-Lszl

    2010-02-19

    A range of applications, from predicting the spread of human and electronic viruses to city planning and resource management in mobile communications, depend on our ability to foresee the whereabouts and mobility of individuals, raising a fundamental question: To what degree is human behavior predictable? Here we explore the limits of predictability in human dynamics by studying the mobility patterns of anonymized mobile phone users. By measuring the entropy of each individual's trajectory, we find a 93% potential predictability in user mobility across the whole user base. Despite the significant differences in the travel patterns, we find a remarkable lack of variability in predictability, which is largely independent of the distance users cover on a regular basis. PMID:20167789

  7. Phosphorus: a limiting nutrient for humanity?

    PubMed

    Elser, James J

    2012-12-01

    Phosphorus is a chemical element that is essential to life because of its role in numerous key molecules, including DNA and RNA; indeed, organisms require large amounts of P to grow rapidly. However, the supply of P from the environment is often limiting to production, including to crops. Thus, large amounts of P are mined annually to produce fertilizer that is applied in support of the 'Green Revolution.' However, much of this fertilizer eventually ends up in rivers, lakes and oceans where it causes costly eutrophication. Furthermore, given increasing human population, expanding meat consumption, and proliferating bioenergy pressures, concerns have recently been raised about the long-term geological, economic, and geopolitical viability of mined P for fertilizer production. Together, these issues highlight the non-sustainable nature of current human P use. To achieve P sustainability, farms need to become more efficient in how they use P while society as a whole must develop technologies and practices to recycle P from the food chain. Such large-scale changes will probably require a radical restructuring of the entire food system, highlighting the need for prompt but sustained action. PMID:22465489

  8. Teleoperator Human Factors Study

    NASA Technical Reports Server (NTRS)

    1986-01-01

    An investigation of the spectrum of space teleoperation activities likely in the 1985 to 1995 decade focused on the resolution of critical human engineering issues and characterization of the technology effect on performance of remote human operators. The study began with the identification and documentation of a set of representative reference teleoperator tasks. For each task, technology, development, and design options, issues, and alternatives that bear on human operator performance were defined and categorized. A literature survey identified existing studies of man/machine issues. For each teleoperations category, an assessment was made of the state of knowledge on a scale from adequate to void. The tests, experiments, and analyses necessary to provide the missing elements of knowledge were then defined. A limited set of tests were actually performed, including operator selection, baseline task definition, control mode study, lighting study, camera study, and preliminary time delay study.

  9. Human exploration mission studies

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.

    1989-01-01

    The Office of Exploration has established a process whereby all NASA field centers and other NASA Headquarters offices participate in the formulation and analysis of a wide range of mission strategies. These strategies were manifested into specific scenarios or candidate case studies. The case studies provided a systematic approach into analyzing each mission element. First, each case study must address several major themes and rationale including: national pride and international prestige, advancement of scientific knowledge, a catalyst for technology, economic benefits, space enterprise, international cooperation, and education and excellence. Second, the set of candidate case studies are formulated to encompass the technology requirement limits in the life sciences, launch capabilities, space transfer, automation, and robotics in space operations, power, and propulsion. The first set of reference case studies identify three major strategies: human expeditions, science outposts, and evolutionary expansion. During the past year, four case studies were examined to explore these strategies. The expeditionary missions include the Human Expedition to Phobos and Human Expedition to Mars case studies. The Lunar Observatory and Lunar Outpost to Early Mars Evolution case studies examined the later two strategies. This set of case studies established the framework to perform detailed mission analysis and system engineering to define a host of concepts and requirements for various space systems and advanced technologies. The details of each mission are described and, specifically, the results affecting the advanced technologies required to accomplish each mission scenario are presented.

  10. Peptidomics for Studying Limited Proteolysis.

    PubMed

    Tsuchiya, Takashi; Osaki, Tsukasa; Minamino, Naoto; Sasaki, Kazuki

    2015-11-01

    Limited proteolysis is a pivotal mechanism regulating protein functions. Identifying physiologically or pathophysiologically relevant cleavage sites helps to develop molecular tools that can be used for diagnostics or therapeutics. During proteolysis of secretory and membrane proteins, part of the cleaved protein is liberated and destined to undergo degradation but should retain original cleavage sites created by proteolytic enzymes. We profiled endogenous peptides accumulated for 4 h in media conditioned by primary cultured rat cardiac fibroblasts. A total of 3916 redundant peptide sequences from 94 secretory proteins and membrane proteins served to identify limited cleavage sites, both annotated and unannotated, for signal peptide or propeptide removal, peptide hormone processing, ectodomain shedding, and regulated intramembrane proteolysis. Incorrectly predicted signal cleavage sites are found in typical proteins such as extracellular matrix proteins and the peptide hormone precursor adrenomedullin ADM. The revealed signal peptide cleavage site for ADM was experimentally verified by identifying the major molecular form of flanking proadrenomedullin N-terminal peptide. We suggest that profiling of endogenous peptides, like transcriptome sequence reads, makes sense in regular cells such as fibroblasts and that peptidomics provides insight into proteolysis-regulated protein functions. PMID:26479776

  11. Ventilatory control in humans: constraints and limitations.

    PubMed

    Ward, Susan A

    2007-03-01

    Below the lactate threshold ((thetaL)), ventilation (V(E))responds in close proportion to CO(2) output to regulate arterial partial pressure of CO(2) (PaCO2). While ventilatory control models have traditionally included proportional feedback (central and carotid chemosensory) and feedforward (central and peripheral neurogenic) elements, the mechanisms involved remain unclear. Regardless, putative control schemes have to accommodate the close dynamic 'coupling' between and V(E) and V(CO2). Above (thetaL), PaCO2 is driven down to constrain the fall of arterial pH by a compensatory hyperventilation, probably of carotid body origin. When V(E) requirements are high (as in highly fit endurance athletes), V(E) can attain limiting proportions. Not only does this impair gas exchange at these work rates, but there may be an associated high metabolic cost for generation of respiratory muscle power, which may be sufficient to divert a fraction of the cardiac output away from the muscles of locomotion to the respiratory muscles, further compromising exercise tolerance. PMID:17234715

  12. Human exposure limits to hypergolic fuels

    NASA Technical Reports Server (NTRS)

    Garcia, H. D.; James, J. T.; Limero, T. F.

    1992-01-01

    Over the past four decades, many studies have been conducted on the toxicities of the rocket propellants hydrazine (HZ) and monomethylhydrazine (MH). Numerous technical challenges have made it difficult to unambiguously interpret the results of these studies, and there is considerable divergence between results obtained by different investigators on the inhalation concentrations (MAC's) for each toxic effect inducible by exposure to hypergolic fuels in spacecraft atmospheres, NASA undertook a critical review of published and unpublished investigations on the toxicities of these compounds. The current state of the art practices for similar studies. While many questions remain unanswered, MAC's were determined using the best available data for a variety of toxic endpoints for potential continuous exposure durations ranging from 1 hour to 180 days. Spacecraft MAC's (SMAC's) were set for each compound based on the most sensitive toxic endpoint at each exposure duration.

  13. 32 CFR 169a.19 - Study limits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Study limits. 169a.19 Section 169a.19 National... PROGRAM PROCEDURES Procedures 169a.19 Study limits. No DoD funds shall be available to perform any cost study pursuant to the provisions of OMB Circular A-76 if the study being performed exceeds a period...

  14. 32 CFR 169a.19 - Study limits.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Study limits. 169a.19 Section 169a.19 National... PROGRAM PROCEDURES Procedures 169a.19 Study limits. No DoD funds shall be available to perform any cost study pursuant to the provisions of OMB Circular A-76 if the study being performed exceeds a period...

  15. 32 CFR 169a.19 - Study limits.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Study limits. 169a.19 Section 169a.19 National... PROGRAM PROCEDURES Procedures 169a.19 Study limits. No DoD funds shall be available to perform any cost study pursuant to the provisions of OMB Circular A-76 if the study being performed exceeds a period...

  16. 32 CFR 169a.19 - Study limits.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false Study limits. 169a.19 Section 169a.19 National... PROGRAM PROCEDURES Procedures 169a.19 Study limits. No DoD funds shall be available to perform any cost study pursuant to the provisions of OMB Circular A-76 if the study being performed exceeds a period...

  17. 32 CFR 169a.19 - Study limits.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false Study limits. 169a.19 Section 169a.19 National... PROGRAM PROCEDURES Procedures 169a.19 Study limits. No DoD funds shall be available to perform any cost study pursuant to the provisions of OMB Circular A-76 if the study being performed exceeds a period...

  18. IMMUNOASSAY HUMAN EXPOSURE STUDIES

    EPA Science Inventory

    The Human Exposure Research Branch has developed several enzyme-linked immunosorbent assay (ELISA) methods to support human exposure assessment studies. Immunoassays to detect low levels (<10 ng/mL) of chlorpyrifos in food, track-in dirt and house dust have been applied to sam...

  19. The Limitation of Human Population: A Natural History

    ERIC Educational Resources Information Center

    Dumond, Don E.

    1975-01-01

    Suggests that overproduction of offspring by early human populations would have tended to work to the selective disadvantage of the entire society. Decisions regarding population limitations have been highly personal ones based on the amount of short run effort that individuals were able and willing to invest in each child. (GS)

  20. Human exploration mission studies

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.

    1990-01-01

    This paper describes several case studies of human space exploration, considered by the NASA's Office of Exploration in 1988. Special attention is given to the mission scenarios, the critical technology required in these expeditions, and the extraterrestrial power requirements of significant system elements. The cases examined include a manned expedition to Phobos, the inner Martian moon; a human expedition to Mars; the Lunar Observatory; and a lunar outpost to early Mars evolution.

  1. Limits and patterns of cytomegalovirus genomic diversity in humans

    PubMed Central

    Renzette, Nicholas; Pokalyuk, Cornelia; Gibson, Laura; Bhattacharjee, Bornali; Schleiss, Mark R.; Hamprecht, Klaus; Yamamoto, Aparecida Y.; Mussi-Pinhata, Marisa M.; Britt, William J.; Jensen, Jeffrey D.; Kowalik, Timothy F.

    2015-01-01

    Human cytomegalovirus (HCMV) exhibits surprisingly high genomic diversity during natural infection although little is known about the limits or patterns of HCMV diversity among humans. To address this deficiency, we analyzed genomic diversity among congenitally infected infants. We show that there is an upper limit to HCMV genomic diversity in these patient samples, with ?25% of the genome being devoid of polymorphisms. These low diversity regions were distributed across 26 loci that were preferentially located in DNA-processing genes. Furthermore, by developing, to our knowledge, the first genome-wide mutation and recombination rate maps for HCMV, we show that genomic diversity is positively correlated with these two rates. In contrast, median levels of viral genomic diversity did not vary between putatively single or mixed strain infections. We also provide evidence that HCMV populations isolated from vascular compartments of hosts from different continents are genetically similar and that polymorphisms in glycoproteins and regulatory proteins are enriched in these viral populations. This analysis provides the most highly detailed map of HCMV genomic diversity in human hosts to date and informs our understanding of the distribution of HCMV genomic diversity within human hosts. PMID:26150505

  2. Limits and patterns of cytomegalovirus genomic diversity in humans.

    PubMed

    Renzette, Nicholas; Pokalyuk, Cornelia; Gibson, Laura; Bhattacharjee, Bornali; Schleiss, Mark R; Hamprecht, Klaus; Yamamoto, Aparecida Y; Mussi-Pinhata, Marisa M; Britt, William J; Jensen, Jeffrey D; Kowalik, Timothy F

    2015-07-28

    Human cytomegalovirus (HCMV) exhibits surprisingly high genomic diversity during natural infection although little is known about the limits or patterns of HCMV diversity among humans. To address this deficiency, we analyzed genomic diversity among congenitally infected infants. We show that there is an upper limit to HCMV genomic diversity in these patient samples, with ∼ 25% of the genome being devoid of polymorphisms. These low diversity regions were distributed across 26 loci that were preferentially located in DNA-processing genes. Furthermore, by developing, to our knowledge, the first genome-wide mutation and recombination rate maps for HCMV, we show that genomic diversity is positively correlated with these two rates. In contrast, median levels of viral genomic diversity did not vary between putatively single or mixed strain infections. We also provide evidence that HCMV populations isolated from vascular compartments of hosts from different continents are genetically similar and that polymorphisms in glycoproteins and regulatory proteins are enriched in these viral populations. This analysis provides the most highly detailed map of HCMV genomic diversity in human hosts to date and informs our understanding of the distribution of HCMV genomic diversity within human hosts. PMID:26150505

  3. Pumped-limiter study for Alcator DCT

    SciTech Connect

    Brooks, J.N.; Mattas, R.F.; Cha, Y.S.; Hassanein, A.M.; Majumdar, S.

    1983-06-01

    A study was performed for a pumped-limiter design for the proposed Alcator DCT device. The study focused on reactor-relevant issues. The main issues examined were configuration, surface erosion, thermal hydraulics, and the choice of structural and surface materials. A bottom, flat limiter, with a copper-alloy substrate, seems to be a reasonable design and should provide an opportunity to test high power and particle loadings. Carbon is recommended as a surface material if acceptable redeposition properties can be demonstrated.

  4. Human surrogate models of neuropathic pain: validity and limitations.

    PubMed

    Binder, Andreas

    2016-02-01

    Human surrogate models of neuropathic pain in healthy subjects are used to study symptoms, signs, and the hypothesized underlying mechanisms. Although different models are available, different spontaneous and evoked symptoms and signs are inducible; 2 key questions need to be answered: are human surrogate models conceptually valid, ie, do they share the sensory phenotype of neuropathic pain states, and are they sufficiently reliable to allow consistent translational research? PMID:26785155

  5. Current limiter performance study; Final report

    SciTech Connect

    Hinkle, L.R.

    1990-10-04

    A study was undertaken at GE Neutron Devices (GEND) to investigate the performance and operation of two current limiters used in weapon testers in the US Department of Energy (DOE) Nuclear Weapons Complex. This work was performed for Sandia National Laboratories (SNL), Albuquerque, under Contract No. 54-1376. Two types of current limiters, Type I and Type II, were studied under a variety of operating conditions. Both types of current-limiting circuits are used in a given tester to independently prevent excess current from reaching a weapon under test. Each individual current limiter is analyzed based on independent performance. Spice-based circuit simulation and physical bench testing are used to support the analyses. Normal mode circuit operation and characteristics are investigated with load variation. Transient analysis is used to study load impedances that are not purely resistive. Component tolerances are examined by considering circuit sensitivity to parameter variation. Consequences of single component failures are investigated. Component power ratings are checked throughout the analyses. Voltage supply variations such as over voltages and reverse polarity are reviewed. Recommendations and possible design improvements are also included in this report. 51 figs., 44 tabs.

  6. Limitations on the Analysis of Relaxation Studies

    NASA Astrophysics Data System (ADS)

    Snyder, Chad; Mopsik, Frederick

    1998-03-01

    Two issues that are commonly ignored in relaxation studies are examined. The first is the issue of interpolation, extrapolation, and analysis of relaxation data over a limited frequency range. We demonstrate that for data without dispersion or overlap, within experimental uncertainty, a Cole-Cole fit cannot be discerned from a Havriliak-Negami fit over a limited, but typical, frequency range. These results have an obvious impact on many of the theoretical models that attempt to give a physical basis to such fitting functions as the Cole-Cole, the Cole-Davidson, the Havriliak-Negami, and the Kohlrausch-Williams-Watts equations. The second issue that is examined is non-isothermal relaxation studies. We examine the question of whether meaningful information can be obtained from relaxation data obtained while scanning in temperature. The implications of these results are generalized to other experiments such as modulated differential scanning calorimetry (MDSC) and dynamic mechanical thermal analysis (DMTA).

  7. The Limits of Human Stereopsis in Space and Time

    PubMed Central

    Kane, David; Guan, Phillip

    2014-01-01

    To encode binocular disparity, the visual system determines the image patches in one eye that yield the highest correlation with patches in the other eye. The computation of interocular correlation occurs after spatiotemporal filtering of monocular signals, which leads to restrictions on disparity variations that can support depth perception. We quantified those restrictions by measuring humans' ability to see disparity variation at a wide range of spatial and temporal frequencies. Lower-disparity thresholds cut off at very low spatiotemporal frequencies, which is consistent with the behavior of V1 neurons. Those thresholds are space–time separable, suggesting that the underlying neural mechanisms are separable. We also found that upper-disparity limits were characterized by a spatiotemporal, disparity-gradient limit; to be visible, disparity variation cannot exceed a fixed amount for a given interval in space–time. Our results illustrate that the disparity variations that humans can see are very restricted compared with the corresponding luminance variations. The results also provide insight into the neural mechanisms underlying depth from disparity, such as why stimuli with long interocular delays can still yield clear depth percepts. PMID:24453329

  8. Human Paraoxonase 1 as a Pharmacologic Agent: Limitations and Perspectives

    PubMed Central

    Bajaj, Priyanka; Tripathy, Rajan K.; Aggarwal, Geetika; Pande, Abhay H.

    2014-01-01

    Human PON1 (h-PON1) is a multifaceted enzyme and can hydrolyze (and inactivate) a wide range of substrates. The enzyme shows anti-inflammatory, antioxidative, antiatherogenic, ant-diabetic, antimicrobial, and organophosphate (OP)-detoxifying properties. However, there are certain limitations regarding large-scale production and use of h-PON1 as a therapeutic candidate. These include difficulties in producing recombinant h-PON1 (rh-PON1) using microbial expression system, low hydrolytic activity of wild-type h-PON1 towards certain substrates, and low storage stability of the purified enzyme. This review summarizes the work done in our laboratory to address these limitations. Our results show that (a) optimized polynucleotide sequence encoding rh-PON1 can express the protein in an active form in E. coli and can be used to generate variant of the enzyme having enhanced hydrolytic activity, (b) in vitro refolding of rh-PON1 enzyme can dramatically increase the yield of an active enzyme, (c) common excipients can be used to stabilize purified rh-PON1 enzyme when stored under different storage conditions, and (d) variants of rh-PON1 enzyme impart significant protection against OP-poisoning in human blood (ex vivo) and mouse (in vivo) model of OP-poisoning. The rh-PON1 variants and their process of production discussed here will help to develop h-PON1 as a therapeutic candidate. PMID:25386619

  9. Limited communication capacity unveils strategies for human interaction

    PubMed Central

    Miritello, Giovanna; Lara, Rubn; Cebrian, Manuel; Moro, Esteban

    2013-01-01

    Connectivity is the key process that characterizes the structural and functional properties of social networks. However, the bursty activity of dyadic interactions may hinder the discrimination of inactive ties from large interevent times in active ones. We develop a principled method to detect tie de-activation and apply it to a large longitudinal, cross-sectional communication dataset (?19 months, ?20 million people). Contrary to the perception of ever-growing connectivity, we observe that individuals exhibit a finite communication capacity, which limits the number of ties they can maintain active in time. On average men display higher capacity than women, and this capacity decreases for both genders over their lifespan. Separating communication capacity from activity reveals a diverse range of tie activation strategies, from stable to exploratory. This allows us to draw novel relationships between individual strategies for human interaction and the evolution of social networks at global scale. PMID:23739519

  10. Limited communication capacity unveils strategies for human interaction

    NASA Astrophysics Data System (ADS)

    Miritello, Giovanna; Lara, Rubén; Cebrian, Manuel; Moro, Esteban

    2013-06-01

    Connectivity is the key process that characterizes the structural and functional properties of social networks. However, the bursty activity of dyadic interactions may hinder the discrimination of inactive ties from large interevent times in active ones. We develop a principled method to detect tie de-activation and apply it to a large longitudinal, cross-sectional communication dataset (~19 months, ~20 million people). Contrary to the perception of ever-growing connectivity, we observe that individuals exhibit a finite communication capacity, which limits the number of ties they can maintain active in time. On average men display higher capacity than women, and this capacity decreases for both genders over their lifespan. Separating communication capacity from activity reveals a diverse range of tie activation strategies, from stable to exploratory. This allows us to draw novel relationships between individual strategies for human interaction and the evolution of social networks at global scale.

  11. Limited communication capacity unveils strategies for human interaction.

    PubMed

    Miritello, Giovanna; Lara, Rubén; Cebrian, Manuel; Moro, Esteban

    2013-01-01

    Connectivity is the key process that characterizes the structural and functional properties of social networks. However, the bursty activity of dyadic interactions may hinder the discrimination of inactive ties from large interevent times in active ones. We develop a principled method to detect tie de-activation and apply it to a large longitudinal, cross-sectional communication dataset (≈19 months, ≈20 million people). Contrary to the perception of ever-growing connectivity, we observe that individuals exhibit a finite communication capacity, which limits the number of ties they can maintain active in time. On average men display higher capacity than women, and this capacity decreases for both genders over their lifespan. Separating communication capacity from activity reveals a diverse range of tie activation strategies, from stable to exploratory. This allows us to draw novel relationships between individual strategies for human interaction and the evolution of social networks at global scale. PMID:23739519

  12. Selective abortion and gene therapy: reflections on human limits.

    PubMed

    Post, S G

    1991-01-01

    The potential impact of the Human Genome Project on selective abortion is considered here, as is human gene therapy. Themes of emphasis are broadly humanistic: human suffering, contingency, and perfection. The chief concerns of the article lie with selective abortion for less than serious reasons, and with the importance of avoiding efforts to "enhance" human beings by gene transfer methods. The style is widely interdisciplinary. PMID:1836362

  13. Human exploration mission studies

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.

    1989-01-01

    The nation's efforts to expand human presence and activity beyond Earth orbit into the solar system was given renewed emphasis in January of 1988 when the Presidential Directive on National Space Policy was signed into effect. The expansion of human presence into the solar system has particular significance, in that it defines long-range goals for NASA's future missions. To embark and achieve such ambitious ventures is a significant undertaking, particularly compared to past space activities. Missions to Mars, the Moon, and Phobos, as well as an observatory based on the dark side of the Moon are discussed.

  14. [Research with human embryo stem cells. Foundations and judicial limits].

    PubMed

    Eser, Albin; Koch, Hans-Georg

    2004-01-01

    Research with human embryos, and particularly, the use for scientific purposes of human embryonic stem cells has given raise to different sort of problems at the international level. One of the most strict regulation in this field, is this lecture Professors Albin Eser and Hans-Georg Koch analyse the german legal framework in relation with the use of embryos and human embryonic stem cells for scientific purposes. PMID:15544142

  15. Limited human infection due to recombinant raccoon pox virus

    USGS Publications Warehouse

    Rocke, T.E.; Dein, F.J.; Fuchsberger, M.; Fox, B.C.; Stinchcomb, D.T.; Osorio, J.G.

    2004-01-01

    A laboratory accident resulted in human exposure to a recombinant raccoon poxvirus (RCN) developed as a vaccine vector for antigens of Yersinia pestis for protection of wild rodents (and other animals) against plague. Within 9 days, the patient developed a small blister that healed within 4 weeks. Raccoon poxvirus was cultured from the lesion, and the patient developed antibody to plague antigen (F1) and RCN. This is the first documented case of human exposure to RCN.

  16. Limiter

    DOEpatents

    Cohen, S.A.; Hosea, J.C.; Timberlake, J.R.

    1984-10-19

    A limiter with a specially contoured front face is provided. The front face of the limiter (the plasma-side face) is flat with a central indentation. In addition, the limiter shape is cylindrically symmetric so that the limiter can be rotated for greater heat distribution. This limiter shape accommodates the various power scrape-off distances lambda p, which depend on the parallel velocity, V/sub parallel/, of the impacting particles.

  17. Flight Controllability Limits and Related Human Transfer Functions as Determined from Simulator and Flight Tests

    NASA Technical Reports Server (NTRS)

    Taylor, Lawrence W., Jr.; Day, Richard E.

    1961-01-01

    A simulator study and flight tests were performed to determine the levels of static stability and damping necessary to enable a pilot to control the longitudinal and lateral-directional dynamics of a vehicle for short periods of time. Although a basic set of aerodynamic characteristics was used, the study was conducted so that the results would be applicable to a wide range of flight conditions and configurations. Novel piloting techniques were found which enabled the pilot to control the vehicle at conditions that were otherwise uncontrollable. The influence of several critical factors in altering the controllability limits was also investigated. Several human transfer functions were used which gave fairly good representations of the controllability limits determined experimentally for the short-period longitudinal, directional, and lateral modes. A transfer function with approximately the same gain and phase angle as the pilot at the controlling frequencies along the controllability limits was also derived.

  18. 47 CFR 5.93 - Limited market studies.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Limited market studies. 5.93 Section 5.93...) Applications and Licenses 5.93 Limited market studies. Unless otherwise stated in the instrument of authorization, licenses granted for the purpose of limited market studies pursuant to 5.3(j) of this part...

  19. Limiter

    DOEpatents

    Cohen, Samuel A. (Hopewell, NJ); Hosea, Joel C. (Princeton, NJ); Timberlake, John R. (Allentown, NJ)

    1986-01-01

    A limiter with a specially contoured front face accommodates the various power scrape-off distances .lambda..sub.p, which depend on the parallel velocity, V.sub..parallel., of the impacting particles. The front face of the limiter (the plasma-side face) is flat with a central indentation. In addition, the limiter shape is cylindrically symmetric so that the limiter can be rotated for greater heat distribution.

  20. Beyond the limits. [Human populations and resource depletion

    SciTech Connect

    Meadows, D.H.; Meadows, D.L.; Randers, J.

    1992-01-01

    Written by the authors of The Limits to Growth, the book reinvigorates the argument that continued population growth and consumption might outstrip the Earth's natural capacities. The authors use updated figures and information to restate the orginal case presended 20 years ago. It is not hostile to technolgical solutions, but it does argue that technology will not replace the capacities of nature.

  1. Cardiovascular Deconditioning in Humans: Human Studies Core

    NASA Technical Reports Server (NTRS)

    Williams, Gordon

    1999-01-01

    Major cardiovascular problems, secondary to cardiovascular deconditioning, may occur on extended space missions. While it is generally assumed that the microgravity state is the primary cause of cardiovascular deconditioning, sleep deprivation and disruption of diurnal rhythms may also play an important role. Factors that could be modified by either or both of these perturbations include: autonomic function and short-term cardiovascular reflexes, vasoreactivity, circadian rhythm of cardiovascular hormones (specifically the renin-angiotensin system) and renal sodium handling and hormonal influences on that process, venous compliance, cardiac mass, and cardiac conduction processes. The purpose of the Human Studies Core is to provide the infrastructure to conduct human experiments which will allow for the assessment of the likely role of such factors in the space travel associated cardiovascular deconditioning process and to develop appropriate countermeasures. The Core takes advantage of a newly-created Intensive Physiologic Monitoring (IPM) Unit at the Brigham and Women's Hospital, Boston, MA, to perform these studies. The Core includes two general experimental protocols. The first protocol involves a head down tilt bed-rest study to simulate microgravity. The second protocol includes the addition of a disruption of circadian rhythms to the simulated microgravity environment. Before and after each of these environmental manipulations, the subjects will undergo acute stressors simulating changes in volume and/or stress, which could occur in space and on return to Earth. The subjects are maintained in a rigidly controlled environment with fixed light/dark cycles, activity pattern, and dietary intake of nutrients, fluids, ions and calories.

  2. Limited energy studies, Fort Rucker, Alabama

    SciTech Connect

    1993-03-01

    There are two main areas of work addressed under this contract, an LP gas storage study for Fort Rucker and the evaluation of two energy conservation opportunities for Lyster Army Community Hospital. The objective of this project was to evaluate the technical and economic feasibility of building and operating a liquified petroleum gas (LPG) storage facility at Fort Rucker. The primary heating fuel at Fort Rucker is natural gas; it is used in central steam plants and in central forced-air furnaces for family housing. Natural gas is purchased from the Southeast Alabama Gas District at their lowest rate. However, Fort Rucker also pays a natural gas demand charge based on the amount of natural gas used during a curtailment period, the natural gas demand is intended to be reduced as much as possible by switching the central steam plants to oil but the family housing area continues to use natural gas.

  3. Limited hair cell induction from human induced pluripotent stem cells using a simple stepwise method.

    PubMed

    Ohnishi, Hiroe; Skerleva, Desislava; Kitajiri, Shin-ichiro; Sakamoto, Tatsunori; Yamamoto, Norio; Ito, Juichi; Nakagawa, Takayuki

    2015-07-10

    Disease-specific induced pluripotent stem cells (iPS) cells are expected to contribute to exploring useful tools for studying the pathophysiology of inner ear diseases and to drug discovery for treating inner ear diseases. For this purpose, stable induction methods for the differentiation of human iPS cells into inner ear hair cells are required. In the present study, we examined the efficacy of a simple induction method for inducing the differentiation of human iPS cells into hair cells. The induction of inner ear hair cell-like cells was performed using a stepwise method mimicking inner ear development. Human iPS cells were sequentially transformed into the preplacodal ectoderm, otic placode, and hair cell-like cells. As a first step, preplacodal ectoderm induction, human iPS cells were seeded on a Matrigel-coated plate and cultured in a serum free N2/B27 medium for 8 days according to a previous study that demonstrated spontaneous differentiation of human ES cells into the preplacodal ectoderm. As the second step, the cells after preplacodal ectoderm induction were treated with basic fibroblast growth factor (bFGF) for induction of differentiation into otic-placode-like cells for 15 days. As the final step, cultured cells were incubated in a serum free medium containing Matrigel for 48 days. After preplacodal ectoderm induction, over 90% of cultured cells expressed the genes that express in preplacodal ectoderm. By culture with bFGF, otic placode marker-positive cells were obtained, although their number was limited. Further 48-day culture in serum free media resulted in the induction of hair cell-like cells, which expressed a hair cell marker and had stereocilia bundle-like constructions on their apical surface. Our results indicate that hair cell-like cells are induced from human iPS cells using a simple stepwise method with only bFGF, without the use of xenogeneic cells. PMID:26003451

  4. Problems and Limitations in Studies on Screening for Language Delay

    ERIC Educational Resources Information Center

    Eriksson, Marten; Westerlund, Monica; Miniscalco, Carmela

    2010-01-01

    This study discusses six common methodological limitations in screening for language delay (LD) as illustrated in 11 recent studies. The limitations are (1) whether the studies define a target population, (2) whether the recruitment procedure is unbiased, (3) attrition, (4) verification bias, (5) small sample size and (6) inconsistencies in choice

  5. Problems and Limitations in Studies on Screening for Language Delay

    ERIC Educational Resources Information Center

    Eriksson, Marten; Westerlund, Monica; Miniscalco, Carmela

    2010-01-01

    This study discusses six common methodological limitations in screening for language delay (LD) as illustrated in 11 recent studies. The limitations are (1) whether the studies define a target population, (2) whether the recruitment procedure is unbiased, (3) attrition, (4) verification bias, (5) small sample size and (6) inconsistencies in choice…

  6. Animal models of human colorectal cancer: Current status, uses and limitations

    PubMed Central

    Mittal, Vijay K; Bhullar, Jasneet Singh; Jayant, Kumar

    2015-01-01

    AIM: To make orthotopic colon cancer murine models a more clearly understood subject. The orthotopic tumor models have been found to be more relevant in replicating the human disease process as compared to heterotopic models, many techniques for making orthotopic colorectal murine models have been reported. METHODS: We evaluated the current literature for various reported orthotopic colon cancer models to understand their techniques, advantages and limitations. An extensive literature review was performed by searching the National Library of Medicine Database (PubMed) using MeSH terms animal model; colon cancer; orthotopic model; murine model. Twenty studies related to colon cancer orthotopic xenograft model were evaluated in detail and discussed here. RESULTS: The detailed analysis of all relevant reports on orthotopic model showed tumor take rate between 42%-100%. While models using the enema technique and minimally invasive technique have reported development of tumor from mucosa with tumor take rate between 87%-100% with metastasis in 76%-90%. CONCLUSION: Over the years, the increased understanding of the murine models of human colon cancer has resulted in the development of various models. Each reported model has some limitations. These latest models have opened up new doors for continuing cancer research for not only understanding the colon cancer pathogenesis but also aid in the development of newer chemotherapeutic drugs as they mimic the human disease closely. PMID:26557009

  7. Safe human exposure limits for airborne linear siloxanes during spaceflight

    PubMed Central

    García, Hector D.; McMullin, Tami S.; Tobin, Joseph M.; James, John T.

    2013-01-01

    Background Low molecular weight siloxanes are used in industrial processes and consumer products, and their vapors have been detected in the atmospheres of the Space Shuttle and International Space Station. Therefore, the National Aeronautics and Space Administration (NASA) developed spacecraft maximum allowable concentrations (SMACs) for siloxane vapors to protect astronaut health. Since publication of these original SMACs, new studies and new risk assessment approaches have been published that warrant re-examination of the SMACs. Objective To reevaluate SMACs published for octamethyltrisiloxane (L3) for exposures ranging from 1 hour to 180 days, to develop a 1000-day SMAC, and to expand the applicability of those values to the family of linear siloxanes. Methods A literature review was conducted to identify studies conducted since the SMACs for L3 were set in 1994. The updated data were reviewed to determine the sensitive toxicity endpoints, and current risk assessment approaches and methods for dosimetric adjustments were evaluated. Results Recent data were used to update the original 1-hour, 24-hour, 30-day, and 180-day SMACs for L3, and a 1000-day SMAC was developed to protect crewmembers during future exploration beyond Earth orbit. Group SMACs for the linear siloxane family, including hexamethyldisiloxane (L2), L3, decamethyltetrasiloxane (L4), and dodecamethylpentasiloxane (L5), were set for exposures of 1-hour to 1000 days. Conclusion New SMACs, based on acute pulmonary and neurotoxicity at high doses only achievable with L2 and potential liver effects following longer-term exposures to L2 and L3, were established to protect crewmembers from the adverse effects of exposure to linear siloxanes. PMID:24255951

  8. Pineal melatonin level disruption in humans due to electromagnetic fields and ICNIRP limits.

    PubMed

    Halgamuge, Malka N

    2013-05-01

    The International Agency for Research on Cancer (IARC) classifies electromagnetic fields (EMFs) as 'possibly carcinogenic' to humans that might transform normal cells into cancer cells. Owing to high utilisation of electricity in day-to-day life, exposure to power-frequency (50 or 60 Hz) EMFs is unavoidable. Melatonin is a natural hormone produced by pineal gland activity in the brain that regulates the body's sleep-wake cycle. How man-made EMFs may influence the pineal gland is still unsolved. The pineal gland is likely to sense EMFs as light but, as a consequence, may decrease the melatonin production. In this study, more than one hundred experimental data of human and animal studies of changes in melatonin levels due to power-frequency electric and magnetic fields exposure were analysed. Then, the results of this study were compared with the International Committee of Non-Ionizing Radiation Protection (ICNIRP) limit and also with the existing experimental results in the literature for the biological effect of magnetic fields, in order to quantify the effects. The results show that this comparison does not seem to be consistent despite the fact that it offers an advantage of drawing attention to the importance of the exposure limits to weak EMFs. In addition to those inconsistent results, the following were also observedfrom this work: (i) the ICNIRP recommendations are meant for the well-known acute effects, because effects of the exposure duration cannot be considered and (ii) the significance of not replicating the existing experimental studies is another limitation in the power-frequency EMFs. Regardless of these issues, the above observation agrees with our earlier study in which it was confirmed that it is not a reliable method to characterise biological effects by observing only the ratio of AC magnetic field strength to frequency. This is because exposure duration does not include the ICNIRP limit. Furthermore, the results show the significance of disruption of melatonin due to exposure to weak EMFs, which may possibly lead to long-term health effects in humans. PMID:23051584

  9. 47 CFR 5.93 - Limited market studies.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Limited market studies. 5.93 Section 5.93 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EXPERIMENTAL RADIO SERVICE (OTHER THAN BROADCAST) Applications and Licenses 5.93 Limited market studies. Unless otherwise stated in the instrument of authorization, licenses granted for...

  10. Utility, Limitations, and Future of Non-Human Primates for Dengue Research and Vaccine Development

    PubMed Central

    Sariol, Carlos A.; White, Laura J.

    2014-01-01

    Dengue is considered the most important emerging, human arboviruses, with worldwide distribution in the tropics. Unfortunately, there are no licensed dengue vaccines available or specific anti-viral drugs. The development of a dengue vaccine faces unique challenges. The four serotypes co-circulate in endemic areas, and pre-existing immunity to one serotype does not protect against infection with other serotypes, and actually may enhance severity of disease. One foremost constraint to test the efficacy of a dengue vaccine is the lack of an animal model that adequately recapitulates the clinical manifestations of a dengue infection in humans. In spite of this limitation, non-human primates (NHP) are considered the best available animal model to evaluate dengue vaccine candidates due to their genetic relatedness to humans and their ability to develop a viremia upon infection and a robust immune response similar to that in humans. Therefore, most dengue vaccines candidates are tested in primates before going into clinical trials. In this article, we present a comprehensive review of published studies on dengue vaccine evaluations using the NHP model, and discuss critical parameters affecting the usefulness of the model. In the light of recent clinical data, we assess the ability of the NHP model to predict immunological parameters of vaccine performances in humans and discuss parameters that should be further examined as potential correlates of protection. Finally, we propose some guidelines toward a more standardized use of the model to maximize its usefulness and to better compare the performance of vaccine candidates from different research groups. PMID:25309540

  11. Genomic signatures of positive selection in humans and the limits of outlier approaches

    PubMed Central

    Kelley, Joanna L.; Madeoy, Jennifer; Calhoun, John C.; Swanson, Willie; Akey, Joshua M.

    2006-01-01

    Identifying regions of the human genome that have been targets of positive selection will provide important insights into recent human evolutionary history and may facilitate the search for complex disease genes. However, the confounding effects of population demographic history and selection on patterns of genetic variation complicate inferences of selection when a small number of loci are studied. To this end, identifying outlier loci from empirical genome-wide distributions of genetic variation is a promising strategy to detect targets of selection. Here, we evaluate the power and efficiency of a simple outlier approach and describe a genome-wide scan for positive selection using a dense catalog of 1.58 million SNPs that were genotyped in three human populations. In total, we analyzed 14,589 genes, 385 of which possess patterns of genetic variation consistent with the hypothesis of positive selection. Furthermore, several extended genomic regions were found, spanning >500 kb, that contained multiple contiguous candidate selection genes. More generally, these data provide important practical insights into the limits of outlier approaches in genome-wide scans for selection, provide strong candidate selection genes to study in greater detail, and may have important implications for disease related research. PMID:16825663

  12. The limiting distribution of the effective population size of the ancestor of humans and chimpanzees.

    PubMed

    Schrago, Carlos G

    2014-09-21

    The effective population size is a fundamental parameter for the understanding of microevolutionary process. Indeed, the consideration of population-level phenomena within phylogenies provides insight into the influence of the past evolutionary demography on the genetic diversity of living species. Although the effective population size of the last common ancestor of humans and chimpanzees has been extensively investigated by molecular evolutionists, variance in the estimates of this parameter among studies is large. However, with the availability of genome sequences, the estimation of evolutionary parameters may be conducted with minimum stochastic error, and the limiting distribution of the estimates may be obtained. This statistical property was utilized in the present study and coupled with analytical derivations from the coalescent theory to examine the limiting distribution of the ancestral effective population size of Homo-Pan. The mean ancestral effective population size of Homo-Pan was inferred at approximately 47,500, and the results showed that the uncertainty of the estimates was large, even under the limiting distribution. Further reductions of the estimates are feasible only if additional calibration information from the fossil record is provided and if a probabilistic model of ancestral generation time is envisioned. PMID:24834834

  13. Limitations to the study of man in space in the U.S. space program

    NASA Technical Reports Server (NTRS)

    Bishop, Phillip A.; Greenisen, Mike

    1993-01-01

    Research on humans conducted during spaceflight is fraught both with great opportunities and great obstacles. The purpose of this paper is to review some of the limitations to research in space in the United States with hope that an informed scientific community may lead to more rapid and efficient solution of these problems. Limitations arise because opportunities to study the same astronauts in well-controlled situations on repeated spaceflights are practically non-existent. Human research opportunities are further limited by the necessity of avoiding simultaneous mutually-interfering experiments. Environmental factors, including diet and other physiological perturbations concomitant with spaceflight, also complicate research design and interpretation. Technical limitations to research methods and opportunities further restrict the development of the knowledge base. Finally, Earth analogues of space travel all suffer from inadequacies. Though all of these obstacles will eventually be overcome, creativity, diligence, and persistence are required to further our knowledge of humans in space.

  14. Limitations to the study of man in the United States space program

    NASA Technical Reports Server (NTRS)

    Bishop, Phillip A.; Greenisen, Mike

    1992-01-01

    Research on humans conducted during space flight is fraught both with great opportunities and great obstacles. The purpose of this paper is to review some of the limitations to United States research in space in the hope that an informed scientific community may lead to more rapid and efficient solution of these problems. Limitations arise because opportunities to study the same astronauts in well-controlled situations on repeated space flights are practically non-existent. Human research opportunities are further limited by the necessity of avoiding simultaneous mutually-interfereing experiments. Environmental factors including diet and other physiological perturbations concomitant with space flight also complicates research design and interpretation. Technical limitations to research methods and opportunities further restrict the development of the knowledge base. Finally, earth analogues of space travel all suffer from inadequacies. Though all of these obstacles will eventually be overcome; creativity, diligence, and persistence are required to further our knowledge of humans in space.

  15. Improvements and Limitations of Humanized Mouse Models for HIV Research: NIH/NIAID "Meet the Experts" 2015 Workshop Summary.

    PubMed

    Akkina, Ramesh; Allam, Atef; Balazs, Alejandro B; Blankson, Joel N; Burnett, John C; Casares, Sofia; Garcia, J Victor; Hasenkrug, Kim J; Kashanchi, Fatah; Kitchen, Scott G; Klein, Florian; Kumar, Priti; Luster, Andrew D; Poluektova, Larisa Y; Rao, Mangala; Sanders-Beer, Brigitte E; Shultz, Leonard D; Zack, Jerome A

    2016-02-01

    The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and other infectious diseases has expanded rapidly over the past 8 years. Highly immunodeficient mouse strains, such as NOD/SCID/gamma chain(null) (NSG, NOG), support better human hematopoietic cell engraftment. Another improvement is the derivation of highly immunodeficient mice, transgenic with human leukocyte antigens (HLAs) and cytokines that supported development of HLA-restricted human T cells and heightened human myeloid cell engraftment. Humanized mice are also used to study the HIV reservoir using new imaging techniques. Despite these advances, there are still limitations in HIV immune responses and deficits in lymphoid structures in these models in addition to xenogeneic graft-versus-host responses. To understand and disseminate the improvements and limitations of humanized mouse models to the scientific community, the NIH sponsored and convened a meeting on April 15, 2015 to discuss the state of knowledge concerning these questions and best practices for selecting a humanized mouse model for a particular scientific investigation. This report summarizes the findings of the NIH meeting. PMID:26670361

  16. Uses and limits of empirical data in measuring and modeling human lead exposure.

    PubMed Central

    Mushak, P

    1998-01-01

    This paper examines the uses and limits of empirical data in evaluating measurement and modeling approaches to human lead exposure. Empirical data from experiment or observation or both have been used in studies of lead exposure. For example, experimental studies have elucidated and quantified physiologic or biokinetic parameters of lead exposure under controlled conditions. Observation, i.e., epidemiology, has been widely applied to study population exposures to lead. There is growing interest in the use of lead exposure prediction models and their evaluation before use in risk assessment. Empirical studies of lead exposure must be fully understood, especially their limits, before they are applied as "standards" or reference information for evaluation of exposure models, especially the U.S. Environmental Protection Agency's lead biokinetic model that is a focus of this article. Empirical and modeled datasets for lead exposure may not agree due to a) problems with the observational data or b) problems with the model; caution should be exercised before either a model or observational data are rejected. There are at least three sources of discordance in cases where there is lack of agreement: a) empirical data are accurate but the model is flawed; b) the model is valid but reference empirical data are inaccurate; or c) neither empirical data nor model is accurate, and each is inaccurate in different ways. This paper evaluates some of the critical empirical input to biokinetic models, especially lead bioavailability. Images Figure 3 PMID:9860906

  17. Deliberate Microbial Infection Research Reveals Limitations to Current Safety Protections of Healthy Human Subjects.

    PubMed

    Evers, David L; Fowler, Carol B; Mason, Jeffrey T; Mimnall, Rebecca K

    2015-08-01

    Here we identify approximately 40,000 healthy human volunteers who were intentionally exposed to infectious pathogens in clinical research studies dating from late World War II to the early 2000s. Microbial challenge experiments continue today under contemporary human subject research requirements. In fact, we estimated 4,000 additional volunteers who were experimentally infected between 2010 and the present day. We examine the risks and benefits of these experiments and present areas for improvement in protections of participants with respect to safety. These are the absence of maximum limits to risk and the potential for institutional review boards to include questionable benefits to subjects and society when weighing the risks and benefits of research protocols. The lack of a duty of medical care by physician-investigators to research subjects is likewise of concern. The transparency of microbial challenge experiments and the safety concerns raised in this work may stimulate further dialogue on the risks to participants of human experimentation. PMID:25150847

  18. Limitations to Thermoregulation and Acclimatization Challenge Human Adaptation to Global Warming.

    PubMed

    Hanna, Elizabeth G; Tait, Peter W

    2015-07-01

    Human thermoregulation and acclimatization are core components of the human coping mechanism for withstanding variations in environmental heat exposure. Amidst growing recognition that curtailing global warming to less than two degrees is becoming increasing improbable, human survival will require increasing reliance on these mechanisms. The projected several fold increase in extreme heat events suggests we need to recalibrate health protection policies and ratchet up adaptation efforts. Climate researchers, epidemiologists, and policy makers engaged in climate change adaptation and health protection are not commonly drawn from heat physiology backgrounds. Injecting a scholarly consideration of physiological limitations to human heat tolerance into the adaptation and policy literature allows for a broader understanding of heat health risks to support effective human adaptation and adaptation planning. This paper details the physiological and external environmental factors that determine human thermoregulation and acclimatization. We present a model to illustrate the interrelationship between elements that modulate the physiological process of thermoregulation. Limitations inherent in these processes, and the constraints imposed by differing exposure levels, and thermal comfort seeking on achieving acclimatization, are then described. Combined, these limitations will restrict the likely contribution that acclimatization can play in future human adaptation to global warming. We postulate that behavioral and technological adaptations will need to become the dominant means for human individual and societal adaptations as global warming progresses. PMID:26184272

  19. Limitations to Thermoregulation and Acclimatization Challenge Human Adaptation to Global Warming

    PubMed Central

    Hanna, Elizabeth G.; Tait, Peter W.

    2015-01-01

    Human thermoregulation and acclimatization are core components of the human coping mechanism for withstanding variations in environmental heat exposure. Amidst growing recognition that curtailing global warming to less than two degrees is becoming increasing improbable, human survival will require increasing reliance on these mechanisms. The projected several fold increase in extreme heat events suggests we need to recalibrate health protection policies and ratchet up adaptation efforts. Climate researchers, epidemiologists, and policy makers engaged in climate change adaptation and health protection are not commonly drawn from heat physiology backgrounds. Injecting a scholarly consideration of physiological limitations to human heat tolerance into the adaptation and policy literature allows for a broader understanding of heat health risks to support effective human adaptation and adaptation planning. This paper details the physiological and external environmental factors that determine human thermoregulation and acclimatization. We present a model to illustrate the interrelationship between elements that modulate the physiological process of thermoregulation. Limitations inherent in these processes, and the constraints imposed by differing exposure levels, and thermal comfort seeking on achieving acclimatization, are then described. Combined, these limitations will restrict the likely contribution that acclimatization can play in future human adaptation to global warming. We postulate that behavioral and technological adaptations will need to become the dominant means for human individual and societal adaptations as global warming progresses. PMID:26184272

  20. MDI Biological Laboratory Arsenic Summit: Approaches to Limiting Human Exposure to Arsenic.

    PubMed

    Stanton, Bruce A; Caldwell, Kathleen; Congdon, Clare Bates; Disney, Jane; Donahue, Maria; Ferguson, Elizabeth; Flemings, Elsie; Golden, Meredith; Guerinot, Mary Lou; Highman, Jay; James, Karen; Kim, Carol; Lantz, R Clark; Marvinney, Robert G; Mayer, Greg; Miller, David; Navas-Acien, Ana; Nordstrom, D Kirk; Postema, Sonia; Rardin, Laurie; Rosen, Barry; SenGupta, Arup; Shaw, Joseph; Stanton, Elizabeth; Susca, Paul

    2015-09-01

    This report is the outcome of the meeting "Environmental and Human Health Consequences of Arsenic" held at the MDI Biological Laboratory in Salisbury Cove, Maine, August 13-15, 2014. Human exposure to arsenic represents a significant health problem worldwide that requires immediate attention according to the World Health Organization (WHO). One billion people are exposed to arsenic in food, and more than 200 million people ingest arsenic via drinking water at concentrations greater than international standards. Although the US Environmental Protection Agency (EPA) has set a limit of 10 μg/L in public water supplies and the WHO has recommended an upper limit of 10 μg/L, recent studies indicate that these limits are not protective enough. In addition, there are currently few standards for arsenic in food. Those who participated in the Summit support citizens, scientists, policymakers, industry, and educators at the local, state, national, and international levels to (1) establish science-based evidence for setting standards at the local, state, national, and global levels for arsenic in water and food; (2) work with government agencies to set regulations for arsenic in water and food, to establish and strengthen non-regulatory programs, and to strengthen collaboration among government agencies, NGOs, academia, the private sector, industry, and others; (3) develop novel and cost-effective technologies for identification and reduction of exposure to arsenic in water; (4) develop novel and cost-effective approaches to reduce arsenic exposure in juice, rice, and other relevant foods; and (5) develop an Arsenic Education Plan to guide the development of science curricula as well as community outreach and education programs that serve to inform students and consumers about arsenic exposure and engage them in well water testing and development of remediation strategies. PMID:26231509

  1. Using diagnostic radiology in human evolutionary studies

    PubMed Central

    SPOOR, FRED; JEFFERY, NATHAN; ZONNEVELD, FRANS

    2000-01-01

    This paper reviews the application of medical imaging and associated computer graphics techniques to the study of human evolutionary history, with an emphasis on basic concepts and on the advantages and limitations of each method. Following a short discussion of plain film radiography and pluridirectional tomography, the principles of computed tomography (CT) and magnetic resonance imaging (MRI) and their role in the investigation of extant and fossil morphology are considered in more detail. The second half of the paper deals with techniques of 3-dimensional visualisation based on CT and MRI and with quantitative analysis of digital images. PMID:10999271

  2. Patterns and Limitations of Urban Human Mobility Resilience under the Influence of Multiple Types of Natural Disaster

    PubMed Central

    Wang, Qi; Taylor, John E.

    2016-01-01

    Natural disasters pose serious threats to large urban areas, therefore understanding and predicting human movements is critical for evaluating a population’s vulnerability and resilience and developing plans for disaster evacuation, response and relief. However, only limited research has been conducted into the effect of natural disasters on human mobility. This study examines how natural disasters influence human mobility patterns in urban populations using individuals’ movement data collected from Twitter. We selected fifteen destructive cases across five types of natural disaster and analyzed the human movement data before, during, and after each event, comparing the perturbed and steady state movement data. The results suggest that the power-law can describe human mobility in most cases and that human mobility patterns observed in steady states are often correlated with those in perturbed states, highlighting their inherent resilience. However, the quantitative analysis shows that this resilience has its limits and can fail in more powerful natural disasters. The findings from this study will deepen our understanding of the interaction between urban dwellers and civil infrastructure, improve our ability to predict human movement patterns during natural disasters, and facilitate contingency planning by policymakers. PMID:26820404

  3. Patterns and Limitations of Urban Human Mobility Resilience under the Influence of Multiple Types of Natural Disaster.

    PubMed

    Wang, Qi; Taylor, John E

    2016-01-01

    Natural disasters pose serious threats to large urban areas, therefore understanding and predicting human movements is critical for evaluating a population's vulnerability and resilience and developing plans for disaster evacuation, response and relief. However, only limited research has been conducted into the effect of natural disasters on human mobility. This study examines how natural disasters influence human mobility patterns in urban populations using individuals' movement data collected from Twitter. We selected fifteen destructive cases across five types of natural disaster and analyzed the human movement data before, during, and after each event, comparing the perturbed and steady state movement data. The results suggest that the power-law can describe human mobility in most cases and that human mobility patterns observed in steady states are often correlated with those in perturbed states, highlighting their inherent resilience. However, the quantitative analysis shows that this resilience has its limits and can fail in more powerful natural disasters. The findings from this study will deepen our understanding of the interaction between urban dwellers and civil infrastructure, improve our ability to predict human movement patterns during natural disasters, and facilitate contingency planning by policymakers. PMID:26820404

  4. Population and prehistory II: Space-limited human populations in constant environments

    PubMed Central

    Puleston, Cedric O.; Tuljapurkar, Shripad

    2010-01-01

    We present a population model to examine the forces that determined the quality and quantity of human life in early agricultural societies where cultivable area is limited. The model is driven by the non-linear and interdependent relationships between the age distribution of a population, its behavior and technology, and the nature of its environment. The common currency in the model is the production of food, on which age-specific rates of birth and death depend. There is a single nontrivial equilibrium population at which productivity balances caloric needs. One of the most powerful controls on equilibrium hunger level is fertility control. Gains against hunger are accompanied by decreases in population size. Increasing worker productivity does increase equilibrium population size but does not improve welfare at equilibrium. As a case study we apply the model to the population of a Polynesian valley before European contact. PMID:18598711

  5. Metabolic profiling in human exposome studies.

    PubMed

    Athersuch, Toby J; Keun, Hector C

    2015-11-01

    The human metabolome-the complement of small molecule metabolites present in biofluids and tissues-represents a significant part of the internal chemical milieu and is therefore an important aspect of the human exposome. Metabolic profiling approaches, commonly referred to as metabonomics or metabolomics, permit detailed and efficient characterisation of human biospecimens; application to population studies holds great promise for uncovering new associations and causal relationships between environmental factors and chronic disease. In addition to the insight metabolic information can provide, metabolic phenotypes anchor other molecular readouts and help formulate a systems-level interpretation of biological phenomena. In this commentary, we discuss the general approach for applying metabolic profiling in exposome studies, alongside recent exemplars. We also comment on the complexity and dynamism of the metabolome and highlight both the limitations such properties impart and the requirements for dealing with such issues in real-world phenotyping studies. Given that several large-scale exposome studies are now underway, we offer a perspective on current and future challenges that will need to be addressed to maximise their utility in environmental health research. PMID:26290610

  6. A study of fundamental limitations of small antennas: MIMO approach

    NASA Astrophysics Data System (ADS)

    Mattigiri, S.; Warty, C.

    In this area of high performance systems and sophistication, the antenna size is shrinking drastically. This paper reviews the fundamental limitations in electrically instigated small antennas and their implications on multiple input multiple output (MIMO) systems. An optimum performance of the antenna can be obtained by considering three main factors. (1) maximum gain for given frequency (2) minimum Q factor (3) maximum ratio of G/Q. It is essential to understand the basic concepts of these small antennas to counter the limitations for next generational systems. In this paper works of three prominent scientists like Wheeler, Hansen and Chu have been studied to understand these limitations. This study can be further expanded to accumulate various space time diverse MIMO systems specified in long Term Evolution-Advanced (LTE-A) standards. The impact of limitations of small antennas can be very significant on the performance of the given node.

  7. Mapping by admixture linkage disequilibrium in human populations: Limits and guidelines

    SciTech Connect

    Stephens, J.C.; Briscoe, D.; O`Brien, S.J.

    1994-10-01

    Certain human hereditary conditions, notably those with low penetrance and those which require an environmental event such as infectious disease exposure, are difficult to localize in pedigree analysis, because of uncertainty in the phenotype of an affected patient`s relatives. An approach to locating these genes in human cohort studies would be to use association analysis, which depends on linkage disequilibrium of flanking polymorphic DNA markers. In theory, a high degree of linkage disequilibrium between genes separated by 10-20 cM will be generated and persist in populations that have a history of recent (3-20 generations ago) admixture between genetically differentiated racial groups, such as has occurred in African Americans and Hispanic populations. We have conducted analytic and computer simulations to quantify the effect of genetic, genomic, and population parameters that affect the amount and ascertainment of linkage disequilibrium in populations with a history of genetic admixture. Our goal is to thoroughly explore the ranges of all relevant parameters or factors (e.g., sample size and degree of genetic differentiation between populations) that may be involved in gene localization studies, in hopes of prescribing guidelines for an efficient mapping strategy. The results provide reasonable limits on sample size (200-300 patients), marker number (200-300 in 20-cM intervals), and allele differentiation (loci with allele frequency difference of {ge}.3 between admixed parent populations) to produce an efficient approach (>95% ascertainment) for locating genes not easily tracked in human pedigrees. 321 refs., 8 figs., 7 tabs.

  8. Physical Performance Limitations in the Childhood Cancer Survivor Study Cohort

    PubMed Central

    Ness, Kirsten K.; Hudson, Melissa M.; Ginsberg, Jill P.; Nagarajan, Rajaram; Kaste, Sue C.; Marina, Neyssa; Whitton, John; Robison, Leslie L.; Gurney, James G.

    2009-01-01

    Physical performance limitations are one of the potential long-term consequences following diagnosis and treatment for childhood cancer. The purpose of this review is to describe the risk factors for and the participation restrictions that result from physical performance limitations among childhood cancer survivors who participated in the Childhood Cancer Survivor Study (CCSS). Articles previously published from the CCSS cohort related to physical performance limitations were reviewed and the results summarized. Our review showed that physical performance limitations are prevalent among childhood cancer survivors and may increase as they age. Host-based risk factors for physical disability include an original diagnosis of bone tumor, brain tumor, or Hodgkin's disease; female sex; and an income less than $20,000 per year. Treatment-based risk factors include radiation and treatment with a combination of alkylating agents and anthracyclines. Musculoskeletal, neurologic, cardiac, pulmonary, sensory, and endocrine organ system dysfunction also increase the risk of developing a physical performance limitation. In summary, monitoring of physical performance limitations in an aging cohort of childhood cancer survivors is important and will help determine the impact of physical performance limitations on morbidity, mortality, and caregiver burden. In addition, in developing restorative and preventive interventions for childhood cancer survivors, we must take into account the special needs of survivors with physical disability to optimize their health and enhance participation in daily living activities. PMID:19332713

  9. 47 CFR 5.93 - Limited market studies.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... shall establish on a case-by-case basis. If the Commission subsequently determines that a market study is not so limited, the study shall be immediately terminated. ... subject to the following conditions: (a) All transmitting and/or receiving equipment used in the...

  10. A limited assessment of the ASEP human reliability analysis procedure using simulator examination results

    SciTech Connect

    Gore, B.R.; Dukelow, J.S. Jr.; Mitts, T.M.; Nicholson, W.L.

    1995-10-01

    This report presents a limited assessment of the conservatism of the Accident Sequence Evaluation Program (ASEP) human reliability analysis (HRA) procedure described in NUREG/CR-4772. In particular, the, ASEP post-accident, post-diagnosis, nominal HRA procedure is assessed within the context of an individual`s performance of critical tasks on the simulator portion of requalification examinations administered to nuclear power plant operators. An assessment of the degree to which operator perforn:Lance during simulator examinations is an accurate reflection of operator performance during actual accident conditions was outside the scope of work for this project; therefore, no direct inference can be made from this report about such performance. The data for this study are derived from simulator examination reports from the NRC requalification examination cycle. A total of 4071 critical tasks were identified, of which 45 had been failed. The ASEP procedure was used to estimate human error probability (HEP) values for critical tasks, and the HEP results were compared with the failure rates observed in the examinations. The ASEP procedure was applied by PNL operator license examiners who supplemented the limited information in the examination reports with expert judgment based upon their extensive simulator examination experience. ASEP analyses were performed for a sample of 162 critical tasks selected randomly from the 4071, and the results were used to characterize the entire population. ASEP analyses were also performed for all of the 45 failed critical tasks. Two tests were performed to assess the bias of the ASEP HEPs compared with the data from the requalification examinations. The first compared the average of the ASEP HEP values with the fraction of the population actually failed and it found a statistically significant factor of two bias on the average.

  11. Human-caused fires limit convection in tropical Africa: First temporal observations and attribution

    NASA Astrophysics Data System (ADS)

    Tosca, M. G.; Diner, D. J.; Garay, M. J.; Kalashnikova, O. V.

    2015-08-01

    It is well established that smoke particles modify clouds, which in turn affects climate. However, no study has quantified the temporal dynamics of aerosol-cloud interactions with direct observations. Here for the first time, we use temporally offset satellite observations from northern Africa between 2006 and 2010 to quantitatively measure the effect of fire aerosols on convective cloud dynamics. We attribute a reduction in cloud fraction during periods of high aerosol optical depths to a smoke-driven inhibition of convection. We find that higher smoke burdens limit upward vertical motion, increase surface pressure, and increase low-level divergencemeteorological indicators of convective suppression. These results are corroborated by climate simulations that show a smoke-driven increase in regionally averaged shortwave tropospheric heating and decrease in convective precipitation during the fire season. Our results suggest that in tropical regions, anthropogenic fire initiates a positive feedback loop where increased aerosol emissions limit convection, dry the surface, and enable increased fire activity via human ignition.

  12. The 36th Harry G. Armstrong Lecture. The limits of human performance: a point of view.

    PubMed

    Rapmund, Garrison

    2002-05-01

    The author describes his experience over the past 20 years in the Pentagon environment advocating greater understanding of the importance of human performance and its limits by military technologist. The human performance research community is a key player in the effort to reverse the present marginalization of the human in a technology-dominated world. The author suggests specific initiatives the community could take to strengthen this effort and reposition itself for a greater leadership role in science and technology of the 21st century. PMID:12014614

  13. Human responses to unfairness with primary rewards and their biological limits.

    PubMed

    Wright, Nicholas D; Hodgson, Karen; Fleming, Stephen M; Symmonds, Mkael; Guitart-Masip, Marc; Dolan, Raymond J

    2012-01-01

    Humans bargaining over money tend to reject unfair offers, whilst chimpanzees bargaining over primary rewards of food do not show this same motivation to reject. Whether such reciprocal fairness represents a predominantly human motivation has generated considerable recent interest. We induced either moderate or severe thirst in humans using intravenous saline, and examined responses to unfairness in an Ultimatum Game with water. We ask if humans also reject unfair offers for primary rewards. Despite the induction of even severe thirst, our subjects rejected unfair offers. Further, our data provide tentative evidence that this fairness motivation was traded-off against the value of the primary reward to the individual, a trade-off determined by the subjective value of water rather than by an objective physiological metric of value. Our data demonstrate humans care about fairness during bargaining with primary rewards, but that subjective self-interest may limit this fairness motivation. PMID:22919460

  14. Studies of the limit order book around large price changes

    NASA Astrophysics Data System (ADS)

    Tóth, B.; Kertész, J.; Farmer, J. D.

    2009-10-01

    We study the dynamics of the limit order book of liquid stocks after experiencing large intra-day price changes. In the data we find large variations in several microscopical measures, e.g., the volatility the bid-ask spread, the bid-ask imbalance, the number of queuing limit orders, the activity (number and volume) of limit orders placed and canceled, etc. The relaxation of the quantities is generally very slow that can be described by a power law of exponent ≈ 0.4. We introduce a numerical model in order to understand the empirical results better. We find that with a zero intelligence deposition model of the order flow the empirical results can be reproduced qualitatively. This suggests that the slow relaxations might not be results of agents' strategic behaviour. Studying the difference between the exponents found empirically and numerically helps us to better identify the role of strategic behaviour in the phenomena. in here

  15. Evaluating Humane Education: The Jefferson County Study.

    ERIC Educational Resources Information Center

    Fitzgerald, Thomas A., Jr.

    1981-01-01

    Describes a study which analyzes the impact of three different humane education treatments, all examples of traditional programs taught by local humane societies to fifth- and sixth-grade students. Results are compared with similar studies previously conducted. (CS)

  16. Simulations to study the static polarization limit for RHIC lattice

    NASA Astrophysics Data System (ADS)

    Zhe, Duan; Qing, Qin

    2016-01-01

    A study of spin dynamics based on simulations with the Polymorphic Tracking Code (PTC) is reported, exploring the dependence of the static polarization limit on various beam parameters and lattice settings for a practical RHIC lattice. It is shown that the behavior of the static polarization limit is dominantly affected by the vertical motion, while the effect of beam-beam interaction is small. In addition, the nonresonant beam polarization observed and studied in the lattice-independent model is also observed in this lattice-dependent model. Therefore, this simulation study gives insights of polarization evolution at fixed beam energies, that are not available in simple spin tracking. Supported by the U.S. Department of Energy (DE-AC02-98CH10886), Hundred-Talent Program (Chinese Academy of Sciences), and National Natural Science Foundation of China (11105164)

  17. Uncertainty and variability in human exposure limits - a chemical-specific approach for ciprofloxacin and methotrexate.

    PubMed

    Oldenkamp, Rik; Huijbregts, Mark A J; Ragas, Ad M J

    2016-03-01

    Human exposure limits (HELs) for chemicals with a toxicological threshold are traditionally derived using default assessment factors that account for variations in exposure duration, species sensitivity and individual sensitivity. The present paper elaborates a probabilistic approach for human hazard characterization and the derivation of HELs. It extends the framework for evaluating and expressing uncertainty in hazard characterization recently proposed by WHO-IPCS, i.e. by the incorporation of chemical-specific data on human variability in toxicokinetics. The incorporation of human variability in toxicodynamics was based on the variation between adverse outcome pathways (AOPs). Furthermore, sources of interindividual variability and uncertainty are propagated separately throughout the derivation process. The outcome is a two-dimensional human dose distribution that quantifies the population fraction exceeding a pre-selected critical effect level with an estimate of the associated uncertainty. This enables policy makers to set separate standards for the fraction of the population to be protected and the confidence level of the assessment. The main sources of uncertainty in the human dose distribution can be identified in order to plan new research for reducing uncertainty. Additionally, the approach enables quantification of the relative risk for specific subpopulations. The approach is demonstrated for two pharmaceuticals, i.e. the antibiotic ciprofloxacin and the antineoplastic methotrexate. For both substances, the probabilistic HEL is mainly influenced by uncertainty originating from: (1) the point of departure (PoD), (2) extrapolation from sub-acute to chronic toxicity and (3) interspecies extrapolation. However, when assessing the tails of the two-dimensional human dose distributions, i.e. the section relevant for the derivation of human exposure limits, interindividual variability in toxicodynamics also becomes important. PMID:26648512

  18. Experimental study on the velocity limits of magnetized rotating plasmas

    NASA Astrophysics Data System (ADS)

    Teodorescu, Catalin; Clary, Ryan; Ellis, Richard; Hassam, Adil; Uzun-Kaymak, Ilker

    2007-11-01

    An experimental study on the physical limits of the rotation velocity of magnetized plasmas is presented. A comprehensive campaign has been carried out on the MCX, a mirror magnetic field plasma rotating azimuthally, to ascertain what physical effects limit attempts to externally boost the velocity. The externally applied parameters that control the plasma characteristics -- applied voltage, external magnetic field and fill pressure -- are scanned across the entire available range of values. It is found that the plasma rotation velocity does not exceed the Alfven velocity, in complete agreement with the equilibrium requirements of magnetically confined plasmas. As the velocity approaches the average Alfven speed, further applied force does not result in an increase past this critical speed. Diamagnetic loop measurements show that the diamagnetically excluded flux increases as the square of the Alfven Mach number, as predicted by equilibrium MHD theory. Measured rotation velocities are also found to stay below the critical ionization velocity in hydrogen, a limit suggested by Alfven. However, an approach to a definite limit has not been proven yet largely because of voltage and magnetic field upper bounds dictated by the available experimental hardware.

  19. Mockups and human productivity studies

    NASA Technical Reports Server (NTRS)

    Fisher, T.

    1985-01-01

    Idea outlines are presented concerning mockup candidates, mockup utilization and schedules/sequence in mockup development. Mockup candidates which aid in human productivity investigations and assessment are given. Areas which are considered in the mockups are the safe haven zone, general purpose workstations, maintenance and servicing area, sleep quaters, multiple docking adapter, airlock, hygiene station, food station, habitation zones, group gathering area and lab areas. Some aesthetic concerns in human productivity are also given.

  20. Use of human tissue explants to study human infectious agents

    PubMed Central

    Grivel, Jean-Charles; Margolis, Leonid

    2012-01-01

    The study of human cellcell and cellpathogen interactions that occur in the context of complex tissue cytoarchitecture is critical for deciphering the mechanisms of many normal and pathogenic processes. This protocol describes methods for culturing and infecting explants of human tissues to study the pathogenesis of human infectious agents and their local interactions. The protocol relies on the use of fresh human tissues dissected into small blocks or biopsies that are cultured at the liquidair interface on collagen rafts. These tissue blocks retain their cytoarchitecture and support productive infection of various pathogens without exogenous stimulation. Experimental details for setting up cultures of human tonsils, lymph nodes and cervicovaginal and rectosigmoid tissues, including protocols for their infection with HIV-1 and other pathogens, are described here. Using this protocol, culture and infections can be set up in 36 h and be maintained for 23 weeks, depending on the tissue used. PMID:19197269

  1. Rate limiting processes in the bohr shift in human red cells

    PubMed Central

    Forster, R. E.; Steen, J. B.

    1968-01-01

    1. The rates of the Bohr shift of human red cells and some of its constituent reactions have been studied with a modified Hartridge—Roughton rapid reaction apparatus using an oxygen electrode to measure the progress of the reaction. 2. The rate of the Bohr shift was compatible with the hypothesis that the transfer of H+ across the membrane by means of CO2 exchange and reaction with buffers is generally the rate-limiting step. (a) When the Bohr off-reaction was produced by a marked increase in PCO2 around the cells, the half-time at 37° C was 0·12 sec. In this case CO2 was available initially to diffuse into the cells, the process being predominantly limited by the rate of intracellular CO2 hydration. (b) When the Bohr off-shift was produced by an increase of [H+] outside the cell, PCO2 being low and equal within and outside the cells, the half time became 0·31 sec. In this case, even at the start, the H2CO3 formed by the almost instantaneous neutralization reaction of H+ and HCO3- had to dehydrate to form CO2 and this in turn had to diffuse into and react within the red cell before the [HbO2] could change. When a carbonic anhydrase inhibitor was added to slow the CO2 reaction inside the cell, the half-time rose to 10 sec. (c) The Bohr off-shift in a haemolysed cell suspension produced by an increase in PCO2 appeared to be limited by the rate at which the CO2 could hydrate to form H+. 3. The Bohr off-shift has an average Q10 of 2·5 between 42·5 and 28° C with an activation energy of 8000 cal. 4. The pronounced importance of the CO2-bicarbonate system for rapid intracellular pH changes is discussed in connexion with some physiological situations. PMID:5664232

  2. Experimental study on the velocity limits of magnetized rotating plasmas

    SciTech Connect

    Teodorescu, C.; Clary, R.; Ellis, R. F.; Hassam, A. B.; Lunsford, R.; Uzun-Kaymak, I.; Young, W. C.

    2008-04-15

    An experimental study on the physical limits of the rotation velocity of magnetized plasmas is presented. Experiments are performed in the Maryland Centrifugal Experiment (MCX) [R. F. Ellis et al., Phys. Plasmas 12, 055704 (2005)], a mirror magnetic field plasma rotating azimuthally. The externally applied parameters that control the plasma characteristics--applied voltage, external magnetic field, and fill pressure--are scanned across the entire available range of values. It is found that the plasma rotation velocity does not exceed the Alfven velocity, in agreement with the equilibrium requirements of magnetically confined plasmas. Measured rotation velocities are also lower than the critical ionization velocity in hydrogen, but a strict limit was not observable within MCX parametric capabilities.

  3. Welfare Time Limits: An Interim Report Card. The Cross-State Study of Time-Limited Welfare.

    ERIC Educational Resources Information Center

    Bloom, Dan

    A study focused on results from seven of the earliest state welfare reform initiatives with some form of welfare time limit. Four programs--Connecticut, Delaware, Florida, and Wisconsin--- included benefit-termination time limits triggering cancellation of a family's entire welfare grant. Arizona and Indiana imposed benefit-reduction time limits,

  4. Scientific research and human rights: a response to Kitcher on the limitations of inquiry.

    PubMed

    Victor, Elizabeth

    2014-12-01

    In his recent work exploring the role of science in democratic societies Kitcher (Science in a democratic society. Prometheus Books, New York, 2011) claims that scientists ought to have a prominent role in setting the agenda for and limits to research. Against the backdrop of the claim that the proper limits of scientific inquiry is John Stuart Mill’s Harm Principle (Kitcher in Science, truth, and democracy. Oxford University Press, New York, 2001), he identifies the limits of inquiry as the point where the outcomes of research could cause harm to already vulnerable populations. Nonetheless, Kitcher argues against explicit limitations on unscrupulous research on the grounds that restrictions would exacerbate underlying social problems. I show that Kitcher’s argument in favor of dissuading inquiry through conventional standards is problematic and falls prey to the same critique he offers in opposition to official bans. I expand the conversation of limiting scientific research by recognizing that the actions that count as ‘science’ are located in the space between ‘thinking’ and ‘doing’. In this space, we often attempt to balance freedom of research, as scientific speech, against the disparate impact citizens might experience in light of such research. I end by exploring if such disparate impact justifies limiting research, within the context of the United States, under Title VII of the Civil Rights Act of 1964 or under international human rights standards more generally. PMID:24235027

  5. Carbon and nitrogen limitation increase chitosan antifungal activity in Neurospora crassa and fungal human pathogens.

    PubMed

    Lopez-Moya, Federico; Colom-Valiente, Maria F; Martinez-Peinado, Pascual; Martinez-Lopez, Jesus E; Puelles, Eduardo; Sempere-Ortells, Jose M; Lopez-Llorca, Luis V

    2015-03-01

    Chitosan permeabilizes plasma membrane and kills sensitive filamentous fungi and yeast. Membrane fluidity and cell energy determine chitosan sensitivity in fungi. A five-fold reduction of both glucose (main carbon (C) source) and nitrogen (N) increased 2-fold Neurospora crassa sensitivity to chitosan. We linked this increase with production of intracellular reactive oxygen species (ROS) and plasma membrane permeabilization. Releasing N. crassa from nutrient limitation reduced chitosan antifungal activity in spite of high ROS intracellular levels. With lactate instead of glucose, C and N limitation increased N. crassa sensitivity to chitosan further (4-fold) than what glucose did. Nutrient limitation also increased sensitivity of filamentous fungi and yeast human pathogens to chitosan. For Fusarium proliferatum, lowering 100-fold C and N content in the growth medium, increased 16-fold chitosan sensitivity. Similar results were found for Candida spp. (including fluconazole resistant strains) and Cryptococcus spp. Severe C and N limitation increased chitosan antifungal activity for all pathogens tested. Chitosan at 100 μg ml(-1) was lethal for most fungal human pathogens tested but non-toxic to HEK293 and COS7 mammalian cell lines. Besides, chitosan increased 90% survival of Galleria mellonella larvae infected with C. albicans. These results are of paramount for developing chitosan as antifungal. PMID:25749367

  6. Robust Lentiviral Gene Delivery But Limited Transduction Capacity of Commonly Used Adeno-Associated Viral Serotypes in Xenotransplanted Human Skin.

    PubMed

    Jakobsen, Maria; Askou, Anne Louise; Stenderup, Karin; Rosada, Cecilia; Dagns-Hansen, Frederik; Jensen, Thomas G; Corydon, Thomas J; Mikkelsen, Jacob Giehm; Aagaard, Lars

    2015-08-01

    Skin is an easily accessible organ, and therapeutic gene transfer to skin remains an attractive alternative for the treatment of skin diseases. Although we have previously documented potent lentiviral gene delivery to human skin, vectors based on adeno-associated virus (AAV) rank among the most promising gene delivery tools for in vivo purposes. Thus, we compared the potential usefulness of various serotypes of recombinant AAV vectors and lentiviral vectors for gene transfer to human skin in a xenotransplanted mouse model. Vector constructs encoding firefly luciferase were packaged in AAV capsids of serotype 1, 2, 5, 6, 8, and 9 and separately administered by intradermal injection in human skin transplants. For all serotypes, live bioimaging demonstrated low levels of transgene expression in the human skin graft, and firefly luciferase expression was observed primarily in neighboring tissue outside of the graft. In contrast, gene delivery by intradermally injected lentiviral vectors was efficient and led to extensive and persistent firefly luciferase expression within the human skin graft only. The study demonstrates the limited capacity of single-stranded AAV vectors of six commonly used serotypes for gene delivery to human skin in vivo. PMID:26204415

  7. Limitations to empirical extrapolation studies: the case of BMD ratios.

    PubMed

    Brand, K P; Catalano, P J; Hammitt, J K; Rhomberg, L; Evans, J S

    2001-08-01

    Extrapolation relationships are of keen interest to chemical risk assessment in which they play a prominent role in translating experimentally derived (usually in animals) toxicity estimates into estimates more relevant to human populations. A standard approach for characterizing each extrapolation relies on ratios of pre-existing toxicity estimates. Applications of this "ratio approach" have overlooked several sources of error. This article examines the case of ratios of benchmark doses, trying to better understand their informativeness. The approach involves mathematically modeling the process by which the ratios are generated in practice. Both closed form and simulation-based models of this "data-generating process" (DGP) are developed, paying special attention to the influence of experimental design. The results show the potential for significant limits to informativeness, and revealing dependencies. Future applications of the ratio approach should take imprecision and bias into account. Bootstrap techniques are recommended for gauging imprecision, but more complicated techniques will be required for gauging bias (and capturing dependencies). Strategies for mitigating the errors are suggested. PMID:11726017

  8. Studies of retroviral infection in humanized mice.

    PubMed

    Marsden, Matthew D; Zack, Jerome A

    2015-05-01

    Many important aspects of human retroviral infections cannot be fully evaluated using only in vitro systems or unmodified animal models. An alternative approach involves the use of humanized mice, which consist of immunodeficient mice that have been transplanted with human cells and/or tissues. Certain humanized mouse models can support robust infection with human retroviruses including different strains of human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV). These models have provided wide-ranging insights into retroviral biology, including detailed information on primary infection, in vivo replication and pathogenesis, latent/persistent reservoir formation, and novel therapeutic interventions. Here we describe the humanized mouse models that are most commonly utilized to study retroviral infections, and outline some of the important discoveries that these models have produced during several decades of intensive research. PMID:25680625

  9. Circumventing storage limitations in variational data assimilation studies

    SciTech Connect

    Restrepo, J.M.; Leaf, G.K.; Griewank, A.

    1998-09-01

    An application of Pontryagin`s maximum principle data assimilation is used to blend possibly incomplete or nonuniformly distributed spatio-temporal observational data into geophysical models. Used extensively in engineering control theory applications, data assimilation has been introduced relatively recently into meteorological forecasting, natural-resource recovery modeling, and climate dynamics. Variational data assimilation is a promising assimilation technique in which it is assumed that the optimal state of the system is an extrema of a carefully chosen cost function. Provided that an adjoint model is available, the required model gradient can be computed by integrating the model forward and its adjoint backward. The gradient is then used to extremize the cost function with a suitable iterative or conjugate gradient solver. The problem addressed in this study is the explosive growth in both on-line computer memory and remote storage requirements of computing the gradient by the forward/adjoint technique which characterizes large-scale assimilation studies. Storage limitations impose severe limitation on the size of assimilation studies, even on the largest computers. By using a recursive strategy, a schedule can be constructed that enables the forward/adjoint model runs to be performed in such a way that storage requirements can be traded for longer computational times. This generally applicable strategy enables data assimilation studies on significantly larger domains than would otherwise be possible, given the particular hardware constraints, without compromising the outcome in any way. Furthermore, it is shown that this tradeoff is indeed viable and that when the schedule is optimized, the storage and computational times grow at most logarithmically.

  10. Double-pass measurement of human eye aberrations: limitations and practical realization

    NASA Astrophysics Data System (ADS)

    Letfullin, Renat R.; Belyakov, Alexey I.; Cherezova, Tatyana Y.; Kudryashov, Alexis V.

    2004-11-01

    The problem of correct eye aberrations measurement is very important with the rising widespread of a surgical procedure for reducing refractive error in the eye, so called, LASIK (laser-assisted in situ keratomileusis). The double-pass technique commonly used for measuring aberrations of a human eye involves some uncertainties. One of them is loosing the information about odd human eye aberrations. We report about investigations of the applicability limit of the double-pass measurements depending upon the aberrations status introduced by human eye and actual size of the entrance pupil. We evaluate the double-pass effects for various aberrations and different pupil diameters. It is shown that for small pupils the double-pass effects are negligible. The testing and alignment of aberrometer was performed using the schematic eye, developed in our lab. We also introduced a model of human eye based on bimorph flexible mirror. We perform calculations to demonstrate that our schematic eye is capable of reproducing spatial-temporal statistics of aberrations of living eye with normal vision or even myopic or hypermetropic or with high aberrations ones.

  11. Limits on efficient human mindreading: convergence across Chinese adults and Semai children.

    PubMed

    Wang, Bo; Hadi, Nur Shafiqah Abdul; Low, Jason

    2015-11-01

    We tested Apperly and Butterfill's (2009, Psychological Review, 116, 753) theory that humans have two mindreading systems whereby the efficient-system guiding anticipatory glances displays signature limits that do not apply to the flexible system guiding verbal predictions. Experiments 1 and 2 tested urban Mainland-Chinese adults (n = 64) and Experiment 3 tested Semai children living in the rainforests of Peninsular Malaysia (3- to 4-year-olds, n = 60). Participants - across different ages, groups and methods - anticipated others' false-beliefs about object-location but not object-identity. Convergence in signature limits signalled that the early-developing efficient system involved minimal theory-of-mind. Chinese adults and older Semai children showed flexibility in their direct predictions. The flexible mindreading system in ascribing others' beliefs as such was task-sensitive and implicated maturational and cultural contributions. PMID:25631400

  12. Deviation of Zipf's and Heaps' Laws in human languages with limited dictionary sizes.

    PubMed

    L, Linyuan; Zhang, Zi-Ke; Zhou, Tao

    2013-01-01

    Zipf's law on word frequency and Heaps' law on the growth of distinct words are observed in Indo-European language family, but it does not hold for languages like Chinese, Japanese and Korean. These languages consist of characters, and are of very limited dictionary sizes. Extensive experiments show that: (i) The character frequency distribution follows a power law with exponent close to one, at which the corresponding Zipf's exponent diverges. Indeed, the character frequency decays exponentially in the Zipf's plot. (ii) The number of distinct characters grows with the text length in three stages: It grows linearly in the beginning, then turns to a logarithmical form, and eventually saturates. A theoretical model for writing process is proposed, which embodies the rich-get-richer mechanism and the effects of limited dictionary size. Experiments, simulations and analytical solutions agree well with each other. This work refines the understanding about Zipf's and Heaps' laws in human language systems. PMID:23378896

  13. Deviation of Zipf's and Heaps' Laws in Human Languages with Limited Dictionary Sizes

    NASA Astrophysics Data System (ADS)

    L, Linyuan; Zhang, Zi-Ke; Zhou, Tao

    2013-01-01

    Zipf's law on word frequency and Heaps' law on the growth of distinct words are observed in Indo-European language family, but it does not hold for languages like Chinese, Japanese and Korean. These languages consist of characters, and are of very limited dictionary sizes. Extensive experiments show that: (i) The character frequency distribution follows a power law with exponent close to one, at which the corresponding Zipf's exponent diverges. Indeed, the character frequency decays exponentially in the Zipf's plot. (ii) The number of distinct characters grows with the text length in three stages: It grows linearly in the beginning, then turns to a logarithmical form, and eventually saturates. A theoretical model for writing process is proposed, which embodies the rich-get-richer mechanism and the effects of limited dictionary size. Experiments, simulations and analytical solutions agree well with each other. This work refines the understanding about Zipf's and Heaps' laws in human language systems.

  14. Fundamental limits of optical critical dimension metrology: a simulation study

    NASA Astrophysics Data System (ADS)

    Silver, Richard; Germer, Thomas; Attota, Ravikiran; Barnes, Bryan M.; Bunday, Benjamin; Allgair, John; Marx, Egon; Jun, Jay

    2007-03-01

    This paper is a comprehensive summary and analysis of a SEMATECH funded project to study the limits of optical critical dimension scatterometry (OCD). The project was focused on two primary elements: 1) the comparison, stability, and validity of industry models and 2) a comprehensive analysis of process stacks to evaluate the ultimate sensitivity and limits of OCD. Modeling methods are a requirement for the interpretation and quantitative analysis of scatterometry data. The four models evaluated show good agreement over a range of targets and geometries for zero order specular reflection as well as higher order diffraction. A number of process stacks and geometries representing semiconductor manufacturing nodes from the 45 nm node to the 18 nm node were simulated using several measurement modalities including angle-resolved scatterometry and spectrally-resolved scatterometry, measuring various combinations of intensity and polarization. It is apparent in the results that large differences are observed between those methods that rely upon unpolarized and single polarization measurements. Using the three parameter fits and assuming that the sensitivity of scatterometry must meet the criterion that the 3σ uncertainty in the bottom dimension must be less than 2% of the linewidth, specular scatterometry solutions exist for all but the isolated lines at 18 nm node. Scatterometry does not have sufficient sensitivity for isolated and semi-isolated lines at the 18 nm node unless the measurement uses wavelengths as short as 200 nm or 150 nm and scans over large angle ranges.

  15. Limiting the impact of light pollution on human health, environment and stellar visibility.

    PubMed

    Falchi, Fabio; Cinzano, Pierantonio; Elvidge, Christopher D; Keith, David M; Haim, Abraham

    2011-10-01

    Light pollution is one of the most rapidly increasing types of environmental degradation. Its levels have been growing exponentially over the natural nocturnal lighting levels provided by starlight and moonlight. To limit this pollution several effective practices have been defined: the use of shielding on lighting fixture to prevent direct upward light, particularly at low angles above the horizon; no over lighting, i.e. avoid using higher lighting levels than strictly needed for the task, constraining illumination to the area where it is needed and the time it will be used. Nevertheless, even after the best control of the light distribution is reached and when the proper quantity of light is used, some upward light emission remains, due to reflections from the lit surfaces and atmospheric scatter. The environmental impact of this "residual light pollution", cannot be neglected and should be limited too. Here we propose a new way to limit the effects of this residual light pollution on wildlife, human health and stellar visibility. We performed analysis of the spectra of common types of lamps for external use, including the new LEDs. We evaluated their emissions relative to the spectral response functions of human eye photoreceptors, in the photopic, scotopic and the 'meltopic' melatonin suppressing bands. We found that the amount of pollution is strongly dependent on the spectral characteristics of the lamps, with the more environmentally friendly lamps being low pressure sodium, followed by high pressure sodium. Most polluting are the lamps with a strong blue emission, like Metal Halide and white LEDs. Migration from the now widely used sodium lamps to white lamps (MH and LEDs) would produce an increase of pollution in the scotopic and melatonin suppression bands of more than five times the present levels, supposing the same photopic installed flux. This increase will exacerbate known and possible unknown effects of light pollution on human health, environment and on visual perception of the Universe by humans. We present quantitative criteria to evaluate the lamps based on their spectral emissions and we suggest regulatory limits for future lighting. PMID:21745709

  16. Fractional desynchronization of human circadian rhythms. A method for evaluating entrainment limits and functional interdependencies.

    PubMed

    Wever, R A

    1983-02-01

    Under the influence of artificial zeitgebers, human circadian rhythms can be entrained only within limited ranges of periods; different overt rhythms may show different entrainment limits. When the period of a zeitgeber is varied slowly but continuously, entrainment limits can be evaluated precisely. An overt rhythm is synchronized to the zeitgeber only up to a certain day, or period respectively, until it breaks away from the zeitgeber and starts to freerun. The interindividual comparison among different subjects shows that the range of entrainment is positioned nearly symmetrically around the freerunning period. Its width depends strongly on the freerunning period; it increases with lengthening freerunning period. As the consequence, subjects with a freerunning period only slightly shorter than 23 h would fail to become synchronized to the natural 24-h day, whereas subjects with a freerunning period even slightly longer 28 h would become synchronized. In the intraindividual comparison, overt rhythms of different variables show different entrainment limits. For instance, rhythms in urinary excretion of different electrolytes can be dissociated for several days; the same is true with the rhythms of deep body temperature and performance. This temporal separation excludes the possibility of functional interdependencies between the variables under consideration. Consequently, results obtained with this method of fractional desynchronization do not only assist in evaluating properties of the circadian system, but also assist in the search for physiological interconnections between different variables. PMID:6835816

  17. Topical Mineralocorticoid Receptor Blockade Limits Glucocorticoid-Induced Epidermal Atrophy in Human Skin.

    PubMed

    Maubec, Eve; Laounan, Cdric; Deschamps, Lydia; Nguyen, Van Tuan; Scheer-Senyarich, Isabelle; Wackenheim-Jacobs, Anne-Catherine; Steff, Maud; Duhamel, Stphanie; Tubiana, Sarah; Brahimi, Nesrine; Leclerc-Mercier, Stphanie; Crickx, Batrice; Perret, Claudine; Aractingi, Selim; Escoubet, Brigitte; Duval, Xavier; Arnaud, Philippe; Jaisser, Frederic; Mentr, France; Farman, Nicolette

    2015-07-01

    A major deleterious side effect of glucocorticoids is skin atrophy. Glucocorticoids activate the glucocorticoid and the mineralocorticoid (MR) receptor, both present in the epidermis. We hypothesized that glucocorticoid-induced epidermal atrophy may be related to inappropriate occupancy of MR by glucocorticoids. We evaluated whether epidermal atrophy induced by the topical glucocorticoid clobetasol could be limited by coadministration of MR antagonist. In cultured human skin explants, the epidermal atrophy induced by clobetasol was significantly limited by MR antagonism (canrenoate and eplerenone). Blockade of the epithelial sodium channel ENaC by phenamil was also efficient, identifying a role of MR-ENaC cascade in keratinocytes, acting through restoration of clobetasol-induced impairment of keratinocyte proliferation. In the SPIREPI randomized double-blind controlled trial, gels containing clobetasol, the MR antagonist spironolactone, both agents, or placebo were applied on four zones of the forearms of 23 healthy volunteers for 28 days. Primary outcome was histological thickness of the epidermis with clobetasol alone or clobetasol+spironolactone. Spironolactone alone did not affect the epidermal thickness but coapplication of clobetasol and spironolactone significantly limited clobetasol-induced atrophy and was well tolerated. Altogether, these findings identify MR as a factor regulating epidermal homeostasis and suggest that topical MR blockade could limit glucocorticoid-induced epidermal atrophy. PMID:25668238

  18. Anxieties of communication: the limits of narrative in the medical humanities.

    PubMed

    McKechnie, Claire Charlotte

    2014-12-01

    This paper aims to provide an initial response to Angela Woods's endeavour to '(re)ignite critical debates around this topic' in her recent essay 'The limits of narrative: provocations for the medical humanities' (Medical Humanities 2011). Woods's essay challenges the validity of the notion of the narrative self through her discussion and use of Galen Strawson's seminal 'Against narrativity' (2004). To some extent in dialogue with Woods, this article will examine three exploratory concepts connected with the topic. First, it will explore ways in which we might seek to re-place narrative at the centre of the philosophy of good medicine and medical practice by reassessing the role of the narratee in the narrative process. Second, it will reconsider the three alternative forms of expression Woods puts forward as non-narrative--metaphor, phenomenology and photography--as narrative. Finally, and connected to the first two areas of discussion, it will reflect on ways in which narrative might be used to interpret illness and suffering in medical humanities contexts. What I hope to show, in relation to Woods's work on this subject, is that in order to be interpreted (indeed interpretable) the types of non-narrative representation and communication she discusses in fact require a narrative response. We employ narratology to engage with illness experience because narrative is so fundamental to meaning-making that it is not just required, it is an inherent human response to creative outputs we encounter. This is a quite different approach to the question of narrativity in the medical humanities, and it is therefore related to, but not entirely hinged upon, the work that Woods has done, but it is intended to spark further discussion across the emergent discipline. PMID:24869471

  19. From Oxford to Hawaii Ecophysiological Barriers Limit Human Progression in Ten Sport Monuments

    PubMed Central

    Desgorces, François-Denis; Berthelot, Geoffroy; El Helou, Nour; Thibault, Valérie; Guillaume, Marion; Tafflet, Muriel; Hermine, Olivier; Toussaint, Jean-François

    2008-01-01

    In order to understand the determinants and trends of human performance evolution, we analyzed ten outdoor events among the oldest and most popular in sports history. Best performances of the Oxford-Cambridge boat race (since 1836), the channel crossing in swimming (1875), the hour cycling record (1893), the Elfstedentocht speed skating race (1909), the cross country ski Vasaloppet (1922), the speed ski record (1930), the Streif down-hill in Kitzbühel (1947), the eastward and westward sailing transatlantic records (1960) and the triathlon Hawaii ironman (1978) all follow a similar evolutive pattern, best described through a piecewise exponential decaying model (r2 = 0.95±0.07). The oldest events present highest progression curvature during their early phase. Performance asymptotic limits predicted from the model may be achieved in fourty years (2049±32 y). Prolonged progression may be anticipated in disciplines which further rely on technology such as sailing and cycling. Human progression in outdoor sports tends to asymptotic limits depending on physiological and environmental parameters and may temporarily benefit from further technological progresses. PMID:18985149

  20. Kitagawa-Takahashi diagrams define the limiting conditions for cyclic fatigue failure in human dentin.

    PubMed

    Kruzic, J J; Ritchie, R O

    2006-12-01

    As cyclic fatigue is considered to be a major cause of clinical tooth fractures, achieving a comprehensive understanding of the fatigue behavior of dentin is of importance. In this note, the fatigue behavior of human dentin is examined in the context of the Kitagawa-Takahashi diagram to define the limiting conditions for fatigue failure. Specifically, this approach incorporates two limiting threshold criteria for fatigue: (i) a threshold stress for fatigue failure, specifically the smooth-bar (unnotched) fatigue endurance strength, at small crack sizes and (ii) a threshold stress-intensity range for fatigue-crack growth at larger crack sizes. The approach provides a "bridge" between the traditional fatigue life and fracture mechanics based damage-tolerant approaches to fatigue-life estimation, and as such defines a "failure envelope" of applied stresses and flaw sizes where fatigue failure is likely in dentin This approach may also be applied to fatigue failure in human cortical bone (i.e. clinical "stress fractures"), which exhibits similar fatigue behavior characteristics, and in principle may aid clinicians in making quantitative evaluations of the risk of fractures in mineralized tissues. PMID:17013865

  1. CCR6 Functions as a New Coreceptor for Limited Primary Human and Simian Immunodeficiency Viruses

    PubMed Central

    Islam, Salequl; Shimizu, Nobuaki; Hoque, Sheikh Ariful; Jinno-Oue, Atsushi; Tanaka, Atsushi; Hoshino, Hiroo

    2013-01-01

    More than 12 chemokine receptors (CKRs) have been identified as coreceptors for the entry of human immunodeficiency virus type 1 (HIV-1), type 2 (HIV-2), and simian immunodeficiency viruses (SIVs) into target cells. The expression of CC chemokine receptor 6 (CCR6) on Th17 cells and regulatory T cells make the host cells vulnerable to HIV/SIV infection preferentially. However, only limited information is available concerning the specific role of CCR6 in HIV/SIV infection. We examined CCR6 as a coreceptor candidate in this study using NP-2 cell line-based in-vitro studies. Normally, CD4-transduced cell line, NP-2/CD4, is strictly resistant to all HIV/SIV infection. When CCR6 was transduced there, the resultant NP-2/CD4/CCR6 cells became susceptible to HIV-1HAN2, HIV-2MIR and SIVsmE660, indicating coreceptor roles of CCR6. Viral antigens in infected cells were detected by IFA and confirmed by detection of proviral DNA. Infection-induced syncytia in NP-2/CD4/CCR6 cells were detected by Giemsa staining. Amount of virus release through CCR6 has been detected by RT assay in spent culture medium. Sequence analysis of proviral DNA showed two common amino acid substitutions in the C2 envelope region of HIV-2MIR clones propagated through NP-2/CD4/CCR6 cells. Conversely, CCR6-origin SIVsmE660 clones resulted two amino acid changes in the V1 region and one change in the C2 region. The substitutions in the C2 region for HIV-2MIR and the V1 region of SIVsmE660 may confer selection advantage for CCR6-use. Together, the results describe CCR6 as an independent coreceptor for HIV and SIV in strain-specific manner. The alteration of CCR6 uses by viruses may influence the susceptibility of CD4+ CCR6+ T-cells and dendritic cell subsets in vivo and therefore, is important for viral pathogenesis in establishing latent infections, trafficking, and transmission. However, clinical relevance of CCR6 as coreceptor in HIV/SIV infections should be investigated further. PMID:24009735

  2. A study on flammability limits of fuel mixtures.

    PubMed

    Kondo, Shigeo; Takizawa, Kenji; Takahashi, Akifumi; Tokuhashi, Kazuaki; Sekiya, Akira

    2008-07-15

    Flammability limit measurements were made for various binary and ternary mixtures prepared from nine different compounds. The compounds treated are methane, propane, ethylene, propylene, methyl ether, methyl formate, 1,1-difluoroethane, ammonia, and carbon monoxide. The observed values of lower flammability limits of mixtures were found to be in good agreement to the calculated values by Le Chatelier's formula. As for the upper limits, however, some are close to the calculated values but some are not. It has been found that the deviations of the observed values of upper flammability limits from the calculated ones are mostly to lower concentrations. Modification of Le Chatelier's formula was made to better fit to the observed values of upper flammability limits. This procedure reduced the average difference between the observed and calculated values of upper flammability limits to one-third of the initial value. PMID:18178003

  3. Technological advances for studying human behavior

    NASA Technical Reports Server (NTRS)

    Roske-Hofstrand, Renate J.

    1990-01-01

    Technological advances for studying human behavior are noted in viewgraph form. It is asserted that performance-aiding systems are proliferating without a fundamental understanding of how they would interact with the humans who must control them. Two views of automation research, the hardware view and the human-centered view, are listed. Other viewgraphs give information on vital elements for human-centered research, a continuum of the research process, available technologies, new technologies for persistent problems, a sample research infrastructure, the need for metrics, and examples of data-link technology.

  4. An Interpretive Approach to Human Communication Study.

    ERIC Educational Resources Information Center

    Crawford, Lyall

    In order to consider the study of human communication from an interpretive perspective, this paper addresses two questions: (1) What count as data? and (2) What do data count as? The paper's first section reviews the 1977 Symposium issue of the Western Journal of Speech Communication to identify what constitutes legitimate human communication

  5. Building local human resources to implement SLMTA with limited donor funding: The Ghana experience

    PubMed Central

    Nkrumah, Bernard; van der Puije, Beatrice; Bekoe, Veronica; Adukpo, Rowland; Kotey, Nii A.; Yao, Katy; Fonjungo, Peter N.; Luman, Elizabeth T.; Duh, Samuel; Njukeng, Patrick A.; Addo, Nii A.; Khan, Fazle N.; Woodfill, Celia J.I.

    2016-01-01

    Background In 2009, Ghana adopted the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme in order to improve laboratory quality. The programme was implemented successfully with limited donor funding and local human resources. Objectives To demonstrate how Ghana, which received very limited PEPFAR funding, was able to achieve marked quality improvement using local human resources. Method Local partners led the SLMTA implementation and local mentors were embedded in each laboratory. An in-country training-of-trainers workshop was conducted in order to increase the pool of local SLMTA implementers. Three laboratory cohorts were enrolled in SLMTA in 2011, 2012 and 2013. Participants from each cohort attended in a series of three workshops interspersed with improvement projects and mentorship. Supplemental training on internal audit was provided. Baseline, exit and follow-up audits were conducted using the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) checklist. In November 2013, four laboratories underwent official SLIPTA audits by the African Society for Laboratory Medicine (ASLM). Results The local SLMTA team successfully implemented three cohorts of SLMTA in 15 laboratories. Seven out of the nine laboratories that underwent follow-up audits have reached at least one star. Three out of the four laboratories that underwent official ASLM audits were awarded four stars. Patient satisfaction increased from 25% to 70% and sample rejection rates decreased from 32% to 10%. On average, $40 000 was spent per laboratory to cover mentors' salaries, SLMTA training and improvement project support. Conclusion Building in-country capacity through local partners is a sustainable model for improving service quality in resource-constrained countries such as Ghana. Such models promote country ownership, capacity building and the use of local human resources for the expansion of SLMTA.

  6. Potential and Limitation of HLA-Based Banking of Human Pluripotent Stem Cells for Cell Therapy

    PubMed Central

    Villard, Jean

    2014-01-01

    Great hopes have been placed on human pluripotent stem (hPS) cells for therapy. Tissues or organs derived from hPS cells could be the best solution to cure many different human diseases, especially those who do not respond to standard medication or drugs, such as neurodegenerative diseases, heart failure, or diabetes. The origin of hPS is critical and the idea of creating a bank of well-characterized hPS cells has emerged, like the one that already exists for cord blood. However, the main obstacle in transplantation is the rejection of tissues or organ by the receiver, due to the three main immunological barriers: the human leukocyte antigen (HLA), the ABO blood group, and minor antigens. The problem could be circumvented by using autologous stem cells, like induced pluripotent stem (iPS) cells, derived directly from the patient. But iPS cells have limitations, especially regarding the disease of the recipient and possible difficulties to handle or prepare autologous iPS cells. Finally, reaching standards of good clinical or manufacturing practices could be challenging. That is why well-characterized and universal hPS cells could be a better solution. In this review, we will discuss the interest and the feasibility to establish hPS cells bank, as well as some economics and ethical issues. PMID:25126584

  7. Study of capabilities and limitations of 3D printing technology

    NASA Astrophysics Data System (ADS)

    Lemu, H. G.

    2012-04-01

    3D printing is one of the developments in rapid prototyping technology. The inception and development of the technology has highly assisted the product development phase of product design and manufacturing. The technology is particularly important in educating product design and 3D modeling because it helps students to visualize their design idea, to enhance their creative design process and enables them to touch and feel the result of their innovative work. The availability of many 3D printers on the market has created a certain level of challenge for the user. Among others, complexity of part geometry, material type, compatibility with 3D CAD models and other technical aspects still need in-depth study. This paper presents results of the experimental work on the capabilities and limitations of the Z510 3D printer from Z-corporation. Several parameters such as dimensional and geometrical accuracy, surface quality and strength as a function of model size, orientation and file exchange format are closely studied.

  8. Exploring the Limits to Observational Diffuse Interstellar Band Studies

    NASA Astrophysics Data System (ADS)

    Foing, B. H.

    2014-02-01

    The status of DIB research (Herbig 1995) has strongly advanced since the DIB conference in Boulder in 1994. In the same year we reported the discovery of two near IR diffuse bands coincident with C60 +, that was confirmed in subsequent years. Since then a number of DIB observational studies have been published such as DIB surveys, measurements of DIB families, correlations and environment dependences as well as DIBs in extra-galactic sources. Resolved substructures were measured and compared to predicted rotational contours of large molecules. Polarisation studies provided constraints on possible carrier molecules and upper limits. DIBs carriers have been linked with several classes of organic molecules observed in the interstellar medium, in particular to the UIR bands (assigned to PAHs), the Extended Red Emission (ERE) or the recently detected Anomalous Microwave Emission (AME, assigned to spinning dust). In particular fullerenes and PAHs have been proposed to explain some DIBs and specific molecules were searched for in DIB spectra. DIB carriers could be present in various dehydrogenation and ionization states. Experiments in the laboratory and in space contribute to our understanding of the photo-stability of possible DIB carriers. In summary, the status of DIB research in the last 20 years has strongly advanced. We review DIB observational results and their interpretation and introduce the relevant plenary discussion.

  9. Virtual online consultations: advantages and limitations (VOCAL) study

    PubMed Central

    Greenhalgh, Trisha; Vijayaraghavan, Shanti; Wherton, Joe; Shaw, Sara; Byrne, Emma; Campbell-Richards, Desirée; Bhattacharya, Satya; Hanson, Philippa; Ramoutar, Seendy; Gutteridge, Charles; Hodkinson, Isabel; Collard, Anna; Morris, Joanne

    2016-01-01

    Introduction Remote video consultations between clinician and patient are technically possible and increasingly acceptable. They are being introduced in some settings alongside (and occasionally replacing) face-to-face or telephone consultations. Methods To explore the advantages and limitations of video consultations, we will conduct in-depth qualitative studies of real consultations (microlevel) embedded in an organisational case study (mesolevel), taking account of national context (macrolevel). The study is based in 2 contrasting clinical settings (diabetes and cancer) in a National Health Service (NHS) acute trust in London, UK. Main data sources are: microlevel—audio, video and screen capture to produce rich multimodal data on 45 remote consultations; mesolevel—interviews, ethnographic observations and analysis of documents within the trust; macrolevel—key informant interviews of national-level stakeholders and document analysis. Data will be analysed and synthesised using a sociotechnical framework developed from structuration theory. Ethics approval City Road and Hampstead NHS Research Ethics Committee, 9 December 2014, reference 14/LO/1883. Planned outputs We plan outputs for 5 main audiences: (1) academics: research publications and conference presentations; (2) service providers: standard operating procedures, provisional operational guidance and key safety issues; (3) professional bodies and defence societies: summary of relevant findings to inform guidance to members; (4) policymakers: summary of key findings; (5) patients and carers: ‘what to expect in your virtual consultation’. Discussion The research literature on video consultations is sparse. Such consultations offer potential advantages to patients (who are spared the cost and inconvenience of travel) and the healthcare system (eg, they may be more cost-effective), but fears have been expressed that they may be clinically risky and/or less acceptable to patients or staff, and they bring significant technical, logistical and regulatory challenges. We anticipate that this study will contribute to a balanced assessment of when, how and in what circumstances this model might be introduced. PMID:26826147

  10. Limits on perceptual encoding can be predicted from known receptive field properties of human visual cortex.

    PubMed

    Cohen, Michael A; Rhee, Juliana Y; Alvarez, George A

    2016-01-01

    Human cognition has a limited capacity that is often attributed to the brain having finite cognitive resources, but the nature of these resources is usually not specified. Here, we show evidence that perceptual interference between items can be predicted by known receptive field properties of the visual cortex, suggesting that competition within representational maps is an important source of the capacity limitations of visual processing. Across the visual hierarchy, receptive fields get larger and represent more complex, high-level features. Thus, when presented simultaneously, high-level items (e.g., faces) will often land within the same receptive fields, while low-level items (e.g., color patches) will often not. Using a perceptual task, we found long-range interference between high-level items, but only short-range interference for low-level items, with both types of interference being weaker across hemifields. Finally, we show that long-range interference between items appears to occur primarily during perceptual encoding and not during working memory maintenance. These results are naturally explained by the distribution of receptive fields and establish a link between perceptual capacity limits and the underlying neural architecture. (PsycINFO Database Record PMID:26322687

  11. Real-Time Human Ambulation, Activity, and Physiological Monitoring: Taxonomy of Issues, Techniques, Applications, Challenges and Limitations

    PubMed Central

    Khusainov, Rinat; Azzi, Djamel; Achumba, Ifeyinwa E.; Bersch, Sebastian D.

    2013-01-01

    Automated methods of real-time, unobtrusive, human ambulation, activity, and wellness monitoring and data analysis using various algorithmic techniques have been subjects of intense research. The general aim is to devise effective means of addressing the demands of assisted living, rehabilitation, and clinical observation and assessment through sensor-based monitoring. The research studies have resulted in a large amount of literature. This paper presents a holistic articulation of the research studies and offers comprehensive insights along four main axes: distribution of existing studies; monitoring device framework and sensor types; data collection, processing and analysis; and applications, limitations and challenges. The aim is to present a systematic and most complete study of literature in the area in order to identify research gaps and prioritize future research directions. PMID:24072027

  12. Community Engagement in Observational Human Exposure Studies

    EPA Science Inventory

    Although observational human exposure studies do not deliberately expose participants to chemicals or environmental conditions, merely involving people as research participants and conducting research inside homes raises ethical issues. Community engagement offers a promising st...

  13. A limited flight study for investigating hyperstereo vision

    NASA Astrophysics Data System (ADS)

    Kalich, Melvyn E.; Rash, Clarence E.; McLean, William E.; Ramiccio, John G.

    2007-04-01

    A number of currently proposed helmet-mounted display (HMD) designs relocate image intensification (I2) tubes to the sides of the helmet. Such a design approach induces a visual condition referred to as hyperstereo vision (or hyperstereopsis). This condition manifests itself to the user as an exaggerated sense of depth perception, causing near- to mid-range objects to appear closer than they actually are. Hyperstereopsis is potentially a major concern for helicopter operations that are conducted at low altitudes. As part of a limited flight study to investigate this phenomenon, five rated U.S. Army aviators, as technical observers, wore a hyperstereo HMD during the conduct of a series if 13 standard maneuvers. Two subject aviators acquired a total of eight hours and three aviators a single hour of flight. Using a post-flight questionnaire, these aviators were asked to compare their visual experiences to that of normal I2-aided flight. Depth perception at distances below 300 feet was identified as the greatest challenge. The two 8-hour aviators reported a 5-8 hour "adaptation" period for most maneuvers.

  14. Studies of human mutation rates

    SciTech Connect

    Neel, J.V.

    1991-07-15

    The three objectives of the program are: To isolate by the technique of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), proteins of special interest because of the relative mutability of the corresponding gene, establish the identity of the protein, and, for selected proteins, move to a characterization of the corresponding gene; To develop a more efficient approach, based on 2-D PAGE, for the detection of variants in DNA, with special reference to the identification of a variant in a child not present in either parent of the child (i.e., a mutation); and, To continue an effective interface with the genetic studies on the children of atomic bomb survivors in Japan, with reference to both the planning and implementation of new studies at the molecular level. For administrative purposes, the program is subdivided into four sections, each under the direction of one of the four co-PIs; the progress during the past year will be summarized in accordance with this sectional structure. 1 tab.

  15. Predicting Nursing Human Resources: An Exploratory Study

    PubMed Central

    Squires, Allison; Beltrán-Sánchez, Hiram

    2010-01-01

    The nurse-to-population ratio (NPOP) is a standard indicator used to indicate a country’s health care human resources capacity for responding to its disease burden. This study sought to explore if socioeconomic development indicators could predict the NPOP in a country. Mexico served as the case example for this exploratory study, with the final five variables selected based on findings from a qualitative study analyzing the development of nursing human resources in the country. Multiple linear regression showed that two variables proved significant predictors of the NPOP and the model itself explained 70% of the variance (r2 = .7; p = .0000). The findings have multiple implications for nursing human resources policy in Mexico and at a global level as governments attempt to build human capital to respond to population health needs. PMID:19628510

  16. Lesson Study by Secondary Humanities Teachers

    ERIC Educational Resources Information Center

    Carpenter, Jeffrey Paul

    2009-01-01

    This study examined the experiences of a group of American secondary humanities teachers engaged in lesson study. Lesson study (LS) is a teacher-driven, collaborative inquiry process grounded in the realities of the classroom. It is an approach to professional development (PD) that originated in Japan, and has been credited there with contributing

  17. On the generality and limits of abstraction in rats and humans

    PubMed Central

    Miller, Ralph R.

    2010-01-01

    In this review, we address the question, central to cognition, of whether nonhuman animals such as rats are capable of extracting and extending information from a given learning situation to a new learning situation without generalizing through a physical dimension of the stimuli. This capacity underlies abstraction, which is a hallmark of human cognition and necessary for complex information processing such as language acquisition. We selectively review recent experiments with rats in which systematic changes in information processing of new stimuli are observed after training with different stimuli. These results strongly suggest that this capacity is present in rats. We also review two articles in which clear limitations to this capacity are detected. We conclude that, within specified limits, rats are capable of using prior experience when faced with a learning situation that involves new stimuli. We interpret this ability as a rudimentary form of abstraction. In the face of these provocative results, new theories of learning should be designed to account for these findings. PMID:20012121

  18. Expanding the limits of human blood metabolite quantitation using NMR spectroscopy.

    PubMed

    Nagana Gowda, G A; Gowda, Yashas N; Raftery, Daniel

    2015-01-01

    A current challenge in metabolomics is the reliable quantitation of many metabolites. Limited resolution and sensitivity combined with the challenges associated with unknown metabolite identification have restricted both the number and the quantitative accuracy of blood metabolites. Focused on alleviating this bottleneck in NMR-based metabolomics, investigations of pooled human serum combining an array of 1D/2D NMR experiments at 800 MHz, database searches, and spiking with authentic compounds enabled the identification of 67 blood metabolites. Many of these (?1/3) are new compared with those reported previously as a part of the Human Serum Metabolome Database. In addition, considering both the high reproducibility and quantitative nature of NMR as well as the sensitivity of NMR chemical shifts to altered sample conditions, experimental protocols and comprehensive peak annotations are provided here as a guide for identification and quantitation of the new pool of blood metabolites for routine applications. Further, investigations focused on the evaluation of quantitation using organic solvents revealed a surprisingly poor performance for protein precipitation using acetonitrile. One-third of the detected metabolites were attenuated by 10-67% compared with methanol precipitation at the same solvent-to-serum ratio of 2:1 (v/v). Nearly 2/3 of the metabolites were further attenuated by up to 65% upon increasing the acetonitrile-to-serum ratio to 4:1 (v/v). These results, combined with the newly established identity for many unknown metabolites in the NMR spectrum, offer new avenues for human serum/plasma-based metabolomics. Further, the ability to quantitatively evaluate nearly 70 blood metabolites that represent numerous classes, including amino acids, organic acids, carbohydrates, and heterocyclic compounds, using a simple and highly reproducible analytical method such as NMR may potentially guide the evaluation of samples for analysis using mass spectrometry. PMID:25485990

  19. Stimulators of Mineralization Limit the Invasive Phenotype of Human Osteosarcoma Cells by a Mechanism Involving Impaired Invadopodia Formation

    PubMed Central

    Cmoch, Anna; Podszywalow-Bartnicka, Paulina; Palczewska, Malgorzata; Piwocka, Katarzyna; Groves, Patrick; Pikula, Slawomir

    2014-01-01

    Background Osteosarcoma (OS) is a highly aggressive bone cancer affecting children and young adults. Growing evidence connects the invasive potential of OS cells with their ability to form invadopodia (structures specialized in extracellular matrix proteolysis). Results In this study, we tested the hypothesis that commonly used in vitro stimulators of mineralization limit the invadopodia formation in OS cells. Here we examined the invasive potential of human osteoblast-like cells (Saos-2) and osteolytic-like (143B) OS cells treated with the stimulators of mineralization (ascorbic acid and B-glycerophosphate) and observed a significant difference in response of the tested cells to the treatment. In contrast to 143B cells, osteoblast-like cells developed a mineralization phenotype that was accompanied by a decreased proliferation rate, prolongation of the cell cycle progression and apoptosis. On the other hand, stimulators of mineralization limited osteolytic-like OS cell invasiveness into collagen matrix. We are the first to evidence the ability of 143B cells to degrade extracellular matrix to be driven by invadopodia. Herein, we show that this ability of osteolytic-like cells in vitro is limited by stimulators of mineralization. Conclusions Our study demonstrates that mineralization competency determines the invasive potential of cancer cells. A better understanding of the molecular mechanisms by which stimulators of mineralization regulate and execute invadopodia formation would reveal novel clinical targets for treating osteosarcoma. PMID:25314307

  20. Limitations to systemic and locomotor limb muscle oxygen delivery and uptake during maximal exercise in humans

    PubMed Central

    Mortensen, Stefan P; Dawson, Ellen A; Yoshiga, Chie C; Dalsgaard, Mads K; Damsgaard, Rasmus; Secher, Niels H; González-Alonso, José

    2005-01-01

    Reductions in systemic and locomotor limb muscle blood flow and O2 delivery limit aerobic capacity in humans. To examine whether O2 delivery limits both aerobic power and capacity, we first measured systemic haemodynamics, O2 transport and O2 uptake during incremental and constant (372 ± 11 W; 85% of peak power; mean ± s.e.m.) cycling exercise to exhaustion (n = 8) and then measured systemic and leg haemodynamics and during incremental cycling and knee-extensor exercise in male subjects (n = 10). During incremental cycling, cardiac output and systemic O2 delivery increased linearly to 80% of peak power (r2 = 0.998, P < 0.001) and then plateaued in parallel to a decline in stroke volume (SV) and an increase in central venous and mean arterial pressures (P < 0.05). In contrast, heart rate and increased linearly until exhaustion (r2 = 0.993; P < 0.001) accompanying a rise in systemic O2 extraction to 84 ± 2%. In the exercising legs, blood flow and O2 delivery levelled off at 73–88% of peak power, blunting leg per unit of work despite increasing O2 extraction. When blood flow increased linearly during one-legged knee-extensor exercise, per unit of work was unaltered on fatigue. During constant cycling, , SV, systemic O2 delivery and reached maximal values within ∼5 min, but dropped before exhaustion (P < 0.05) despite increasing or stable central venous and mean arterial pressures. In both types of maximal cycling, the impaired systemic O2 delivery was due to the decline or plateau in because arterial O2 content continued to increase. These results indicate that an inability of the circulatory system to sustain a linear increase in O2 delivery to the locomotor muscles restrains aerobic power. The similar impairment in SV and O2 delivery during incremental and constant load cycling provides evidence for a central limitation to aerobic power and capacity in humans. PMID:15860533

  1. Limitations to systemic and locomotor limb muscle oxygen delivery and uptake during maximal exercise in humans.

    PubMed

    Mortensen, Stefan P; Dawson, Ellen A; Yoshiga, Chie C; Dalsgaard, Mads K; Damsgaard, Rasmus; Secher, Niels H; Gonzlez-Alonso, Jos

    2005-07-01

    Reductions in systemic and locomotor limb muscle blood flow and O2 delivery limit aerobic capacity in humans. To examine whether O2 delivery limits both aerobic power and capacity, we first measured systemic haemodynamics, O2 transport and O2 uptake during incremental and constant (372 +/- 11 W; 85% of peak power; mean +/- S.E.M.) cycling exercise to exhaustion (n = 8) and then measured systemic and leg haemodynamics and during incremental cycling and knee-extensor exercise in male subjects (n = 10). During incremental cycling, cardiac output and systemic O2 delivery increased linearly to 80% of peak power (r2 = 0.998, P < 0.001) and then plateaued in parallel to a decline in stroke volume (SV) and an increase in central venous and mean arterial pressures (P < 0.05). In contrast, heart rate and increased linearly until exhaustion (r2 = 0.993; P < 0.001) accompanying a rise in systemic O2 extraction to 84 +/- 2%. In the exercising legs, blood flow and O2 delivery levelled off at 73-88% of peak power, blunting leg per unit of work despite increasing O2 extraction. When blood flow increased linearly during one-legged knee-extensor exercise, per unit of work was unaltered on fatigue. During constant cycling, , SV, systemic O2 delivery and reached maximal values within approximately 5 min, but dropped before exhaustion (P < 0.05) despite increasing or stable central venous and mean arterial pressures. In both types of maximal cycling, the impaired systemic O2 delivery was due to the decline or plateau in because arterial O2 content continued to increase. These results indicate that an inability of the circulatory system to sustain a linear increase in O2 delivery to the locomotor muscles restrains aerobic power. The similar impairment in SV and O2 delivery during incremental and constant load cycling provides evidence for a central limitation to aerobic power and capacity in humans. PMID:15860533

  2. Background of Civil Defense and Current Damage Limiting Studies.

    ERIC Educational Resources Information Center

    Romm, Joseph

    A brief history of civil defense administration precedes analysis of nuclear attack conditions and the influence of protective measures. Damage limitation procedure is explained in terms of--(1) blast effects, (2) radiation doses, (3) geographical fallout distribution patterns, and (4) national shelter needs. Major concept emphasis relates to--(1)

  3. Risk and maximum residue limits: a study of hops production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This paper examines how maximum residue limits (MRLs) affect the optimal choice by growers of chemical applications to control pests and diseases. In practice, growers who export balance both yield risk and pesticide residue uncertainty when making chemical application decisions. To address these is...

  4. Study of human bone tumor slice by SRXRF microprobe

    NASA Astrophysics Data System (ADS)

    Huang, Y. Y.; Lu, J. X.; He, R. G.; Zhao, L. M.; Wang, Z. G.; He, W.; Zhang, Y. X.

    2001-07-01

    The SRXRF microprobe at the BSRF is described. The minimum detection limits (MDLs) of trace elements were measured to determine the capability for biological sample analysis. The changes of the trace elements and their ratios in the normal and tumor parts of a human osteosarcoma tissue were investigated. It was found that our results were in agreement with those of other analytical methods, such as spectrophotometric analysis, NAA and PIXE as well as an early clinic study of serum.

  5. Limited proteolysis of human leukocyte interferon-. cap alpha. 2 and localization of the monoclonal antibody-binding antigenic determinant

    SciTech Connect

    Kostrov, S.V.; Chernovskaya, T.V.; Khodova, O.M.; Borukhov, S.I.; Ryzhavskaya, A.S.; Izotova, L.S.; Strongin, A.Ya.

    1986-05-20

    Large peptide fragments of human leukocyte interferon-..cap alpha..2 (INF-..cap alpha..2) were produced by limited proteolysis with trypsin, pepsin, thermolysin, and Bacillus amyloliquefaciens serine proteinase, and the ability of the fragments to react with murine monoclonal antibodies NK2, directed toward INF-..cap alpha..2, was studied by the immunoblotting technique. The region of the sequence 110-149 is the most sensitive to proteinase attack and evidently is exposed on the surface of the INF-..cap alpha..2 molecule. The INF-..cap alpha..2 fragments 1-139, 1-147, and 1-149 react with antibodies, whereas the fragments 1-109 and 1-112 do not bind NK2 antibodies. A comparison of the primary structure of the families of human leukocyte and murine leukocyte INF in the region of the sequence 110-139 and an analysis of the ability of human INF differing in amino acid sequence to interact with NK2 antibodies suggested that the antigenic determinant that binds monoclonal antibodies NK2 is the sequence Glu/sub 114/-Asp/sub 115/-Ser/sub 116/-He/sub 117/ of the INF-..cap alpha..2 molecule.

  6. Limits of Human Performance. Annual Meeting (56th, Eugene, Oregon, July 19-26, 1984). American Academy of Physical Education Papers, No. 18.

    ERIC Educational Resources Information Center

    Clarke, David H., Ed.; Eckert, Helen M., Ed.

    The following papers are included in this collection: (1) "The Scientific Study of Athletes and Athletics" (Henry J. Montoye); (2) "The Limits of Human Performance" (David H. Clarke); (3) "Observations of Extraordinary Performances in an Extreme Environment and in a Training Environment" (E.R. Buskirk); (4) "Metabolic Requirements of Distance

  7. Limits of Human Performance. Annual Meeting (56th, Eugene, Oregon, July 19-26, 1984). American Academy of Physical Education Papers, No. 18.

    ERIC Educational Resources Information Center

    Clarke, David H., Ed.; Eckert, Helen M., Ed.

    The following papers are included in this collection: (1) "The Scientific Study of Athletes and Athletics" (Henry J. Montoye); (2) "The Limits of Human Performance" (David H. Clarke); (3) "Observations of Extraordinary Performances in an Extreme Environment and in a Training Environment" (E.R. Buskirk); (4) "Metabolic Requirements of Distance…

  8. EVA Health and Human Performance Benchmarking Study

    NASA Technical Reports Server (NTRS)

    Abercromby, A. F.; Norcross, J.; Jarvis, S. L.

    2016-01-01

    Multiple HRP Risks and Gaps require detailed characterization of human health and performance during exploration extravehicular activity (EVA) tasks; however, a rigorous and comprehensive methodology for characterizing and comparing the health and human performance implications of current and future EVA spacesuit designs does not exist. This study will identify and implement functional tasks and metrics, both objective and subjective, that are relevant to health and human performance, such as metabolic expenditure, suit fit, discomfort, suited postural stability, cognitive performance, and potentially biochemical responses for humans working inside different EVA suits doing functional tasks under the appropriate simulated reduced gravity environments. This study will provide health and human performance benchmark data for humans working in current EVA suits (EMU, Mark III, and Z2) as well as shirtsleeves using a standard set of tasks and metrics with quantified reliability. Results and methodologies developed during this test will provide benchmark data against which future EVA suits, and different suit configurations (eg, varied pressure, mass, CG) may be reliably compared in subsequent tests. Results will also inform fitness for duty standards as well as design requirements and operations concepts for future EVA suits and other exploration systems.

  9. Demonstrating the Efficacy of the FoneAstra Pasteurization Monitor for Human Milk Pasteurization in Resource-Limited Settings

    PubMed Central

    Coutsoudis, Anna; Israel-Ballard, Kiersten; Chaudhri, Rohit; Perin, Noah; Mlisana, Koleka

    2015-01-01

    Abstract Human milk provides crucial nutrition and immunologic protection for infants. When a mother's own milk is unavailable, donated human milk, pasteurized to destroy bacteria and viruses, is a lifesaving replacement. Flash-heat pasteurization is a simple, low-cost, and commonly used method to make milk safe, but currently there is no system to monitor milk temperature, which challenges quality control. FoneAstra, a smartphone-based mobile pasteurization monitor, removes this barrier by guiding users through pasteurization and documenting consistent and safe practice. This study evaluated FoneAstra's efficacy as a quality control system, particularly in resource-limited settings, by comparing bacterial growth in donor milk flash-heated with and without the device at a neonatal intensive care unit in Durban, South Africa. Materials and Methods: For 100 samples of donor milk, one aliquot each of prepasteurized milk, milk flash-heated without FoneAstra, and milk pasteurized with FoneAstra was cultured on routine agar for bacterial growth. Isolated bacteria were identified and enumerated. Results: In total, 300 samples (three from each donor sample) were analyzed. Bacterial growth was found in 86 of the 100 samples before any pasteurization and one of the 100 postpasteurized samples without FoneAstra. None of the samples pasteurized using FoneAstra showed bacterial growth. Conclusions: Both pasteurization methods were safe and effective. FoneAstra, however, provides the additional benefits of user-guided temperature monitoring and data tracking. By improving quality assurance and standardizing the pasteurization process, FoneAstra can support wide-scale implementation of human milk banks in resource-limited settings, increasing access and saving lives. PMID:25668396

  10. Innovation-diffusion: a geographical study of the transition of family limitation practice in Taiwan.

    PubMed

    Ting, T Y

    1984-09-01

    This paper uses map analysis to study the transition of family limitation practice in Taiwan between 1961-80. The innovation-diffusion perspective emphasizes that birth control, particularly contraception, is a recent innovation and is essentially new in human culture. The innovation-diffusion theory assumes that the decline of fertility began in a setting where there was no, or at most very limited, previous practice of birth control. The theory emphasizes the importance of the spread of information. It also assumes that innovation starts in metropolitan centers, diffuses to other urban places with some delay, and penetrates to rural areas still later. Innovation behavior also diffuses from 1 area to another which is culturally and linguistically similar. Although there was some urban to rural diffusion from the Taiwan family planning program, the government supported program provided services more evenly between urban and rural areas, thus somewhat limiting the diffusion effect from the program. For the diffusion of family practice in Taiwan, it is expected that the availability of of information about and means of family limitation practice may effect the rate of the increase of small m values -- an index of family limitation -- in an area. The case study of Pingtung county shows that the demand-side diffusion from urban to rural areas was important in the earlier decade of the transition of family plimitation practice, but distance from urban center was less important as practice became more uniform through diffusion. Ethnicity, whether or not the township was dominated by Hakka or Fukienese, also seems to have played an important role in determining the pace at which the local residents adopted family practice limitation. Hakka townships seem to have adopted family limitation practice more slowly than Fukienese townships about the same distance from the urban center. The map analysis of Pingtung county provides descriptive evidence to support the diffusion of family limitation from urban centers to distant areas, while ethnic variables like Hakka population tend to delay the adoption of family limitation practice. In general, the urban center had higher m values than the surrounding rural areas in Pingtung county and for areas other than the urban center the the level of m values is a negative function of the distance to the urban center. PMID:12266924

  11. Nutrient Limitation Governs Staphylococcus aureus Metabolism and Niche Adaptation in the Human Nose

    PubMed Central

    Krismer, Bernhard; Liebeke, Manuel; Janek, Daniela; Nega, Mulugeta; Rautenberg, Maren; Hornig, Gabriele; Unger, Clemens; Weidenmaier, Christopher; Lalk, Michael; Peschel, Andreas

    2014-01-01

    Colonization of the human nose by Staphylococcus aureus in one-third of the population represents a major risk factor for invasive infections. The basis for adaptation of S. aureus to this specific habitat and reasons for the human predisposition to become colonized have remained largely unknown. Human nasal secretions were analyzed by metabolomics and found to contain potential nutrients in rather low amounts. No significant differences were found between S. aureus carriers and non-carriers, indicating that carriage is not associated with individual differences in nutrient supply. A synthetic nasal medium (SNM3) was composed based on the metabolomics data that permits consistent growth of S. aureus isolates. Key genes were expressed in SNM3 in a similar way as in the human nose, indicating that SNM3 represents a suitable surrogate environment for in vitro simulation studies. While the majority of S. aureus strains grew well in SNM3, most of the tested coagulase-negative staphylococci (CoNS) had major problems to multiply in SNM3 supporting the notion that CoNS are less well adapted to the nose and colonize preferentially the human skin. Global gene expression analysis revealed that, during growth in SNM3, S. aureus depends heavily on de novo synthesis of methionine. Accordingly, the methionine-biosynthesis enzyme cysteine-γ-synthase (MetI) was indispensable for growth in SNM3, and the MetI inhibitor DL-propargylglycine inhibited S. aureus growth in SNM3 but not in the presence of methionine. Of note, metI was strongly up-regulated by S. aureus in human noses, and metI mutants were strongly abrogated in their capacity to colonize the noses of cotton rats. These findings indicate that the methionine biosynthetic pathway may include promising antimicrobial targets that have previously remained unrecognized. Hence, exploring the environmental conditions facultative pathogens are exposed to during colonization can be useful for understanding niche adaptation and identifying targets for new antimicrobial strategies. PMID:24453967

  12. Potential Limitations of the NSG Humanized Mouse as a Model System to Optimize Engineered Human T cell Therapy for Cancer

    PubMed Central

    Alcantar-Orozco, Erik M.; Gornall, Hannah; Baldan, Vania; Hawkins, Robert E.

    2013-01-01

    Abstract The genetic modification of peripheral blood lymphocytes using retroviral vectors to redirect T cells against tumor cells has been recently used as a means to generate large numbers of antigen-specific T cells for adoptive cell therapy protocols. However, commonly used retroviral vector-based genetic modification requires T cells to be driven into cell division; this potent mitogenic stimulus is associated with the development of an effector phenotype that may adversely impact upon the long-term engraftment potential and subsequent antitumor effects of T cells. To investigate whether the cytokines used during culture impact upon the engraftment potential of gene-modified T cells, a humanized model employing T cells engrafted with a MART-1-specific T cell receptor adoptively transferred into NOD/Shi-scid IL-2rγ−/− (NSG) immune-deficient mice bearing established melanoma tumors was used to compare the effects of the common γ chain cytokines IL-2, IL-7, and IL-15 upon gene-modified T cell activity. MART-1-specific T cells cultured in IL-7 and IL-15 demonstrated greater relative in vitro proliferation and viability of T cells compared with the extensively used IL-2. Moreover, the IL-15 culture prolonged the survival of animals bearing melanoma tumors after adoptive transfer. However, the combination of IL-7 and IL-15 produced T cells with improved engraftment potential compared with IL-15 alone; however, a high rate of xenogeneic graft-versus-host disease prevented the identification of a clear improvement in antitumor effect of these T cells. These results clearly demonstrate modulation of gene-modified T cell engraftment in the NSG mouse, which supports the future testing of the combination of IL-7 and IL-15 in adoptive cell therapy protocols; however, this improved engraftment is also associated with the long-term maintenance of xenoreactive T cells, which limits the ultimate usefulness of the NSG mouse model in this situation. PMID:23931270

  13. A limited bibliography of the Federal Government-funded human radiation experiments.

    PubMed

    Samei, E; Kearfott, K J

    1995-12-01

    From the early 1940's thousands of U.S. citizens have been the subjects of federally supported scientific experiments that involved the administration of ionizing radiation or radioactive substances. Recently, many questions have been raised regarding the nature, scientific value, and ethics of these experiments. Although the results of many of the early human experiments involving radiation have been crucial to the establishment of nuclear medicine, radiation therapy, and radiological protection standards, the underlying ethical basis for a small number of these studies is being questioned. A thorough analysis of these studies and their ethical basis is beyond the scope of this article. Rather, in order to quickly provide the health physics community with some of the available resources in the open literature, a list of bibliographic citations of the 47 studies primarily funded by the Atomic Energy Commission (AEC) and other predecessors of the Department of Energy is presented and briefly summarized. A classification scheme for the human radiation experiments is also developed. PMID:7493803

  14. Trans locus inhibitors limit concomitant polysaccharide synthesis in the human gut symbiont Bacteroides fragilis.

    PubMed

    Chatzidaki-Livanis, Maria; Weinacht, Katja G; Comstock, Laurie E

    2010-06-29

    Bacteroides is an abundant genus of bacteria of the human intestinal microbiota. Bacteroides species synthesize a large number of capsular polysaccharides (PS), a biological property not shared with closely related oral species, suggesting importance for intestinal survival. Bacteroides fragilis, for example, synthesizes eight capsular polysaccharides per strain, each of which phase varies via inversion of the promoters located upstream of seven of the eight polysaccharide biosynthesis operons. In a single cell, many of these polysaccharide loci promoters can be simultaneously oriented on for transcription of the downstream biosynthesis operons. Here, we demonstrate that despite the promoter orientations, concomitant transcription of multiple polysaccharide loci within a cell is inhibited. The proteins encoded by the second gene of each of these eight loci, collectively designated the UpxZ proteins, inhibit the synthesis of heterologous polysaccharides. These unique proteins interfere with the ability of UpxY proteins encoded by other polysaccharide loci to function in transcriptional antitermination of their respective operon. The eight UpxZs have different inhibitory spectra, thus establishing a hierarchical regulatory network for polysaccharide synthesis. Limitation of concurrent polysaccharide synthesis strongly suggests that these bacteria evolved this property as an evasion-type mechanism to avoid killing by polysaccharide-targeting factors in the ecosystem. PMID:20547868

  15. Trans locus inhibitors limit concomitant polysaccharide synthesis in the human gut symbiont Bacteroides fragilis

    PubMed Central

    Chatzidaki-Livanis, Maria; Comstock, Laurie E.

    2010-01-01

    Bacteroides is an abundant genus of bacteria of the human intestinal microbiota. Bacteroides species synthesize a large number of capsular polysaccharides (PS), a biological property not shared with closely related oral species, suggesting importance for intestinal survival. Bacteroides fragilis, for example, synthesizes eight capsular polysaccharides per strain, each of which phase varies via inversion of the promoters located upstream of seven of the eight polysaccharide biosynthesis operons. In a single cell, many of these polysaccharide loci promoters can be simultaneously oriented on for transcription of the downstream biosynthesis operons. Here, we demonstrate that despite the promoter orientations, concomitant transcription of multiple polysaccharide loci within a cell is inhibited. The proteins encoded by the second gene of each of these eight loci, collectively designated the UpxZ proteins, inhibit the synthesis of heterologous polysaccharides. These unique proteins interfere with the ability of UpxY proteins encoded by other polysaccharide loci to function in transcriptional antitermination of their respective operon. The eight UpxZs have different inhibitory spectra, thus establishing a hierarchical regulatory network for polysaccharide synthesis. Limitation of concurrent polysaccharide synthesis strongly suggests that these bacteria evolved this property as an evasion-type mechanism to avoid killing by polysaccharide-targeting factors in the ecosystem. PMID:20547868

  16. Designing and Interpreting Limiting Dilution Assays: General Principles and Applications to the Latent Reservoir for Human Immunodeficiency Virus-1.

    PubMed

    Rosenbloom, Daniel I S; Elliott, Oliver; Hill, Alison L; Henrich, Timothy J; Siliciano, Janet M; Siliciano, Robert F

    2015-12-01

    Limiting dilution assays are widely used in infectious disease research. These assays are crucial for current human immunodeficiency virus (HIV)-1 cure research in particular. In this study, we offer new tools to help investigators design and analyze dilution assays based on their specific research needs. Limiting dilution assays are commonly used to measure the extent of infection, and in the context of HIV they represent an essential tool for studying latency and potential curative strategies. Yet standard assay designs may not discern whether an intervention reduces an already miniscule latent infection. This review addresses challenges arising in this setting and in the general use of dilution assays. We illustrate the major statistical method for estimating frequency of infectious units from assay results, and we offer an online tool for computing this estimate. We recommend a procedure for customizing assay design to achieve desired sensitivity and precision goals, subject to experimental constraints. We consider experiments in which no viral outgrowth is observed and explain how using alternatives to viral outgrowth may make measurement of HIV latency more efficient. Finally, we discuss how biological complications, such as probabilistic growth of small infections, alter interpretations of experimental results. PMID:26478893

  17. Designing and Interpreting Limiting Dilution Assays: General Principles and Applications to the Latent Reservoir for Human Immunodeficiency Virus-1

    PubMed Central

    Rosenbloom, Daniel I. S.; Elliott, Oliver; Hill, Alison L.; Henrich, Timothy J.; Siliciano, Janet M.; Siliciano, Robert F.

    2015-01-01

    Limiting dilution assays are widely used in infectious disease research. These assays are crucial for current human immunodeficiency virus (HIV)-1 cure research in particular. In this study, we offer new tools to help investigators design and analyze dilution assays based on their specific research needs. Limiting dilution assays are commonly used to measure the extent of infection, and in the context of HIV they represent an essential tool for studying latency and potential curative strategies. Yet standard assay designs may not discern whether an intervention reduces an already miniscule latent infection. This review addresses challenges arising in this setting and in the general use of dilution assays. We illustrate the major statistical method for estimating frequency of infectious units from assay results, and we offer an online tool for computing this estimate. We recommend a procedure for customizing assay design to achieve desired sensitivity and precision goals, subject to experimental constraints. We consider experiments in which no viral outgrowth is observed and explain how using alternatives to viral outgrowth may make measurement of HIV latency more efficient. Finally, we discuss how biological complications, such as probabilistic growth of small infections, alter interpretations of experimental results. PMID:26478893

  18. Hanford study: a review of its limitations and controversial conclusions

    SciTech Connect

    Gilbert, E.S.

    1984-10-01

    The Hanford data set has attracted attention primarily because of analyses conducted by Mancuso, Stewart, and Kneale (MSK). These investigators claim that the Hanford data provide evidence that our current estimates of cancer mortality resulting from radiation exposure are too low, and advocate replacing estimates based on populations exposed at relatively high doses (such as the Japanese atom bomb survivors) with estimates based on the Hanford data. In this paper, it is shown that the only evidence of association of radiation exposure and mortality provided by the Hanford data is a small excess of multiple myeloma, and that this data set is not adequate for reliable risk estimation. It is demonstrated that confidence limits for risk estimates are very wide, and that the data are not adequate to differentiate among models. The more recent MSK analyses, which claim to provide adequate models and risk estimates, are critiqued. 18 references, 1 table.

  19. Genomic approaches to studying the human microbiota

    PubMed Central

    Weinstock, George M.

    2013-01-01

    The human body is colonized by a vast array of microbes, which form communities of bacteria, viruses and microbial eukaryotes that are specific to each anatomical environment. Every community must be studied as a whole because many organisms have never been cultured independently, and this poses formidable challenges. The advent of next-generation DNA sequencing has allowed more sophisticated analysis and sampling of these complex systems by culture-independent methods. These methods are revealing differences in community structure between anatomical sites, between individuals, and between healthy and diseased states, and are transforming our view of human biology. PMID:22972298

  20. Human Transportation System (HTS) study: Executive summary

    NASA Technical Reports Server (NTRS)

    Lance, N.; Geyer, M. S.; Gaunce, M. T.

    1993-01-01

    Work completed under the Human Transportation System Study is summarized. This study was conducted by the New Initiatives Office at JSC with the technical support of Boeing, General Dynamics, Lockheed, McDonnell-Douglas, Martin Marietta, and Rockwell. The study was designed to generate information on determining the appropriate path to follow for new system development to meet the Nation's space transportation needs. The study evaluates 18 transportation architecture options using a parametric set of mission requirements. These options include use of current systems as well as proposed systems to assess the impact of various considerations, such as the cost of alternate access, or the benefit of separating people and cargo. The architecture options are compared to each other with six measurable evaluation criteria or attributes. They are the following: funding profile, human safety, probability of mission success, architecture cost risk, launch schedule confidence, and environmental impact. Values for these attributes are presented for the architecture options, with pertinent conclusions and recommendations.

  1. Human Transportation System (HTS) study, volume 1

    NASA Technical Reports Server (NTRS)

    Lance, N.; Geyer, M. S.; Gaunce, M. T.

    1993-01-01

    Work completed under the Human Transportation System Study is summarized. This study was conducted by the New Initiatives Office at JSC with the technical support of Boeing, General Dynamics, Lockheed, McDonnell-Douglas, Martin Marietta, and Rockwell. The study was designed to generate information on determining the appropriate path to follow for new system development to meet the Nation's space transportation needs. The study evaluates 18 transportation architecture options using a parametric set of mission requirements. These options include use of current systems as well as proposed systems to assess the impact of various considerations, such as the cost of alternate access, or the benefit of separating people and cargo. The architecture options are compared to each other with six measurable evaluation criteria or attributes. They are the following: funding profile, human safety, probability of mission success, architecture cost risk, launch schedule confidence, and environmental impact. Values for these attributes are presented for the architecture options, with pertinent conclusions and recommendations.

  2. The human studies database project: federating human studies design data using the ontology of clinical research.

    PubMed

    Sim, Ida; Carini, Simona; Tu, Samson; Wynden, Rob; Pollock, Brad H; Mollah, Shamim A; Gabriel, Davera; Hagler, Herbert K; Scheuermann, Richard H; Lehmann, Harold P; Wittkowski, Knut M; Nahm, Meredith; Bakken, Suzanne

    2010-01-01

    Human studies, encompassing interventional and observational studies, are the most important source of evidence for advancing our understanding of health, disease, and treatment options. To promote discovery, the design and results of these studies should be made machine-readable for large-scale data mining, synthesis, and re-analysis. The Human Studies Database Project aims to define and implement an informatics infrastructure for institutions to share the design of their human studies. We have developed the Ontology of Clinical Research (OCRe) to model study features such as design type, interventions, and outcomes to support scientific query and analysis. We are using OCRe as the reference semantics for federated data sharing of human studies over caGrid, and are piloting this implementation with several Clinical and Translational Science Award (CTSA) institutions. PMID:21347149

  3. Normal human alveolar macrophages obtained by bronchoalveolar lavage have a limited capacity to release interleukin-1.

    PubMed Central

    Wewers, M D; Rennard, S I; Hance, A J; Bitterman, P B; Crystal, R G

    1984-01-01

    Interleukin-1 (IL-1) is a mediator released by stimulated mononuclear phagocytes that is thought to play an important role in modulating T and B lymphocyte activation as well as in contributing to the febrile response and other inflammatory processes. Circulating mononuclear phagocytes, blood monocytes, readily release IL-1 when stimulated. However, the ability of lung mononuclear phagocytes, alveolar macrophages, to dispose of the large daily burden of inhaled antigens without stimulating an inflammatory response suggests that the release of IL-1 by alveolar macrophages may differ significantly from that of blood monocytes. To evaluate this hypothesis, normal autologous alveolar macrophages, obtained by bronchoalveolar lavage, were compared with blood monocytes for their ability to release IL-1 in response to a standard stimulus, lipopolysaccharide (LPS). Alveolar macrophages were found to be at least 1,000 times less sensitive to LPS than blood monocytes. Furthermore, alveolar macrophages released significantly less IL-1 than blood monocytes (26 +/- 11 vs. 128 +/- 21 U/10(6) cells X 24 h, respectively, after stimulation with 10 micrograms/ml of LPS, P less than 0.001). This difference was not due to the release of substances by macrophages, which inhibited lymphocyte proliferation in response to IL-1, or to degradation of IL-1 by macrophages. Culturing macrophages in the presence of indomethacin and dialysis of macrophage supernatants did not affect the difference, and culturing macrophages with monocytes did not decrease detectable IL-1 activity from the monocytes. The IL-1 produced by the two cell types was indistinguishable by anion-exchange chromatography, gel filtration, and isoelectric focusing. In addition, consistent with the findings for alveolar macrophages, macrophages generated by the in vitro maturation of blood monocytes were also deficient in their ability to release IL-1. These findings suggest that if the population of alveolar macrophages obtained by bronchoalveolar lavage represents the total in vivo population of alveolar macrophages, although normal human macrophages are capable of IL-1 release, they are relatively limited in this ability, and this limitation seems to be linked to the maturational state of the mononuclear phagocyte. These observations may explain, in part, the ability of alveolar macrophages to clear the airspaces of foreign antigens without extensive activation of other pulmonary inflammatory and immune effector cells. Images PMID:6334697

  4. Feasibility study of astronaut standardized career dose limits in LEO and the outlook for BLEO

    NASA Astrophysics Data System (ADS)

    McKenna-Lawlor, Susan; Bhardwaj, A.; Ferrari, Franco; Kuznetsov, Nikolay; Lal, A. K.; Li, Yinghui; Nagamatsu, Aiko; Nymmik, Rikho; Panasyuk, Michael; Petrov, Vladislav; Reitz, Guenther; Pinsky, Lawrence; Muszaphar Shukor, Sheikh; Singhvi, A. K.; Straube, Ulrich; Tomi, Leena; Townsend, Lawrence

    2014-11-01

    Cosmic Study Group SG 3.19/1.10 was established in February 2013 under the aegis of the International Academy of Astronautics to consider and compare the dose limits adopted by various space agencies for astronauts in Low Earth Orbit. A preliminary definition of the limits that might later be adopted by crews exploring Beyond Low Earth Orbit was, in addition, to be made. The present paper presents preliminary results of the study reported at a Symposium held in Turin by the Academy in July 2013. First, an account is provided of exposure limits assigned by various partner space agencies to those of their astronauts that work aboard the International Space Station. Then, gaps in the scientific and technical information required to safely implement human missions beyond the shielding provided by the geomagnetic field (to the Moon, Mars and beyond) are identified. Among many recommendations for actions to mitigate the health risks potentially posed to personnel Beyond Low Earth Orbit is the development of a preliminary concept for a Human Space Awareness System to: provide for crewed missions the means of prompt onboard detection of the ambient arrival of hazardous particles; develop a strategy for the implementation of onboard responses to hazardous radiation levels; support modeling/model validation that would enable reliable predictions to be made of the arrival of hazardous radiation at a distant spacecraft; provide for the timely transmission of particle alerts to a distant crewed vehicle at an emergency frequency using suitably located support spacecraft. Implementation of the various recommendations of the study can be realized based on a two pronged strategy whereby Space Agencies/Space Companies/Private Entrepreneurial Organizations etc. address the mastering of required key technologies (e.g. fast transportation; customized spacecraft design) while the International Academy of Astronautics, in a role of handling global international co-operation, organizes complementary studies aimed at harnessing the strengths and facilities of emerging nations in investigating/solving related problems (e.g. advanced space radiation modeling/model validation; predicting the arrivals of Solar Energetic Particles and shocks at a distant spacecraft). Ongoing progress in pursuing these complementary parallel programs could be jointly reviewed bi-annually by the Space Agencies and the International Academy of Astronautics so as to maintain momentum and direction in globally progressing towards feasible human exploration of interplanetary space.

  5. Identification of host miRNAs that may limit human rhinovirus replication

    PubMed Central

    Bondanese, Victor Paky; Francisco-Garcia, Ana; Bedke, Nicole; Davies, Donna E; Sanchez-Elsner, Tilman

    2014-01-01

    AIM: To test whether the replication of human rhinovirus (HRV) is regulated by microRNAs in human bronchial epithelial cells. METHODS: For the present study, the human cell line BEAS-2B (derived from normal human bronchial epithelial cells) was adopted. DICER knock-down, by siRNA transfection in BEAS-2B cells, was performed in order to inhibit microRNA maturation globally. Alternatively, antisense oligonucleotides (anti-miRs) were transfected to inhibit the activity of specific microRNAs. Cells were infected with HRV-1B. Viral replication was assessed by measuring the genomic viral RNA by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Association between microRNA-induced-silencing-complex and viral RNA was detected by Ago2 co-immunoprecipitation followed by RT-qPCR. Targetscan v.6 was used to predict microRNA target sites on several HRV strains. RESULTS: Here, we show that microRNAs affect replication of HRV-1B. DICER knock-down significantly reduced the expression of mature microRNAs in a bronchial epithelial cell line (BEAS-2B) and in turn, increased the synthesis of HRV-1B RNA. Additionally, HRV-1B RNA co-immunoprecipitated with argonaute 2 protein, an important effector for microRNA activity suggesting that microRNAs bind to viral RNA during infection. In order to identify specific microRNAs involved in this interaction, we employed bioinformatics analysis, and selected a group of microRNAs that have been reported to be under-expressed in asthmatic bronchial epithelial cells and were predicted to target different strains of rhinoviruses (HRV-1B, -16, -14, -27). Our results suggest that, out of this group of microRNAs, miR-128 and miR-155 contribute to the innate defense against HRV-1B: transfection of specific anti-miRs increased viral replication, as anticipated in-silico. CONCLUSION: Taken together, our results suggest that pathological changes in microRNA expression, as already reported for asthma or chronic obstructive pulmonary disease have the potential to affect Rhinovirus replication and therefore may play a role in virus-induced exacerbations. PMID:25426267

  6. Pushing the limits of in vivo diffusion MRI for the Human Connectome Project

    PubMed Central

    Setsompop, K.; Kimmlingen, R.; Eberlein, E.; Witzel, T.; Cohen-Adad, J.; McNab, J.A.; Keil, B.; Tisdall, M.D.; Hoecht, P.; Dietz, P.; Cauley, S.F.; Tountcheva, V.; Matschl, V.; Lenz, V. H.; Heberlein, K.; Potthast, A.; Thein, H.; Van Horn, J.; Toga, A.; Schmitt, F.; Lehne, D.; Rosen, B.R.; Wedeen, V.; Wald, L.L.

    2013-01-01

    Perhaps more than any other -omics endeavor, the accuracy and level of detail obtained from mapping the major connection pathways in the living human brain with diffusion MRI depends on the capabilities of the imaging technology used. The current tools are remarkable; allowing the formation of an image of the water diffusion probability distribution in regions of complex crossing fibers at each of half a million voxels in the brain. Nonetheless our ability to map the connection pathways is limited by the image sensitivity and resolution, and also the contrast and resolution in encoding of the diffusion probability distribution. The goal of our Human Connectome Project (HCP) is to address these limiting factors by re-engineering the scanner from the ground up to optimize the high b-value, high angular resolution diffusion imaging needed for sensitive and accurate mapping of the brains structural connections. Our efforts were directed based on the relative contributions of each scanner component. The gradient subsection was a major focus since gradient amplitude is central to determining the diffusion contrast, the amount of T2 signal loss, and the blurring of the water PDF over the course of the diffusion time. By implementing a novel 4-port drive geometry and optimizing size and linearity for the brain, we demonstrate a whole-body sized scanner with Gmax = 300mT/m on each axis capable of the sustained duty cycle needed for diffusion imaging. The system is capable of slewing the gradient at a rate of 200 T/m/s as needed for the EPI image encoding. In order to enhance the efficiency of the diffusion sequence we implemented a FOV shifting approach to Simultaneous MultiSlice (SMS) EPI capable of unaliasing 3 slices excited simultaneously with a modest g-factor penalty allowing us to diffusion encode whole brain volumes with low TR and TE. Finally we combine the multi-slice approach with a compressive sampling reconstruction to sufficiently undersample q-space to achieve a DSI scan in less than 5 minutes. To augment this accelerated imaging approach we developed a 64-channel, tight-fitting brain array coil and show its performance benefit compared to a commercial 32-channel coils at all locations in the brain for these accelerated acquisitions. The technical challenges of developing the over-all system are discussed as well as results from SNR comparisons, ODF metrics and fiber tracking comparisons. The ultra-high gradients yielded substantial and immediate gains in the sensitivity through reduction of TE and improved signal detection and increased efficiency of the DSI or HARDI acquisition, accuracy and resolution of diffusion tractography, as defined by identification of known structure and fiber crossing. PMID:23707579

  7. Descriptive Study of Services to Limited English Proficient Students. Volume 3: Case Studies.

    ERIC Educational Resources Information Center

    Fleischman, Howard L., Ed.; Dervaric, Charles, Ed.; Leighton, Ed.; Said, Mary Staples, Ed.

    The report presents results of a study of: the type, content, duration, and intensity of instructional services provided to limited-English-proficient (LEP) students in the United States; administrative procedures associated with these services (including procedures for identifying students for entry into and exit from these special services); the

  8. Study on Optical Filter Heating in Background Limited Detector Experiments

    NASA Astrophysics Data System (ADS)

    Bueno, J.; de Visser, P. J.; Doyle, S.; Baselmans, J. J. A.

    2014-09-01

    Cryogenic test setups with controlled stray light environments capable of reaching ultra-low radiative background levels are required to test far infrared (FIR) and submillimeter (sub-mm) wave radiation detectors for future space based observatories. In recent experiments (Nature Commun 5:3130, 2014), in which 1.54 THz radiation was coupled onto an antenna-coupled kinetic inductance detector (KID), we found a higher than expected optical loading. We show that this can be explained by assuming heating of the metal mesh IR filters and re-radiation onto the KID. Note that the total power from the cryogenic black body source used in the experiments (at T = - K) is much larger than the power inside the - THz band we use to calibrate our detector. The out-of-band radiation can have up to 5 orders of magnitude more power than inside the - THz band of interest. A strategy to mitigate the filter heating problem is presented, and when it is implemented, the validated upper limit for stray light at the detector level is down to few aW.

  9. Genetic studies in human prion diseases.

    PubMed

    Jeong, Byung-Hoon; Kim, Yong-Sun

    2014-05-01

    Human prion diseases are fatal neurodegenerative disorders that are characterized by spongiform changes, astrogliosis, and the accumulation of an abnormal prion protein (PrP(Sc)). Approximately 10%-15% of human prion diseases are familial variants that are caused by pathogenic mutations in the prion protein gene (PRNP). Point mutations or the insertions of one or more copies of a 24 bp repeat are associated with familial human prion diseases including familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. These mutations vary significantly in frequency between countries. Here, we compare the frequency of PRNP mutations between European countries and East Asians. Associations between single nucleotide polymorphisms (SNPs) of several candidate genes including PRNP and CJD have been reported. The SNP of PRNP at codon 129 has been shown to be associated with sporadic, iatrogenic, and variant CJD. The SNPs of several genes other than PRNP have been showed contradictory results. Case-control studies and genome-wide association studies have also been performed to identify candidate genes correlated with variant and/or sporadic CJD. This review provides a general overview of the genetic mutations and polymorphisms that have been analyzed in association with human prion diseases to date. PMID:24851016

  10. Factors which Limit the Value of Additional Redundancy in Human Rated Launch Vehicle Systems

    NASA Technical Reports Server (NTRS)

    Anderson, Joel M.; Stott, James E.; Ring, Robert W.; Hatfield, Spencer; Kaltz, Gregory M.

    2008-01-01

    The National Aeronautics and Space Administration (NASA) has embarked on an ambitious program to return humans to the moon and beyond. As NASA moves forward in the development and design of new launch vehicles for future space exploration, it must fully consider the implications that rule-based requirements of redundancy or fault tolerance have on system reliability/risk. These considerations include common cause failure, increased system complexity, combined serial and parallel configurations, and the impact of design features implemented to control premature activation. These factors and others must be considered in trade studies to support design decisions that balance safety, reliability, performance and system complexity to achieve a relatively simple, operable system that provides the safest and most reliable system within the specified performance requirements. This paper describes conditions under which additional functional redundancy can impede improved system reliability. Examples from current NASA programs including the Ares I Upper Stage will be shown.

  11. Limited forward trafficking of connexin 43 reduces cell-cell coupling in stressed human and mouse myocardium

    PubMed Central

    Smyth, James W.; Hong, Ting-Ting; Gao, Danchen; Vogan, Jacob M.; Jensen, Brian C.; Fong, Tina S.; Simpson, Paul C.; Stainier, Didier Y.R.; Chi, Neil C.; Shaw, Robin M.

    2009-01-01

    Gap junctions form electrical conduits between adjacent myocardial cells, permitting rapid spatial passage of the excitation current essential to each heartbeat. Arrhythmogenic decreases in gap junction coupling are a characteristic of stressed, failing, and aging myocardium, but the mechanisms of decreased coupling are poorly understood. We previously found that microtubules bearing gap junction hemichannels (connexons) can deliver their cargo directly to adherens junctions. The specificity of this delivery requires the microtubule plus-end tracking protein EB1. We performed this study to investigate the hypothesis that the oxidative stress that accompanies acute and chronic ischemic disease perturbs connexon forward trafficking. We found that EB1 was displaced in ischemic human hearts, stressed mouse hearts, and isolated cells subjected to oxidative stress. As a result, we observed limited microtubule interaction with adherens junctions at intercalated discs and reduced connexon delivery and gap junction coupling. A point mutation within the tubulin-binding domain of EB1 reproduced EB1 displacement and diminished connexon delivery, confirming that EB1 displacement can limit gap junction coupling. In zebrafish hearts, oxidative stress also reduced the membrane localization of connexin and slowed the spatial spread of excitation. We anticipate that protecting the microtubule-based forward delivery apparatus of connexons could improve cell-cell coupling and reduce ischemia-related cardiac arrhythmias. PMID:20038810

  12. An immunosufficient murine model for the study of human islets.

    PubMed

    Zhao, Gaoping; Moore, Daniel J; Kim, James I; Lee, Kang Mi; O'Connor, Matthew; Yang, Maozhu; Marshall, Andrew F; Lei, Ji; Schuetz, Christian; Markmann, James F; Deng, Shaoping

    2014-01-01

    For the sake of therapy of diabetes, it is critical to understand human beta cell function in detail in health and disease. Current studies of human beta cell physiology in vivo are mostly limited to immunodeficient mouse models, which possess significant technical limitations. This study aimed to create a new model for the study of human islets through induction of transplant tolerance in immunosufficient mice. B6 diabetic mice were transplanted with human islets and treated with anti-CD45RB. To assess whether anti-CD45RB-induced transplant tolerance requires B cells, B6 recipients received additional anti-CD20 or B6?MT-/- mice were used. For some anti-CD45RB-treated B6?MT-/- mice, additional anti-CD25 mAb was applied at the early or late stage post-transplant. Immunohistology was performed to show the Foxp3 cells in grafted anti-CD45RB/anti-CD20-treated Foxp3-GFP B6 mice. The results showed that anti-CD45RB alone allowed indefinite graft survival in 26.6% of B6 mice, however 100% of xenografts were accepted in mice treated simultaneously with anti-CD20, and 88.9% of xenografts accepted in anti-CD45RB-treated ?MT-/- mice. These ?MT-/- mice accepted the islets from another human donor but rejected the islets from baboon. Additional administration of anti-CD25 mAb at the time of transplantation resulted in 100% rejection, whereas 40% of grafts were rejected while the antibody was administrated at days 60 post-transplant. Immunohistologic examination showed Foxp3+ cells accumulated around grafts. We conclude that induction of tolerance to human islets in an immunosufficient mouse model could be generated by targeting murine CD45RB and CD20. This new system will facilitate study of human islets and accelerate the dissection of the critical mechanisms underlying islet health in human disease. PMID:25041432

  13. Challenges in the Management of Disseminated Progressive Histoplasmosis in Human Immunodeficiency Virus-Infected Patients in Resource-Limited Settings

    PubMed Central

    Murphy, Richard A.; Gounder, Lilishia; Manzini, Thandekile C.; Ramdial, Pratistadevi K.; Castilla, Carmen; Moosa, Mahomed-Yunus S.

    2015-01-01

    The diagnosis of histoplasmosis in patients with human immunodeficiency virus in southern Africa is complicated by the nonspecific presentation of the disease in this patient group and the unavailability of sensitive diagnostics including antigen assays. Treatment options are also limited due to the unavailability of liposomal amphotericin and itraconazole, and the inability to perform therapeutic drug monitoring further confounds management. We present 3 clinical cases to illustrate the limits of diagnosis and management in the southern African context, and we highlight the need for additional diagnostic tools and treatment options in resource-limited settings. PMID:26034774

  14. Overcoming phytoremediation limitations. A case study of Hg contaminated soil

    NASA Astrophysics Data System (ADS)

    Barbafieri, Meri

    2013-04-01

    Phytoremediation is a broad term that comprises several technologies to clean up water and soil. Despite the numerous articles appearing in scientific journals, very few field applications of phytoextraction have been successfully realized. The research here reported on Phytoextraction, the use the plant to "extract" metals from contaminated soil, is focused on implementations to overcome two main drawbacks: the survival of plants in unfavorable environmental conditions (contaminant toxicity, low fertility, etc.) and the often lengthy time it takes to reduce contaminants to the requested level. Moreover, to overcome the imbalance between the technology's potential and its drawbacks, there is growing interest in the use of plants to reduce only the fraction that is the most hazardous to the environment and human health, that is to target the bioavailable fractions of metals in soil. Bioavailable Contaminant Stripping (BCS) would be a remediation approach focused to remove the bioavailable metal fractions. BCS have been used in a mercury contaminated soil from Italian industrial site. Bioavailable fractions were determined by sequential extraction with H2O and NH4Cl.Combined treatments of plant hormone and thioligand to strength Hg uptake by crop plants (Brassica juncea and Helianthus annuus) were tested. Plant biomass, evapotranspiration, Hg uptake and distribution following treatments were compared. Results indicate the plant hormone, cytokinine (CK) foliar treatment, increased evapotranspiration rate in both tested plants. The Hg uptake and translocation in both tested plants increased with simultaneous addition of CK and TS treatments. B. juncea was the most effective in Hg uptake. Application of CK to plants grown in TS-treated soil lead to an increase in Hg concentration of 232% in shoots and 39% in roots with respect to control. While H. annuus gave a better response in plant biomass production, the application of CK to plants grown in TS-treated soil lead to an increase in Hg concentration of 248% in shoots and 185% in roots with respect to control plants. The BCS efficiency were evaluated analyzing the labile-Hg residue in the soil after the plant growing. Plants grown with CK and TS in one growing cycle significantly affected labile-Hg pools in soil characterized by sequential extraction, but did not significantly reduce the total metals in the soil. Moreover, if properly optimized, the use of a coupled phytohormone/thioligand system may be a viable strategy to strength Hg uptake by crop plants.

  15. Tea and health: studies in humans.

    PubMed

    Khan, Naghma; Mukhtar, Hasan

    2013-01-01

    Tea, next to water is the cheapest beverage humans consume. Drinking the beverage tea has been considered a healthpromoting habit since ancient times. The modern medicinal research is providing a scientific basis for this belief. The evidence supporting the health benefits of tea drinking grows stronger with each new study that is published in the scientific literature. Tea plant Camellia sinensis has been cultivated for thousands of years and its leaves have been used for medicinal purposes. Tea is used as a popular beverage worldwide and its ingredients are now finding medicinal benefits. Encouraging data showing cancer-preventive effects of green tea from cell-culture, animal and human studies have emerged. Evidence is accumulating that black tea may have similar beneficial effects. Tea consumption has also been shown to be useful for prevention of many debilitating human diseases that include maintenance of cardiovascular and metabolic health. Various studies suggest that polyphenolic compounds present in green and black tea are associated with beneficial effects in prevention of cardiovascular diseases, particularly of atherosclerosis and coronary heart disease. In addition, anti-aging, antidiabetic and many other health beneficial effects associated with tea consumption are described. Evidence is accumulating that catechins and theaflavins, which are the main polyphenolic compounds of green and black tea, respectively, are responsible for most of the physiological effects of tea. This article describes the evidences from clinical and epidemiological studies in the prevention of chronic diseases like cancer and cardiovascular diseases and general health promotion associated with tea consumption. PMID:23448443

  16. Physical Limitations on Salmonella typhi Entry into Cultured Human Intestinal Epithelial Cells

    PubMed Central

    Huang, Xiao-Zhe; Tall, Ben; Schwan, William R.; Kopecko, Dennis J.

    1998-01-01

    Kinetic studies of Salmonella typhi invasion of INT407 cells at different multiplicities of infection (MOIs) have revealed a strict physical limitation on S. typhi entry at MOIs of ≥40. Staining of infected monolayers to distinguish intracellular from extracellular bacteria revealed that all monolayer cells are susceptible to infection and that internalized bacteria are typically contained in one to three separate clusters per cell during the first 60 min. Scanning and transmission electron microscopic analyses of time course-infected monolayers showed that at early times postinfection, bacteria bind to shortened, coalesced microvilli in one to three focal aggregate structures per host cell surface. As reported previously for S. typhimurium, focal aggregates progress to conical membrane ruffles that appear to engulf one or a few centrally contained S. typhi cells by a macropinocytic process, which enhanced the entry of simultaneously added Escherichia coli HB101 about 30-fold. Additionally, kinetic studies showed that at an MOI of ≃400, maximal S. typhi entry is virtually completed within 30 to 35 min. Monolayers pretreated with S. typhi for 30 min to saturate the entry process were severely reduced in the ability to internalize subsequently added kanamycin-resistant strains of S. typhi or S. typhimurium, but E. coli HB101(pRI203) expressing the cloned Yersinia inv gene was not reduced in entry. In invasion inhibition assays, anti-β1 integrin antibodies markedly reduced E. coli HB101(pRI203) invasion efficiency but did not reduce S. typhi entry. Collectively, these data provide direct physical and visual evidence which indicates that S. typhi organisms are internalized at a limited number (i.e., two to four) of sites on host cells. S. typhi and S. typhimurium likely share INT407 cell entry receptors which do not appear to be members of the β1 integrin superfamily. PMID:9596769

  17. Flow motifs reveal limitations of the static framework to represent human interactions

    NASA Astrophysics Data System (ADS)

    Rocha, Luis E. C.; Blondel, Vincent D.

    2013-04-01

    Networks are commonly used to define underlying interaction structures where infections, information, or other quantities may spread. Although the standard approach has been to aggregate all links into a static structure, some studies have shown that the time order in which the links are established may alter the dynamics of spreading. In this paper, we study the impact of the time ordering in the limits of flow on various empirical temporal networks. By using a random walk dynamics, we estimate the flow on links and convert the original undirected network (temporal and static) into a directed flow network. We then introduce the concept of flow motifs and quantify the divergence in the representativity of motifs when using the temporal and static frameworks. We find that the regularity of contacts and persistence of vertices (common in email communication and face-to-face interactions) result on little differences in the limits of flow for both frameworks. On the other hand, in the case of communication within a dating site and of a sexual network, the flow between vertices changes significantly in the temporal framework such that the static approximation poorly represents the structure of contacts. We have also observed that cliques with 3 and 4 vertices containing only low-flow links are more represented than the same cliques with all high-flow links. The representativity of these low-flow cliques is higher in the temporal framework. Our results suggest that the flow between vertices connected in cliques depend on the topological context in which they are placed and in the time sequence in which the links are established. The structure of the clique alone does not completely characterize the potential of flow between the vertices.

  18. Study made of ductility limitations of aluminum-silicon alloys

    NASA Technical Reports Server (NTRS)

    Bailey, W. A.; Frederick, S. F.

    1967-01-01

    Study of the relation between microstructure and mechanical properties of aluminum-silicon alloys determines the cause of the variations in properties resulting from differences in solidification rate. It was found that variations in strength are a consequence of variations in ductility and that ductility is inversely proportional to dendrite cell size.

  19. Gene regulation of UDP-galactose synthesis and transport: Potential rate limiting processes in initiation of milk production in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lactose synthesis is believed to be rate-limiting for milk production. However, understanding the molecular events controlling lactose synthesis in humans is still rudimentary. We have utilized our established model of the RNA isolated from breast milk fat globule from 7 healthy exclusively breastfe...

  20. Limitations of Parallel Global Optimization for Large-Scale Human Movement Problems

    PubMed Central

    Koh, Byung-Il; Reinbolt, Jeffrey A.; George, Alan D.; Haftka, Raphael T.; Fregly, Benjamin J.

    2009-01-01

    Global optimization algorithms (e.g., simulated annealing, genetic, and particle swarm) have been gaining popularity in biomechanics research, in part due to advances in parallel computing. To date, such algorithms have only been applied to small- or medium-scale optimization problems (< 100 design variables). This study evaluates the applicability of a parallel particle swarm global optimization algorithm to large-scale human movement problems. The evaluation was performed using two large-scale (660 design variables) optimization problems that utilized a dynamic, 27 degree-of-freedom, full-body gait model to predict new gait motions from a nominal gait motion. Both cost functions minimized a quantity that reduced the knee adduction torque. The first one minimized foot path errors corresponding to an increased toe out angle of 15 deg, while the second one minimized the knee adduction torque directly without changing the foot path. Constraints on allowable changes in trunk orientation, joint angles, joint torques, centers of pressure, and ground reactions were handled using a penalty method. For both problems, a single run with a gradient-based nonlinear least squares algorithm found a significantly better solution than did 10 runs with the global particle swarm algorithm. Due to the penalty terms, the physically-realistic gradient-based solutions were located within a narrow channel in design space that was difficult to enter without gradient information. Researchers should exercise caution when extrapolating the performance of parallel global optimizers to human movement problems with hundreds of design variables, especially when penalty terms are included in the cost function. PMID:19036629

  1. Monoamine oxidase: Radiotracer chemistry and human studies

    SciTech Connect

    Fowler, Joanna S.; Logan, Jean; Shumay, Elena; Alia-Klein, Nelly; Wang, Gene-Jack; Volkow, Nora D.

    2015-03-01

    Monoamine oxidase (MAO) oxidizes amines from both endogenous and exogenous sources thereby regulating the concentration of neurotransmitter amines such as serot onin, norepinephrine and dopamine as well as many xenobiotics. MAO inhibitor drugs are used in the treatment of Parkinsons disease and in depression stimulating the development of radiotracer tools to probe the role of MAO in normal human biology and in disease. Over the past 30 since the first radiotracers were developed and the first PET images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variables which have contributed to different MAO levels in brain and in peripheral organs. MAO radiotracers and PET have also been used to study the current and developing MAO inhibitor drugs including the selection of doses for clinical trials. In this article, we describe (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological and psychiatric disorders; (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers which are currently used and possible new applications.

  2. Human studies on polyglycerol polyricinoleate (PGPR).

    PubMed

    Wilson, R; Smith, M

    1998-01-01

    A series of toxicology studies was conducted in the 1950s and 1960s to investigate the toxicity of ADMUL WOL, a brand of polyglycerol polyricinoleate (PGPR). A component of these investigations included studies in human subjects. During 1964 and 1965, PGPR was fed to 19 human volunteers whose diet contained constant levels of fat and protein. Up to 10 g/day PGPR was fed to each volunteer in soups, cakes and toffee bars for 2 weeks. Pre-exposure normal values of biochemical parameters were established. Fat balance tests confirmed that digestion and absorption of PGPR took place. No consistent effect of PGPR on the various biochemical parameters was observed, nor had PGPR any toxic effect on liver and kidneys. The consumption of PGPR by humans produced no adverse effects. The quantities consumed, up to 10g/day, was equivalent to approximately 63 times the estimated maximum per capita mean daily intake by man of 2.64 mg kg body weight/day. It is therefore concluded from this study that the consumption of ADMUL WOL, a brand of PGPR, has no adverse effects in man. PMID:9737420

  3. Functional neuroimaging studies of human somatosensory cortex.

    PubMed

    McGlone, Francis; Kelly, Edward F; Trulsson, Mats; Francis, Susan T; Westling, Gran; Bowtell, Richard

    2002-09-20

    Two studies were carried out to assess the applicability of echoplanar fMRI at 3.0 T to the analysis of somatosensory mechanisms in humans. Vibrotactile stimulation of the tips of digits two and five reliably generated significant clusters of activation in primary (SI) and secondary (SII) somatosensory cortex, area 43, the pre-central gyrus, posterior insula, posterior parietal cortex and posterior cingulate. Separation of these responses by digit in SI was possible in all subjects and the activation sites reflected the known lateral position of the representation of digit 2 relative to that of digit 5. A second study employed microneurographic techniques in which individual median-nerve mechanoreceptive afferents were isolated, physiologically characterized, and microstimulated in conjunction with fMRI. Hemodynamic responses, observed in every case, were robust, focal, and physiologically orderly. These techniques will enable more detailed studies of the representation of the body surface in human somatosensory cortex, the relationship of that organization to short-term plasticity in responses to natural tactile stimuli, and effects of stimulus patterning and unimodal/cross-modal attentional manipulations. They also present unique opportunities to investigate the basic physiology of the BOLD effect, and to optimize the operating characteristics of two important human functional neuroimaging modalities-high-field fMRI and high-resolution EEG-in an unusually specific and well-characterized neurophysiological setting. PMID:12356445

  4. Monoamine oxidase: Radiotracer chemistry and human studies

    DOE PAGESBeta

    Fowler, Joanna S.; Logan, Jean; Shumay, Elena; Alia-Klein, Nelly; Wang, Gene-Jack; Volkow, Nora D.

    2015-03-01

    Monoamine oxidase (MAO) oxidizes amines from both endogenous and exogenous sources thereby regulating the concentration of neurotransmitter amines such as serot onin, norepinephrine and dopamine as well as many xenobiotics. MAO inhibitor drugs are used in the treatment of Parkinson’s disease and in depression stimulating the development of radiotracer tools to probe the role of MAO in normal human biology and in disease. Over the past 30 since the first radiotracers were developed and the first PET images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variablesmore » which have contributed to different MAO levels in brain and in peripheral organs. MAO radiotracers and PET have also been used to study the current and developing MAO inhibitor drugs including the selection of doses for clinical trials. In this article, we describe (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological and psychiatric disorders; (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers which are currently used and possible new applications.« less

  5. Monoamine oxidase: Radiotracer chemistry and human studies

    SciTech Connect

    Fowler, Joanna S.; Logan, Jean; Shumay, Elena; Alia-Klein, Nelly; Wang, Gene-Jack; Volkow, Nora D.

    2015-03-01

    Monoamine oxidase (MAO) oxidizes amines from both endogenous and exogenous sources thereby regulating the concentration of neurotransmitter amines such as serot onin, norepinephrine and dopamine as well as many xenobiotics. MAO inhibitor drugs are used in the treatment of Parkinson’s disease and in depression stimulating the development of radiotracer tools to probe the role of MAO in normal human biology and in disease. Over the past 30 since the first radiotracers were developed and the first PET images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variables which have contributed to different MAO levels in brain and in peripheral organs. MAO radiotracers and PET have also been used to study the current and developing MAO inhibitor drugs including the selection of doses for clinical trials. In this article, we describe (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological and psychiatric disorders; (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers which are currently used and possible new applications.

  6. Selenium neurotoxicity in humans: bridging laboratory and epidemiologic studies.

    PubMed

    Vinceti, Marco; Mandrioli, Jessica; Borella, Paola; Michalke, Bernhard; Tsatsakis, Aristidis; Finkelstein, Yoram

    2014-10-15

    Selenium is a metalloid of considerable interest in the human from both a toxicological and a nutritional perspective, with a very narrow safe range of intake. Acute selenium intoxication is followed by adverse effects on the nervous system with special clinical relevance, while the neurotoxicity of long-term overexposure is less characterized and recognized. We aimed to address this issue from a public health perspective, focusing on both laboratory studies and the few epidemiologic human studies available, with emphasis on their methodological strengths and limitations. The frequently overlooked differences in toxicity and biological activity of selenium compounds are also outlined. In addition to lethargy, dizziness, motor weakness and paresthesias, an excess risk of amyotrophic lateral sclerosis is the effect on the nervous system which has been more consistently associated with chronic low-level selenium overexposure, particularly to its inorganic compounds. Additional research efforts are needed to better elucidate the neurotoxic effects exerted by selenium overexposure. PMID:24269718

  7. The Fractalkine-Receptor Axis Improves Human Colorectal Cancer Prognosis by Limiting Tumor Metastatic Dissemination.

    PubMed

    Erreni, Marco; Siddiqui, Imran; Marelli, Giulia; Grizzi, Fabio; Bianchi, Paolo; Morone, Diego; Marchesi, Federica; Celesti, Giuseppe; Pesce, Samantha; Doni, Andrea; Rumio, Cristiano; Roncalli, Massimo G; Laghi, Luigi; Mantovani, Alberto; Allavena, Paola

    2016-01-15

    Human colorectal cancer (CRC) is a frequent neoplasia in Western countries, and its metastatic progression is a major cause of cancer-related death. In search of specific molecules upregulated in CRC, with possible clinical relevance, we performed a differential gene-profiling analysis in surgery-derived CRC samples and adjacent uninvolved intestinal mucosa. The chemokine CX3CL1 and its specific receptor CX3CR1 were significantly upregulated in tumors. Higher expression of CX3CL1 and CX3CR1 was confirmed by immunohistochemistry in 100 CRC tumor samples (stages I-III). Unexpectedly, high immune scores of CX3CL1 did not correlate with the density of tumor-infiltrating CD3(+) T cells or CD68(+) macrophages. Coexpression of ligand and receptor by tumor cells (axis-positive tumors) significantly associated with longer disease-free (p = 0.01) and disease-specific survival (p = 0.001). Conversely, axis-negative tumors (with low expression of both ligand and receptor) had increased risk of tumor relapse (p = 0.02), and increased likelihood of metachronous metastasis (p = 0.001), including after stage adjustment (p = 0.006). Transduction of CX3CL1 and CX3CR1 in CRC tumor cell lines induced cell aggregation that strongly inhibited in vitro migration in chemotaxis assays. In a mouse model of spleen-liver metastases, cancer dissemination to liver was dramatically reduced in CX3CL1-CX3CR1-expressing tumors, and ligand-receptor interaction was confirmed in cancer cells in vivo by fluorescence resonance energy transfer analysis. In conclusion, tumoral expression of the CX3CL1-CX3CR1 chemokine axis functions as a retention factor, increasing homotypic cell adhesion and limiting tumor spreading to metastatic sites. Lack or low levels of expression of CX3CL1-CX3CR1 by tumor cells identifies a group of CRC patients at increased risk of metastatic progression. PMID:26673138

  8. Pooled biological specimens for human biomonitoring of environmental chemicals: opportunities and limitations.

    PubMed

    Heffernan, Amy L; Aylward, Lesa L; Toms, Leisa-Maree L; Sly, Peter D; Macleod, Matthew; Mueller, Jochen F

    2014-01-01

    Biomonitoring has become the "gold standard" in assessing chemical exposures, and has an important role in risk assessment. The pooling of biological specimens-combining multiple individual specimens into a single sample-can be used in biomonitoring studies to monitor levels of exposure and identify exposure trends or to identify susceptible populations in a cost-effective manner. Pooled samples provide an estimate of central tendency and may also reveal information about variation within the population. The development of a pooling strategy requires careful consideration of the type and number of samples collected, the number of pools required and the number of specimens to combine per pool in order to maximise the type and robustness of the data. Creative pooling strategies can be used to explore exposure-outcome associations, and extrapolation from other larger studies can be useful in identifying elevated exposures in specific individuals. The use of pooled specimens is advantageous as it saves significantly on analytical costs, may reduce the time and resources required for recruitment and, in certain circumstances, allows quantification of samples approaching the limit of detection. In addition, the use of pooled samples can provide population estimates while avoiding ethical difficulties that may be associated with reporting individual results. PMID:24192659

  9. Prevention and treatment of human immunodeficiency virus/acquired immunodeficiency syndrome in resource-limited settings.

    PubMed Central

    Hogan, Daniel R.; Salomon, Joshua A.

    2005-01-01

    Strategies for confronting the epidemic of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) have included a range of different approaches that focus on prevention and treatment. However, debate persists over what levels of emphasis are appropriate for the different components of the global response. This paper presents an overview of this debate and briefly summarizes the evidence on a range of interventions designed to prevent the spread of HIV infection, paying particular attention to voluntary counselling and testing, treatment for sexually transmitted infections and prevention of mother-to-child transmission. We also review the experience with antiretroviral therapy to date in terms of response rates and survival rates, adherence, drug resistance, behavioural change and epidemiological impact. Although various studies have identified strategies with proven effectiveness in reducing the risks of HIV infection and AIDS mortality, considerable uncertainties remain. Successful integration of treatment and prevention of HIV/AIDS will require a balanced approach and rigorous monitoring of the impact of programmes in terms of both individual and population outcomes. PMID:15744406

  10. Tea and Health: Studies in Humans

    PubMed Central

    Khan, Naghma; Mukhtar, Hasan

    2014-01-01

    Tea, next to water is the cheapest beverage humans consume. Drinking the beverage tea has been considered a health-promoting habit since ancient times. The modern medicinal research is providing a scientific basis for this belief. The evidence supporting the health benefits of tea drinking grows stronger with each new study that is published in the scientific literature. Tea plant Camellia sinensis has been cultivated for thousands of years and its leaves have been used for medicinal purposes. Tea is used as a popular beverage worldwide and its ingredients are now finding medicinal benefits. Encouraging data showing cancer-preventive effects of green tea from cell-culture, animal and human studies have emerged. Evidence is accumulating that black tea may have similar beneficial effects. Tea consumption has also been shown to be useful for prevention of many debilitating human diseases that include maintenance of cardiovascular and metabolic health. Various studies suggest that polyphenolic compounds present in green and black tea are associated with beneficial effects in prevention of cardiovascular diseases, particularly of atherosclerosis and coronary heart disease. In addition, anti-aging, antidiabetic and many other health beneficial effects associated with tea consumption are described. Evidence is accumulating that catechins and theaflavins, which are the main polyphenolic compounds of green and black tea, respectively, are responsible for most of the physiological effects of tea. This article describes the evidences from clinical and epidemiological studies in the prevention of chronic diseases like cancer and cardiovascular diseases and general health promotion associated with tea consumption. PMID:23448443

  11. Formally verifying humanautomation interaction as part of a system model: limitations and tradeoffs

    PubMed Central

    Bass, Ellen J.

    2011-01-01

    Both the human factors engineering (HFE) and formal methods communities are concerned with improving the design of safety-critical systems. This work discusses a modeling effort that leveraged methods from both fields to perform formal verification of humanautomation interaction with a programmable device. This effort utilizes a system architecture composed of independent models of the human mission, human task behavior, human-device interface, device automation, and operational environment. The goals of this architecture were to allow HFE practitioners to perform formal verifications of realistic systems that depend on humanautomation interaction in a reasonable amount of time using representative models, intuitive modeling constructs, and decoupled models of system components that could be easily changed to support multiple analyses. This framework was instantiated using a patient controlled analgesia pump in a two phased process where models in each phase were verified using a common set of specifications. The first phase focused on the mission, human-device interface, and device automation; and included a simple, unconstrained human task behavior model. The second phase replaced the unconstrained task model with one representing normative pump programming behavior. Because models produced in the first phase were too large for the model checker to verify, a number of model revisions were undertaken that affected the goals of the effort. While the use of human task behavior models in the second phase helped mitigate model complexity, verification time increased. Additional modeling tools and technological developments are necessary for model checking to become a more usable technique for HFE. PMID:21572930

  12. Human Transportation System (HTS) study, volume 2

    NASA Technical Reports Server (NTRS)

    Lance, N.; Geyer, M. S.; Gaunce, M. T.

    1993-01-01

    This report summarizes work completed under the Human Transportation System Study. This study was conducted by the New Initiatives Office at JSC with the technical support of Boeing, General Dynamics, Lockheed, McDonnell-Douglas, Martin Marietta, and Rockwell. The study was designed to generate information on determining the appropriate path to follow for new system development to meet the Nation's space transportation needs. The study evaluates 18 transportation architecture options using a parametric set of mission requirements. These options include use of current systems (e.g., Shuttle, Titan, etc. ) as well as proposed systems (e.g., PLS, Single-Stage-to-Orbit, etc.) to assess the impact of various considerations, such as the cost of alternate access, or the benefit of separating people and cargo. The architecture options are compared to each other with six measurable evaluation criteria or attributes. They are: funding profile, human safety, probability of mission success, architecture cost risk, launch schedule confidence, and environmental impact. Values for these attributes are presented for the architecture options, with pertinent conclusions and recommendations.

  13. Structural Studies of Human Pyruvate Dehydrogenase

    NASA Technical Reports Server (NTRS)

    Ciszak, Ewa; Korotchkina, Lioubov G.; Dominiak, Paulina; Sidhu, Sukhdeep; Patel, Mulchand S.; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Human pyruvate dehydrogenase (E1) catalyzes the irreversible decarboxylation of pyruvate in the presence of Mg(2+) and thiamin pyrophosphate (TPP) followed by the rate-limiting reductive acetylation of the lipoyl moiety linked to dihydrolipoamide acetyltransferase. The three-dimensional structure of human E1 is elucidated using the methods of macromolecular X-ray crystallography. The structure is an alpha, alpha', beta and beta' tetramer with the protein units being in the tetrahedral arrangement. Each 361-residue alpha-subunit and 329-residue beta-subunit is composed of a beta-sheet core surrounded by alpha-helical domains. Each subunit is in extensive contact with all the three subunits involving TPP and magnesium cofactors, and potassium ions. The two binding sites for TPP are at the alpha-beta' and alpha'-beta interfaces, each involving a magnesium ion and Phe6l, His63, Tyr89, and Met200 from the alpha-subunit (or alpha'-subunit), and Met81 Phe85, His128 from the beta-subunit (or beta'-subunit). K+ ions are nestled between two beta-sheets and the end of an alpha-helix in each beta-subunit, where they are coordinated by four carbonyl oxygen groups from Ile12, Ala160, Asp163, and Asnl65, and a water molecule. The catalytic C2 carbon of thiazolium ring in this structure forms a 3.2 A contact with a water molecule involved in a series of H-bonds with other water molecules, and indirectly with amino acids including those involved in the catalysis and regulation of the enzyme.

  14. Bioavailability of tocotrienols: evidence in human studies

    PubMed Central

    2014-01-01

    As a minor component of vitamin E, tocotrienols were evident in exhibiting biological activities such as neuroprotection, radio-protection, anti-cancer, anti-inflammatory and lipid lowering properties which are not shared by tocopherols. However, available data on the therapeutic window of tocotrienols remains controversial. It is important to understand the absorption and bioavailability mechanisms before conducting in-depth investigations into the therapeutic efficacy of tocotrienols in humans. In this review, we updated current evidence on the bioavailability of tocotrienols from human studies. Available data from five studies suggested that tocotrienols may reach its target destination through an alternative pathway despite its low affinity for ?-tocopherol transfer protein. This was evident when studies reported considerable amount of tocotrienols detected in HDL particles and adipose tissues after oral consumption. Besides, plasma concentrations of tocotrienols were shown to be higher when administered with food while self-emulsifying preparation of tocotrienols was shown to enhance the absorption of tocotrienols. Nevertheless, mixed results were observed based on the outcome from 24 clinical studies, focusing on the dosages, study populations and formulations used. This may be due to the variation of compositions and dosages of tocotrienols used, suggesting a need to understand the formulation of tocotrienols in the study design. Essentially, implementation of a control diet such as AHA Step 1 diet may influence the study outcomes, especially in hypercholesterolemic subjects when lipid profile might be modified due to synergistic interaction between tocotrienols and control diet. We also found that the bioavailability of tocotrienols were inconsistent in different target populations, from healthy subjects to smokers and diseased patients. In this review, the effect of dosage, composition and formulation of tocotrienols as well as study populations on the bioavailability of tocotrienols will be discussed. PMID:24410975

  15. Work, Productivity, and Human Performance: Practical Case Studies in Ergonomics, Human Factors and Human Engineering.

    ERIC Educational Resources Information Center

    Fraser, T. M.; Pityn, P. J.

    This book contains 12 case histories, each based on a real-life problem, that show how a manager can use common sense, knowledge, and interpersonal skills to solve problems in human performance at work. Each case study describes a worker's problem and provides background information and an assignment; solutions are suggested. The following cases…

  16. Work, Productivity, and Human Performance: Practical Case Studies in Ergonomics, Human Factors and Human Engineering.

    ERIC Educational Resources Information Center

    Fraser, T. M.; Pityn, P. J.

    This book contains 12 case histories, each based on a real-life problem, that show how a manager can use common sense, knowledge, and interpersonal skills to solve problems in human performance at work. Each case study describes a worker's problem and provides background information and an assignment; solutions are suggested. The following cases

  17. Telomerase Inhibitor Imetelstat (GRN163L) Limits the Lifespan of Human Pancreatic Cancer Cells

    PubMed Central

    Burchett, Katrina M.; Yan, Ying; Ouellette, Michel M.

    2014-01-01

    Telomerase is required for the unlimited lifespan of cancer cells. The vast majority of pancreatic adenocarcinomas overexpress telomerase activity and blocking telomerase could limit their lifespan. GRN163L (Imetelstat) is a lipid-conjugated N3′→P5′ thio-phosphoramidate oligonucleotide that blocks the template region of telomerase. The aim of this study was to define the effects of long-term GRN163L exposure on the maintenance of telomeres and lifespan of pancreatic cancer cells. Telomere size, telomerase activity, and telomerase inhibition response to GRN163L were measured in a panel of 10 pancreatic cancer cell lines. The cell lines exhibited large differences in levels of telomerase activity (46-fold variation), but most lines had very short telomeres (2–3 kb in size). GRN163L inhibited telomerase in all 10 pancreatic cancer cell lines, with IC50 ranging from 50 nM to 200 nM. Continuous GRN163L exposure of CAPAN1 (IC50 = 75 nM) and CD18 cells (IC50 = 204 nM) resulted in an initial rapid shortening of the telomeres followed by the maintenance of extremely short but stable telomeres. Continuous exposure to the drug eventually led to crisis and to a complete loss of viability after 47 (CAPAN1) and 69 (CD18) doublings. Crisis In these cells was accompanied by activation of a DNA damage response (γ-H2AX) and evidence of both senescence (SA-β-galactosidase activity) and apoptosis (sub-G1 DNA content, PARP cleavage). Removal of the drug after long-term GRN163L exposure led to a reactivation of telomerase and re-elongation of telomeres in the third week of cultivation without GRN163L. These findings show that the lifespan of pancreatic cancer cells can be limited by continuous telomerase inhibition. These results should facilitate the design of future clinical trials of GRN163L in patients with pancreatic cancer. PMID:24409321

  18. Telomerase inhibitor Imetelstat (GRN163L) limits the lifespan of human pancreatic cancer cells.

    PubMed

    Burchett, Katrina M; Yan, Ying; Ouellette, Michel M

    2014-01-01

    Telomerase is required for the unlimited lifespan of cancer cells. The vast majority of pancreatic adenocarcinomas overexpress telomerase activity and blocking telomerase could limit their lifespan. GRN163L (Imetelstat) is a lipid-conjugated N3'→P5' thio-phosphoramidate oligonucleotide that blocks the template region of telomerase. The aim of this study was to define the effects of long-term GRN163L exposure on the maintenance of telomeres and lifespan of pancreatic cancer cells. Telomere size, telomerase activity, and telomerase inhibition response to GRN163L were measured in a panel of 10 pancreatic cancer cell lines. The cell lines exhibited large differences in levels of telomerase activity (46-fold variation), but most lines had very short telomeres (2-3 kb in size). GRN163L inhibited telomerase in all 10 pancreatic cancer cell lines, with IC50 ranging from 50 nM to 200 nM. Continuous GRN163L exposure of CAPAN1 (IC50 = 75 nM) and CD18 cells (IC50 = 204 nM) resulted in an initial rapid shortening of the telomeres followed by the maintenance of extremely short but stable telomeres. Continuous exposure to the drug eventually led to crisis and to a complete loss of viability after 47 (CAPAN1) and 69 (CD18) doublings. Crisis In these cells was accompanied by activation of a DNA damage response (γ-H2AX) and evidence of both senescence (SA-β-galactosidase activity) and apoptosis (sub-G1 DNA content, PARP cleavage). Removal of the drug after long-term GRN163L exposure led to a reactivation of telomerase and re-elongation of telomeres in the third week of cultivation without GRN163L. These findings show that the lifespan of pancreatic cancer cells can be limited by continuous telomerase inhibition. These results should facilitate the design of future clinical trials of GRN163L in patients with pancreatic cancer. PMID:24409321

  19. Dual rover human habitation field study

    NASA Astrophysics Data System (ADS)

    Litaker, Harry L.; Thompson, Shelby G.; Szabo, Richard; Twyford, Evan S.; Conlee, Carl S.; Howard, Robert L.

    2013-10-01

    For the last 3 years, the National Aeronautics and Space Administration (NASA) has been testing a pressurized rover prototype in the deserts of Arizona to obtain human-in-the-loop performance data. This year's field trial consisted of operating two rovers simultaneously while embarking on two 7-day flight-like exploration missions. During the 2010 Desert Research and Technology Studies (DRATS) at Black Point Lava Flow and SP Mountain in Arizona, NASA human factors investigators, in cooperation with other engineers and scientists, collected data on both the daily living and working within and around the Space Exploration Vehicle (SEV). Both objective and subjective data were collected using standard human factors metrics. Over 305 h of crew habitability data were recorded during the field trial with 65 elements of habitation examined. Acceptability of the vehicles over the course of the missions was considered satisfactory by the majority of the crews. As with previous testing, habitation was considered acceptable by the crews, but some issues concerning stowage, Waste Containment System (WCS) volume, and sleep curtains need to be considered for redesign for the next generation vehicle.

  20. A PILOT STUDY TO COMPARE MICROBIAL AND CHEMICAL INDICATORS OF HUMAN FECAL CONTAMINATION IN WATER

    EPA Science Inventory

    Limitations exist in applying traditional microbial methods for the detection of human fecal contamination of water. A pilot study was undertaken to compare the microbial and chemical indicators of human fecal contamination of water. Sixty-four water samples were collected in O...

  1. The limits of adaptation: humans and the predator-prey arms race.

    PubMed

    Vermeij, Geerat J

    2012-07-01

    In the history of life, species have adapted to their consumers by evolving a wide variety of defenses. By contrast, animal species harvested in the wild by humans have not adapted structurally. Nonhuman predators have high failure rates at one or more stages of an attack, indicating that victim species have spatial refuges or phenotypic defenses that permit further functional improvement. A new compilation confirms that species in the wild cannot achieve immunity from human predation with structural defenses. The only remaining options are to become undesirable or to live in or escape to places where harvesting by people is curtailed. Escalation between prey defenses and predators' weapons may be restricted under human dominance to interactions involving those low-level predators that have benefited from human overexploitation of top consumers. PMID:22759280

  2. Sorption studies of human keratinized tissues

    NASA Astrophysics Data System (ADS)

    Johnsen, G. K.; Martinsen, Ø. G.; Grimnes, Sverre

    2010-04-01

    Water content is known to be the most important single parameter for keratinized tissue to remain its vital functions. In that sense, a general knowledge of the water binding properties is of great interest, and a reliable measurement setup must be found. Also, revealing the sorption properties of human keratinized tissues is vital towards a calibration of susceptance based skin hydration measurements that already is an important diagnostic tool in clinical dermatology, and we will see that any hysteresis will complicate such a calibration further. In this study we investigated the sorption properties of keratinized tissues such as human epidermal stratum corneum (SC), hair and nail. The study was performed under controlled environmental conditions with a dynamic vapor sorption (DVS) instrument, and the water uptake of the keratinized test samples was measured as the relative humidity in the ambient air was altered step-wisely. In this study, vital and characteristic water sorption properties such as the isotherm, relative water uptake, and hysteresis were investigated and will be discussed.

  3. Limited independent flexion of the thumb and fingers in human subjects.

    PubMed Central

    Kilbreath, S L; Gandevia, S C

    1994-01-01

    1. We investigated whether human subjects can activate selectively flexor pollicis longus (FPL) and digital portions of flexor digitorum profundus (FDP). These muscles were selected because they are the only flexors of the distal phalanges. 2. Electromyographic activity (EMG) was recorded with intramuscular electrodes from one digital component of the deep flexors ('test') while subjects lifted weights by flexing the distal interphalangeal joint of the other digits in turn ('lifting' digits). Only recording sites at which single motor units were recruited selectively at low forces were used. The weights lifted represented 2.5-50% of the maximal voluntary contraction (MVC). We measured the lowest weight lifted which produced phasic and tonic coactivation in the 'test' muscle. 3. The extent of coactivation varied with the 'distance' between the test and lifting digits although no significant difference occurred in the pattern of coactivation thresholds among the digital flexors. The extent of coactivation increased when angular displacement or velocity at the distal interphalangeal joint of the lifting digit increased but was not critically dependent on restraint of the hand. 4. Because mechanical 'connections' could interfere with the ability to move a distal phalanx independently, the arms of nine cadavers were studied. The separation of tendons between the thumb (FPL) and the index portion of FDP, and between the index and middle portions of FDP, usually extended more proximally in the forearm than separation between the tendons to the middle and ring fingers and between the ring and little fingers. Direct intertendinous links were also noted. 5. It is not possible to direct a sufficiently focal motor command to flex selectively the distal joint of the fingers and thumb when forces exceeding 2.5% MVC are generated. For the middle, ring and little fingers in particular, movement of adjacent digits may also involve 'in-series' mechanical links between adjacent components of FDP. Images Figure 6 PMID:7837104

  4. Assessing the Potential and Limitations of Leveraging Food Sovereignty to Improve Human Health

    PubMed Central

    Jones, Andrew D.; Fink Shapiro, Lilly; Wilson, Mark L.

    2015-01-01

    Food sovereignty has been defined as “the right of peoples to healthy and culturally appropriate food produced through ecologically sound and sustainable methods, and their right to define their own food and agriculture systems.” Human health is an implied component of this definition through the principle of healthy food. In fact, improved human health is commonly cited as a benefit of transforming food production away from the dominant practices of industrial agriculture. Yet, does the use of “ecologically sound and sustainable methods” of food production necessarily translate into better human health outcomes? Does greater choice in defining an agricultural or food system create gains in health and well-being? We elucidate the conceptual linkages between food sovereignty and human health, critically examine the empirical evidence supporting or refuting these linkages, and identify research gaps and key priorities for the food sovereignty-human health research agenda. Five domains of food sovereignty are discussed including: (1) use of agroecological management practices for food production, (2) the localization of food production and consumption, (3) promotion of social justice and equity, (4) valuation of traditional knowledge, and (5) the transformation of economic and political institutions and structures to support self-determination. We find that although there are many plausible linkages between food sovereignty and human health, the empirical evidence in support of the hypothesis that increasing food sovereignty yields improvements to human health is weak. We propose that a concerted effort to generate new empirical evidence on the health implications of these domains of food sovereignty is urgently needed, and suggest areas of research that may be crucial for addressing the gaps in the evidence base. PMID:26636062

  5. Limited Spillover to Humans from West Nile Virus Viremic Birds in Atlanta, Georgia

    PubMed Central

    Mead, Daniel G.; Kitron, Uriel D.

    2013-01-01

    Abstract West Nile Virus (WNV) is a mosquito-borne pathogen that impacts the health of its passerine bird hosts as well as incidentally infected humans in the United States. Intensive enzootic activity among the hosts and vectors does not always lead to human outbreaks, as is the situation throughout much of the southeastern United States. In Georgia, substantial yearly evidence of WNV in the mosquito vectors and avian hosts since 2001 has only led to 324 human cases. Although virus has been consistently isolated from mosquitoes trapped in Atlanta, GA, little is known about viral activity among the passerine hosts. A possible reason for the suppression of WNV spillover to humans is that viremic birds are absent from high human-use areas of the city. To test this hypothesis, multiseason, multihabitat, longitudinal WNV surveillance for active WNV viremia was conducted within the avian host community of urban Atlanta by collection of blood samples from wild passerine birds in five urban microhabitats. WNV was isolated from the serum of six blood samples collected from 630 (0.95%) wild passerine birds in Atlanta during 20102012, a proportion similar to that found in the Chicago, IL, area in 2005, when over 200 human cases were reported. Most of the viremic birds were Northern Cardinals, suggesting they may be of particular importance to the WNV transmission cycle in Georgia. Results indicated active WNV transmission in all microhabitats of urban Atlanta, except in the old-growth forest patches. The number of viremic birds was highest in Zoo Atlanta, where 3.5% of samples were viremic. Although not significant, these observations may suggest a possible transmission reduction effect of urban old-growth forests and a potential role in WNV amplification for Zoo Atlanta. Overall, spillover to humans remains a rare occurrence in urban Atlanta settings despite active WNV transmission in the avian population. PMID:24107200

  6. Limited Expression of Slow Tonic Myosin Heavy Chain in Human Cranial Muscles

    PubMed Central

    Sokoloff, Alan J.; Li, Haiyan; Burkholder, Thomas J.

    2013-01-01

    Recent reports of slow tonic myosin heavy chain (MHCst) in human masticatory and laryngeal muscles suggest that MHCst may have a wider distribution in humans than previously thought. Because of the novelty of this finding, we sought to confirm the presence of MHCst in human masticatory and laryngeal muscles by reacting tissue from these muscles and controls from extraocular, intrafusal, cardiac, appendicular and developmental muscle with antibodies (Abs) ALD-58 and S46 considered highly specific for MHCst. At Ab dilutions producing minimal reaction to muscle fibers positive for MHCI, only extraocular, intrafusal and fetal tongue tissue reacted with Ab S46 had strong immunoreaction in an appreciable number of muscle fibers. In immunoblots Ab S46, but not Ab ALD-58, labeled adult extraocular muscles; no other muscles were labeled with either Ab. We conclude that, in humans, Ab S46 has greater specificity for MHCst than does Ab ALD-58. We suggest that reports of MHCst in human masticatory and laryngeal muscles reflect false-positive identification of MHCst due to cross-reactivity of Ab ALD-58 with another MHC isoform. PMID:17486578

  7. Human Laboratory Studies on Cannabinoids and Psychosis.

    PubMed

    Sherif, Mohamed; Radhakrishnan, Rajiv; D'Souza, Deepak Cyril; Ranganathan, Mohini

    2016-04-01

    Some of the most compelling evidence supporting an association between cannabinoid agonists and psychosis comes from controlled laboratory studies in humans. Randomized, double-blind, placebo-controlled, crossover laboratory studies demonstrate that cannabinoid agonists, including phytocannabinoids and synthetic cannabinoids, produce a wide range of positive, negative, and cognitive symptoms and psychophysiologic deficits in healthy human subjects that resemble the phenomenology of schizophrenia. These effects are time locked to drug administration, are dose related, and are transient and rarely necessitate intervention. The magnitude of effects is similar to the effects of ketamine but qualitatively distinct from other psychotomimetic drugs, including ketamine, amphetamine, and salvinorin A. Cannabinoid agonists have also been shown to transiently exacerbate symptoms in individuals with schizophrenia in laboratory studies. Patients with schizophrenia are more vulnerable than healthy control subjects to the acute behavioral and cognitive effects of cannabinoid agonists and experience transient exacerbation of symptoms despite treatment with antipsychotic medications. Furthermore, laboratory studies have failed to demonstrate any "beneficial" effects of cannabinoid agonists in individuals with schizophrenia-challenging the cannabis self-medication hypothesis. Emerging evidence suggests that polymorphisms of several genes related to dopamine metabolism (e.g., COMT, DAT1, and AKT1) may moderate the effects of cannabinoid agonists in laboratory studies. Cannabinoid agonists induce dopamine release, although the magnitude of release does not appear to be commensurate to the magnitude and spectrum of their acute psychotomimetic effects. Interactions between the endocannabinoid, gamma-aminobutyric acid, and glutamate systems and their individual and interactive effects on neural oscillations provide a plausible mechanism underlying the psychotomimetic effects of cannabinoids. PMID:26970363

  8. MONOAMINE OXIDASE: RADIOTRACER DEVELOPMENT AND HUMAN STUDIES.

    SciTech Connect

    FOWLER,J.S.; LOGAN,J.; VOLKOW,N.D.; WANG,G.J.; MACGREGOR,R.R.; DING,Y.S.

    2000-09-28

    PET is uniquely capable of providing information on biochemical transformations in the living human body. Although most of the studies of monoamine oxidase (MAO) have focused on measurements in the brain, the role of peripheral MAO as a phase 1 enzyme for the metabolism of drugs and xenobiotics is gaining attention (Strolin Benedetti and Tipton, 1998; Castagnoli et al., 1997.). MAO is well suited for this role because its concentration in organs such as kidneys, liver and digestive organs is high sometimes exceeding that in the brain. Knowledge of the distribution of the MAO subtypes within different organs and different cells is important in determining which substrates (and which drugs and xenobiotics) have access to which MAO subtypes. The highly variable subtype distribution with different species makes human studies even more important. In addition, the deleterious side effects of combining MAO inhibitors with other drugs and with foodstuffs makes it important to know the MAO inhibitory potency of different drugs both in the brain and in peripheral organs (Ulus et al., 2000). Clearly PET can play a role in answering these questions, in drug research and development and in discovering some of the factors which contribute to the highly variable MAO levels in different individuals.

  9. Genome-wide association studies of hematologic phenotypes: a window into human hematopoiesis

    PubMed Central

    Sankaran, Vijay G.; Orkin, Stuart H.

    2016-01-01

    The study of human hematopoiesis is often limited by the inability to manipulate this process in vivo and differences that exist between humans and commonly employed model organisms. However, human genetics provides a way to gain insight into natural variation in a variety of hematologic phenotypes and creates an opportunity to better understand hematopoiesis. In this review, we discuss how genome-wide association studies are revealing common genetic variation that is associated with hematologic traits and diseases. We discuss how the resulting insight from these studies promises to increase our understanding of human hematopoiesis and outline the challenges that lay ahead in this field. PMID:23477921

  10. [Animal protection without limits? Human-animal relations in between anthropomorphism and objectification].

    PubMed

    Grimm, Herwig; Hartnack, Sonja

    2013-01-01

    In view of recent developments in human-animal relations, vets and ethicists face a new problem: On the one hand, animals such as mammals and birds are used extensively and are in danger to be reduced to mere production units e. g. in the agricultural production, measuring devices in laboratories, sports equipment etc. On the other hand, biologically similar animals are perceived as family members or partners and are almost treated like humans. The article summarizes the results of a workshop that dealt with reductionism and anthropomorphism in human-animal relations. Vets and ethicists tackled the question how the unequal treatment of biologically similar animals can be better understood and whether it can be ethically justified. In the first section, the problem of inconsistency in human-animals relations is briefly sketched. The second part of the article addresses the ethics of unequal treatment of similar animals in different contexts. The following section inquires possible solutions and the advantages and disadvantages of biological criteria versus social criteria in animal protection. Finally, the background and reasons for our moral intuitions of injustice associated with the inconsistencies in human-animal relations are outlined. This fourth section refers to the presentation of Peter Kunzmann during the workshop on the unequal treatment of equals.The article closes with some general remarks on the issue. One main result of the workshop can be stated as follows: Due to the fact that the various human-animal relations gain their ethical justification from different ethical reasons, the unequal treatment of similar animals in different contexts is not ethically wrong per se. However, every intrusive dealing or interaction with animals is in itself in need of ethical justification. PMID:24199378

  11. A pair of roseate terns fledges three young with limited human assistance

    USGS Publications Warehouse

    Spendelow, J.A.; Zingo, J.M.; Foss, S.

    1997-01-01

    In 1994 when the availability of small fish appeared to be relatively good, the smallest chick from an inadvertantly artificially-created 3-egg clutch received occasional supplemental feedings by humans for two weeks. These supplemental feedings probably prevented this chick from starving. During its period of most rapid growth (after the linear growth phase of its two siblings had ended), however, it did not receive supplemental feedings from humans, but was instead was fed only by the two adult birds attending the nest. All the chicks in this brood eventually fledged, indicating that the pair was capable of meeting the feeding demands of three large chicks.

  12. PUSH(ing) Limits: Using Fiction in the Classroom for Human Behavior and the Social Environment

    ERIC Educational Resources Information Center

    Mendoza, Natasha S.; Bonta, Kimberly; Horn, Philip; Moore, Erin; Gibson, Allison; Simmons, David

    2012-01-01

    The use of fiction and autobiography in social science course work has been shown to enhance students' learning experience. Using the novel PUSH, by Sapphire, we designed a curriculum supplement for the social work course, human behavior and the social environment (HBSE) that encourages students to integrate course content in an innovative way and…

  13. PUSH(ing) Limits: Using Fiction in the Classroom for Human Behavior and the Social Environment

    ERIC Educational Resources Information Center

    Mendoza, Natasha S.; Bonta, Kimberly; Horn, Philip; Moore, Erin; Gibson, Allison; Simmons, David

    2012-01-01

    The use of fiction and autobiography in social science course work has been shown to enhance students' learning experience. Using the novel PUSH, by Sapphire, we designed a curriculum supplement for the social work course, human behavior and the social environment (HBSE) that encourages students to integrate course content in an innovative way and

  14. Repression of mammary adipogenesis by genistein limits mammosphere formation of human MCF-7 cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary adipose tissue may contribute to breast cancer development and progression by altering neighboring epithelial cell behavior and phenotype through paracrine signaling. Dietary exposure to soy foods is associated with lower mammary tumor risk and reduced body weight and adiposity in humans and...

  15. Variation in human brains may facilitate evolutionary change toward a limited range of phenotypes

    PubMed Central

    Charvet, Christine J.; Darlington, Richard B.; Finlay, Barbara L.

    2013-01-01

    Individual variation is the foundation for evolutionary change, but little is known about the nature of normal variation between brains. Phylogenetic variation across mammalian brains is characterized by high inter-correlations in brain region volumes, distinct allometric scaling for each brain region and the relative independence in olfactory and limbic structures volumes from the rest of the brain. Previous work examining brain variation in individuals of some domesticated species showed that these three features of phylogenetic variation were mirrored in individual variation. We extend this analysis to the human brain and 10 of its subdivisions (e.g., isocortex, hippocampus) by using magnetic resonance imaging scans of 90 human brains ranging between 16 to 25 years of age. Human brain variation resembles both the individual variation seen in other species, and variation observed across mammalian species. That is, the relative differences in the slopes of each brain region compared to medulla size within humans and between mammals are concordant, and limbic structures scale with relative independence from other brain regions. This non-random pattern of variation suggests that developmental programs channel the variation available for selection. PMID:23363667

  16. Reasonable Limits and Exemptions: Victoria's Human Rights Charter and its Implications for Young People

    ERIC Educational Resources Information Center

    Bessant, Judith

    2009-01-01

    Many people had great expectations of the Victorian Charter of Human Rights and Responsibilities when it came into effect in January 2008. However, Judith Bessant asks whether the provision for seeking exemptions from the charter has undermined its capacity to effectively counter age-based discrimination and, paradoxically, permitted practices

  17. Vision of Space Exploration Possibilities and limits of a human space conquest.

    NASA Astrophysics Data System (ADS)

    Zelenyi, Lev

    Few generations of a schoolboys, which later become active and productive space researchers, have been brought up on a science fiction books. These books told us about travels to other Galaxies with velocities larger then velocity of light, meetings with friendly aliens (necessarily with communistic mentalities in Soviet Union books), star wars with ugly space monsters (in the western hemisphere books), etc. Beginning of Space age (4/10/1957) opened the door to a magic box, full of scientific discoveries, made mostly by robotic satellites and spacecraft. However, already the first human space trips clearly demonstrated that space is vigorously hostile to a human beings. Space medicine during the years since Gagarin flight, made an outstanding progress in supporting human presence at orbital stations, but the radiation hazards and problem of hypomagnetism are still opened and there is no visible path to their solution. So the optimistic slogan of 60-ies “Space is Our Place” is not supported by an almost half a century practice. Space never will be a comfortable place for soft and vulnerable humans? There is a general consensus that man will be on Mars during this century (or even its first part). This is very difficult but task it seems to be realistic after the significant advance of modern technologies will be made. But, is there any real need for humans to travel beyond the Mars orbit or to the inner regions of the Solar system? Will the age of Solar system exploration comes to its logical as it was described by Stanislav Lem in his famous book “Return from stars”? The author of this talk has more questions than answers, and thinks that PEX1 Panel on Exploration is just a right place to discuss these usually by passed topics.

  18. Drosophila melanogaster in the Study of Human Neurodegeneration

    PubMed Central

    Hirth, Frank

    2010-01-01

    Human neurodegenerative diseases are devastating illnesses that predominantly affect elderly people. The majority of the diseases are associated with pathogenic oligomers from misfolded proteins, eventually causing the formation of aggregates and the progressive loss of neurons in the brain and nervous system. Several of these proteinopathies are sporadic and the cause of pathogenesis remains elusive. Heritable forms are associated with genetic defects, suggesting that the affected protein is causally related to disease formation and/or progression. The limitations of human genetics, however, make it necessary to use model systems to analyse affected genes and pathways in more detail. During the last two decades, research using the genetically amenable fruitfly has established Drosophila melanogaster as a valuable model system in the study of human neurodegeneration. These studies offer reliable models for Alzheimer’s, Parkinson’s, and motor neuron diseases, as well as models for trinucleotide repeat expansion diseases, including ataxias and Huntington’s disease. As a result of these studies, several signalling pathways including phosphatidylinositol 3-kinase (PI3K)/Akt and target of rapamycin (TOR), c-Jun N-terminal kinase (JNK) and bone morphogenetic protein (BMP) signalling, have been shown to be deregulated in models of proteinopathies, suggesting that two or more initiating events may trigger disease formation in an age-related manner. Moreover, these studies also demonstrate that the fruitfly can be used to screen chemical compounds for their potential to prevent or ameliorate the disease, which in turn can directly guide clinical research and the development of novel therapeutic strategies for the treatment of human neurodegenerative diseases. PMID:20522007

  19. In vitro bidirectional permeability studies identify pharmacokinetic limitations of NKCC1 inhibitor bumetanide.

    PubMed

    Donovan, Maria D; Schellekens, Harrit; Boylan, Geraldine B; Cryan, John F; Griffin, Brendan T

    2016-01-01

    Recently, it has been suggested that bumetanide, an inhibitor of the Na-K-2Cl co-transporter (NKCC1), may be useful in the treatment of central nervous system (CNS) disorders. However, from a physicochemical perspective, bumetanide may not cross the blood-brain barrier to the extent that is necessary for it to be an effective brain NKCC1 inhibitor in vivo. High plasma-protein binding, potentially high brain-tissue binding and putative efflux transporters including organic anion transporter 3 (OAT3) contribute to the poor pharmacokinetic profile of bumetanide. Bidirectional permeability assays are an in vitro method to determine the impact of plasma-protein/brain tissue binding, as well as efflux transport, on the permeability of a compound. We established and validated a cell line stably overexpressing human OAT3 using lentiviral cloning techniques for use in in vitro bidirectional permeability assays. Using efflux transport studies, we show that bumetanide is a transported substrate of human OAT3, exhibiting a transport ratio of ?1.5, which is attenuated by OAT3 inhibitors. Bidirectional permeability assays were carried out in the presence and absence of either albumin or brain homogenate to elucidate the effect of plasma-protein/brain tissue binding. These tests confirmed the pharmacokinetic limitations for brain delivery of bumetanide. In this experiment, bumetanide is 53% bound to albumin, 77% bound to brain tissue and accumulates in brain cells. Moreover, we conclusively established that bumetanide is a transported substrate of OAT3. Taken together, these bidirectional permeability studies highlight the potential of efflux transporter inhibition as an augmentation strategy for enhanced delivery of bumetanide to the CNS. PMID:26673740

  20. Epidemiologic studies of behavioral health following the Deepwater Horizon oil spill: limited impact or limited ability to measure?

    PubMed

    Teich, Judith L; Pemberton, Michael R

    2015-01-01

    Two large-scale epidemiologic federal surveys conducted in the Gulf Coast following the Deepwater Horizon oil spill and intended to measure its impact on mental disorders and substance use found less dramatic results than had been anticipated. However, several smaller-scale studies conducted shortly after the spill did find increases in the prevalence of certain psychological problems among individuals surveyed. Previous federal studies conducted following two disasters-the destruction of the World Trade Center (WTC) and Hurricanes Katrina and Rita-found few statistically significant changes in behavioral disorders in the wake of those events, except for individuals displaced from their homes by Katrina for 2weeks or more. In this commentary, the authors discuss questions raised by these mixed results regarding the limitations of such studies, the behavioral health impact of the Deepwater Horizon spill compared to disasters causing more widespread loss of life and destruction of property, and the ways in which data collection following disasters might be improved to benefit public health planners. PMID:24557855

  1. 40 CFR 26.1606 - Human Studies Review Board review of proposed human research.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Human Studies Review Board review of proposed human research. 26.1606 Section 26.1606 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1606...

  2. 40 CFR 26.1607 - Human Studies Review Board review of completed human research.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Human Studies Review Board review of completed human research. 26.1607 Section 26.1607 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1607...

  3. 40 CFR 26.1607 - Human Studies Review Board review of completed human research.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Human Studies Review Board review of completed human research. 26.1607 Section 26.1607 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1607...

  4. 40 CFR 26.1606 - Human Studies Review Board review of proposed human research.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Human Studies Review Board review of proposed human research. 26.1606 Section 26.1606 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1606...

  5. ERBS human factors analysis: A case study

    NASA Technical Reports Server (NTRS)

    Moe, K. L.; Weger, C.

    1983-01-01

    The incorporation of human factors into the system development process and the benefits derived are discussed. The human factors analysis task for the Earth radiation budget satellite (ERBS) payload operations control center (POCC) is a pathfinder in the new applications approach to this discipline within the mission and data operations directorate. The topics covered include: discussions of the motivation for human factors analysis; the involvement of the human factors research group (HFRG) with project and system developers, and some examples of human factors issues addressed in the ERBS analysis task.

  6. Metabolomic studies of human gastric cancer: Review

    PubMed Central

    Jayavelu, Naresh Doni; Bar, Nadav S

    2014-01-01

    Metabolomics is a field of study in systems biology that involves the identification and quantification of metabolites present in a biological system. Analyzing metabolic differences between unperturbed and perturbed networks, such as cancerous and non-cancerous samples, can provide insight into underlying disease pathology, disease prognosis and diagnosis. Despite the large number of review articles concerning metabolomics and its application in cancer research, biomarker and drug discovery, these reviews do not focus on a specific type of cancer. Metabolomics may provide biomarkers useful for identification of early stage gastric cancer, potentially addressing an important clinical need. Here, we present a short review on metabolomics as a tool for biomarker discovery in human gastric cancer, with a primary focus on its use as a predictor of anticancer drug chemosensitivity, diagnosis, prognosis, and metastasis. PMID:25009381

  7. Katanin p80 regulates human cortical development by limiting centriole and cilia number.

    PubMed

    Hu, Wen F; Pomp, Oz; Ben-Omran, Tawfeg; Kodani, Andrew; Henke, Katrin; Mochida, Ganeshwaran H; Yu, Timothy W; Woodworth, Mollie B; Bonnard, Carine; Raj, Grace Selva; Tan, Thong Teck; Hamamy, Hanan; Masri, Amira; Shboul, Mohammad; Al Saffar, Muna; Partlow, Jennifer N; Al-Dosari, Mohammed; Alazami, Anas; Alowain, Mohammed; Alkuraya, Fowzan S; Reiter, Jeremy F; Harris, Matthew P; Reversade, Bruno; Walsh, Christopher A

    2014-12-17

    Katanin is a microtubule-severing complex whose catalytic activities are well characterized, but whose invivo functions are incompletely understood. Human mutations in KATNB1, which encodes the noncatalytic regulatory p80 subunit of katanin, cause severe microlissencephaly. Loss of Katnb1 in mice confirms essential roles in neurogenesis and cell survival, while loss of zebrafish katnb1 reveals specific roles for katnin p80 in early and late developmental stages. Surprisingly, Katnb1 null mutant mouse embryos display hallmarks of aberrant Sonic hedgehog signaling, including holoprosencephaly. KATNB1-deficient human cells show defective proliferation and spindle structure, while Katnb1 null fibroblasts also demonstrate a remarkable excess of centrioles, with supernumerary cilia but deficient Hedgehog signaling. Our results reveal unexpected functions for KATNB1 inregulating overall centriole, mother centriole, and cilia number, and as an essential gene for normal Hedgehog signaling during neocortical development. PMID:25521379

  8. Katanin p80 Regulates Human Cortical Development by Limiting Centriole and Cilia Number

    PubMed Central

    Hu, Wen F.; Pomp, Oz; Ben-Omran, Tawfeg; Kodani, Andrew; Henke, Katrin; Mochida, Ganeshwaran H.; Yu, Timothy W.; Woodworth, Mollie B.; Bonnard, Carine; Raj, Grace Selva; Tan, Thong Teck; Hamamy, Hanan; Masri, Amira; Shboul, Mohammad; Al Saffar, Muna; Partlow, Jennifer N.; Al-Dosari, Mohammed; Alazami, Anas; Alowain, Mohammed; Alkuraya, Fowzan S.; Reiter, Jeremy F.; Harris, Matthew P.; Reversade, Bruno; Walsh, Christopher A.

    2015-01-01

    SUMMARY Katanin is a microtubule-severing complex whose catalytic activities are well characterized, but whose in vivo functions are incompletely understood. Human mutations in KATNB1, which encodes the noncatalytic regulatory p80 subunit of katanin, cause severe microlissencephaly. Loss of Katnb1 in mice confirms essential roles in neurogenesis and cell survival, while loss of zebrafish katnb1 reveals specific roles for katnin p80 in early and late developmental stages. Surprisingly, Katnb1 null mutant mouse embryos display hallmarks of aberrant Sonic hedgehog signaling, including holoprosencephaly. KATNB1-deficient human cells show defective proliferation and spindle structure, while Katnb1 null fibroblasts also demonstrate a remarkable excess of centrioles, with supernumerary cilia but deficient Hedgehog signaling. Our results reveal unexpected functions for KATNB1 in regulating overall centriole, mother centriole, and cilia number, and as an essential gene for normal Hedgehog signaling during neocortical development. PMID:25521379

  9. Use of a thermoplastic material for identification of human remains is limited.

    PubMed

    2004-01-01

    There has been a recent effort to promote the use of a thermoplastic bite impression material for the identification of children. The American Board of Forensic Odontology (ABFO) is a certification board for forensic dentists in the United States and Canada. It is the position of the ABFO that this technique is of limited value when used for the dental identification of children. PMID:15672511

  10. Evaluation of streams in selected communities for the application of limited-detail study methods for flood-insurance studies

    USGS Publications Warehouse

    Cobb, Ernest D.

    1986-01-01

    The U.S. Geological Survey evaluated 2,349 communities in 1984 for the application of limited-detail flood-insurance study methods, that is, methods with a reduced effort and cost compared to the detailed studies. Limited-detail study methods were found to be appropriate for 1,705 communities, while detailed studies were appropriate for 62 communities and no studies were appropriate for 582 communities. The total length of streams for which limited-detail studies are recommended is 9 ,327 miles with a corresponding cost of $23,007,000. This results in average estimated costs for conducting limited-detail studies of $2,500 per mile of studied stream length. The purpose of the report is to document the limited-detail study methods and the results of the evaluation. (USGS)

  11. Study of human sperm motility post cryopreservation

    PubMed Central

    Oberoi, Bhavni; Kumar, Sushil; Talwar, Pankaj

    2014-01-01

    Background Cryopreservation of spermatozoa is a widely used technique to preserve the fertility of males. It can also benefit the armed forces personnel who are to be sent for long recruitments, while leaving their families behind. This study, apart from studying the effects of freezing and thawing, reveals the effect of the post thaw interval on the motility of the human spermatozoa and thus widens the insemination window period. Methods A detailed semen analysis was carried out as per the WHO guidelines for 25 samples. The samples were then washed, analysed and frozen in liquid nitrogen. The semen samples were subsequently thawed and similarly analysed after 20min and 40min of thawing. This was then followed by statistical analysis of the comparative motilities. Results Motility of sperms is found to decrease after cryopreservation. However, the study revealed that after thawing a significant increase in the motility of the sperms was noted with the progression of time (p<0.05). Conclusion By simulating conditions similar to the invivo conditions for the post thaw semen samples, we can safely wait, confirm the parameters like motility and count, and then inseminate the samples instead of blindly inseminating them immediately after thawing. PMID:25382909

  12. Antiviral Responses by Swine Primary Bronchoepithelial Cells Are Limited Compared to Human Bronchoepithelial Cells Following Influenza Virus Infection

    PubMed Central

    Hauser, Mary J.; Dlugolenski, Daniel; Culhane, Marie R.; Wentworth, David E.; Tompkins, S. Mark; Tripp, Ralph A.

    2013-01-01

    Swine generate reassortant influenza viruses because they can be simultaneously infected with avian and human influenza; however, the features that restrict influenza reassortment in swine and human hosts are not fully understood. Type I and III interferons (IFNs) act as the first line of defense against influenza virus infection of respiratory epithelium. To determine if human and swine have different capacities to mount an antiviral response the expression of IFN and IFN-stimulated genes (ISG) in normal human bronchial epithelial (NHBE) cells and normal swine bronchial epithelial (NSBE) cells was evaluated following infection with human (H3N2), swine (H1N1), and avian (H5N3, H5N2, H5N1) influenza A viruses. Expression of IFNλ and ISGs were substantially higher in NHBE cells compared to NSBE cells following H5 avian influenza virus infection compared to human or swine influenza virus infection. This effect was associated with reduced H5 avian influenza virus replication in human cells at late times post infection. Further, RIG-I expression was lower in NSBE cells compared to NHBE cells suggesting reduced virus sensing. Together, these studies identify key differences in the antiviral response between human and swine respiratory epithelium alluding to differences that may govern influenza reassortment. PMID:23875024

  13. Understanding the limits of animal models as predictors of human biology: lessons learned from the sbv IMPROVER Species Translation Challenge

    PubMed Central

    Mathis, Carole; Dulize, Rémi H. J.; Ivanov, Nikolai V.; Alexopoulos, Leonidas; Jeremy Rice, J.; Peitsch, Manuel C.; Stolovitzky, Gustavo; Meyer, Pablo; Hoeng, Julia

    2015-01-01

    Motivation: Inferring how humans respond to external cues such as drugs, chemicals, viruses or hormones is an essential question in biomedicine. Very often, however, this question cannot be addressed because it is not possible to perform experiments in humans. A reasonable alternative consists of generating responses in animal models and ‘translating’ those results to humans. The limitations of such translation, however, are far from clear, and systematic assessments of its actual potential are urgently needed. sbv IMPROVER (systems biology verification for Industrial Methodology for PROcess VErification in Research) was designed as a series of challenges to address translatability between humans and rodents. This collaborative crowd-sourcing initiative invited scientists from around the world to apply their own computational methodologies on a multilayer systems biology dataset composed of phosphoproteomics, transcriptomics and cytokine data derived from normal human and rat bronchial epithelial cells exposed in parallel to 52 different stimuli under identical conditions. Our aim was to understand the limits of species-to-species translatability at different levels of biological organization: signaling, transcriptional and release of secreted factors (such as cytokines). Participating teams submitted 49 different solutions across the sub-challenges, two-thirds of which were statistically significantly better than random. Additionally, similar computational methods were found to range widely in their performance within the same challenge, and no single method emerged as a clear winner across all sub-challenges. Finally, computational methods were able to effectively translate some specific stimuli and biological processes in the lung epithelial system, such as DNA synthesis, cytoskeleton and extracellular matrix, translation, immune/inflammation and growth factor/proliferation pathways, better than the expected response similarity between species. Contact: pmeyerr@us.ibm.com or Julia.Hoeng@pmi.com Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25236459

  14. A Brief History of Soils and Human Health Studies

    NASA Astrophysics Data System (ADS)

    Brevik, Eric C.; Sauer, Thomas J.

    2013-04-01

    The idea that there are links between soils and human health is an ancient one. The Bible depicts Moses as understanding that fertile soil was essential to the well-being of his people in approximately 1400 B.C. as they entered Canaan, and in 400 B.C. Hippocrates provided a list of things that should be considered in a proper medical evaluation, including the ground. Moving into the 18th and 19th Centuries, some North American farmers have been documented as recognizing a link between soils and human vitality. However, the recognition of links between soils and human health by these early people was based on casual observations leading to logical conclusions rather than scientific investigation. In the 1900s the idea that soils influence human health gained considerable traction. At least three chapters in the 1938 USDA Yearbook of Agriculture included recognition of the importance of soil as the origin of many of the mineral elements necessary for human health and in the 1957 USDA Yearbook of Agriculture scientists realized that soils were not only important in the supply of essential nutrients, but that they could also supply toxic levels of elements to the human diet. The U.S. Department of Agriculture established the Plant, Soil and Nutrition Research Unit (PSNRU) on the Cornell University campus in 1940 with a mission to conduct research at the interface of human nutrition and agriculture to improve the nutritional quality and health-promoting properties of food crops. A major human health breakthrough in 1940 was the isolation of antibiotic compounds from soil organisms by the research group at Rutgers University lead by Selman Waksman. Soil microorganisms create antibiotic compounds in an effort to gain a competitive advantage in the soil ecosystem. Humans have been able to isolate those compounds and use them advantageously in the fight against bacterial infections. Waksman was awarded the Nobel Prize in Physiology or Medicine in 1952, the only soil scientist to date to be awarded a Nobel Prize. In the 1940s and 50s William Albrecht of the University of Missouri became interested in links between soils and human health, an interest that lead to the publication of several papers. Albrecht's works focused on links between soil fertility and dental health, with a particular focus on the relationships between soil fertility and dental cavities. However, Albrecht did extend the relationships between soil fertility and human health out to broader, more general health issues in some of his writings as well. Well-known figures such as Sir Albert Howard and J.I. Rodale also published works in the 1940s that included soils and human health components. Then André Voisin published "Soil, Grass, and Cancer" in 1959. Much of Voisin's work focused on nutrient content in soils, including both nutrient deficiencies and imbalances, and how that influences nutrient status in plants and animals that are in turn consumed by humans. Several health problems are discussed, including but not limited to birth defects, goiter, mental illness, diabetes, and cancer. Voisin concluded that the medical profession had largely ignored soils in their efforts to improve human health, but that soil science should be the foundation of preventative medicine. Soils and human health studies continued in the later part of the 20th Century. The health effects of exposures to radioactive elements in soils received considerable attention after the 1986 Chernobyl incident, however, even prior to Chernobyl radionuclides in the soil and how they may affect human health were receiving attention. Investigations into the effects of heavy metals in soils became a common theme as did organic chemicals in soils and the effects of trace elements on human health. Following up on the discovery of antibiotics, soil organisms received increased attention as they related to human health. By the end of the 1900s, M.A. Oliver (1997) noted that "… there is a dearth of quantitative information on the relations between elements in the soil and human health;…there is much speculation and anecdotal evidence." The idea that soils influence human health is not new, it has existed for thousands of years and gained considerable attention in the 20th Century. However, the scientific study of soils and human health is a recent undertaking. Reference Oliver, M.A. 1997. Soil and human health: a review. European Journal of Soil Science 48:573-592.

  15. "Revolting to humanity": oversights, limitations, and complications of the English Legitimacy Act of 1926.

    PubMed

    Frost, Ginger

    2011-01-01

    This article analyses three areas that limited the effectiveness of the English Legitimacy Act of 1926. First, re-registration was public, expensive, and time-consuming. Second, the Treasury Office used the change in the law of intestacy to refuse more distant relatives' claims on estates. Third, the law separated legitimacy from nationality, thus denying citizenship to legitimated children born abroad of British fathers and foreign mothers. In short, both because of parliamentary oversights and civil servants' narrow interpretations of the law, relatively few children took advantage of the Act, and the minority who did, rather than being 'illegitimate' or 'legitimate', were a third category, the 'legitimated'. PMID:21299009

  16. [Treatment of the human body : the possibilities and limits of plastic surgery].

    PubMed

    Bermes, C

    2015-01-01

    The desire for authenticity is often cited as a motive for making use of plastic surgery. This article aims to elaborate on the meaning of this particular authenticity. At the same time, it discusses reasons that justify or forbid a plastic surgery intervention in the light of ethics. For this purpose, a distinction is made between "objective body" (Krper) and "subjective body" (Leib), and the objectives of medical actions are questioned. Through the terminological differentiation between integrity (Integritt), prosperity (Wohlergehen), and well-being (Wohlbefinden), these objectives are qualified and the limits of medical actions are determined. PMID:25604537

  17. Generation of a suite of 3D computer-generated breast phantoms from a limited set of human subject data

    PubMed Central

    Hsu, Christina M. L.; Palmeri, Mark L.; Segars, W. Paul; Veress, Alexander I.; Dobbins, James T.

    2013-01-01

    Purpose: The authors previously reported on a three-dimensional computer-generated breast phantom, based on empirical human image data, including a realistic finite-element based compression model that was capable of simulating multimodality imaging data. The computerized breast phantoms are a hybrid of two phantom generation techniques, combining empirical breast CT (bCT) data with flexible computer graphics techniques. However, to date, these phantoms have been based on single human subjects. In this paper, the authors report on a new method to generate multiple phantoms, simulating additional subjects from the limited set of original dedicated breast CT data. The authors developed an image morphing technique to construct new phantoms by gradually transitioning between two human subject datasets, with the potential to generate hundreds of additional pseudoindependent phantoms from the limited bCT cases. The authors conducted a preliminary subjective assessment with a limited number of observers (n = 4) to illustrate how realistic the simulated images generated with the pseudoindependent phantoms appeared. Methods: Several mesh-based geometric transformations were developed to generate distorted breast datasets from the original human subject data. Segmented bCT data from two different human subjects were used as the base and target for morphing. Several combinations of transformations were applied to morph between the base and target datasets such as changing the breast shape, rotating the glandular data, and changing the distribution of the glandular tissue. Following the morphing, regions of skin and fat were assigned to the morphed dataset in order to appropriately assign mechanical properties during the compression simulation. The resulting morphed breast was compressed using a finite element algorithm and simulated mammograms were generated using techniques described previously. Sixty-two simulated mammograms, generated from morphing three human subject datasets, were used in a preliminary observer evaluation where four board certified breast radiologists with varying amounts of experience ranked the level of realism (from 1 = fake to 10 = real) of the simulated images. Results: The morphing technique was able to successfully generate new and unique morphed datasets from the original human subject data. The radiologists evaluated the realism of simulated mammograms generated from the morphed and unmorphed human subject datasets and scored the realism with an average ranking of 5.87 1.99, confirming that overall the phantom image datasets appeared more real than fake. Moreover, there was not a significant difference (p > 0.1) between the realism of the unmorphed datasets (6.0 1.95) compared to the morphed datasets (5.86 1.99). Three of the four observers had overall average rankings of 6.89 0.89, 6.9 1.24, 6.76 1.22, whereas the fourth observer ranked them noticeably lower at 2.94 0.7. Conclusions: This work presents a technique that can be used to generate a suite of realistic computerized breast phantoms from a limited number of human subjects. This suite of flexible breast phantoms can be used for multimodality imaging research to provide a known truth while concurrently producing realistic simulated imaging data. PMID:23556929

  18. Generation of a suite of 3D computer-generated breast phantoms from a limited set of human subject data

    SciTech Connect

    Hsu, Christina M. L.; Palmeri, Mark L.; Segars, W. Paul; Veress, Alexander I.; Dobbins, James T. III

    2013-04-15

    Purpose: The authors previously reported on a three-dimensional computer-generated breast phantom, based on empirical human image data, including a realistic finite-element based compression model that was capable of simulating multimodality imaging data. The computerized breast phantoms are a hybrid of two phantom generation techniques, combining empirical breast CT (bCT) data with flexible computer graphics techniques. However, to date, these phantoms have been based on single human subjects. In this paper, the authors report on a new method to generate multiple phantoms, simulating additional subjects from the limited set of original dedicated breast CT data. The authors developed an image morphing technique to construct new phantoms by gradually transitioning between two human subject datasets, with the potential to generate hundreds of additional pseudoindependent phantoms from the limited bCT cases. The authors conducted a preliminary subjective assessment with a limited number of observers (n= 4) to illustrate how realistic the simulated images generated with the pseudoindependent phantoms appeared. Methods: Several mesh-based geometric transformations were developed to generate distorted breast datasets from the original human subject data. Segmented bCT data from two different human subjects were used as the 'base' and 'target' for morphing. Several combinations of transformations were applied to morph between the 'base' and 'target' datasets such as changing the breast shape, rotating the glandular data, and changing the distribution of the glandular tissue. Following the morphing, regions of skin and fat were assigned to the morphed dataset in order to appropriately assign mechanical properties during the compression simulation. The resulting morphed breast was compressed using a finite element algorithm and simulated mammograms were generated using techniques described previously. Sixty-two simulated mammograms, generated from morphing three human subject datasets, were used in a preliminary observer evaluation where four board certified breast radiologists with varying amounts of experience ranked the level of realism (from 1 ='fake' to 10 ='real') of the simulated images. Results: The morphing technique was able to successfully generate new and unique morphed datasets from the original human subject data. The radiologists evaluated the realism of simulated mammograms generated from the morphed and unmorphed human subject datasets and scored the realism with an average ranking of 5.87 {+-} 1.99, confirming that overall the phantom image datasets appeared more 'real' than 'fake.' Moreover, there was not a significant difference (p > 0.1) between the realism of the unmorphed datasets (6.0 {+-} 1.95) compared to the morphed datasets (5.86 {+-} 1.99). Three of the four observers had overall average rankings of 6.89 {+-} 0.89, 6.9 {+-} 1.24, 6.76 {+-} 1.22, whereas the fourth observer ranked them noticeably lower at 2.94 {+-} 0.7. Conclusions: This work presents a technique that can be used to generate a suite of realistic computerized breast phantoms from a limited number of human subjects. This suite of flexible breast phantoms can be used for multimodality imaging research to provide a known truth while concurrently producing realistic simulated imaging data.

  19. A Critical Review of Biomarkers Used for Monitoring Human Exposure to Lead: Advantages, Limitations, and Future Needs

    PubMed Central

    Barbosa, Fernando; Tanus-Santos, Jos Eduardo; Gerlach, Raquel Fernanda; Parsons, Patrick J.

    2005-01-01

    Lead concentration in whole blood (BPb) is the primary biomarker used to monitor exposure to this metallic element. The U.S. Centers for Disease Control and Prevention and the World Health Organization define a BPb of 10 ?g/dL (0.48 ?mol/L) as the threshold of concern in young children. However, recent studies have reported the possibility of adverse health effects, including intellectual impairment in young children, at BPb levels < 10 ?g/dL, suggesting that there is no safe level of exposure. It appears impossible to differentiate between low-level chronic Pb exposure and a high-level short Pb exposure based on a single BPb measurement; therefore, serial BPb measurements offer a better estimation of possible health outcomes. The difficulty in assessing the exact nature of Pb exposure is dependent not so much on problems with current analytical methodologies, but rather on the complex toxicokinetics of Pb within various body compartments (i.e., cycling of Pb between bone, blood, and soft tissues). If we are to differentiate more effectively between Pb stored in the body for years and Pb from recent exposure, information on other biomarkers of exposure may be needed. None of the current biomarkers of internal Pb dose have yet been accepted by the scientific community as a reliable substitute for a BPb measurement. This review focuses on the limitations of biomarkers of Pb exposure and the need to improve the accuracy of their measurement. We present here only the traditional analytical protocols in current use, and we attempt to assess the influence of confounding variables on BPb levels. Finally, we discuss the interpretation of BPb data with respect to both external and endogenous Pb exposure, past or recent exposure, as well as the significance of Pb determinations in human specimens including hair, nails, saliva, bone, blood (plasma, whole blood), urine, feces, and exfoliated teeth. PMID:16330345

  20. Combined spectrophotometry and tensile measurements of human connective tissues: potentials and limitations

    NASA Astrophysics Data System (ADS)

    Ernstberger, Markus; Sichting, Freddy; Baselt, Tobias; Hartmann, Peter; Aust, Gabriela; Hammer, Niels

    2013-06-01

    Strain-dependent transmission data of nine iliotibial tract specimens are determined using a custom-built optical setup with a halogen light source and an industrial norm material testing machine. Polarized light microscopy and hematoxylin-eosin staining indicated that lateral contraction of collagen structures is responsible for total intensity variations during a 20-cycle preconditioning and a 5-cycle tensile test. Tensile force progress is opposite to total transmission progress. Due to dehydration, wavelength-specific radiation intensity shifting is determined during the test, primarily noticeable in a water absorption band between 1400 and 1500 nm. The results show the capability of integrating spectrophotometry technology into biomechanics for determining structural alterations of human collagen due to applied strain. Being more sensitive to drying, spectrophotometry may likely serve as a quality control in stress-strain testing of biological structures.

  1. Combined spectrophotometry and tensile measurements of human connective tissues: potentials and limitations.

    PubMed

    Ernstberger, Markus; Sichting, Freddy; Baselt, Tobias; Hartmann, Peter; Aust, Gabriela; Hammer, Niels

    2013-06-01

    Strain-dependent transmission data of nine iliotibial tract specimens are determined using a custom-built optical setup with a halogen light source and an industrial norm material testing machine. Polarized light microscopy and hematoxylin-eosin staining indicated that lateral contraction of collagen structures is responsible for total intensity variations during a 20-cycle preconditioning and a 5-cycle tensile test. Tensile force progress is opposite to total transmission progress. Due to dehydration, wavelength-specific radiation intensity shifting is determined during the test, primarily noticeable in a water absorption band between 1400 and 1500 nm. The results show the capability of integrating spectrophotometry technology into biomechanics for determining structural alterations of human collagen due to applied strain. Being more sensitive to drying, spectrophotometry may likely serve as a quality control in stress-strain testing of biological structures. PMID:23797894

  2. Antecedent Avian Immunity Limits Tangential Transmission of West Nile Virus to Humans

    PubMed Central

    Kwan, Jennifer L.; Kluh, Susanne; Reisen, William K.

    2012-01-01

    Background West Nile virus (WNV) is a mosquito-borne flavivirus maintained and amplified among birds and tangentially transmitted to humans and horses which may develop terminal neuroinvasive disease. Outbreaks typically have a three-year pattern of silent introduction, rapid amplification and subsidence, followed by intermittent recrudescence. Our hypothesis that amplification to outbreak levels is contingent upon antecedent seroprevalence within maintenance host populations was tested by tracking WNV transmission in Los Angeles, California from 2003 through 2011. Methods Prevalence of antibodies against WNV was monitored weekly in House Finches and House Sparrows. Tangential or spillover transmission was measured by seroconversions in sentinel chickens and by the number of West Nile neuroinvasive disease (WNND) cases reported to the Los Angeles County Department of Public Health. Results Elevated seroprevalence in these avian populations was associated with the subsidence of outbreaks and in the antecedent dampening of amplification during succeeding years. Dilution of seroprevalence by recruitment resulted in the progressive loss of herd immunity following the 2004 outbreak, leading to recrudescence during 2008 and 2011. WNV appeared to be a significant cause of death in these avian species, because the survivorship of antibody positive birds significantly exceeded that of antibody negative birds. Cross-correlation analysis showed that seroprevalence was negatively correlated prior to the onset of human cases and then positively correlated, peaking at 46 weeks after the onset of tangential transmission. Antecedent seroprevalence during winter (Jan Mar) was negatively correlated with the number of WNND cases during the succeeding summer (JulSep). Conclusions Herd immunity levels within after hatching year avian maintenance host populations <10% during the antecedent late winter and spring period were followed on three occasions by outbreaks of WNND cases during the succeeding summer. Because mosquitoes feed almost exclusively on these avian species, amplification was directly related to the availability of receptive non-immune hosts. PMID:22457819

  3. O{sub 2}-mediated oxidation of ferrous nitrosylated human serum heme-albumin is limited by nitrogen monoxide dissociation

    SciTech Connect

    Ascenzi, Paolo; National Institute for Infectious Diseases I.R.C.C.S. 'Lazzaro Spallanzani', Via Portuense 292, I-00149 Roma ; Gullotta, Francesca; Gioia, Magda; Coletta, Massimo; Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems, Piazza Umberto I 1, I-87100 Bari ; Fasano, Mauro

    2011-03-04

    Research highlights: {yields} Human serum heme-albumin displays globin-like properties. {yields} O{sub 2}-mediated oxidation of ferrous nitrosylated human serum heme-albumin. {yields} Allosteric modulation of human serum heme-albumin reactivity. {yields} Rifampicin is an allosteric effector of human serum heme-albumin. {yields} Human serum heme-albumin is a ROS and NOS scavenger. -- Abstract: Human serum heme-albumin (HSA-heme-Fe) displays globin-like properties. Here, kinetics of O{sub 2}-mediated oxidation of ferrous nitrosylated HSA-heme-Fe (HSA-heme-Fe(II)-NO) is reported. Values of the first-order rate constants for O{sub 2}-mediated oxidation of HSA-heme-Fe(II)-NO (i.e., for ferric HSA-heme-Fe formation) and for NO dissociation from HSA-heme-Fe(II)-NO (i.e., for NO replacement by CO) are k = 9.8 x 10{sup -5} and 8.3 x 10{sup -4} s{sup -1}, and h = 1.3 x 10{sup -4} and 8.5 x 10{sup -4} s{sup -1}, in the absence and presence of rifampicin, respectively, at pH = 7.0 and T = 20.0 {sup o}C. The coincidence of values of k and h indicates that NO dissociation represents the rate limiting step of O{sub 2}-mediated oxidation of HSA-heme-Fe(II)-NO. Mixing HSA-heme-Fe(II)-NO with O{sub 2} does not lead to the formation of the transient adduct(s), but leads to the final ferric HSA-heme-Fe derivative. These results reflect the fast O{sub 2}-mediated oxidation of ferrous HSA-heme-Fe and highlight the role of drugs in modulating allosterically the heme-Fe-atom reactivity.

  4. PLESA: Program for Persons of Limited English-Speaking Ability. Ten Case Studies.

    ERIC Educational Resources Information Center

    Reynolds, Jack; And Others

    These ten case studies of the Program for Persons of Limited English-Speaking Ability (PLESA) report different approaches to providing training and employment assistance to unemployed persons of limited English-speaking ability. (A summary report of forty-seven projects is available separately. See Note.) The first four describe projects conducted

  5. Red, Yellow, Blue: A Primary Study of the Strengths, Limitations and Challenges of Arts Magnet Schools.

    ERIC Educational Resources Information Center

    Halquist, Don

    This primary, exploratory study combines the limited literature on arts magnet schools with the writings of arts activists and the narratives of several arts magnet school administrators in an attempt to understand arts magnet schools better. The paper illuminates some of the strengths of arts magnet schools as well as some of the limitations and…

  6. Kinetics of human immunodeficiency virus type 1 reverse transcription in blood mononuclear phagocytes are slowed by limitations of nucleotide precursors.

    PubMed Central

    O'Brien, W A; Namazi, A; Kalhor, H; Mao, S H; Zack, J A; Chen, I S

    1994-01-01

    Human immunodeficiency virus type 1 infection of mononuclear phagocytes has been implicated in disease manifestations, but postentry viral replication events in these cells have not been well characterized. Productive infection of activated T cells is associated with cell proliferation and accumulation of full-length viral DNA within 6 h. In infected, nondividing quiescent peripheral blood lymphocytes, reverse transcription is aborted prior to full-length viral DNA formation. For nondividing, cultured mononuclear phagocytes, we now report a third pattern of reverse transcription with relatively slow kinetics, in which full-length viral DNA did not accumulate until 36 to 48 h. The reverse transcription rate in mononuclear phagocytes could be accelerated by addition of exogenous nucleotide precursors, but still not to the rate seen in activated T cells. These results indicate that substrate limitations in mononuclear phagocytes slow but do not arrest human immunodeficiency virus type 1 reverse transcription. Images PMID:7507180

  7. Studying Food Reward and Motivation in Humans

    PubMed Central

    Ziauddeen, Hisham; Subramaniam, Naresh; Cambridge, Victoria C.; Medic, Nenad; Farooqi, Ismaa Sadaf; Fletcher, Paul C.

    2014-01-01

    A key challenge in studying reward processing in humans is to go beyond subjective self-report measures and quantify different aspects of reward such as hedonics, motivation, and goal value in more objective ways. This is particularly relevant for the understanding of overeating and obesity as well as their potential treatments. In this paper are described a set of measures of food-related motivation using handgrip force as a motivational measure. These methods can be used to examine changes in food related motivation with metabolic (satiety) and pharmacological manipulations and can be used to evaluate interventions targeted at overeating and obesity. However to understand food-related decision making in the complex food environment it is essential to be able to ascertain the reward goal values that guide the decisions and behavioral choices that people make. These values are hidden but it is possible to ascertain them more objectively using metrics such as the willingness to pay and a method for this is described. Both these sets of methods provide quantitative measures of motivation and goal value that can be compared within and between individuals. PMID:24686284

  8. Studying Human Dynamics Through Web Analytics

    NASA Astrophysics Data System (ADS)

    Ramasco, Jose; Goncalves, Bruno

    2008-03-01

    When Tim Berners Lee, a physicist at the European Center for Nuclear Research (CERN) first conceived the World Wide Web (WWW) in 1990 as a way to facilitate the sharing of scientific information and results among the centers different researchers and groups, even the most ingenious of science fiction writers could not have imagined the role it would come to play in the following decades. The increasing ubiquitousness of Internet access and the frequency with which people interact with it raise the possibility of using it to better observe, understand, and even monitor several aspects of human social behavior. Websites with large numbers of frequently returning users, such as search engines, company or university websites, are ideal for this task. The properly anonymized logs detailing the access history to Emory University's website is studied. We find that a small number of users is responsible for a finite fraction of the total activity. A saturation phenomenon is observed where, certain connections age, becoming less attractive to new activity over time. Finally, by measuring the average activity as a function of the day of the week, we find that productivity seems to be higher on Tuesdays and Wednesdays, with Sundays being the least active day.

  9. Maximal heart rate does not limit cardiovascular capacity in healthy humans: insight from right atrial pacing during maximal exercise

    PubMed Central

    Munch, G D W; Svendsen, J H; Damsgaard, R; Secher, N H; González-Alonso, J; Mortensen, S P

    2014-01-01

    In humans, maximal aerobic power () is associated with a plateau in cardiac output (), but the mechanisms regulating the interplay between maximal heart rate (HRmax) and stroke volume (SV) are unclear. To evaluate the effect of tachycardia and elevations in HRmax on cardiovascular function and capacity during maximal exercise in healthy humans, 12 young male cyclists performed incremental cycling and one-legged knee-extensor exercise (KEE) to exhaustion with and without right atrial pacing to increase HR. During control cycling, and leg blood flow increased up to 85% of maximal workload (WLmax) and remained unchanged until exhaustion. SV initially increased, plateaued and then decreased before exhaustion (P < 0.05) despite an increase in right atrial pressure (RAP) and a tendency (P = 0.056) for a reduction in left ventricular transmural filling pressure (LVFP). Atrial pacing increased HRmax from 184 ± 2 to 206 ± 3 beats min−1 (P < 0.05), but remained similar to the control condition at all intensities because of a lower SV and LVFP (P < 0.05). No differences in arterial pressure, peripheral haemodynamics, catecholamines or were observed, but pacing increased the rate pressure product and RAP (P < 0.05). Atrial pacing had a similar effect on haemodynamics during KEE, except that pacing decreased RAP. In conclusion, the human heart can be paced to a higher HR than observed during maximal exercise, suggesting that HRmax and myocardial work capacity do not limit in healthy individuals. A limited left ventricular filling and possibly altered contractility reduce SV during atrial pacing, whereas a plateau in LVFP appears to restrict close to . Key points During high intensity whole-body exercise, systemic and contracting skeletal muscle O2 delivery and uptake (>) are compromised, but the underlying mechanisms remain unclear. We evaluated the effect of a ∼20 beats min−1 increase in heart rate (HR) by right atrial pacing during incremental cycling and knee-extensor exercise on cardiac output () and stroke volume (SV). An increase in HR during both exercise modalities did not alter due to a proportional decrease in SV. The lower SV during atrial pacing in the cycling trial was associated with a diminished cardiac filling pressure, but similar arterial pressure. The results demonstrate that the human heart can achieve a higher HR than observed during maximal exercise, suggesting that HRmax and myocardial work capacity do not limit cardiac performance in trained human subjects. Instead, restrictions in ventricular filling appear to compromise cardiac preload, SV and at exercise intensities close to . PMID:24190933

  10. Design and testing of a high-speed treadmill to measure ground reaction forces at the limit of human gait.

    PubMed

    Bundle, Matthew W; Powell, Michael O; Ryan, Laurence J

    2015-09-01

    Investigations focused on the gait and physiological limits of human speed have been on-going for more than a century. However, due to measurement limitation a kinetic understanding of the foot-ground collision and how these dynamics differ between individuals to confer speed and limit gait has only recently begun to come forth. Therefore, we designed and tested an instrumented high-speed force treadmill to measure the forces occurring at the limits of human performance. The treadmill was designed to maximize flexural stiffness and natural frequency by using a honeycomb sandwich panel as the bed surface and a flexible drive shaft between the drive roller and servo motor to reduce the mass of the supported elements which contribute to the system's response frequency. The functional performance of the force treadmill met or exceeded the measurement criteria established for ideal force plates: high natural frequency (z-axis = 113 Hz), low crosstalk between components of the force (Fx/Fz = 0.0020[SD = 0.0010]; Fy/Fz = 0.0016[SD = 0.0003]), a linear response (R(2) > 0.999) for loading with known weights (range: 44-3857 N), and an accuracy of 2.5[SD = 1.7] mm and 2.8[SD = 1.5] mm in the x and y-axes, respectively, for the point of force application. In dynamic testing at running speeds up to 10 m s(-1), the measured durations and magnitudes of force application were similar between the treadmill and over-ground running using a force platform. This design provides a precise instrumented treadmill capable of recording multi-axis ground reaction forces applied during the foot ground contacts of the fastest men and animals known to science. PMID:26143150

  11. Zebrafish xenografts as a tool for in vivo studies on human cancer.

    PubMed

    Konantz, Martina; Balci, Tugce B; Hartwig, Udo F; Dellaire, Graham; Andr, Maya C; Berman, Jason N; Lengerke, Claudia

    2012-08-01

    The zebrafish has become a powerful vertebrate model for genetic studies of embryonic development and organogenesis and increasingly for studies in cancer biology. Zebrafish facilitate the performance of reverse and forward genetic approaches, including mutagenesis and small molecule screens. Moreover, several studies report the feasibility of xenotransplanting human cells into zebrafish embryos and adult fish. This model provides a unique opportunity to monitor tumor-induced angiogenesis, invasiveness, and response to a range of treatments in vivo and in real time. Despite the high conservation of gene function between fish and humans, concern remains that potential differences in zebrafish tissue niches and/or missing microenvironmental cues could limit the relevance and translational utility of data obtained from zebrafish human cancer cell xenograft models. Here, we summarize current data on xenotransplantation of human cells into zebrafish, highlighting the advantages and limitations of this model in comparison to classical murine models of xenotransplantation. PMID:22901264

  12. Today's ``safe" radiofrequency (RF) exposure limits DON'T protect human health near transmitters!

    NASA Astrophysics Data System (ADS)

    Lundquist, Marjorie

    2005-03-01

    Maxwell's theory implies that electromagnetic (EM) radiation carries both energy and momentum. ``The momentum may have both linear and angular contributions; angular momentum [AM] has a spin part associated with polarization and an orbital part associated with spatial distribution. Any interaction between radiation and matter is inevitably accompanied by an exchange of momentum. This often has mechanical consequences ..."^2 Voluntary consensus standards [ANSI C95; NCRP; INCIRP] protect human health from most thermal [energy transfer] effects, but no standards yet exist to protect health against athermal [momentum transfer] effects, though laboratory transfer of spin AM was reported by 1935^3 and of orbital AM by 1992^2 for an optical vortex [tip of Poynting vector (PV) traces a helix about the beam axis]. In the far field of a dipole RF transmitter, radiation is linearly polarized (minimal spin AM) and locally approximated by a plane wave (zero orbital AM), but in the near field the orbital AM is non-zero [tip of PV traces an ellipse^4 in air] implying an athermal hazard [e.g., brain tumors in cellular phone users] against which no standard now in use anywhere in the world protects! ^2 L. Allen et al. Phys. Rev. A 45:8185-9(1992). ^3 R.A. Beth, Phys. Rev. 48:471(1935); 50:115-25 (1936). ^4 F. Landstorfer, Archiv fr Elektronik und bertragungstechnik 26:189-96(1972) [in German].

  13. Studying Risk Factors Associated with Human Leptospirosis

    PubMed Central

    Kamath, Ramachandra; Swain, Subhashisa; Pattanshetty, Sanjay; Nair, N Sreekumaran

    2014-01-01

    Background: Leptospirosis is one of the most under diagnosed and underreported disease in both developed and developing countries including India. It is established that environmental conditions and occupational habit of the individuals put them at risk of acquiring disease, which varies from community to community. Various seroprevalence studies across the world have documented emerging situation of this neglected tropical disease, but limited have probed to identify the risk factors, especially in India. Objectives: The objective of this study was to identify the environmental and occupational risk factors associated with the disease in Udupi District. Materials and Methods: This population-based case-control study was carried out in Udupi, a District in Southern India from April 2012 until August 2012. Udupi is considered to be endemic for Leptospirosis and reported 116 confirmed cases in the year 2011. Seventy of 116 laboratory confirmed cases and 140 sex matched neighborhood healthy controls participated in the study. A predesigned, semi-structured and validated questionnaire was used for data collection through house to house visit and observations were noted about environmental conditions. Univariate analysis followed by multivariate analysis (back ward conditional logistic regression) was performed by using STATA version 9.2 (StataCorp, College Station, TX, USA) to identify potential risk factors. Results: Occupational factors such as outdoor activities (matched odds ratio [OR] of 3.95, 95% confidence interval [CI]: 1.19-13.0), presence of cut or wound at body parts during work (matched OR: 4.88, CI: 1.83-13.02) and environmental factors such as contact with rodents through using the food materials ate by rat (matched OR: 4.29, CI: 1.45-12.73) and contact with soil or water contaminated with urine of rat (matched OR: 4.58, CI: 1.43-14.67) were the risk factors identified to be associated with disease. Conclusion: Leptospirosis is still considered as neglected disease in the district. Early diagnosis and prompt treatment of cases can save many lives. However, there is a need of integrated rodent control measures with great effort to increase awareness and education among subjects in controlling the disease. PMID:24741223

  14. Activated endothelial cells limit inflammatory response, but increase chemoattractant potential and bacterial clearance by human monocytes.

    PubMed

    Mancilla-Herrera, Ismael; Alvarado-Moreno, José Antonio; Cérbulo-Vázquez, Arturo; Prieto-Chávez, Jessica L; Ferat-Osorio, Eduardo; López-Macías, Constantino; Estrada-Parra, Sergio; Isibasi, Armando; Arriaga-Pizano, Lourdes

    2015-06-01

    Inflammation is the normal immune response of vascularized tissues to damage and bacterial products, for which leukocyte transendothelial migration (TEM) is critical. The effects of cell-to-cell contact seen in both leukocyte and endothelial cells include cytoskeleton rearrangement, and dynamic expression of adhesion molecules and metalloproteinases. TEM induces expression of anti-apoptotic molecules, costimulatory molecules associated with antigen presentation, and pattern recognition receptors (PRR), such as TLR-4, in monocytes. However, little is known about how TLR-4 increment operates in monocytes during an inflammatory response. To understand it better, we used an in vitro model in which monocytes crossed a layer of IL-1β stimulated Human Umbilical Vein Endothelial Cells (HUVEC). After TEM, monocytes were tested for the secretion of inflammatory cytokines and chemokines, their phenotype (CD14, CD16, TLR-4 expression), and TLR-4 canonical [Nuclear Factor kappa B, (NF-κB) pathway] and non-canonical [p38, extracellular signal-regulated kinases (ERK) 1/2 pathway] signal transduction induced by lipopolysaccharide (LPS). Phagocytosis and bacterial clearance were also measured. There was diminished secretion of LPS-induced inflammatory cytokines (IL-1β, IL-6, and TNF-α) and higher secretion of chemokines (CXCL8/IL-8 and CCL2/MCP-1) in supernatant of TEM monocytes. These changes were accompanied by increases in TLR-4, CD14 (surfaces expression), p38, and ERK1/2 phosphorylated cytoplasmic forms, without affecting NF-κB activation. It also increased bacterial clearance after TEM by an O2 -independent mechanism. The data suggest that interaction between endothelial cells and monocytes fine-tunes the inflammatory response and promotes bacterial elimination. PMID:25598193

  15. Oxygen kinetics and debt during recovery from expiratory flow-limited exercise in healthy humans

    PubMed Central

    Zakynthinos, S.; Georgiadou, O.; Golemati, S.; Pedotti, A.; Macklem, P. T.; Roussos, C.; Aliverti, A.

    2006-01-01

    In healthy subjects expiratory flow limitation (EFL) during exercise can lower O2 delivery to the working muscles. We hypothesized that if this affects exercise performance it should influence O2 kinetics at the end of exercise when the O2 debt is repaid. We performed an incremental exercise test on six healthy males with a Starling resistor in the expiratory line limiting expiratory flow to ? 1ls?1 to determine maximal EFL exercise workload (Wmax). In two more square-wave exercise runs subjects exercised with and without EFL at Wmax for 6min, while measuring arterial O2 saturation (% SaO2), end-tidal pressure of CO2(PETCO2) and breath-by-breath O2 consumption \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${({\\dot{V}}\\hbox{O}_{2})}$$\\end{document} taking into account changes in O2 stored in the lungs. Over the last minute of EFL exercise, mean PETCO2 (54.79.9mmHg) was significantly higher (P<0.05) compared to control (41.43.9mmHg). At the end of EFL exercise %SaO2 fell significantly by 43%. When exercise stopped, EFL was removed, and we continued to measure \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\\dot{V}}\\hbox{O}_{2}.}$$\\end{document} During recovery, there was an immediate step increase in \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\\dot{V}}\\hbox{O}_{2},}$$\\end{document} so that repayment of EFL O2 debt started at a higher \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\\dot{V}}\\hbox{O}_{2}}$$\\end{document} than control. Recovery \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${{\\dot{V}}\\hbox{O}_{2}}$$\\end{document} kinetics after EFL exercise was best characterized by a double-exponential function with fundamental and slow time constants of 2711 and 1,020305s, compared to control values of 4110 and 1,358320s, respectively. EFL O2 debt was 5222% greater than control (2.190.58 vs. 1.490.38l). We conclude that EFL exercise increases the O2 debt and leads to hypoxemia in part due to hypercapnia. PMID:17149607

  16. Adenovirus-mediated expression of human coagulation factor IX in the rhesus macaque is associated with dose-limiting toxicity.

    PubMed

    Lozier, J N; Metzger, M E; Donahue, R E; Morgan, R A

    1999-12-15

    We used a first-generation adenovirus vector (AVC3FIX5) to assess whether human factor IX could be expressed and detected in the rhesus macaque, which we have shown does not make high-titer antibodies to human factor IX protein. Three animals received 1 x 10(10) to 1 x 10(11) plaque-forming units per kilogram by intravenous injection. Human factor IX was present within 24 hours of vector administration and peaked 4 days later at 4,000 ng/mL in the high-dose recipient, and lower levels were seen in the intermediate-dose recipient. No human factor IX was detected in the low-dose recipient's plasma. Serum cytokine analysis and early hypoferremia suggested a dose-dependent acute-phase response to the vector. Human factor IX was detectable in rhesus plasma for 2 to 3 weeks for the high- and intermediate-dose recipients, but disappeared concomitant with high-titer antihuman factor IX antibody development. There was substantial, dose-dependent, dose-limiting liver toxicity that was manifest as elevated serum transaminase levels, hyperbilirubinemia, hypoalbuminemia, and prolongation of clotting times. Of particular interest was prolongation of the thrombin clotting time, an indicator of decreased fibrinogen or fibrinogen dysfunction. All evidence of liver toxicity resolved except for persistent hypofibrinogenemia in the high-dose recipient, indicating possible permanent liver damage. Our data suggest a narrow therapeutic window for first-generation adenovirus-mediated gene transfer. The development of antihuman factor IX antibodies and abnormalities of fibrinogen in the rhesus macaque is of concern for application of adenovirus (or other viral) vectors to hemophilia gene therapy. PMID:10590040

  17. Experimental study of plasma properties in the shadow of the T--10 mushroom limiter

    SciTech Connect

    Alferov, A.A.; Vershkov, V.A.; Grashin, S.A.; Chankin, A.V.

    1988-04-01

    The plasma properties in the shadow of a mushroom-shaped limiter installed in a lower port of the tokamak have been studied. A study of the asymmetry of the plasma streams on the ion and electron sides of the limiter leads to the conclusion that there are two mechanisms for the occurrence of the asymmetry: the toroidal rotation of the plasma and a predominant escape of plasma to the wall through the outer part of the torus. The asymmetry observed in the plasma floating potentials near the limiter leads to the flow of a current close to the Spitzer value j/sub S/ through the limiter. With increasing plasma density, the plasma density in the channels of the limiter increases, and the temperature of this plasma decreases, so the loss of charged particles to the limiter depends only weakly on the average density. This circumstance is related to the degradation of the plasma confinement with decreasing density. The total flux of charged particles to the limiter is comparable to the flux of these particles out of the plasma column. The plasma stream into the channels is approximately ambipolar, and the power levels drawn by the neutralization plate are on the order of 10j/sub S/T/sub e//e. The behavior of the neutral gas pressure in the volume near the limiter as a function of the plasma streams into the channels is nonlinear. The maximum pressure is 3x10/sup -2/ torr.

  18. Understanding Motivation for Study: Human Capital or Human Capability?

    ERIC Educational Resources Information Center

    Fredman, Nick

    2014-01-01

    Much research into the reasons students undertake tertiary study is at least implicitly based on rational choice theory: students calculate costs in order to maximize direct individual gain. The policy emphasis on pathways has somewhat broader bases including social inclusion as well as economic productivity, but narrowly focuses on institutional…

  19. Studies on Human Thyroxine-Binding Globulin

    PubMed Central

    Marshall, James S.; Pensky, Jack; Green, Allan M.

    1972-01-01

    A model system utilizing a highly purified partially desialylated thyroxine-(T4) binding protein (STBG) was studied. STBG was prepared by the same affinity chromatographic method we have reported for preparation of highly purified T4-binding globulin (TBG). The necessary prerequisite for preparation of STBG was the use of T4-substituted Sepharose which had been repeatedly exposed to large volumes of serum for purification of TBG. STBG moved more slowly on cellulose acetate electrophoresis than TBG but had the same molecular weight and antigenic determinants as TBG. It bound T4 with a 1: 1 molar ratio but its affinity for T4 was about 10 times less than that of TB. STBG had about onefourth the sialic acid content of TBG and the electrophoretic mobility of this protein was similar to that of a T4-binding protein with a mobility slower than that of TBG which has been seen in the electrophoretic patterns of some normal human serums and in serums of patients with hepatic cirrhosis and which does not appear to be an artifact caused by storage and freezing of serum. This fourth slowly migrating T4-binding region in electrophoretograms of cirrhotic serums is completely abolished by prior incubation with rabbit antiserum to TBG. The in vitro production of partially desialylated TBG from T4-Sepharose which had been previously exposed to large volumes of serum may be due to adsorption of neuraminidases to the Sepharose either directly from serum or as the result of bacterial contamination. Partial desialylation of TBG in vivo may be an early step in the catabolism of this protein. Images PMID:4118356

  20. Quantifying planetary limits of Earth system processes relevant to human activity using a thermodynamic view of the whole Earth system

    NASA Astrophysics Data System (ADS)

    Kleidon, Axel

    2014-05-01

    Food, water, and energy play, obviously, a central role in maintaining human activity. In this contribution, I derive estimates for the fundamental limits on the rates by which these resources are provided by Earth system processes and the levels at which these can be used sustainably. The key idea here is that these resources are, directly or indirectly, generated out of the energy associated with the absorption of sunlight, and that the energy conversions from sunlight to other forms ultimately limit the generation of these resources. In order to derive these conversion limits, we need to trace the links between the processes that generate food, water and energy to the absorption of sunlight. The resource "food" results from biomass production by photosynthesis, which requires light and a sufficient magnitude of gas exchange of carbon dioxide at the surface, which is maintained by atmospheric motion which in turn is generated out of differential radiative heating and cooling. The resource "water" is linked to hydrologic cycling, with its magnitude being linked to the latent heat flux of the surface energy balance and water vapor transport in the atmosphere which is also driven by differential radiative heating and cooling. The availability of (renewable) energy is directly related to the generation of different forms of energy of climate system processes, such as the kinetic energy of atmospheric motion, which, again, relates to radiative heating differences. I use thermodynamics and its limits as a basis to establish the planetary limits of these processes and use a simple model to derive first-order estimates. These estimates compare quite well with observations, suggesting that this thermodynamic view of the whole Earth system provides an objective, physical basis to define and quantify planetary boundaries as well as the factors that shape these boundaries.

  1. AN APPROACH TO METHODS DEVELOPMENT FOR HUMAN EXPOSURE ASSESSMENT STUDIES

    EPA Science Inventory

    Human exposure assessment studies require methods that are rapid, cost-effective and have a high sample through-put. The development of analytical methods for exposure studies should be based on specific information for individual studies. Human exposure studies suggest that di...

  2. Studying the immune response to human viral infections using zebrafish

    PubMed Central

    Goody, Michelle F.; Sullivan, Con; Kim, Carol H.

    2014-01-01

    Humans and viruses have a long co-evolutionary history. Viral illnesses have and will continue to shape human history: from smallpox, to influenza, to HIV, and beyond. Animal models of human viral illnesses are needed in order to generate safe and effective antiviral medicines, adjuvant therapies, and vaccines. These animal models must support the replication of human viruses, recapitulate aspects of human viral illnesses, and respond with conserved immune signaling cascades. The zebrafish is perhaps the simplest, most commonly used laboratory model organism in which innate and/or adaptive immunity can be studied. Herein, we will discuss the current zebrafish models of human viral illnesses and the insights they have provided. We will highlight advantages of early life stage zebrafish and the importance of innate immunity in human viral illnesses. We will also discuss viral characteristics to consider before infecting zebrafish with human viruses as well as predict other human viruses that may be able to infect zebrafish. PMID:24718256

  3. Retrohoming of a Mobile Group II Intron in Human Cells Suggests How Eukaryotes Limit Group II Intron Proliferation

    PubMed Central

    Truong, David M.; Hewitt, F. Curtis; Hanson, Joseph H.; Cui, Xiaoxia; Lambowitz, Alan M.

    2015-01-01

    Mobile bacterial group II introns are evolutionary ancestors of spliceosomal introns and retroelements in eukaryotes. They consist of an autocatalytic intron RNA (a “ribozyme”) and an intron-encoded reverse transcriptase, which function together to promote intron integration into new DNA sites by a mechanism termed “retrohoming”. Although mobile group II introns splice and retrohome efficiently in bacteria, all examined thus far function inefficiently in eukaryotes, where their ribozyme activity is limited by low Mg2+ concentrations, and intron-containing transcripts are subject to nonsense-mediated decay (NMD) and translational repression. Here, by using RNA polymerase II to express a humanized group II intron reverse transcriptase and T7 RNA polymerase to express intron transcripts resistant to NMD, we find that simply supplementing culture medium with Mg2+ induces the Lactococcus lactis Ll.LtrB intron to retrohome into plasmid and chromosomal sites, the latter at frequencies up to ~0.1%, in viable HEK-293 cells. Surprisingly, under these conditions, the Ll.LtrB intron reverse transcriptase is required for retrohoming but not for RNA splicing as in bacteria. By using a genetic assay for in vivo selections combined with deep sequencing, we identified intron RNA mutations that enhance retrohoming in human cells, but <4-fold and not without added Mg2+. Further, the selected mutations lie outside the ribozyme catalytic core, which appears not readily modified to function efficiently at low Mg2+ concentrations. Our results reveal differences between group II intron retrohoming in human cells and bacteria and suggest constraints on critical nucleotide residues of the ribozyme core that limit how much group II intron retrohoming in eukaryotes can be enhanced. These findings have implications for group II intron use for gene targeting in eukaryotes and suggest how differences in intracellular Mg2+ concentrations between bacteria and eukarya may have impacted the evolution of introns and gene expression mechanisms. PMID:26241656

  4. Mars Rotorcraft: Possibilities, Limitations, and Implications For Human/Robotic Exploration

    NASA Technical Reports Server (NTRS)

    Young, Larry A.; Aiken, Edwin; Lee, Pascal; Briggs, Geoffrey

    2005-01-01

    Several research investigations have examined the challenges and opportunities in the use of small robotic rotorcraft for the exploration of Mars. To date, only vehicles smaller than 150 kg have been studied. This paper proposes to examine the question of maximum Mars rotorcraft size, range, and payload/cargo capacity. Implications for the issue of whether or not (from an extreme design standpoint) a manned Mars rotorcraft is viable are also discussed.

  5. Quantifying the performance limits of human saccadic targeting during visual search

    NASA Technical Reports Server (NTRS)

    Eckstein, M. P.; Beutter, B. R.; Stone, L. S.

    2001-01-01

    In previous studies of saccadic targeting, the issue how visually guided saccades to unambiguous targets are programmed and executed has been examined. These studies have found different degrees of guidance for saccades depending on the task and task difficulty. In this study, we use ideal-observer analysis to estimate the visual information used for the first saccade during a search for a target disk in noise. We quantitatively compare the performance of the first saccadic decision to that of the ideal observer (ie absolute efficiency of the first saccade) and to that of the associated final perceptual decision at the end of the search (ie relative efficiency of the first saccade). Our results show, first, that at all levels of salience tested, the first saccade is based on visual information from the stimulus display, and its highest absolute efficiency is approximately 20%. Second, the efficiency of the first saccade is lower than that of the final perceptual decision after active search (with eye movements) and has a minimum relative efficiency of 19% at the lowest level of saliency investigated. Third, we found that requiring observers to maintain central fixation (no saccades allowed) decreased the absolute efficiency of their perceptual decision by up to a factor of two, but that the magnitude of this effect depended on target salience. Our results demonstrate that ideal-observer analysis can be extended to measure the visual information mediating saccadic target-selection decisions during visual search, which enables direct comparison of saccadic and perceptual efficiencies.

  6. Students' Conceptual Knowledge of Limits in Calculus: A Two-Part Constructivist Case Study

    ERIC Educational Resources Information Center

    Adams, Margaret Smolinka

    2013-01-01

    This case study investigated students' conceptual knowledge of limits in calculus by implementing semi-structured interviews. The constructivist learning principles of Piaget and Inhelder as well as theories of understanding by Skemp guided the study. In Phase I, a pilot study was conducted with 15 students from a Calculus III class. By using

  7. Approaches for scaling up human immunodeficiency virus testing and counseling in prevention of mother-to-child human immunodeficiency virus transmission settings in resource-limited countries.

    PubMed

    Bolu, Omotayo O; Allread, Virginia; Creek, Tracy; Stringer, Elizabeth; Forna, Fatu; Bulterys, Marc; Shaffer, Nathan

    2007-09-01

    Prevention of mother-to-child human immunodeficiency virus (HIV) transmission (PMTCT) programs have nearly eliminated mother-to-child transmission of HIV in developed countries, but progress in resource-limited countries has been slow. A key factor limiting the scale-up of PMTCT programs is lack of knowledge of HIV serostatus. Increasing the availability and acceptability of HIV testing and counseling services will encourage more women to learn their status, providing a gateway to PMTCT interventions. Key factors contributing to the scale-up of testing and counseling include a policy of provider-initiated testing and counseling with right to refuse (opt-out); group pretest counseling; rapid HIV testing; innovative staffing strategies; and community and male involvement. Integration of testing and counseling within the community and all maternal and child health settings are critical for scaling-up and for linking women and their families to care and treatment services. This paper will review best practices needed for expansion of testing and counseling in PMTCT settings in resource-limited countries. PMID:17825654

  8. Do worsening knee radiographs mean greater chance of severe functional limitation? The Multicenter Osteoarthritis Study

    PubMed Central

    White, Daniel K.; Zhang, Yuqing; Niu, Jingbo; Keysor, Julie J.; Nevitt, Michael C.; Lewis, Cora E.; Torner, James C.; Neogi, Tuhina

    2010-01-01

    Objective Development of functional limitation is thought to be unrelated to changes in severity of radiographic knee osteoarthritis (ROA). We evaluated the relation of change in ROA to the incidence of severe functional limitation. Methods Participants of the Multicenter Osteoarthritis (MOST) Study, a cohort study of persons with or at high risk of knee OA were evaluated at 0 and 30 months. Subjects were classified as having no, incident, stable, or worsening ROA. Incidence of severe functional limitation was defined as 1) WOMAC physical function scores (? 36/68) and 2) walking speed (? 1.0 m/s) at 30 months. The relation of change in ROA to the incidence of severe functional limitation was evaluated by calculating risk ratios adjusted for potential confounders. Results Of the 2110 subjects included (mean age 62, mean BMI 30 kg/m2, female 60%), 53% had no, 6% incident, 14% stable, and 27% worsening ROA. Persons with incident ROA had 1.9 and 1.8 times the risk by WOMAC physical function and walking speed, respectively, to have incident severe functional limitation compared with those with no ROA over 30 months. Compared with those with stable ROA, persons with worsening ROA had 2.2 and 2.5 times the risk of incident severe functional limitation, respectively. Conclusion Changes in structural disease are associated with the development of severe functional limitations in persons with or even those at high risk of knee OA. PMID:20506398

  9. Human Fetal Behavior: 100 Years of Study.

    ERIC Educational Resources Information Center

    Kisilevsky, B. S.; Low, J. A.

    1998-01-01

    Reviews literature on human fetal behavior. Includes descriptions of coupling of body movements and fetal heart rate and behavior maturation from conception to term. Discusses use of stimulus-induced behavior to examine sensory and cognitive development, and spontaneous and stimulus-induced behavior to assess fetal well-being. Notes research focus

  10. Radical Feminism, Humanism and Women's Studies.

    ERIC Educational Resources Information Center

    Shibles, Warren

    1989-01-01

    Feminists now characterize radical feminism as involving sexism, views of the superiority of women over men, and the goal to establish a separate world without men, a gynocracy is discussed. Radical feminism is contrasted with humanism and seen to be antihumanistic. (Author/MLW)

  11. An epidemiologic study of the human bite.

    PubMed Central

    Marr, J S; Beck, A M; Lugo, J A

    1979-01-01

    The 892 human bites reported to the New York City Department of Health in 1977 were analyzed by time, place, and the victim's characteristics. The bites appeared to have a seasonality, increasing in March and exceeding the mean monthly average through August. The bite rate for the entire city, 10.7 per 100,000 population, was exceeded in 5 of the 10 Brooklyn health districts; one of these districts reported a rate of 60.9 human bites per 100,000 population. Most of the bites with identifiable locations occurred indoors (63.2 percent). In 72.8 percent of the bite episodes in which the activities surrounding them were known, these activities were aggressive in nature. Males exceeded females as bite victims in all age groups except those 10-20 and 55-60 years. Bites of the upper extremity accounted for 61.2 percent of the total bites. Left-sided bites exceeded right-sided, except for the hand. In frequency of reported occurrence, the human bite ranks third, after the dog bite and the cat bite. Human bites may be a useful indicator of antisocial behavior. PMID:515337

  12. An intermittent control model of flexible human gait using a stable manifold of saddle-type unstable limit cycle dynamics

    PubMed Central

    Fu, Chunjiang; Suzuki, Yasuyuki; Kiyono, Ken; Morasso, Pietro; Nomura, Taishin

    2014-01-01

    Stability of human gait is the ability to maintain upright posture during walking against external perturbations. It is a complex process determined by a number of cross-related factors, including gait trajectory, joint impedance and neural control strategies. Here, we consider a control strategy that can achieve stable steady-state periodic gait while maintaining joint flexibility with the lowest possible joint impedance. To this end, we carried out a simulation study of a heel-toe footed biped model with hip, knee and ankle joints and a heavy head-arms-trunk element, working in the sagittal plane. For simplicity, the model assumes a periodic desired joint angle trajectory and joint torques generated by a set of feed-forward and proportional-derivative feedback controllers, whereby the joint impedance is parametrized by the feedback gains. We could show that a desired steady-state gait accompanied by the desired joint angle trajectory can be established as a stable limit cycle (LC) for the feedback controller with an appropriate set of large feedback gains. Moreover, as the feedback gains are decreased for lowering the joint stiffness, stability of the LC is lost only in a few dimensions, while leaving the remaining large number of dimensions quite stable: this means that the LC becomes saddle-type, with a low-dimensional unstable manifold and a high-dimensional stable manifold. Remarkably, the unstable manifold remains of low dimensionality even when the feedback gains are decreased far below the instability point. We then developed an intermittent neural feedback controller that is activated only for short periods of time at an optimal phase of each gait stride. We characterized the robustness of this design by showing that it can better stabilize the unstable LC with small feedback gains, leading to a flexible gait, and in particular we demonstrated that such an intermittent controller performs better if it drives the state point to the stable manifold, rather than directly to the LC. The proposed intermittent control strategy might have a high affinity for the inverted pendulum analogy of biped gait, providing a dynamic view of how the step-to-step transition from one pendular stance to the next can be achieved stably in a robust manner by a well-timed neural intervention that exploits the stable modes embedded in the unstable dynamics. PMID:25339687

  13. An intermittent control model of flexible human gait using a stable manifold of saddle-type unstable limit cycle dynamics.

    PubMed

    Fu, Chunjiang; Suzuki, Yasuyuki; Kiyono, Ken; Morasso, Pietro; Nomura, Taishin

    2014-12-01

    Stability of human gait is the ability to maintain upright posture during walking against external perturbations. It is a complex process determined by a number of cross-related factors, including gait trajectory, joint impedance and neural control strategies. Here, we consider a control strategy that can achieve stable steady-state periodic gait while maintaining joint flexibility with the lowest possible joint impedance. To this end, we carried out a simulation study of a heel-toe footed biped model with hip, knee and ankle joints and a heavy head-arms-trunk element, working in the sagittal plane. For simplicity, the model assumes a periodic desired joint angle trajectory and joint torques generated by a set of feed-forward and proportional-derivative feedback controllers, whereby the joint impedance is parametrized by the feedback gains. We could show that a desired steady-state gait accompanied by the desired joint angle trajectory can be established as a stable limit cycle (LC) for the feedback controller with an appropriate set of large feedback gains. Moreover, as the feedback gains are decreased for lowering the joint stiffness, stability of the LC is lost only in a few dimensions, while leaving the remaining large number of dimensions quite stable: this means that the LC becomes saddle-type, with a low-dimensional unstable manifold and a high-dimensional stable manifold. Remarkably, the unstable manifold remains of low dimensionality even when the feedback gains are decreased far below the instability point. We then developed an intermittent neural feedback controller that is activated only for short periods of time at an optimal phase of each gait stride. We characterized the robustness of this design by showing that it can better stabilize the unstable LC with small feedback gains, leading to a flexible gait, and in particular we demonstrated that such an intermittent controller performs better if it drives the state point to the stable manifold, rather than directly to the LC. The proposed intermittent control strategy might have a high affinity for the inverted pendulum analogy of biped gait, providing a dynamic view of how the step-to-step transition from one pendular stance to the next can be achieved stably in a robust manner by a well-timed neural intervention that exploits the stable modes embedded in the unstable dynamics. PMID:25339687

  14. Teacher Leader Human Relations Skills: A Comparative Study

    ERIC Educational Resources Information Center

    Roby, Douglas E.

    2012-01-01

    In this study, 142 graduate school teachers working in schools throughout southwestern Ohio assessed their human relation skills. A human relations survey was used for the study, and results were compared with colleagues assessing the teachers in the study. The survey was developed using a Likert-type scale, and was based on key elements affecting

  15. Teacher Leader Human Relations Skills: A Comparative Study

    ERIC Educational Resources Information Center

    Roby, Douglas E.

    2012-01-01

    In this study, 142 graduate school teachers working in schools throughout southwestern Ohio assessed their human relation skills. A human relations survey was used for the study, and results were compared with colleagues assessing the teachers in the study. The survey was developed using a Likert-type scale, and was based on key elements affecting…

  16. Quantification of manganese in human hand bones: a feasibility study.

    PubMed

    Aslam; Pejovi?-Mili?, A; Chettle, D R; McNeill, F E

    2008-08-01

    Manganese is both an essential element to human health and also toxic when humans are exposed to excessive levels, particularly by means of inhalation. Biological monitoring of manganese exposure is problematic. It is subject to homeostasis; levels in blood (or serum/plasma) reflect only the most recent exposure and rapidly return to within normal ranges, even when there has been a temporary excursion in response to exposure. In this context, we have been developing a non-invasive technique for measurement of manganese stored in bone, using in vivo neutron activation analysis. Following preliminary feasibility studies, the technique has been enhanced by two significant infrastructure advances. A specially designed irradiation facility serves to maximize the activation of manganese with respect to the dose of ionizing radiation. Secondly, an array of eight NaI(Tl) crystals provides a detection system with very close to 4 pi geometry. This feasibility study, using neutron activation analysis to measure manganese in the bones of the hand, takes two features into account. Firstly, there is considerable magnesium present in the bone and this produces a spectral interference with the manganese. The 26 Mg(n,gamma)27 Mg reaction produces gamma -rays of 0.843 MeV from the decay of 27 Mg, which interfere with the 0.847 MeV gamma -rays from the decay of 56 Mn,produced by the 55 Mn(n,gamma)56 Mn reaction. Secondly, this work provides estimates of the levels of manganese to be expected in referent subjects. A revised estimate has been made from the most recent literature to explore the potential of the technique as a suitable means of screening patients and people exposed to excessive amounts of Mn who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. This report presents the enhancements to the neutron activation system, by which manganese can be measured, which resulted in a detection limit in the hand of human subjects of 1.6 microg/g Ca. It also provides a revised estimate of expected referent levels of manganese in bone, now estimated to be 0.63 microg/g Ca and highlights the extent to which technical improvements will be required to further extend the application of the technique for in vivo measurements in non-exposed human subjects. PMID:18782941

  17. Intrinsic near-24-h pacemaker period determines limits of circadian entrainment to a weak synchronizer in humans

    NASA Technical Reports Server (NTRS)

    Wright, K. P. Jr; Hughes, R. J.; Kronauer, R. E.; Dijk, D. J.; Czeisler, C. A.

    2001-01-01

    Endogenous circadian clocks are robust regulators of physiology and behavior. Synchronization or entrainment of biological clocks to environmental time is adaptive and important for physiological homeostasis and for the proper timing of species-specific behaviors. We studied subjects in the laboratory for up to 55 days each to determine the ability to entrain the human clock to a weak circadian synchronizing stimulus [scheduled activity-rest cycle in very dim (approximately 1.5 lux in the angle of gaze) light-dark cycle] at three approximately 24-h periods: 23.5, 24.0, and 24.6 h. These studies allowed us to test two competing hypotheses as to whether the period of the human circadian pacemaker is near to or much longer than 24 h. We report here that imposition of a sleep-wake schedule with exposure to the equivalent of candle light during wakefulness and darkness during sleep is usually sufficient to maintain circadian entrainment to the 24-h day but not to a 23.5- or 24.6-h day. Our results demonstrate functionally that, in normally entrained sighted adults, the average intrinsic circadian period of the human biological clock is very close to 24 h. Either exposure to very dim light and/or the scheduled sleep-wake cycle itself can entrain this near-24-h intrinsic period of the human circadian pacemaker to the 24-h day.

  18. Study of human gallstones by Raman spectroscopy

    NASA Astrophysics Data System (ADS)

    Liu, Gang; Xing, Da

    1999-09-01

    A suit of human gallstones was investigated by a new type of grating Raman spectrometer. The spectra of cholesterol stone, mixed stone, and brown pigment stone were obtained. A strong Raman band at 1748 cm-1 attributed to fatty salts indicates that some stones may contain more fatty salts than other gallstones. The results suggest that fatty salts may play an important rule for some gallstones. The formation mechanism is discussed in the paper. Such information is very useful to clinical application.

  19. Empirical study on human acupuncture point network

    NASA Astrophysics Data System (ADS)

    Li, Jian; Shen, Dan; Chang, Hui; He, Da-Ren

    2007-03-01

    Chinese medical theory is ancient and profound, however is confined by qualitative and faint understanding. The effect of Chinese acupuncture in clinical practice is unique and effective, and the human acupuncture points play a mysterious and special role, however there is no modern scientific understanding on human acupuncture points until today. For this reason, we attend to use complex network theory, one of the frontiers in the statistical physics, for describing the human acupuncture points and their connections. In the network nodes are defined as the acupuncture points, two nodes are connected by an edge when they are used for a medical treatment of a common disease. A disease is defined as an act. Some statistical properties have been obtained. The results certify that the degree distribution, act degree distribution, and the dependence of the clustering coefficient on both of them obey SPL distribution function, which show a function interpolating between a power law and an exponential decay. The results may be helpful for understanding Chinese medical theory.

  20. 2012 North Plains research field 12-200 limited irrigation corn production study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    2012 represented the third sequential year of research regarding the limited irrigation 12-200 corn production assessment study at the North Plains Research Field (NPRF) with the yield results being improved from that of the 2011 season but less than of the 2010 season. The study's purpose was to ev...

  1. Human olfactory consciousness and cognition: its unusual features may not result from unusual functions but from limited neocortical processing resources

    PubMed Central

    Stevenson, Richard J.; Attuquayefio, Tuki

    2013-01-01

    Human and animal olfactory perception is shaped both by functional demands and by various environmental constraints seemingly peculiar to chemical stimuli. These demands and constraints may have generated a sensory system that is cognitively distinct from the major senses. In this article we identify these various functional demands and constraints, and examine whether they can be used to account for olfaction's unique cognitive features on a case-by-case basis. We then use this as grounds to argue that specific conscious processes do have functional value, a finding that naturally emerges when a comparative approach to consciousness across the senses is adopted. More generally, we conclude that certain peculiar features of olfactory cognition may owe more to limited neocortical processing resources, than they do to the challenges faced by perceiving chemical stimuli. PMID:24198808

  2. critcial human health issues in connection with future human missions to mMars: the HUMEX study of ESA

    NASA Astrophysics Data System (ADS)

    Horneck, G.; Humex Team

    ESA has recently initiated a study of the human responses, limits and needs with regard to the stress environments of interplanetary and planetary missions. Emphasis was laid on human health and performance care as well as Advanced Life Support Developments including Bioregenerative Life Support Systems and environmental monitoring. The overall study goals were as follows: (i) to define reference scenarios for a European participation in human exploration and to estimate their influence on the Life Sciences and Life Support requirements; (ii) for selected mission scenarios, to critically assess the limiting factors for human health, wellbeing, and performance and to recommend relevant countermeasures; (iii) for selected mission scenarios, to critically assess the potential of Advanced Life Support Developments and to pro-pose a European strategy including terrestrial applications; (iv) to critically assess the feasibility of existing facilities and technologies on ground and in space as test-beds in preparation for human exploratory missions and to develop a test plan for ground and ISS campaigns; (v) to develop a roadmap for a future European strategy towards human exploratory missions, including preparatory activities and terrestrial applications and benefits. Two scenarios for a Mars mission were selected: (i) with a 30 days stay on Mars, and (ii) with about 500 days stay on Mars. The impact on human health, perform-ance and well being has been investigated from the view point of (i) the effects of microgravity (during space travel), reduced gravity (on Mars) and abrupt gravity changes (during launch and landing), (ii) the effects of cosmic radiation including solar particle events, (iii) psychological issues as well as general health care. Coun-termeasures as well as necessary research using ground-based testbeds and/or the ISS have been defined. The need for highly intelligent autonomous diagnostic and therapy systems was emphasized. Advanced life support systems with a high degree of autonomy and regenerative capacity and synergy effects were considered where bioregenerative life support systems and biodiagnostic systems become essential especially for the long-term Mars scenario. The considerations have been incorpo-rated into a roadmap for a future European strategy in human health issues for a potential European participation in a cooperative international exploration of our solar system by humans. Ref. Horneck et al, 2003, HUMEX, study on the Survivability and Adaptation of Humans to Long-Duration Exploratory Missions, ESA SP 1264

  3. Electrophysiological Studies of Face Perception in Humans

    PubMed Central

    Bentin, Shlomo; Allison, Truett; Puce, Aina; Perez, Erik; McCarthy, Gregory

    2009-01-01

    Event-related potentials (ERPs) associated with face perception were recorded with scalp electrodes from normal volunteers. Subjects performed a visual target detection task in which they mentally counted the number of occurrences of pictorial stimuli from a designated category such us butterflies. In separate experiments, target stimuli were embedded within a series of other stimuli including unfamiliar human faces and isolated face components, inverted faces, distorted faces, animal faces, and other nonface stimuli. Unman faces evoked a negative potential at 172 msec (N170), which was absent from the ERPs elicited by other animate and inanimate nonface stimuli. N170 was largest over the posterior temporal scalp and was larger over the right than the left hemisphere. N170 was delayed when faces were presented upside-down, but its amplitude did not change. When presented in isolation, eyes elicited an N170 that was significantly larger than that elicited by whole faces, while noses and lips elicited small negative ERPs about 50 msec later than N170. Distorted human faces, in which the locations of inner face components were altered, elicited an N170 similar in amplitude to that elicited by normal faces. However, faces of animals, human hands, cars, and items of furniture did not evoke N170. N170 may reflect the operation of a neural mechanism tuned to detect (as opposed to identify) human faces, similar to the structural encoder suggested by Bruce and Young (1986). A similar function has been proposed for the face-selective N200 ERP recorded from the middle fusiform and posterior inferior temporal gyri using subdural electrodes in humans (Allison, McCarthy, Nobre, Puce, & Belger, 1994c). However, the differential sensitivity of N170 to eyes in isolation suggests that N170 may reflect the activation of an eye-sensitive region of cortex. The voltage distribution of N170 over the scalp is consistent with a neural generator located in the occipitotemporal sulcus lateral to the fusiform/inferior temporal region that generates N200. PMID:20740065

  4. Refinement of a limit cycle oscillator model of the effects of light on the human circadian pacemaker

    NASA Technical Reports Server (NTRS)

    Jewett, M. E.; Kronauer, R. E.; Brown, E. N. (Principal Investigator)

    1998-01-01

    In 1990, Kronauer proposed a mathematical model of the effects of light on the human circadian pacemaker. Although this model predicted many general features of the response of the human circadian pacemaker to light exposure, additional data now available enable us to refine the original model. We first refined the original model by incorporating the results of a dose response curve to light into the model's predicted relationship between light intensity and the strength of the drive onto the pacemaker. Data from three bright light phase resetting experiments were then used to refine the amplitude recovery characteristics of the model. Finally, the model was tested and further refined using data from an extensive phase resetting experiment in which a 3-cycle bright light stimulus was presented against a background of dim light. In order to describe the results of the four resetting experiments, the following major refinements to the original model were necessary: (i) the relationship between light intensity (I) and drive onto the pacemaker was reduced from I1/3 to I0.23 for light levels between 150 and 10,000 lux; (ii) the van der Pol oscillator from the original model was replaced with a higher-order limit cycle oscillator so that amplitude recovery is slower near the singularity and faster near the limit cycle; (iii) a direct effect of light on circadian period (tau x) was incorporated into the model such that as I increases, tau x decreases, which is in accordance with "Aschoff's rule". This refined model generates the following testable predictions: it should be difficult to enhance normal circadian amplitude via bright light; near the critical point of a type 0 phase response curve (PRC) the slope should be steeper than it is in a type 1 PRC; and circadian period measured during forced desynchrony should be directly affected by ambient light intensity.

  5. Looking toward the Future: A Case Study of Open Source Software in the Humanities

    ERIC Educational Resources Information Center

    Quamen, Harvey

    2006-01-01

    In this article Harvey Quamen examines how the philosophy of open source software might be of particular benefit to humanities scholars in the near future--particularly for academic journals with limited financial resources. To this end he provides a case study in which he describes his use of open source technology (MySQL database software and

  6. Looking toward the Future: A Case Study of Open Source Software in the Humanities

    ERIC Educational Resources Information Center

    Quamen, Harvey

    2006-01-01

    In this article Harvey Quamen examines how the philosophy of open source software might be of particular benefit to humanities scholars in the near future--particularly for academic journals with limited financial resources. To this end he provides a case study in which he describes his use of open source technology (MySQL database software and…

  7. Fourier transform Raman spectroscopic studies of human and animal skins

    NASA Astrophysics Data System (ADS)

    Barry, Brian W.; Edwards, Howell G.; Williams, Adrian C.

    1994-01-01

    The stratum corneum is the outermost layer of the skin and provides the principal barrier for the ingress of chemicals and environmental toxins into human and animal tissues. However, human skin has several advantages for the administration of therapeutic agents (transdermal drug delivery), but problems occur with the supply, storage, and biohazardous nature of human tissue. Hence, alternative animal tissues have been prepared to model drug diffusion across human skin but the molecular basis for comparison is lacking. Here, FT-Raman spectra of mammalian (human and pig) and reptilian (snake) skins have been obtained and the structural dissimilarities are correlated with drug diffusion studies across the tissues.

  8. Daily walking and the risk of incident functional limitation in knee OA: An observational study

    PubMed Central

    White, Daniel K.; Tudor-Locke, Catrine; Zhang, Yuqing; Fielding, Roger; LaValley, Michael; Felson, David T.; Gross, K. Douglas; Nevitt, Michael C.; Lewis, Cora E.; Torner, James; Neogi, Tuhina

    2014-01-01

    Background Physical activity is recommended to mitigate functional limitations associated with knee osteoarthritis (OA). However, it is unclear whether walking on its own protects against the development of functional limitation. Methods Walking over 7 days was objectively measured as steps/day within a cohort of people with or at risk of knee OA from the Multicenter Osteoarthritis Study. Incident functional limitation over two years was defined by performance-based (gait speed ≤ 1.0 m/s) and self-report (WOMAC physical function ≥ 28/68) measures. We evaluated the association of steps/day at baseline with developing functional limitation two years later by calculating risk ratios adjusted for potential confounders. The number of steps/day that best distinguished risk for developing functional limitation was estimated from the maximum distance from chance on Receiver Operator Characteristic curves. Results Among 1788 participants (mean age 67, mean BMI 31 kg/m2, female 60%), each additional 1000 steps/day was associated with a 16% and 18% reduction in incident functional limitation by performance-based and self-report measures, respectively. Walking < 6000 and < 5900 steps/day were the best thresholds to distinguish incident functional limitation by performance-based (67.3%/71.8% [sensitivity/specificity]) and self-report (58.7%/68.9%) measures, respectively. Conclusions More walking was associated with less risk of functional limitation over two years. Walking ≥ 6000 steps/day provides a preliminary estimate of the level of walking activity to protect against developing functional limitation in people with or at risk of knee OA. PMID:24923633

  9. Twins for epigenetic studies of human aging and development.

    PubMed

    Tan, Qihua; Christiansen, Lene; Thomassen, Mads; Kruse, Torben A; Christensen, Kaare

    2013-01-01

    Most of the complex traits including aging phenotypes are caused by the interaction between genome and environmental conditions and the interface of epigenetics may be a central mechanism. Although modern technologies allow us high-throughput profiling of epigenetic patterns already at genome level, our understanding of genetic and environmental influences on the epigenetic processes remains limited. Twins are of special interest for genetic studies due to their genetic similarity and rearing-environment sharing. The classical twin design has made a great contribution in dissecting the genetic and environmental contributions to human diseases and complex traits. In the era of functional genomics, the valuable sample of twins is helping to bridge the gap between gene activity and the environments through epigenetic mechanisms unlimited by DNA sequence variations. We propose to extend the classical twin design to study the aging-related molecular epigenetic phenotypes and link them with environmental exposures especially early life events. Different study designs and application issues will be highlighted and novel approaches introduced with aim at making uses of twins in assessing the environmental impact on epigenetic changes during development and in the aging process. PMID:22750314

  10. Radium in humans: A review of U.S. studies

    SciTech Connect

    Rowland, R.E.

    1994-09-01

    This document was originally conceived as a compilation of activities at Argonne National Laboratory that were directed toward the study of radium in humans. However, it soon became obvious that this was a very limited approach, because such a compilation would include no background on the widespread uses of radium in industry and in the medical profession, nor would it address the early history of the discovery of the hazards of radium. Such an approach would also ignore contributions to the study of radium effects made at other laboratories. This document now addresses these topics, in order to give an overall picture of what might be called the radium era, that period from the early part of this century, when radium was rapidly exploited as a tool and a medication, to the present time, when radium is not generally used and the study of its effects has been terminated. The appendix to this review lists all of the measured radium cases, a total of 2,403 individuals whose records were in the files at the end of 1990. For each case the route of exposure, the dates of exposure, the years of birth and death, the measured body content, the calculated intake and dose, and the cause of death have been listed. 165 refs.

  11. Implications of Limits of Detection of Various Methods for Bacillus anthracis in Computing Risks to Human Health?

    PubMed Central

    Herzog, Amanda B.; McLennan, S. Devin; Pandey, Alok K.; Gerba, Charles P.; Haas, Charles N.; Rose, Joan B.; Hashsham, Syed A.

    2009-01-01

    Used for decades for biological warfare, Bacillus anthracis (category A agent) has proven to be highly stable and lethal. Quantitative risk assessment modeling requires descriptive statistics of the limit of detection to assist in defining the exposure. Furthermore, the sensitivities of various detection methods in environmental matrices are vital information for first responders. A literature review of peer-reviewed journal articles related to methods for detection of B. anthracis was undertaken. Articles focused on the development or evaluation of various detection approaches, such as PCR, real-time PCR, immunoassay, etc. Real-time PCR and PCR were the most sensitive methods for the detection of B. anthracis, with median instrument limits of detection of 430 and 440 cells/ml, respectively. There were very few peer-reviewed articles on the detection methods for B. anthracis in the environment. The most sensitive limits of detection for the environmental samples were 0.1 CFU/g for soil using PCR-enzyme-linked immunosorbent assay (ELISA), 17 CFU/liter for air using an ELISA-biochip system, 1 CFU/liter for water using cultivation, and 1 CFU/cm2 for stainless steel fomites using cultivation. An exponential dose-response model for the inhalation of B. anthracis estimates of risk at concentrations equal to the environmental limit of detection determined the probability of death if untreated to be as high as 0.520. Though more data on the environmental limit of detection would improve the assumptions made for the risk assessment, this study's quantification of the risk posed by current limitations in the knowledge of detection methods should be considered when employing those methods in environmental monitoring and cleanup strategies. PMID:19648357

  12. Noncanonical NOTCH signaling limits self-renewal of human epithelial and induced pluripotent stem cells through ROCK activation.

    PubMed

    Yugawa, Takashi; Nishino, Koichiro; Ohno, Shin-Ichi; Nakahara, Tomomi; Fujita, Masatoshi; Goshima, Naoki; Umezawa, Akihiro; Kiyono, Tohru

    2013-11-01

    NOTCH plays essential roles in cell fate specification during embryonic development and in adult tissue maintenance. In keratinocytes, it is a key inducer of differentiation. ROCK, an effector of the small GTPase Rho, is also implicated in keratinocyte differentiation, and its inhibition efficiently potentiates immortalization of human keratinocytes and greatly improves survival of dissociated human pluripotent stem cells. However, the molecular basis for ROCK activation is not fully established in these contexts. Here we provide evidence that intracellular forms of NOTCH1 trigger the immediate activation of ROCK1 independent of its transcriptional activity, promoting differentiation and resulting in decreased clonogenicity of normal human keratinocytes. Knockdown of NOTCH1 abrogated ROCK1 activation and conferred sustained clonogenicity upon differentiation stimuli. Treatment with a ROCK inhibitor, Y-27632, or ROCK1 silencing substantially rescued the growth defect induced by activated NOTCH1. Furthermore, we revealed that impaired self-renewal of human induced pluripotent stem cells upon dissociation is, at least in part, attributable to NOTCH-dependent ROCK activation. Thus, the present study unveils a novel NOTCH-ROCK pathway critical for cellular differentiation and loss of self-renewal capacity in a subset of immature cells. PMID:24019071

  13. Noncanonical NOTCH Signaling Limits Self-Renewal of Human Epithelial and Induced Pluripotent Stem Cells through ROCK Activation

    PubMed Central

    Yugawa, Takashi; Nishino, Koichiro; Ohno, Shin-ichi; Nakahara, Tomomi; Fujita, Masatoshi; Goshima, Naoki; Umezawa, Akihiro

    2013-01-01

    NOTCH plays essential roles in cell fate specification during embryonic development and in adult tissue maintenance. In keratinocytes, it is a key inducer of differentiation. ROCK, an effector of the small GTPase Rho, is also implicated in keratinocyte differentiation, and its inhibition efficiently potentiates immortalization of human keratinocytes and greatly improves survival of dissociated human pluripotent stem cells. However, the molecular basis for ROCK activation is not fully established in these contexts. Here we provide evidence that intracellular forms of NOTCH1 trigger the immediate activation of ROCK1 independent of its transcriptional activity, promoting differentiation and resulting in decreased clonogenicity of normal human keratinocytes. Knockdown of NOTCH1 abrogated ROCK1 activation and conferred sustained clonogenicity upon differentiation stimuli. Treatment with a ROCK inhibitor, Y-27632, or ROCK1 silencing substantially rescued the growth defect induced by activated NOTCH1. Furthermore, we revealed that impaired self-renewal of human induced pluripotent stem cells upon dissociation is, at least in part, attributable to NOTCH-dependent ROCK activation. Thus, the present study unveils a novel NOTCH-ROCK pathway critical for cellular differentiation and loss of self-renewal capacity in a subset of immature cells. PMID:24019071

  14. Community Environmental Factors Are Associated With Disability in Older Adults With Functional Limitations: The MOST Study

    PubMed Central

    Jette, Alan M.; LaValley, Michael P.; Lewis, Cora E.; Torner, James C.; Nevitt, Michael C.; Felson, Dave T.

    2010-01-01

    Background There is limited evidence supporting the hypothesized environmentdisability link. The objectives of this study were to (a) identify the prevalence of community mobility barriers and transportation facilitators and (b) examine whether barriers and facilitators were associated with disability among older adults with functional limitations. Methods Four hundred and thirty-five participants aged 65+ years old with functional limitations were recruited from the Multicenter Osteoarthritis Study, a prospective study of community-dwelling adults with or at risk of developing symptomatic knee osteoarthritis. Presence of community barriers and facilitators was ascertained by the Home and Community Environment survey. Two domains of disability, (a) daily activity limitation (DAL) and (b) daily activity frequency (DAF), were assessed with the Late-Life Disability Instrument. Covariates included age, gender, education, race, comorbidity, body mass index, knee pain, and functional limitation. Multivariable logistic regression was used to examine adjusted associations of community factors with presence of DAL and DAF. Results Approximately one third of the participants lived in a community with high mobility barriers and low transportation facilitators. High mobility barriers was associated with greater odds of DAL (odds ratio [OR] = 2.0, 95% confidence interval [CI] 1.23.1) after adjusting for covariates, and high transportation facilitators was associated with lower odds of DAL (OR = 0.5, 95% CI 0.30.8) but not with DAF in adjusted models. Conclusion People with functional limitations who live in communities that were more restrictive felt more limited in doing daily activities but did not perform these daily activities any less frequently. PMID:19995830

  15. Two photon microscopy for studies of xenobiotics in human skin

    NASA Astrophysics Data System (ADS)

    Simonsson, Carl; Smedh, Maria; Jonson, Charlotte; Karlberg, Ann-Therese; Ericson, Marica B.

    2007-07-01

    For successful uptake and distribution of drugs from transdermal formulations, it is important to understand the skin barrier function. Innovative advances in modern microscopy have provided valuable tools to study the interaction between the skin and xenobiotics. Two-photon microscopy (TPM) allows non-invasive visualization of fluorescent compounds in the skin. The advantages of TPM over conventional confocal microscopy are better light penetration into highly scattering and absorbing tissue such as human skin, improved detection efficiency, limited out of focus photobleaching and reduced phototoxic effects. We present TPM as an alternative non-invasive in vitro method to study chemical penetration enhancement of fluorescent model drugs. The permeability of sulforhodamine B (SRB) through human epidermis was measured with vertical diffusion cells. The absorption was visualized using TPM after 24 h passive diffusion. We have evaluated variations in physicochemical parameters controlling dermal drug uptake induced by the penetration enhancer oleic acid according to methods previously described by Yu et al. Optical sectioning by TPM was compared with cryosectioning. Oleic acid significantly increased penetration of sulforhodamine. TPM images demonstrate a four-fold increase in the partition coefficient. In addition, a six-fold increase in the concentration gradient was found over stratum corneum. Better light penetration and detection efficiency increase maximum imaging depth in TPM compared to conventional confocal microscopy, however loss of signal due to scattering and absorption is still significant and will affect distribution profiles generated by optical sectioning. A true concentration profile cannot be established without better knowledge about signal losses in the skin.

  16. Antisense tools for functional studies of human Argonaute proteins.

    PubMed

    Mescalchin, Alessandra; Detzer, Anke; Weirauch, Ulrike; Hahnel, Maximilian J; Engel, Christina; Sczakiel, Georg

    2010-12-01

    The Argonaute proteins play essential roles in development and cellular metabolism in many organisms, including plants, flies, worms, and mammals. Whereas in organisms such as Caenorhabditis elegans and Arabidopsis thaliana, creation of Argonaute mutant strains allowed the study of their biological functions, in mammals the application of this approach is limited by its difficulty and in the specific case of Ago2 gene, by the lethality of such mutation. Hence, in human cells, functional studies of Ago proteins relied on phenotypic suppression using small interfering RNA (siRNA) which involves Ago proteins and the RNA interference mechanism. This bears the danger of undesired or unknown interference effects which may lead to misleading results. Thus, alternative methods acting by different regulatory mechanisms would be advantageous in order to exclude unspecific effects. The knockdown may be achieved by using specific antisense oligonucleotides (asONs) which act via an RNase H-dependent mechanism, not thought to interfere with processes in which Agos are involved. Different functional observations in the use of siRNA versus asONs indicate the relevance of this assumption. We developed asONs specific for the four human Agos (hAgos) and compared their activities with those obtained by siRNA. We confirm that hAgo2 is involved in microRNA (miRNA)- and in siRNA-mediated silencing pathways, while the other hAgos play a role only in miRNA-based gene regulation. Using combinations of asONs we found that the simultaneous down-regulation of hAgo1, hAgo2, and hAgo4 led to the strongest decrease in miRNA activity, indicating a main role of these proteins. PMID:20935067

  17. Theoretical assessment of the maximum obtainable power in wireless power transfer constrained by human body exposure limits in a typical room scenario.

    TOXLINE Toxicology Bibliographic Information

    Chen XL; De Santis V; Umenei AE

    2014-07-07

    In this study, the maximum received power obtainable through wireless power transfer (WPT) by a small receiver (Rx) coil from a relatively large transmitter (Tx) coil is numerically estimated in the frequency range from 100 kHz to 10 MHz based on human body exposure limits. Analytical calculations were first conducted to determine the worst-case coupling between a homogeneous cylindrical phantom with a radius of 0.65 m and a Tx coil positioned 0.1 m away with the radius ranging from 0.25 to 2.5 m. Subsequently, three high-resolution anatomical models were employed to compute the peak induced field intensities with respect to various Tx coil locations and dimensions. Based on the computational results, scaling factors which correlate the cylindrical phantom and anatomical model results were derived. Next, the optimal operating frequency, at which the highest transmitter source power can be utilized without exceeding the exposure limits, is found to be around 2 MHz. Finally, a formulation is proposed to estimate the maximum obtainable power of WPT in a typical room scenario while adhering to the human body exposure compliance mandates.

  18. Theoretical assessment of the maximum obtainable power in wireless power transfer constrained by human body exposure limits in a typical room scenario.

    PubMed

    Chen, Xi Lin; De Santis, Valerio; Umenei, Aghuinyue Esai

    2014-07-01

    In this study, the maximum received power obtainable through wireless power transfer (WPT) by a small receiver (Rx) coil from a relatively large transmitter (Tx) coil is numerically estimated in the frequency range from 100 kHz to 10 MHz based on human body exposure limits. Analytical calculations were first conducted to determine the worst-case coupling between a homogeneous cylindrical phantom with a radius of 0.65 m and a Tx coil positioned 0.1 m away with the radius ranging from 0.25 to 2.5 m. Subsequently, three high-resolution anatomical models were employed to compute the peak induced field intensities with respect to various Tx coil locations and dimensions. Based on the computational results, scaling factors which correlate the cylindrical phantom and anatomical model results were derived. Next, the optimal operating frequency, at which the highest transmitter source power can be utilized without exceeding the exposure limits, is found to be around 2 MHz. Finally, a formulation is proposed to estimate the maximum obtainable power of WPT in a typical room scenario while adhering to the human body exposure compliance mandates. PMID:24889372

  19. Theoretical assessment of the maximum obtainable power in wireless power transfer constrained by human body exposure limits in a typical room scenario

    NASA Astrophysics Data System (ADS)

    Chen, Xi Lin; De Santis, Valerio; Esai Umenei, Aghuinyue

    2014-07-01

    In this study, the maximum received power obtainable through wireless power transfer (WPT) by a small receiver (Rx) coil from a relatively large transmitter (Tx) coil is numerically estimated in the frequency range from 100 kHz to 10 MHz based on human body exposure limits. Analytical calculations were first conducted to determine the worst-case coupling between a homogeneous cylindrical phantom with a radius of 0.65 m and a Tx coil positioned 0.1 m away with the radius ranging from 0.25 to 2.5 m. Subsequently, three high-resolution anatomical models were employed to compute the peak induced field intensities with respect to various Tx coil locations and dimensions. Based on the computational results, scaling factors which correlate the cylindrical phantom and anatomical model results were derived. Next, the optimal operating frequency, at which the highest transmitter source power can be utilized without exceeding the exposure limits, is found to be around 2 MHz. Finally, a formulation is proposed to estimate the maximum obtainable power of WPT in a typical room scenario while adhering to the human body exposure compliance mandates.

  20. MEG studies of human vision: Retinotopic organization of V1

    SciTech Connect

    Aine, C.; George, J.; Ranken, D.; Best, E.; Tiee, W.; Vigil, V.; Flynn, E.; Wood, C.; Supek, S.

    1993-12-31

    A primary goal of noninvasive studies of human vision is to identify and characterize multiple visual areas in the human brain analogous to those identified in studies of nonhuman primates. By combining functional MEG measurements with images of individual anatomy derived from MRI, the authors hope to determine the location and arrangement of multiple visual areas in human cortex and to probe their functional significance. The authors have identified several different visual areas thus far which appear to be topographically organized. This paper focuses on the retinotopic characterization of the primary visual area (V1) in humans.

  1. Rabbit models for the study of human atherosclerosis: from pathophysiological mechanisms to translational medicine

    PubMed Central

    Fan, Jianglin; Kitajima, Shuji; Watanabe, Teruo; Xu, Jie; Zhang, Jifeng; Liu, Enqi; Chen, Y. Eugene

    2014-01-01

    Laboratory animal models play an important role in the study of human diseases. Using appropriate animals is critical not only for basic research but also for the development of therapeutics and diagnostic tools. Rabbits are widely used for the study of human atherosclerosis. Because rabbits have a unique feature of lipoprotein metabolism (like humans but unlike rodents) and are sensitive to a cholesterol diet, rabbit models have not only provided many insights into the pathogenesis and development of human atherosclerosis but also made a great contribution to translational research. In fact, rabbit was the first animal model used for studying human atherosclerosis, more than a century ago. Currently, three types of rabbit model are commonly used for the study of human atherosclerosis and lipid metabolism: (1) cholesterol-fed rabbits, (2) Watanabe heritable hyperlipidemic rabbits, analogous to human familial hypercholesterolemia due to genetic deficiency of LDL receptors, and (3) genetically modified (transgenic and knock-out) rabbits. Despite their importance, compared with the mouse, the most widely used laboratory animal model nowadays, the use of rabbit models is still limited. In this review, we focus on the features of rabbit lipoprotein metabolism and pathology of atherosclerotic lesions that make it the optimal model for human atherosclerotic disease, especially for the translational medicine. For the sake of clarity, the review is not an attempt to be completely inclusive, but instead attempts to summarize substantial information concisely and provide a guideline for experiments using rabbits. PMID:25277507

  2. Epidemiological study of zoonoses derived from humans in captive chimpanzees.

    PubMed

    Kooriyama, Takanori; Okamoto, Michiko; Yoshida, Tomoyuki; Nishida, Toshisada; Tsubota, Toshio; Saito, Akatsuki; Tomonaga, Masaki; Matsuzawa, Tetsuro; Akari, Hirofumi; Nishimura, Hidekazu; Miyabe-Nishiwaki, Takako

    2013-01-01

    Emerging infectious diseases (EIDs) in wildlife are major threats both to human health and to biodiversity conservation. An estimated 71.8% of zoonotic EID events are caused by pathogens in wildlife and the incidence of such diseases is increasing significantly in humans. In addition, human diseases are starting to infect wildlife, especially non-human primates. The chimpanzee is an endangered species that is threatened by human activity such as deforestation, poaching, and human disease transmission. Recently, several respiratory disease outbreaks that are suspected of having been transmitted by humans have been reported in wild chimpanzees. Therefore, we need to study zoonotic pathogens that can threaten captive chimpanzees in primate research institutes. Serological surveillance is one of several methods used to reveal infection history. We examined serum from 14 captive chimpanzees in Japanese primate research institutes for antibodies against 62 human pathogens and 1 chimpanzee-borne infectious disease. Antibodies tested positive against 29 pathogens at high or low prevalence in the chimpanzees. These results suggest that the proportions of human-borne infections may reflect the chimpanzee's history, management system in the institute, or regional epidemics. Furthermore, captive chimpanzees are highly susceptible to human pathogens, and their induced antibodies reveal not only their history of infection, but also the possibility of protection against human pathogens. PMID:22890486

  3. Limiting Nonresponse in Longitudinal Research: Three Strategies for School-Based Studies. A RAND Note.

    ERIC Educational Resources Information Center

    Ellickson, Phyllis L.

    Longitudinal studies conducted with children typically experience non-response problems that can make substantial inroads on sample size and introduce bias into the analysis. Three methods for limiting non-response in school-based research programs were assessed: (1) asking parents to return consent forms only if they do not want their children to…

  4. COMPARATIVE KINETIC STUDIES OF PHOSPHATE-LIMITED GROWTH AND PHOSPHATE UPTAKE IN PHYTOPLANKTON IN CONTINUOUS CULTURE

    EPA Science Inventory

    A comparative kinetic study of phosphate-limited growth and phosphate uptake was carried out in chemostat cultures of Anabaena flos-aquae Lyng. Breb., Ankistrodesmus falcatus (Corda) Ralfs, Asterionella formosa Hass., Fragilaria crotonensis Kitt., and Microcystis sp. Lemm. For ea...

  5. Review of DIII-D H-Mode Density Limit Studies

    SciTech Connect

    Maingi, R.; Mahdavi, M.A.

    2005-10-15

    Density limit studies over the past 10 yr on DIII-D have successfully identified several processes that limit plasma density in various operating modes. The recent focus of these studies has been on maintenance of the high-density operational window with good H-mode level energy confinement. We find that detachment and onset of multifaceted axisymmetric radiation from the edge (MARFE), fueling efficiency, particle confinement, and magnetohydrodynamic activity can impose density limits in certain regimes. By studying these processes, we have devised techniques with either pellets or gas fueling and divertor pumping to achieve line average density above Greenwald scaling, relying on increasing the ratio of pedestal to separatrix density, as well as density profile peaking. The scaling of several of these processes to next-step devices (e.g., the International Thermonuclear Experimental Reactor) has indicated that sufficiently high pedestal density can be achieved with conventional fueling techniques while ensuring divertor partial detachment needed for heat flux reduction. One density limit process requiring further study is neoclassical tearing mode (NTM) onset, and techniques for avoidance/mitigation of NTMs need additional development in present-day devices operated at high density.

  6. Descriptive Study of Services to Limited English Proficient Students. Volume 2: Survey Results.

    ERIC Educational Resources Information Center

    Hopstock, Paul J.; Bucaro, Bonnie J.; Fleischman, Howard L.; Zehler, Annette M.; Eu, Hongsook

    The report presents results of a study of: the type, content, duration, and intensity of instructional services provided to limited-English-proficient (LEP) students in the United States; administrative procedures associated with these services (including procedures for identifying students for entry into and exit from these special services); the

  7. Descriptive Study of Services to Limited English Proficient Students, Volume 1. Summary of Findings and Conclusions.

    ERIC Educational Resources Information Center

    Fleischman, Howard L.; Hopstock, Paul J.

    This report summarizes a study of: the type, content, duration, and intensity of instructional services provided to limited-English-proficient (LEP) students in the United States; administrative procedures associated with these services (including procedures for identifying students for entry into and exit from these special services); the

  8. 78 FR 76888 - MAP-21 Comprehensive Truck Size and Weight Limits Study Materials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-19

    ... were referenced in a notice published on November 29, 2013, at 78 FR 71707. The original meeting notice..., 2013, at 78 FR 71707, the FHWA published in the Federal Register a notice to announce two upcoming... Federal Highway Administration MAP-21 Comprehensive Truck Size and Weight Limits Study Materials...

  9. Scientific Study of Malnutrition as a Limiting Factor in the Development of Education.

    ERIC Educational Resources Information Center

    Picasso de Oyague, Alfredo

    This study on malnutrition as a limiting factor in the development of education (and, hence, in socioeconomic development generally) was presented to the UNESCO Seminar on Education, Nutrition, Agriculture and Man. The paper reports on recent research showing that the development of the central nervous system in very young children (including the…

  10. Limiting Nonresponse in Longitudinal Research: Three Strategies for School-Based Studies. A RAND Note.

    ERIC Educational Resources Information Center

    Ellickson, Phyllis L.

    Longitudinal studies conducted with children typically experience non-response problems that can make substantial inroads on sample size and introduce bias into the analysis. Three methods for limiting non-response in school-based research programs were assessed: (1) asking parents to return consent forms only if they do not want their children to

  11. Helium exhaust and transport studies with the ALT-II pump limiter in the TEXTOR tokamak

    NASA Astrophysics Data System (ADS)

    Hillis, D. L.; Finken, K. H.; Hogan, J. T.; Dippel, K. H.; Moyer, R. A.; Pospieszczyk, A.; Rusbldt, D.; Akaishi, K.; Conn, R. W.; Euringer, H.; Gray, D. S.; Horton, L. D.; Hulse, R. A.; Isler, R. C.; Klepper, C. C.; Mioduszewski, P. K.; Miyahara, A.; Wolf, G. H.

    1990-11-01

    The first encouraging experiments demonstrating direct, explicit control of the He2+ density in a tokamak plasma have been performed in the TEXTOR tokamak with the Advanced Limiter Test-II pump limiter. Helium is injected in a short gas puff from the outside of the plasma, is observed to reach the plasma core, and then is readily removed from the plasma. An exhaust efficiency of ~8% is obtained. Active charge-exchange spectroscopy is used to study the exhaust and transport of He2+ within the plasma, and the density evolution is modeled with a diffusive-convective transport code.

  12. A human laboratory pilot study with baclofen in alcoholic individuals

    PubMed Central

    Leggio, Lorenzo; Zywiak, William H.; McGeary, John E.; Edwards, Steven; Fricchione, Samuel R.; Shoaff, Jessica R.; Addolorato, Giovanni; Swift, Robert M.; Kenna, George A.

    2015-01-01

    Preclinical and clinical studies show that the GABAB receptor agonist baclofen may represent a pharmacotherapy for alcohol dependence (AD). However, the mechanisms by which baclofen affects drinking are not well characterized; thus this pilot study investigated possible baclofens biobehavioral mechanisms. The design was a double-blind controlled randomized human laboratory pilot study. Fourteen non-treatment seeking alcohol-dependent heavy drinking subjects received either baclofen 10 mg t.i.d. or an active placebo (cyproheptadine 2 mg t.i.d., to control for sedation) for a 7-day period. At day 8, participants performed an alcohol cue-reactivity (CR) followed by an alcohol self-administration (ASA). Additionally, we explored possible moderators that might guide future larger studies, i.e. anxiety, family history and onset of alcoholism, and D4 dopamine receptor (DRD4) and 5-HTTLPR polymorphisms. The main results were a significant effect of baclofen for increasing stimulation (p=.001) and sedation (p<.01). Furthermore, when drinking during the ASA and the 2 days before was analyzed as a composite variable, there was a significant effect of baclofen to reduce alcohol consumption (p<.01). As for the exploratory analyses, baclofens effects to increase alcohol sedation and to reduce alcohol consumption were limited to those individuals with DRD4 ?7 repeats (DRD4L). Yet, baclofens effects on alcohol consumption were also moderated by 5-HTTLPR LL genotype. In conclusion, baclofens ability to reduce alcohol drinking may be related to its effects on the biphasic effects of alcohol, but larger studies are needed to confirm these preliminary findings. PMID:23262301

  13. The ability of animal studies to detect serious post marketing adverse events is limited.

    PubMed

    van Meer, Peter J K; Kooijman, Marlous; Gispen-de Wied, Christine C; Moors, Ellen H M; Schellekens, Huub

    2012-12-01

    The value of animal studies to assess drug safety is unclear because many such studies are biased and have methodological shortcomings. We studied whether post-marketing serious adverse reactions to small molecule drugs could have been detected on the basis of animal study data included in drug registration files. Of 93 serious adverse reactions related to 43 small molecule drugs, only 19% were identified in animal studies as a true positive outcome, which suggests that data from animal studies are of limited value to pharmacovigilance activities. Our study shows that drug registration files can be used to study the predictive value of animal studies and that the value of animal studies in all stages of the drug development should be investigated in a collaborative endeavour between regulatory authorities, industry, and academia. PMID:22982732

  14. Human Needs and Human Interdependence. Social Studies Interim Grade Guide for Grade One.

    ERIC Educational Resources Information Center

    Manitoba Dept. of Education, Winnipeg. Curriculum Development Branch.

    The social studies curriculum for grade 1 in Manitoba, Canada is presented. The focus of this guide is human needs and human interdependence. Some objectives are to explore: (1) distinctions between needs and wants; (2) various groupings and relationships, such as families, friendships, and communities; (3) ways people are dependent upon their…

  15. Z-scan studies and optical limiting of nanosecond laser pulses in neutral red dye

    NASA Astrophysics Data System (ADS)

    George, Mathew; Muneera, C. I.; Singh, C. P.; Bindra, K. S.; Oak, S. M.

    2008-03-01

    The nonlinear optical absorption, refraction and optical limiting behaviour of an organic dye, neutral red, were investigated under excitation with nanosecond laser pulses at 532 nm. The nonlinear optical responses of the material were studied both in solution and solid film, made in methanol and polyvinyl alcohol, respectively, using single-beam Z-scan technique. The open aperture Z-scans of the solution samples displayed a switch over from saturable absorption to enhanced absorption with increase in input intensity. Theoretical fit to the experimental data indicated that the dominant mechanism of nonlinear absorption is two-photon absorption. The closed aperture Z-scans of both the samples denoted positive nonlinearity, which was three orders larger in magnitude in solid film, compared with that in solution. The results of optical limiting experiments revealed that neutral red exhibited strong optical limiting of nanosecond laser pulses with a threshold lower than that of C 60 in toluene.

  16. Human Ecology. Study Guide and Course Outline.

    ERIC Educational Resources Information Center

    Zaki, Gamal

    An inservice course offered to elementary and secondary teachers and other concerned citizens in Rhode Island was presented in fifteen television programs. This study guide includes a description of the fifteen sessions. For each there is given a brief introduction and summary, an outline, questions for further study, and a bibliography of

  17. No monkey business: why studying NK cells in non-human primates pays off.

    PubMed

    Hong, Henoch S; Rajakumar, Premeela A; Billingsley, James M; Reeves, R Keith; Johnson, R Paul

    2013-01-01

    Human NK (hNK) cells play a key role in mediating host immune responses against various infectious diseases. For practical reasons, the majority of the data on hNK cells has been generated using peripheral blood lymphocytes. In contrast, our knowledge of NK cells in human tissues is limited, and not much is known about developmental pathways of hNK cell subpopulations in vivo. Although research in mice has elucidated a number of fundamental features of NK cell biology, mouse, and hNK cells significantly differ in their subpopulations, functions, and receptor repertoires. Thus, there is a need for a model that is more closely related to humans and yet allows experimental manipulations. Non-human primate models offer numerous opportunities for the study of NK cells, including the study of the role of NK cells after solid organ and stem cell transplantation, as well as in acute viral infection. Macaque NK cells can be depleted in vivo or adoptively transferred in an autologous system. All of these studies are either difficult or unethical to carry out in humans. Here we highlight recent advances in rhesus NK cell research and their parallels in humans. Using high-throughput transcriptional profiling, we demonstrate that the human CD56(bright) and CD56(dim) NK cell subsets have phenotypically and functionally analogous counterparts in rhesus macaques. Thus, the use of non-human primate models offers the potential to substantially advance hNK cell research. PMID:23423644

  18. Ethics of studies involving human volunteers. I. Historical background.

    PubMed

    Carson, P A; Holt, J

    2006-01-01

    The evaluation of personal products using panels of human volunteers is crucial to the continued development of the industry. Nowadays, however, it is increasingly important to ensure that such studies are both safe for the participants and are ethical. As a means of defining general rules for judging and justifying the ethics of human testing, historical milestones in the development of human experimentation are given. While most experience originates from biomedical research, findings help establish standards of ethical review of non-therapeutic human testing used in the cosmetics industry. PMID:16832572

  19. Automated Essay Scoring versus Human Scoring: A Correlational Study

    ERIC Educational Resources Information Center

    Wang, Jinhao; Brown, Michelle Stallone

    2008-01-01

    The purpose of the current study was to analyze the relationship between automated essay scoring (AES) and human scoring in order to determine the validity and usefulness of AES for large-scale placement tests. Specifically, a correlational research design was used to examine the correlations between AES performance and human raters' performance.

  20. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 25 2012-07-01 2012-07-01 false Human epidemiological and exposure... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns... that a correlation may exist between exposure to a pesticide and observed adverse effects in...

  1. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 25 2013-07-01 2013-07-01 false Human epidemiological and exposure... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns... that a correlation may exist between exposure to a pesticide and observed adverse effects in...

  2. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 24 2014-07-01 2014-07-01 false Human epidemiological and exposure... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns... that a correlation may exist between exposure to a pesticide and observed adverse effects in...

  3. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 24 2011-07-01 2011-07-01 false Human epidemiological and exposure... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns... that a correlation may exist between exposure to a pesticide and observed adverse effects in...

  4. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Human epidemiological and exposure... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns... that a correlation may exist between exposure to a pesticide and observed adverse effects in...

  5. Humans as a Case Study for the Evidence of Evolution.

    ERIC Educational Resources Information Center

    Nickels, Martin

    1998-01-01

    Discusses the strengths of the many lines of scientific evidence supporting the idea of human evolution and the importance of the agreement that exists between them. Argues that using humans as a case study in evolution allows educators to illustrate broader aspects of the nature of science and how the overall strength of any scientific

  6. Human Rights and History Education: An Australian Study

    ERIC Educational Resources Information Center

    Burridge Nina; Buchanan, John; Chodkiewicz, Andrew

    2014-01-01

    The place of education for and about human rights within the school curriculum remains contested and this paper reports on the first national cross-sectoral investigation of its place in Australian curricula and more specifically in national and state History curriculum documents. Opportunities for the inclusion of human rights based studies were…

  7. Comparative Analysis, Global Policy Studies and the Human Condition.

    ERIC Educational Resources Information Center

    Bertsch, Gary K.

    This paper examines the role that comparative analysis and global policy studies can play in explaining the human condition in the contemporary world. It investigates economic well-being, one dimension of the human condition, and examines some of the attributes that represent it and some of the forces that affect it in villages, social groupings,

  8. The human ecological approach to the study of population dynamics.

    PubMed

    Namboodiri, K

    1994-01-01

    Human ecology is a specialization of ecology, tailored to suit the characteristic features of human populations. This essay focuses upon human ecology as set forth by Hawley and Duncan, although other conceptualizations are referred to. The bio-ecological framework is described together with an introduction of the distinction between population ecology and community ecology. Bio-ecology is an important subdiscipline of biology, but its subject has never been as complex as that of human ecology. Human ecologists developed their own theoretical framework distinct from that of bio-ecology. The author briefly outlines the history of human ecology, emphasizing the initial phase of the Chicago School, which focused upon spatial patterns of human phenomena, and the succeeding one, in which a reorientation focused upon the organizational aspects of population dynamics. The author then reviews some of the basic features of human ecology, discusses population ecology and its applications, with reference to the study of populations of households, and outlines the use of graph theory, input-output frameworks, and multilevel modeling to improve the formal and methodological aspects of human ecology. The spatial concern of human ecology is considered and situated in a broader context. PMID:12290834

  9. Further studies of human whole-body radiofrequency absorption rates.

    PubMed

    Hill, D A

    1985-01-01

    Further studies of human whole-body radiofrequency (RF) absorption rates were carried out using a TEM-cell exposure system. Experiments were done at one frequency near the grounded resonance frequency (approximately 40 MHz), and at several below-resonance frequencies. Absorption rates are small for the K and H orientations of the body, even when grounded. For the body trunk in an E orientation, the absorption rate of a sitting person is about half of the rate for the same person standing with arms at the sides; the latter in turn is about half the rate for the same subject standing with arms over the head. Two-body interactions cause no increase in absorption rates for grounded people. They do, however, increase the absorption rates for subjects in an E orientation in free space; the largest interaction occurs when one subject is lambda/2 behind the other (as seen by the incident wave). When these results are applied to practical occupational exposure situations, the whole-body specific absorption rate does not exceed the ANSI limit of 0.4 W/kg for exposures permitted by the ANSI standard (C95.1-1982) at frequencies from 7 to 40 MHz. PMID:3977967

  10. Development of humanized mouse models to study human malaria parasite infection

    PubMed Central

    Vaughan, Ashley M; Kappe, Stefan HI; Ploss, Alexander; Mikolajczak, Sebastian A

    2013-01-01

    Malaria is a disease caused by infection with Plasmodium parasites that are transmitted by mosquito bite. Five different species of Plasmodium infect humans with severe disease, but human malaria is primarily caused by Plasmodium falciparum. The burden of malaria on the developing world is enormous, and a fully protective vaccine is still elusive. One of the biggest challenges in the quest for the development of new antimalarial drugs and vaccines is the lack of accessible animal models to study P. falciparum infection because the parasite is restricted to the great apes and human hosts. Here, we review the current state of research in this field and provide an outlook of the development of humanized small animal models to study P. falciparum infection that will accelerate fundamental research into human parasite biology and could accelerate drug and vaccine design in the future. PMID:22568719

  11. Mathematical modelling of [C]-(+)-PHNO human competition studies.

    PubMed

    Searle, Graham E; Beaver, John D; Tziortzi, Andri; Comley, Robert A; Bani, Massimo; Ghibellini, Giulia; Merlo-Pich, Emilio; Rabiner, Eugenii A; Laruelle, Marc; Gunn, Roger N

    2013-03-01

    The D(2)/D(3) agonist radioligand [(11)C]-(+)-PHNO is currently the most suitable D(3) imaging agent available, despite its limited selectivity for the D(3) over the D(2). Given the collocation of D(2) and D(3) receptors, and generally higher densities of D(2), the separation of D(2) and D(3) information from [(11)C]-(+)-PHNO PET data are somewhat complex. This complexity is compounded by recent data suggesting that [(11)C]-(+)-PHNO PET scans might be routinely performed in non-tracer conditions (with respect to D(3) receptors), and that the cerebellum (used as a reference region) might manifest some displaceable binding signal. Here we present the modelling and analysis of data from two human studies which employed an adequate dose range of selective D(3) antagonists (GSK598809 and GSK618334) to interrogate the [(11)C]-(+)-PHNO PET signal. Models describing the changes observed in the PET volume of distribution (V(T)) and binding potential (BP(ND)) were used to identify and quantify a [(11)C]-(+)-PHNO mass dose effect at the D(3), and displaceable signal in the cerebellum, as well as providing refined estimates of regional D(3) fractions of [(11)C]-(+)-PHNO BP(ND). The dose of (+)-PHNO required to occupy half of the available D(3) receptors (ED(50)(PHNO,D3)) was estimated as 40ng/kg, and the cerebellum BP(ND) was estimated as 0.40. These findings confirm that [(11)C]-(+)-PHNO human PET studies are in fact routinely performed under non-tracer conditions. This suggests that (+)-PHNO injection masses should be minimised and tightly controlled in order to mitigate the mass dose effect. The specific binding detected in the cerebellum was modest but could have a significant effect, for example on estimates of D(3) potency in drug occupancy studies. A range of methods for the analysis of future [(11)C]-(+)-PHNO data, incorporating models for the effects quantified here, were developed and evaluated. The comparisons and conclusions drawn from these can inform the design and analysis of future PET studies with [(11)C]-(+)-PHNO. PMID:23207573

  12. Space station human productivity study, volume 1

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The primary goal was to develop design and operations requirements for direct support of intra-vehicular activity (IVA) crew performance and productivity. It was recognized that much work had already been accomplished which provided sufficient data for the definition of the desired requirements. It was necessary, therefore, to assess the status of such data to extract definable requirements, and then to define the remaining study needs. The explicit objectives of the study were to: review existing data to identify potential problems of space station crew productivity and to define requirements for support of productivity insofar as they could be justified by current information; identify those areas that lack adequate data; and prepare plans for managing studies to develop the lacking data, so that results can be input to the space station program in a timely manner.

  13. The limited capacity of humans to identify the components of taste mixtures and taste-odour mixtures.

    PubMed

    Laing, David G; Link, Catherine; Jinks, Anthony L; Hutchinson, Ian

    2002-01-01

    The capacity of humans to identify the components of taste mixtures and odour-taste mixtures was investigated in two experiments. Subjects were trained to identify the components presented alone and to use a 'yes/no' procedure to identify them in mixtures. All stimuli were presented with a retronasal (by mouth) technique. A maximum of three tastants were identified in both types of mixtures, only one tastant was identified in five-component taste mixtures, and no component was identified in four-component odour-taste mixtures. Importantly, in no instance was the olfactory stimulus identified in any mixture with tastes, including binary mixtures. Loss of identity of the odorant in binary and ternary mixtures may have been due to suppression as a consequence of temporal processing, or to the absence of an association between the odorant and tastants that had established an identifiable percept. In contrast, poor identification of the components of the quaternary odour-taste mixture and quinternary taste mixture is attributed to the limited capacity of working memory. Overall, the poorer ability to identify components in odour-taste mixtures than in taste mixtures indicates that interactions occurred between the two senses, challenging the proposal that odours and tastes are processed independently when present in complex chemosensory stimuli. PMID:12044101

  14. A review on thiazolidinediones and bladder cancer in human studies.

    PubMed

    Tseng, Chin-Hsiao

    2014-01-01

    There is a concern of an increased risk of bladder cancer associated with the use of thiazolidinediones, a class of oral glucose-lowering drugs commonly used in patients with type 2 diabetes with a mechanism of improving insulin resistance. Human studies on related issues are reviewed, followed by a discussion on potential concerns on the causal inference in current studies. Pioglitazone and rosiglitazone are discussed separately, and findings from different geographical regions are presented. Randomized controlled trials designed for primarily answering such a cancer link are lacking, and evidence from clinical trials with available data for evaluating the association may not be informative. Observational studies have been reported with the use of population-based administrative databases, single-hospital records, drug adverse event reporting system, and case series collection. Meta-analysis has also been performed by six different groups of investigators. These studies showed a signal of higher risk of bladder cancer associated with pioglitazone, especially at a higher cumulative dose or after prolonged exposure; however, a weaker signal or null association is observed with rosiglitazone. In addition, there are some concerns on the causal inference, which may be related to the use of secondary databases, biases in sampling, differential detection, and confounding by indications. Lack of full control of smoking and potential biases related to study designs and statistical approaches such as prevalent user bias and immortal time bias may be major limitations in some studies. Overlapping populations and opposing conclusions in studies using the same databases may be of concern and weaken the reported conclusions of the studies. Because randomized controlled trials are expensive and unethical in providing an answer to this cancer issue, observational studies are expected to be the main source in providing an answer in the future. Furthermore, international comparison studies using well-designed and uniform methodology to clarify the risk in specific sexes, ethnicities, and other subgroups and to evaluate the interaction with other environmental risk factors or medications will be helpful to identify patients at risk. PMID:24598039

  15. Lesson Study as a Human Science

    ERIC Educational Resources Information Center

    Lewis, Catherine C.; Akita, Kiyomi; Sato, Manabu

    2010-01-01

    Neither experimental nor design research in education is as well developed in Japan as in the United States. Yet Japanese educational practice employs a type of educational research called "lesson study" that is credited for instructional improvements, including the shift from "teaching as telling" to "teaching for understanding" in science and

  16. Use of human pluripotent stem cells to study and treat retinopathies

    PubMed Central

    Ben MBarek, Karim; Regent, Florian; Monville, Christelle

    2015-01-01

    Human cell types affected by retinal diseases (such as age-related macular degeneration or retinitis pimentosa) are limited in cell number and of reduced accessibility. As a consequence, their isolation for in vitro studies of disease mechanisms or for drug screening efforts is fastidious. Human pluripotent stem cells (hPSCs), either of embryonic origin or through reprogramming of adult somatic cells, represent a new promising way to generate models of human retinopathies, explore the physiopathological mechanisms and develop novel therapeutic strategies. Disease-specific human embryonic stem cells were the first source of material to be used to study certain disease states. The recent demonstration that human somatic cells, such as fibroblasts or blood cells, can be genetically converted to induce pluripotent stem cells together with the continuous improvement of methods to differentiate these cells into disease-affected cellular subtypes opens new perspectives to model and understand a large number of human pathologies, including retinopathies. This review focuses on the added value of hPSCs for the disease modeling of human retinopathies and the study of their molecular pathological mechanisms. We also discuss the recent use of these cells for establishing the validation studies for therapeutic intervention and for the screening of large compound libraries to identify candidate drugs. PMID:25914766

  17. Large prospective birth cohort studies on environmental contaminants and child health Goals, challenges, limitations and needs

    PubMed Central

    Luo, Zhong-Cheng; Liu, Jian-Meng; Fraser, William D.

    2011-01-01

    SUMMARY The adverse health effects of environmental contaminants (ECs) are a rising public health concern, and a major threat to sustainable socioeconomic development. The developing fetuses and growing children are particularly vulnerable to the adverse effects of ECs. However, assessing the health impact of ECs presents a major challenge, given that multiple outcomes may arise from one exposure, multiple exposures may result in one outcome, and the complex interactions between ECs, and between ECs, nutrients and genetic factors, and the dynamic temporal changes in EC exposures during the life course. Large-scale prospective birth cohort studies collecting extensive data and specimen starting from the prenatal or pre-conception period, although costly, hold promise as a means to more clearly quantify the health effects of ECs, and to unravel the complex interactions between ECs, nutrients and genotypes. A number of such large-scale studies have been launched in some developed counties. We present an overview of why, what and how behind these efforts with an objective to uncover major unidentified limitations and needs. Three major limitations were identified: (1) limited data and bio-specimens regarding early life EC exposure assessments in some birth cohort studies; (2) heavy participant burdens in some birth cohort studies may bias participant recruitment, and risk substantial loss to follow-up, protocol deviations limiting the quality of data and specimens collection, with an overall potential bias towards the null effect; (3) lack of concerted efforts in building comparable birth cohorts across countries to take advantage of natural experiments (large EC exposure level differences between countries) for more in-depth assessments of doseresponse relationships, threshold exposure levels, and positive and negative effect modifiers. Addressing these concerns in current or future large-scale birth cohort studies may help to produce better evidence on the health effects of ECs. PMID:19765909

  18. Human Rights Attitude Scale: A Validity and Reliability Study

    ERIC Educational Resources Information Center

    Ercan, Recep; Yaman, Tugba; Demir, Selcuk Besir

    2015-01-01

    The objective of this study is to develop a valid and reliable attitude scale having quality psychometric features that can measure secondary school students' attitudes towards human rights. The study group of the research is comprised by 710 6th, 7th and 8th grade students who study at 4 secondary schools in the centre of Sivas. The study group…

  19. EPA'S HUMAN STUDIES FACILITY AT CHAPEL HILL (BROCHURE)

    EPA Science Inventory

    EPA's Human Studies Facility is distiguished by unique, state-of-the art exposure systems designed for studing the health effects of airborne pollutants. The chambers can deliver most gaseous pollutants at precise concentrations and atmospheric conditions. Instrumentation enable...

  20. USE OF EXHALED BREATH CONDENSATE IN A HUMAN EXPOSURE STUDY

    EPA Science Inventory

    Exhaled breath condensate (EBC) is a noninvasive, repeatable collection technique to sample biomarkers of lung inflammation, oxidative stress, and environmental exposure. It is unclear whether EBC is an effective tool in human environmental exposure studies with multi-day samplin...

  1. Succession of Ephemeral Secondary Forests and Their Limited Role for the Conservation of Floristic Diversity in a Human-Modified Tropical Landscape

    PubMed Central

    van Breugel, Michiel; Hall, Jefferson S.; Craven, Dylan; Bailon, Mario; Hernandez, Andres; Abbene, Michele; van Breugel, Paulo

    2013-01-01

    Both local- and landscape-scale processes drive succession of secondary forests in human-modified tropical landscapes. Nonetheless, until recently successional changes in composition and diversity have been predominantly studied at the patch level. Here, we used a unique dataset with 45 randomly selected sites across a mixed-use tropical landscape in central Panama to study forest succession simultaneously on local and landscape scales and across both life stages (seedling, sapling, juvenile and adult trees) and life forms (shrubs, trees, lianas, and palms). To understand the potential of these secondary forests to conserve tree species diversity, we also evaluated the diversity of species that can persist as viable metapopulations in a dynamic patchwork of short-lived successional forests, using different assumptions about the average relative size at reproductive maturity. We found a deterministic shift in the diversity and composition of the local plant communities as well as the metacommunity, driven by variation in the rate at which species recruited into and disappeared from the secondary forests across the landscape. Our results indicate that dispersal limitation and the successional niche operate simultaneously and shape successional dynamics of the metacommunity of these early secondary forests. A high diversity of plant species across the metacommunity of early secondary forests shows a potential for restoration of diverse forests through natural succession, when trees and fragments of older forests are maintained in the agricultural matrix and land is abandoned or set aside for a long period of time. On the other hand, during the first 32 years the number of species with mature-sized individuals was a relatively small and strongly biased sub-sample of the total species pool. This implies that ephemeral secondary forests have a limited role in the long-term conservation of tree species diversity in human-modified tropical landscapes. PMID:24349283

  2. Succession of ephemeral secondary forests and their limited role for the conservation of floristic diversity in a human-modified tropical landscape.

    PubMed

    van Breugel, Michiel; Hall, Jefferson S; Craven, Dylan; Bailon, Mario; Hernandez, Andres; Abbene, Michele; van Breugel, Paulo

    2013-01-01

    Both local- and landscape-scale processes drive succession of secondary forests in human-modified tropical landscapes. Nonetheless, until recently successional changes in composition and diversity have been predominantly studied at the patch level. Here, we used a unique dataset with 45 randomly selected sites across a mixed-use tropical landscape in central Panama to study forest succession simultaneously on local and landscape scales and across both life stages (seedling, sapling, juvenile and adult trees) and life forms (shrubs, trees, lianas, and palms). To understand the potential of these secondary forests to conserve tree species diversity, we also evaluated the diversity of species that can persist as viable metapopulations in a dynamic patchwork of short-lived successional forests, using different assumptions about the average relative size at reproductive maturity. We found a deterministic shift in the diversity and composition of the local plant communities as well as the metacommunity, driven by variation in the rate at which species recruited into and disappeared from the secondary forests across the landscape. Our results indicate that dispersal limitation and the successional niche operate simultaneously and shape successional dynamics of the metacommunity of these early secondary forests. A high diversity of plant species across the metacommunity of early secondary forests shows a potential for restoration of diverse forests through natural succession, when trees and fragments of older forests are maintained in the agricultural matrix and land is abandoned or set aside for a long period of time. On the other hand, during the first 32 years the number of species with mature-sized individuals was a relatively small and strongly biased sub-sample of the total species pool. This implies that ephemeral secondary forests have a limited role in the long-term conservation of tree species diversity in human-modified tropical landscapes. PMID:24349283

  3. Use of human epidermal cells in the study of carcinogenesis

    SciTech Connect

    Kuroki, T.; Chida, K.; Hosomi, J.; Kondo, S. )

    1989-05-01

    Because of the importance of human cells, particularly human epithelial cells, in cancer research, we have studied certain phases or events of carcinogenesis using human epidermal cells in primary culture. (1) We found that human epidermal cells are capable of metabolizing benzo(a)pyrene. Large inter-individual variations are found in the basal and induced arylhydrocarbon-hydroxylase activities. (2) UV-induced unscheduled DNA synthesis was demonstrated in human epidermal cells on autoradiographs. We also found that DNA repair is defective in epidermal cells isolated from xeroderma pigmentosum by a new explant-outgrowth culture. (3) Human epidermal cells are unique in that there is a large number of binding sites to phorbol esters compared with mouse epidermal cells, but there is no down-regulation. Further, human epidermal cells show essentially negative responses to tumor promoters, i.e., no stimulation of DNA synthesis, sugar uptake, and no induction of ornithine decarboxylase activity. (4) Human epidermal cells contain 1.5 x 10(5) binding sites per cell for epidermal growth factor (EGF), whereas squamous cell carcinomas of skin and oral cavity have larger amounts of EGF receptors in the order of 10(6) per cell. (5) Based on the above results, we attempted to transform human epidermal cells by the treatment with chemical carcinogens, but until now no transformation was obtained. 16 references.

  4. A Guide to Studying Human Hair Follicle Cycling In Vivo.

    PubMed

    Oh, Ji Won; Kloepper, Jennifer; Langan, Ewan A; Kim, Yongsoo; Yeo, Joongyeub; Kim, Min Ji; Hsi, Tsai-Ching; Rose, Christian; Yoon, Ghil Suk; Lee, Seok-Jong; Seykora, John; Kim, Jung Chul; Sung, Young Kwan; Kim, Moonkyu; Paus, Ralf; Plikus, Maksim V

    2016-01-01

    Hair follicles (HFs) undergo lifelong cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative "quiescence" (telogen). Given that HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. Although available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. In this article, we present such a guide, which uses objective, well-defined, and reproducible criteria, and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in suboptimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field. PMID:26763421

  5. Study of ultrasonic attenuation in f-electron systems in the paramagnetic limit of Coulomb interaction

    SciTech Connect

    Shadangi, Asit Ku.; Rout, G. C.

    2015-05-15

    We report here a microscopic model study of ultrasonic attenuation in f-electron systems based on Periodic Anderson Model in which Coulomb interaction is considered within a mean-field approximation for a weak interaction. The Phonon is coupled to the conduction band and f-electrons. The phonon Green's function is calculated by Zubarev's technique of the Green's function method. The temperature dependent ultrasonic attenuation co-efficient is calculated from the imaginary part of the phonon self-energy in the dynamic and long wave length limit. The f-electron occupation number is calculated self-consistently in paramagnetic limit of Coulomb interaction. The effect of the Coulomb interaction on ultrasonic attenuation is studied by varying the phonon coupling parameters to the conduction and f-electrons, hybridization strength, the position of f-level and the Coulomb interaction Strength. Results are discussed on the basis of experimental results.

  6. Reconstructed human epidermis: A model to study the barrier function

    NASA Astrophysics Data System (ADS)

    Barbotteau, Y.; Gontier, E.; Barberet, P.; Cappadoro, M.; De Wever, B.; Habchi, C.; Incerti, S.; Mavon, A.; Moretto, P.; Pouthier, T.; Smith, R. W.; Ynsa, M. D.

    2005-04-01

    The use of in vitro reconstructed human epidermis (RHE) by the cosmetic and pharmaceutical industries is increasing because of its similar physiological mechanisms to native human skin. With the advent of ethic laws on animal experimentation, RHE provides an helpful alternative for the test of formulations. The aim of this study is to check that the RHE mineral status is comparable to that of human native skin by investigating the elemental distributions in the epidermis strata. In addition, possible deleterious effects of the transport on the epidermis ionic content were studied by nuclear microscopy.

  7. Functional Analysis of the Human Genome:. Study of Genetic Disease

    NASA Astrophysics Data System (ADS)

    Tsui, Lap-Chee

    2003-04-01

    I will divide my remarks into 3 parts. First, I will give a brief summary of the Human Genome Project. Second, I will describe our work on human chromosome 7 to illustrate how we could contribute to the Project and disease research. Third, I would like to bring across the argument that study of genetic disease is an integral component of the Human Genome Project. In particular, I will use cystic fibrosis as an example to elaborate why I consider disease study is a part of functional genomics.

  8. The study of human mutation rates

    SciTech Connect

    Neel, J.V.

    1992-01-01

    We will describe recent developments regarding the question of induced mutations in the survivors of the atomic bombings of Hiroshima and Nagasaki. As part of that work we, describe some developments with respect to the Amerindian blood samples collected under DoE sponsorship between 1964 and 1982. Then developments regarding the application of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to the study of genetic variation and mutation affecting protein characteristics. In particular, we will report on the identification and isolation of genes of especial interest as reflected in the behavior of the proteins which they encode.

  9. Exploring the Limits of Trigonometric Functions: Results and Reflections from a Pilot Study

    ERIC Educational Resources Information Center

    Man, Yiu-Kwong; Poon, Kin-Keung

    2014-01-01

    In this paper, we report a pilot study on engaging a group of undergraduate students to explore the limits of sin(x)/x and tan(x)/x as x approaches to 0, with the use of non-graphic scientific calculators. By comparing the results in the pretest and the post-test, we found that the students had improvements in the tested items, which involved the

  10. Numerical study of the long wavelength limit of the Toda lattice

    NASA Astrophysics Data System (ADS)

    Klein, C.; Roidot, K.

    2015-08-01

    We present the first detailed numerical study of the Toda equations in 2???+???1 dimensions in the limit of long wavelengths, both for the hyperbolic and elliptic case. We first study the continuum limit of the Toda equations and solve initial value problems for the resulting system up to the point of gradient catastrophe. It is shown that the break-up of the solution in the hyperbolic case is similar to the shock formation in the Hopf equation, a 1???+???1 dimensional singularity. In the elliptic case, it is found that the break-up is given by a cusp as for the semiclassical system of the focusing nonlinear Schrdinger equation in 1???+???1 dimensions. The full Toda system is then studied for finite small values of the dispersion parameter ? in the vicinity of the shocks of the dispersionless Toda equations. We determine the scaling in ? of the difference between the Toda solution for small ? and the singular solution of the continuum Toda system. In the hyperbolic case, the same scaling proportional to {?2/7} is found as in the small dispersion limit of the Korteweg-de Vries and the defocusing nonlinear Schrdinger equations. In the elliptic case, we obtain the same scaling proportional to {?2/5} as in the semiclassical limit for the focusing nonlinear Schrdinger equation. We also study the formation of dispersive shocks for times much larger than the break-up time in the hyperbolic case. In the elliptic case, an {{L}?} blow-up is observed instead of a dispersive shock for finite times greater than the break-up time. The ? -dependence of the blow-up time is determined.

  11. Cannabis and psychosis/schizophrenia: human studies

    PubMed Central

    Sewell, Richard Andrew; Ranganathan, Mohini

    2010-01-01

    The association between cannabis use and psychosis has long been recognized. Recent advances in knowledge about cannabinoid receptor function have renewed interest in this association. Converging lines of evidence suggest that cannabinoids can produce a full range of transient schizophrenia-like positive, negative, and cognitive symptoms in some healthy individuals. Also clear is that in individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. The mechanisms by which cannabinoids produce transient psychotic symptoms, while unclear may involve dopamine, GABA, and glutamate neurotransmission. However, only a very small proportion of the general population exposed to cannabinoids develop a psychotic illness. It is likely that cannabis exposure is a component cause that interacts with other factors to cause schizophrenia or a psychotic disorder, but is neither necessary nor sufficient to do so alone. Nevertheless, in the absence of known causes of schizophrenia, the role of component causes remains important and warrants further study. Dose, duration of exposure, and the age of first exposure to cannabinoids may be important factors, and genetic factors that interact with cannabinoid exposure to moderate or amplify the risk of a psychotic disorder are beginning to be elucidated. The mechanisms by which exposure to cannabinoids increase the risk for developing a psychotic disorder are unknown. However, novel hypotheses including the role of cannabinoids on neurodevelopmental processes relevant to psychotic disorders are being studied. PMID:19609589

  12. Human Studies of Angiogenic Gene Therapy

    PubMed Central

    Gupta, Rajesh; Tongers, Jrn; Losordo, Douglas W.

    2009-01-01

    Despite significant advances in medical, interventional, and surgical therapy for coronary and peripheral arterial disease, the burden of these illnesses remains high. To address this unmet need, the science of therapeutic angiogenesis has been evolving for almost two decades. Early pre-clinical studies and phase I clinical trials achieved promising results with growth factors administered as recombinant proteins or as single-agent gene therapies, and data accumulated through 10 years of clinical trials indicate that gene therapy has an acceptable safety profile. However, more rigorous phase II and phase III clinical trials have failed to unequivocally demonstrate that angiogenic agents are beneficial under the conditions and in the patients studied to date. Investigators have worked to understand the biology of the vascular system and to incorporate their findings into new treatments for patients with ischemic disease. Recent gene- and cell-therapy trials have demonstrated the bioactivity of several new agents and treatment strategies. Collectively, these observations have renewed interest in the mechanisms of angiogenesis and deepened our understanding of the complexity of vascular regeneration. Gene therapy that incorporates multiple growth factors, approaches that combine cell and gene therapy, and the administration of "master switch" agents that activate numerous downstream pathways are among the credible and plausible steps forward. In this review, we will examine the clinical development of angiogenic therapy, summarize several of the lessons learned during the conduct of these trials, and suggest how this prior experience may guide the conduct of future preclinical investigations and clinical trials. PMID:19815827

  13. A parametric study on the lean misfiring and knocking limits of gas fueled spark ignition engines

    SciTech Connect

    Badr, O.; Alsayed, N.; Manaf, M.

    1995-12-31

    Increasing emphasis on gaseous fuels as clean, economical and abundant fuels encourages the search for optimum operating conditions of gas fueled internal combustion engines. In this context, this paper presents the experimental results of a parametric study on the lean operational limits of a Ricardo E6 engine using propane and liquefied petroleum gas (LPG) as fuels. The engine is a single cylinder, four stroke, water cooled, unthrottled, supercharged, variable compression, spark ignition engine having a swept volume of 507 cc. Three different criteria for defining the engine lean limit are used. The first is associated with the first detectable misfire on leaning the mixture, the second is the first detectable firing under motoring conditions when the mixture is being enriched slowly, while the third is that when the torque reaches zero on leaning the mixture. In addition, the lean knocking limit is presented for some experiments. The effects of speed, spark timing, compression ratio, intake temperature, intake pressure (supercharging), and relative humidity of intake air on the engine operational limits are presented and discussed in relation to chemical reaction rates, ignition delay, amount of residuals, turbulence, and heat transfer.

  14. S1PR4 Signaling Attenuates ILT 7 Internalization To Limit IFN-? Production by Human Plasmacytoid Dendritic Cells.

    PubMed

    Dillmann, Christina; Ringel, Christian; Ringleb, Julia; Mora, Javier; Olesch, Catherine; Fink, Annika F; Roberts, Edward; Brne, Bernhard; Weigert, Andreas

    2016-02-15

    Plasmacytoid dendritic cells (pDCs) produce large amounts of type I IFN in response to TLR7/9 ligands. This conveys antiviral effects, activates other immune cells (NK cells, conventional DCs, B, and T cells), and causes the induction and expansion of a strong inflammatory response. pDCs are key players in various type I IFN-driven autoimmune diseases such as systemic lupus erythematosus or psoriasis, but pDCs are also involved in (anti-)tumor immunity. The sphingolipid sphingosine-1-phosphate (S1P) signals through five G-protein-coupled receptors (S1PR1-5) to regulate, among other activities, immune cell migration and activation. The present study shows that S1P stimulation of human, primary pDCs substantially decreases IFN-? production after TLR7/9 activation with different types of CpG oligodeoxynucleotides or tick-borne encephalitis vaccine, which occurred in an S1PR4-dependent manner. Mechanistically, S1PR4 activation preserves the surface expression of the human pDC-specific inhibitory receptor Ig-like transcript 7. We provide novel information that Ig-like transcript 7 is rapidly internalized upon receptor-mediated endocytosis of TLR7/9 ligands to allow high IFN-? production. This is antagonized by S1PR4 signaling, thus decreasing TLR-induced IFN-? secretion. At a functional level, attenuated IFN-? production failed to alter Ag-driven T cell proliferation in pDC-dependent T cell activation assays, but shifted cytokine production of T cells from a Th1 (IFN-?) to a regulatory (IL-10) profile. In conclusion, S1PR4 agonists block human pDC activation and may therefore be a promising tool to restrict pathogenic IFN-? production. PMID:26783340

  15. Mass Transfer Limited Enhanced Bioremediation at Dnapl Source Zones: a Numerical Study

    NASA Astrophysics Data System (ADS)

    Kokkinaki, A.; Sleep, B. E.

    2011-12-01

    The success of enhanced bioremediation of dense non-aqueous phase liquids (DNAPLs) relies on accelerating contaminant mass transfer from the organic to the aqueous phase, thus enhancing the depletion of DNAPL source zones compared to natural dissolution. This is achieved by promoting biological activity that reduces the contaminant's aqueous phase concentration. Although laboratory studies have demonstrated that high reaction rates are attainable by specialized microbial cultures in DNAPL source zones, field applications of the technology report lower reaction rates and prolonged remediation times. One possible explanation for this phenomenon is that the reaction rates are limited by the rate at which the contaminant partitions from the DNAPL to the aqueous phase. In such cases, slow mass transfer to the aqueous phase reduces the bioavailability of the contaminant and consequently decreases the potential source zone depletion enhancement. In this work, the effect of rate limited mass transfer on bio-enhanced dissolution of DNAPL chlorinated ethenes is investigated through a numerical study. A multi-phase, multi-component groundwater transport model is employed to simulate DNAPL mass depletion for a range of source zone scenarios. Rate limited mass transfer is modeled by a linear driving force model, employing a thermodynamic approach for the calculation of the DNAPL - water interfacial area. Metabolic reductive dechlorination is modeled by Monod kinetics, considering microbial growth and self-inhibition. The model was utilized to identify conditions in which mass transfer, rather than reaction, is the limiting process, as indicated by the bioavailability number. In such cases, reaction is slower than expected, and further increase in the reaction rate does not enhance mass depletion. Mass transfer rate limitations were shown to affect both dechlorination and microbial growth kinetics. The complex dynamics between mass transfer, DNAPL transport and distribution, and dechlorination kinetics were reflected in a transient, spatially heterogeneous bioavailability number and dissolution enhancement. In agreement with the literature, source zone architecture largely determined the impact of mass transfer on potential dissolution enhancement, with bioavailability decreasing the most at high ganglia to pool ratios. The results of this study suggest that if mass transfer rate limitations are not considered in designing bioremediation applications at DNAPL source zones, the enhancement of DNAPL depletion and the overall effectiveness of enhanced bioremediation may be significantly overestimated.

  16. Hepatitis C Virus Sensing by Human Trophoblasts Induces Innate Immune Responses and Recruitment of Maternal NK Cells: Potential Implications for Limiting Vertical Transmission.

    PubMed

    Giugliano, Silvia; Petroff, Margaret G; Warren, Bryce D; Jasti, Susmita; Linscheid, Caitlin; Ward, Ashley; Kramer, Anita; Dobrinskikh, Evgenia; Sheiko, Melissa A; Gale, Michael; Golden-Mason, Lucy; Winn, Virginia D; Rosen, Hugo R

    2015-10-15

    Hepatitis C virus (HCV) is the world's most common blood-borne viral infection for which there is no vaccine. The rates of vertical transmission range between 3 and 6% with odds 90% higher in the presence of HIV coinfection. Prevention of vertical transmission is not possible because of lack of an approved therapy for use in pregnancy or an effective vaccine. Recently, HCV has been identified as an independent risk factor for preterm delivery, perinatal mortality, and other complications. In this study, we characterized the immune responses that contribute to the control of viral infection at the maternal-fetal interface (MFI) in the early gestational stages. In this study, we show that primary human trophoblast cells and an extravillous trophoblast cell line (HTR8), from first and second trimester of pregnancy, express receptors relevant for HCV binding/entry and are permissive for HCV uptake. We found that HCV-RNA sensing by human trophoblast cells induces robust upregulation of type I/III IFNs and secretion of multiple chemokines that elicit recruitment and activation of decidual NK cells. Furthermore, we observed that HCV-RNA transfection induces a proapoptotic response within HTR8 that could affect the morphology of the placenta. To our knowledge, for the first time, we demonstrate that HCV-RNA sensing by human trophoblast cells elicits a strong antiviral response that alters the recruitment and activation of innate immune cells at the MFI. This work provides a paradigm shift in our understanding of HCV-specific immunity at the MFI as well as novel insights into mechanisms that limit vertical transmission but may paradoxically lead to virus-related pregnancy complications. PMID:26342030

  17. Immunology studies in non-human primate models of tuberculosis.

    PubMed

    Flynn, JoAnne L; Gideon, Hannah P; Mattila, Joshua T; Lin, Philana Ling

    2015-03-01

    Non-human primates, primarily macaques, have been used to study tuberculosis for decades. However, in the last 15 years, this model has been refined substantially to allow careful investigations of the immune response and host-pathogen interactions in Mycobacterium tuberculosis infection. Low-dose challenge with fully virulent strains in cynomolgus macaques result in the full clinical spectrum seen in humans, including latent and active infection. Reagents from humans are usually cross-reactive with macaques, further facilitating the use of this model system to study tuberculosis. Finally, macaques develop the spectrum of granuloma types seen in humans, providing a unique opportunity to investigate bacterial and host factors at the local (lung and lymph node) level. Here, we review the past decade of immunology and pathology studies in macaque models of tuberculosis. PMID:25703552

  18. Limitations of the semisynthetic library approach for obtaining human monoclonal autoantibodies to the thyrotropin receptor of Graves' disease

    PubMed Central

    Van Der Heijden, J H W; De Bruin, T W A; Glaudemans, K A F M; De Kruif, J; Banga, J P; Logtenberg, T

    1999-01-01

    Graves' disease (GD) is characterized by the presence of autoantibodies against the TSH-receptor (TSH-R) which are pathogenic and, upon binding to the receptor, trigger intracellular signal transduction. The autoantibodies are oligoclonal and as they are responsible for disease activity, their characterization would lead to a better understanding of the development of GD. Attempts to isolate anti-TSH-R antibodies from patients have proved to be difficult due to the exceedingly low serum levels due to rarity of these B cells, together with difficulties in obtaining purified TSH-R capable of interacting with patients autoantibodies. We employed phage antibody display technology and performed selection with a previously characterized semisynthetic antibody library on the purified extracellular ectodomain of the TSH-R. We report the isolation of six different anti-TSH-R monoclonal phage antibodies (moPhabs) from this library. All the moPhabs recognized TSH-R and its recombinant fragments by Western blotting, but failed to recognize the native TSH-R by flow cytometry. Consequently, the moPhabs did not lead to TSH-R activation. As these were the first moPhabs to TSH-R, they were analysed in terms of nucleotide and amino acid sequence and epitope specificity on the receptor. The moPhabs used immunoglobulin VH1 and VH3 germ line genes, all associated with V?3 genes. Interestingly, the CDR3 regions of all moPhabs were remarkably similar, though not identical. In light of the common CDR3 usage, the epitopes recognized on TSH-R appeared to be restricted to amino acids residues 405411 and 357364. In summary, our results show that semisynthetic libraries may be limited in isolating human monoclonal antibodies that resemble pathogenic antithyrotropin receptor autoantibodies present in patients with GD. It is likely that until preparations of purified TSH-R that can be recognized by patients autoantibodies become available, similar to the recently described glycosylphosphatidylinositol (GPI) anchored TSH-R ectodomain, monoclonal antibodies from phage antibody display to TSH-R will be limited for isolating the rare, pathogenic antibodies of GD. PMID:10540180

  19. Study of photodynamic reactions in human blood

    NASA Astrophysics Data System (ADS)

    Douplik, Alexandre Y.; Stratonnikov, Alexander A.; Loschenov, Victor B.; Lebedeva, Victoria S.; Derkacheva, V. M.; Vitkin, I. A.; Rumyanceva, V. D.; Kusmin, S. G.; Mironov, Andrei F.; Lukyanets, Eugeny A.

    2000-07-01

    Comparative studies of oxygen consumption, changes of photosensitizer fluorescence, and photodestruction of erythrocytes, and photodestruction of oxygen transport protein hemoglobin were performed during photodynamic reaction in whole and hemolyzed blood with phthalocyanines, chlorines, porphyrins, and methylene blue photosensitizers in vitro and in selected cases in vivo. The present work deals with the investigation of blood oxygen saturation SO2 and photosensitizer fluorescence during and immediately after light irradiation in the photodynamic therapy process. It has been observed that SO2 behavior strongly correlates with the type of photosensitizer. The decrease of photosensitizer fluorescence (photobleaching) during light irradiation can be followed by the recovery of the photosensitizer fluorescence immediately after interruption of the irradiation within 6 - 8 min. The levels of photodestruction of erythrocytes in whole blood and photodestruction of hemoglobin in hemolyzed blood in combination with the above photosensitizers reveal the influence of photodynamic reactions upon the ability of blood to transport oxygen. Maximal photohemolysis activity has been found with chlorine p6 photosensitizers.

  20. Limited sequence heterogeneity among biologically distinct human immunodeficiency virus type 1 isolates from individuals involved in a clustered infectious outbreak.

    PubMed Central

    McNearney, T; Westervelt, P; Thielan, B J; Trowbridge, D B; Garcia, J; Whittier, R; Ratner, L

    1990-01-01

    Human immunodeficiency virus type 1 isolates were obtained over a 3-year period from blood, brain, and lung of three patients in a clustered infectious outbreak. This included a blood donor who was initially asymptomatic but subsequently developed AIDS-related complex and two neonatal transfusion recipients who developed AIDS. Isolates from brain and lung replicated to greater than 30-fold higher levels in primary monocyte cultures than did those from blood; no growth differences on primary lymphocytes were observed. Thirteen clones were obtained from seven isolates, and env sequences were determined. The predicted amino acid sequences among these clones differed by only 0.01% but differed by 15-27% when compared to previously sequenced isolates from other patients. The level of envelope amino acid sequence divergence noted among these isolates is considerably lower than that previously reported for other human immunodeficiency virus isolates. No differences in the envelope unique to lung or brain isolates compared to blood isolates were noted. This study provides evidence that mutations in the envelope may not be necessary for disease progression and that other portions of the viral genome may contribute to cell-specific tropism. Images PMID:2308953

  1. Proinsulin multi-peptide immunotherapy induces antigen-specific regulatory T cells and limits autoimmunity in a humanized model.

    PubMed

    Gibson, V B; Nikolic, T; Pearce, V Q; Demengeot, J; Roep, B O; Peakman, M

    2015-12-01

    Peptide immunotherapy (PIT) is a targeted therapeutic approach, involving administration of disease-associated peptides, with the aim of restoring antigen-specific immunological tolerance without generalized immunosuppression. In type 1 diabetes, proinsulin is a primary antigen targeted by the autoimmune response, and is therefore a strong candidate for exploitation via PIT in this setting. To elucidate the optimal conditions for proinsulin-based PIT and explore mechanisms of action, we developed a preclinical model of proinsulin autoimmunity in a humanized HLA-DRB1*0401 transgenic HLA-DR4 Tg mouse. Once proinsulin-specific tolerance is broken, HLA-DR4 Tg mice develop autoinflammatory responses, including proinsulin-specific T cell proliferation, interferon (IFN)-γ and autoantibody production. These are preventable and quenchable by pre- and post-induction treatment, respectively, using intradermal proinsulin-PIT injections. Intradermal proinsulin-PIT enhances proliferation of regulatory [forkhead box protein 3 (FoxP3(+))CD25(high) ] CD4 T cells, including those capable of proinsulin-specific regulation, suggesting this as its main mode of action. In contrast, peptide delivered intradermally on the surface of vitamin D3-modulated (tolerogenic) dendritic cells, controls autoimmunity in association with proinsulin-specific IL-10 production, but no change in regulatory CD4 T cells. These studies define a humanized, translational model for in vivo optimization of PIT to control autoimmunity in type 1 diabetes and indicate that dominant mechanisms of action differ according to mode of peptide delivery. PMID:26206289

  2. Comparative Study of the Limitations and Challenges in Atom-Transfer C-H Oxidations.

    PubMed

    Adams, Ashley M; Du Bois, J; Malik, Hasnain A

    2015-12-18

    A comparative study is disclosed that seeks to highlight the current limitations and challenges that exist in the field of atom-transfer C-H oxidations. State-of-the-art methods are benchmarked in order to showcase clear differences and similarities. A novel Mn-mediated method for C-H oxidation is disclosed that serves as a rapid and simple method for aliphatic C-H hydroxylation. Finally, two methods that allow for C-H oxidation in the presence of pyridine-containing substrates are studied, something that is rare in the field but of great interest to the chemical community. PMID:26649767

  3. Impact of Design Trade Studies on System Human Resources.

    ERIC Educational Resources Information Center

    Whalen, Gary V.; Askren, William B.

    This study focused on two objectives. The first objective was to identify and classify the characteristics of conceptual design trade studies that have high potential impact on human resource requirements of Air Force weapon systems. The approach used was a case history review and analysis of 129 F-15 aircraft design trade studies. The analysis…

  4. Gene regulation of UDP-galactose synthesis and transport: potential rate-limiting processes in initiation of milk production in humans.

    PubMed

    Mohammad, Mahmoud A; Hadsell, Darryl L; Haymond, Morey W

    2012-08-01

    Lactose synthesis is believed to be rate limiting for milk production. However, understanding the molecular events controlling lactose synthesis in humans is still rudimentary. We have utilized our established model of the RNA isolated from breast milk fat globule from seven healthy, exclusively breastfeeding women from 6 h to 42 days following delivery to determine the temporal coordination of changes in gene expression in the carbohydrate metabolic processes emphasizing the lactose synthesis pathway in human mammary epithelial cell. We showed that milk lactose concentrations increased from 75 to 200 mM from 6 to 96 h. Milk progesterone concentrations fell by 65% at 24 h and were undetectable by day 3. Milk prolactin peaked at 36 h and then declined progressively afterward. In concordance with lactose synthesis, gene expression of galactose kinase 2, UDP-glucose pyrophosphorylase 2 (UGP2), and phosphoglucomutase 1 increased 18-, 10-, and threefold, respectively, between 6 and 72 h. Between 6 and 96 h, gene expression of UDP-galactose transporter 2 (SLC35A2) increased threefold, whereas glucose transporter 1 was unchanged. Gene expression of lactose synthase no. 3 increased 1.7-fold by 96 h, whereas ?-lactalbumin did not change over the entire study duration. Gene expression of prolactin receptor (PRLR) and its downstream signal transducer and activator of transcription complex 5 (STAT5) were increased 10- and 2.5-fold, respectively, by 72 h. In summary, lactose synthesis paralleled the induction of gene expression of proteins involved in UDP-galactose synthesis and transport, suggesting that they are potentially rate limiting in lactose synthesis and thus milk production. Progesterone withdrawal may be the signal that triggers PRLR signaling via STAT5, which may in turn induce UGP2 and SLC35A2 expression. PMID:22649065

  5. Drosophila tools and assays for the study of human diseases.

    PubMed

    Ugur, Berrak; Chen, Kuchuan; Bellen, Hugo J

    2016-03-01

    Many of the internal organ systems of Drosophila melanogaster are functionally analogous to those in vertebrates, including humans. Although humans and flies differ greatly in terms of their gross morphological and cellular features, many of the molecular mechanisms that govern development and drive cellular and physiological processes are conserved between both organisms. The morphological differences are deceiving and have led researchers to undervalue the study of invertebrate organs in unraveling pathogenic mechanisms of diseases. In this review and accompanying poster, we highlight the physiological and molecular parallels between fly and human organs that validate the use of Drosophila to study the molecular pathogenesis underlying human diseases. We discuss assays that have been developed in flies to study the function of specific genes in the central nervous system, heart, liver and kidney, and provide examples of the use of these assays to address questions related to human diseases. These assays provide us with simple yet powerful tools to study the pathogenic mechanisms associated with human disease-causing genes. PMID:26935102

  6. Study of electrical properties of meridian on human body surface

    NASA Astrophysics Data System (ADS)

    Wang, Feng; Uematsu, Haruyuki; Otani, Nobuo

    2007-12-01

    This paper presents the study of the subcutaneous electrical impedance on the human body surface. Measurements of the electrical impedance on five adult male subjects were carried out and analyzed for the possible detection of the acupuncture meridian lines of ancient Chinese medicine on the human body. The distribution of electrical impedance measured at 40 points over the volar side of the right upper limb of the subjects. The results show that electrical impedance varies at different locations of the human body surface, and the locations with lower electrical impedance coincide with the locations where the meridian is believed to exist.

  7. Brain activity and human unilateral chewing: an FMRI study.

    PubMed

    Quintero, A; Ichesco, E; Myers, C; Schutt, R; Gerstner, G E

    2013-02-01

    Brain mechanisms underlying mastication have been studied in non-human mammals but less so in humans. We used functional magnetic resonance imaging (fMRI) to evaluate brain activity in humans during gum chewing. Chewing was associated with activations in the cerebellum, motor cortex and caudate, cingulate, and brainstem. We also divided the 25-second chew-blocks into 5 segments of equal 5-second durations and evaluated activations within and between each of the 5 segments. This analysis revealed activation clusters unique to the initial segment, which may indicate brain regions involved with initiating chewing. Several clusters were uniquely activated during the last segment as well, which may represent brain regions involved with anticipatory or motor events associated with the end of the chew-block. In conclusion, this study provided evidence for specific brain areas associated with chewing in humans and demonstrated that brain activation patterns may dynamically change over the course of chewing sequences. PMID:23103631

  8. HUMEX. A study on the survivability and adaptation of humans to long-duration exploratory missions

    NASA Astrophysics Data System (ADS)

    Harris, Robert A.

    2003-11-01

    After the realisation of the International Space Station (ISS), human exploratory missions to the Moon or Mars, i.e. beyond low Earth orbit (LEO), are widely considered as the next logical step in worldwide peaceful cooperation in space. The HUMEX study has concentrated on human health related aspects: it provides a critical assessment of the human responses, limits and needs with regard to the stress environments of interplanetary and planetary missions. Emphasis has been put on human health, well-being and performance care, such as radiation health issues, adaptation to microgravity and reduced gravity, psychology issues and health, well-being and performance care, such as radiation health issues, adaptation to microgravity and reduced gravity, psychology issues and health maintenance and on advanced life support developments. The overall study goals are: to define reference scenarios for European participation in human exploration and to estimate their influence on the Life Sciences and Life Support requirements; for selected mission scenarios, to critically assess the limiting factors for human health, well-being, and performance and to recommend relevant countermeasures; for selected mission scenarios, to critically assess the potential of advanced life support developments and to propose a European strategy for this field, including terrestrial applications; to critically assess the applicability of existing facilities and technologies on the ground and in space as test beds for human exploratory missions and to develop a test plan for ground and ISS campaigns; to develop a roadmap for future European activities, in preparation for human exploratory missions, including preparatory activities and terrestrial applications and benefits.

  9. A qualitative case study to identify possible barriers that limit effective elementary science education

    NASA Astrophysics Data System (ADS)

    Foster, Donald Carey

    The purpose of this case study was to identify barriers that limit the effectiveness of elementary teachers in the teaching of science. It is of the utmost urgency that barriers be first identified, so that possible solutions can be explored to bring about the improvement of elementary science education. This urgency has been imposed by the scheduled national testing of students in science by 2007, as mandated by the No Child Left Behind Act of 2001. Using qualitative case study methods, the researcher conducted interviews with 8 elementary teachers from two schools within one school district who taught 3rd, 4th, and 5th grade. These interviews were designed to gain insight into barriers these elementary teachers perceived as factors limiting their effectiveness in teaching science and preparing students for high-stakes testing. Barriers in the areas of teacher background, typical teaching day, curriculum, inservices, and legislative influences were explored. This study concluded that the barriers explored do have a substantial negative affect on the teaching and learning of science in the elementary grades. Specifically, the barriers revealed in this study include the limited science background of elementary teachers, inadequate class time devoted to science, non-comprehensive curriculum, ineffective or lack of inservice training, and pressures from legislated mandates. But it is also clear that these barriers are so intertwined that one cannot remove these barriers one at a time. It will take a collective effort from all involved, including legislators, administrators, teachers, parents, and students, to alleviate these barriers and discover effective solutions to improve elementary science education.

  10. Animal Models to Study Placental Development and Function throughout Normal and Dysfunctional Human Pregnancy

    PubMed Central

    Grigsby, Peta L.

    2016-01-01

    Abnormalities of placental development and function are known to underlie many pathologies of pregnancy, including spontaneous preterm birth, fetal growth restriction and preeclampsia. A growing body of evidence also underscores the importance of placental dysfunction in the lifelong health of both mother and offspring. However, our knowledge regarding placental structure and function throughout pregnancy remains limited. Understanding the temporal growth and functionality of the human placenta throughout the entirety of gestation is important if we are to gain a better understanding of placental dysfunction. The utilization of new technologies and imaging techniques that could enable safe monitoring of placental growth and function in vivo has become a major focus area for the National Institutes of Child Health & Human Development, as evident by the establishment of the “Human Placenta Project”. Many of the objectives of the Human Placenta Project will necessitate pre-clinical studies and testing in appropriately designed animal models that can be readily translated to the clinical setting. This review will describe the advantages and limitations of relevant animals such as the guinea pig, sheep and non-human primate models that have been used to study the role of the placenta in fetal growth disorders, preeclampsia or other maternal diseases during pregnancy. PMID:26752715

  11. Studies of Limits on Uncontrolled Heavy Ion Beam Losses for Allowing Hands-On Maintenance

    SciTech Connect

    Reginald M. Ronningen; Igor Remec

    2010-09-11

    Dose rates from accelerator components activated by 1 W/m beam losses are obtained semiempirically for a 1 GeV proton beam and by use of Monte Carlo transport codes for the proton beam and for 777 MeV/u 3He, 500 MeV/u 48Ca, 86Kr, 136Xe, and 400 MeV/u 238U ions. The dose rate obtained by the semi-empirical method, 0.99 mSv/h (99 mrem/h) at 30 cm, 4 h after 100 d irradiation by a 1-GeV proton beam, is consistent with studies at several accelerator facilities and with adopted hands-on maintenance dose rate limits. Monte Carlo simulations verify this result for protons and extend studies to heavy ion beam losses in drift-tube linac and superconducting linac accelerating structures. The studies indicate that the 1 W/m limit imposed on uncontrolled beam losses for high-energy proton beams might be relaxed for heavy ion beams. These studies further suggest that using the ratio of neutrons produced by a heavy ion beam to neutrons produced by a proton beam along with the dose rate from the proton beam (for thin-target scenarios) should allow an estimate of the dose rates expected from heavy ion beam losses.

  12. Identifying selective inhibitors against the human cytosolic sialidase NEU2 by substrate specificity studies.

    PubMed

    Li, Yanhong; Cao, Hongzhi; Yu, Hai; Chen, Yi; Lau, Kam; Qu, Jingyao; Thon, Vireak; Sugiarto, Go; Chen, Xi

    2011-04-01

    Aberrant expression of human sialidases has been shown to associate with various pathological conditions. Despite the effort in the sialidase inhibitor design, less attention has been paid to designing specific inhibitors against human sialidases and characterizing the substrate specificity of different sialidases regarding diverse terminal sialic acid forms and sialyl linkages. This is mainly due to the lack of sialoside probes and efficient screening methods, as well as limited access to human sialidases. A low cellular expression level of the human sialidase NEU2 hampers its functional and inhibitory studies. Here we report the successful cloning and expression of the human sialidase NEU2 in E. coli. About 11 mg of soluble active NEU2 was routinely obtained from 1 L of E. coli cell culture. Substrate specificity studies of the recombinant human NEU2 using twenty p-nitrophenol (pNP)-tagged ?2-3- or ?2-6-linked sialyl galactosides containing different terminal sialic acid forms including common N-acetylneuraminic acid (Neu5Ac), non-human N-glycolylneuraminic acid (Neu5Gc), 2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid (Kdn), or their C5-derivatives in a microtiter plate-based high-throughput colorimetric assay identified a unique structural feature specifically recognized by the human NEU2 but not two bacterial sialidases. The results obtained from substrate specificity studies were used to guide the design of a sialidase inhibitor that was selective against human NEU2. The selectivity of the inhibitor was revealed by the comparison of sialidase crystal structures and inhibitor docking studies. PMID:21206954

  13. Perfluorochemicals and Human Semen Quality: The LIFE Study

    PubMed Central

    Chen, Zhen; Schisterman, Enrique F.; Kim, Sungduk; Sweeney, Anne M.; Sundaram, Rajeshwari; Lynch, Courtney D.; Gore-Langton, Robert E.; Barr, Dana Boyd

    2014-01-01

    Background: The relation between persistent environmental chemicals and semen quality is evolving, although limited data exist for men recruited from general populations. Objectives: We examined the relation between perfluorinated chemicals (PFCs) and semen quality among 501 male partners of couples planning pregnancy. Methods: Using population-based sampling strategies, we recruited 501 couples discontinuing contraception from two U.S. geographic regions from 2005 through 2009. Baseline interviews and anthropometric assessments were conducted, followed by blood collection for the quantification of seven serum PFCs (perfluorosulfonates, perfluorocarboxylates, and perfluorosulfonamides) using tandem mass spectrometry. Men collected a baseline semen sample and another approximately 1 month later. Semen samples were shipped with freezer packs, and analyses were performed on the day after collection. We used linear regression to estimate the difference in each semen parameter associated with a one unit increase in the natural logtransformed PFC concentration after adjusting for confounders and modeling repeated semen samples. Sensitivity analyses included optimal Box-Cox transformation of semen quality end points. Results: Six PFCs [2-(N-methyl-perfluorooctane sulfonamido) acetate (Me-PFOSA-AcOH), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), perfluorooctane sulfonamide (PFOSA), perfluorooctane sulfonate (PFOS), and perfluorooctanoic acid (PFOA)] were associated with 17 semen quality end points before Box-Cox transformation. PFOSA was associated with smaller sperm head area and perimeter, a lower percentage of DNA stainability, and a higher percentage of bicephalic and immature sperm. PFDeA, PFNA, PFOA, and PFOS were associated with a lower percentage of sperm with coiled tails. Conclusions: Select PFCs were associated with certain semen end points, with the most significant associations observed for PFOSA but with results in varying directions. Citation: Buck Louis GM, Chen Z, Schisterman EF, Kim S, Sweeney AM, Sundaram R, Lynch CD, Gore-Langton RE, Barr DB. 2015. Perfluorochemicals and human semen quality: the LIFE Study. Environ Health Perspect 123:5763;?http://dx.doi.org/10.1289/ehp.1307621 PMID:25127343

  14. A Comparative Study Between Strain And Stress Based Forming Limit Analysis By Applying Several Phenomenological Yield Criteria

    SciTech Connect

    Butuc, Marilena C.; Vincze, Gabriela T.; Gracio, Jose J.; Barata da Rocha, A.

    2005-08-05

    The present work aims at analyzing a comparative study between the strain-based forming limit criterion (FLD) and the stress-based forming limit criterion (FLSD), under linear and complex strain paths. The selected material is an AA5182-0 aluminium alloy. Some relevant remarks about stress-based forming limit criterion concept are presented.

  15. Reprint of: In-vitro model systems for the study of human embryo-endometrium interactions.

    PubMed

    Weimar, Charlotte H E; Post Uiterweer, Emiel D; Teklenburg, Gijs; Heijnen, Cobi J; Macklon, Nick S

    2013-12-01

    Implantation requires highly orchestrated interactions between the developing embryo and maternal endometrium. The association between abnormal implantation and reproductive failure is evident, both in normal pregnancy and in assisted reproduction patients. Failure of implantation is the pregnancy rate-limiting step in assisted reproduction, but, as yet, empirical interventions have largely failed to address this problem. Better understanding of the mechanisms underlying human embryo-endometrium signalling is a prerequisite for the further improvement of assisted reproduction outcomes and the development of effective interventions to prevent early pregnancy loss. Studying human embryo implantation is challenging since in-vivo experiments are impractical and unethical, and studies in animal models do not always translate well to humans. However, in recent years in-vitro models have been shown to provide a promising way forward. This review discusses the principal models used to study early human embryo development and initial stages of implantation in vitro. While each model has limitations, exploiting these models will improve understanding of the molecular mechanisms and embryo-endometrium cross-talk at the early implantation site. They provide valuable tools to study early embryo development and pathophysiology of reproductive disorders and have revealed novel disease mechanisms such as the role of epigenetic modifications in recurrent miscarriage. PMID:24161843

  16. In-vitro model systems for the study of human embryo-endometrium interactions.

    PubMed

    Weimar, Charlotte H E; Post Uiterweer, Emiel D; Teklenburg, Gijs; Heijnen, Cobi J; Macklon, Nick S

    2013-11-01

    Implantation requires highly orchestrated interactions between the developing embryo and maternal endometrium. The association between abnormal implantation and reproductive failure is evident, both in normal pregnancy and in assisted reproduction patients. Failure of implantation is the pregnancy rate-limiting step in assisted reproduction, but, as yet, empirical interventions have largely failed to address this problem. Better understanding of the mechanisms underlying human embryo-endometrium signalling is a prerequisite for the further improvement of assisted reproduction outcomes and the development of effective interventions to prevent early pregnancy loss. Studying human embryo implantation is challenging since in-vivo experiments are impractical and unethical, and studies in animal models do not always translate well to humans. However, in recent years in-vitro models have been shown to provide a promising way forward. This review discusses the principal models used to study early human embryo development and initial stages of implantation in vitro. While each model has limitations, exploiting these models will improve understanding of the molecular mechanisms and embryo-endometrium cross-talk at the early implantation site. They provide valuable tools to study early embryo development and pathophysiology of reproductive disorders and have revealed novel disease mechanisms such as the role of epigenetic modifications in recurrent miscarriage. PMID:24055530

  17. Vestibular schwannoma and cell-phones. Results, limits and perspectives of clinical studies.

    PubMed

    Mornet, E; Kania, R; Sauvaget, E; Herman, P; Tran Ba Huy, P

    2013-11-01

    The widespread development of cell-phones entails novel user exposure to electromagnetic fields. Health impact is a public health issue and a source of anxiety in the population. Some clinical studies reported an association between cell and cordless phone use and vestibular schwannoma; others found none. A systematic review was performed of all published clinical studies (cohort, registry, case-control and validation studies), with analysis of results, to determine the nature of the association and the level of evidence. Cohort studies were inconclusive due to short exposure durations and poor representativeness. Registry studies showed no correlation between evolution of cell-phone use and incidence of vestibular schwannoma. Case-control studies reported contradictory results, with methodological flaws. Only a small number of subjects were included in long-term studies (>10 years), and these failed to demonstrate any indisputable causal relationship. Exposure assessment methods were debatable, and long-term assessment was lacking. An on-going prospective study should determine any major effect of electromagnetic fields; schwannoma being a rare pathology, absence of association will be difficult to prove. No clinical association has been demonstrated between cell and cordless phone use and vestibular schwannoma. Existing studies are limited by their retrospective assessment of exposure. PMID:23725662

  18. Studies of the human c-myb gene and its product in human acute leukemias.

    PubMed

    Slamon, D J; Boone, T C; Murdock, D C; Keith, D E; Press, M F; Larson, R A; Souza, L M

    1986-07-18

    The myb gene is the transforming oncogene of the avian myeloblastosis virus (AMV); its normal cellular homolog, c-myb, is conserved across a broad span of evolution. In humans, c-myb is expressed in malignant hematopoietic cell lines and in primary hematopoietic tumors. Partial complementary DNA clones were generated from blast cells of patients with acute myelogenous leukemia. The sequences of the clones were compared to the c-myb of other species, as well as the v-myb of AMV. In addition, the carboxyl terminal region of human c-myb was placed in an expression vector to obtain protein for the generation of antiserum, which was used to identify the human c-myb gene product. Like v-myb, this protein was found within the nucleus of leukemic cells where it was associated with the nuclear matrix. These studies provide further evidence that c-myb might be involved in human leukemia. PMID:3014652

  19. Field theoretic study of a cold Fermi gas in the unitary limit

    NASA Astrophysics Data System (ADS)

    Wingate, Matthew

    2006-12-01

    Trapped and cooled gases of alkali atoms can be manipulated to exhibit a variety of interesting phenomena. For example, dilute gases of fermionic atoms, in 2 hyperfine states, can be cooled to temperatures where they become superfluid. An external field can be applied to tune the scat- tering length a. When |a| exceeds the interparticle spacing, nonperturbative tools are needed to study the system theoretically. The unitary limit, |a| ? ?, is particularly interesting due to its universality and symmetry. Lattice field theory and effective field theory can be used to system- atically calculate properties of this system. Results are presented for the finite temperature phase transition and for behavior near zero temperature.

  20. An Experimental Study of the Emergence of Human Communication Systems

    ERIC Educational Resources Information Center

    Galantucci, Bruno

    2005-01-01

    The emergence of human communication systems is typically investigated via 2 approaches with complementary strengths and weaknesses: naturalistic studies and computer simulations. This study was conducted with a method that combines these approaches. Pairs of participants played video games requiring communication. Members of a pair were…

  1. Toward a Humane World: Making a Difference with Social Studies.

    ERIC Educational Resources Information Center

    Levy, Tedd

    1999-01-01

    Presents the address delivered by President Tedd Levy at the 78th National Council for Social Studies (NCSS) Annual Conference. Stresses that social studies offers students a place to discuss social-environmental problems the culture is suffering from and gives teachers a chance to promote values inherent in a more humane world. (CMK)

  2. Ecology and Human Values: A Course of Study. (Working Draft).

    ERIC Educational Resources Information Center

    Wisconsin State Dept. of Public Instruction, Madison.

    This interdisciplinary course is designed for senior year high school students in social studies and/or science. Its main thrust is the investigation of human values as they relate to the environment, although rooted in the natural sciences as a means of understanding the complexities inherent in the environment. Use is made of the case study

  3. A Phylogenetic Comparative Study of Bantu Kinship Terminology Finds Limited Support for Its Co-Evolution with Social Organisation

    PubMed Central

    Guillon, Myrtille; Mace, Ruth

    2016-01-01

    The classification of kin into structured groups is a diverse phenomenon which is ubiquitous in human culture. For populations which are organized into large agropastoral groupings of sedentary residence but not governed within the context of a centralised state, such as our study sample of 83 historical Bantu-speaking groups of sub-Saharan Africa, cultural kinship norms guide all aspects of everyday life and social organization. Such rules operate in part through the use of differing terminological referential systems of familial organization. Although the cross-cultural study of kinship terminology was foundational in Anthropology, few modern studies have made use of statistical advances to further our sparse understanding of the structuring and diversification of terminological systems of kinship over time. In this study we use Bayesian Markov Chain Monte Carlo methods of phylogenetic comparison to investigate the evolution of Bantu kinship terminology and reconstruct the ancestral state and diversification of cousin terminology in this family of sub-Saharan ethnolinguistic groups. Using a phylogenetic tree of Bantu languages, we then test the prominent hypothesis that structured variation in systems of cousin terminology has co-evolved alongside adaptive change in patterns of descent organization, as well as rules of residence. We find limited support for this hypothesis, and argue that the shaping of systems of kinship terminology is a multifactorial process, concluding with possible avenues of future research. PMID:27008364

  4. Intraoperative intravital microscopy permits the study of human tumour vessels.

    PubMed

    Fisher, Daniel T; Muhitch, Jason B; Kim, Minhyung; Doyen, Kurt C; Bogner, Paul N; Evans, Sharon S; Skitzki, Joseph J

    2016-01-01

    Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ∼50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment. PMID:26883450

  5. Intraoperative intravital microscopy permits the study of human tumour vessels

    PubMed Central

    Fisher, Daniel T.; Muhitch, Jason B.; Kim, Minhyung; Doyen, Kurt C.; Bogner, Paul N.; Evans, Sharon S.; Skitzki, Joseph J.

    2016-01-01

    Tumour vessels have been studied extensively as they are critical sites for drug delivery, anti-angiogenic therapies and immunotherapy. As a preclinical tool, intravital microscopy (IVM) allows for in vivo real-time direct observation of vessels at the cellular level. However, to date there are no reports of intravital high-resolution imaging of human tumours in the clinical setting. Here we report the feasibility of IVM examinations of human malignant disease with an emphasis on tumour vasculature as the major site of tumour-host interactions. Consistent with preclinical observations, we show that patient tumour vessels are disorganized, tortuous and ∼50% do not support blood flow. Human tumour vessel diameters are larger than predicted from immunohistochemistry or preclinical IVM, and thereby have lower wall shear stress, which influences delivery of drugs and cellular immunotherapies. Thus, real-time clinical imaging of living human tumours is feasible and allows for detection of characteristics within the tumour microenvironment. PMID:26883450

  6. A Simple Mouse Model for the Study of Human Immunodeficiency Virus.

    PubMed

    Kim, Kang Chang; Choi, Byeong-Sun; Kim, Kyung-Chang; Park, Ki Hoon; Lee, Hee Jung; Cho, Young Keol; Kim, Sang Il; Kim, Sung Soon; Oh, Yu-Kyoung; Kim, Young Bong

    2016-02-01

    Humanized mouse models derived from immune-deficient mice have been the primary tool for studies of human infectious viruses, such as human immunodeficiency virus (HIV). However, the current protocol for constructing humanized mice requires elaborate procedures and complicated techniques, limiting the supply of such mice for viral studies. Here, we report a convenient method for constructing a simple HIV-1 mouse model. Without prior irradiation, NOD/SCID/IL2Rγ-null (NSG) mice were intraperitoneally injected with 1 × 10(7) adult human peripheral blood mononuclear cells (hu-PBMCs). Four weeks after PBMC inoculation, human CD45(+) cells, and CD3(+)CD4(+) and CD3(+)CD8(+) T cells were detected in peripheral blood, lymph nodes, spleen, and liver, whereas human CD19(+) cells were observed in lymph nodes and spleen. To examine the usefulness of hu-PBMC-inoculated NSG (hu-PBMC-NSG) mice as an HIV-1 infection model, we intravenously injected these mice with dual-tropic HIV-1DH12 and X4-tropic HIV-1NL4-3 strains. HIV-1-infected hu-PBMC-NSG mice showed significantly lower human CD4(+) T cell counts and high HIV viral loads in the peripheral blood compared with noninfected hu-PBMC-NSG mice. Following highly active antiretroviral therapy (HAART) and neutralizing antibody treatment, HIV-1 replication was significantly suppressed in HIV-1-infected hu-PBMC-NSG mice without detectable viremia or CD4(+) T cell depletion. Moreover, the numbers of human T cells were maintained in hu-PBMC-NSG mice for at least 10 weeks. Taken together, our results suggest that hu-PBMC-NSG mice may serve as a relevant HIV-1 infection and pathogenesis model that could facilitate in vivo studies of HIV-1 infection and candidate HIV-1 protective drugs. PMID:26564392

  7. Reinforcing properties of caffeine: studies in humans and laboratory animals.

    PubMed

    Griffiths, R R; Woodson, P P

    1988-02-01

    Three types of experimental studies are reviewed: (1) intravenous and oral caffeine self-administration by laboratory animals, (2) oral caffeine self-administration by humans, and (3) human subjective effects of caffeine relevant to reinforcing effects. These studies show that, under appropriate conditions, caffeine can serve as a reinforcer and can produce elevations in subjective drug liking and/or euphoria. In this regard, caffeine can be distinguished from a wide range of behaviorally active compounds, such as the amphetamine analog fenfluramine and the major tranquilizer chlorpromazine, which do not produce such effects. Caffeine can also be distinguished from classic drugs of abuse such as cocaine, d-amphetamine or pentobarbital which generally maintain high levels of self-administration (or liking) in contrast to caffeine which tends to maintain lower levels of self-administration (or liking) or maintain self-administration under a more narrow range of parametric conditions. Several human studies and one animal experiment suggest that physical dependence substantially potentiates the reinforcing effects of caffeine. Other human and animal studies indicate that there may be substantial differences between individual subjects in the reinforcing effects of caffeine. An important challenge for future human and animal drug self-administration research will be to delineate more precisely the conditions under which caffeine does and does not serve reliably as a reinforcer. PMID:3283780

  8. Restless legs syndrome and functional limitations among American elders in the Health and Retirement Study

    PubMed Central

    2012-01-01

    Background Restless legs syndrome (RLS) is a common condition associated with decreased quality of life in older adults. This study estimates the prevalence, risk factors, and functional correlates of among U.S. elders. Methods Subjects (n?=?1,008) were sub-sampled from the 2002 cross-sectional interview survey of the Health and Retirement Study (HRS), a nationally representative study of U.S. elders. Symptoms and sleep disturbances consistent with RLS were identified. Activities of daily living (ADL), instrumental activities of daily living (IADL), and limitations for mobility, large muscle groups, gross and fine motor function were measured using standardized questions. Incident functional limitations were detected over six years of observation. Results The prevalence of RLS among U.S. elders born before 1947 was 10.6%. Factors associated with increased prevalence RLS at baseline included: overweight body mass index (multivariate adjusted prevalence ratio?=?1.77; 95% confidence interval (CI) 1.05-2.99); mild-to-moderate pain (2.67, 1.47-4.84) or pain inferring with activity (3.44, 2.00-5.93); three or more chronic medications (2.54, 1.26-5.12), highest quartile of out-of-pocket medical expenses (2.12, 1.17-3.86), frequent falls (2.63, 1.49-4.66), health limiting ability to work (2.91, 1.75-4.85), or problems with early waking or frequent wakening (1.69, 1.09-2.62 and 1.55, 1.00-2.41, respectively). Current alcohol consumption (0.59, 0.37-0.92) and frequent healthcare provider visits (0.49, 0.27-0.90) were associated with decreased RLS prevalence. RLS did not predict incident disability for aggregate measures but was associated with increased risk for specific limitations, including: difficulty climbing several stair flights (multivariate-adjusted hazard ratio?=?2.38, 95% CI 1.39-4.06), prolonged sitting (2.17, 1.25-3.75), rising from a chair (2.54, 1.62-3.99), stooping (2.66, 1.71-4.15), moving heavy objects (1.79, 1.08-2.99), carrying ten pounds (1.61, 1.05-2.97), raising arms (1.76, 1.05-2.97), or picking up a dime (1.97, 1.12-3.46). Conclusions RLS sufferers are more likely to have functional disability, even after adjusting for health status and pain syndrome correlates. PMID:22834914

  9. Human trigeminal ganglionic explants as a model to study alphaherpesvirus reactivation

    PubMed Central

    Azarkh, Yevgeniy; Bos, Nathan; Gilden, Don

    2013-01-01

    Varicella zoster virus (VZV) latency is characterized by limited virus gene expression and the absence of virus DNA replication. Investigations of VZV latency and reactivation have been hindered by the lack of an in vitro model of virus latency. Since VZV is an exclusively human pathogen, we used naturally infected human trigeminal ganglia (TG) obtained at autopsy to study virus latency. Herein, we report optimization of medium to maintain TG integrity as determined by histology and immunohisto-chemistry. Using the optimized culture medium, we also found that both herpes simplex virus-1 (HSV-1) and VZV DNA replicated in TG explants after 5 days in culture. The increase in HSV-1 DNA was fourfold greater than the increase in VZV DNA. Overall, we present a model for alphaherpesvirus latency in human neurons in which the key molecular events leading to virus reactivation can be studied. PMID:22851387

  10. Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

    SciTech Connect

    Fabrikant, J.I.

    1982-08-01

    The present review provides an understanding of our current knowledge of the carcinogenic effect of low-dose radiation in man, and surveys the epidemiological studies of human populations exposed to nuclear explosions and medical radiation. Discussion centers on the contributions of quantitative epidemiology to present knowledge, the reliability of the dose-incidence data, and those relevant epidemiological studies that provide the most useful information for risk estimation of cancer-induction in man. Reference is made to dose-incidence relationships from laboratory animal experiments where they may obtain for problems and difficulties in extrapolation from data obtained at high doses to low doses, and from animal data to the human situation. The paper describes the methods of application of such epidemiological data for estimation of excess risk of radiation-induced cancer in exposed human populations, and discusses the strengths and limitations of epidemiology in guiding radiation protection philosophy and public health policy.

  11. A mouse model replicating hippocampal sparing cranial irradiation in humans: A tool for identifying new strategies to limit neurocognitive decline

    PubMed Central

    Tom, Wolfgang A.; Gkhan, ?len; Brodin, N. Patrik; Gulinello, Maria E.; Heard, John; Mehler, Mark F.; Guha, Chandan

    2015-01-01

    Cancer patients undergoing cranial irradiation are at risk of developing neurocognitive impairments. Recent evidence suggests that radiation-induced injury to the hippocampi could play an important role in this cognitive decline. As a tool for studying the mechanisms of hippocampal-dependent cognitive decline, we developed a mouse model replicating the results of the recent clinical RTOG 0933 study of hippocampal sparing whole-brain irradiation. We irradiated 16-week-old female C57BL/6J mice to a single dose of 10?Gy using either whole-brain irradiation (WBRT) or hippocampal sparing irradiation (HSI). These animals, as well as sham-irradiated controls, were subjected to behavioral/cognitive assessments distinguishing between hippocampal-dependent and hippocampal-independent functions. Irradiation was well tolerated by all animals and only limited cell death of proliferating cells was found within the generative zones. Animals exposed to WBRT showed significant deficits compared to sham-irradiated controls in the hippocampal-dependent behavioral task. In contrast, HSI mice did not perform significantly different from sham-irradiated mice (control group) and performed significantly better when compared to WBRT mice. This is consistent with the results from the RTOG 0933 clinical trial, and as such this animal model could prove a helpful tool for exploring new strategies for mitigating cognitive decline in cancer patients receiving cranial irradiation. PMID:26399509

  12. Ontology-based federated data access to human studies information.

    PubMed

    Sim, Ida; Carini, Simona; Tu, Samson W; Detwiler, Landon T; Brinkley, James; Mollah, Shamim A; Burke, Karl; Lehmann, Harold P; Chakraborty, Swati; Wittkowski, Knut M; Pollock, Brad H; Johnson, Thomas M; Huser, Vojtech

    2012-01-01

    Human studies are one of the most valuable sources of knowledge in biomedical research, but data about their design and results are currently widely dispersed in siloed systems. Federation of these data is needed to facilitate large-scale data analysis to realize the goals of evidence-based medicine. The Human Studies Database project has developed an informatics infrastructure for federated query of human studies databases, using a generalizable approach to ontology-based data access. Our approach has three main components. First, the Ontology of Clinical Research (OCRe) provides the reference semantics. Second, a data model, automatically derived from OCRe into XSD, maintains semantic synchrony of the underlying representations while facilitating data acquisition using common XML technologies. Finally, the Query Integrator issues queries distributed over the data, OCRe, and other ontologies such as SNOMED in BioPortal. We report on a demonstration of this infrastructure on data acquired from institutional systems and from ClinicalTrials.gov. PMID:23304360

  13. Baboons as a Model to Study Genetics and Epigenetics of Human Disease

    PubMed Central

    Cox, Laura A.; Comuzzie, Anthony G.; Havill, Lorena M.; Karere, Genesio M.; Spradling, Kimberly D.; Mahaney, Michael C.; Nathanielsz, Peter W.; Nicolella, Daniel P.; Shade, Robert E.; Voruganti, Saroja; VandeBerg, John L.

    2013-01-01

    A major challenge for understanding susceptibility to common human diseases is determining genetic and environmental factors that influence mechanisms underlying variation in disease-related traits. The most common diseases afflicting the US population are complex diseases that develop as a result of defects in multiple genetically controlled systems in response to environmental challenges. Unraveling the etiology of these diseases is exceedingly difficult because of the many genetic and environmental factors involved. Studies of complex disease genetics in humans are challenging because it is not possible to control pedigree structure and often not practical to control environmental conditions over an extended period of time. Furthermore, access to tissues relevant to many diseases from healthy individuals is quite limited. The baboon is a well-established research model for the study of a wide array of common complex diseases, including dyslipidemia, hypertension, obesity, and osteoporosis. It is possible to acquire tissues from healthy, genetically characterized baboons that have been exposed to defined environmental stimuli. In this review, we describe the genetic and physiologic similarity of baboons with humans, the ability and usefulness of controlling environment and breeding, and current genetic and genomic resources. We discuss studies on genetics of heart disease, obesity, diabetes, metabolic syndrome, hypertension, osteoporosis, osteoarthritis, and intrauterine growth restriction using the baboon as a model for human disease. We also summarize new studies and resources under development, providing examples of potential translational studies for targeted interventions and therapies for human disease. PMID:24174436

  14. Characterizing interspecies uncertainty using data from studies of anti-neoplastic agents in animals and humans

    SciTech Connect

    Price, Paul S. Keenan, Russell E.; Swartout, Jeffrey C.

    2008-11-15

    For most chemicals, the Reference Dose (RfD) is based on data from animal testing. The uncertainty introduced by the use of animal models has been termed interspecies uncertainty. The magnitude of the differences between the toxicity of a chemical in humans and test animals and its uncertainty can be investigated by evaluating the inter-chemical variation in the ratios of the doses associated with similar toxicological endpoints in test animals and humans. This study performs such an evaluation on a data set of 64 anti-neoplastic drugs. The data set provides matched responses in humans and four species of test animals: mice, rats, monkeys, and dogs. While the data have a number of limitations, the data show that when the drugs are evaluated on a body weight basis: 1) toxicity generally increases with a species' body weight; however, humans are not always more sensitive than test animals; 2) the animal to human dose ratios were less than 10 for most, but not all, drugs; 3) the current practice of using data from multiple species when setting RfDs lowers the probability of having a large value for the ratio. These findings provide insight into inter-chemical variation in animal to human extrapolations and suggest the need for additional collection and analysis of matched toxicity data in humans and test animals.

  15. Low power optical limiting studies of copper doped lithium tetraborate nanoparticles

    NASA Astrophysics Data System (ADS)

    Dhanuskodi, S.; Mohandoss, R.; Vinitha, G.; Pathinettam Padiyan, D.

    2015-04-01

    The copper doped lithium tetraborate (LTB:Cu) nanoparticles were synthesized by sol-gel method and characterized by XRD (tetragonal structure) and by FESEM (sphere-like nanoparticle). UV-Vis studies show that there is no strong absorption in the visible region. In the luminescence spectrum, the emission peak at 370 nm reveals the presence of Cu+ in LTB lattice. The relative powder second harmonic generation efficiency of pure and doped LTB is equal to the standard NLO material, KDP. The nonlinear optical parameters of LTB:Cu nanoparticles say, nonlinear refractive index, nonlinear absorption coefficient and third order nonlinear optical susceptibility were determined to be of the order of 10-8 cm2/W, 10-2 cm/W and 10-5 esu, respectively. The optical power limiting behavior of the samples were studied by Z-scan technique with (532 nm, 50 mW) Nd:YAG laser and the limiting threshold values are found to be 22.7 mW for 0.01 M and 24.9 mW for 0.03 and 0.05 M LTB:Cu nanoparticles.

  16. Low power optical limiting studies of copper doped lithium tetraborate nanoparticles.

    PubMed

    Dhanuskodi, S; Mohandoss, R; Vinitha, G; Pathinettam Padiyan, D

    2015-04-01

    The copper doped lithium tetraborate (LTB:Cu) nanoparticles were synthesized by sol-gel method and characterized by XRD (tetragonal structure) and by FESEM (sphere-like nanoparticle). UV-Vis studies show that there is no strong absorption in the visible region. In the luminescence spectrum, the emission peak at 370 nm reveals the presence of Cu+ in LTB lattice. The relative powder second harmonic generation efficiency of pure and doped LTB is equal to the standard NLO material, KDP. The nonlinear optical parameters of LTB:Cu nanoparticles say, nonlinear refractive index, nonlinear absorption coefficient and third order nonlinear optical susceptibility were determined to be of the order of 10(-8)cm2/W, 10(-2) cm/W and 10(-5) esu, respectively. The optical power limiting behavior of the samples were studied by Z-scan technique with (532 nm, 50 mW) Nd:YAG laser and the limiting threshold values are found to be 22.7 mW for 0.01 M and 24.9 mW for 0.03 and 0.05 M LTB:Cu nanoparticles. PMID:25615676

  17. Distribution limits of Batrachochytrium dendrobatidis: a case study in the Rocky Mountains, USA.

    PubMed

    Hossack, Blake R; Muths, Erin; Anderson, Chauncey W; Kirshtein, Julie D; Corn, Paul Stephen

    2009-10-01

    Knowledge of the environmental constraints on a pathogen is critical to predicting its dynamics and effects on populations. Batrachochytrium dendrobatidis (Bd), an aquatic fungus that has been linked with widespread amphibian declines, is ubiquitous in the Rocky Mountains. As part of assessing the distribution limits of Bd in our study area, we sampled the water column and sediments for Bd zoospores in 30 high-elevation water bodies that lacked amphibians. All water bodies were in areas where Bd has been documented from neighboring, lower-elevation areas. We targeted areas lacking amphibians because existence of Bd independent of amphibians would have both ecologic and management implications. We did not detect Bd, which supports the hypothesis that it does not live independently of amphibians. However, assuming a detection sensitivity of 59.5% (based on sampling of water where amphibians tested positive for Bd), we only had 95% confidence of detecting Bd if it was in > or =16% of our sites. Further investigation into potential abiotic reservoirs is needed, but our results provide a strategic step in determining the distributional and environmental limitations of Bd in our study region. PMID:19901397

  18. Passive optical limiting studies of nanostructured Cu doped ZnO-PVA composite thin films

    NASA Astrophysics Data System (ADS)

    Tamgadge, Y. S.; Sunatkari, A. L.; Talwatkar, S. S.; Pahurkar, V. G.; Muley, G. G.

    2016-01-01

    We prepared undoped and Cu doped ZnO semiconducting nanoparticles (NPs) by chemical co-precipitation method and obtained Cu doped ZnO-polyvinyl alcohol (PVA) nanocomposite thin films by spin coating to investigate third order nonlinear optical and optical limiting properties under cw laser excitation. Powder samples of NPs were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), energy dispersive spectroscopy, transmission electron microscopy, ultraviolet-visible (UV-vis) and Fourier transform infrared spectroscopy. XRD pattern and FE-SEM micrograph revealed the presence of hexagonal wurtzite phase ZnO NPs having uniform morphology with average particle size of 20 nm. The presence of excitons and absorption peaks in the range 343-360 nm, revealed by UV-vis study, were attributed to excitons in n = 1 quantum state. Third order NLO properties of all composite thin films were investigated by He-Ne continuous wave (cw) laser of wavelength 632.8 nm using Z-scan technique. Thermally stimulated enhanced values of nonlinear refraction and absorption coefficients were obtained which may be attributed to self-defocusing effect, reverse saturable absorption, weak free carrier absorption and surface states properties originated from thermo optic effect. Optical limiting properties have been studied using cw diode laser of wavelength 808 nm and results are presented.

  19. Distribution limits of Batrachochytrium dendrobatidis: a case study in the Rocky Mountains, USA.

    USGS Publications Warehouse

    Hossack, B.R.; Muths, E.; Anderson, C.W.; Kirshtein, J.D.; Corn, P.S.

    2009-01-01

    Knowledge of the environmental constraints on a pathogen is critical to predicting its dynamics and effects on populations. Batrachochytrium dendrobatidis (Bd), an aquatic fungus that has been linked with widespread amphibian declines, is ubiquitous in the Rocky Mountains. As part of assessing the distribution limits of Bd in our study area, we sampled the water column and sediments for Bd zoospores in 30 high-elevation water bodies that lacked amphibians. All water bodies were in areas where Bd has been documented from neighboring, lower-elevation areas. We targeted areas lacking amphibians because existence of Bd independent of amphibians would have both ecologic and management implications. We did not detect Bd, which supports the hypothesis that it does not live independently of amphibians. However, assuming a detection sensitivity of 59.5% (based on sampling of water where amphibians tested positive for Bd), we only had 95% confidence of detecting Bd if it was in > or =16% of our sites. Further investigation into potential abiotic reservoirs is needed, but our results provide a strategic step in determining the distributional and environmental limitations of Bd in our study region.

  20. Limitations and relative utility of screening assays to assess engineered nanoparticle toxicity in a human cell line

    SciTech Connect

    Monteiro-Riviere, N.A.; Inman, A.O.; Zhang, L.W.

    2009-01-15

    Single-walled carbon nanotubes (SWCNT), fullerenes (C{sub 60}), carbon black (CB), nC{sub 60}, and quantum dots (QD) have been studied in vitro to determine their toxicity in a number of cell types. Here, we report that classical dye-based assays such as MTT and neutral red (NR) that determine cell viability produce invalid results with some NM (nanomaterials) due to NM/dye interactions and/or NM adsorption of the dye/dye products. In this study, human epidermal keratinocytes (HEK) were exposed in vitro to CB, SWCNT, C{sub 60}, nC{sub 60}, and QD to assess viability with calcein AM (CAM), Live/Dead (LD), NR, MTT, Celltiter 96 AQueous One (96 AQ), alamar Blue (aB), Celltiter-Blue (CTB), CytoTox One{sup TM} (CTO), and flow cytometry. In addition, trypan blue (TB) was quantitated by light microscopy. Assay linearity (R{sup 2} value) was determined with HEK plated at concentrations from 0 to 25,000 cells per well in 96-well plates. HEK were treated with serial dilutions of each NM for 24 h and assessed with each of the viability assays. TB, CAM and LD assays, which depend on direct staining of living and/or dead cells, were difficult to interpret due to physical interference of the NM with cells. Results of the dye-based assays varied a great deal, depending on the interactions of the dye/dye product with the carbon nanomaterials (CNM). Results show the optimal high throughput assay for use with carbon and noncarbon NM was 96 AQ. This study shows that, unlike small molecules, CNM interact with assay markers to cause variable results with classical toxicology assays and may not be suitable for assessing nanoparticle cytotoxicity. Therefore, more than one assay may be required when determining nanoparticle toxicity for risk assessment.

  1. Ten-dimensional anthropomorphic arm control in a human brain-machine interface: difficulties, solutions, and limitations

    NASA Astrophysics Data System (ADS)

    Wodlinger, B.; Downey, J. E.; Tyler-Kabara, E. C.; Schwartz, A. B.; Boninger, M. L.; Collinger, J. L.

    2015-02-01

    Objective. In a previous study we demonstrated continuous translation, orientation and one-dimensional grasping control of a prosthetic limb (seven degrees of freedom) by a human subject with tetraplegia using a brain-machine interface (BMI). The current study, in the same subject, immediately followed the previous work and expanded the scope of the control signal by also extracting hand-shape commands from the two 96-channel intracortical electrode arrays implanted in the subject’s left motor cortex. Approach. Four new control signals, dictating prosthetic hand shape, replaced the one-dimensional grasping in the previous study, allowing the subject to control the prosthetic limb with ten degrees of freedom (three-dimensional (3D) translation, 3D orientation, four-dimensional hand shaping) simultaneously. Main results. Robust neural tuning to hand shaping was found, leading to ten-dimensional (10D) performance well above chance levels in all tests. Neural unit preferred directions were broadly distributed through the 10D space, with the majority of units significantly tuned to all ten dimensions, instead of being restricted to isolated domains (e.g. translation, orientation or hand shape). The addition of hand shaping emphasized object-interaction behavior. A fundamental component of BMIs is the calibration used to associate neural activity to intended movement. We found that the presence of an object during calibration enhanced successful shaping of the prosthetic hand as it closed around the object during grasping. Significance. Our results show that individual motor cortical neurons encode many parameters of movement, that object interaction is an important factor when extracting these signals, and that high-dimensional operation of prosthetic devices can be achieved with simple decoding algorithms. ClinicalTrials.gov Identifier: NCT01364480.

  2. An applied study of human detection in single images

    NASA Astrophysics Data System (ADS)

    Liu, Ren; Xie, Xianghua

    2012-01-01

    In this paper we perform an applied comparative study of popular HOG based human detection and a state-of-the-art pose adaptive method that uses shape-based model construction. Both methods are implemented with kernel SVM, instead of linear SVM. Detailed performance evaluation is carried out on MIT pedestrian dataset and INRIA person dataset. This study shows that, although pose adaptive method has no significant advantage compared to the HOG based approach on those datasets, the pose adaptive approach is more efficient in detection and it has the capability to segment the human shape from images while carrying out detection which can be advantageous in many applications.

  3. Literary works as case studies for teaching human experimentation ethics.

    PubMed

    Cassidy, V R

    1996-03-01

    Case studies are widely used as a teaching strategy for a variety of topics in various disciplines. They are particularly valued as a teaching strategy in the teaching of ethics because they provide a context for understanding the complexities of situations involving ethical dilemmas. This article describes the successful use of two literary works as case studies in teaching master's students about the ethical issues in human experimentation. Pygmalion and Flowers for Algernon were selected to exemplify the ethical considerations important in the conduct of research with human subjects. Students found the assignment both personally and professionally stimulating and recommended continued use of the assignment in the course. PMID:8676212

  4. Study on Market Stability and Price Limit of Chinese Stock Index Futures Market: An Agent-Based Modeling Perspective.

    PubMed

    Xiong, Xiong; Nan, Ding; Yang, Yang; Yongjie, Zhang

    2015-01-01

    This paper explores a method of managing the risk of the stock index futures market and the cross-market through analyzing the effectiveness of price limits on the Chinese Stock Index 300 futures market. We adopt a cross-market artificial financial market (include the stock market and the stock index futures market) as a platform on which to simulate the operation of the CSI 300 futures market by changing the settings of price limits. After comparing the market stability under different price limits by appropriate liquidity and volatility indicators, we find that enhancing price limits or removing price limits both play a negative impact on market stability. In contrast, a positive impact exists on market stability if the existing price limit is maintained (increase of limit by10%, down by 10%) or it is broadened to a proper extent. Our study provides reasonable advice for a price limit setting and risk management for CSI 300 futures. PMID:26571135

  5. Study on Market Stability and Price Limit of Chinese Stock Index Futures Market: An Agent-Based Modeling Perspective

    PubMed Central

    2015-01-01

    This paper explores a method of managing the risk of the stock index futures market and the cross-market through analyzing the effectiveness of price limits on the Chinese Stock Index 300 futures market. We adopt a cross-market artificial financial market (include the stock market and the stock index futures market) as a platform on which to simulate the operation of the CSI 300 futures market by changing the settings of price limits. After comparing the market stability under different price limits by appropriate liquidity and volatility indicators, we find that enhancing price limits or removing price limits both play a negative impact on market stability. In contrast, a positive impact exists on market stability if the existing price limit is maintained (increase of limit by10%, down by 10%) or it is broadened to a proper extent. Our study provides reasonable advice for a price limit setting and risk management for CSI 300 futures. PMID:26571135

  6. The human leukocyte antigen TAP2 gene defines the centromeric limit of melanoma susceptibility on chromosome 6p.

    PubMed

    Lee, J E; Loflin, P T; Laud, P R; Lu, M; Reveille, J D; Lawlor, D A

    1996-02-01

    A single human leukocyte antigen (HLA) class II allele, DQB1*0301, is strongly associated with melanoma, and the HLA-DR locus provides the telomeric boundary for melanoma susceptibility in the HLA class II region of chromosome 6. However, the centromeric boundary is unknown. This study was designed to determine whether the adjacent upstream transporter associated with antigen processing (TAP) locus, TAP2, constitutes the centromeric boundary of disease susceptibility in melanoma. Molecular oligotyping of TAP2 genes was performed for 36 Caucasian patients with melanoma and for 32 Caucasian control individuals by both amplification refractory mutation system (ARMS) polymerase chain reaction (PCR) and PCR-sequence-specific oligonucleotide (SSO) typing. TAP2 allele frequencies in the melanoma patients were compared to those in non-melanoma Caucasian control populations, and to HLA-DQ allele frequencies determined by molecular oligotyping. While HLA-DQB1*0301 was more common in this group of 36 melanoma patients compared to a group of 200 controls (56 percent vs. 27 percent, Bonferoni-corrected chi-square p < = 0.01), no significant differences were observed in TAP2 allele frequencies between melanoma patients and controls. The TAP2 locus represents the centromeric boundary of disease susceptibility for melanoma in the class II region of chromosome 6p. These results support an etiologic role for HLA-DQB1*0301 in melanoma susceptibility. PMID:8851724

  7. Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

    PubMed Central

    Atkinson, Stuart P.; Quionero, Alicia; Martnez, Sebastin; Pellicer, Antonio; Simn, Carlos

    2012-01-01

    Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expression of tissue remodeling enzymes and activity of human endometrial stromal cells (hESCs) related to trophoblast invasion control. Treatment of hESCs with the HDAC inhibitor trichostatin A (TSA) increased the expression of TIMP-1 and TIMP-3 while decreased MMP-2, MMP-9 and uPA and have an inhibitory effect on trophoblast invasion. Moreover, histone acetylation is detected at the promoters of TIMP-1 and TIMP-3 genes in TSA-treated. In addition, in an in vitro decidualized hESCs model, the increase of TIMP-1 and TIMP-3 expression is associated with histone acetylation at the promoters of these genes. Our results demonstrate that histone acetylation disrupt the balance of ECM modulators provoking a restrain of trophoblast invasion. These findings are important as an epigenetic mechanism that can be used to control trophoblast invasion. PMID:22291969

  8. Epidemiologic studies of the human microbiome and cancer.

    PubMed

    Vogtmann, Emily; Goedert, James J

    2016-02-01

    The human microbiome, which includes the collective genome of all bacteria, archaea, fungi, protists, and viruses found in and on the human body, is altered in many diseases and may substantially affect cancer risk. Previously detected associations of individual bacteria (e.g., Helicobacter pylori), periodontal disease, and inflammation with specific cancers have motivated studies considering the association between the human microbiome and cancer risk. This short review summarises microbiome research, focusing on published epidemiological associations with gastric, oesophageal, hepatobiliary, pancreatic, lung, colorectal, and other cancers. Large, prospective studies of the microbiome that employ multidisciplinary laboratory and analysis methods, as well as rigorous validation of case status, are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, screening, and treatment. PMID:26730578

  9. Epidemiologic studies of the human microbiome and cancer

    PubMed Central

    Vogtmann, Emily; Goedert, James J

    2016-01-01

    The human microbiome, which includes the collective genome of all bacteria, archaea, fungi, protists, and viruses found in and on the human body, is altered in many diseases and may substantially affect cancer risk. Previously detected associations of individual bacteria (e.g., Helicobacter pylori), periodontal disease, and inflammation with specific cancers have motivated studies considering the association between the human microbiome and cancer risk. This short review summarises microbiome research, focusing on published epidemiological associations with gastric, oesophageal, hepatobiliary, pancreatic, lung, colorectal, and other cancers. Large, prospective studies of the microbiome that employ multidisciplinary laboratory and analysis methods, as well as rigorous validation of case status, are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, screening, and treatment. PMID:26730578

  10. Study of the art: canine olfaction used for cancer detection on the basis of breath odour. Perspectives and limitations.

    PubMed

    Jezierski, Tadeusz; Walczak, Marta; Ligor, Tomasz; Rudnicka, Joanna; Buszewski, Bogus?aw

    2015-06-01

    Experimental studies using trained dogs to identify breath odour markers of human cancer, published in the recent decade, have been analyzed and compared with the authors' own results. Particular published studies differ as regards the experimental setup, kind of odour samples (breath, urine, tumor tissue, serum), sample collection methods, dogs' characteristics and dog training methods as well as in results presented in terms of detection sensitivity and specificity. Generally it can be stated that trained dogs are able to distinguish breath odour samples typical for patients with lung cancer and other cancers from samples typical for healthy humans at a 'better than by chance' rate. Dogs' indications were positively correlated with content of 2-pentanone and ethyl acetate (r = 0.97 and r = 0.85 respectively) and negatively correlated with 1-propanol and propanal in breath samples (r = -0.98 and -0.87 respectively). The canine method has some advantages as a potential cancer-screening method, due to its non-invasiveness, simplicity of odour sampling and storage, ease of testing and interpretation of results and relatively low costs. Disadvantages and limitations of this method are related to the fact that it is still not known exactly to which chemical compounds and/or their combinations the dogs react. So far it could not be confirmed that dogs are able to sniff out early preclinical cancer stages with approximately the same accuracy as already diagnosed cases. The detection accuracy may vary due to failure in conditioning of dogs, decreasing motivation or confounding factors. The dogs' performance should be systematically checked in rigorous double-blind procedures. Recommendations for methodological standardization have been proposed. PMID:25944810

  11. To boil or not to boil -- A study of bubble embryo dormancy limits

    SciTech Connect

    Martin-Dominguez, I.R.; McDonald, T.W.

    1997-12-31

    In the literature, particularly for refrigerants, experimental studies on the superheat required to initiate nucleate boiling tend to be widely scattered, not only among investigators but even for repeated tests by the same investigator. This study provides an explanation of why this occurs and how to avoid such scatter in future tests. With few exceptions, only re-entrant surface cavities are capable of containing dormant vapor bubble embryos. These dormant embryos are essential to initiate nucleate boiling from a cavity. The temperature (wall superheat) range over which an embryo is stable depends upon the cavity shape, neck size, and the fluid surface tension and thermal properties. Above the upper wall-superheat limit, nucleate boiling occurs. Below the lower limit, the embryo will quench (vanish) and cannot be reactivated by increasing the wall superheat. This study makes the following points, for a given cavity shape, fluid, and pressure (1) The larger the cavity neck radius, the smaller the wall-superheat range over which an embryo can exist. (2) Upon cooling any surface, the boiling cavity with the smallest neck radius will be the first to stop boiling but will require the greatest reduction in wall superheat to quench its embryo. (3) Each site that retains a (dormant) vapor embryo will resume boiling at the same wall-superheat at which it ceased boiling. (4) Small cavities can have a shape such that their vapor embryos will always exist, regardless of the wall temperature. Boiling can always be reinitiated from them. (5) Any wall subject to boiling has a memory. The greater the past wall-subcooling, the greater will be the wall-superheat required to initiate boiling. (6) The wall memory can be erased with sufficient wall-superheat and the presence of vapor.

  12. A Practical Study of the 66kV Fault Current Limiter (FCL) System with Rectifier

    NASA Astrophysics Data System (ADS)

    Tokuda, Noriaki; Matsubara, Yoshio; Yuguchi, Kyosuke; Ohkuma, Takeshi; Hobara, Natsuro; Takahashi, Yoshihisa

    A fault current limiter (FCL) is extensively expected to suppress fault current, particularly required for trunk power systems heavily connected high-voltage transmission lines, such as 500kV class power system which constitutes the nucleus of the electric power system. By installing such FCL in the power system, the system interconnection is possible without the need to raise the capacity of the circuit breakers, and facilities can be configured for efficiency, among other benefits. For these reasons, fault current limiters based on various principles of operation have been developed both in Japan and abroad. In this paper, we have proposed a new type of FCL system, consisting of solid-state diodes, DC coil and bypass AC coil, and described the specification of distribution power system and 66kV model at the island power system and the superconducting cable power system. Also we have made a practical study of 66kV class, which is the testing items and the future subjects of the rectifier type FCL system.

  13. Animal Models to Study Placental Development and Function throughout Normal and Dysfunctional Human Pregnancy.

    PubMed

    Grigsby, Peta L

    2016-01-01

    Abnormalities of placental development and function are known to underlie many pathologies of pregnancy, including spontaneous preterm birth, fetal growth restriction, and preeclampsia. A growing body of evidence also underscores the importance of placental dysfunction in the lifelong health of both mother and offspring. However, our knowledge regarding placental structure and function throughout pregnancy remains limited. Understanding the temporal growth and functionality of the human placenta throughout the entirety of gestation is important if we are to gain a better understanding of placental dysfunction. The utilization of new technologies and imaging techniques that could enable safe monitoring of placental growth and function in vivo has become a major focus area for the National Institutes of Child Health and Human Development, as evident by the establishment of the "Human Placenta Project." Many of the objectives of the Human Placenta Project will necessitate preclinical studies and testing in appropriately designed animal models that can be readily translated to the clinical setting. This review will describe the advantages and limitations of relevant animals such as the guinea pig, sheep, and nonhuman primate models that have been used to study the role of the placenta in fetal growth disorders, preeclampsia, or other maternal diseases during pregnancy. PMID:26752715

  14. Meta-analyses of studies of the human microbiota

    PubMed Central

    Lozupone, Catherine A.; Stombaugh, Jesse; Gonzalez, Antonio; Ackermann, Gail; Wendel, Doug; Vzquez-Baeza, Yoshiki; Jansson, Janet K.; Gordon, Jeffrey I.; Knight, Rob

    2013-01-01

    Our body habitat-associated microbial communities are of intense research interest because of their influence on human health. Because many studies of the microbiota are based on the same bacterial 16S ribosomal RNA (rRNA) gene target, they can, in principle, be compared to determine the relative importance of different disease/physiologic/developmental states. However, differences in experimental protocols used may produce variation that outweighs biological differences. By comparing 16S rRNA gene sequences generated from diverse studies of the human microbiota using the QIIME database, we found that variation in composition of the microbiota across different body sites was consistently larger than technical variability across studies. However, samples from different studies of the Western adult fecal microbiota generally clustered by study, and the 16S rRNA target region, DNA extraction technique, and sequencing platform produced systematic biases in observed diversity that could obscure biologically meaningful compositional differences. In contrast, systematic compositional differences in the fecal microbiota that occurred with age and between Western and more agrarian cultures were great enough to outweigh technical variation. Furthermore, individuals with ileal Crohn's disease and in their third trimester of pregnancy often resembled infants from different studies more than controls from the same study, indicating parallel compositional attributes of these distinct developmental/physiological/disease states. Together, these results show that cross-study comparisons of human microbiota are valuable when the studied parameter has a large effect size, but studies of more subtle effects on the human microbiota require carefully selected control populations and standardized protocols. PMID:23861384

  15. Meta-analyses of studies of the human microbiota.

    PubMed

    Lozupone, Catherine A; Stombaugh, Jesse; Gonzalez, Antonio; Ackermann, Gail; Wendel, Doug; Vzquez-Baeza, Yoshiki; Jansson, Janet K; Gordon, Jeffrey I; Knight, Rob

    2013-10-01

    Our body habitat-associated microbial communities are of intense research interest because of their influence on human health. Because many studies of the microbiota are based on the same bacterial 16S ribosomal RNA (rRNA) gene target, they can, in principle, be compared to determine the relative importance of different disease/physiologic/developmental states. However, differences in experimental protocols used may produce variation that outweighs biological differences. By comparing 16S rRNA gene sequences generated from diverse studies of the human microbiota using the QIIME database, we found that variation in composition of the microbiota across different body sites was consistently larger than technical variability across studies. However, samples from different studies of the Western adult fecal microbiota generally clustered by study, and the 16S rRNA target region, DNA extraction technique, and sequencing platform produced systematic biases in observed diversity that could obscure biologically meaningful compositional differences. In contrast, systematic compositional differences in the fecal microbiota that occurred with age and between Western and more agrarian cultures were great enough to outweigh technical variation. Furthermore, individuals with ileal Crohn's disease and in their third trimester of pregnancy often resembled infants from different studies more than controls from the same study, indicating parallel compositional attributes of these distinct developmental/physiological/disease states. Together, these results show that cross-study comparisons of human microbiota are valuable when the studied parameter has a large effect size, but studies of more subtle effects on the human microbiota require carefully selected control populations and standardized protocols. PMID:23861384

  16. 76 FR 34703 - Human Studies Review Board Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-14

    ... research (71 FR 24 6138) that called for creating a new, independent human studies review board (i.e., HSRB..., appearance of a lack of impartiality, or prior involvement with matters likely to be reviewed by the Board... appearance of a lack of impartiality, or lack of independence, or bias; and the availability to...

  17. Preparing Global Citizens through the Study of Human Rights

    ERIC Educational Resources Information Center

    Kirkwood-Tucker, Toni Fuss

    2012-01-01

    The preparation of students for global citizenship represents a central challenge to social studies educators in the twenty-first century. Two-thirds of the world's poor are steeped in abject poverty and its grim consequences. The world refugee problem has reached staggering proportions. There is an international epidemic of human trafficking, and

  18. Moral Disengagement in Business and Humanities Majors: An Exploratory Study

    ERIC Educational Resources Information Center

    Cory, Suzanne N.; Hernandez, Abigail R.

    2014-01-01

    This study measures moral disengagement of undergraduate business and humanities students with a focus on differences in moral disengagement between genders. Students completed a survey that consisted of 32 statements and were asked to determine the degree to which they agreed with each, using a 7-point Likert scale. The questions measured moral…

  19. Preparing Global Citizens through the Study of Human Rights

    ERIC Educational Resources Information Center

    Kirkwood-Tucker, Toni Fuss

    2012-01-01

    The preparation of students for global citizenship represents a central challenge to social studies educators in the twenty-first century. Two-thirds of the world's poor are steeped in abject poverty and its grim consequences. The world refugee problem has reached staggering proportions. There is an international epidemic of human trafficking, and…

  20. USE OF BIOMARKERS OF OXIDATIVE STRESS IN HUMAN STUDIES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In human studies, biomarkers can be employed to reflect environmental pro-oxidant exposures and dietary antioxidant intake or to serve as a surrogate measure of a disease process like carcinogenesis. While a number of challenges must be overcome in using biomarkers to obtain a better understanding ...

  1. Arts & Humanities in the Social Studies. NCSS Publications Bulletin 90.

    ERIC Educational Resources Information Center

    Selwyn, Douglas

    This bulletin is designed to help teachers integrate the arts and humanities into the social studies curriculum. The volume includes three chapters. Chapter 1, "Learning Through the Arts," features the following sections: (1) "Integration"; (2) "Assessment"; and (3) "References and For Further Reading." Chapter 2, "Using Theater in the Classroom,"

  2. ORD BEST PRACTICES FOR OBSERVATIONAL HUMAN EXPOSURE MEASUREMENT STUDIES

    EPA Science Inventory

    This abstract describes a presentation for the 2007 Society of Toxicology Annual Meeting in Charlotte, NC on March 27, 2007. It will be included in a special Issues Session titled "Scientific and Ethical Considerations in Human Exposure Studies." The presentation desc...

  3. Arts & Humanities in the Social Studies. NCSS Publications Bulletin 90.

    ERIC Educational Resources Information Center

    Selwyn, Douglas

    This bulletin is designed to help teachers integrate the arts and humanities into the social studies curriculum. The volume includes three chapters. Chapter 1, "Learning Through the Arts," features the following sections: (1) "Integration"; (2) "Assessment"; and (3) "References and For Further Reading." Chapter 2, "Using Theater in the Classroom,"…

  4. Human Exposures to PAHs: an Eastern United States Pilot Study

    EPA Science Inventory

    Personal exposure monitoring for select polycyclic aromatic hydrocarbons (PAHs) was performed as part of the National Human Exposure Assessment Survey (NHEXAS) Pilot Study in Baltimore, MD and in four surrounding counties (NHEXAS-Maryland). An objective of this effort was to esta...

  5. Capabilities and limitations of neutron imaging for studying soil-root system (Invited)

    NASA Astrophysics Data System (ADS)

    Moradi, A. B.

    2010-12-01

    Soil is heterogeneous by nature. Additional heterogeneity is added to soil as a result of the activities of soil biota and vegetation. Plant roots and soil microorganisms exude organic and inorganic substances into the soil and change the soil properties in their vicinity. They take up water and nutrients and change the distribution of water and ions in the soil. Therefore, most of the soil physical, chemical, and biological parameters in the root-zone have a dynamic character and vary over time and space. Traditional methods of accessing soil parameters such as point-like measurements and extraction of soil solution are for many purposes too invasive, tedious, expensive, and insufficient with respect to spatial and temporal resolution. There is a growing need for the direct, non-destructive and non-invasive measurements of processes such as water flow and solute transport in soils. Imaging techniques provide an opportunity to measure dynamic processes in soil without disturbing the system. Numerous imaging methods have recently been developed and successfully tested in soil and other porous media. However, each method has its own benefits and limitations in applications and often a compromise between real soil conditions and the requirements of each technique is necessary. Neutron imaging is a unique tool to study water dynamics in soil, root developments, and root-soil interactions. This is due to the high interaction probability of hydrogen nuclei with neutrons. Therefore, all proton-bearing materials such as water and roots are easily visualized in great details. For quantitative studies of the processes, however, neutron imaging needs to be combined with proper image analysis techniques. Modeling simulations can also be employed for interpretation of results and for testing our understanding of the system. This study discusses the theory and potential application of neutron imaging as compared with other techniques such as MRI and X-ray. It evaluates the capabilities and limitations of neutron imaging technique for root-zone studies with particular emphasize on soil moisture and root developments in soil. Necessary corrections and quantifications of the neutron images will be discussed and the quantified results extracted from the images will be compared with the theoretical values. A range of neutron radiography and tomography experiments have been carried out in recent years focusing on water distribution in soil, water uptake by roots, and root-metal interactions. Selected examples of these studies at various scales of micrometers to decimeters will be presented. These applications demonstrate the heterogeneous character of soil and highlight the need for combining imaging methods with image analysis tools and modeling simulations. Further hardware and software developments are needed to improve the spatial resolution of neutron imaging for more detailed soil studies.

  6. FY95 limited energy study for the area `a` package boiler. Final report

    SciTech Connect

    1995-11-03

    In March 1995, Affiliated Engineers SE, Inc. (AESE) was retained by the Mobile District U.S. Army Corps of Engineers to perform a Limited Energy Study for Holston Army Ammunition Plant, Kingsport, Tennessee. The results of this field survey were subsequently tabulated and used to generate single line building drawings on Autocad. This report summarizes the results obtained from this field investigation and the analysis of various alternative Energy Conservation Opportunities (ECO`s). To develop the field data into various alternative ECO concepts or models, we utilized an Excel spreadsheet to tabulate and compare energy consumption, installation and operating costs for various ECO`s. These ECO`s were then analyzed for suitability for the Energy Conservation Investment Program (ECIP) using the government`s software package called Life Cycle Cost in Design (LCCID).

  7. Magnetotransport studies of mobility limiting mechanisms in undoped Si/SiGe heterostructures

    NASA Astrophysics Data System (ADS)

    Mi, X.; Hazard, T. M.; Payette, C.; Wang, K.; Zajac, D. M.; Cady, J. V.; Petta, J. R.

    2015-07-01

    We perform detailed magnetotransport studies on two-dimensional electron gases (2DEGs) formed in undoped Si/SiGe heterostructures in order to identify the electron mobility limiting mechanisms. By analyzing data from 26 different heterostructures, we observe a strong correlation between the background oxygen concentration in the Si quantum well and the maximum mobility. The highest-quality wafer supports a 2DEG with mobility ? =160 000 cm 2/Vs at a density n =2.17 1011 /cm 2 and exhibits a metal-to-insulator transition at a critical density nc=0.46 1011 /cm 2. We extract a valley splitting ?v150 ? eV at a magnetic field B =1.8 T. These results provide evidence that undoped Si/SiGe heterostructures are suitable for the fabrication of few-electron quantum dots.

  8. Understanding the limits of Marxist approaches to sociocultural studies of science education

    NASA Astrophysics Data System (ADS)

    Lima Junior, Paulo; Ostermann, Fernanda; Rezende, Flavia

    2014-09-01

    In the first three sections of this paper we comment on some of the ideas developed in the forum papers, pointing out possible misunderstandings and constructing new explanations that clarify arguments we made in the original article. In the last section we expand the discussion raised in the original paper, elaborating on the limits of the use of Marxist approaches to sociocultural studies of science education. Following insights suggested by Loxley et al. (Cult Stud Sci Edu. doi: 10.1007/s11422-013-9554-z, 2013) and detailed by Zuss (Cult Stud Sci Edu, 2014) on the commodification of knowledge, we sketch an analysis of how knowledge is transformed into capital to understand why contemporary scholars are likely to be engaged in a relation of production that resembles capitalist exploitation.

  9. Understanding the limits of Marxist approaches to sociocultural studies of science education

    NASA Astrophysics Data System (ADS)

    Lima, Paulo; Ostermann, Fernanda; Rezende, Flavia

    2014-12-01

    In the first three sections of this paper we comment on some of the ideas developed in the forum papers, pointing out possible misunderstandings and constructing new explanations that clarify arguments we made in the original article. In the last section we expand the discussion raised in the original paper, elaborating on the limits of the use of Marxist approaches to sociocultural studies of science education. Following insights suggested by Loxley et al. (Cult Stud Sci Educ. doi: 10.1007/s11422-013-9554-z, 2013) and detailed by Zuss (Cult Stud Sci Educ. doi: 10.1007/s11422-013-9555-y, 2014) on the commodification of knowledge, we sketch an analysis of how knowledge is transformed into capital to understand why contemporary scholars are likely to be engaged in a relation of production that resembles capitalist exploitation.

  10. Simplified detection system for neuroreceptor studies in the human brain

    SciTech Connect

    Bice, A.N.; Wagner, H.N. Jr.; Frost, J.J.; Natarajan, T.K.; Lee, M.C.; Wong, D.F.; Dannals, R.F.; Ravert, H.T.; Wilson, A.A.; Links, J.M.

    1986-02-01

    A simple, inexpensive dual-detector system has been developed for measurement of positronemitting receptor-binding drugs in the human brain. This high efficiency coincidence counting system requires that only a few hundred microcuries of labeled drug be administered to the subject, thereby allowing for multiple studies without an excessive radiation dose. Measurement of the binding of (11C)carfentanil, a high affinity synthetic opiate, to opiate receptors in the presence and in the absence of a competitive opiate antagonist indicates the potential utility of this system for estimating different degrees of receptor occupation in the human brain.

  11. A review of studies on maternal occupational exposures and birth defects, and the limitations associated with these studies.

    PubMed

    Shi, L; Chia, S E

    2001-06-01

    The proportion of pregnant women who work during pregnancy is increasing as more women move into previously male-dominated occupations. With this move, occupational exposure to chemical or physical factors during pregnancy could be further increased. In the last decade, there have been many reports on the causes of birth defects. Unfortunately, most reported associations between occupational exposures and adverse reproductive outcomes in epidemiological studies are equivocal and often controversial. Many reported associations are only suggestive. More information is needed before firm conclusions can be drawn. The major reasons for ambiguous findings are due to limitations of study methodology, e.g. inappropriate endpoints, multiple confounders, low study power and inadequate analysis methods. It must also be noted that maternal work, and therefore exposure, may also differ greatly from country to country. PMID:11463868

  12. Impairment of a pregnant woman's acquired ability to limit Plasmodium falciparum by infection with human immunodeficiency virus type-1.

    PubMed

    Steketee, R W; Wirima, J J; Bloland, P B; Chilima, B; Mermin, J H; Chitsulo, L; Breman, J G

    1996-01-01

    In Africa, the human immunodeficiency virus (HIV) is the most serious emerging infection and Plasmodium falciparum malaria is one of the most prevalent infectious diseases. Both infections have serious consequences in pregnant women, their fetuses, and infants. We examined the association between HIV and P. falciparum in pregnant women enrolled in a malaria chemoprophylaxis study in rural Malawi. Pregnant women (n = 2,946) were enrolled at their first antenatal clinic visit (mean 5.6 months of pregnancy), placed on one of three chloroquine regimens, and followed through delivery. Plasmodium falciparum parasitemia was measured at enrollment, monthly thereafter, at delivery, and 2-6 months postpartum; placental and newborn (umbilical cord blood) infection was measured for hospital-delivered infants. Serum collected during pregnancy was tested for antibodies to HIV by enzyme-linked immunoassay with Western blot confirmation. Parasitemia was detected in 46% of 2,946 women at enrollment and 19.1% at delivery; HIV seroprevalence was 5.5%. The prevalence and geometric mean density (GMPD) of parasitemia at enrollment and at delivery were higher in HIV-seropositive(+) than in HIV-seronegative(-) women (at enrollment: 57% prevalence and a GMPD of 1,558 parasites/mm3 versus 44% and 670/mm3, respectively; P < 0.0001; and at delivery: 35% and 1,589/mm3 versus 18% and 373/mm3; P < 0.0005). Placental infection rates were higher in HIV(+) compared with HIV(-) women, (38% versus 23%; P < 0.0005). This association was strongest in multigravidas. Compared with infants born to HIV(-) women, newborns born to HIV(+) women had higher rates of umbilical cord blood parasitemia. Both HIV(+) and HIV(-) women had similar rates of parasitemia 2-6 months postpartum. The HIV infection diminishes a pregnant woman's capacity to control P. falciparum parasitemia and placental and newborn infection, the major determinants of the impact of P. falciparum on fetal growth and infant survival. PMID:8702036

  13. Effects of limited access dressing in chronic wounds: A biochemical and histological study

    PubMed Central

    Honnegowda, Thittamaranahalli Muguregowda; Kumar, Pramod; Padmanabha Udupa, E G; Sharan, Anurag; Singh, Rekha; Prasad, Hemanth K.; Rao, Pragna

    2015-01-01

    Background: Negative pressure wound therapy has emerged as an attractive treatment modality for the management and healing of chronic ulcers. Though numerous clinical studies are available, there is a lack of biochemical and histological studies evaluating the healing of chronic wounds. Materials and Methods: In the present study, a total 60 patients were divided into two groups: Limited access dressing (LAD) group (n = 30) and conventional dressing group (n = 30). Various biochemical parameters such as hydroxyproline, total protein and antioxidants such as reduced glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT) and oxidative biomarker malondialdhyde (MDA) are measured in the granulation tissue. Histologically amount of inflammatory infiltrate, angiogenesis, and collagen deposition are studied to assess wound healing. Results: Patients treated with LAD have shown significant increase in the mean (standard deviation) hydroxyproline (77.3 30.1 vs. 32.3 16.18; P = 0.026), total protein (13.89 9.0 vs. 8.9 4.59; P = 0.004), GSH (7.4 1.91 vs. 5.1 1.28; P = 0.039), GPx (122.3 59.3 vs. 88.7 34.11; P = 0.030), CAT (1.80 1.14 vs. 0.9 0.71; P = 0.002) and decrease in MDA (13.4 5.5 vs. 8.6 3.8; P = 0.004). Histological study showed comparatively fewer inflammatory cells, increased and well organised collagen bundles, and more angiogenesis in the LAD group when compared with that with conventional dressing after 10 days of treatment. Conclusion: In the present study, we have found beneficial effect of newer intermittent negative pressure therapy in combination with moist environment (LAD) on chronic wound healing by increasing collagen deposition and angiogenesis; and reducing oxidative stress and inflammatory infiltrate. PMID:25991881

  14. Theoretical study of resolution limits for time-resolved imaging of human breast

    NASA Astrophysics Data System (ADS)

    Gandjbakhche, Amir H.; Nossal, Ralph J.; Bonner, Robert F.

    1994-05-01

    Photon migration theory is employed to calculate the line spread function of time-resolved photons as they cross different planes inside a finite slab. Results are used to determine the spatial resolution for objects imbedded at each depth, shown to be proportional to the square root of the excess transit time (Delta) t. However, the light intensities available at small excess transit times, required to obtain finer resolutions, are severely reduced as tissue thickness is increased. Optical parameters of breast tissues are used in our theoretical findings in order to analyze the feasibility of breast screening. For 5- cm-thick tissues that mimic targets of interest in clinical mammography, were predict vanishingly small detectable intensity at the small values of (Delta) t needed in order to achieve 2-mm resolution. Additionally, because normal breast is a spatially heterogeneous mixture of glandular and adipose tissues, which have significantly different optical scattering parameters, the analysis indicates large-amplitude background variations, particularly at short delay times.

  15. Human Robotic Study at Houghton Crater - virtual reality study from NASA Ames (FFC) Future Fight

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Human Robotic Study at Houghton Crater - virtual reality study from NASA Ames (FFC) Future Fight Central simulator tower L-R: Dr Geoffrey Briggs; Jen Jasper (seated); Dr Jan Akins and Mr. Tony Gross, Ames

  16. 40 CFR 26.1603 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Operation of the Human Studies Review... PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1603 Operation of the Human Studies Review Board. EPA shall establish and operate a Human Studies Review Board as follows:...

  17. 40 CFR 26.1605 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Operation of the Human Studies Review... PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1605 Operation of the Human Studies Review Board. EPA shall establish and operate a Human Studies Review Board as follows:...

  18. 40 CFR 26.1605 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Operation of the Human Studies Review... PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1605 Operation of the Human Studies Review Board. EPA shall establish and operate a Human Studies Review Board as follows:...

  19. 40 CFR 26.1603 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Operation of the Human Studies Review... PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1603 Operation of the Human Studies Review Board. EPA shall establish and operate a Human Studies Review Board as follows:...

  20. 40 CFR 26.1603 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Operation of the Human Studies Review... PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1603 Operation of the Human Studies Review Board. EPA shall establish and operate a Human Studies Review Board as follows:...

  1. Isolation of highly enriched primary human microglia for functional studies.

    PubMed

    Rustenhoven, Justin; Park, Thomas I-H; Schweder, Patrick; Scotter, John; Correia, Jason; Smith, Amy M; Gibbons, Hannah M; Oldfield, Robyn L; Bergin, Peter S; Mee, Edward W; Faull, Richard L M; Curtis, Maurice A; Scott Graham, E; Dragunow, Mike

    2016-01-01

    Microglia, the resident macrophages of the central nervous system play vital roles in brain homeostasis through clearance of pathogenic material. Microglia are also implicated in neurological disorders through uncontrolled activation and inflammatory responses. To date, the vast majority of microglial studies have been performed using rodent models. Human microglia differ from rodent counterparts in several aspects including their response to pharmacological substances and their inflammatory secretions. Such differences highlight the need for studies on primary adult human brain microglia and methods to isolate them are therefore required. Our procedure generates microglial cultures of >95% purity from both biopsy and autopsy human brain tissue using a very simple media-based culture procedure that takes advantage of the adherent properties of these cells. Microglia obtained in this manner can be utilised for research within a week. Isolated microglia demonstrate phagocytic ability and respond to inflammatory stimuli and their purity makes them suitable for numerous other forms of in vitro studies, including secretome and transcriptome analysis. Furthermore, this protocol allows for the simultaneous isolation of neural precursor cells during the microglial isolation procedure. As human brain tissue is such a precious and valuable resource the simultaneous isolation of multiple cell types is highly beneficial. PMID:26778406

  2. Isolation of highly enriched primary human microglia for functional studies

    PubMed Central

    Rustenhoven, Justin; Park, Thomas I-H; Schweder, Patrick; Scotter, John; Correia, Jason; Smith, Amy M.; Gibbons, Hannah M.; Oldfield, Robyn L.; Bergin, Peter S.; Mee, Edward W.; Faull, Richard L. M.; Curtis, Maurice A.; Scott Graham, E.; Dragunow, Mike

    2016-01-01

    Microglia, the resident macrophages of the central nervous system play vital roles in brain homeostasis through clearance of pathogenic material. Microglia are also implicated in neurological disorders through uncontrolled activation and inflammatory responses. To date, the vast majority of microglial studies have been performed using rodent models. Human microglia differ from rodent counterparts in several aspects including their response to pharmacological substances and their inflammatory secretions. Such differences highlight the need for studies on primary adult human brain microglia and methods to isolate them are therefore required. Our procedure generates microglial cultures of >95% purity from both biopsy and autopsy human brain tissue using a very simple media-based culture procedure that takes advantage of the adherent properties of these cells. Microglia obtained in this manner can be utilised for research within a week. Isolated microglia demonstrate phagocytic ability and respond to inflammatory stimuli and their purity makes them suitable for numerous other forms of in vitro studies, including secretome and transcriptome analysis. Furthermore, this protocol allows for the simultaneous isolation of neural precursor cells during the microglial isolation procedure. As human brain tissue is such a precious and valuable resource the simultaneous isolation of multiple cell types is highly beneficial. PMID:26778406

  3. The Watershed as A Conceptual Framework for the Study of Environmental and Human Health

    PubMed Central

    Kolok, Alan S.; Beseler, Cheryl L.; Chen, Xun-Hong; Shea, Patrick J.

    2009-01-01

    The watershed provides a physical basis for establishing linkages between aquatic contaminants, environmental health and human health. Current attempts to establish such linkages are limited by environmental and epidemiological constraints. Environmental limitations include difficulties in characterizing the temporal and spatial dynamics of agricultural runoff, in fully understanding the degradation and metabolism of these compounds in the environment, and in understanding complex mixtures. Epidemiological limitations include difficulties associated with the organization of risk factor data and uncertainty about which measurable endpoints are most appropriate for an agricultural setting. Nevertheless, it is our contention that an adoption of the watershed concept can alleviate some of these difficulties. From an environmental perspective, the watershed concept helps identify differences in land use and application of agrichemicals at a level of resolution relevant to human health outcomes. From an epidemiological perspective, the watershed concept places data into a construct with environmental relevance. In this perspectives paper, we discuss how the watershed can provide a conceptual framework for studies in environmental and human health. PMID:20508751

  4. A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough.

    PubMed

    Nguyen, Annalee W; Wagner, Ellen K; Laber, Joshua R; Goodfield, Laura L; Smallridge, William E; Harvill, Eric T; Papin, James F; Wolf, Roman F; Padlan, Eduardo A; Bristol, Andy; Kaleko, Michael; Maynard, Jennifer A

    2015-12-01

    Despite widespread vaccination, pertussis rates are rising in industrialized countries and remain high worldwide. With no specific therapeutics to treat disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin is a major contributor to disease, responsible for local and systemic effects including leukocytosis and immunosuppression. We humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human immunoglobulin G1 molecules with no loss of affinity or in vitro neutralization activity. When administered prophylactically to mice as a binary cocktail, antibody treatment completely mitigated the Bordetella pertussis-induced rise in white blood cell counts and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated, but not untreated control animals, experienced a blunted rise in white blood cell counts and accelerated bacterial clearance rates. These preliminary findings support further investigation into the use of these antibodies to treat human neonatal pertussis in conjunction with antibiotics and supportive care. PMID:26631634

  5. HUMEX, a study on the survivability and adaptation of humans to long- duration exploratory missions

    NASA Astrophysics Data System (ADS)

    Horneck, G.

    ESA has recently initiated a study of the human responses, limits and needs with regard to the stress environments of interplanetary and planetary missions. Emphasis was laid on human health and performance care as well as Advanced Life Support Developments including Bioregenerative Life Support Systems and environmental monitoring. The overall study goals were as follows: (i) to define reference scenarios for a European participation in human exploration and to estimate their influence on the Life Sciences and Life Support requirements; (ii) for selected mission scenarios, to critically assess the limiting factors for human health, wellbeing, and performance and to recommend relevant countermeasures; (iii) for selected mission scenarios, to critically assess the potential of Advanced Life Support Developments and to propose a European strategy including terrestrial applications; (iv) to critically assess the feasibility of existing facilities and technologies on ground and in space as testbeds in preparation for human exploratory missions and to develop a test plan for ground and ISS campaigns; (v) to develop a roadmap for a future European strategy towards human exploratory missions, including preparatory activities and terrestrial applications and benefits. A lunar base at the south pole where constant sunlight and potential water ice deposits could be assumed was selected as the moon scenario. the impact on human health, performance and well being has been investigated from the view point of the effects of microgravity (during space travel), reduced gravity (on the Moon) and abrupt gravity changes (during launch and landing), of the effects of cosmic radiation including solar particle events, of psychological issues as well as general health care. Countermeasures as well as necessary research using ground- based testbeds and/or the ISS have been defined. The need for highly intelligent autonomous diagnostic and therapy systems was considered as a driver also for terrestrial applications. Likewise advanced life support systems with a high degree of autonomy and regenerative capacity and synergy effects were considered where bioregenerative life support systems and biodiagnistic systems become essential especially for the long-term Mars scenario. A roadmap for a future European strategy leading to a potential European participation in a cooperative human exploratory mission, either to the Moon or to Mars, was produced. Ref. Horneck et al. HUMEX, study on the Survivability and Adaptation of Humans to Long-Duration Exploratory Missions, ESA SP (in press)

  6. Evidence for human-mediated dispersal of exotic earthworms: support for exploring strategies to limit further spread.

    PubMed

    Hale, Cindy M

    2008-03-01

    As potent ecosystem engineers, non-native earthworms are altering the fundamental structure and function of previously earthworm-free cold-temperate hardwood forests in North America. Discarded earthworms used for fishing bait has been presumed to be an important vector for the continued spread of non-native earthworms because epicentres of invasion often include boat landings, lakeshores and roads. However, controversy has remained about the overall importance of human-mediated spread vs. natural expansion of established earthworm populations. In this issue of Molecular Ecology, Cameron et al. explore the continued role of humans in dispersing non-native earthworms. PMID:18302681

  7. Studying synapses in human brain with array tomography and electron microscopy

    PubMed Central

    Kay, Kevin R.; Smith, Colin; Wright, Ann K.; Serrano-Pozo, Alberto; Pooler, Amy M.; Koffie, Robert; Bastin, Mark E.; Bak, Thomas H.; Abrahams, Sharon; Kopeikina, Katherine J.; McGuone, Declan; Frosch, Matthew P.; Gillingwater, Thomas H.; Hyman, Bradley T.; Spires-Jones, Tara L.

    2013-01-01

    Postmortem studies of synapses in human brain are problematic due to the axial resolution limit of light microscopy and the difficulty preserving and analyzing ultrastructure with electron microscopy. Array tomography overcomes these problems by embedding autopsy tissue in resin and cutting ribbons of ultrathin serial sections. Ribbons are imaged with immunofluorescence, allowing high-throughput imaging of tens of thousands of synapses to assess synapse density and protein composition. The protocol takes approximately 3 days per case, excluding image analysis, which is done at the end of the study. Parallel processing for transmission electron microscopy (TEM) using a protocol modified to preserve structure in human samples allows complimentary ultrastructural studies. Incorporation of array tomography and TEM into brain banking is a potent way of phenotyping synapses in well-characterized clinical cohorts to develop clinico-pathological correlations at the synapse level. This will be important for research in neurodegenerative disease, developmental diseases, and psychiatric illness. PMID:23787894

  8. Reconstructed epidermis versus human and animal skin in skin absorption studies.

    PubMed

    Schreiber, S; Mahmoud, A; Vuia, A; Rübbelke, M K; Schmidt, E; Schaller, M; Kandárová, H; Haberland, A; Schäfer, U F; Bock, U; Korting, H C; Liebsch, M; Schäfer-Korting, M

    2005-09-01

    European chemical policy in general and the REACH initiative in particular will increase the number of chemical substances submitted to toxicological evaluation by several orders of magnitude compared to the current status. To limit animal exposure the resulting enormous increase in testing, however, asks for validated in vitro test systems. While the OECD favours in vitro testing for cutaneous absorption using viable human and animal skin (Guideline 428) the availability of viable human skin is already limited today. We present a comparison of various in vitro techniques suitable for routine skin absorption studies including commercially available reconstructed human epidermis which may be a reliable alternative to excised human and animal skin. In order to develop a protocol for the subsequent transfer to partner laboratories the experimental set-up was analysed stepwise using the OECD reference compounds caffeine and testosterone. Franz cell type, the donor and receptor media for hydrophilic/lipophilic substances, albumin and tensid addition, and storage conditions of the excised skins were systematically varied. A protocol has been developed which now allows to proceed to the pre-validation process. PMID:15913948

  9. An update on molecular genetic studies of human personality traits.

    PubMed

    Ebstein, Richard P; Zohar, Ada H; Benjamin, Jonathan; Belmaker, Robert H

    2002-01-01

    Personality is a complex phenotype and people differ considerably when they are evaluated by self-report questionnaires. There is convincing evidence from twin studies that basic personality dimensions in men and women have a considerable genetic component. However, only recently have common genetic polymorphisms been associated with particular personality traits, especially the dopamine D4 receptor with novelty seeking and the serotonin transporter with anxiety-related traits or neuroticism. The current review examines progress in the past few years in molecular personality genetics and focuses on the reasons for difficulties in replicating first findings as well as the prospects for future studies in this area. The molecular genetic structure of human personality is worth studying both for its intrinsic interest in helping us to understand individual differences in human behaviour and the light it will shed on more complex behavioural disorders that are likely to partially share some common genetic variants. PMID:15130845

  10. Life and Microgravity Sciences Spacelab Mission: Human Research Pilot Study

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B. (Editor); Walker, Karen R. (Editor); Hargens, Alan (Editor)

    1996-01-01

    The Life Sciences, Microgravity Science and Spacelab Mission contains a number of human experiments directed toward identifying the functional, metabolic and neurological characteristics of muscle weakness and atrophy during space flight. To ensure the successful completion of the flight experiments, a ground-based pilot study, designed to mimic the flight protocols as closely as possible, was carried out in the head-down tilt bed rest model. This report records the rationales, procedures, preliminary results and estimated value of the pilot study, the first of its kind, for 12 of the 13 planned experiments in human research. The bed rest study was conducted in the Human Research Facility at Ames Research Center from July 11 - August 28, 1995. Eight healthy male volunteers performed the experiments before, during and after 17 days bed rest. The immediate purposes of this simulation were to integrate the experiments, provide data in a large enough sample for publication of results, enable investigators to review individual experiments in the framework of a multi-disciplinary study and relay the experience of the pilot study to the mission specialists prior to launch.

  11. Microbial culturomics: paradigm shift in the human gut microbiome study.

    PubMed

    Lagier, J-C; Armougom, F; Million, M; Hugon, P; Pagnier, I; Robert, C; Bittar, F; Fournous, G; Gimenez, G; Maraninchi, M; Trape, J-F; Koonin, E V; La Scola, B; Raoult, D

    2012-12-01

    Comprehensive determination of the microbial composition of the gut microbiota and the relationships with health and disease are major challenges in the 21st century. Metagenomic analysis of the human gut microbiota detects mostly uncultured bacteria. We studied stools from two lean Africans and one obese European, using 212 different culture conditions (microbial culturomics), and tested the colonies by using mass spectrometry and 16S rRNA amplification and sequencing. In parallel, we analysed the same three samples by pyrosequencing 16S rRNA amplicons targeting the V6 region. The 32 500 colonies obtained by culturomics have yielded 340 species of bacteria from seven phyla and 117 genera, including two species from rare phyla (Deinococcus-Thermus and Synergistetes, five fungi, and a giant virus (Senegalvirus). The microbiome identified by culturomics included 174 species never described previously in the human gut, including 31 new species and genera for which the genomes were sequenced, generating c. 10 000 new unknown genes (ORFans), which will help in future molecular studies. Among these, the new species Microvirga massiliensis has the largest bacterial genome so far obtained from a human, and Senegalvirus is the largest virus reported in the human gut. Concurrent metagenomic analysis of the same samples produced 698 phylotypes, including 282 known species, 51 of which overlapped with the microbiome identified by culturomics. Thus, culturomics complements metagenomics by overcoming the depth bias inherent in metagenomic approaches. PMID:23033984

  12. Framework for Human-Automation Collaboration: Conclusions from Four Studies

    SciTech Connect

    Johanna Oxstrand; Katya L. Le Blanc; John O'Hara; Jeffrey C. Joe; April M. Whaley; Heather Medema

    2013-11-01

    The Human Automation Collaboration (HAC) research project is investigating how advanced technologies that are planned for Advanced Small Modular Reactors (AdvSMR) will affect the performance and the reliability of the plant from a human factors and human performance perspective. The HAC research effort investigates the consequences of allocating functions between the operators and automated systems. More specifically, the research team is addressing how to best design the collaboration between the operators and the automated systems in a manner that has the greatest positive impact on overall plant performance and reliability. Oxstrand et al. (2013 - March) describes the efforts conducted by the researchers to identify the research needs for HAC. The research team reviewed the literature on HAC, developed a model of HAC, and identified gaps in the existing knowledge of human-automation collaboration. As described in Oxstrand et al. (2013 – June), the team then prioritized the research topics identified based on the specific needs in the context of AdvSMR. The prioritization was based on two sources of input: 1) The preliminary functions and tasks, and 2) The model of HAC. As a result, three analytical studies were planned and conduced; 1) Models of Teamwork, 2) Standardized HAC Performance Measurement Battery, and 3) Initiators and Triggering Conditions for Adaptive Automation. Additionally, one field study was also conducted at Idaho Falls Power.

  13. A validation study of a stochastic model of human interaction

    NASA Astrophysics Data System (ADS)

    Burchfield, Mitchel Talmadge

    The purpose of this dissertation is to validate a stochastic model of human interactions which is part of a developmentalism paradigm. Incorporating elements of ancient and contemporary philosophy and science, developmentalism defines human development as a progression of increasing competence and utilizes compatible theories of developmental psychology, cognitive psychology, educational psychology, social psychology, curriculum development, neurology, psychophysics, and physics. To validate a stochastic model of human interactions, the study addressed four research questions: (a) Does attitude vary over time? (b) What are the distributional assumptions underlying attitudes? (c) Does the stochastic model, {-}N{intlimitssbsp{-infty}{infty}}varphi(chi,tau)\\ Psi(tau)dtau, have utility for the study of attitudinal distributions and dynamics? (d) Are the Maxwell-Boltzmann, Fermi-Dirac, and Bose-Einstein theories applicable to human groups? Approximately 25,000 attitude observations were made using the Semantic Differential Scale. Positions of individuals varied over time and the logistic model predicted observed distributions with correlations between 0.98 and 1.0, with estimated standard errors significantly less than the magnitudes of the parameters. The results bring into question the applicability of Fisherian research designs (Fisher, 1922, 1928, 1938) for behavioral research based on the apparent failure of two fundamental assumptions-the noninteractive nature of the objects being studied and normal distribution of attributes. The findings indicate that individual belief structures are representable in terms of a psychological space which has the same or similar properties as physical space. The psychological space not only has dimension, but individuals interact by force equations similar to those described in theoretical physics models. Nonlinear regression techniques were used to estimate Fermi-Dirac parameters from the data. The model explained a high degree of the variance in each probability distribution. The correlation between predicted and observed probabilities ranged from a low of 0.955 to a high value of 0.998, indicating that humans behave in psychological space as Fermions behave in momentum space.

  14. Optimization of a mega-ampere spherical tokamak for beta-limit and confinement studies

    SciTech Connect

    McCool, S.C.; Wootton, A.J.; Bravenec, R.V.

    1994-10-01

    Recent favorable results on the START experiment have caused renewed interest in the potential of low aspect ratio tokamaks. To aid in designing a next-step spherical tokamak to study confinement scaling, high beta, and high normalized beta plasmas for minimal cost, the authors have developed a transport scaling and device optimization code. This code STOP, benchmarked against START, includes 10 empirical confinement scaling laws and essential tokamak physics such as stability limits. Parameters are optimized separately for each scaling law and physical goal. Using STOP the authors find for R/a = 1.2 to 2.0 one can achieve {beta}{sub N} = 5, ({beta}) = 31--44%, and easily study predicted confinement degradation with auxiliary heating with just two neutral beams (P{sub NB} < 3.5 MW) for I{sub p} {ge} 0.75 MA, and R{sub 0} {ge} 0.6 m. In contrast, if one insists on using the nominal device parameters, i.e. I{sub p} = 1 MA and R{sub 0} = 0.8 m, with each scaling law, achieving {beta}{sub N} = 5 requires typically P{sub NB} {approx} 7.5 MW. They also conclude that while running D{sup 0} {yields} D{sup +} increases {tau}{sub E} {approx} 25%, with {tau}{sub E} already uncertain by 2--3{times}, one incurs restricted machine access and compromised physics operation.

  15. A comparative investigation of methods for longitudinal data with limits of detection through a case study.

    PubMed

    Fu, P; Hughes, J; Zeng, G; Hanook, S; Orem, J; Mwanda, O W; Remick, S C

    2016-02-01

    The statistical analysis of continuous longitudinal data may be complicated since quantitative levels of bioassay cannot always be determined. Values beyond the limits of detection (LOD) in the assays may not be observed and thus censored, rendering complexity to the analysis of such data. This article examines how both left-censoring and right censoring of HIV-1 plasma RNA measurements, collected for the study on AIDS-related Non-Hodgkin's lymphoma (AR-NHL) in East Africa, affects the quantification of viral load and explores the natural history of viral load measurements over time in AR-NHL patients receiving anticancer chemotherapy. Data analyses using Monte Carlo EM algorithm (MCEM) are compared to analyses where the LOD or LOD/2 (left censoring) value is substituted for the censored observations, and also to other methods such as multiple imputation, and maximum likelihood estimation for censored data (generalized Tobit regression). Simulations are used to explore the sensitivity of the results to changes in the model parameters. In conclusion, the antiretroviral treatment was associated with a significant decrease in viral load after controlling the effects of other covariates. A simulation study with finite sample size shows MCEM is the least biased method and the estimates are least sensitive to the censoring mechanism. PMID:22504231

  16. Comparative study of objective functions to overcome noise and bandwidth limitations in full waveform inversion

    NASA Astrophysics Data System (ADS)

    Jimnez Tejero, C. E.; Dagnino, D.; Sallars, V.; Ranero, C. R.

    2015-10-01

    Ongoing works on full waveform inversion (FWI) are yielding an increasing number of objective functions as alternative to the traditional L2-waveform. These studies aim at designing more robust functions and inversion strategies to reduce the intrinsic dependence of the FWI results on (1) the initial model and (2) the lowest frequency present in field data. In this work, we perform a comparative study of five objective functions in time domain under a common 2-D-acoustic FWI scheme using the Marmousi model as benchmark. In particular, we compare results obtained with L2-based functions that consider the minimization of different wave attributes; the waveform-based, non-integration-method; instantaneous envelope; a modified version of the wrapped instantaneous phase and an improved version of the cross-correlation travel time (CCTT) method; and hybrid strategies combining some of them. We evaluate the robustness of these functionals as a function of their performance with and without low frequencies in the data and the presence of random white Gaussian noise. Our results reveal promising strategies to invert noisy data with limited low-frequency content (?4 Hz), which is the single strategy using the instantaneous phase objective function followed by the hybrid strategies using the instantaneous phase or CCTT as initial models, in particular the combinations [I. Phase + Waveform], [CCTT + Waveform] and [CCTT + I. Phase].

  17. Raman microspectroscopic approach to the study of human granulocytes.

    PubMed Central

    Puppels, G J; Garritsen, H S; Segers-Nolten, G M; de Mul, F F; Greve, J

    1991-01-01

    A sensitive confocal Raman microspectrometer was employed to record spectra of nuclei and cytoplasmic regions of single living human granulocytes. Conditions were used that ensured cell viability and reproducibility of the spectra. Identical spectra were obtained from the nuclei of neutrophilic, eosinophilic, and basophilic granulocytes, which yield information about DNA and protein secondary structure and DNA-protein ratio. The cytoplasmic Raman spectra of the three cell types are very different. This was found to be mainly due to the abundant presence of peroxidases in the cytoplasmic granules of neutrophilic granulocytes (myeloperoxidase) and eosinophilic granulocytes (eosinophil peroxidase). Strong signal contributions of the active site heme group(s) of these enzymes were found. This paper illustrates the potentials and limitations for Raman spectroscopic analysis of cellular constituents and processes. PMID:1760504

  18. Integrative Review of the Literature on Adults with Limited Education and Skills and the Implications for Human Resource Development

    ERIC Educational Resources Information Center

    Hamilton, David W.; Torraco, Richard J.

    2013-01-01

    Adults with limited education and skills--those who lack the education and skills needed for full participation in U.S. culture and economy--are increasing in numbers. However, the knowledge base addressing this population and their educational needs is fragmented across the literature of several disciplines. A comprehensive review and critique of

  19. Integrative Review of the Literature on Adults with Limited Education and Skills and the Implications for Human Resource Development

    ERIC Educational Resources Information Center

    Hamilton, David W.; Torraco, Richard J.

    2013-01-01

    Adults with limited education and skills--those who lack the education and skills needed for full participation in U.S. culture and economy--are increasing in numbers. However, the knowledge base addressing this population and their educational needs is fragmented across the literature of several disciplines. A comprehensive review and critique of…

  20. A human neuron injury model for molecular studies of axonal regeneration.

    PubMed

    Ziegler, Lina; Segal-Ruder, Yael; Coppola, Giovanni; Reis, Arbel; Geschwind, Daniel; Fainzilber, Mike; Goldstein, Ronald S

    2010-05-01

    The enhancement of regeneration of damaged axons in both the peripheral and central nervous systems is a widely pursued goal in clinical medicine. Although some of the molecular mechanisms involved in the intrinsic neurite regeneration program have been elucidated, much additional study is required for development of new therapeutics. The majority of studies in the field of axonal regeneration have utilized animal models due to obvious limitations of the accessibility of human neural tissues. Here we describe the use of human embryonic stem cell (hESC)-derived neurons as a novel model for studying neuronal responses to axonal injury. Neurons were generated using PA6 induction and neurites injured in vitro using trituration or laser microdissection. Lesioned neurons re-extended neurites with distinct growth cones. Expression of proteins associated with regeneration were observed in this human in vitro system, including appearance of importin beta1 in processes after neuritomy. Laser-transected hESC-derived neuronal cultures were analyzed for their transcriptional response to injury using Affymetrix expression microarrays. Profound changes in gene expression were observed over a time course of 2 to 24 hours after lesion. The expression of several genes reported to be involved in axonal injury responses in animal models changed following injury of hESC-derived neurons. Thus, hESC-derived neurons may be a useful in vitro model system for mechanistic studies on human axonal injury and regeneration. PMID:19804775

  1. Improved Neuropsychological and Neurological Functioning Across Three Antiretroviral Regimens in Diverse Resource-Limited Settings: AIDS Clinical Trials Group Study A5199, the International Neurological Study

    PubMed Central

    Robertson, K.; Jiang, H.; Kumwenda, J.; Supparatpinyo, K.; Evans, S.; Campbell, T. B.; Price, R.; Tripathy, S.; Kumarasamy, N.; La Rosa, A.; Santos, B.; Silva, M. T.; Montano, S.; Kanyama, C.; Faesen, S.; Murphy, R.; Hall, C.; Marra, C. M.; Marcus, C.; Berzins, B.; Allen, R.; Housseinipour, M.; Amod, F.; Sanne, I.; Hakim, J.; Walawander, A.; Nair, A.

    2012-01-01

    Background.?AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings. Methods.?Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n=289), B (atazanavir, emtricitabine, and didanosine-EC, n=293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n=278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations. Results.?The median weeks on study was 168 (Q1=96, Q3=192) for the 860 participants. NP test scores improved (P<.05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P>.10). Significant country effects were noted on all NP tests and neurological outcomes (P<.01). Conclusions.?The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction. Clinical trials registration.?NCT00096824. PMID:22661489

  2. A Comparative Study of Definitions on Limit and Continuity of Functions

    ERIC Educational Resources Information Center

    Shipman, Barbara A.

    2012-01-01

    Differences in definitions of limit and continuity of functions as treated in courses on calculus and in rigorous undergraduate analysis yield contradictory outcomes and unexpected language. There are results about limits in calculus that are false by the definitions of analysis, functions not continuous by one definition and continuous by

  3. A Comparative Study of Definitions on Limit and Continuity of Functions

    ERIC Educational Resources Information Center

    Shipman, Barbara A.

    2012-01-01

    Differences in definitions of limit and continuity of functions as treated in courses on calculus and in rigorous undergraduate analysis yield contradictory outcomes and unexpected language. There are results about limits in calculus that are false by the definitions of analysis, functions not continuous by one definition and continuous by…

  4. Limits on quark-lepton compositeness and studies of W asymmetry at the Tevatron collider

    SciTech Connect

    Bodek, A.

    1996-10-01

    Drell-Yan dilepton production at high invariant mass place strong limits on quark substructure. Compositeness limits from CDF Run 1, and expected sensitivity in Run II and TEV33 are presented. The W asymmetry data constrains the slope of the d/u quark distributions and significantly reduces the systematic error on the extracted value of the W mass.

  5. Modelling Human Regulatory Variation in Mouse: Finding the Function in Genome-Wide Association Studies and Whole-Genome Sequencing

    PubMed Central

    Schmouth, Jean-Franois; Bonaguro, Russell J.; Corso-Diaz, Ximena; Simpson, Elizabeth M.

    2012-01-01

    An increasing body of literature from genome-wide association studies and human whole-genome sequencing highlights the identification of large numbers of candidate regulatory variants of potential therapeutic interest in numerous diseases. Our relatively poor understanding of the functions of non-coding genomic sequence, and the slow and laborious process of experimental validation of the functional significance of human regulatory variants, limits our ability to fully benefit from this information in our efforts to comprehend human disease. Humanized mouse models (HuMMs), in which human genes are introduced into the mouse, suggest an approach to this problem. In the past, HuMMs have been used successfully to study human disease variants; e.g., the complex genetic condition arising from Down syndrome, common monogenic disorders such as Huntington disease and ?-thalassemia, and cancer susceptibility genes such as BRCA1. In this commentary, we highlight a novel method for high-throughput single-copy site-specific generation of HuMMs entitled High-throughput Human Genes on the X Chromosome (HuGX). This method can be applied to most human genes for which a bacterial artificial chromosome (BAC) construct can be derived and a mouse-null allele exists. This strategy comprises (1) the use of recombineering technology to create a human variantharbouring BAC, (2) knock-in of this BAC into the mouse genome using Hprt docking technology, and (3) allele comparison by interspecies complementation. We demonstrate the throughput of the HuGX method by generating a series of seven different alleles for the human NR2E1 gene at Hprt. In future challenges, we consider the current limitations of experimental approaches and call for a concerted effort by the genetics community, for both human and mouse, to solve the challenge of the functional analysis of human regulatory variation. PMID:22396661

  6. Biocompatibility of electrospun human albumin: a pilot study.

    PubMed

    Noszczyk, B H; Kowalczyk, T; Łyżniak, M; Zembrzycki, K; Mikułowski, G; Wysocki, J; Kawiak, J; Pojda, Z

    2015-01-01

    Albumin is rarely used for electrospinning because it does not form fibres in its native globular form. This paper presents a novel method for electrospinning human albumin from a solution containing pharmaceutical grade protein and 25% polyethylene oxide (PEO) used as the fibre-forming agent. After spontaneous cross-linking at body temperature, with no further chemicals added, the fibres become insoluble and the excess PEO can be washed out. Albumin deposited along the fibres retains its native characteristics, such as its non-adhesiveness to cells and its susceptibility for degradation by macrophages. To demonstrate this we evaluated the mechanical properties, biocompatibility and biodegradability of this novel product. After subcutaneous implantation in mice, albumin mats were completely resorbable within six days and elicited only a limited local inflammatory response. In vitro, the mats suppressed cell attachment and migration. As this product is inexpensive, produced from human pharmaceutical grade albumin without chemical modifications, retains its native protein properties and fulfils the specific requirements for anti-adhesive dressings, its clinical use can be expedited. We believe that it could specifically be used when treating paediatric patients with epidermolysis bullosa, in whom non-healing wounds occur after minor hand injuries which lead to rapid adhesions and devastating contractures. PMID:25727172

  7. Study of Gap Junctions in Human Embryonic Stem Cells.

    PubMed

    Pbay, Alice; Wong, Raymond C B

    2016-01-01

    Gap junctional intercellular communication (GJIC) has been described in different cell types including stem cells and has been involved in different biological events. GJIC is required for mouse embryonic stem cell maintenance and proliferation and various studies suggest that functional GJIC is a common characteristic of human embryonic stem cells (hESC) maintained in different culture conditions. This chapter introduces methods to study gap junctions in hESC, from expression of gap junction proteins to functional study of GJIC in hESC proliferation, apoptosis, colony growth, and pluripotency. PMID:24859928

  8. Polarization and charge limit studies of strained GaAs photocathodes

    SciTech Connect

    Saez, P.J.

    1997-03-01

    This thesis presents studies on the polarization and charge limit behavior of electron beams produced by strained GaAs photocathodes. These photocathodes are the source of high-intensity, high-polarization electron beams used for a variety of high-energy physics experiments at the Stanford Linear Accelerator Center. Recent developments on P-type, biaxially-strained GaAs photocathodes have produced longitudinal polarization in excess of 80% while yielding beam intensities of {approximately} 2.5 A/cm{sup 2} at an operating voltage of 120 kV. The SLAC Gun Test Laboratory, which has a replica of the SLAC injector, was upgraded with a Mott polarimeter to study the polarization properties of photocathodes operating in a high-voltage DC gun. Both the maximum beam polarization and the maximum charge obtainable from these photocathodes have shown a strong dependence on the wavelength of illumination, on the doping concentration, and on the negative electron affinity levels. The experiments performed for this thesis included studying the effects of temperature, cesiation, quantum efficiency, and laser intensity on the polarization of high-intensity beams. It was found that, although low temperatures have been shown to reduce the spin relaxation rate in bulk semiconductors, they don`t have a large impact on the polarization of thin photocathodes. It seems that the short active region in thin photocathodes does not allow spin relaxation mechanisms enough time to cause depolarization. Previous observations that lower QE areas on the photocathode yield higher polarization beams were confirmed. In addition, high-intensity, small-area laser pulses were shown to produce lower polarization beams. Based on these results, together with some findings in the existing literature, a new proposal for a high-intensity, high-polarization photocathode is given. It is hoped that the results of this thesis will promote further investigation on the properties of GaAs photocathodes.

  9. The Background-Limited Infrared Submillimeter Spectrograph (BLISS) for SPICA: A Design Study

    NASA Astrophysics Data System (ADS)

    Bradford, Charles; BLISS-SPICA Study Team

    2010-05-01

    The far-IR waveband carries half of the photon energy ever produced in galaxies and quasars, evidence of the major role of dust-obscured processes in bringing about the modern Universe. The bulk of this appears to have occurred in the first half of the Universe's history (z>1). We are developing the Background-Limited Infrared-Submillimeter Spectrograph (BLISS) to capitalize on SPICA's cold telescope and provide a breakthrough far-IR spectroscopy capability. BLISS-SPICA is 6 orders of magnitude faster than the spectrometers on Herschel and SOFIA in obtaining full-band spectra, and will observe dust-obscured galaxies at all epochs back to the first billion years after the Big Bang (redshift 6), BLISS-SPICA thus probes the complete history of dust-obscured star formation and black-hole growth. It will also be extremely powerful for studying ice-giant planet formation in protoplanetary disks, with its sensitivity to very small amounts of gas. BLISS covers the 38-433 micron range in five grating-spectrometer bands, with two simultaneous sky positions. The detector package is 4224 silicon-nitride micro-mesh leg-isolated bolometers with superconducting transition-edge-sensed (TES) thermistors, read out with a cryogenic time-domain multiplexer, all cooled to 50mK for optimal sensitivity. All technical elements of BLISS have heritage in mature scientific instruments, and many have flown. We report on our design study in which we are optimizing performance while accommodating SPICA's constraints, including the stringent cryogenic mass budget. We present the science case for BLISS, as well as our progress in all key technical aspects: 1) opto-mechanical instrument architecture, 2) detector and readout approach, and 3) sub-K cooling approach. We thank the NASA for support of the BLISS study.

  10. Study of Light Scattering in the Human Eye

    NASA Astrophysics Data System (ADS)

    Perez, I. Kelly; Bruce, N. C.; Valdos, L. R. Berriel

    2008-04-01

    In this paper we present a numerical model of the human eye to be used in studies of the scattering of light in different components of the eye's optical system. Different parts of the eye are susceptible to produce scattering for different reasons; age, illness or injury. For example, cataracts can appear in the human lens or injuries or fungi can appear on the cornea. The aim of the study is to relate the backscattered light, which is what doctors measure or detect, to the forward scattered light, which is what affects the patient's vision. We present the model to be used, the raytrace procedure and some preliminary results for the image on the retina without scattering.

  11. Noninvasive studies of human visual cortex using neuromagnetic techniques

    SciTech Connect

    Aine, C.J.; George, J.S.; Supek, S. ); Maclin, E.L. . Center for Magnetoencephalography)

    1990-01-01

    The major goals of noninvasive studies of the human visual cortex are: to increase knowledge of the functional organization of cortical visual pathways; and to develop noninvasive clinical tests for the assessment of cortical function. Noninvasive techniques suitable for studies of the structure and function of human visual cortex include magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission tomography (SPECT), scalp recorded event-related potentials (ERPs), and event-related magnetic fields (ERFs). The primary challenge faced by noninvasive functional measures is to optimize the spatial and temporal resolution of the measurement and analytic techniques in order to effectively characterize the spatial and temporal variations in patterns of neuronal activity. In this paper we review the use of neuromagnetic techniques for this purpose. 8 refs., 3 figs.

  12. Sequencing studies in human genetics: design and interpretation

    PubMed Central

    Goldstein, David B.; Allen, Andrew; Keebler, Jonathan; Margulies, Elliott H.; Petrou, Steven; Petrovski, Slav; Sunyaev, Shamil

    2014-01-01

    Next-gene ration sequencing is becoming the primary discovery tool in human genetics. There have been many clear successes in identifying genes that are responsible for Mendelian diseases, and sequencing approaches are now poised to identify the mutations that cause undiagnosed childhood genetic diseases and those that predispose individuals to more common complex diseases. There are, however, growing concerns that the complexity and magnitude of complete sequence data could lead to an explosion of weakly justified claims of association between genetic variants and disease. Here, we provide an overview of the basic workflow in next-generation sequencing studies and emphasize, where possible, measures and considerations that facilitate accurate inferences from human sequencing studies. PMID:23752795

  13. Drosophila as a genetic model for studying pathogenic human viruses

    PubMed Central

    Hughes, Tamara T.; Allen, Amanda L.; Bardin, Joseph E.; Christian, Megan N.; Daimon, Kansei; Dozier, Kelsey D.; Hansen, Caom L.; Holcomb, Lisa M.; Ahlander, Joseph

    2011-01-01

    Viruses are infectious particles whose viability is dependent on the cells of living organisms, such as bacteria, plants, and animals. It is of great interest to discover how viruses function inside host cells in order to develop therapies to treat virally infected organisms. The fruit fly Drosophila melanogaster is an excellent model system for studying the molecular mechanisms of replication, amplification, and cellular consequences of human viruses. In this review, we describe the advantages of using Drosophila as a model system to study human viruses, and highlight how Drosophila has been used to provide unique insight into the gene function of several pathogenic viruses. We also propose possible directions for future research in this area. PMID:22177780

  14. Nitrobenzene potential human cancer risk based on animal studies.

    PubMed

    Holder, J W

    1999-08-01

    Inhaled nitrobenzene (NB) in animals produces cancer at eight sites in three rodent strains. B6C3F1 mice respond with mammary gland malignant tumors and male lung and thyroid benign tumors, and F344/N male rats respond with liver malignant tumors and thyroid and kidney benign tumors, while females respond with endometrial polyps. Male Sprague-Dawley male rats (CD strain) respond with liver benign tumors. NB is oxidized to various phenolic metabolites, while also being reduced to nitrosobenzene (NOB), phenylhydroxylamine (PH), related free radicals, and aniline (AN) in the cecum by bacteria and in the body by the microsomes. In reduction, NB first forms the nitroanion free radical, which can react with O2 to form O2*-. Repeated NB dosing produces a persistent redox couple NOB<==>PH in red blood cells that generates met-Hb and expends NAD(P)H. NOB forms activated glutathione conjugates. These biochemical effects may lead to critical redox imbalances and macromolecular binding. Known effects are hemosiderosis, methemoglobinemia, and anemia--and now dispersed cancer in rodents. Based on structural and mechanistic similarities, NB compares with other animal and human carcinogenic nitroarenes and aromatic amines. The cancer hazard evaluation of NB is that it is a probable human carcinogen by any route of exposure. The maximum response is in F344/N male rats which is used for dose-response modelling. The model to estimate the upper 95% confidence limit (UCL95%) of NB human carcinogenicity is a no-threshold, linear low-dose, and multistaged animal model (LMS). The UCL95% of cancer slope is estimated to be 0.11(6) mg/kg/day (mkd). At de minimus risk (1:10(6)), the virtually safe dose (VSD) is estimated to be 9.1 ng/kg/day (nkd). PMID:10487356

  15. The Limits of Collaboration: A Qualitative Study of Community Ethical Review of Environmental Health Research

    PubMed Central

    Fullilove, Robert E.; Kaufman, Molly Rose; Wallace, Rodrick; Fullilove, Mindy Thompson

    2009-01-01

    Objectives. We assessed the effectiveness of various systems of community participation in ethical review of environmental health research. Methods. We used situation analysis methods and a global workspace theoretical framework to conduct comparative case studies of 3 research organizations at 1 medical center. Results. We found a general institutional commitment to community review as well as personal commitment from some participants in the process. However, difficulty in communicating across divides of knowledge and privilege created serious gaps in implementation, leaving research vulnerable to validity threats (such as misinterpretation of findings) and communities vulnerable to harm. The methods used in each collaboration solved some, but not all, of the problems that hindered communication. Conclusions. Researchers, community spokespersons, and institutional review boards constitute organizational groups with strong internal ties and highly developed cultures. Few cross-linkages and little knowledge of each other cause significant distortion of information and other forms of miscommunication between groups. Our data suggest that organizations designed to protect human volunteers are in the best position to take the lead in implementing community review. PMID:19542033

  16. Lost in Virtual Space: Studies in Human and Ideal Spatial Navigation

    ERIC Educational Resources Information Center

    Stankiewicz, Brian J.; Legge, Gordon E.; Mansfield, J. Stephen; Schlicht, Erik J.

    2006-01-01

    The authors describe 3 human spatial navigation experiments that investigate how limitations of perception, memory, uncertainty, and decision strategy affect human spatial navigation performance. To better understand the effect of these variables on human navigation performance, the authors developed an ideal-navigator model for indoor navigation…

  17. Lost in Virtual Space: Studies in Human and Ideal Spatial Navigation

    ERIC Educational Resources Information Center

    Stankiewicz, Brian J.; Legge, Gordon E.; Mansfield, J. Stephen; Schlicht, Erik J.

    2006-01-01

    The authors describe 3 human spatial navigation experiments that investigate how limitations of perception, memory, uncertainty, and decision strategy affect human spatial navigation performance. To better understand the effect of these variables on human navigation performance, the authors developed an ideal-navigator model for indoor navigation

  18. Tamoxifen experimental carcinogenicity studies: Implications for human effects

    SciTech Connect

    Williams, G.M.

    1995-02-01

    Tamoxifen is an effective antiestrogen in the treatment of breast cancer and is considered highly safe. In recent years, several trials have been initiated in women to evaluate its potential for the prevention of breast cancer. Such long-term administration of a medication to healthy people requires a substantial degree of safety. This review examines experimental carcinogenicity and mechanistic studies on tamoxifen and the implications for human effects. 25 refs.

  19. Genetically Engineered Humanized Mouse Models for Preclinical Antibody Studies

    PubMed Central

    Proetzel, Gabriele; Wiles, Michael V.; Roopenian, Derry C.

    2015-01-01

    The use of genetic engineering has vastly improved our capabilities to create animal models relevant in preclinical research. With the recent advances in gene-editing technologies, it is now possible to very rapidly create highly tunable mouse models as needs arise. Here, we provide an overview of genetic engineering methods, as well as the development of humanized neonatal Fc receptor (FcRn) models and their use for monoclonal antibody in vivo studies. PMID:24150980

  20. Trait Mindfulness as a Limiting Factor for Residual Depressive Symptoms: An Explorative Study Using Quantile Regression

    PubMed Central

    Radford, Sholto; Eames, Catrin; Brennan, Kate; Lambert, Gwladys; Crane, Catherine; Williams, J. Mark G.; Duggan, Danielle S.; Barnhofer, Thorsten

    2014-01-01

    Mindfulness has been suggested to be an important protective factor for emotional health. However, this effect might vary with regard to context. This study applied a novel statistical approach, quantile regression, in order to investigate the relation between trait mindfulness and residual depressive symptoms in individuals with a history of recurrent depression, while taking into account symptom severity and number of episodes as contextual factors. Rather than fitting to a single indicator of central tendency, quantile regression allows exploration of relations across the entire range of the response variable. Analysis of self-report data from 274 participants with a history of three or more previous episodes of depression showed that relatively higher levels of mindfulness were associated with relatively lower levels of residual depressive symptoms. This relationship was most pronounced near the upper end of the response distribution and moderated by the number of previous episodes of depression at the higher quantiles. The findings suggest that with lower levels of mindfulness, residual symptoms are less constrained and more likely to be influenced by other factors. Further, the limiting effect of mindfulness on residual symptoms is most salient in those with higher numbers of episodes. PMID:24988072

  1. Employer-Sponsored Health Insurance Coverage Limitations: Results from the Childhood Cancer Survivor Study

    PubMed Central

    Kirchhoff, Anne C.; Kuhlthau, Karen; Pajolek, Hannah; Leisenring, Wendy; Armstrong, Greg T.; Robison, Leslie L.; Park, Elyse R.

    2013-01-01

    Purpose The Affordable Care Act (ACA) will expand health insurance options for cancer survivors in the United States. It is unclear how this legislation will affect their access to employer-sponsored health insurance (ESI). We describe the health insurance experiences for survivors of childhood cancer with and without ESI. Methods We conducted a series of qualitative interviews with 32 adult survivors from the Childhood Cancer Survivor Study to assess their employment-related concerns and decisions regarding health insurance coverage. Interviews were performed from August to December 2009 and were recorded, transcribed, and content analyzed using NVivo 8. Results Uninsured survivors described ongoing employment limitations, such as being employed at part-time capacity, which affected their access to ESI coverage. These survivors acknowledged they could not afford insurance without employer support. Survivors on ESI had previously been denied health insurance due to their pre-existing health conditions until they obtained coverage through an employer. Survivors feared losing their ESI coverage, which created a disincentive to making career transitions. Others reported worries about insurance rescission if their cancer history was discovered. Survivors on ESI reported financial barriers in their ability to pay for health care. Conclusions Childhood cancer survivors face barriers to obtaining employer-sponsored health insurance. While Affordable Care Act provisions may mitigate insurance barriers for cancer survivors, many will still face cost barriers to affording health care without employer support. PMID:22717916

  2. Symptom-limited graded treadmill exercise testing in young adults in the CARDIA study.

    PubMed

    Sidney, S; Haskell, W L; Crow, R; Sternfeld, B; Oberman, A; Armstrong, M A; Cutter, G R; Jacobs, D R; Savage, P J; Van Horn, L

    1992-02-01

    Symptom-limited, graded exercise treadmill testing was performed by 4,968 white and black adults, ages 18-30 yr, during the baseline examination for the CARDIA study. The mean estimated maximal exercise capacity by race/gender, expressed as metabolic units (METS), was: white men 13.8, black men 13.0, white women 11.1, and black women 9.4. Exercise test duration was higher in nonsmokers, positively related to physical activity score and pulmonary function (FEV1.ht-2), and inversely related to body mass index. Men had higher mean values than women for both test duration and a measure of submaximal performance, the workload 130 (WL130, the exercise test duration to a heart rate of 130 beats.min-1). Adjusted for age and education, white men had a longer mean test duration than black men (53 s longer, P less than 0.001), but nearly equal mean WL130. White women had higher mean values than black women for both test duration (114 s longer, P less than 0.001) and WL130 (36 s longer, P less than 0.001). Men had higher mean values than women for both outcome measures (P less than 0.001). Thus, in young adults significant gender and ethnic differences exist for exercise test performance, part of which can be explained by personal habits or traits. PMID:1549006

  3. Voice-Activated Lightweight Reacher to Assist with Upper Extremity Movement Limitations: A Case Study.

    PubMed

    Khalid, Umer; Conti, Gerry E; Erlandson, Robert F; Ellis, Richard D; Brown, Vince; Pandya, Abhilash K

    2015-01-01

    The focus of this research was to design a functional and user-friendly reacher for people with spinal cord injuries (SCIs). Engineering advancements have taken assistive robotics to new dimensions. Technologies such as wheelchair robotics and myo-electronically controlled systems have opened up a wide range of new applications to assist people with physical disabilities. Similarly, exo-skeletal limbs and body suits have provided new foundations from which technologies can aid function. Unfortunately, these devices have issues of usability, weight, and discomfort with donning. The Smart Assistive Reacher Arm (SARA) system, developed in this research, is a voice-activated, lightweight, mobile device that can be used when needed. SARA was built to help overcome daily reach challenges faced by individuals with limited arm and hand movement capability, such as people with cervical level 5-6 (C5-6) SCI. This article shows that a functional reacher arm with voice control can be beneficial for this population. Comparison study with healthy participants and an SCI participant shows that, when using SARA, a person with SCI can perform simple reach and grasp tasks independently, without someone else's help. This suggests that the interface is intuitive and can be easily used to a high level of proficiency by a SCI individual. PMID:26132355

  4. Suicide in the Greek penal system and the problem of various limitations in relevant studies.

    PubMed

    Themeli, Olga

    2006-01-01

    Suicides in prison are not merely self-destructive acts or a "cry for help." They reflect the inherent need for freedom and the repercussions of imprisonment. SPACE statistics on suicides in prison reveal a rate above 10 per 10,000 in 10 European countries, 4 of which have a rate above 20. Greek data do not appear in all SPACE statistics. This fact has stimulated the present paper. Unpublished data obtained from the Greek Ministry of Justice reveal that Greece belongs to the group of countries with a rate below 10 in 1995 (the year of SPACE statistics). However, the suicide rates fluctuated widely in Greece from a low rate of 3.2 per 10,000 prisoners (convicted, on remand, or hospitalized) in 1982 to the incredibly high rate of nearly 40 in the year 1979 (11 suicides, 10 of which occurred in prison hospitals). A review of the literature indicates that various limitations mentioned in relevant studies lie in the unreliability of data (doubts about the validity of official statistics, missing data in archives, missing files on the victims, suicide in juvenile institutions not always recorded separately, etc.). The research emphasizes the importance of improving suicide statistics (recording, clearing up the incidents of deaths that are recorded without specification of cause, etc.) in order to plan and enforce suicide prevention and intervention strategies that seem to "work" in a particular milieu and are not debatable (e.g., the use of "suicide proof" cells). PMID:17091824

  5. Biochemical Markers of Aging for Longitudinal Studies in Humans

    PubMed Central

    Engelfriet, Peter M.; Jansen, Eugène H. J. M.; Picavet, H. Susan J.; Dollé, Martijn E. T.

    2013-01-01

    Much progress has been made in the past decades in unraveling the mechanisms that are responsible for aging. The discovery that particular gene mutations in experimental species such as yeast, flies, and nematodes are associated with longevity has led to many important insights into pathways that regulate aging processes. However, extrapolating laboratory findings in experimental species to knowledge that is valid for the complexity of human physiology remains a major challenge. Apart from the restricted experimental possibilities, studying aging in humans is further complicated by the development of various age-related diseases. The availability of a set of biomarkers that really reflect underlying aging processes would be of much value in disentangling age-associated pathology from specific aging mechanisms. In this review, we survey the literature to identify promising biochemical markers of aging, with a particular focus on using them in longitudinal studies of aging in humans that entail repeated measurements on easily obtainable material, such as blood samples. Our search strategy was a 2-pronged approach, one focused on general mechanisms of aging and one including studies on clinical biomarkers of age-related diseases. PMID:23382477

  6. Machine Learning for Big Data: A Study to Understand Limits at Scale

    SciTech Connect

    Sukumar, Sreenivas R.; Del-Castillo-Negrete, Carlos Emilio

    2015-12-21

    This report aims to empirically understand the limits of machine learning when applied to Big Data. We observe that recent innovations in being able to collect, access, organize, integrate, and query massive amounts of data from a wide variety of data sources have brought statistical data mining and machine learning under more scrutiny, evaluation and application for gleaning insights from the data than ever before. Much is expected from algorithms without understanding their limitations at scale while dealing with massive datasets. In that context, we pose and address the following questions How does a machine learning algorithm perform on measures such as accuracy and execution time with increasing sample size and feature dimensionality? Does training with more samples guarantee better accuracy? How many features to compute for a given problem? Do more features guarantee better accuracy? Do efforts to derive and calculate more features and train on larger samples worth the effort? As problems become more complex and traditional binary classification algorithms are replaced with multi-task, multi-class categorization algorithms do parallel learners perform better? What happens to the accuracy of the learning algorithm when trained to categorize multiple classes within the same feature space? Towards finding answers to these questions, we describe the design of an empirical study and present the results. We conclude with the following observations (i) accuracy of the learning algorithm increases with increasing sample size but saturates at a point, beyond which more samples do not contribute to better accuracy/learning, (ii) the richness of the feature space dictates performance - both accuracy and training time, (iii) increased dimensionality often reflected in better performance (higher accuracy in spite of longer training times) but the improvements are not commensurate the efforts for feature computation and training and (iv) accuracy of the learning algorithms drop significantly with multi-class learners training on the same feature matrix and (v) learning algorithms perform well when categories in labeled data are independent (i.e., no relationship or hierarchy exists among categories).

  7. Mummified remains from the Archaeological Museum in Zagreb, Croatia - Reviewing peculiarities and limitations of human and non-human radiological identification and analysis in mummified remains.

    PubMed

    Petaros, Anja; Janković, Ivor; Cavalli, Fabio; Ivanac, Gordana; Brkljačić, Boris; Čavka, Mislav

    2015-10-01

    Forensic protocols and medico-legal techniques are increasingly being employed in investigations of museological material. The final findings of such investigations may reveal interesting facts on historical figures, customs and habits, as well as provide meaningful data for forensic use. Herein we present a case review where forensic experts were requested to identify taxonomic affinities, stage of preservation and provide skeletal analysis of mummified non-human archaeological remains, and verify whether two mummified hands are human or not. The manuscript offers a short review on the process and particularities of radiological species identification, the impact of post-mortem changes in the analysis and imaging of mummified remains as well as the macroscopical interpretation of trauma, pathology and authenticity in mummified remains, which can all turn useful when dealing with forensic cases. PMID:26344461

  8. Reconciling Human Smoking Behavior and Machine Smoking Patterns: Implications for Understanding Smoking Behavior and the Impact on Laboratory Studies

    PubMed Central

    Marian, Catalin; O'Connor, Richard J.; Djordjevic, Mirjana; Rees, Vaughan W.; Hatsukami, Dorothy K.; Shields, Peter G.

    2009-01-01

    Introduction Recent Food and Drug Administration legislation enables the mandating of product performance standards for cigarette smoke and the evaluation of manufacturers’ health claims for modified tobacco products. Laboratory studies used for these evaluations, and also to understand tobacco smoke toxicology, use machines to generate smoke. The goal of this review is to critically evaluate methods to assess human smoking behavior and replicate this in the laboratory. Methods Smoking behavior and smoking machine studies were identified using PubMed and publically available databases for internal tobacco company documents. Results The smoking machine was developed to generate smoke to allow for comparing cigarette tar and nicotine yields. The intent was to infer relative human disease risk, but this concept was flawed because humans tailor their smoking to the product and chemical yields and toxicological effects change with different smoking profiles. While smoking machines also allow for mechanistic assessments of smoking-related diseases, the interpretations also are limited. However, available methods to assess how humans puff could be used to provide better laboratory assessments, but these need to be validated. Separately, the contribution of smoke mouth-holding and inhalation to dose need to be assessed, because these parts of smoking are not captured by the smoking machine. Better comparisons of cigarettes might be done by tailoring human puff profiles to the product based on human studies and comparing results across regimens. Conclusions There are major research gaps that limit the use of smoking machine studies for informing tobacco control regulation and mechanistic studies. PMID:19959678

  9. Rapid-throughput glycomics applied to human milk oligosaccharide profiling for large human studies.

    PubMed

    Totten, Sarah M; Wu, Lauren D; Parker, Evan A; Davis, Jasmine C C; Hua, Serenus; Stroble, Carol; Ruhaak, L Renee; Smilowitz, Jennifer T; German, J Bruce; Lebrilla, Carlito B

    2014-12-01

    Glycomic analysis is the comprehensive determination of glycan (oligosaccharide) structures with quantitative information in a biological sample. Rapid-throughput glycomics is complicated due to the lack of a template, which has greatly facilitated analysis in the field of proteomics. Furthermore, the large similarities in structures make fragmentation spectra (as obtained in electron impact ionization and tandem mass spectrometry) less definitive for identification as it has been in metabolomics. In this study, we develop a concept of rapid-throughput glycomics on human milk oligosaccharides, which have proven to be an important bioactive component of breast milk, providing the infant with protection against pathogenic infection and supporting the establishment of a healthy microbiota. To better understand the relationship between diverse oligosaccharides structures and their biological function as anti-pathogenic and prebiotic compounds, large human studies are needed, which necessitate rapid- to high-throughput analytical platforms. Herein, a complete glycomics methodology is presented, evaluating the most effective human milk oligosaccharide (HMO) extraction protocols, the linearity and reproducibility of the nano-liquid chromatography chip time-of-flight mass spectrometry (nano-LC chip-TOF MS) method, and the efficacy of newly developed, in-house software for chromatographic peak alignment that allows for rapid data analysis. High instrument stability and retention time reproducibility, together with the successful automated alignment of hundreds of features in hundreds of milk samples, allow for the use of an HMO library for rapid assignment of fully annotated structures. PMID:25358913

  10. Improved Detection Limit in Rapid Detection of Human Enterovirus 71 and Coxsackievirus A16 by a Novel Reverse TranscriptionIsothermal Multiple-Self-Matching-Initiated Amplification Assay

    PubMed Central

    Ding, Xiong; Nie, Kai; Shi, Lei; Zhang, Yong; Guan, Li; Zhang, Dan

    2014-01-01

    Rapid detection of human enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) is important in the early phase of hand-foot-and-mouth disease (HFMD). In this study, we developed and evaluated a novel reverse transcriptionisothermal multiple-self-matching-initiated amplification (RT-IMSA) assay for the rapid detection of EV71 and CVA16 by use of reverse transcriptase, together with a strand displacement DNA polymerase. Real-time RT-IMSA assays using a turbidimeter and visual RT-IMSA assays to detect EV71 and CVA16 were established and completed in 1 h, and the reported corresponding real-time reverse transcriptionloop-mediated isothermal amplification (RT-LAMP) assays targeting the same regions of the VP1 gene were adopted as parallel tests. Through testing VP1 RNAs transcribed in vitro, the real-time RT-IMSA assays exhibited better linearity of quantification, with R2 values of 0.952 (for EV71) and 0.967 (for CVA16), than the real-time RT-LAMP assays, which had R2 values of 0.803 (for EV71) and 0.904 (for CVA16). Additionally, the detection limits of the real-time RT-IMSA assays (approximately 937 for EV71 and 67 for CVA16 copies/reaction) were higher than those of real-time RT-LAMP assays (approximately 3,266 for EV71 and 430 for CVA16 copies/reaction), and similar results were observed in the visual RT-IMSA assays. The new approaches also possess high specificities for the corresponding targets, with no cross-reactivity observed. In clinical assessment, compared to commercial reverse transcription-quantitative PCR (qRT-PCR) kits, the diagnostic sensitivities of the real-time RT-IMSA assays (96.4% for EV71 and 94.6% for CVA16) were higher than those of the real-time RT-LAMP assays (91.1% for EV71 and 90.8% for CVA16). The visual RT-IMSA assays also exhibited the same results. In conclusion, this proof-of-concept study suggests that the novel RT-IMSA assay is superior to the RT-LAMP assay in terms of detection limit and has the potential to rapidly detect EV71 and CVA16 viruses. PMID:24648558

  11. Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves.

    PubMed

    Chen, Kun; Fu, Xing; Dorantes-Gonzalez, Dante J; Lu, Zimo; Li, Tingting; Li, Yanning; Wu, Sen; Hu, Xiaotang

    2014-01-01

    Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAWs are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin. PMID:25057963

  12. Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves

    NASA Astrophysics Data System (ADS)

    Chen, Kun; Fu, Xing; Dorantes-Gonzalez, Dante J.; Lu, Zimo; Li, Tingting; Li, Yanning; Wu, Sen; Hu, Xiaotang

    2014-07-01

    Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAW's are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin.

  13. Feasibility of a 3D human airway epithelial model to study respiratory absorption.

    PubMed

    Reus, Astrid A; Maas, Wilfred J M; Jansen, Harm T; Constant, Samuel; Staal, Yvonne C M; van Triel, Jos J; Kuper, C Frieke

    2014-03-01

    The respiratory route is an important portal for human exposure to a large variety of substances. Consequently, there is an urgent need for realistic in vitro strategies for evaluation of the absorption of airborne substances with regard to safety and efficacy assessment. The present study investigated feasibility of a 3D human airway epithelial model to study respiratory absorption, in particular to differentiate between low and high absorption of substances. Bronchial epithelial models (MucilAir), cultured at the air-liquid interface, were exposed to eight radiolabeled model substances via the apical epithelial surface. Absorption was evaluated by measuring radioactivity in the apical compartment, the epithelial cells and the basolateral culture medium. Antipyrine, caffeine, naproxen and propranolol were highly transported across the epithelial cell layer (>5%), whereas atenolol, mannitol, PEG-400 and insulin were limitedly transported (<5%). Results indicate that the 3D human airway epithelial model used in this study is able to differentiate between substances with low and high absorption. The intra-experimental reproducibility of the results was considered adequate based on an average coefficient of variation (CV) of 15%. The inter-experimental reproducibility of highly absorbed compounds was in a similar range (CV of 15%), but this value was considerably higher for those compounds that were limitedly absorbed. No statistical significant differences between different donors and experiments were observed. The present study provides a simple method transposable in any lab, which can be used to rank the absorption of chemicals and pharmaceuticals, and is ready for further validation with respect to reproducibility and capacity of the method to predict respiratory transport in humans. PMID:24216300

  14. FIRST-IN-HUMAN STUDY DEMONSTRATING PHARMACOLOGICAL ACTIVATION OF HEME OXYGENASE-1 IN HUMANS

    PubMed Central

    Bharucha, Adil E.; Kulkarni, Anuja; Choi, Kyoung Moo; Camilleri, Michael; Lempke, Mary; Brunn, Gregory J.; Gibbons, Simon J.; Zinsmeister, Alan R; Farrugia, Gianrico

    2010-01-01

    Heme-oxygenase 1 (HO-1) degrades heme and protects against oxidative stress, but has not been pharmacologically induced in humans. In this randomized study (10 healthy volunteers), hemin (3 mg/kg. i.v in 25% albumin) increased plasma HO-1 protein concentration by 45 fold and HO-1 activity by ~15 fold over baseline at 24 and 48 h (placebo ? 56.41 6.31 [baseline], 77.44 10.62 [48h] versus hemin ? 71.70 9.20 [baseline], 1192.20 333.30 [48h]) in 4 of 5 subjects compared to albumin (p ? 0.03), thereby overcoming a fundamental challenge to HO-1 research in humans. PMID:19956091

  15. Density limit studies in the tokamak and the reversed-field pinch

    NASA Astrophysics Data System (ADS)

    Spizzo, G.; Pucella, G.; Tudisco, O.; Zuin, M.; Agostini, M.; Alessi, E.; Auriemma, F.; Bin, W.; Buratti, P.; Carraro, L.; Cavazzana, R.; Ciaccio, G.; De Masi, G.; Esposito, B.; Galperti, C.; Garavaglia, S.; Granucci, G.; Marinucci, M.; Marrelli, L.; Martines, E.; Mazzotta, C.; Minelli, D.; Moro, A.; Puiatti, M. E.; Scarin, P.; Sozzi, C.; Spolaore, M.; Schmitz, O.; Vianello, N.; White, R. B.

    2015-04-01

    The ITER scenarios and the project of DEMO involve stable operation above the Greenwald density, which justifies efforts to understand and overcome the density limit, this last observed as a disruptive termination of tokamak discharges and a thermal crash (with no disruption) of stellarator and reversed-field pinch (RFP) ones. Both in the tokamak and the RFP, new findings show that the high density limit is not governed by a unique, theoretically well-determined physical phenomenon, but by a combination of complex mechanisms involving two-fluid effects, electrostatic plasma response to magnetic islands and plasma-wall interaction. In this paper we will show new evidence challenging the traditional picture of the Greenwald limit, in particular with reference to the role of thermal instabilities and the edge radial electric field Er in the development of this limit.

  16. Quantification of mequitazine in human plasma by gas chromatography- quadrupole mass spectrometry and its application to a human pharmacokinetic study.

    PubMed

    Ahn, Sung-Hoon; Maeng, Han-Joo

    2016-04-01

    A specific and sensitive gas chromatography-mass spectrometry (GC-MS) with quadrupole mass analyzer type was developed and validated for the quantitative analysis of mequitazine in human plasma. After liquid-liquid extraction of plasma samples containing mequitazine and promethazine (internal standard, IS) using hexane with pH adjustment, the extract was evaporated and an aliquot of reconstituted residue was injected into the GC-MS system. The assay showed linearity over a concentration range from 1 to 50?ng/mL. Intra- and inter-day precision for mequitazine was <9.09 and 9.29%, respectively, and intra- and inter-day accuracy ranged from -7.97 to 9.05% and from -1.51 to 7.89%, respectively. The lower limit of quantification was 1?ng/mL in the present assay. The developed analytical method was successfully applied to a pharmacokinetic study after a single oral administration of mequitazine in human subjects. Copyright 2015 John Wiley & Sons, Ltd. PMID:26268745

  17. Study of the optical properties of human hair.

    PubMed

    Guiolet, A; Garson, J C; Levecque, J L

    1987-06-01

    Synopsis The optical properties of human hair were studied by photogoniometry. Starting from an optical model of hair, we developed a computerized method of decomposition of the goniophotometric curve. From our analysis we obtained structural parameters of the hair surface, average scale angle and cosmetic parameters like lustre and pigmentation. This method gave us new results in the following areas: - the effects of bleaching on scale and internally reflected light; - the study, from root to tip, of surface damage and hair pigmentation; - the effects of stretching the hair on scale angle and lustre; - the effects of sebum and dust on hair lustre. PMID:19456974

  18. Studying the Human Immunome: The Complexity of Comprehensive Leukocyte Immunophenotyping

    PubMed Central

    Biancotto, Angélique

    2014-01-01

    A comprehensive study of the cellular components of the immune system requires both deep and broad immunophenotyping of numerous cell populations in an efficient and practical manner. In this chapter, we describe the technical aspects of studying the human immunome using high-dimensional (15 color) fluorescence-based immunophenotyping. We focus on the technical aspects of polychromatic flow cytometry and the initial stages in developing a panel for comprehensive leukocyte immunophenotyping (CLIP). We also briefly discuss how this panel is being used and the challenges of encyclopedic analysis of these rich data sets. PMID:23975032

  19. Objectives and Model Payload Definition for NEO Human Mission Studies

    NASA Astrophysics Data System (ADS)

    Carnelli, I.; Galvez, A.; Carpenter, J.

    2011-10-01

    ESA has supported studies on NEO threat assessment systems and deflection concepts in the context of the General Studies Programme and in close cooperation with the directorates of Technical and Quality Management and of the Scientific Programme. This work has made it possible to identify a project for Europe to make a significant - yet realistic - contribution to the international efforts in this field: the Don Quijote NEO technology demonstration mission. This paper describes what such a small mission can do to prepare future human exploration and what is the in-situ data that can be obtained through such a project.

  20. FT-Raman spectroscopy study of human breast tissue

    NASA Astrophysics Data System (ADS)

    Bitar Carter, Renata A.; Martin, Airton A.; Netto, Mario M.; Soares, Fernando A.

    2004-07-01

    Optical spectroscopy has been extensively studied as a potential in vivo diagnostic tool to provide information about the chemical and morphologic structure of tissue. Raman Spectroscpy is an inelastic scattering process that can provide a wealth of spectral features that can be related to the specific molecular structure of the sample. This article reports results of an in vitro study of the FT-Raman human breast tissue spectra. An Nd:YAG laser at 1064nm was used as the excitation source in the FT-Raman Spectrometer. The neoplastic human breast samples, both Fibroadenoma and ICD, were obtained during therapeutical routine medical procedures required by the primary disease, and the non-diseased human tissue was obtained in plastic surgery. No sample preparation was needed for the FT-Raman spectra collection. The FT-Raman spectra were recorded from normal, benign (Fibroadenomas) and malignant (IDC-Intraductal Carcinoma) samples, adding up 51 different areas. The main spectral differences of a typical FT-Raman spectra of a Normal (Non-diseased), Fibroadenoma, and Infiltrating Ductal Carcinoma (IDC) breast tissue at the interval of 600 to 1800cm-1, which may differentiate diagnostically the sample, were found in the bands of 1230 to 1295cm-1, 1440 to 1460 cm-1 and 1650 to 1680 cm-1, assigned to the vibrational bands of the carbohydrate-amide III, proteins and lipids, and carbohydrate-amide I, respectively.

  1. Design, recruitment, and microbiological considerations in human challenge studies.

    PubMed

    Darton, Thomas C; Blohmke, Christoph J; Moorthy, Vasee S; Altmann, Daniel M; Hayden, Frederick G; Clutterbuck, Elizabeth A; Levine, Myron M; Hill, Adrian V S; Pollard, Andrew J

    2015-07-01

    Since the 18th century a wealth of knowledge regarding infectious disease pathogenesis, prevention, and treatment has been accumulated from findings of infection challenges in human beings. Partly because of improvements to ethical and regulatory guidance, human challenge studies-involving the deliberate exposure of participants to infectious substances-have had a resurgence in popularity in the past few years, in particular for the assessment of vaccines. To provide an overview of the potential use of challenge models, we present historical reports and contemporary views from experts in this type of research. A range of challenge models and practical approaches to generate important data exist and are used to expedite vaccine and therapeutic development and to support public health modelling and interventions. Although human challenge studies provide a unique opportunity to address complex research questions, participant and investigator safety is paramount. To increase the collaborative effort and future success of this area of research, we recommend the development of consensus frameworks and sharing of best practices between investigators. Furthermore, standardisation of challenge procedures and regulatory guidance will help with the feasibility for using challenge models in clinical testing of new disease intervention strategies. PMID:26026195

  2. A functional anatomical study of associative learning in humans.

    PubMed Central

    Molchan, S E; Sunderland, T; McIntosh, A R; Herscovitch, P; Schreurs, B G

    1994-01-01

    The purpose of the study was to map the functional neuroanatomy of simple associative learning in humans. Eyeblink conditioning was studied in eight normal volunteers using positron emission tomography and H215O. Regional cerebral blood flow was assessed during three sequential phases: (i) explicitly unpaired presentations of the unconditioned stimulus (air puff to the right eye) and conditioned stimulus (binaural tone), (ii) paired presentations of the two stimuli (associative learning), and (iii) presentation of the conditioned stimulus alone. During associative learning, relative to the unpaired phase, blood flow was significantly increased in primary auditory and left posterior cingulate cortices and significantly decreased in areas of the right cerebellar, right prefrontal, right parietal, and insular cortices and right neostriatum. The lateralization of the changes may relate to the functional organization of memory and learning processes in the brain. The activation in primary auditory cortex is an example, using a neuroimaging technique, of a learning-related change in primary sensory cortex in humans. The changes in areas such as the cerebellum, prefrontal cortex, and neostriatum provide support for their roles in associative learning as proposed by animal models. Moreover, these findings show that in humans, even simple classical conditioning involves distributed changes in multiple neural systems. Images PMID:8058767

  3. The Influences of Genetic and Environmental Factors on Methylome-wide Association Studies for Human Diseases

    PubMed Central

    Sun, Yan V.

    2014-01-01

    DNA methylation (DNAm) is an essential epigenetic mechanism for normal development, and its variation may be associated with diseases. High-throughput technology allows robust measurement of DNA methylome in population studies. Methylome-wide association studies (MWAS) scan DNA methylome to detect new epigenetic loci affecting disease susceptibility. MWAS is an emerging approach to unraveling the mechanism linking genetics, environment, and human diseases. Here I review the recent studies of genetic determinants and environmental modifiers of DNAm, and the concept for partitioning genetic and environmental contribution to DNAm. These studies establish the correlation maps between genome and methylome, and enable the interpretation of epigenetic association with disease traits. Recent findings suggested that MWAS was a promising genomic method to identify epigenetic predictors accounting for unexplained disease risk. However, new study designs, analytical methods and shared resources need to be implemented to address the limitations and challenges in future epigenomic epidemiologic studies. PMID:25422794

  4. Simple instrument for biochemical studies of the living human brain

    SciTech Connect

    Bice, A.N.; Wagner, H.N. Jr.; Lee, M.C.; Frost, J.J.

    1986-09-01

    A simple, relatively inexpensive radiation detection system was developed for measurement of positron-emitting receptor-binding drugs in the human brain. This high-efficiency coincidence counting system requires that only a few hundred microcuries of labeled drug be administered to the subject, thereby allowing for multiple studies without an excessive radiation dose. Measurement of the binding of (/sup 11/C)-carfentanil, a high-affinity synthetic opiate, to opiate receptors in the presence and in the absence of a competitive opiate antagonist exemplifies the use of this system for estimating different degrees of receptor binding of drugs in the human brain. The instrument has also been used for measurement of the transport into the brain of other positron-emitting radiotracers, such as large neutral amino acids.

  5. Resveratrol: A review of preclinical studies for human cancer prevention

    SciTech Connect

    Athar, Mohammad; Back, Jung Ho; Tang Xiuwei; Kim, Kwang Ho; Kopelovich, Levy; Bickers, David R.; Kim, Arianna L.

    2007-11-01

    The search for novel and effective cancer chemopreventive agents has led to the identification of various naturally occurring compounds one of which is resveratrol (trans-3,4',5-trihydroxystilbene), a phytoalexin derived from the skin of grapes and other fruits. Resveratrol is known to have potent anti-inflammatory and antioxidant effects and to inhibit platelet aggregation and the growth of a variety of cancer cells. Its potential chemopreventive and chemotherapeutic activities have been demonstrated in all three stages of carcinogenesis (initiation, promotion, and progression), in both chemically and UVB-induced skin carcinogenesis in mice, as well as in various murine models of human cancers. Evidence from numerous in vitro and in vivo studies has confirmed its ability to modulate various targets and signaling pathways. This review discusses the current preclinical and mechanistic data available and assesses resveratrol's anticancer effects to support its potential as an anticancer agent in human populations.

  6. Functional MRI studies of human vision on a clinical imager

    SciTech Connect

    George, J.S.; Lewine, J.D.; Aine, C.J.; van Hulsteyn, D.; Wood, C.C. ); Sanders, J.; Maclin, E. ); Belliveau, J.W. ); Caprihan, A. )

    1992-01-01

    During the past decade, Magnetic Resonance Imaging (MRI) has become the method of choice for imaging the anatomy of the human brain. Recently, Belliveau and colleagues have reported the use of echo planar magnetic resonance imaging (EPI) to image patterns of neural activity. Here, we report functional MR imaging in response to visual stimulation without the use of contrast agents, and without the extensive hardware modifications required for EPI. Regions of activity were observed near the expected locations of V1, V2 and possibly V3 and another active region was observed near the parietal-occipital sulcus on the superior surface of the cerebrum. These locations are consistent with sources observed in neuromagnetic studies of the human visual response.

  7. Functional MRI studies of human vision on a clinical imager

    SciTech Connect

    George, J.S.; Lewine, J.D.; Aine, C.J.; van Hulsteyn, D.; Wood, C.C.; Sanders, J.; Maclin, E.; Belliveau, J.W.; Caprihan, A.

    1992-09-01

    During the past decade, Magnetic Resonance Imaging (MRI) has become the method of choice for imaging the anatomy of the human brain. Recently, Belliveau and colleagues have reported the use of echo planar magnetic resonance imaging (EPI) to image patterns of neural activity. Here, we report functional MR imaging in response to visual stimulation without the use of contrast agents, and without the extensive hardware modifications required for EPI. Regions of activity were observed near the expected locations of V1, V2 and possibly V3 and another active region was observed near the parietal-occipital sulcus on the superior surface of the cerebrum. These locations are consistent with sources observed in neuromagnetic studies of the human visual response.

  8. Strengths and Limitations of Model Systems for the Study of Urinary Tract Infections and Related Pathologies.

    PubMed

    Barber, Amelia E; Norton, J Paul; Wiles, Travis J; Mulvey, Matthew A

    2016-06-01

    Urinary tract infections (UTIs) are some of the most common bacterial infections worldwide and are a source of substantial morbidity among otherwise healthy women. UTIs can be caused by a variety of microbes, but the predominant etiologic agent of these infections is uropathogenic Escherichia coli (UPEC). An especially troubling feature of UPEC-associated UTIs is their high rate of recurrence. This problem is compounded by the drastic increase in the global incidence of antibiotic-resistant UPEC strains over the past 15 years. The need for more-effective treatments for UTIs is driving research aimed at bettering our understanding of the virulence mechanisms and host-pathogen interactions that occur during the course of these infections. Surrogate models of human infection, including cell culture systems and the use of murine, porcine, avian, teleost (zebrafish), and nematode hosts, are being employed to define host and bacterial factors that modulate the pathogenesis of UTIs. These model systems are revealing how UPEC strains can avoid or overcome host defenses and acquire scarce nutrients while also providing insight into the virulence mechanisms used by UPEC within compromised individuals, such as catheterized patients. Here, we summarize our current understanding of UTI pathogenesis while also giving an overview of the model systems used to study the initiation, persistence, and recurrence of UTIs and life-threatening sequelae like urosepsis. Although we focus on UPEC, the experimental systems described here can also provide valuable insight into the disease processes associated with other bacterial pathogens both within the urinary tract and elsewhere within the host. PMID:26935136

  9. Foot pain and functional limitation in healthy adults with hallux valgus: a cross-sectional study

    PubMed Central

    2012-01-01

    Background Hallux valgus (HV) is a very common deformity of the first metatarsophalangeal joint that often requires surgical correction. However, the association between structural HV deformity and related foot pain and disability is unclear. Furthermore, no previous studies have investigated concerns about appearance and difficulty with footwear in a population with HV not seeking surgical correction. The aim of this cross-sectional study was to investigate foot pain, functional limitation, concern about appearance and difficulty with footwear in otherwise healthy adults with HV compared to controls. Methods Thirty volunteers with HV (radiographic HV angle >15 degrees) and 30 matched controls were recruited for this study (50 women, 10 men; mean age 44.4 years, range 20 to 76 years). Differences between groups were examined for self-reported foot pain and disability, satisfaction with appearance, footwear difficulty, and pressure-pain threshold at the first metatarsophalangeal joint. Functional measures included balance tests, walking performance, and hallux muscle strength (abduction and plantarflexion). Mean differences (MD) and 95% confidence intervals (CI) were calculated. Results All self-report measures showed that HV was associated with higher levels of foot pain and disability and significant concerns about appearance and footwear (p < 0.001). Lower pressure-pain threshold was measured at the medial first metatarsophalangeal joint in participants with HV (MD = ?133.3 kPa, CI: -251.5 to ?15.1). Participants with HV also showed reduced hallux plantarflexion strength (MD = ?37.1 N, CI: -55.4 to ?18.8) and abduction strength (MD = ?9.8 N, CI: -15.6 to ?4.0), and increased mediolateral sway when standing with both feet with eyes closed (MD = 0.34 cm, CI: 0.04 to 0.63). Conclusions These findings show that HV negatively impacts on self-reported foot pain and function, and concerns about foot appearance and footwear in otherwise healthy adults. There was also evidence of impaired hallux muscle strength and increased postural sway in HV subjects compared to controls, although general physical functioning and participation in physical activity were not adversely affected. PMID:23067345

  10. Further Studies of Accretion onto Hot, Massive, White Dwarfs: The Growth to the Chandrasekhar Limit

    NASA Astrophysics Data System (ADS)

    Starrfield, S.; Timmes, F. X.; Hix, W. R.; Sion, E. M.; Sparks, W. M.; Dwyer, S.

    2004-05-01

    We report on further studies of accretion (Solar Composition material) at a variety of rates onto hot, massive white dwarfs (WDs: Starrfield et al. 2003, Atlanta Meeting, poster 45.10). Our initial models are 1.0 M⊙, 1.25 M⊙, and 1.35 M⊙ WDs with luminosities of 30 L⊙. We have now run evolutionary sequences with mass accretion rates varying from 1.6×10-10 M⊙ yr-1 to 3.5×10-7 M⊙ yr-1 and, in all cases, the WDs grow in mass to near the Chandrasekhar Limit. We use the 1D, hydrodynamic computer code as described in Starrfield et al. (APJS, 127,485, 2000) and have updated the nuclear reaction network, since the calculations reported at Atlanta, to that found at www.cococubed.com/code_pages/net_hhe.shtml. This network combines the pp + hot cno + rp breakout network used previously with an alpha-chain that runs to 56Ni. This will allow us to report on whether or not elements such as Si, S, and Ca are produced in the outer layers during the evolution to explosion so that they do not have to be produced by the explosion. We will also report on simulations done with a lower metallicity for the accreting material - characteristic of that of the LMC. S. Starrfield acknowledges support from NSF and NASA grants to ASU, FXT is supported by the National Security Fellow program at Los Alamos National Laboratory, WRH is partially supported by the National Science Foundation under contracts PHY-0244783 and AST-9877130 and by the Department of Energy, through the Scientific Discovery through Advanced Computing Program. Oak Ridge National Laboratory is managed by UT-Battelle, LLC, for the U.S. Department of Energy under contract DE-AC05-00OR22725. EMS is supported by NASA ADP grant NAG5-11182.

  11. Limited Expression of APRIL and its Receptors Prior to Intestinal IgA Plasma Cell Development During Human Infancy

    PubMed Central

    Gustafson, Claire E.; Higbee, Dana; Yeckes, Alyson R.; Wilson, Cara C.; de Zoeten, Edwin F.; Jedlicka, Paul; Janoff, Edward N.

    2013-01-01

    The absence of immunoglobulin A (IgA) in the intestinal tract renders young infants highly susceptible to enteric infections. However, mediators of initial IgA induction in this population are undefined. We determined the temporal acquisition of plasma cells by isotype and expression of T cell-independent (TI) and -dependent (TD) IgA class switch factors in the human intestinal tract during early infancy. We found that IgA plasma cells were largely absent in the infant intestine until after one month of age, approaching adult densities later in infancy than both IgM and IgG. The restricted development of IgA plasma cells in the first month was accompanied by reduced expression of the TI factor APRIL and its receptors TACI and BCMA within isolated lymphoid follicles (ILFs). Moreover, APRIL and BCMA expression both strongly correlated with increasing IgA plasma cell densities over time. Conversely, TD mediators (CD40L and CD40) were expressed within ILFs prior to one month and were not associated with IgA plasma cell generation. In addition, preterm infants had lower densities of IgA plasma cells and reduced APRIL expression compared with full term infants. Thus, blunted TI responses may contribute to the delayed induction of intestinal IgA during early human infancy. PMID:24045575

  12. Limited expression of APRIL and its receptors prior to intestinal IgA plasma cell development during human infancy.

    PubMed

    Gustafson, C E; Higbee, D; Yeckes, A R; Wilson, C C; De Zoeten, E F; Jedlicka, P; Janoff, E N

    2014-05-01

    The absence of immunoglobulin A (IgA) in the intestinal tract renders young infants highly susceptible to enteric infections. However, mediators of initial IgA induction in this population are undefined. We determined the temporal acquisition of plasma cells by isotype and expression of T cell-independent (TI) and -dependent (TD) IgA class switch factors in the human intestinal tract during early infancy. We found that IgA plasma cells were largely absent in the infant intestine until after 1 month of age, approaching adult densities later in infancy than both IgM and IgG. The restricted development of IgA plasma cells in the first month was accompanied by reduced expression of the TI factor a proliferation-inducing ligand (APRIL) and its receptors TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) and B cell maturation antigen (BCMA) within isolated lymphoid follicles (ILFs). Moreover, both APRIL and BCMA expression strongly correlated with increasing IgA plasma cell densities over time. Conversely, TD mediators (CD40 ligand (CD40L) and CD40) were expressed within ILFs before 1 month and were not associated with IgA plasma cell generation. In addition, preterm infants had lower densities of IgA plasma cells and reduced APRIL expression compared with full-term infants. Thus, blunted TI responses may contribute to the delayed induction of intestinal IgA during early human infancy. PMID:24045575

  13. Limited Applicability of GW9662 to Elucidate PPAR?-Mediated Fatty Acid Effects in Primary Human T-Helper Cells

    PubMed Central

    Jaudszus, Anke; Gruen, Michael; Roth, Alexander; Jahreis, Gerhard

    2014-01-01

    Synthetic antagonists of the nuclear receptor PPAR? such as GW9662 are widely used to elucidate receptor-mediated ligand effects. In addition and complementary to recent work, we examined whether GW9662 is suitable to serve for mechanistic investigation in T-helper cells. Human peripheral blood mononuclear cells (PBMC) were preincubated with increasing concentrations of GW9662 (0, 0.4, 2, and 10??mol/L) 30?min before adding the c9,t11-isomer of conjugated linoleic acid (c9,t11-CLA) as representative of PPAR?-activating fatty acids with immunomodulatory properties. Corresponding cultures were incubated with GW9662 in the absence of the fatty acid. After 19?h, cells were mitogen stimulated for further 5?h. Subsequently, intracellular IL-2 was measured in CD3+CD4+ lymphocytes by means of flow cytometry. 100??mol/L c9,t11-CLA reduced the number of T-helper cells expressing IL-2 by 68%. GW9662 failed to abrogate this fatty acid effect, likely due to the fact that the compound exerted an own inhibitory effect on IL-2 production. Moreover, GW9662 dose-dependently induced cell death in human leukocytes. These results suggest that application of GW9662 is not conducive in this experimental setting. PMID:25054074

  14. Fully validated LCMS bioanalysis of Bevacizumab in human plasma using nano-surface and molecular-orientation limited (nSMOL) proteolysis.

    PubMed

    Iwamoto, Noriko; Umino, Yukari; Aoki, Chikage; Yamane, Naoe; Hamada, Akinobu; Shimada, Takashi

    2016-02-01

    The chemistry of nano-surface and molecular-orientation limited (nSMOL) proteolysis is the Fab-selective limited proteolysis by making use the difference of protease nanoparticle diameter (200nm) and antibody resin pore diameter (100nm). In this report, we have demonstrated that the full validation for Bevacizumab bioanalysis in human plasma using nSMOL. The immunoglobulin fraction was collected by Protein A resin from plasma, then nSMOL reaction was performed using the FG nanoparticle-immobilized trypsin under the nondenaturing physiological condition at 50C for 6h. After removal of resin and nanoparticles, the signature peptide of Bevacizumab complementarity-determining region (CDR) and internal standard P14R were simultaneously quantified by LCMS multiple reaction monitoring (MRM). This nSMOL method quantification of Bevacizumab showed sensitivity of 0.146?g/ml and linearity of 0.146-300?g/ml. The intra- and inter-assay precision of lower limit of quantification (LLOQ), low quality control (LQC), middle quality control (MQC), and high quality control (HQC) was 7.94-15.2% and 14.6%, 7.15-13.5% and 11.7%, 2.63-6.47% and 5.83%, and 3.09-4.35% and 4.45%, respectively. These results indicate that nSMOL is also significant method for Bevacizumab bioanalysis in human plasma. PMID:26830079

  15. Pollution gets personal! A first population-based human biomonitoring study in Austria.

    PubMed

    Hohenblum, Philipp; Steinbichl, Philipp; Raffesberg, Wolfgang; Weiss, Stefan; Moche, Wolfgang; Vallant, Birgit; Scharf, Sigrid; Haluza, Daniela; Moshammer, Hanns; Kundi, Michael; Piegler, Brigitte; Wallner, Peter; Hutter, Hans-Peter

    2012-02-01

    Humans are exposed to a broad variety of man-made chemicals. Human biomonitoring (HBM) data reveal the individual body burden irrespective of sources and routes of uptake. A first population-based study was started in Austria in 2008 and was finished at the end of May 2011. This cross sectional study aims at documenting the extent, the distribution and the determinants of human exposure to industrial chemicals as well as proving the feasibility of a representative HBM study. Overall, 150 volunteers (50 families) were selected by stratified random sampling. Exposure to phthalates, trisphosphates, polybrominated diphenyl ethers (PBDE), bisphenol A (along with nonyl- and octyl phenol) and methyl mercury was assessed. Sixteen of 18 PBDE determined were detected above the limit of quantification (LOQ) in blood samples with #153 and #197 the most abundant species. Bisphenol A in urine was measured in a subsample of 25 with only 4 samples found above the LOQ. In 3 of 100 urine samples at least one of 8 trisphosphate compounds assessed was above the LOQ. These first analytical results of the human biomonitoring data show that the body burden of the Austrian population with respect to the assessed compounds is comparable to or even lower than in other European countries. Overall, the study revealed that in order to develop a feasible protocol for representative human biomonitoring studies procedures have to be optimized to allow for non-invasive sampling of body tissues in accordance with the main metabolic pathways. Procedures of participants' recruitment were, however, labor intensive and have to be improved. PMID:21968335

  16. Dietary flavonoid intake and colorectal cancer risk: evidence from human population studies.

    PubMed

    Kocic, B; Kitic, D; Brankovic, S

    2013-01-01

    Flavonoids are biologically active polyphenolic compounds widely distributed in plants. More than 5000 individual flavonoids have been identified, which are classified into at least 10 subgroups according to their chemical structure. Flavonoids of 6 principal subgroups- flavonols, flavones, anthocyanidins, catechins, flavanones, and isoflavones- are relatively common in human diets. Flavonoids are a large and diverse group of phytochemicals and research into their anti-carcinogenic potential with animal and cellular model systems supports a protective role. Whether dietary intake of flavonoids is protective against colorectal cancer in humans cannot be easily extrapolated from cell line and animal findings. Epidemiological assessment of the relationship between dietary flavonoid intake and colorectal cancer is limited, with different case-control and cohort study design investigating different combinations of flavonoids. Epidemiologic studies on flavonoid intake and colorectal cancer risk that were conducted yielded inconsistent results, with positive, inverse, and null associations. Because only a very limited number of epidemiological studies have been conducted to examine the associations of dietary intake of flavonoids with colorectal cancer risk, it is premature to make public health recommendations at this time. However, the data to date are promising and emphasize the need for further investigation of these important bioactive plant compounds. This review summarises the epidemiological evidence from case-control and cohort studies on the associations of dietary flavonoid intake with the risk for colorectal cancer. The difficulties in investigating this topic and possibilities for further research are then discussed. PMID:23613386

  17. A critical review of epidemiologic studies of radiofrequency exposure and human cancers.

    PubMed Central

    Elwood, J M

    1999-01-01

    This paper reviews studies that have assessed associations between likely exposure to radiofrequency (RF) transmissions and various types of human cancer. These studies include three cluster investigations and five studies relating to general populations; all of these studies consider place of residence at the time of cancer diagnosis in regard to proximity to radio or television transmitters. There are also five relevant occupational cohort studies and several case-control studies of particular types of cancer. These studies assessed a large number of possible associations. Several positive associations suggesting an increased risk of some types of cancer in those who may have had greater exposure to RF emissions have been reported. However, the results are inconsistent: there is no type of cancer that has been consistently associated with RF exposures. The epidemiologic evidence falls short of the strength and consistency of evidence that is required to come to a reasonable conclusion that RF emissions are a likely cause of one or more types of human cancer. The evidence is weak in regard to its inconsistency, the design of the studies, the lack of detail on actual exposures, and the limitations of the studies in their ability to deal with other likely relevant factors. In some studies there may be biases in the data used PMID:10229715

  18. Comparison of polychlorinated biphenyl levels across studies of human neurodevelopment.

    PubMed Central

    Longnecker, Matthew P; Wolff, Mary S; Gladen, Beth C; Brock, John W; Grandjean, Philippe; Jacobson, Joseph L; Korrick, Susan A; Rogan, Walter J; Weisglas-Kuperus, Nynke; Hertz-Picciotto, Irva; Ayotte, Pierre; Stewart, Paul; Winneke, Gerhard; Charles, M Judith; Jacobson, Sandra W; Dewailly, Eric; Boersma, E Rudy; Altshul, Larisa M; Heinzow, Birger; Pagano, James J; Jensen, Allan A

    2003-01-01

    Polychlorinated biphenyls (PCBs) are persistent pollutants that are ubiquitous in the food chain, and detectable amounts are in the blood of almost every person in most populations that have been examined. Extensive evidence from animal studies shows that PCBs are neurotoxins, even at low doses. Interpretation of human data regarding low-level, early-life PCB exposure and subsequent neurodevelopment is problematic because levels of exposure were not similarly quantified across studies. We expressed the exposure levels from 10 studies of PCB and neurodevelopment in a uniform manner using a combination of data from original investigators, laboratory reanalyses, calculations based on published data, and expert opinion. The mainstay of our comparison was the median level of PCB 153 in maternal pregnancy serum. The median concentration of PCB 153 in the 10 studies ranged from 30 to 450 ng/g serum lipid, and the median of the 10 medians was 110 ng/g. We found that (a)) the distribution of PCB 153 exposure in most studies overlapped substantially, (b)) exposure levels in the Faroe Islands study were about 3-4-fold higher than in most other studies, and (c)) the exposure levels in the two recent U.S. studies were about one-third of those in the four earlier U.S. studies or recent Dutch, German, and northern Qubec studies. Our results will facilitate a direct comparison of the findings on PCBs and neurodevelopment when they are published for all 10 studies. PMID:12515680

  19. Lower body negative pressure as a model to study progression to acute hemorrhagic shock in humans.

    PubMed

    Cooke, William H; Ryan, Kathy L; Convertino, Victor A

    2004-04-01

    Hemorrhage is a leading cause of death in both civilian and battlefield trauma. Survival rates increase when victims requiring immediate intervention are correctly identified in a mass-casualty situation, but methods of prioritizing casualties based on current triage algorithms are severely limited. Development of effective procedures to predict the magnitude of hemorrhage and the likelihood for progression to hemorrhagic shock must necessarily be based on carefully controlled human experimentation, but controlled study of severe hemorrhage in humans is not possible. It may be possible to simulate hemorrhage, as many of the physiological compensations to acute hemorrhage can be mimicked in the laboratory by applying negative pressure to the lower extremities. Lower body negative pressure (LBNP) sequesters blood from the thorax into dependent regions of the pelvis and legs, effectively decreasing central blood volume in a similar fashion as acute hemorrhage. In this review, we compare physiological responses to hemorrhage and LBNP with particular emphasis on cardiovascular compensations that both share in common. Through evaluation of animal and human data, we present evidence that supports the hypothesis that LBNP, and resulting volume sequestration, is an effective technique to study physiological responses and mechanisms associated with acute hemorrhage in humans. Such experiments could lead to clinical algorithms that identify bleeding victims who will likely progress to hemorrhagic shock and require lifesaving intervention(s). PMID:15016789

  20. Two open states and rate-limiting gating steps revealed by intracellular Na+ block of human KCNQ1 and KCNQ1/KCNE1 K+ channels.

    PubMed

    Pusch, M; Ferrera, L; Friedrich, T

    2001-05-15

    KCNQ1, the first member of a new K+ channel family, associates with the small KCNE1 subunit to form the slow cardiac delayed rectifier current, IKs. Mutations in both genes encoding these channels lead to cardiac arrhythmia. We studied the block by intracellular Na+ of human homomeric KCNQ1 (homomers) and heteromeric KCNQ1/KCNE1 (heteromers) expressed in CHO cells (Chinese hamster ovary cell line) using whole-cell patch recording. In the nominal absence of extracellular K+ and with 65 mM intracellular K+, the replacement of 65 mM intracellular N-methyl-D-glucamine (NMDG+) by 65 mM Na+ induced a decay of outward (K+) currents through homomers after maximal activation reminiscent of an inactivation process. The decay had a time constant in the hundreds of milliseconds range. The inactivation process of homomers was, however, not directly dependent on [Na+]i, as evidenced by unaltered biphasic deactivation at negative voltages. An instantaneous voltage-dependent Na+ block of homomers was revealed using tail current protocols with activating prepulses that saturated the gating processes of the channel. The instantaneous block was partially relieved at very large positive voltages (> or = 60 mV) and in 20 mM extracellular K+. The instantaneous block of homomers was much less pronounced if the tail currents were measured after short activating prepulses, demonstrating the presence of (at least) two open states: a first, relatively [Na+]i-insensitive and a subsequent [Na+]i-sensitive open state; the current decay reflects the transition between the two open states. Heteromers exhibited a very similar instantaneous block by Na+i independently of the prepulse duration. Heteromers did not show a Na+i-induced current decay. Our results demonstrate the presence of two open states of KCNQ1 channels with different [Na+]i sensitivities. The rate-limiting step of homomeric KCNQ1 gating at positive voltages is the transition between these two open states. The rate-limiting step of the gating of KCNQ1/KCNE1 channels appears to be the entry into the first open state. PMID:11351022