Science.gov

Sample records for limited human studies

  1. 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.

  2. Human reproduction: dominion and limits.

    PubMed

    McCormick, Richard A

    1996-12-01

    The general struggle throughout Christian history has been to seek the proper balance between dominion and limits, intervention and nonintervention, givenness, and creativity. This struggle has worked itself out in six areas that touch human life. In this essay, I will revisit the Catholic tradition's treatment of these in terms of dominion and limits to see whether we can discern developmental patterns that might suggest an approach to issues pertaining to the sources of life (reproductive ethics) as we move into the next century.

  3. The promise and limitations of population exomics for human evolution studies

    PubMed Central

    2011-01-01

    Exome sequencing is poised to yield substantial insights into human genetic variation and evolutionary history, but there are significant challenges to overcome before this becomes a reality. PMID:21920050

  4. Limit cycle oscillations in standing human posture.

    PubMed

    Chagdes, James R; Rietdyk, Shirley; Haddad, Jeffrey M; Zelaznik, Howard N; Cinelli, Michael E; Denomme, Luke T; Powers, Kaley C; Raman, Arvind

    2016-05-01

    Limit cycle oscillations (LCOs) are a hallmark of dynamic instability in time-delayed and nonlinear systems such as climate change models, biological oscillators, and robotics. Here we study the links between the human neuromuscular system and LCOs in standing posture. First, we demonstrate through a simple mathematical model that the observation of LCOs in posture is indicative of excessive neuromuscular time-delay. To test this hypothesis we study LCOs in the postural sway of individuals with multiple sclerosis and concussed athletes representing two different populations with chronically and acutely increased neuromuscular time-delays. Using a wavelet analysis method we demonstrate that 67% of individuals with multiple sclerosis and 44% of individuals with concussion exhibit intermittent LCOs; 8% of MS-controls, 0% of older adults, and 0% of concussion-controls displayed LCOs. Thus, LCOs are not only key to understanding postural instability but also may have important applications for the detection of neuromuscular deficiencies. PMID:27018157

  5. Limitations of human occipital scalp hair follicle organ culture for studying the effects of minoxidil as a hair growth enhancer.

    PubMed

    Magerl, Markus; Paus, Ralf; Farjo, Nilofer; Müller-Röver, Sven; Peters, Eva M J; Foitzik, Kerstin; Tobin, Desmond J

    2004-10-01

    Minoxidil induces new hair growth in approximately one-third of patients with androgenetic alopecia after 1 year of treatment. With several conflicting reports in the literature based on small-scale studies, the current study aimed to clarify whether organ culture of human scalp anagen VI hair follicles is a suitable in vitro test system for reproducing, and experimentally dissecting, the recognized in vivo hair-growth-promoting capacity of minoxidil. Hair shaft elongation was studied in terminal anagen VI hair follicles microdissected from the occipital scalp of 36 healthy adults. A total of 2300 hair follicles, approximately 65 per individual, were tested using modifications of a basic organ culture protocol. It is shown here that minoxidil does not significantly increase hair shaft elongation or the duration of anagen VI in ex vivo culture despite several enhancements on the conventional methodology. This disparity to what is seen clinically in minoxidil responders may be explained by the following: (i) use of occipital (rather than frontotemporal or vertex) hair follicles; (ii) use of, already maximally growing, anagen VI hair follicles; (iii) a predominance of hair follicles from minoxidil unresponsive-donors; (iv) use of minoxidil rather than its sulfate metabolite; and/or (v) use of a suboptimal minoxidil dosage. This disparity questions the usefulness of standard human hair follicle organ culture in minoxidil research. Unexpectedly, minoxidil even inhibited hair shaft elongation in the absence of insulin, which may indicate that the actual hair-growth-modulatory effects of minoxidil depend on the concomitant local presence/absence of other growth modulators.

  6. 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.

  7. 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.

  8. Experimental studies on pump limiters

    NASA Astrophysics Data System (ADS)

    Mioduszewski, P.

    1982-12-01

    Pump limiters are mechanical devices for He-ash removal, fuel particle control, and possibly impurity control. Different designs have been suggested by various authors over the past decade. However, the magnetic divertor concepts seemed to be more promising, mainly because of their remote plasma-material interactions. All of the characteristics of magnetic divertors have been proven experimentally, but the overall performance and complexity cause concern about their application to tokamak reactors. Consequently, it is now time to explore the potential of mechanical particle control devices, i.e. pump limiters. Because of the high recycling at the limiter, it is sufficient to exhaust only a small fraction, about 1-10%, of the limiter particle flux to remove e.g. He at its rate of production. Pump limiter experiments have been conducted so far on Alcator, PDX, Macrotor, and ISX. Depending on the experimental design, a pressure build-up of between 1 mTorr and 50 mTorr has been reported. The closed configuration pump limiters provide high collection efficiencies, but have to accomodate high power fluxes at the leading edge. An open configuration, on the other hand, avoids leading edges but provides only fairly low collection efficiencies. The pump limiter development program now calls for a full pump limiter to be implemented in a major tokamak device. Presently, full-size pump limiter experiments on PDX, ISX, and TEXTOR are in preparation.

  9. Experimental studies on pump limiters

    SciTech Connect

    Mioduszewski, P.

    1982-01-01

    Pump limiters are mechanical devices for He-ash removal, fuel particle control, and possibly impurity control. Different designs have been suggested by various authors over the past decade. However, the magnetic divertor concepts seemed to be more promising, mainly because of their remote plasma-material interactions. All of the characteristics of magnetic divertors have been proven experimentally, but the overall performance and complexity cause concern about their application to tokamak reactors. Consequently, it is time now to explore the potential of mechanical particle control devices, i.e. pump limiters. Because of the high recycling at the limiter, it is sufficient to exhaust only a small fraction, about 1 to 10%, of the limiter particle flux to remove e.g. He at its rate of production. Pump limiter experiments have been conducted so far on Alcator, PDX, Macrotor, and ISX. Depending on the experimental design, a pressure build-up of between 1 mTorr and 50 mTorr has been reported.

  10. Phase I and pharmacological study of the pulmonary cytotoxin 4-ipomeanol on a single dose schedule in lung cancer patients: hepatotoxicity is dose limiting in humans.

    PubMed

    Rowinsky, E K; Noe, D A; Ettinger, D S; Christian, M C; Lubejko, B G; Fishman, E K; Sartorius, S E; Boyd, M R; Donehower, R C

    1993-04-15

    4-Ipomeanol (IPO), a naturally occurring pulmonary toxin, is the first cytotoxic agent to undergo clinical development based on a biochemical-biological rationale as an antineoplastic agent targeted specifically against lung cancer. This rationale is based on preclinical observations that metabolic activation and intracellular binding of IPO, as well as cytotoxicity, occurred selectively in tissues and cancers derived from tissues that are rich in specific P450 mixed function oxidase enzymes. Although tissues capable of activating IPO to cytotoxic intermediates in vitro include liver, lung, and kidney, IPO has been demonstrated in rodents and dogs to undergo in situ activation, bind covalently, and induce cytotoxicity preferentially in lung tissue at doses not similarly affecting liver or kidneys. Although the drug was devoid of antitumor activity in the conventional murine preclinical screening models, cytotoxic activity was observed in human lung cancers in vitro and in human lung cancer xenografts in vivo, adding to the rationale for clinical development. Somewhat unexpectantly, hepatocellular toxicity was the dose-limiting principal toxicity of IPO administered as a 30-min infusion every 3 weeks to patients with lung cancer. In this study, 55 patients received 254 courses at doses almost spanning 3 orders of magnitude, 6.5 to 1612 mg/m2. Transient and isolated elevations in hepatocellular enzymes, predominantly alanine aminotransferase, occurred in the majority of courses of IPO at 1032 mg/m2, which is the recommended IPO dose for subsequent phase II trials. At higher doses, hepatocellular toxicity was more severe and was often associated with right upper quadrant pain and severe malaise. Toxic effects were also noted in other tissues capable of activating IPO, including possible nephrotoxicity in a patient treated with one course of IPO at 154 mg/m2 and severe, reversible pulmonary toxicity in another patient who received nine courses of IPO at doses ranging

  11. 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.

  12. Studying the Human Microbiota.

    PubMed

    Walker, Alan W

    2016-01-01

    There are a range of methodologies available to study the human microbiota, ranging from traditional approaches such as culturing through to state-of-the-art developments in next generation DNA sequencing technologies. The advent of molecular techniques in particular has opened up tremendous new avenues for research, and has galvanised interest in the study of our microbial inhabitants. Given the dazzling array of available options, however, it is important to understand the inherent advantages and limitations of each technique so that the best approach can be employed to address the particular research objective. In this chapter we cover some of the most widely used current techniques in human microbiota research and highlight the particular strengths and caveats associated with each approach. PMID:27161348

  13. 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.

  14. Limited Diversity among Human Isolates of Bartonella henselae

    PubMed Central

    Dillon, B.; Valenzuela, J.; Don, R.; Blanckenberg, D.; Wigney, D. I.; Malik, R.; Morris, A. J.; Robson, J. M.; Iredell, J.

    2002-01-01

    A study of 59 isolates of Bartonella henselae reveals relatively limited diversity among those of human origin (n = 28). Either of two distinct alleles of both gltA and 16S ribosomal DNA (rDNA) was found in all isolates, with a high level of congruity between 16S and gltA inheritance among proven human pathogens. Human isolates from all over Eastern Australia were most commonly 16S rDNA (Bergmans) type I, with the same gltA allele as the type strain (Houston-1). Comparable feline isolates were more commonly 16S type II, with less congruity of inheritance between 16S and gltA alleles. Previously described arbitrarily primed PCR and EagI-HhaI infrequent restriction site PCR fingerprinting techniques separated Bartonella species effectively but lacked discriminating power within B. henselae. Examination of the 16-23S intergenic spacer region revealed for several strains several point mutations as well as a repeat sequence of unknown significance which is readily detected by HaeIII restriction fragment length polymorphism analysis. The bacteriophage-associated papA gene was present in all isolates. Enterobacterial repetitive intergenic consensus PCR proved to be a useful and robust typing tool and clearly separated human isolates (including imported strains) from the majority of feline isolates. Our data are consistent with published evidence and with previous suggestions of intragenomic rearrangements in the type strain and suggest that human isolates come from a limited subset of B. henselae strains. They strengthen arguments for careful exploration of genotype-phenotype relationships and for the development of a multilocus enzyme electrophoresis and multilocus sequence typing-based approach to the phylogeny of B. henselae. PMID:12454174

  15. Approaching the Limit of Predictability in Human Mobility

    NASA Astrophysics Data System (ADS)

    Lu, Xin; Wetter, Erik; Bharti, Nita; Tatem, Andrew J.; Bengtsson, Linus

    2013-10-01

    In this study we analyze the travel patterns of 500,000 individuals in Cote d'Ivoire using mobile phone call data records. By measuring the uncertainties of movements using entropy, considering both the frequencies and temporal correlations of individual trajectories, we find that the theoretical maximum predictability is as high as 88%. To verify whether such a theoretical limit can be approached, we implement a series of Markov chain (MC) based models to predict the actual locations visited by each user. Results show that MC models can produce a prediction accuracy of 87% for stationary trajectories and 95% for non-stationary trajectories. Our findings indicate that human mobility is highly dependent on historical behaviors, and that the maximum predictability is not only a fundamental theoretical limit for potential predictive power, but also an approachable target for actual prediction accuracy.

  16. Approaching the limit of predictability in human mobility.

    PubMed

    Lu, Xin; Wetter, Erik; Bharti, Nita; Tatem, Andrew J; Bengtsson, Linus

    2013-01-01

    In this study we analyze the travel patterns of 500,000 individuals in Cote d'Ivoire using mobile phone call data records. By measuring the uncertainties of movements using entropy, considering both the frequencies and temporal correlations of individual trajectories, we find that the theoretical maximum predictability is as high as 88%. To verify whether such a theoretical limit can be approached, we implement a series of Markov chain (MC) based models to predict the actual locations visited by each user. Results show that MC models can produce a prediction accuracy of 87% for stationary trajectories and 95% for non-stationary trajectories. Our findings indicate that human mobility is highly dependent on historical behaviors, and that the maximum predictability is not only a fundamental theoretical limit for potential predictive power, but also an approachable target for actual prediction accuracy. PMID:24113276

  17. Approaching the Limit of Predictability in Human Mobility

    PubMed Central

    Lu, Xin; Wetter, Erik; Bharti, Nita; Tatem, Andrew J.; Bengtsson, Linus

    2013-01-01

    In this study we analyze the travel patterns of 500,000 individuals in Cote d'Ivoire using mobile phone call data records. By measuring the uncertainties of movements using entropy, considering both the frequencies and temporal correlations of individual trajectories, we find that the theoretical maximum predictability is as high as 88%. To verify whether such a theoretical limit can be approached, we implement a series of Markov chain (MC) based models to predict the actual locations visited by each user. Results show that MC models can produce a prediction accuracy of 87% for stationary trajectories and 95% for non-stationary trajectories. Our findings indicate that human mobility is highly dependent on historical behaviors, and that the maximum predictability is not only a fundamental theoretical limit for potential predictive power, but also an approachable target for actual prediction accuracy. PMID:24113276

  18. 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...

  19. 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...

  20. Food availability at birth limited reproductive success in historical humans.

    PubMed

    Rickard, Ian J; Holopainen, Jari; Helama, Samuli; Helle, Samuli; Russell, Andrew F; Lummaa, Virpi

    2010-12-01

    Environmental conditions in early life can profoundly affect individual development and have consequences for reproductive success. Limited food availability may be one of the reasons for this, but direct evidence linking variation in early-life nutrition to reproductive performance in adulthood in natural populations is sparse. We combined historical agricultural data with detailed demographic church records to investigate the effect of food availability around the time of birth on the reproductive success of 927 men and women born in 18th-century Finland. Our study population exhibits natural mortality and fertility rates typical of many preindustrial societies, and individuals experienced differing access to resources due to social stratification. We found that among both men and women born into landless families (i.e., with low access to resources), marital prospects, probability of reproduction, and offspring viability were all positively related to local crop yield during the birth year. Such effects were generally absent among those born into landowning families. Among landless individuals born when yields of the two main crops, rye and barley, were both below median, only 50% of adult males and 55% of adult females gained any reproductive success in their lifetime, whereas 97% and 95% of those born when both yields were above the median did so. Our results suggest that maternal investment in offspring in prenatal or early postnatal life may have profound implications for the evolutionary fitness of human offspring, particularly among those for which resources are more limiting. Our study adds support to the idea that early nutrition can limit reproductive success in natural animal populations, and provides the most direct evidence to date that this process applies to humans.

  1. Human-caused fires limit rainfall in tropical Africa

    NASA Astrophysics Data System (ADS)

    Tosca, M. G., Jr.

    2015-12-01

    It is well established that smoke particles modify clouds, which in turn affects climate. However, no studies have 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 divergence -- meteorological indicators of convective suppression. The resulting decrease in rainfall is substantial and may increase human ignitions during the dry season. 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.

  2. 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 Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING COMMERCIAL ACTIVITIES PROGRAM PROCEDURES Procedures § 169a.19 Study limits. No DoD funds shall be available to perform any...

  3. 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 Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING COMMERCIAL ACTIVITIES PROGRAM PROCEDURES Procedures § 169a.19 Study limits. No DoD funds shall be available to perform any...

  4. 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 Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING COMMERCIAL ACTIVITIES PROGRAM PROCEDURES Procedures § 169a.19 Study limits. No DoD funds shall be available to perform any...

  5. The Limits of Narrative: Provocations for the Medical Humanities

    PubMed Central

    Woods, Angela

    2014-01-01

    This paper aims to (re)ignite debate about the role of narrative in the medical humanities. It begins with a critical review of the ways in which narrative has been mobilised by humanities and social science scholars to understand the experience of health and illness. I highlight seven dangers or blind spots in the dominant medical humanities approach to narrative, including the frequently unexamined assumption that all human beings are “naturally narrative.” I then explore this assumption further through an analysis of philosopher Galen Strawson’s influential article “Against Narrativity.” Strawson rejects the descriptive claim that “human beings typically see or live or experience their lives as a narrative” and the normative claim that “a richly Narrative outlook is essential to a well-lived life, to true or full personhood.” His work has been taken up across a range of disciplines but its implications in the context of health and illness have not yet been sufficiently discussed. This article argues that “Against Narrativity” can and should stimulate robust debate within the medical humanities regarding the limits of narrative, and concludes by discussing a range of possibilities for venturing “beyond narrative.” PMID:22038696

  6. 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...

  7. 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

  8. Transcending the Limitations of the Social Sciences: Insight, Understanding, and the Humanities in Educational Administration.

    ERIC Educational Resources Information Center

    Ryan, James

    1994-01-01

    Considers the role of the humanities in the study and practice of educational administration, offering significant insights into the human condition and the philosophical and moral aspects of education. Discusses the limitations of the subject-object dualism underpinning traditional social science. Explains how Slipperjack's "Honor the Sun,"…

  9. 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?

  10. A network model of human aging: Limits, errors, and information

    NASA Astrophysics Data System (ADS)

    Farrell, Spencer; Mitnitski, Arnold; Rockwood, Kenneth; Rutenberg, Andrew

    The Frailty Index (FI) quantifies human aging using the fraction of accumulated age-related deficits. The FI correlates strongly with mortality and accumulates non-linearly and stochastically with age. Clinical data shows a nearly universal limit of FI <= 0 . 7 . We computationally model an aging population using a network model of interacting deficits. Deficits damage and repair at rates that depend upon the average damage of connected nodes. The model is parametrized to fit clinical data. We find that attribution errors, especially false negative, allow the model to recover the frailty limit. Mutual information allows us to assess how well the FI can predict mortality. Mutual information provides a non-parametric measure of how the FI predicts mortality. We find that attribution errors have a small effect on the mutual information when many deficits are included in the model. The mutual information of our model and of the clinical data are comparable.

  11. 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.

  12. Density limit studies on DIII-D

    SciTech Connect

    Maingi, R.; Mahdavi, M.A.; Petrie, T.W.

    1998-08-01

    The authors have studied the processes limiting plasma density and successfully achieved discharges with density {approximately}50% above the empirical Greenwald density limit with H-mode confinement. This was accomplished by density profile control, enabled through pellet injection and divertor pumping. By examining carefully the criterion for MARFE formation, the authors have derived an edge density limit with scaling very similar to Greenwald scaling. Finally, they have looked in detail at the first and most common density limit process in DIII-D, total divertor detachment, and found that the local upstream separatrix density (n{sub e}{sup sep,det}) at detachment onset (partial detachment) increases with the scrape-off layer heating power, P{sub heat}, i.e., n{sub e}{sup sep,det} {approximately} P{sub heat}{sup 0.76}. This is in marked contrast to the line-average density at detachment which is insensitive to the heating power. The data are in reasonable agreement with the Borass model, which predicted that the upstream density at detachment would increase as P{sub heat}{sup 0.7}.

  13. [Biofunctional age diagnosis in humans. Potentials and limits].

    PubMed

    Pöthig, D; Gerdes, W; Viol, M; Wagner, P; Simm, A

    2011-06-01

    The demand and requirements for valid, practicable, and reliable procedures for age diagnosis are increasing worldwide. In contrast, few studies and only a small number of procedures exist. The authors review the theoretical and methodological requirements for the development of models for age diagnostics. They describe the fundamentals for further studies, based on an analysis of current gerontological research in this area. A following publication will report the valid systems measuring vitality and biofunctional age(ing) of human beings. PMID:21505938

  14. Constraints limiting the rate of human expansion into the Galaxy

    NASA Astrophysics Data System (ADS)

    Smith, A. G.

    1981-09-01

    It is pointed out that human expansion into a largely lifeless Galaxy will be constrained by ecological and engineering factors. Bringing a barren planet to a stable habitable state will require a long series of biological introductions, each tailored to the particular planet. The difficulties in transporting complete ecosystems will mean that even a first-generation colony will have no more than a skeleton ecology. Settlers will be hard put to it to persuade older colonies, or earth itself, to send them extra life forms. This will be difficult in view of the fact that information is the only commodity that can be traded easily in return. Colonization will therefore proceed more slowly after the first expansion from earth. It is thought that extraterrestrial civilizations are probably limited in the same ways.

  15. Zebrafish models of human motor neuron diseases: advantages and limitations.

    PubMed

    Babin, Patrick J; Goizet, Cyril; Raldúa, Demetrio

    2014-07-01

    Motor neuron diseases (MNDs) are an etiologically heterogeneous group of disorders of neurodegenerative origin, which result in degeneration of lower (LMNs) and/or upper motor neurons (UMNs). Neurodegenerative MNDs include pure hereditary spastic paraplegia (HSP), which involves specific degeneration of UMNs, leading to progressive spasticity of the lower limbs. In contrast, spinal muscular atrophy (SMA) involves the specific degeneration of LMNs, with symmetrical muscle weakness and atrophy. Amyotrophic lateral sclerosis (ALS), the most common adult-onset MND, is characterized by the degeneration of both UMNs and LMNs, leading to progressive muscle weakness, atrophy, and spasticity. A review of the comparative neuroanatomy of the human and zebrafish motor systems showed that, while the zebrafish was a homologous model for LMN disorders, such as SMA, it was only partially relevant in the case of UMN disorders, due to the absence of corticospinal and rubrospinal tracts in its central nervous system. Even considering the limitation of this model to fully reproduce the human UMN disorders, zebrafish offer an excellent alternative vertebrate model for the molecular and genetic dissection of MND mechanisms. Its advantages include the conservation of genome and physiological processes and applicable in vivo tools, including easy imaging, loss or gain of function methods, behavioral tests to examine changes in motor activity, and the ease of simultaneous chemical/drug testing on large numbers of animals. This facilitates the assessment of the environmental origin of MNDs, alone or in combination with genetic traits and putative modifier genes. Positive hits obtained by phenotype-based small-molecule screening using zebrafish may potentially be effective drugs for treatment of human MNDs.

  16. Zebrafish models of human motor neuron diseases: advantages and limitations.

    PubMed

    Babin, Patrick J; Goizet, Cyril; Raldúa, Demetrio

    2014-07-01

    Motor neuron diseases (MNDs) are an etiologically heterogeneous group of disorders of neurodegenerative origin, which result in degeneration of lower (LMNs) and/or upper motor neurons (UMNs). Neurodegenerative MNDs include pure hereditary spastic paraplegia (HSP), which involves specific degeneration of UMNs, leading to progressive spasticity of the lower limbs. In contrast, spinal muscular atrophy (SMA) involves the specific degeneration of LMNs, with symmetrical muscle weakness and atrophy. Amyotrophic lateral sclerosis (ALS), the most common adult-onset MND, is characterized by the degeneration of both UMNs and LMNs, leading to progressive muscle weakness, atrophy, and spasticity. A review of the comparative neuroanatomy of the human and zebrafish motor systems showed that, while the zebrafish was a homologous model for LMN disorders, such as SMA, it was only partially relevant in the case of UMN disorders, due to the absence of corticospinal and rubrospinal tracts in its central nervous system. Even considering the limitation of this model to fully reproduce the human UMN disorders, zebrafish offer an excellent alternative vertebrate model for the molecular and genetic dissection of MND mechanisms. Its advantages include the conservation of genome and physiological processes and applicable in vivo tools, including easy imaging, loss or gain of function methods, behavioral tests to examine changes in motor activity, and the ease of simultaneous chemical/drug testing on large numbers of animals. This facilitates the assessment of the environmental origin of MNDs, alone or in combination with genetic traits and putative modifier genes. Positive hits obtained by phenotype-based small-molecule screening using zebrafish may potentially be effective drugs for treatment of human MNDs. PMID:24705136

  17. [The advantages and limitations of observational studies].

    PubMed

    Onder, Graziano

    2013-03-01

    Randomized clinical trials are considered the gold standard for establishing treatment efficacy and generate evidence-based medicine. Nonetheless, because of the stringent exclusion criteria used in selecting study populations, concerns are raised about the limited generalizability of evidence they provide. Indeed, randomized clinical trials assess treatment efficacy for an "average" patient, quite often far from older adults characterized by chronic comorbidities of different severity, or by functional and/or cognitive impairment. Observational studies have been proposed as alternative means of testing intervention effectiveness in older populations with multifaceted problems. Unlike randomized clinical trials, they assess outcomes in regular clinical practice, thereby reflecting real adherence to treatment/intervention. The availability of huge, high quality databases offers the potential to bring research closer to practice and audit. Databases provide fertile grounds for observational studies, and can generate hypotheses and provide ready access to trialists as well, setting new possibilities for epidemiological research. They must include complete data on all consecutive patients, use standard definitions of conditions and outcomes, and include all clinical characteristics likely to affect outcomes. In addition, their potential for research and audit is greatly enhanced by linking to other databases, like the census ones, which allow evaluation of geographical and contextual information.

  18. Overcoming the limited availability of human milk oligosaccharides: challenges and opportunities for research and application.

    PubMed

    Bode, Lars; Contractor, Nikhat; Barile, Daniela; Pohl, Nicola; Prudden, Anthony R; Boons, Geert-Jan; Jin, Yong-Su; Jennewein, Stefan

    2016-10-01

    Human milk oligosaccharides (HMOs) are complex sugars highly abundant in human milk but currently not present in infant formula. Rapidly accumulating evidence from in vitro and in vivo studies, combined with epidemiological associations and correlations, suggests that HMOs benefit infants through multiple mechanisms and in a variety of clinical contexts. Until recently, however, research on HMOs has been limited by an insufficient availability of HMOs. Most HMOs are found uniquely in human milk, and thus far it has been prohibitively tedious and expensive to isolate and synthesize them. This article reviews new strategies to overcome this lack of availability by generating HMOs through chemoenzymatic synthesis, microbial metabolic engineering, and isolation from human donor milk or dairy streams. Each approach has its advantages and comes with its own challenges, but combining the different methods and acknowledging their limitations creates new opportunities for research and application with the goal of improving maternal and infant health. PMID:27634978

  19. Overcoming the limited availability of human milk oligosaccharides: challenges and opportunities for research and application.

    PubMed

    Bode, Lars; Contractor, Nikhat; Barile, Daniela; Pohl, Nicola; Prudden, Anthony R; Boons, Geert-Jan; Jin, Yong-Su; Jennewein, Stefan

    2016-10-01

    Human milk oligosaccharides (HMOs) are complex sugars highly abundant in human milk but currently not present in infant formula. Rapidly accumulating evidence from in vitro and in vivo studies, combined with epidemiological associations and correlations, suggests that HMOs benefit infants through multiple mechanisms and in a variety of clinical contexts. Until recently, however, research on HMOs has been limited by an insufficient availability of HMOs. Most HMOs are found uniquely in human milk, and thus far it has been prohibitively tedious and expensive to isolate and synthesize them. This article reviews new strategies to overcome this lack of availability by generating HMOs through chemoenzymatic synthesis, microbial metabolic engineering, and isolation from human donor milk or dairy streams. Each approach has its advantages and comes with its own challenges, but combining the different methods and acknowledging their limitations creates new opportunities for research and application with the goal of improving maternal and infant health.

  20. Limited Trabecular Bone Density Heterogeneity in the Human Skeleton

    PubMed Central

    Chirchir, Habiba

    2016-01-01

    There is evidence for variation in trabecular bone density and volume within an individual skeleton, albeit in a few anatomical sites, which is partly dependent on mechanical loading. However, little is known regarding the basic variation in trabecular bone density throughout the skeleton in healthy human adults. This is because research on bone density has been confined to a few skeletal elements, which can be readily measured using available imaging technology particularly in clinical settings. This study comprehensively investigates the distribution of trabecular bone density within the human skeleton in nine skeletal sites (femur, proximal and distal tibia, third metatarsal, humerus, ulna, radius, third metacarpal, and axis) in a sample of N = 20 individuals (11 males and 9 females). pQCT results showed that the proximal ulna (mean = 231.3 mg/cm3) and axis vertebra (mean = 234.3 mg/cm3) displayed significantly greater (p < 0.01) trabecular bone density than other elements, whereas there was no significant variation among the rest of the elements (p > 0.01). The homogeneity of the majority of elements suggests that these sites are potentially responsive to site-specific genetic factors. Secondly, the lack of correlation between elements (p > 0.05) suggests that density measurements of one anatomical region are not necessarily accurate measures of other anatomical regions. PMID:27148458

  1. Limited Trabecular Bone Density Heterogeneity in the Human Skeleton.

    PubMed

    Chirchir, Habiba

    2016-01-01

    There is evidence for variation in trabecular bone density and volume within an individual skeleton, albeit in a few anatomical sites, which is partly dependent on mechanical loading. However, little is known regarding the basic variation in trabecular bone density throughout the skeleton in healthy human adults. This is because research on bone density has been confined to a few skeletal elements, which can be readily measured using available imaging technology particularly in clinical settings. This study comprehensively investigates the distribution of trabecular bone density within the human skeleton in nine skeletal sites (femur, proximal and distal tibia, third metatarsal, humerus, ulna, radius, third metacarpal, and axis) in a sample of N = 20 individuals (11 males and 9 females). pQCT results showed that the proximal ulna (mean = 231.3 mg/cm(3)) and axis vertebra (mean = 234.3 mg/cm(3)) displayed significantly greater (p < 0.01) trabecular bone density than other elements, whereas there was no significant variation among the rest of the elements (p > 0.01). The homogeneity of the majority of elements suggests that these sites are potentially responsive to site-specific genetic factors. Secondly, the lack of correlation between elements (p > 0.05) suggests that density measurements of one anatomical region are not necessarily accurate measures of other anatomical regions.

  2. On the Limits of the Human in the Curriculum Field

    ERIC Educational Resources Information Center

    de Oliveira, Thiago Ranniery Moreira; Lopes, Danielle Bastos

    2016-01-01

    Humanism and the concept of the human that informs pedagogical discourse have been increasingly questioned by what has been called "post-human times." In this paper, we situate Paulo Freire's (1970) "Pedagogy of the Oppressed," and Nathan Snaza and John Weaver's (2014) "Posthumanism and Educational Research" within…

  3. 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.

  4. Studies of human vision recognition: some improvements

    NASA Astrophysics Data System (ADS)

    Wu, Bo-Wen; Fang, Yi-Chin; Chang, Lin-Song

    2010-01-01

    This paper proposes a new method to improve human recognition by artificial intelligence, specifically of images without the interference of high frequencies. The human eye is the most delicate optical system. Notwithstanding the dramatic progression of its structure and functions through a long evolution, the capability of visual recognition is not yet close to perfection. This paper is a study, based on the limitations of recognition by the human eye, of image recognition through the application of artificial intelligence. Those aspects which have been explored focus on human eye modeling, including aberration analysis, creative models of the human eye, human vision recognition characteristics and various mathematical models for verification. By using images consisting of four black and white bands and modulation transfer function (MTF) curve evaluation recognition capability on all the studied models, the optimum model most compatible with the physiology of the human eye is found.

  5. [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.

  6. Limiter

    DOEpatents

    Cohen, Samuel A.; Hosea, Joel C.; Timberlake, John R.

    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.

  7. Limited interaction between translation and visual motion aftereffects in humans.

    PubMed

    Crane, Benjamin T

    2013-01-01

    After exposure to a moving sensory stimulus, subsequent perception is often biased in the opposite direction. This phenomenon, known as an aftereffect, has been extensively studied for optic flow stimuli where it is known as the visual motion aftereffect (MAE). Such visual motion can also generate the sensation of self-motion or vection. It has recently been demonstrated that fore-aft translation in darkness also produces an aftereffect. The current study examines the interaction between visual MAE and vestibular translation aftereffects. Human subjects participated in a two-interval experiment in which the first interval (adapter) was visual, translation, or both combined congruently or in conflict. Subjects identified the direction of the second (test) interval of either visual or translation using a forced-choice technique. The translation adapter had no influence on visual test stimulus perception, and the visual adapter did not influence vestibular test stimulus perception in any subjects. However, congruent visual and translation induced a significantly larger perceptual bias on the translation test stimulus than was observed for a translation only adapter. The congruent adapter caused the MAE to be diminished relative to a visual only adapter. Conflicting visual and vestibular adapters produced an aftereffect similar to that seen when the single adapting stimulus was the same modality as the test stimulus. These results suggest that unlike visual and translation stimuli whose combined influence on perception can be predicted based on the effects of each stimulus individually, the effects of combined visual and translation stimuli on aftereffects cannot be predicted from the influences of each stimulus individually.

  8. Study on the limited hardenability steel

    SciTech Connect

    Xu, L.P.; Li, L.; Min, Y.A.; Xu, M.H.; Le, J.P.; Liu, R.H.

    1998-12-31

    A series of measurements were taken in the limited hardenability bearing steel rings which were induction hardened and tempered. Measurements showed several features which strengthened the rings: (1) Compressive residual stress are generated from surface to a depth of 3.2 mm and high residual compressive stress at the location where fatigue fracture initiates. (2) The matrix of the hardened layer was composed mainly of lath martensite with dispersed carbides whose formula was Me{sub 3} according to the X-ray spectrum analysis. The carbon content of martensite was estimated to be lower than 0.58% (by weight). The core was constituted of troostite transformed from spheroidal carbide. (3) The amount of retained austenite in the hardened layer was about 5% (in volume) which ensures the high dimensional stability of bearing.

  9. 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.

  10. 47 CFR 5.93 - Limited market studies.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 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...

  11. 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...

  12. 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...) 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...

  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. Gaia limits for brown dwarf studies.

    NASA Astrophysics Data System (ADS)

    Sarro, L. M.; Barrado, D.; Carrión, C.; Caballero, J. A.

    In this work we present a study of the expected properties of the Gaia sample of ultracool dwarfs (UCDs). This is defined preliminary (at a stage where we do not have real Gaia data yet) by analysing the detectability by Gaia of known UCDs in the Dwarf Archive. We complement the observations listed in the Dwarf Archive (J-, H-, and K- band magnitudes) with SDSS magnitudes and compare them with the BT-Settl model library in order to assess detectability. We also discuss the fraction of UCDs that will have accompanying RVS spectra in the Calcium triplet wavelength region.

  15. The same type of visual working memory limitations in humans and monkeys.

    PubMed

    Devkar, Deepna T; Wright, Anthony A; Ma, Wei Ji

    2015-01-01

    Rhesus monkeys are widely used as an animal model for human memory, including visual working memory (VWM). It is, however, unknown whether the same principles govern VWM in humans and rhesus monkeys. Here, we tested both species in nearly identical change-localization paradigms and formally compared the same set of models of VWM limitations. These models include the classic item-limit model and recent noise-based (resource) models, as well as hybrid models that combine a noise-based representation with an item limit. By varying the magnitude of the change in addition to the typical set size manipulation, we were able to show large differences in goodness of fit among the five models tested. In spite of quantitative performance differences between the species, we find that the variable-precision model--a noise-based model--best describes the behavior of both species. Adding an item limit to this model does not help to account for the data. Our results suggest evolutionary continuity of VWM across primates and help establish the rhesus monkey as a model system for studying the neural substrates of multiple-item VWM. PMID:26720277

  16. The same type of visual working memory limitations in humans and monkeys

    PubMed Central

    Devkar, Deepna T.; Wright, Anthony A.; Ma, Wei Ji

    2015-01-01

    Rhesus monkeys are widely used as an animal model for human memory, including visual working memory (VWM). It is, however, unknown whether the same principles govern VWM in humans and rhesus monkeys. Here, we tested both species in nearly identical change-localization paradigms and formally compared the same set of models of VWM limitations. These models include the classic item-limit model and recent noise-based (resource) models, as well as hybrid models that combine a noise-based representation with an item limit. By varying the magnitude of the change in addition to the typical set size manipulation, we were able to show large differences in goodness of fit among the five models tested. In spite of quantitative performance differences between the species, we find that the variable-precision model—a noise-based model—best describes the behavior of both species. Adding an item limit to this model does not help to account for the data. Our results suggest evolutionary continuity of VWM across primates and help establish the rhesus monkey as a model system for studying the neural substrates of multiple-item VWM. PMID:26720277

  17. Perspectives: Why Study Human Genetics?

    ERIC Educational Resources Information Center

    Childs, Barton

    1983-01-01

    Reasons for studying human genetics are discussed. These include philosophical reasons, reasons of health, and social reasons. While content, interpretation, and emphasis of human genetics study will vary depending upon schools, teachers, and developmental stages of students, it is suggested that teachers address these three domains. (Author/JN)

  18. Ionic mechanisms limiting cardiac repolarization reserve in humans compared to dogs.

    PubMed

    Jost, Norbert; Virág, László; Comtois, Philippe; Ordög, Balázs; Szuts, Viktória; Seprényi, György; Bitay, Miklós; Kohajda, Zsófia; Koncz, István; Nagy, Norbert; Szél, Tamás; Magyar, János; Kovács, Mária; Puskás, László G; Lengyel, Csaba; Wettwer, Erich; Ravens, Ursula; Nánási, Péter P; Papp, Julius Gy; Varró, András; Nattel, Stanley

    2013-09-01

    The species-specific determinants of repolarization are poorly understood. This study compared the contribution of various currents to cardiac repolarization in canine and human ventricle. Conventional microelectrode, whole-cell patch-clamp, molecular biological and mathematical modelling techniques were used. Selective IKr block (50-100 nmol l(-1) dofetilide) lengthened AP duration at 90% of repolarization (APD90) >3-fold more in human than dog, suggesting smaller repolarization reserve in humans. Selective IK1 block (10 μmol l(-1) BaCl2) and IKs block (1 μmol l(-1) HMR-1556) increased APD90 more in canine than human right ventricular papillary muscle. Ion current measurements in isolated cardiomyocytes showed that IK1 and IKs densities were 3- and 4.5-fold larger in dogs than humans, respectively. IKr density and kinetics were similar in human versus dog. ICa and Ito were respectively ~30% larger and ~29% smaller in human, and Na(+)-Ca(2+) exchange current was comparable. Cardiac mRNA levels for the main IK1 ion channel subunit Kir2.1 and the IKs accessory subunit minK were significantly lower, but mRNA expression of ERG and KvLQT1 (IKr and IKs α-subunits) were not significantly different, in human versus dog. Immunostaining suggested lower Kir2.1 and minK, and higher KvLQT1 protein expression in human versus canine cardiomyocytes. IK1 and IKs inhibition increased the APD-prolonging effect of IKr block more in dog (by 56% and 49%, respectively) than human (34 and 16%), indicating that both currents contribute to increased repolarization reserve in the dog. A mathematical model incorporating observed human-canine ion current differences confirmed the role of IK1 and IKs in repolarization reserve differences. Thus, humans show greater repolarization-delaying effects of IKr block than dogs, because of lower repolarization reserve contributions from IK1 and IKs, emphasizing species-specific determinants of repolarization and the limitations of animal models for

  19. A signature of neural coding at human perceptual limits

    PubMed Central

    Bays, Paul M.

    2016-01-01

    Simple visual features, such as orientation, are thought to be represented in the spiking of visual neurons using population codes. I show that optimal decoding of such activity predicts characteristic deviations from the normal distribution of errors at low gains. Examining human perception of orientation stimuli, I show that these predicted deviations are present at near-threshold levels of contrast. The findings may provide a neural-level explanation for the appearance of a threshold in perceptual awareness whereby stimuli are categorized as seen or unseen. As well as varying in error magnitude, perceptual judgments differ in certainty about what was observed. I demonstrate that variations in the total spiking activity of a neural population can account for the empirical relationship between subjective confidence and precision. These results establish population coding and decoding as the neural basis of perception and perceptual confidence. PMID:27604067

  20. A signature of neural coding at human perceptual limits.

    PubMed

    Bays, Paul M

    2016-09-01

    Simple visual features, such as orientation, are thought to be represented in the spiking of visual neurons using population codes. I show that optimal decoding of such activity predicts characteristic deviations from the normal distribution of errors at low gains. Examining human perception of orientation stimuli, I show that these predicted deviations are present at near-threshold levels of contrast. The findings may provide a neural-level explanation for the appearance of a threshold in perceptual awareness whereby stimuli are categorized as seen or unseen. As well as varying in error magnitude, perceptual judgments differ in certainty about what was observed. I demonstrate that variations in the total spiking activity of a neural population can account for the empirical relationship between subjective confidence and precision. These results establish population coding and decoding as the neural basis of perception and perceptual confidence. PMID:27604067

  1. Seed, dispersal, microsite, habitat and recruitment limitation: identification of terms and concepts in studies of limitations.

    PubMed

    Münzbergová, Zuzana; Herben, Tomás

    2005-08-01

    Recently, there is an increase in number of studies concerned with the effect of various types of limitations on species local population size and distribution pattern at the landscape scale. The terminology used to describe these limitations is, however, very inconsistent. Since the different terms often appear in conclusions of the papers, the inconsistency in their use obscures the message of these papers. In this study, we review the current uses of these terms, identify the basic concepts involved in the discussion of a limitation and link the concepts with the currently used terms. Finally, we discuss the experimental approaches used to assess the different types of limitations. We differentiated four basic concepts resulting from the combination of limitation by environment versus ability to grow and spread, and two spatial scales (local and regional scale). The two concepts at each spatial scale are expected to form a gradient of all possible combinations of the two respective types of limitations. In the considerations of various experimental approaches used to assess these limitations, we conclude that sowing experiments, i.e. seed addition into existing populations or seed introduction into unoccupied habitats, are the only reliable types of evidence for the different types of limitations.

  2. Cdc45 is limiting for replication initiation in humans

    PubMed Central

    Köhler, Carsten; Koalick, Dennis; Fabricius, Anja; Parplys, Ann Christin; Borgmann, Kerstin; Pospiech, Helmut; Grosse, Frank

    2016-01-01

    ABSTRACT Cdc45 is an essential protein that together with Mcm2-7 and GINS forms the eukaryotic replicative helicase CMG. Cdc45 seems to be rate limiting for the initial unwinding or firing of replication origins. In line with this view, Cdc45-overexpressing cells fired at least twice as many origins as control cells. However, these cells displayed an about 2-fold diminished fork elongation rate, a pronounced asymmetry of replication fork extension, and an early S phase arrest. This was accompanied by H2AX-phosphorylation and subsequent apoptosis. Unexpectedly, we did not observe increased ATR/Chk1 signaling but rather a mild ATM/Chk2 response. In addition, we detected accumulation of long stretches of single-stranded DNA, a hallmark of replication catastrophe. We conclude that increased origin firing by upregulated Cdc45 caused exhaustion of the single-strand binding protein RPA, which in consequence diminished the ATR/Chk1 response; the subsequently occurring fork breaks led to an ATM/Chk2 mediated phosphorylation of H2AX and eventually to apoptosis. PMID:26919204

  3. Cyclodextrins in Food Technology and Human Nutrition: Benefits and Limitations.

    PubMed

    Fenyvesi, É; Vikmon, M; Szente, L

    2016-09-01

    Cyclodextrins are tasteless, odorless, nondigestible, noncaloric, noncariogenic saccharides, which reduce the digestion of carbohydrates and lipids. They have low glycemic index and decrease the glycemic index of the food. They are either non- or only partly digestible by the enzymes of the human gastrointestinal (GI) tract and fermented by the gut microflora. Based on these properties, cyclodextrins are dietary fibers useful for controlling the body weight and blood lipid profile. They are prebiotics, improve the intestinal microflora by selective proliferation of bifidobacteria. These antiobesity and anti-diabetic effects make them bioactive food supplements and nutraceuticals. In this review, these features are evaluated for α-, β- and γ-cyclodextrins, which are the cyclodextrin variants approved by authorities for food applications. The mechanisms behind these effects are reviewed together with the applications as solubilizers, stabilizers of dietary lipids, such as unsaturated fatty acids, phytosterols, vitamins, flavonoids, carotenoids and other nutraceuticals. The recent applications of cyclodextrins for reducing unwanted components, such as trans-fats, allergens, mycotoxins, acrylamides, bitter compounds, as well as in smart active packaging of foods are also overviewed. PMID:25764389

  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. Limitations of Reliability for Long-Endurance Human Spaceflight

    NASA Technical Reports Server (NTRS)

    Owens, Andrew C.; de Weck, Olivier L.

    2016-01-01

    Long-endurance human spaceflight - such as missions to Mars or its moons - will present a never-before-seen maintenance logistics challenge. Crews will be in space for longer and be farther way from Earth than ever before. Resupply and abort options will be heavily constrained, and will have timescales much longer than current and past experience. Spare parts and/or redundant systems will have to be included to reduce risk. However, the high cost of transportation means that this risk reduction must be achieved while also minimizing mass. The concept of increasing system and component reliability is commonly discussed as a means to reduce risk and mass by reducing the probability that components will fail during a mission. While increased reliability can reduce maintenance logistics mass requirements, the rate of mass reduction decreases over time. In addition, reliability growth requires increased test time and cost. This paper assesses trends in test time requirements, cost, and maintenance logistics mass savings as a function of increase in Mean Time Between Failures (MTBF) for some or all of the components in a system. In general, reliability growth results in superlinear growth in test time requirements, exponential growth in cost, and sublinear benefits (in terms of logistics mass saved). These trends indicate that it is unlikely that reliability growth alone will be a cost-effective approach to maintenance logistics mass reduction and risk mitigation for long-endurance missions. This paper discusses these trends as well as other options to reduce logistics mass such as direct reduction of part mass, commonality, or In-Space Manufacturing (ISM). Overall, it is likely that some combination of all available options - including reliability growth - will be required to reduce mass and mitigate risk for future deep space missions.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. [Measuring the contrast resolution limits of human vision based on the modern digital image processing].

    PubMed

    Wang, Zhifang; Liu, Yuhong; Wang, Ying; Li, Hong; Li, Zhangyong; Zhao, Zhiqiang; Xie, Zhengxiang

    2008-10-01

    In the literatures on the human vision physiology and physics, there were reports about space resolution limit of 1' visual angle, frequency resolution limit of 5 nm and time resolution limit of 0.1" of human vision. However, there has been no report about the contrast resolution limit of human vision,especially the report of measuring method and result about the contrast resolution limit of human vision based on the modern digital image processing. Here we report a modern method for measuring the contrast resolution limit of human vision based on computer digital image processing technology, and we present the measured results and their mathematical models. The function relationships of contrast resolution limit varying with background gray in a photopic or a scotopic sights were illuminated respectively. It can be expected that such investigations with regard to human vision will establish the physiological foundation of the theories and techniques in hiding bodies and hiding figures (stealth), in anti-hiding bodies and anti-hiding figures, in the night vision system independent of infrared, as well as in their relative industries.

  11. 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

  12. Haplotype Block Partition with Limited Resources and Applications to Human Chromosome 21 Haplotype Data

    PubMed Central

    Zhang, Kui; Sun, Fengzhu; Waterman, Michael S.; Chen, Ting

    2003-01-01

    Recent studies have shown that the human genome has a haplotype block structure such that it can be decomposed into large blocks with high linkage disequilibrium (LD) and relatively limited haplotype diversity, separated by short regions of low LD. One of the practical implications of this observation is that only a small fraction of all the single-nucleotide polymorphisms (SNPs) (referred as “tag SNPs”) can be chosen for mapping genes responsible for human complex diseases, which can significantly reduce genotyping effort, without much loss of power. Algorithms have been developed to partition haplotypes into blocks with the minimum number of tag SNPs for an entire chromosome. In practice, investigators may have limited resources, and only a certain number of SNPs can be genotyped. In the present article, we first formulate this problem as finding a block partition with a fixed number of tag SNPs that can cover the maximal percentage of the whole genome, and we then develop two dynamic programming algorithms to solve this problem. The algorithms are sufficiently flexible to permit knowledge of functional polymorphisms to be considered. We apply the algorithms to a data set of SNPs on human chromosome 21, combining the information of coding and noncoding regions. We study the density of SNPs in intergenic regions, introns, and exons, and we find that the SNP density in intergenic regions is similar to that in introns and is higher than that in exons, results that are consistent with previous studies. We also calculate the distribution of block break points in intergenic regions, genes, exons, and coding regions and do not find any significant differences. PMID:12802783

  13. Pump limiter studies on the Heliotron-E device

    SciTech Connect

    Hillis, D.L.; Mioduszewski, P.K.; Zuhr, R.A.; Clausing, R.E.; Baity, F.W.; Fowler, R.H.; Rome, J.A.; Motojima, O.; Mitzuuchi, T.; Mutoh, T..

    1986-05-01

    Particle control with pump limiters has been successfully demonstrated in a variety of tokamaks. This experiment has obtained, for the first time, experimental data on pump limiter operation in a heliotron configuration. A movable pump limiter module was installed on a horizontal midplane port of Heliotron-E. The limiter assembly consists of a TiC-coated graphite head with single-sided particle collection and active pumping. The location of the limiter is varied from near the vacuum vessel wall or up to 8 cm inside the last closed magnetic flux surface. This flexibility permits the study of a heliotron plasma that is limited either by the magnetic separatrix or by a material limiter. In the configuration investigated, only very low pressures are observed in the pump limiter when it is located outside the last closed flux surface, indicating that the scrape-off layer density is very low (<5 x 10/sup 11/cm/sup -3/). For limiter positions inside the last closed flux surface, pressures of 2 to 6 mTorr are observed (similar to comparable tokamak operation). Erosion patterns on the vacuum vessel, as well as hot spots on the limiter head, indicate that the particle flow out of the confined plasma exhibits complicated patterns.

  14. Human epididymis protein 4 reference limits and natural variation in a Nordic reference population.

    PubMed

    Bolstad, Nils; Øijordsbakken, Miriam; Nustad, Kjell; Bjerner, Johan

    2012-02-01

    The objectives of this study are to establish reference limits for human epididymis protein 4, HE4, and investigate factors influencing HE4 levels in healthy subjects. HE4 was measured in 1,591 samples from the Nordic Reference Interval Project Bio-bank and Database biobank, using the manual HE4 EIA (Fujirebio) for 802 samples and the Architect HE4 (Abbott) for 792 samples. Reference limits were calculated using the statistical software R. The influence of donor characteristics such as age, sex, body mass index, smoking habits, and creatinine on HE4 levels was investigated using a multivariate model. The study showed that age is the main determinant of HE4 in healthy subjects, corresponding to 2% higher HE4 levels at 30 years (compared to 20 years), 9% at 40 years, 20% at 50 years, 37% at 60 years, 63% at 70 years, and 101% at 80 years. HE4 levels are 29% higher in smokers than in nonsmokers. In conclusion, HE4 levels in healthy subjects are associated with age and smoking status. Age-dependent reference limits are suggested.

  15. Numerical human models for accident research and safety - potentials and limitations.

    PubMed

    Praxl, Norbert; Adamec, Jiri; Muggenthaler, Holger; von Merten, Katja

    2008-01-01

    The method of numerical simulation is frequently used in the area of automotive safety. Recently, numerical models of the human body have been developed for the numerical simulation of occupants. Different approaches in modelling the human body have been used: the finite-element and the multibody technique. Numerical human models representing the two modelling approaches are introduced and the potentials and limitations of these models are discussed.

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

    PubMed

    Bishop, P A; Greenisen, M

    1993-03-01

    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.

  17. 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.

  18. 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.

  19. 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

  20. Limited By Cost: The Case Against Humans In The Scientific Exploration Of Space

    NASA Astrophysics Data System (ADS)

    Coates, Andrew J.

    2001-11-01

    Human space flight represents a heady mix of bravery and drama which can be inspirational to nations and to humankind but at huge economic cost. Due to the current high launch costs only a handful of people have ventured beyond low Earth orbit and walked on the Moon, propelled by aspirations related more to the Cold War than to science. Problems with reusable launch vehicle development mean that severe launch cost limitations will exist for some time. Meanwhile, cheaper robotic probes have visited all the planets except Pluto, flown by comets, landed on Mars, Venus and an asteroid, have probed Jupiter's atmosphere and studied the Universe beyond our own solar system with telescopes. Using these data we are determining mankind's place in the Universe. Public interest in the historic Eros landing eclipsed a simultaneous space walk at the fledgling International Space Station and the Mars Pathfinder landing generated hundreds of millions of website hits in a few days. Given the fact that hundreds of Mars missions could be flown for the still-escalating cost of the International Space Station, the unsuitability of human bodies for deep space exploration, and the advances in 3-d and virtual reality techniques, we discuss whether human exploration needs a place in a realistic, useful and inspirational space programme.

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

    PubMed Central

    Stanton, Bruce A.

    2015-01-01

    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 U.S. Environmental Protection Agency (EPA) has set a limit of 10 micrograms per liter (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

  2. 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.

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

    PubMed

    Hanna, Elizabeth G; Tait, Peter W

    2015-07-15

    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.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. Physical performance limitations in the Childhood Cancer Survivor Study cohort.

    PubMed

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

    2009-05-10

    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

  10. 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.

  11. Spontaneous hypothermia in human sepsis is a transient, self-limiting, and nonterminal response.

    PubMed

    Fonseca, Monique T; Rodrigues, Abner C; Cezar, Luana C; Fujita, Andre; Soriano, Francisco G; Steiner, Alexandre A

    2016-06-15

    Hypothermia in sepsis is generally perceived as something dysregulated and progressive although there has been no assessment on the natural course of this phenomenon in humans. This was the first study on the dynamics of hypothermia in septic patients not subjected to active rewarming, and the results were surprising. A sample of 50 subjects presenting with spontaneous hypothermia during sepsis was drawn from the 2005-2012 database of an academic hospital. Hypothermia was defined as body temperature below 36.0°C for longer than 2 h, with at least one reading of 35.5°C or less. The patients presented with 138 episodes of hypothermia, 21 at the time of the sepsis diagnosis and 117 with a later onset. However, hypothermia was uncommon in the final 12 h of life of the patients that succumbed. The majority (97.1%) of the hypothermic episodes were transient and self-limited; the median recovery time was 6 h; body temperature rarely fell below 34.0°C. Bidirectional oscillations in body temperature were evident in the course of hypothermia. Nearly half of the hypothermic episodes had onset in the absence of shock or respiratory distress, and the incidence of hypothermia was not increased during either of these conditions. Usage of antipyretic drugs, sedatives, neuroleptics, or other medications did not predict the onset of hypothermia. In conclusion, hypothermia appears to be a predominantly transient, self-limiting, and nonterminal phenomenon that is inherent to human sepsis. These characteristics resemble those of the regulated hypothermia shown to replace fever in animal models of severe systemic inflammation.

  12. Spontaneous hypothermia in human sepsis is a transient, self-limiting, and nonterminal response.

    PubMed

    Fonseca, Monique T; Rodrigues, Abner C; Cezar, Luana C; Fujita, Andre; Soriano, Francisco G; Steiner, Alexandre A

    2016-06-15

    Hypothermia in sepsis is generally perceived as something dysregulated and progressive although there has been no assessment on the natural course of this phenomenon in humans. This was the first study on the dynamics of hypothermia in septic patients not subjected to active rewarming, and the results were surprising. A sample of 50 subjects presenting with spontaneous hypothermia during sepsis was drawn from the 2005-2012 database of an academic hospital. Hypothermia was defined as body temperature below 36.0°C for longer than 2 h, with at least one reading of 35.5°C or less. The patients presented with 138 episodes of hypothermia, 21 at the time of the sepsis diagnosis and 117 with a later onset. However, hypothermia was uncommon in the final 12 h of life of the patients that succumbed. The majority (97.1%) of the hypothermic episodes were transient and self-limited; the median recovery time was 6 h; body temperature rarely fell below 34.0°C. Bidirectional oscillations in body temperature were evident in the course of hypothermia. Nearly half of the hypothermic episodes had onset in the absence of shock or respiratory distress, and the incidence of hypothermia was not increased during either of these conditions. Usage of antipyretic drugs, sedatives, neuroleptics, or other medications did not predict the onset of hypothermia. In conclusion, hypothermia appears to be a predominantly transient, self-limiting, and nonterminal phenomenon that is inherent to human sepsis. These characteristics resemble those of the regulated hypothermia shown to replace fever in animal models of severe systemic inflammation. PMID:26989218

  13. 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.

  14. 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 divergence—meteorological 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.

  15. 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

  16. How to accommodate women with mobility limitations in biological studies.

    PubMed

    Walker, Janiece L; Tovar, Marlene; Harrison, Tracie C; Wommack, Joel

    2015-01-01

    People with disabilities should be routinely included in research studies if there is no specific reason for their exclusion. Regardless, they may be inadvertently excluded because of the procedures of the study. By conducting a community-based biological study with women aging with mobility limitations, these authors gained further understanding of their accommodation needs during research participation. The women aging with mobility limitations offered specific physical, cultural, or environmental needs that could have influenced the methods, procedures, and possible outcomes involved when conducting a biological study with this community living population. The authors and participants identified methodological challenges for women with mobility impairments within three key areas: recruitment procedures, laboratory procedures, and community-based data collection. The authors propose possible solutions to these identified challenges. It is our hope that this will begin a larger dialogue on how to routinely accommodate people with disabilities in biological research studies.

  17. On the design of experiments to study extreme field limits

    NASA Astrophysics Data System (ADS)

    Bulanov, S. S.; Chen, M.; Schroeder, C. B.; Esarey, E.; Leemans, W. P.; Bulanov, S. V.; Esirkepov, T. Zh.; Kando, M.; Koga, J. K.; Zhidkov, A. G.; Chen, P.; Mur, V. D.; Narozhny, N. B.; Popov, V. S.; Thomas, A. G. R.; Korn, G.

    2012-12-01

    We propose experiments on the collision of high intensity electromagnetic pulses with electron bunches and on the collision of multiple electromagnetic pulses for studying extreme field limits in the nonlinear interaction of electromagnetic waves. The effects of nonlinear QED will be revealed in these laser plasma experiments.

  18. Limited Immersion in Cued Speech: A Case Study.

    ERIC Educational Resources Information Center

    Gordon, Malcolm; And Others

    The case study examines the effects on the receptive and expressive English language of a deaf 14 year old after a period of limited language immersion using Cued Speech, in which every sound in a word is represented both expressively and receptively. In a four week period the S spent approximately 14 hours per week with a modeler who cued speech…

  19. Humanized Mice for Studying Human Leukocyte Integrins In Vivo

    PubMed Central

    Kim, Sang-Soo; Kumar, Priti; Ye, Chunting; Shankar, Premlata

    2015-01-01

    Humanized mice have recently emerged as powerful translational animal models for studying human hematopoiesis, immune interactions, and diseases of the human immune system. Several important advances in the humanized mouse technology have been reported over the last few years, thereby resulting in improved engraftment, high levels of human chimerism, and sustained human hematopoiesis. This chapter describes the detailed procedures for generating various humanized mouse models including hu-PBL, hu-HSC, and BLT models and discusses considerations for choosing the appropriate model system. PMID:21909931

  20. The limits of chimpanzee-human comparisons for understanding human cognition.

    PubMed

    Reader, Simon M; Hrotic, Steven M

    2012-08-01

    Evolutionary questions require specialized approaches, part of which are comparisons between close relatives. However, to understand the origins of human tool behavior, comparisons with solely chimpanzees are insufficient, lacking the power to identify derived traits. Moreover, tool use is unlikely a unitary phenomenon. Large-scale comparative analyses provide an alternative and suggest that tool use co-evolves with a suite of cognitive traits.

  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. Studies on human urinary arylamidases

    NASA Technical Reports Server (NTRS)

    Raina, P. N.; Ellis, S.

    1975-01-01

    Human urinary protein was found to contain enzymes that hydrolyze leucyl-, alanyl-, and glycyl-prolyl-beta-naphthylamides. The kinetic constants of these enzymes were determined and their chemical properties studied. The pH optima for the hydrolysis of the various naphthylamides were also determined. Glycyl-prolyl-arylaminade was inhibited by Co(2+) and Mn(2+), while two other arylamidases were slightly activated by Co(2+). p-Chloromercuriphenyl-sulfonate and puromycin significantly inhibited leucyl and alanyl arylamidases. The mean values for 24-hour urinary output for leucyl-, alanyl-, and glycyl-prolyl arylamidases in normal human male subjects were 4.32, 9.97, and 2.2 units, respectively.

  3. Numerical study of polaron problem in the adiabatic limit

    NASA Astrophysics Data System (ADS)

    Marsiglio, Frank; Li, Zhou; Blois, Cindy; Baillie, Devin

    2010-03-01

    We study the polaron problem in a one dimensional chain and on a two dimensional square lattice. The models we have used are the Holstein model and the Su-Schrieffer-Heeger (SSH) model. By a variational procedure based on the Lanczos method, we are able to examine the polaron problem in the limit when the mass of the ion is very large, i.e. close to the adiabatic limit. It is known that for the Holstein model there is no phase transition [1] for any nonzero phonon energy. It is also known that for the one dimensional Holstein or SSH model there will be long range order [2] (e.g. dimerization) in the adiabatic limit at half-filling. It is then interesting to study the long range order on a two dimensional square lattice in and away from the adiabatic limit. Moreover, recent progress for the single polaron near an impurity (disorder) [3] make it an interesting problem for studying bond length disorder which can change the hopping energy in a specific direction in the Holstein model. Reference: [1] H. Lowen, Phys.Rev.B 37, 8661 (1988) [2] J.E.Hirsch and E. Frandkin, Phys. Rev. Lett. 49, 402 (1982) [3]A.S.Mishchenko et.al Phys.Rev.B 79(2009) 180301(R)

  4. Study of radiation limits in fusion reactor scenarios

    NASA Astrophysics Data System (ADS)

    Becker, G.

    1999-07-01

    Radiative mantle scenarios of the ignited ITER FDR (Final Design Report) with argon and neon seeding are explored by self-consistent simulations with a special version of the 1.5-D BALDUR predictive transport code. The calculations apply empirical transport coefficients and are carried out both in the bulk and in the SOL. Operation relevant upper limits to the radiative power losses from the main chamber, from closed flux surfaces and from the SOL are found. Both simulations and an analytic study of power balances show that these limits are set by the radiation profile and by the cross-field heat conduction in the SOL. For given heating power, the conductive heat flux across the separatrix and the energy flow to the divertor are also restricted. With high edge density, the required thermal energy confinement times at the radiation limits are found to be 4.4 s in the argon and 4.0 s in the neon scenario. The assumption of flat density profiles and no inward pinch in the whole plasma is supported by simulations using a new scaling relation for the anomalous inward drift. The dependence of the radiation limits on the separatrix density is investigated. Formulas for relevant power limits are presented.

  5. Sprint mechanics in world-class athletes: a new insight into the limits of human locomotion.

    PubMed

    Rabita, G; Dorel, S; Slawinski, J; Sàez-de-Villarreal, E; Couturier, A; Samozino, P; Morin, J-B

    2015-10-01

    The objective of this study was to characterize the mechanics of maximal running sprint acceleration in high-level athletes. Four elite (100-m best time 9.95-10.29 s) and five sub-elite (10.40-10.60 s) sprinters performed seven sprints in overground conditions. A single virtual 40-m sprint was reconstructed and kinetics parameters were calculated for each step using a force platform system and video analyses. Anteroposterior force (FY), power (PY), and the ratio of the horizontal force component to the resultant (total) force (RF, which reflects the orientation of the resultant ground reaction force for each support phase) were computed as a function of velocity (V). FY-V, RF-V, and PY-V relationships were well described by significant linear (mean R(2) of 0.892 ± 0.049 and 0.950 ± 0.023) and quadratic (mean R(2) = 0.732 ± 0.114) models, respectively. The current study allows a better understanding of the mechanics of the sprint acceleration notably by modeling the relationships between the forward velocity and the main mechanical key variables of the sprint. As these findings partly concern world-class sprinters tested in overground conditions, they give new insights into some aspects of the biomechanical limits of human locomotion.

  6. Diffusion into human islets is limited to molecules below 10 kDa.

    PubMed

    Williams, S J; Schwasinger-Schmidt, T; Zamierowski, D; Stehno-Bittel, L

    2012-10-01

    Isolated islets are important tools in diabetes research and are used for islet transplantation as a treatment for type 1 diabetes. Yet these cell clusters have a dramatic diffusion barrier that leads to core cell death. Computer modeling has provided theoretical size limitations, but little has been done to measure the actual rate of diffusion in islets. The purpose of this study was to directly measure the diffusion barrier in intact human islets and determine its role in restricting insulin secretion. Impeded diffusion into islets was monitored with fluorescent dextran beads. Dextran beads of 10-70 kDa failed to diffuse into the core of the intact islets, while 0.9 kDa probe was observed within the core of smaller islets. Diffusion of the fluorescent form of glucose, 2-NBDG, had similar diffusion limitations as the beads, with an average intra-islet diffusion rate of 1.5 ± 0.2 μm/min. The poor diffusion properties were associated with core cell death from necrosis, not apoptosis. Short-term exposure to a mild papain/0 Ca(2+) cocktail, dramatically reduced the diffusion barrier so that all cells within islets were exposed to media components. Lowering the diffusion barrier increased the immediate and long-term viability of islet cells, and tended to increase the amount of insulin released, especially in low glucose conditions. However, it failed to improve the large islet's glucose-stimulated insulin secretion. Thus, the islet diffusion barrier leads to low viability and poor survival of large islets, but is not solely responsible for the reduced insulin secretion of large isolated islets.

  7. 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

  8. 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

  9. 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.

  10. Limitations of wind power availability over Europe: a conceptual study

    NASA Astrophysics Data System (ADS)

    Kiss, P.; Jánosi, I. M.

    2008-11-01

    Wind field statistics are evaluated from the ERA-40 data bank covering a period of 44 years with a temporal resolution of 6 h. Instantaneous wind speed values are provided in geographic cells of size 1°×1° (lat/long) for surface (10 m) and 1000 hPa pressure heights. Potential wind power generation is estimated in two steps. Firstly, the wind speed at hub height is approximated from surface data based on the statistical analysis of the wind and geopotential records for 1000 hPa pressure level. Secondly, the wind speed values are transformed by an idealised power curve fitted for measured data. The model time series are fed into various hypothetical electric networks. The main quantity of interest is the aggregated output from the networks. A reference power time series is determined for a static network connecting each continental site and an envelope of 1° around the shorelines (representing off-shore locations) over Europe. This time series exhibits a low average value and a marked annual periodicity. Wind power integration over limited areas results in higher average outputs at the expense of stronger fluctuations. The long-range spatial correlations of the wind field limit the level of fluctuations strongly which can not be eliminated either by an increase of the area of integration or by dynamic control. This study is fully conceptual, however it demonstrates the limitations of wind power integration over Europe.

  11. 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; Dagnæs-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

  12. Interpreting Disasters From Limited Data Availability: A Guatemalan Study Case

    NASA Astrophysics Data System (ADS)

    Soto Gomez, A.

    2012-12-01

    Guatemala is located in a geographical area exposed to multiple natural hazards. Although Guatemalan populations live in hazardous conditions, limited scientific research is being focused in this particular geographical area. Thorough studies are needed to understand the disasters occurring in the country and consequently enable decision makers and professionals to plan future actions, yet available data is limited. Data comprised in the available data sources is limited by their timespan or the size of the events included and therefore is insufficient to provide the whole picture of the disasters in the country. This study proposes a methodology to use the available data within one of the most important catchments in the country, the Samala River basin, to look for answers to what kind of disasters occurs? Where such events happen? And, why do they happen? Three datasets from different source agencies -one global, one regional, and one local- have been analyzed numerically and spatially using spreadsheets, numerical computing software, and geographic information systems. Analyses results have been coupled in order to search for possible answers to the established questions. It has been found a relation between the compositions of data of two of the three datasets analyzed. The third has shown a very different composition probably because the inclusion criteria of the dataset exclude smaller but more frequent disasters in its records. In all the datasets the most frequent type of disasters are those caused by hydrometeorological hazards i.e. floods and landslides. It has been found a relation between the occurrences of disasters and the records of precipitation in the area, but this relation is not strong enough to affirm that the disasters are the direct result of rain in the area and further studies must be carried out to explore other potential causes. Analyzing the existing data contributes to identify what kind of data is needed and this would be useful to

  13. Mass spectrometric characterization of limited proteolysis activity in human plasma samples under mild acidic conditions.

    PubMed

    Yang, Jingzhi; Röwer, Claudia; Koy, Cornelia; Ruß, Manuela; Rüger, Christopher P; Zimmermann, Ralf; von Fritschen, Uwe; Bredell, Marius; Finke, Juliane C; Glocker, Michael O

    2015-11-01

    We developed a limited proteolysis assay for estimating dynamics in plasma-borne protease activities using MALDI ToF MS analysis as readout. A highly specific limited proteolysis activity was elicited in human plasma by shifting the pH to 6. Mass spectrometry showed that two singly charged ion signals at m/z 2753.44 and m/z 2937.56 significantly increased in abundance under mild acidic conditions as a function of incubation time. For proving that a provoked proteolytic activity in mild acidic solution caused the appearance of the observed peptides, control measurements were performed (i) with pepstatin as protease inhibitor, (ii) with heat-denatured samples, (iii) at pH 1.7, and (iv) at pH 7.5. Mass spectrometric fragmentation analysis showed that the observed peptides encompass the amino acid sequences 1-24 and 1-26 from the N-terminus of human serum albumin. Investigations on peptidase specificities suggest that the two best candidates for the observed serum albumin cleavages are cathepsin D and E. Reproducibility, robustness, and sensitivity prove the potential of the developed limited proteolysis assay to become of clinical importance for estimating dynamics of plasma-borne proteases with respect to associated pathophysiological tissue conditions.

  14. Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature

    PubMed Central

    Melican, Keira; Aubey, Flore; Duménil, Guillaume

    2014-01-01

    Neisseria meningitidis causes a severe, frequently fatal sepsis when it enters the human blood stream. Infection leads to extensive damage of the blood vessels resulting in vascular leak, the development of purpuric rashes and eventual tissue necrosis. Studying the pathogenesis of this infection was previously limited by the human specificity of the bacteria, which makes in vivo models difficult. In this protocol, we describe a humanized model for this infection in which human skin, containing dermal microvessels, is grafted onto immunocompromised mice. These vessels anastomose with the mouse circulation while maintaining their human characteristics. Once introduced into this model, N. meningitidis adhere exclusively to the human vessels, resulting in extensive vascular damage, inflammation and in some cases the development of purpuric rash. This protocol describes the grafting, infection and evaluation steps of this model in the context of N. meningitidis infection. The technique may be applied to numerous human specific pathogens that infect the blood stream. PMID:24747976

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

    NASA Astrophysics Data System (ADS)

    Lü, 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.

  16. 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.

  17. 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

  18. Discussing study limitations in reports of biomedical studies- the need for more transparency.

    PubMed

    Puhan, Milo A; Akl, Elie A; Bryant, Dianne; Xie, Feng; Apolone, Giovanni; ter Riet, Gerben

    2012-02-23

    Unbiased and frank discussion of study limitations by authors represents a crucial part of the scientific discourse and progress. In today's culture of publishing many authors or scientific teams probably balance 'utter honesty' when discussing limitations of their research with the risk of being unable to publish their work. Currently, too few papers in the medical literature frankly discuss how limitations could have affected the study findings and interpretations. The goals of this commentary are to review how limitations are currently acknowledged in the medical literature, to discuss the implications of limitations in biomedical studies, and to make suggestions as to how to openly discuss limitations for scientists submitting their papers to journals. This commentary was developed through discussion and logical arguments by the authors who are doing research in the area of hedging (use of language to express uncertainty) and who have extensive experience as authors and editors of biomedical papers. We strongly encourage authors to report on all potentially important limitations that may have affected the quality and interpretation of the evidence being presented. This will not only benefit science but also offers incentives for authors: If not all important limitations are acknowledged readers and reviewers of scientific articles may perceive that the authors were unaware of them. Authors should take advantage of their content knowledge and familiarity with the study to prevent misinterpretations of the limitations by reviewers and readers. Articles discussing limitations help shape the future research agenda and are likely to be cited because they have informed the design and conduct of future studies. Instead of perceiving acknowledgment of limitations negatively, authors, reviewers and editors should recognize the potential of a frank and unbiased discussion of study limitations that should not jeopardize acceptance of manuscripts.

  19. 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

  20. Similarity of polygenic profiles limits the potential for elite human physical performance

    PubMed Central

    Williams, Alun G; Folland, Jonathan P

    2008-01-01

    Human physical capability is influenced by many environmental and genetic factors, and it is generally accepted that physical capability phenotypes are highly polygenic. However, the ways in which relevant polymorphisms combine to influence the physical capability of individuals and populations are unknown. Initially, the literature was searched to identify associations between 23 genetic polymorphisms and human endurance phenotypes. Next, typical genotype frequencies of those polymorphisms in the general population were obtained from suitable literature. Using probability calculations, we found only a 0.0005% chance of a single individual in the world having the ‘preferable’ form of all 23 polymorphisms. As the number of DNA variants shown to be associated with human endurance phenotypes continues to increase, the probability of any single individual possessing the ‘preferable’ form of each polymorphism will become even lower. However, with population turnover, the chance of such genetically gifted individuals existing increases. To examine the polygenic endurance potential of a human population, a ‘total genotype score’ (for the 23 polymorphisms) was calculated for each individual within a hypothetical population of 1000 000. There was considerable homogeneity in terms of genetic predisposition to high endurance potential, with 99% of people differing by no more than seven genotypes from the typical profile. Consequently, with population turnover world and Olympic records should improve even without further enhancement of environmental factors, as more ‘advantageous’ polygenic profiles occasionally, though rarely, emerge. More broadly, human potential appears limited by the similarity of polygenic profiles at both the ‘elite sport’ and ‘chronic disorder’ ends of the performance continuum. PMID:17901117

  1. From Oxford to Hawaii ecophysiological barriers limit human progression in ten sport monuments.

    PubMed

    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 (r(2) = 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.

  2. 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

  3. 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

  4. Human search with a limited field of view: the effect of scanning parameters and scene content

    NASA Astrophysics Data System (ADS)

    Hogervorst, Maarten A.; Bijl, Piet; Toet, Alexander; Valeton, J. M.

    2002-08-01

    In order to find an optimal scanning strategy we determined the relationship between search performance and several scanning- and scene parameters in human observer experiments. The observers searched with a limited field of view (FOV) through a large search sector for a target (a camouflaged person) on a heath. From trial to trial the target appeared at a different location. Predefined (horizontal) scan paths were used with constant speed. The subjects hit a button as soon as the target was spotted. We determined the effect of scanning speed, zoom factor, FOV width and target location on search performance (detection time and probability). We also obtained estimates of target conspicuity for all targets and determined the relationship between conspicuity and search performance. We found that search performance was largely determined by the angular scanning speed of the simulated camera, and largely independent of zoom factor. The results show that conspicuity can be used to predict search performance in search with a limited FOV (this was previously shown for unrestricted search). Target conspicuity decreased when the targets appeared closer to the horizon (and where therefore more distant). Such a systematic dependency between target conspicuity and target location can be (and is probably) used by the observers to optimized search performance. The results further show that a reduction in the FOV width affects search performance when the time that a target is visible falls below a certain value (in our case about 1 sec). These findings can be used in future models of search performance with a limited FOV.

  5. Potential and limitation of HLA-based banking of human pluripotent stem cells for cell therapy.

    PubMed

    de Rham, Casimir; 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

  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. 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.

  8. Nitrogen limited biobarriers remove atrazine from contaminated water: Laboratory studies

    NASA Astrophysics Data System (ADS)

    Hunter, William J.; Shaner, Dale L.

    2009-01-01

    Atrazine is one of the most frequently used herbicides. This usage coupled with its mobility and recalcitrant nature in deeper soils and aquifers makes it a frequently encountered groundwater contaminant. We formed biobarriers in sand filled columns by coating the sand with soybean oil; after which, we inoculated the barriers with a consortium of atrazine-degrading microorganisms and evaluated the ability of the barriers to remove atrazine from a simulated groundwater containing 1 mg L - 1 atrazine. The soybean oil provided a carbon rich and nitrogen poor substrate to the microbial consortium. Under these nitrogen-limiting conditions it was hypothesized that bacteria capable of using atrazine as a source of nitrogen would remove atrazine from the flowing water. Our hypothesis proved correct and the biobarriers were effective at removing atrazine when the nitrogen content of the influent water was low. Levels of atrazine in the biobarrier effluents declined with time and by the 24th week of the study no detectable atrazine was present (limit of detection < 0.005 mg L - 1 ). Larger amounts of atrazine were also removed by the biobarriers; when biobarriers were fed 16.3 mg L - 1 atrazine 97% was degraded. When nitrate (5 mg L - 1 N), an alternate source of nitrogen, was added to the influent water the atrazine removal efficiency of the barriers was reduced by almost 60%. This result supports the hypothesis that atrazine was degraded as a source of nitrogen. Poisoning of the biobarriers with mercury chloride resulted in an immediate and large increase in the amount of atrazine in the barrier effluents confirming that biological activity and not abiotic factors were responsible for most of the atrazine degradation. The presence of hydroxyatrazine in the barrier effluents indicated that dehalogenation was one of the pathways of atrazine degradation. Permeable barriers might be formed in-situ by the injection of innocuous vegetable oil emulsions into an aquifer or sandy

  9. 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.

  10. Studies of retroviral infection in humanized mice

    PubMed Central

    Marsden, Matthew D.; Zack, Jerome A.

    2015-01-01

    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

  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. Multilocus Genotyping of Human Giardia Isolates Suggests Limited Zoonotic Transmission and Association between Assemblage B and Flatulence in Children

    PubMed Central

    Lebbad, Marianne; Petersson, Ingvor; Karlsson, Lillemor; Botero-Kleiven, Silvia; Andersson, Jan O.; Svenungsson, Bo; Svärd, Staffan G.

    2011-01-01

    Background Giardia intestinalis is one of the most common diarrhea-related parasites in humans, where infection ranges from asymptomatic to acute or chronic disease. G. intestinalis consists of eight genetically distinct genotypes or assemblages, designated A–H, and assemblages A and B can infect humans. Giardiasis has been classified as a possible zoonotic disease but the role of animals in human disease transmission still needs to be proven. We tried to link different assemblages and sub-assemblages of G. intestinalis isolates from Swedish human patients to clinical symptoms and zoonotic transmission. Methodology/Principal Findings Multilocus sequence-based genotyping of 207 human Giardia isolates using three gene loci: ß-giardin, glutamate dehydrogenase (gdh), and triose phosphate isomerase (tpi) was combined with assemblage-specific tpi PCRs. This analysis identified 73 patients infected with assemblage A, 128 with assemblage B, and six with mixed assemblages A+B. Multilocus genotypes (MLGs) were easily determined for the assemblage A isolates, and most patients with this genotype had apparently been infected through anthroponotic transmission. However, we also found evidence of limited zoonotic transmission of Giardia in Sweden, since a few domestic human infections involved the same assemblage A MLGs previously reported in Swedish cats and ruminants. Assemblage B was detected more frequently than assemblage A and it was also more common in patients with suspected treatment failure. However, a large genetic variability made determination of assemblage B MLGs problematic. Correlation between symptoms and assemblages was found only for flatulence, which was significantly more common in children less than six years of age infected with assemblage B. Conclusions/Significance This study shows that certain assemblage A subtypes are potentially zoonotic and that flatulence is connected to assemblage B infections in young children. Determination of MLGs from

  13. Racism and human genome diversity research: the ethical limits of "population thinking".

    PubMed

    Gannett, L

    2001-01-01

    This paper questions the prevailing historical understanding that scientific racism "retreated" in the 1950s when anthropology adopted the concepts and methods of population genetics and race was recognized to be a social construct and replaced by the concept of population. More accurately, a "populational" concept of race was substituted for a "typological one"--this is demonstrated by looking at the work of Theodosius Dobzhansky circa 1950. The potential for contemporary research in human population genetics to contribute to racism needs to be considered with respect to the ability of the typological-population distinction to arbitrate boundaries between racist society and nonracist, even anti-racist, science. I point out some ethical limits of "population thinking" in doing so.

  14. Human stereopsis is not limited by the optics of the well-focused eye.

    PubMed

    Vlaskamp, Björn N S; Yoon, Geunyoung; Banks, Martin S

    2011-07-01

    Human stereopsis, the perception of depth from differences in the two eyes' images, is very precise: image differences smaller than a single photoreceptor can be converted into a perceived difference in depth. To better understand what determines this precision, we examined how the eyes' optics affects stereo resolution. We did this by comparing performance with normal, well-focused optics and with optics improved by eliminating chromatic aberration and correcting higher-order aberrations. We first measured luminance contrast sensitivity in both eyes and showed that we had indeed improved optical quality significantly. We then measured stereo resolution in two ways: by finding the finest corrugation in depth that one can perceive, and by finding the smallest disparity one can perceive as different from zero. Our optical manipulation had no effect on stereo performance. We checked this by redoing the experiments at low contrast and again found no effect of improving optical quality. Thus, the resolution of human stereopsis is not limited by the optics of the well-focused eye. We discuss the implications of this remarkable finding.

  15. Initial ALT-I pump limiter studies on TEXOR

    SciTech Connect

    Pontau, A.E.; Guthrie, S.E.; Malinowski, M.E.; Ver Berkmoes, A.A.; Whitley, J.B.; McDonald, J.M.; Watson, R.D.; Gauster, W.B.; Campbell, G.A.; Goebel, D.M.

    1984-05-01

    The ALT-I pump limiter has been used to control the fueling and recycling characteristics of TEXTOR during stable, reproducible tokamak discharges. The module has been operated in three modes: (1) Normal Limiter, with no particle collection, (2) Particle Scoop, with a maximum approx. 2 x 10/sup -3/ torr pressure rise in the 700 liter unpumped collection chamber, and (3) Pump Limiter, with up to approx. 10,000 1/s pumping speed and particle removal rates of up to 6 x 10/sup 20//s. In a comparison of operation in modes (1) and (3) using identical gas fueling programs, the total core electron number decreased by as much as 50%. The effective TEXTOR particle confinement time, tau/sub p/* = tau/sub p//(1-R), was decreased by a similar ratio. Within the throat region, during typical operation, electron densities and temperatures were 6 x 10/sup 11/ to 2 x 10/sup 12//cm/sup 3/ and 15 to 30 eV. These conditions are representative of an operating regime in which there is high reionization of neutrals, but no change in incoming plasma parameters in the throat region. Energetic particles near the deflector plate were observed. During a gradual insertion of TiC-coated ALT-I beyond the stainless steel TEXTOR main limiters, the density of Ti in the plasma increased to a level similar to those of Cr and Fe. The gas injection fueling efficiency while puffing hydrogen directly into the plasma at the pump limiter tangency point was measured to be > 0.9. These results are discussed in conjunction with measurements of particle flows within ALT-I and other plasma diagnostics to characterize pump limiter operation on TEXTOR.

  16. 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

  17. Muscle coordination limits efficiency and power output of human limb movement under a wide range of mechanical demands.

    PubMed

    Blake, Ollie M; Wakeling, James M

    2015-12-01

    This study investigated the influence of cycle frequency and workload on muscle coordination and the ensuing relationship with mechanical efficiency and power output of human limb movement. Eleven trained cyclists completed an array of cycle frequency (cadence)-power output conditions while excitation from 10 leg muscles and power output were recorded. Mechanical efficiency was maximized at increasing cadences for increasing power outputs and corresponded to muscle coordination and muscle fiber type recruitment that minimized both the total muscle excitation across all muscles and the ineffective pedal forces. Also, maximum efficiency was characterized by muscle coordination at the top and bottom of the pedal cycle and progressive excitation through the uniarticulate knee, hip, and ankle muscles. Inefficiencies were characterized by excessive excitation of biarticulate muscles and larger duty cycles. Power output and efficiency were limited by the duration of muscle excitation beyond a critical cadence (120-140 rpm), with larger duty cycles and disproportionate increases in muscle excitation suggesting deteriorating muscle coordination and limitations of the activation-deactivation capabilities. Most muscles displayed systematic phase shifts of the muscle excitation relative to the pedal cycle that were dependent on cadence and, to a lesser extent, power output. Phase shifts were different for each muscle, thereby altering their mechanical contribution to the pedaling action. This study shows that muscle coordination is a key determinant of mechanical efficiency and power output of limb movement across a wide range of mechanical demands and that the excitation and coordination of the muscles is limited at very high cycle frequencies.

  18. Rabbit Models for Studying Human Infectious Diseases

    PubMed Central

    Peng, Xuwen; Knouse, John A; Hernon, Krista M

    2015-01-01

    Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia–lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described. PMID:26678367

  19. Rabbit Models for Studying Human Infectious Diseases.

    PubMed

    Peng, Xuwen; Knouse, John A; Hernon, Krista M

    2015-12-01

    Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia-lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described. PMID:26678367

  20. 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...

  1. 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)…

  2. Parasites of importance for human health in Nigerian dogs: high prevalence and limited knowledge of pet owners

    PubMed Central

    Ugbomoiko, Uade Samuel; Ariza, Liana; Heukelbach, Jorg

    2008-01-01

    Background Dogs are the most common pet animals worldwide. They may harbour a wide range of parasites with zoonotic potential, thus causing a health risk to humans. In Nigeria, epidemiological knowledge on these parasites is limited. Methods In a community-based study, we examined 396 dogs in urban and rural areas of Ilorin (Kwara State, Central Nigeria) for ectoparasites and intestinal helminths. In addition, a questionnaire regarding knowledge and practices was applied to pet owners. Results Nine ectoparasite species belonging to four taxa and six intestinal helminth species were identified: fleas (Ctenocephalides canis, Pulex irritans, Tunga penetrans), mites (Demodex canis, Otodectes sp., Sarcoptes scabiei var. canis), ticks (Rhipicephalus sanguineus, Ixodes sp.), and lice (Trichodectes canis); and Toxocara canis, Ancylostoma sp., Trichuris vulpis, Dipylidium caninum, Taenidae and Strongyloides sp. Overall prevalence of ectoparasites was 60.4% and of intestinal helminths 68.4%. The occurrence of C. canis, R. sanguineus, T. canis, Ancylostoma sp. and T. vulpis was most common (prevalence 14.4% to 41.7%). Prevalence patterns in helminths were age-dependent, with T. canis showing a decreasing prevalence with age of host, and a reverse trend in other parasite species. Knowledge regarding zoonoses was very limited and the diseases not considered a major health problem. Treatment with antiparasitic drugs was more frequent in urban areas. Conclusion Parasites of importance for human health were highly prevalent in Nigerian dogs. Interventions should include health education provided to dog owners and the establishment of a program focusing on zoonotic diseases. PMID:19068110

  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. The neural basis of temporal individuation and its capacity limits in the human brain.

    PubMed

    Naughtin, Claire K; Tamber-Rosenau, Benjamin J; Dux, Paul E

    2014-02-01

    Individuation refers to individuals' use of spatial and temporal properties to register an object as a distinct perceptual event relative to other stimuli. Although behavioral studies have examined both spatial and temporal individuation, neuroimaging investigations of individuation have been restricted to the spatial domain and at relatively late stages of information processing. In this study we used univariate and multivoxel pattern analyses of functional magnetic resonance imaging data to identify brain regions involved in individuating temporally distinct visual items and the neural consequences that arise when this process reaches its capacity limit (repetition blindness, RB). First, we found that regional patterns of blood oxygen level-dependent activity in a large group of brain regions involved in "lower-level" perceptual and "higher-level" attentional/executive processing discriminated between instances where repeated and nonrepeated stimuli were successfully individuated, conditions that placed differential demands on temporal individuation. These results could not be attributed to repetition suppression, stimulus or response factors, task difficulty, regional activation differences, other capacity-limited processes, or artifacts in the data or analyses. Consistent with the global workplace model of consciousness, this finding suggests that temporal individuation is supported by a distributed set of brain regions, rather than a single neural correlate. Second, conditions that reflect the capacity limit of individuation (instances of RB) modulated the amplitude, rather than spatial pattern, of activity in the left hemisphere premotor cortex. This finding could not be attributed to response conflict/ambiguity and likely reflects a candidate brain region underlying the capacity-limited process that gives rise to RB.

  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. Limiting the Scope of Needs Assessment Studies or (How We Learned to Set Limits--And Feel No Guilt).

    ERIC Educational Resources Information Center

    Eastmond, J. Nicholls, Jr.; And Others

    Needs assessment is an activity undertaken for planning purposes. It is important to define the limits of the study and design it on a scale appropriate to the entire planning process. This paper suggests that a needs assessment be structured into two phases. In the pre-assessment phase, a conceptual framework and well-defined exploratory…

  7. 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

  8. The Viral E8^E2C Repressor Limits Productive Replication of Human Papillomavirus 16

    PubMed Central

    Straub, Elke; Dreer, Marcel; Fertey, Jasmin; Iftner, Thomas

    2014-01-01

    Productive replication of human papillomavirus type 16 (HPV16) occurs only in differentiated keratinocyte cells. In addition to the viral E2 activator protein, HPV16 and related HPV types express transcripts coding for an E8^E2C fusion protein, which limits genome replication in undifferentiated keratinocytes. To address E8^E2C's role in productive replication of HPV16, stable keratinocyte cell lines containing wild-type (wt), E8^E2C knockout (E8−), or E8 KWK mutant (mt) genomes, in which conserved E8 residues were inactivated, were established. Copy numbers of E8− and E8 KWK mt genomes and amounts of early and late viral transcripts were greatly increased compared to those for the wt in undifferentiated keratinocytes, suggesting that HPV16 E8^E2C activities are highly dependent upon the E8 part. Upon differentiation in organotypic cultures, E8 mt genomes displayed higher early viral transcript levels, but no changes in cellular differentiation or virus-induced cellular DNA replication in suprabasal cells were observed. E8 mt genomes were amplified to higher copy numbers and showed increased L1 transcripts compared to wt genomes. Furthermore, the number of cells expressing the viral late protein E4 or L1 or amplifying viral genomes was greatly increased in E8 mt cell lines. In wild-type cells, E8^E2C transcript levels did not decrease by differentiation. Our data indicate that the E8^E2C repressor limits viral transcription and replication throughout the complete life cycle of HPV16. PMID:24198405

  9. 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…

  10. Studies of human mutation rates

    SciTech Connect

    Neel, J.V.

    1990-01-01

    November 1989, marked the beginning of a new three-year cycle of DOE grant support, in connection with which the program underwent a major reorganization. This document presents the progress on the three objectives of the present program which 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 mutations in the parents of the individual whose DNA is being examined; 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.

  11. 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...

  12. Investigation of the human pathogen Acinetobacter baumannii under iron limiting conditions

    PubMed Central

    2011-01-01

    Background Iron acquisition systems are important virulence factors in pathogenic bacteria. To identify these systems in Acinetobacter baumannii, the transcriptomic response of the completely sequenced strain ATCC 17978 under iron limiting conditions was investigated using a genomic microarray that contained probes for all annotated open reading frames. Results Under low iron conditions, transcription levels were more than 2-fold up-regulated for 463 genes, including 95 genes that were up-regulated more than 4-fold. Of particular significance, three siderophore biosynthesis gene clusters, including one novel cluster, were highly up-regulated. Binding sites for the ferric uptake regulator were identified in the promoter regions of many up-regulated genes, suggesting a prominent role for this regulator in the Acinetobacter iron acquisition response. Down-regulation under iron limitation was less dramatic as the transcription of only 202 genes varied more than 2-fold. Various genes involved in motility featured prominently amongst the genes down-regulated when iron was less readily available. Motility assays confirmed that these transcriptional changes are manifested at the phenotypic level. The siderophore biosynthesis gene clusters were further investigated by means of comparative genomic analysis of 10 sequenced Acinetobacter isolates. These analyses revealed important roles for mobile genetic elements in shaping the siderophore meditated iron acquisition mechanisms between different Acinetobacter strains. Conclusions A. baumannii grown under iron limited conditions resulted in major transcriptional changes of not only many iron acquisition related genes, but also genes involved in other processes such as motility. Overall, this study showed that A. baumannii is well adaptable to growth in an environment which has limiting iron availability. PMID:21342532

  13. 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

  14. A limited bibliography of the federal government-funded human radiation experiments

    SciTech Connect

    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.

  15. 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.

  16. Oxidative damage to RPA limits the nucleotide excision repair capacity of human cells

    PubMed Central

    Guven, Melisa; Brem, Reto; Macpherson, Peter; Peacock, Matthew; Karran, Peter

    2015-01-01

    Nucleotide excision repair (NER) protects against sunlight-induced skin cancer. Defective NER is associated with photosensitivity and a high skin cancer incidence. Some clinical treatments that cause photosensitivity can also increase skin cancer risk. Among these, the immunosuppressant azathioprine and the fluoroquinolone antibiotics ciprofloxacin and ofloxacin, interact with UVA radiation to generate reactive oxygen species (ROS) that diminish NER capacity by causing protein damage. The RPA DNA binding protein plays a pivotal role in DNA metabolism and is an essential component of NER. The relationship between protein oxidation and NER inhibition was investigated in cultured human cells expressing different levels of RPA. We show here that RPA is limiting for NER and that oxidative damage to RPA compromises NER capability. Our findings reveal that cellular RPA is surprisingly vulnerable to oxidation and we identify oxidized forms of RPA that are associated with impaired NER. The vulnerability of NER to inhibition by oxidation provides a connection between cutaneous photosensitivity, protein damage and increased skin cancer risk. Our findings emphasize that damage to DNA repair proteins, as well as to DNA itself is likely to be an important contributor to skin cancer risk. PMID:26134950

  17. 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.

  18. 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

  19. New horizons for studying human hepatotropic infections

    PubMed Central

    de Jong, Ype P.; Rice, Charles M.; Ploss, Alexander

    2010-01-01

    The liver serves as a target organ for several important pathogens, including hepatitis B and C viruses (HBV and HCV, respectively) and the human malaria parasites, all of which represent serious global health problems. Because these pathogens are restricted to human hepatocytes, research in small animals has been compromised by the frailty of the current mouse xenotransplantation models. In this issue of the JCI, Bissig et al. demonstrate robust HBV and HCV infection in a novel xenotransplantation model in which large numbers of immunodeficient mice with liver injury were engrafted with significant quantities of human hepatocytes. This technical advance paves the way for more widespread use of human liver chimeric mice and forms the basis for creating increasingly complex humanized mouse models that could prove useful for studying immunopathogenesis and vaccine development against hepatotropic pathogens. PMID:20179350

  20. 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…

  1. 75 FR 359 - Guidance on Simultaneous Transmission Import Limit Studies; Notice Allowing Post-Technical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-05

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF ENERGY Federal Energy Regulatory Commission Guidance on Simultaneous Transmission Import Limit Studies; Notice Allowing... provide guidance for performing Simultaneous Transmission Import Limit (SIL) studies. All...

  2. 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.

  3. Cultural Studies and the Limits of Self-Reflexivity.

    ERIC Educational Resources Information Center

    Knapp, James F.

    Among the changes that have characterized English studies over the past 25 years is an increase in self-reflection. The rise of various kinds of writing collectively labeled "theory" has influenced this move to scrutinize actions and motives. Composition studies have developed classroom strategies for asking students to reflect on their own…

  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

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

    PubMed

    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

    2013-10-15

    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 depend 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 brain's 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 G(max) = 300 mT/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

  6. Protein western array analysis in human pituitary tumours: insights and limitations.

    PubMed

    Ribeiro-Oliveira, Antônio; Franchi, Giulia; Kola, Blerina; Dalino, Paolo; Pinheiro, Sérgio Veloso Brant; Salahuddin, Nabila; Musat, Madalina; Góth, Miklós I; Czirják, Sándor; Hanzély, Zoltán; da Silva, Deivid Augusto; Paulino, Eduardo; Grossman, Ashley B; Korbonits, Márta

    2008-12-01

    The molecular analysis of pituitary tumours has received a great deal of attention, although the majority of studies have concentrated on the genome and the transcriptome. We aimed to study the proteome of human pituitary adenomas. A protein array using 1005 monoclonal antibodies was used to study GH-, corticotrophin- and prolactin-secreting as well as non-functioning pituitary adenomas (NFPAs). Individual protein expression levels in the tumours were compared with the expression profile of normal pituitary tissue. Out of 316 proteins that were detected in the pituitary tissue samples, 116 proteins had not previously been described in human pituitary tissue. Four prominent differentially expressed proteins with potential importance to tumorigenesis were chosen for validation by immunohistochemistry and western blotting. In the protein array analysis heat shock protein 110 (HSP110), a chaperone associated with protein folding, and B2 bradykinin receptor, a potential regulator of prolactin secretion, were significantly overexpressed in all adenoma subtypes, while C-terminal Src kinase (CSK), an inhibitor of proto-oncogenic enzymes, and annexin II, a calcium-dependent binding protein, were significantly underexpressed in all adenoma subtypes. The immunohistochemical analysis confirmed the overexpression of HSP110 and B2 bradykinin receptor and underexpression of CSK and annexin II in pituitary adenoma cells when compared with their corresponding normal pituitary cells. Western blotting only partially confirmed the proteomics data: HSP110 was significantly overexpressed in prolactinomas and NFPAs, the B2 bradykinin receptor was significantly overexpressed in prolactinomas, annexin II was significantly underexpressed in somatotrophinomas, while CSK did not show significant underexpression in any tumour. Protein expression analysis of pituitary samples disclosed both novel proteins and putative protein candidates for pituitary tumorigenesis, though validation using

  7. 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

  8. 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

  9. The Limits of Cultural Competence: An Indigenous Studies Perspective

    ERIC Educational Resources Information Center

    Carey, Michelle

    2015-01-01

    Taking the Universities Australia report, "National best practice framework for Indigenous cultural competency in Australian universities" (2011) as the starting point for its discussion, this paper examines the applicability of cultural competence in the design and delivery of Australian Indigenous Studies. It argues that both the…

  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. Assessment of drug-induced arrhythmic risk using limit cycle and autocorrelation analysis of human iPSC-cardiomyocyte contractility.

    PubMed

    Kirby, R Jason; Qi, Feng; Phatak, Sharangdhar; Smith, Layton H; Malany, Siobhan

    2016-08-15

    Cardiac safety assays incorporating label-free detection of human stem-cell derived cardiomyocyte contractility provide human relevance and medium throughput screening to assess compound-induced cardiotoxicity. In an effort to provide quantitative analysis of the large kinetic datasets resulting from these real-time studies, we applied bioinformatic approaches based on nonlinear dynamical system analysis, including limit cycle analysis and autocorrelation function, to systematically assess beat irregularity. The algorithms were integrated into a software program to seamlessly generate results for 96-well impedance-based data. Our approach was validated by analyzing dose- and time-dependent changes in beat patterns induced by known proarrhythmic compounds and screening a cardiotoxicity library to rank order compounds based on their proarrhythmic potential. We demonstrate a strong correlation for dose-dependent beat irregularity monitored by electrical impedance and quantified by autocorrelation analysis to traditional manual patch clamp potency values for hERG blockers. In addition, our platform identifies non-hERG blockers known to cause clinical arrhythmia. Our method provides a novel suite of medium-throughput quantitative tools for assessing compound effects on cardiac contractility and predicting compounds with potential proarrhythmia and may be applied to in vitro paradigms for pre-clinical cardiac safety evaluation. PMID:27343406

  12. 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.

  13. 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.

  14. Catalytic characterization of human microsomal glutathione S-transferase 2: identification of rate-limiting steps.

    PubMed

    Ahmad, Shabbir; Niegowski, Damian; Wetterholm, Anders; Haeggström, Jesper Z; Morgenstern, Ralf; Rinaldo-Matthis, Agnes

    2013-03-12

    Microsomal glutathione S-transferase 2 (MGST2) is a 17 kDa trimeric integral membrane protein homologous to leukotriene C4 synthase (LTC4S). MGST2 has been suggested to catalyze the biosynthesis of the pro-inflammatory mediator leukotriene C4 (LTC4) in cells devoid of LTC4S. A detailed biochemical study of MGST2 is critical for the understanding of its cellular function and potential role as an LTC4-producing enzyme. Here we have characterized the substrate specificity and catalytic properties of purified MGST2 by steady-state and pre-steady-state kinetic experiments. In comparison with LTC4S, which has a catalytic efficiency of 8.7 × 10(5) M(-1) s(-1), MGST2, with a catalytic efficiency of 1.8 × 10(4) M(-1) s(-1), is considerably less efficient in producing LTC4. However, the two enzymes display a similar KM(LTA4) of 30-40 μM. While LTC4S has one activated glutathione (GSH) (forming a thiolate) per enzyme monomer, the MGST2 trimer seems to display only third-of-the-sites reactivity for thiolate activation, which in part would explain its lower catalytic efficiency. Furthermore, MGST2 displays GSH-dependent peroxidase activity of ∼0.2 μmol min(-1) mg(-1) toward several lipid hydroperoxides. MGST2, but not LTC4S, is efficient in catalyzing conjugation of the electrophilic substrate 1-chloro-2,4-dinitrobenzene (CDNB) and the lipid peroxidation product 4-hydroxy-2-nonenal with GSH. Using stopped-flow pre-steady-state kinetics, we have characterized the full catalytic reaction of MGST2 with CDNB and GSH as substrates, showing an initial rapid equilibrium binding of GSH followed by thiolate formation. Burst kinetics for the CDNB-GSH conjugation step was observed only at low GSH concentrations (thiolate anion formation becoming rate-limiting under these conditions). Product release is rapid and does not limit the overall reaction. Therefore, in general, the chemical conjugation step is rate-limiting for MGST2 at physiological GSH concentrations. MGST2 and LTC4S

  15. Sociology and American Studies: A Case Study in the Limits of Interdisciplinarity.

    PubMed

    Dubrow, Joshua Kjerulf

    2011-12-01

    American Studies is an academic discipline whose object of study is the United States of America and everything associated with it, and American sociologists largely ignore it. American Studies largely ignores American sociology. What causes this mutual exclusion? An outline of the disciplinary history of American Studies and journal article citation data show that the relationship between sociology and American Studies is weak and asymmetrical; American Studies cites sociology more often, but very little and not by much. I argue that mutual exclusion is due to mutual distrust in methods: sociology sees itself as a science, while American Studies, with roots in history and literature, does not. This article serves as a case study in the limits of interdisciplinarity.

  16. 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...

  17. Simulation study of PET detector limitations using continuous crystals

    NASA Astrophysics Data System (ADS)

    Cabello, Jorge; Etxebeste, Ane; Llosá, Gabriela; Ziegler, Sibylle I.

    2015-05-01

    Continuous crystals can potentially obtain better intrinsic detector spatial resolution compared to pixelated crystals, additionally providing depth of interaction (DoI) information from the light distribution. To achieve high performance sophisticated interaction position estimation algorithms are required. There are a number of algorithms in the literature applied to different crystal dimensions and different photodetectors. However, the different crystal properties and photodetector array geometries have an impact on the algorithm performance. In this work we analysed, through Monte Carlo simulations, different combinations of realistic crystals and photodetector parameters to better understand their influence on the interaction position estimation accuracy, with special emphasis on the DoI. We used an interaction position estimation based on an analytical model for the present work. Different photodetector granulation schemes were investigated. The impact of the number of crystal faces readout by photodetectors was studied by simulating scenarios with one and two photodetectors. In addition, crystals with different levels of reflection and aspect ratios (AR) were analysed. Results showed that the impact of photodetector granularity is mainly shown near the edges and specially in the corners of the crystal. The resulting intrinsic spatial resolution near the centre with a 12 × 12 × 10 mm3 LYSO crystal was 0.7-0.9 mm, while the average spatial resolution calculated on the entire crystal was 0.77 ± 0.18 mm for all the simulated geometries with one and two photodetectors. Having front and back photodetectors reduced the DoI bias (Euclidean distance between estimated DoI and real DoI) and improved the transversal resolution near the corners. In scenarios with one photodetector, small AR resulted in DoI inaccuracies for absorbed events at the entrance of the crystal. These inaccuracies were slightly reduced either by increasing the AR or reducing the amount of

  18. Simulation study of PET detector limitations using continuous crystals.

    PubMed

    Cabello, Jorge; Etxebeste, Ane; Llosá, Gabriela; Ziegler, Sibylle I

    2015-05-01

    Continuous crystals can potentially obtain better intrinsic detector spatial resolution compared to pixelated crystals, additionally providing depth of interaction (DoI) information from the light distribution. To achieve high performance sophisticated interaction position estimation algorithms are required. There are a number of algorithms in the literature applied to different crystal dimensions and different photodetectors. However, the different crystal properties and photodetector array geometries have an impact on the algorithm performance. In this work we analysed, through Monte Carlo simulations, different combinations of realistic crystals and photodetector parameters to better understand their influence on the interaction position estimation accuracy, with special emphasis on the DoI. We used an interaction position estimation based on an analytical model for the present work. Different photodetector granulation schemes were investigated. The impact of the number of crystal faces readout by photodetectors was studied by simulating scenarios with one and two photodetectors. In addition, crystals with different levels of reflection and aspect ratios (AR) were analysed. Results showed that the impact of photodetector granularity is mainly shown near the edges and specially in the corners of the crystal. The resulting intrinsic spatial resolution near the centre with a 12 × 12 × 10 mm(3) LYSO crystal was 0.7-0.9 mm, while the average spatial resolution calculated on the entire crystal was 0.77 ± 0.18 mm for all the simulated geometries with one and two photodetectors. Having front and back photodetectors reduced the DoI bias (Euclidean distance between estimated DoI and real DoI) and improved the transversal resolution near the corners. In scenarios with one photodetector, small AR resulted in DoI inaccuracies for absorbed events at the entrance of the crystal. These inaccuracies were slightly reduced either by increasing the AR or reducing the amount

  19. Protective headgear for midwestern agriculture: a limited wear study.

    PubMed

    Stone, J F; Hanna, M; Guo, C; Imerman, P

    2001-03-01

    Baseball caps are popular with farm workers, but have been criticized because they do not sufficiently shade the face, neck, and ears. U.S. Environmental Protection Agency standards require workers to wear chemical-resistant hoods or chemical-resistant hats with wide brims during the application of pesticides whose labels call for head protection. In this study, four farm workers wore baseball caps and two alternative types of headgear with wide brims for 20 to 36 hours during planting of corn and soybeans to compare performance features and practicality. Afterwards, researchers analyzed the headgear fabrics by gas chromatography or high-performance liquid chromatography to determine the levels at which five herbicides were deposited on the headgear: 2,4-D, metolachlor, acetochlor, ethalfluralin, and glyphosate. Chemical analysis revealed that 12 percent of specimens had detectable residue: levels of glyphosate in the nanograms-per-square-centimeter (ng/cm2) range and levels of 2,4-D in the micrograms-per-square-centimeter (microgram/cm2) range. Workers, however, preferred the baseball caps because of problems with the wind and feelings of embarrassment about wearing other types of headgear. An acceptable, protective substitute for the baseball cap has yet to be designed.

  20. Biological effects of weak blast waves and safety limits for internal organ injury in the human body.

    PubMed

    Yang, Z; Wang, Z; Tang, C; Ying, Y

    1996-03-01

    One hundred and seventeen adult sheep of both sexes, each weighing 15.2-42.4 kg, were used for this study. The purpose of this study was to investigate the relationship of the physical parameters of the waves to internal organ injury by exposing sheep to weak blast waves in TNT (trinitrotoluene) explosions, biological shock tube, and gun muzzle blasts. The results showed that the organ most sensitive to the TNT explosion was the lungs, whereas the upper respiratory tract was most sensitive to muzzle blast waves. The injury thresholds of overpressure were 29.0, 29.5, and 41.2 kPa for upper respiratory tract, lungs, and gastrointestinal tract respectively at a single exposure. Repeated exposure to 60 blasts reduced the injury threshold of the internal organs. The injury thresholds for upper respiratory tract, lungs, and gastrointestinal tract were 21.0, 18.0, and 40.4 kPa, respectively. The duration of overpressure of weak blast waves was 2.4-4.2 milliseconds, which did not significantly affect the severity of injury. The safety limits of weak blast waves to internal organ injury of human body were as follows: Ps = 37-3Ln.Tc.N/4(Tc.N < or = 1000) and Ps = 20.4(Tc.N > 1000). The results suggest that repeated exposures decrease the injury threshold of the internal organs. The safety limits proposed could protect 90% of the exposed population against internal organ injury caused by weak blast waves. PMID:8606431

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. Formally verifying human-automation interaction as part of a system model: limitations and tradeoffs.

    PubMed

    Bolton, Matthew L; Bass, Ellen J

    2010-03-25

    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 human-automation 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 human-automation 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.

  6. Activation of Human T Cells in Hypertension: Studies of Humanized Mice and Hypertensive Humans.

    PubMed

    Itani, Hana A; McMaster, William G; Saleh, Mohamed A; Nazarewicz, Rafal R; Mikolajczyk, Tomasz P; Kaszuba, Anna M; Konior, Anna; Prejbisz, Aleksander; Januszewicz, Andrzej; Norlander, Allison E; Chen, Wei; Bonami, Rachel H; Marshall, Andrew F; Poffenberger, Greg; Weyand, Cornelia M; Madhur, Meena S; Moore, Daniel J; Harrison, David G; Guzik, Tomasz J

    2016-07-01

    Emerging evidence supports an important role for T cells in the genesis of hypertension. Because this work has predominantly been performed in experimental animals, we sought to determine whether human T cells are activated in hypertension. We used a humanized mouse model in which the murine immune system is replaced by the human immune system. Angiotensin II increased systolic pressure to 162 versus 116 mm Hg for sham-treated animals. Flow cytometry of thoracic lymph nodes, thoracic aorta, and kidney revealed increased infiltration of human leukocytes (CD45(+)) and T lymphocytes (CD3(+) and CD4(+)) in response to angiotensin II infusion. Interestingly, there was also an increase in the memory T cells (CD3(+)/CD45RO(+)) in the aortas and lymph nodes. Prevention of hypertension using hydralazine and hydrochlorothiazide prevented the accumulation of T cells in these tissues. Studies of isolated human T cells and monocytes indicated that angiotensin II had no direct effect on cytokine production by T cells or the ability of dendritic cells to drive T-cell proliferation. We also observed an increase in circulating interleukin-17A producing CD4(+) T cells and both CD4(+) and CD8(+) T cells that produce interferon-γ in hypertensive compared with normotensive humans. Thus, human T cells become activated and invade critical end-organ tissues in response to hypertension in a humanized mouse model. This response likely reflects the hypertensive milieu encountered in vivo and is not a direct effect of the hormone angiotensin II.

  7. Activation of Human T Cells in Hypertension: Studies of Humanized Mice and Hypertensive Humans.

    PubMed

    Itani, Hana A; McMaster, William G; Saleh, Mohamed A; Nazarewicz, Rafal R; Mikolajczyk, Tomasz P; Kaszuba, Anna M; Konior, Anna; Prejbisz, Aleksander; Januszewicz, Andrzej; Norlander, Allison E; Chen, Wei; Bonami, Rachel H; Marshall, Andrew F; Poffenberger, Greg; Weyand, Cornelia M; Madhur, Meena S; Moore, Daniel J; Harrison, David G; Guzik, Tomasz J

    2016-07-01

    Emerging evidence supports an important role for T cells in the genesis of hypertension. Because this work has predominantly been performed in experimental animals, we sought to determine whether human T cells are activated in hypertension. We used a humanized mouse model in which the murine immune system is replaced by the human immune system. Angiotensin II increased systolic pressure to 162 versus 116 mm Hg for sham-treated animals. Flow cytometry of thoracic lymph nodes, thoracic aorta, and kidney revealed increased infiltration of human leukocytes (CD45(+)) and T lymphocytes (CD3(+) and CD4(+)) in response to angiotensin II infusion. Interestingly, there was also an increase in the memory T cells (CD3(+)/CD45RO(+)) in the aortas and lymph nodes. Prevention of hypertension using hydralazine and hydrochlorothiazide prevented the accumulation of T cells in these tissues. Studies of isolated human T cells and monocytes indicated that angiotensin II had no direct effect on cytokine production by T cells or the ability of dendritic cells to drive T-cell proliferation. We also observed an increase in circulating interleukin-17A producing CD4(+) T cells and both CD4(+) and CD8(+) T cells that produce interferon-γ in hypertensive compared with normotensive humans. Thus, human T cells become activated and invade critical end-organ tissues in response to hypertension in a humanized mouse model. This response likely reflects the hypertensive milieu encountered in vivo and is not a direct effect of the hormone angiotensin II. PMID:27217403

  8. 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.

  9. Limited infection upon human exposure to a recombinant raccoon pox vaccine vector.

    PubMed

    Rocke, Tonie E; Dein, F Joshua; Fuchsberger, Martina; Fox, Barry C; Stinchcomb, Dan T; Osorio, Jorge E

    2004-07-29

    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.

  10. Access to human, animal, and environmental journals is still limited for the One Health community*

    PubMed Central

    Vreeland, Carol E.; Alpi, Kristine M.; Pike, Caitlin A.; Whitman, Elisabeth E.; Kennedy-Stoskopf, Suzanne

    2016-01-01

    Objective “One Health” is an interdisciplinary approach to evaluating and managing the health and well-being of humans, animals, and the environments they share that relies on knowledge from the domains of human health, animal health, and the environmental sciences. The authors' objective was to evaluate the extent of open access (OA) to journal articles in a sample of literature from these domains. We hypothesized that OA to articles in human health or environmental journals was greater than access to animal health literature. Methods A One Health seminar series provided fifteen topics. One librarian translated each topic into a search strategy and searched four databases for articles from 2011 to 2012. Two independent investigators assigned each article to human health, the environment, animal health, all, other, or combined categories. Article and journal-level OA were determined. Each journal was also assigned a subject category and its indexing evaluated. Results Searches retrieved 2,651 unique articles from 1,138 journals; 1,919 (72%) articles came from 406 journals that contributed more than 1 article. Seventy-seven (7%) journals dealt with all 3 One Health domains; the remaining journals represented human health 487 (43%), environment 172 (15%), animal health 141 (12%), and other/combined categories 261 (23%). The proportion of OA journals in animal health (40%) differed significantly from journals categorized as human (28%), environment (28%), and more than 1 category (29%). The proportion of OA for articles by subject categories ranged from 25%–34%; only the difference between human (34%) and environment (25%) was significant. Conclusions OA to human health literature is more comparable to animal health than hypothesized. Environmental journals had less OA than anticipated. PMID:27076796

  11. Human exposure to airborne aniline and formation of methemoglobin: a contribution to occupational exposure limits.

    PubMed

    Käfferlein, Heiko Udo; Broding, Horst Christoph; Bünger, Jürgen; Jettkant, Birger; Koslitz, Stephan; Lehnert, Martin; Marek, Eike Maximilian; Blaszkewicz, Meinolf; Monsé, Christian; Weiss, Tobias; Brüning, Thomas

    2014-07-01

    Aniline is an important starting material in the manufacture of polyurethane-based plastic materials. Aniline-derived methemoglobinemia (Met-Hb) is well described in exposed workers although information on the dose-response association is limited. We used an experimental design to study the association between aniline in air with the formation of Met-Hb in blood and the elimination of aniline in urine. A 6-h exposure of 2 ppm aniline in 19 non-smoking volunteers resulted in a time-dependent increase in Met-Hb in blood and aniline in urine. The maximum Met-Hb level in blood (mean 1.21 ± 0.29 %, range 0.80-2.07 %) and aniline excretion in urine (mean 168.0 ± 51.8 µg/L, range 79.5-418.3 µg/L) were observed at the end of exposure, with both parameters rapidly decreasing after the end of exposure. After 24 h, the mean level of Met-Hb (0.65 ± 0.18 %) returned to the basal level observed prior to the exposure (0.72 ± 0.19 %); whereas, slightly elevated levels of aniline were still present in urine (means 17.0 ± 17.1 vs. 5.7 ± 3.8 µg/L). No differences between males and females as well as between slow and fast acetylators were found. The results obtained after 6-h exposure were also comparable to those observed in four non-smoking volunteers after 8-h exposure. Maximum levels of Met-Hb and aniline in urine were 1.57 % and 305.6 µg/L, respectively. Overall, our results contribute to the risk assessment of aniline and as a result, the protection of workers from aniline-derived adverse health effects at the workplace.

  12. Human exposure to airborne aniline and formation of methemoglobin: a contribution to occupational exposure limits.

    PubMed

    Käfferlein, Heiko Udo; Broding, Horst Christoph; Bünger, Jürgen; Jettkant, Birger; Koslitz, Stephan; Lehnert, Martin; Marek, Eike Maximilian; Blaszkewicz, Meinolf; Monsé, Christian; Weiss, Tobias; Brüning, Thomas

    2014-07-01

    Aniline is an important starting material in the manufacture of polyurethane-based plastic materials. Aniline-derived methemoglobinemia (Met-Hb) is well described in exposed workers although information on the dose-response association is limited. We used an experimental design to study the association between aniline in air with the formation of Met-Hb in blood and the elimination of aniline in urine. A 6-h exposure of 2 ppm aniline in 19 non-smoking volunteers resulted in a time-dependent increase in Met-Hb in blood and aniline in urine. The maximum Met-Hb level in blood (mean 1.21 ± 0.29 %, range 0.80-2.07 %) and aniline excretion in urine (mean 168.0 ± 51.8 µg/L, range 79.5-418.3 µg/L) were observed at the end of exposure, with both parameters rapidly decreasing after the end of exposure. After 24 h, the mean level of Met-Hb (0.65 ± 0.18 %) returned to the basal level observed prior to the exposure (0.72 ± 0.19 %); whereas, slightly elevated levels of aniline were still present in urine (means 17.0 ± 17.1 vs. 5.7 ± 3.8 µg/L). No differences between males and females as well as between slow and fast acetylators were found. The results obtained after 6-h exposure were also comparable to those observed in four non-smoking volunteers after 8-h exposure. Maximum levels of Met-Hb and aniline in urine were 1.57 % and 305.6 µg/L, respectively. Overall, our results contribute to the risk assessment of aniline and as a result, the protection of workers from aniline-derived adverse health effects at the workplace. PMID:24899222

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

    PubMed

    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

  14. 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

  15. Limited spillover to humans from West Nile Virus viremic birds in Atlanta, Georgia.

    PubMed

    Levine, Rebecca S; Mead, Daniel G; Kitron, Uriel D

    2013-11-01

    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 2010-2012, 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.

  16. 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 2010–2012, 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

  17. [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.

  18. 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.

  19. Light for nurses' work in the 21st century: a review of lighting, human vision limitations, and medication administration.

    PubMed

    Graves, Krisanne; Symes, Lene; Cesario, Sandra K

    2014-01-01

    A literature review was conducted to determine the state of the science related to medication errors and light. The limited literature is discussed in relationship to human vision and light needs. Little systematic action has been taken to increase nurses' awareness of the connection between lighting and potential medication errors. Implications for nursing practice and research about light conditions are provided. Interventions from other industries may aid nursing in making decisions about light conditions.

  20. [Aviation and high-altitude medicine for anaesthetists. Part 4: human performance limitations and crew resource management].

    PubMed

    Egerth, Martin; Pump, Stefan; Graf, Jürgen

    2013-06-01

    For pilots and doctors, as well as a variety of other professions the knowledge of human performance limitations is essential, especially in critical situations. Crew resource management was developed in the 1980s in the aviation industry in order to ensure systematic training and support in such instances. Just recently, the value is recognized not only in other high reliability organizations but also in medicine. PMID:23828086

  1. [Aviation and high-altitude medicine for anaesthetists. Part 4: human performance limitations and crew resource management].

    PubMed

    Egerth, Martin; Pump, Stefan; Graf, Jürgen

    2013-06-01

    For pilots and doctors, as well as a variety of other professions the knowledge of human performance limitations is essential, especially in critical situations. Crew resource management was developed in the 1980s in the aviation industry in order to ensure systematic training and support in such instances. Just recently, the value is recognized not only in other high reliability organizations but also in medicine.

  2. Studies in human skin epithelial cell carcinogenesis

    SciTech Connect

    Lehman, T.A.

    1987-01-01

    Metabolism and DNA adduct formation of benzo(a)pyrene (BP) by human epidermal keratinocytes pretreated with inhibitors or inducer of cytochrame P450 was studied. To study DNA adduct analysis, cultures were pretreated as described above, and then treated with non-radiolabeled BP. DNA was prepared from these cultures, digested to the nucleotide level, and /sup 32/P-postlabeled for adduct analysis. Cultures pretreated with BHA, 7,8-BF or disulfiralm formed significantly fewer BPDE I-dB adducts than non-pretreated cultures, while cultures pretreated with MeBHA formed more BPDE-I-dG adducts. MeBHA increased BP activation and adduct formation inhuman keratinocyte in cultures by inducing a specific isoenzyme of cytochrome P450 which preferentially increases the oxidative metabolism of BP to 7,8 diol BP and 7,8 diol BP to BPDE I. To approximate an in vivo human system, metabolism of BPDE I by human skin xenografts treated with cell cycles modulators was studied. When treated with BPDE I, specific carcinogen-DNA adducts were formed. Separation and identification of these adducts by the /sup 32/P-postlabeling technique indicated that the 7R- and 7S-BPDE I-dG adducts were the major adducts.

  3. Monoamine oxidase: radiotracer chemistry and human studies.

    PubMed

    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 serotonin, 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 years since the first radiotracers were developed and the first positron emission tomography (PET) images of MAO in humans were carried out, PET studies of brain MAO in healthy volunteers and in patients have identified different variables that 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 the following: (1) the development of MAO radiotracers; (2) human studies including the relationship of brain MAO levels to genotype, personality, neurological, and psychiatric disorders; and (3) examples of the use of MAO radiotracers in drug research and development. We will conclude with outstanding needs to improve the radiotracers that are currently used and possible new applications.

  4. Monoamine oxidase: Radiotracer chemistry and human studies

    DOE PAGES

    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. 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 2 weeks 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.

  7. 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…

  8. 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...

  9. 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…

  10. 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.

  11. All That Glitters Isn't Gold: A Survey on Acknowledgment of Limitations in Biomedical Studies

    PubMed Central

    ter Riet, Gerben; Chesley, Paula; Gross, Alan G.; Siebeling, Lara; Muggensturm, Patrick; Heller, Nadine; Umbehr, Martin; Vollenweider, Daniela; Yu, Tsung; Akl, Elie A.; Brewster, Lizzy; Dekkers, Olaf M.; Mühlhauser, Ingrid; Richter, Bernd; Singh, Sonal; Goodman, Steven; Puhan, Milo A.

    2013-01-01

    Background Acknowledgment of all serious limitations to research evidence is important for patient care and scientific progress. Formal research on how biomedical authors acknowledge limitations is scarce. Objectives To assess the extent to which limitations are acknowledged in biomedical publications explicitly, and implicitly by investigating the use of phrases that express uncertainty, so-called hedges; to assess the association between industry support and the extent of hedging. Design We analyzed reporting of limitations and use of hedges in 300 biomedical publications published in 30 high and medium -ranked journals in 2007. Hedges were assessed using linguistic software that assigned weights between 1 and 5 to each expression of uncertainty. Results Twenty-seven percent of publications (81/300) did not mention any limitations, while 73% acknowledged a median of 3 (range 1–8) limitations. Five percent mentioned a limitation in the abstract. After controlling for confounders, publications on industry-supported studies used significantly fewer hedges than publications not so supported (p = 0.028). Limitations Detection and classification of limitations was – to some extent – subjective. The weighting scheme used by the hedging detection software has subjective elements. Conclusions Reporting of limitations in biomedical publications is probably very incomplete. Transparent reporting of limitations may protect clinicians and guideline committees against overly confident beliefs and decisions and support scientific progress through better design, conduct or analysis of new studies. PMID:24324540

  12. Cytochemical study of pseudoisocyanine stained human chromosomes.

    PubMed

    Vagner-Capodano, A M; Pinna-Delgrossi, M H; Stahl, A

    1976-01-28

    Human meiotic and mitotic chromosomes were studied with N-N' diethyl pseudoisocyanine stain. Following methylation and oxydation, the staining allowed microscopic observation of slides with both monochromatic light and fluorescence. In addition, stained preparations can be permanently conserved. Preceeded by diverse methods of chromosome denaturation or 5-BUDR incorporation, PIC lends itself to a large number of banding techniques. Cytochemical study of stained chromosomes demonstrated a certain PIC affinity for DNA although tests performed do not exclude the possibility of PIC reaction with certain proteins.

  13. 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

  14. 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 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.

  15. Human interaural time difference thresholds for sine tones: The high-frequency limit

    PubMed Central

    Brughera, Andrew; Dunai, Larisa; Hartmann, William M.

    2013-01-01

    The smallest detectable interaural time difference (ITD) for sine tones was measured for four human listeners to determine the dependence on tone frequency. At low frequencies, 250–700 Hz, threshold ITDs were approximately inversely proportional to tone frequency. At mid-frequencies, 700–1000 Hz, threshold ITDs were smallest. At high frequencies, above 1000 Hz, thresholds increased faster than exponentially with increasing frequency becoming unmeasurably high just above 1400 Hz. A model for ITD detection began with a biophysically based computational model for a medial superior olive (MSO) neuron that produced robust ITD responses up to 1000 Hz, and demonstrated a dramatic reduction in ITD-dependence from 1000 to 1500 Hz. Rate-ITD functions from the MSO model became inputs to binaural display models—both place based and rate-difference based. A place-based, centroid model with a rigid internal threshold reproduced almost all features of the human data. A signal-detection version of this model reproduced the high-frequency divergence but badly underestimated low-frequency thresholds. A rate-difference model incorporating fast contralateral inhibition reproduced the major features of the human threshold data except for the divergence. A combined, hybrid model could reproduce all the threshold data. PMID:23654390

  16. Evaluation of Bag-Valve-Mask Ventilation in Manikin Studies: What Are the Current Limitations?

    PubMed Central

    Pugin, A.; Pili-Floury, S.; Pazart, L.; Capellier, G.

    2016-01-01

    Introduction. Manikin-based studies for evaluation of ventilation performance show high heterogeneity in the analysis and experimental methods used as we pointed out in previous studies. In this work, we aim to evaluate these potential limitations and propose a new analysis methodology to reliably assess ventilation performance. Methods. One hundred forty healthcare providers were selected to ventilate a manikin with two adult self-inflating bags in random order. Ventilation parameters were analysed using different published analysis methods compared to ours. Results. Using different methods impacts the evaluation of ventilation efficiency which ranges from 0% to 45.71%. Our new method proved relevant and showed that all professionals tend to cause hyperventilation and revealed a significant relationship between professional category, grip strength of the hand keeping the mask, and ventilation performance (p = 0.0049 and p = 0.0297, resp.). Conclusion. Using adequate analysis methods is crucial to avoid many biases. Extrapolations to humans still have to be taken with caution as many factors impact the evaluation of ventilation performance. Healthcare professionals tend to cause hyperventilation with current devices. We believe this problem could be prevented by implementing monitoring tools in order to give direct feedback to healthcare professionals regarding ventilation efficiency and ventilatory parameter values. PMID:27294119

  17. 75 FR 18497 - Guidance on Simultaneous Transmission Import Limit Studies for the Northwest Region; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-12

    ... Energy Regulatory Commission Guidance on Simultaneous Transmission Import Limit Studies for the Northwest... in the Northwest region an opportunity to ask questions regarding the Simultaneous Transmission... on SIL studies \\1\\ and the December 16, 2009 Technical Conference ``Guidance on...

  18. An autoradiographic study of neurotensin receptors in the human hypothalamus.

    PubMed

    Najimi, Mohamed; Sarrieau, Alain; Kopp, Nicolas; Chigr, Fatiha

    2014-03-01

    The aim of the present investigation was to determine a detailed mapping of neurotensin (NT) in the human hypothalamus, the brain region involved in neuroendocrine control. For this, we investigated the presence and the distribution of neurotensin binding sites in the human hypothalamus, using an in vitro quantitative autoradiography technique and the selective radioligand monoiodo-Tyr3-neurotensin (2000Ci/mM). This study was performed on nine adult human postmortem hypothalami. We first determined the biochemical kinetics of the binding and found that binding affinity constants were of high affinity and do not differ significantly between all cases investigated. Our analysis of the autoradiographic distribution shows that NT binding sites are widely distributed throughout the rostrocaudal extent of the hypothalamus. However, the distribution of NT binding sites is not homogenous and regional variations exist. In general, the highest densities are mainly present in the anterior hypothalamic level, particularly in the preoptic region and the anterior boarding limit (i.e. the diagonal band of Broca). Important NT binding site densities are also present at the mediobasal hypothalamic level, particularly in the paraventricular, parafornical and dorsomedial nuclei. At the posterior level, relatively moderate densities could be observed in the mammillary complex subdivisions, apart from the supramammillary nucleus and the posterior hypothalamic area. In conclusion, the present study demonstrates the occurrence of high concentrations of NT binding sites in various structures in many regions in the human adult hypothalamus, involved in the control of neuroendocrine and/or neurovegetative functions.

  19. Suppression of plasma virus load below the detection limit of a human immunodeficiency virus kit is associated with longer virologic response than suppression below the limit of quantitation.

    PubMed

    Raboud, J M; Rae, S; Hogg, R S; Yip, B; Sherlock, C H; Harrigan, P R; O'Shaughnessy, M V; Montaner, J S

    1999-10-01

    Suppression of human immunodeficiency virus type 1 plasma virus load (PVL) to <20 copies/mL is associated with a longer virologic response after initiation of antiretroviral therapy. The relationship between duration of virologic response and PVL nadir according to a less sensitive assay was explored. When compared with subjects with a PVL nadir >500 copies/mL, the relative risks of PVL rising above 1000 copies/mL for participants in the INCAS trial and the British Columbia Drug Treatment Program with a PVL nadir below the limit of detection (LOD) were 0.04 (95% confidence interval [CI], 0.02-0.09) and 0.06 (95% CI, 0.03-0.12), respectively. The corresponding relative risks for persons with a detectable but not quantifiable PVL nadir were 0.25 (95% CI, 0.13-0.50) and 0.54 (95% CI, 0.25-1.19). The relative risks of virologic failure associated with a PVL nadir detectable but not quantifiable and a PVL nadir below the LOD were statistically different (P<.0001) in both data sets.

  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. Limited human-to-human transmission of avian influenza A(H7N9) virus, Shanghai, China, March to April 2013.

    PubMed

    Hu, J; Zhu, Y; Zhao, B; Li, J; Liu, L; Gu, K; Zhang, W; Su, H; Teng, Z; Tang, S; Yuan, Z; Feng, Z; Wu, F

    2014-01-01

    In April 2013, two members of one family were successively confirmed as cases of avian influenza A(H7N9) virus infection in Shanghai, China. Respiratory specimens from the two cases and their close contacts were tested using real-time reverse-transcription (RT)-PCR. Paired serum specimens from contacts were tested by haemagglutination inhibition assay and microneutralisation test. The index patient developed severe pneumonia. Her husband presented with pneumonia shortly thereafter. Both cases had highly similar clinical features and infection with A(H7N9) virus was confirmed in both cases by genetic analysis. Phylogenetic analysis revealed a high level of similarity between the sequences from the two patients and environmental samples collected from wet markets in Minhang and Changning districts. Six samples from the Changning wet market were confirmed as A(H7N9) positive. Of 27 close contacts, one developed mild respiratory symptoms and another tested positive for A(H7N9) antibodies, but both were negative by real-time RT-PCR. The other 25 close contacts of both cases were A(H7N9) negative. Limited human-to-human transmission of the virus most likely occurred in the family cluster. However, other close contacts did not test positive for the virus, suggesting limited potential for extensive human-to-human transmission of the virus.

  2. 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)

  3. 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.

  4. 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.

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

    NASA Astrophysics Data System (ADS)

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

    1993-10-01

    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.

  6. 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…

  7. 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 α-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

  8. Creating humans: an ethical study of human cloning.

    PubMed

    Haman, K H

    2001-01-01

    What does it mean to clone an individual? A clone is created directly from the cells of one individual through several different mechanisms. The most popular of these mechanisms, which created Dolly, is Somatic Cell Nuclear Transfer. It is this type that is predicted to accomplish the feat of cloning a human. With the increasing amount of technology readily available the ethical questions regarding human cloning must be addressed.

  9. 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.

  10. [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" (Körper) and "subjective body" (Leib), and the objectives of medical actions are questioned. Through the terminological differentiation between integrity (Integrität), prosperity (Wohlergehen), and well-being (Wohlbefinden), these objectives are qualified and the limits of medical actions are determined.

  11. "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'.

  12. 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

  13. A demonstration of within-subjects latent inhibition in the human: limitations and advantages.

    PubMed

    Gray, Nicola S; Snowden, Robert J; Peoples, Michelle; Hemsley, David R; Gray, Jeffrey A

    2003-01-01

    The magnitude of latent inhibition (LI) (a retardation of associative learning due to prior exposure to the conditioning stimulus) was measured in healthy volunteers using both a within- and a between-subjects version of the task. Reliable LI was demonstrated for the within-subjects paradigm (using a design that fully counter-balanced stimulus of pre-exposure) but the magnitude of the effect was smaller than for the between-subjects version. Measures of schizotypal personality were found to be associated with reduced LI for the between-subjects task, but not for the within-subjects task. We hypothesised that for the within-subjects task learning about the first stimulus-consequence association (usually that for the not pre-exposed (NPE) stimulus) primes learning about the second stimulus, thus reducing the effect of pre-exposure and restricting the range of LI scores. In turn, this restricted range of LI scores does not allow subtle differences on schizotypal personality dimensions to reveal their effect using this within-subjects paradigm. In conclusion, a within-subjects LI task has been developed which is not open to explanation in terms of differences in stimulus salience. However, the limited range of pre-exposure scores in the current within-subject paradigm may severely limit it is use as an indicator of subtle performance changes.

  14. Potentials and limitations for human control over historic fire regimes in the boreal forest.

    PubMed

    Granström, Anders; Niklasson, Mats

    2008-07-12

    Fire, being both a natural and cultural phenomenon, presents problems in disentangling the historical effect of humans from that of climate change. Here, we investigate the potential impact of humans on boreal fire regimes from a perspective of fuels, ignitions and culture. Two ways for a low technology culture to impact the fire regime are as follows: (i) by altering the number of ignitions and their spatial distribution and timing and (ii) by hindering fire spread. Different cultures should be expected to have quite different impacts on the fire regimes. In northern Fennoscandia, there is evidence for fire regime changes associated with the following: a reindeer herding culture associated with few ignitions above the natural; an era of cattle husbandry with dramatically increased ignitions and somewhat higher fire frequency; and a timber exploitation era with decreasing fire sizes and diminishing fire frequency. In other regions of the boreal zone, such schemes can look quite different, but we suggest that a close look at the resource extraction and land use of different cultures should be part of any analysis of past fire regimes.

  15. Optimizing human apyrase to treat arterial thrombosis and limit reperfusion injury without increasing bleeding risk.

    PubMed

    Moeckel, Douglas; Jeong, Soon Soeg; Sun, Xiaofeng; Broekman, M Johan; Nguyen, Annie; Drosopoulos, Joan H F; Marcus, Aaron J; Robson, Simon C; Chen, Ridong; Abendschein, Dana

    2014-08-01

    In patients with acute myocardial infarction undergoing reperfusion therapy to restore blood flow through blocked arteries, simultaneous inhibition of platelet P2Y12 receptors with the current standard of care neither completely prevents recurrent thrombosis nor provides satisfactory protection against reperfusion injury. Additionally, these antiplatelet drugs increase the risk of bleeding. To devise a different strategy, we engineered and optimized the apyrase activity of human nucleoside triphosphate diphosphohydrolase-3 (CD39L3) to enhance scavenging of extracellular adenosine diphosphate, a predominant ligand of P2Y12 receptors. The resulting recombinant protein, APT102, exhibited greater than four times higher adenosine diphosphatase activity and a 50 times longer plasma half-life than did native apyrase. Treatment with APT102 before coronary fibrinolysis with intravenous recombinant human tissue-type plasminogen activator in conscious dogs completely prevented thrombotic reocclusion and significantly decreased infarction size by 81% without increasing bleeding time. In contrast, clopidogrel did not prevent coronary reocclusion and increased bleeding time. In a murine model of myocardial reperfusion injury caused by transient coronary artery occlusion, APT102 also decreased infarct size by 51%, whereas clopidogrel was not effective. These preclinical data suggest that APT102 should be tested for its ability to safely and effectively maximize the benefits of myocardial reperfusion therapy in patients with arterial thrombosis.

  16. 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

  17. The Limits of Functional Analysis in the Study of Mass Communication.

    ERIC Educational Resources Information Center

    Anderson, James A.; Meyer, Timothy P.

    The fundamental limits of the functional approach to the study of mass communication are embodied in two of its criticisms. The first weakness is in its logical structure and the second involves the limits that are set by known methods. Functional analysis has difficulties as a meaningful research perspective because the process of mass…

  18. The limitations of "vulnerability" as a protection for human research participants.

    PubMed

    Levine, Carol; Faden, Ruth; Grady, Christine; Hammerschmidt, Dale; Eckenwiler, Lisa; Sugarman, Jeremy

    2004-01-01

    Vulnerability is one of the least examined concepts in research ethics. Vulnerability was linked in the Belmont Report to questions of justice in the selection of subjects. Regulations and policy documents regarding the ethical conduct of research have focused on vulnerability in terms of limitations of the capacity to provide informed consent. Other interpretations of vulnerability have emphasized unequal power relationships between politically and economically disadvantaged groups and investigators or sponsors. So many groups are now considered to be vulnerable in the context of research, particularly international research, that the concept has lost force. In addition, classifying groups as vulnerable not only stereotypes them, but also may not reliably protect many individuals from harm. Certain individuals require ongoing protections of the kind already established in law and regulation, but attention must also be focused on characteristics of the research protocol and environment that present ethical challenges.

  19. Passwords Usage and Human Memory Limitations: A Survey across Age and Educational Background

    PubMed Central

    Pilar, Denise Ranghetti; Jaeger, Antonio; Gomes, Carlos F. A.; Stein, Lilian Milnitsky

    2012-01-01

    The present article reports a survey conducted to identify the practices on passwords usage, focusing particularly on memory limitations and the use of passwords across individuals with different age and education backgrounds. A total of 263 participants were interviewed, with ages ranging from 18 to 93 years, and education level ranging from grade school to graduate degree. Contrary to our expectations, effects of cognitive decline due to aging were not observed on memory performance for passwords. The results suggested instead, that the number of password uses was the most influential factor on memory performance. That is, as the number of circumstances in which individuals utilized passwords increased, the incidence of forgotten and mixed-up passwords also increased. The theoretical significance of these findings and their implications for good practices on password usage are discussed. PMID:23227232

  20. Safety, identity and consent: a limited defense of reproductive human cloning.

    PubMed

    Lane, Robert

    2006-06-01

    Some opponents of reproductive human cloning have argued that, because of its experimental nature, any attempt to create a child by way of cloning would risk serious birth defects or genetic abnormalities and would therefore be immoral. Some versions of this argument appeal to the consent of the person to be conceived in this way. In particular, they assume that if an experimental reproductive technology has not yet been shown to be safe, then, before we use it, we are morally obligated to get either the actual consent or the presumed consent of the person to be conceived. In this article, I attempt to explain the appeal of such consent-based arguments as deriving from a mistaken view of personal identity. I then argue that since this view is false, such arguments are unsound. Finally, I argue that even if reproductive cloning is unsafe, it may still be morally permissible in some circumstances.

  1. 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.

  2. 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.

  3. Antibody and T-cell responses associated with experimental human malaria infection or vaccination show limited relationships.

    PubMed

    Walker, Karen M; Okitsu, Shinji; Porter, David W; Duncan, Christopher; Amacker, Mario; Pluschke, Gerd; Cavanagh, David R; Hill, Adrian V S; Todryk, Stephen M

    2015-05-01

    This study examined specific antibody and T-cell responses associated with experimental malaria infection or malaria vaccination, in malaria-naive human volunteers within phase I/IIa vaccine trials, with a view to investigating inter-relationships between these types of response. Malaria infection was via five bites of Plasmodium falciparum-infected mosquitoes, with individuals reaching patent infection by 11-12 days, having harboured four or five blood-stage cycles before drug clearance. Infection elicited a robust antibody response against merozoite surface protein-119 , correlating with parasite load. Classical class switching was seen from an early IgM to an IgG1-dominant response of increasing affinity. Malaria-specific T-cell responses were detected in the form of interferon-γ and interleukin-4 (IL-4) ELIspot, but their magnitude did not correlate with the magnitude of antibody or its avidity, or with parasite load. Different individuals who were immunized with a virosome vaccine comprising influenza antigens combined with P. falciparum antigens, demonstrated pre-existing interferon-γ, IL-2 and IL-5 ELIspot responses against the influenza antigens, and showed boosting of anti-influenza T-cell responses only for IL-5. The large IgG1-dominated anti-parasite responses showed limited correlation with T-cell responses for magnitude or avidity, both parameters being only negatively correlated for IL-5 secretion versus anti-apical membrane antigen-1 antibody titres. Overall, these findings suggest that cognate T-cell responses across a range of magnitudes contribute towards driving potentially effective antibody responses in infection-induced and vaccine-induced immunity against malaria, and their existence during immunization is beneficial, but magnitudes are mostly not inter-related. PMID:25471322

  4. 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

  5. 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.

  6. Human Intestinal Enteroids: a New Model To Study Human Rotavirus Infection, Host Restriction, and Pathophysiology

    PubMed Central

    Saxena, Kapil; Blutt, Sarah E.; Ettayebi, Khalil; Zeng, Xi-Lei; Broughman, James R.; Crawford, Sue E.; Karandikar, Umesh C.; Sastri, Narayan P.; Conner, Margaret E.; Opekun, Antone R.; Graham, David Y.; Qureshi, Waqar; Sherman, Vadim; Foulke-Abel, Jennifer; In, Julie; Kovbasnjuk, Olga; Zachos, Nicholas C.; Donowitz, Mark

    2015-01-01

    ABSTRACT Human gastrointestinal tract research is limited by the paucity of in vitro intestinal cell models that recapitulate the cellular diversity and complex functions of human physiology and disease pathology. Human intestinal enteroid (HIE) cultures contain multiple intestinal epithelial cell types that comprise the intestinal epithelium (enterocytes and goblet, enteroendocrine, and Paneth cells) and are physiologically active based on responses to agonists. We evaluated these nontransformed, three-dimensional HIE cultures as models for pathogenic infections in the small intestine by examining whether HIEs from different regions of the small intestine from different patients are susceptible to human rotavirus (HRV) infection. Little is known about HRVs, as they generally replicate poorly in transformed cell lines, and host range restriction prevents their replication in many animal models, whereas many animal rotaviruses (ARVs) exhibit a broader host range and replicate in mice. Using HRVs, including the Rotarix RV1 vaccine strain, and ARVs, we evaluated host susceptibility, virus production, and cellular responses of HIEs. HRVs infect at higher rates and grow to higher titers than do ARVs. HRVs infect differentiated enterocytes and enteroendocrine cells, and viroplasms and lipid droplets are induced. Heterogeneity in replication was seen in HIEs from different patients. HRV infection and RV enterotoxin treatment of HIEs caused physiological lumenal expansion detected by time-lapse microscopy, recapitulating one of the hallmarks of rotavirus-induced diarrhea. These results demonstrate that HIEs are a novel pathophysiological model that will allow the study of HRV biology, including host restriction, cell type restriction, and virus-induced fluid secretion. IMPORTANCE Our research establishes HIEs as nontransformed cell culture models to understand human intestinal physiology and pathophysiology and the epithelial response, including host restriction of

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

    SciTech Connect

    Ascenzi, Paolo; Gullotta, Francesca; Gioia, Magda; Coletta, Massimo; 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.

  8. 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

  9. Limitations of the clonal agar assay for the assessment of primary human ovarian tumour biopsies.

    PubMed Central

    Bertoncello, I.; Bradley, T. R.; Campbell, J. J.; Day, A. J.; McDonald, I. A.; McLeish, G. R.; Quinn, M. A.; Rome, R.; Hodgson, G. S.

    1982-01-01

    114 biopsy specimens from 70 patients with ovarian carcinoma at all stages of disease were submitted for assessment of clonogenic capacity in agar. A highly significant correlation was found between agar clonogenicity and patient survival after biopsy. However, problems related to inherent tumour heterogeneity, quality of sample and tissue disaggregation indicate that this technique may have limited applicability in the routine assessment of patients. Only 41 biopsy specimens (36%) from 31 patients (44.3%) complied with the prerequisite criteria for agar clonogenic assessment, namely: (a) the confirmed presence of malignant cells in the biopsy, (b) the ability to prepare a single-cell suspension, and (c) adequate viable cell numbers for assay. Furthermore, although the dominant patterns of agar clonogenic growth could be identified and correlated with stage of disease, the heterogeneity in both initial clonogenic capacity and "self-renewal" capacity assessed by the ability of primary clones to propagate in liquid culture and reclone in agar was too inconsistent for the assay to be used as a prognostic index for the individual patient. Images Figure PMID:7093117

  10. 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 für Elektronik und übertragungstechnik 26:189-96(1972) [in German].

  11. 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

  12. Drosophila melanogaster in the study of human neurodegeneration.

    PubMed

    Hirth, Frank

    2010-08-01

    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.

  13. 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.

  14. [Study of the relationship between human quality and reliability].

    PubMed

    Long, S; Wang, C; Wang, L i; Yuan, J; Liu, H; Jiao, X

    1997-02-01

    To clarify the relationship between human quality and reliability, 1925 experiments in 20 subjects were carried out to study the relationship between disposition character, digital memory, graphic memory, multi-reaction time and education level and simulated aircraft operation. Meanwhile, effects of task difficulty and enviromental factor on human reliability were also studied. The results showed that human quality can be predicted and evaluated through experimental methods. The better the human quality, the higher the human reliability. PMID:11539889

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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.

  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. 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…

  2. 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.

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

    PubMed

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

    2015-08-01

    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

  4. 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

  5. A Brief History of Soils and Human Health Studies

    NASA Astrophysics Data System (ADS)

    Brevik, Eric C.; Sauer, Thomas J.

    2013-04-01

    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

  6. Meiosis in a Bottle: New Approaches to Overcome Mammalian Meiocyte Study Limitations

    PubMed Central

    Roig, Ignasi; Brieno-Enriquez, Miguel Angel; Caldes, Montserrat Garcia

    2011-01-01

    The study of meiosis is limited because of the intrinsic nature of gametogenesis in mammals. One way to overcome these limitations would be the use of culture systems that would allow meiotic progression in vitro. There have been some attempts to culture mammalian meiocytes in recent years. In this review we will summarize all the efforts to-date in order to culture mammalian sperm and oocyte precursor cells. PMID:24710142

  7. 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

  8. Human Elimination of Organochlorine Pesticides: Blood, Urine, and Sweat Study

    PubMed Central

    Lane, Kevin; Birkholz, Detlef

    2016-01-01

    Background. Many individuals have been exposed to organochlorinated pesticides (OCPs) through food, water, air, dermal exposure, and/or vertical transmission. Due to enterohepatic reabsorption and affinity to adipose tissue, OCPs are not efficiently eliminated from the human body and may accrue in tissues. Many epidemiological studies demonstrate significant exposure-disease relationships suggesting OCPs can alter metabolic function and potentially lead to illness. There is limited study of interventions to facilitate OCP elimination from the human body. This study explored the efficacy of induced perspiration as a means to eliminate OCPs. Methods. Blood, urine, and sweat (BUS) were collected from 20 individuals. Analysis of 23 OCPs was performed using dual-column gas chromatography with electron-capture detectors. Results. Various OCPs and metabolites, including DDT, DDE, methoxychlor, endrin, and endosulfan sulfate, were excreted into perspiration. Generally, sweat samples showed more frequent OCP detection than serum or urine analysis. Many OCPs were not readily detected in blood testing while still being excreted and identified in sweat. No direct correlation was found among OCP concentrations in the blood, urine, or sweat compartments. Conclusions. Sweat analysis may be useful in detecting some accrued OCPs not found in regular serum testing. Induced perspiration may be a viable clinical tool for eliminating some OCPs. PMID:27800487

  9. 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...

  10. Prodromal Markers in Parkinson's Disease: Limitations in Longitudinal Studies and Lessons Learned.

    PubMed

    Heinzel, Sebastian; Roeben, Benjamin; Ben-Shlomo, Yoav; Lerche, Stefanie; Alves, Guido; Barone, Paolo; Behnke, Stefanie; Berendse, Henk W; Bloem, Bastiaan R; Burn, David; Dodel, Richard; Grosset, Donald G; Hu, Michele; Kasten, Meike; Krüger, Rejko; Moccia, Marcello; Mollenhauer, Brit; Oertel, Wolfgang; Suenkel, Ulrike; Walter, Uwe; Wirdefeldt, Karin; Liepelt-Scarfone, Inga; Maetzler, Walter; Berg, Daniela

    2016-01-01

    A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson's disease (PD). Studies have identified several different prodromal markers that may have the potential to predict the conversion from healthy to clinical PD but use considerably different approaches. We systematically reviewed 35 longitudinal studies reporting prodromal PD features and evaluated the methodological quality across 10 different predefined domains. We found limitations in the following domains: PD diagnosis (57% of studies), prodromal marker assessments (51%), temporal information on prodromal markers or PD diagnosis (34%), generalizability of results (17%), statistical methods (accounting for at least age as confounder; 17%), study design (14%), and sample size (9%). However, no limitations regarding drop-out (or bias investigation), or report of inclusion/exclusion criteria or prodromal marker associations were revealed. Lessons learned from these limitations and additional aspects of current prodromal marker studies in PD are discussed to provide a basis for the evaluation of findings and the improvement of future research in prodromal PD. The observed heterogeneity of studies, limitations and analyses might be addressed in future longitudinal studies using a, yet to be established, modular minimal set of assessments improving comparability of findings and enabling data sharing and combined analyses across studies. PMID:27445791

  11. 78 FR 76888 - MAP-21 Comprehensive Truck Size and Weight Limits Study Materials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-19

    ... legal questions, please contact Michael Harkins, FHWA Office of the Chief Counsel, (202) 366-4928, or by... to deliver this Study to Congress within the required timeframe, the closing date is changed from... for Progress in the 21st Century Act (MAP-21) Comprehensive Truck Size and Weight Limits Study,...

  12. Prodromal Markers in Parkinson’s Disease: Limitations in Longitudinal Studies and Lessons Learned

    PubMed Central

    Heinzel, Sebastian; Roeben, Benjamin; Ben-Shlomo, Yoav; Lerche, Stefanie; Alves, Guido; Barone, Paolo; Behnke, Stefanie; Berendse, Henk W.; Bloem, Bastiaan R.; Burn, David; Dodel, Richard; Grosset, Donald G.; Hu, Michele; Kasten, Meike; Krüger, Rejko; Moccia, Marcello; Mollenhauer, Brit; Oertel, Wolfgang; Suenkel, Ulrike; Walter, Uwe; Wirdefeldt, Karin; Liepelt-Scarfone, Inga; Maetzler, Walter; Berg, Daniela

    2016-01-01

    A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson’s disease (PD). Studies have identified several different prodromal markers that may have the potential to predict the conversion from healthy to clinical PD but use considerably different approaches. We systematically reviewed 35 longitudinal studies reporting prodromal PD features and evaluated the methodological quality across 10 different predefined domains. We found limitations in the following domains: PD diagnosis (57% of studies), prodromal marker assessments (51%), temporal information on prodromal markers or PD diagnosis (34%), generalizability of results (17%), statistical methods (accounting for at least age as confounder; 17%), study design (14%), and sample size (9%). However, no limitations regarding drop-out (or bias investigation), or report of inclusion/exclusion criteria or prodromal marker associations were revealed. Lessons learned from these limitations and additional aspects of current prodromal marker studies in PD are discussed to provide a basis for the evaluation of findings and the improvement of future research in prodromal PD. The observed heterogeneity of studies, limitations and analyses might be addressed in future longitudinal studies using a, yet to be established, modular minimal set of assessments improving comparability of findings and enabling data sharing and combined analyses across studies. PMID:27445791

  13. Introduction: The Humanities and Nontraditional Studies.

    ERIC Educational Resources Information Center

    Burnett, David G.

    1981-01-01

    The difficulty in defining the terms "the humanities" and "nontraditional learners," it is suggested, lies in the breadth of the terms. The programs described involve people who have reached an age of legal and social responsibility and who are exploring the best ideas and things humans have produced. (MLW)

  14. 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.

  15. 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

  16. 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

  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. Studies on Lipolysis in Human Adipose Cells *

    PubMed Central

    Galton, David J.; Bray, George A.

    1967-01-01

    Epinephrine stimulated lipolysis and the uptake of oxygen by subcutaneous adipose cells of man. When glucose-14C was present in the medium, its utilization was not increased by epinephrine, although lipolysis was accelerated. Insulin did not reduce the production of fatty acids that had been stimulated by epinephrine. The combination of human growth hormone and cortisol stimulated the production of fatty acids by isolated human adipose cells to a lesser extent than epinephrine. When human growth hormone or cortisol was used singly, or when bovine growth hormone was added in combination with cortisol, no effect on fatty acid production was observed. Furthermore, an acetone-dried preparation of human pituitary glands, which was shown to stimulate lipolysis in rat adipose cells, had no effect on fatty acid formation in human adipose cells. This suggested that the human pituitary gland contained no more potent lipolytic agents than growth hormone and was supported by the lack of response of human adipose cells to purified corticotropin. PMID:6021210

  19. 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.

  20. Global proficiency study of human papillomavirus genotyping.

    PubMed

    Eklund, Carina; Zhou, Tiequn; Dillner, Joakim

    2010-11-01

    Internationally comparable quality assurance of Human Papillomavirus (HPV) DNA detection and typing methods is essential for evaluation of HPV vaccines and effective monitoring and implementation of HPV vaccination programs. Therefore, the World Health Organization (WHO) HPV Laboratory Network (LabNet) designed an international proficiency study. Following announcement at the WHO website, the responding laboratories performed HPV typing using one or more of their usual assays on 43 coded samples composed of titration series of purified plasmids of 16 HPV types (HPV6, -11, -16, -18, -31, -33, -35, -39, -45, -51, -52, -56, -58, -59, -66, and -68). Detection of at least 50 IU of HPV16 or HPV18 DNA and of 500 genome equivalents (GE) of the other 14 HPV types (in samples with single and multiple HPV types) was considered proficient. Fifty-four laboratories worldwide submitted a total of 84 data sets. More than 21 HPV-genotyping assays were used. Commonly used methods were Linear Array, Lineblot, InnoLiPa, Clinical Array, type-specific real-time PCR, PCR-Luminex and microarray assays. The major oncogenic HPV types (HPV16 and -18) were detected in 89.7% (70/78) and 92.2% (71/77) of the data sets, respectively. HPV types 56, 59, and 68 were the least commonly detected types (in less than 80% of the data sets). Twenty-eight data sets reported multiple false-positive results and were considered nonproficient. In conclusion, we found that international proficiency studies, traceable to international standards, allow standardized quality assurance for different HPV-typing assays and enable the comparison of data generated from different laboratories worldwide.

  1. Maintenance of DNA methylation level in SV40-infected human fibroblasts during their in vitro limited proliferative life span.

    PubMed

    Matsumura, T; Hunter, J L; Farooq, M; Holliday, R

    1989-09-01

    Methylation level as expressed by the molar ratio of 5-methylcytosine content to the combined content of cytosine and 5-methylcytosine was determined by HPLC and uv adsorption of cellular DNA extracted from SV40-infected and pretransformed MRC-5 human diploid fibroblasts (HDFs) during their limited in vitro life span. The level decreased slightly during early passages, and then was maintained within a certain range in the subsequent pretransformed stage of serial passages. When HDFs were treated with 5-aza-2'-deoxycytidine (5-aza-CdR) at an effective concentration shortly after the SV40 infection, the level decreased and then increased or was maintained again within a certain range in the subsequent pretransformed state. The proliferative life span potential of SV40-infected HDFs was not significantly decreased by the 5-aza-CdR treatment. These results are in contrast to the established observations for uninfected HDFs, that methylation level decreases during serial passages, and that, after treatment with 5-aza-CdR, the level, as well as the proliferative life span, is decreased in comparison to untreated populations. These results show that SV40-infected pretransformed HDFs are in an intermediate state between normal finite growth and an established permanent line, in that they retain limited in vitro cell proliferation, while acquiring the ability to maintain methylation levels.

  2. Genetic modeling of ovarian phenotypes in mice for the study of human polycystic ovary syndrome.

    PubMed

    Feng, Yi; Li, Xin; Shao, Ruijin

    2013-01-01

    Polycystic ovary syndrome (PCOS) presents with a range of clinical complications including hyperandrogenism, polycystic ovaries, chronic oligo/anovulation, infertility, and metabolic alterations related to insulin resistance. Because the mechanism by which this disorder develops is poorly understood, information from experimental models of human disease phenotypes may help to define the mechanisms for the initiation and development of PCOS-related pathological events. The establishment of animal models compatible with human PCOS is challenging, and applying the lessons learned from these models to human PCOS is often complicated. In this mini-review we provide examples of currently available genetic mouse models, their ovarian phenotypes, and their possible relationship to different aspects of human PCOS. Because of the practical and ethical limitations of studying PCOS-related events in humans, our understanding of the mechanisms that contribute to the etiology of human PCOS may be enhanced through further study of these transgenic and knockout mouse models. PMID:23390562

  3. A Brief History of Soils and Human Health Studies

    NASA Astrophysics Data System (ADS)

    Brevik, Eric C.; Sauer, Thomas J.

    2013-04-01

    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

  4. 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…

  5. Morphological changes in human and animal enamel rods with heating--especially limits in temperature allowing discrimination between human and animal teeth.

    PubMed

    Yamamoto, K; Ohtani, S; Kato, S; Sugimoto, H; Miake, K; Nakamura, T

    1990-03-01

    Little has been revealed about making discrimination between human and animal using a piece of tooth found in a burned cadaver. From the viewpoint of forensic dental medicine, it is a theme no less valuable. This experimental study was attempted for this reason. Teeth from an individual body of human, monkey, dog, rabbit and rat were heated in turn on the muffle furnace. The heating temperatures were from 200 degrees C to 1,000 degrees C in time spans of 5, 30 and 60 minutes. After heating, each tooth and its control were observed by a scanning electron microscope (magnifying power: 3,500 x or 3,600 x). At heating temperature of 500 degrees C or 600 degrees C, enamel starts to come off in lumps and cracks appear in the enamel rods. The arcaded form in human and monkey, hexagon in dog, elongated chain in rabbit, rows of short, diagonal parallel lines equally directed at every other row in rat--these basic morphological features of the enamel rods--are retained till the heat reaches 700 degrees C. The enamel rods in monkey yield to heat more easily than those in human. At 600 degrees C many cracks appear and deformation of the arcaded form starts. With heating of 5 minutes at 800 degrees C the outline of the pattern is obscured. Human and animal teeth get varied forms of cracks in the enamel rods with heating more than 5 minutes at 800 degrees C. The structure of the enamel rods is broken and morphological characteristics are lost. This makes discrimination of human and animal quite difficult.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2133796

  6. [Melanoma and Human Papillomaviruses: Is There an Outlook for Study?].

    PubMed

    Volgareva, G M; Mikhaylova, I N; Golovina, D A

    2016-01-01

    Melanoma is one of the most aggressive human malignant tumors. Its incidence and mortality are growing steadily. Ultraviolet irradiation is the main risk factor for melanoma involved in melanomagenesis. The probability of viral etiology of melanoma has been discussed. Human papillomaviruses (HPV) have been mentioned among candidates for its etiologic agents because some HPV types are the powerful carcinogens causing cervical cancer and other cancers. The review analyses the literature data on the association of melanoma with HPV Several groupsfound HPVin skin melanomas as well as in mucosa; viruses of high oncogenic risk were detected in some cases. For some organs the etiological role of high-risk HPV as inducers of invasive carcinomas is confirmed. These organs require special mention: cervix uteri, vulva, vagina, penis, anal region, and oral cavity. However in the majority of the studies in which viral DNA-positive melanomas were found, testing for viral genome expression was not done while this is the fact of primary importance. HPVare found in normal skin and mucous membranes thus creating justifiable threat of tumor specimen contamination with viral DNA in vivo. There are limited data on aggravation of the disease prognosis in papillomavirus-positive melanomas. However, any systematic observation of a sizeable patient group distinguished by that tumor type has not been performed yet. Viral E6 and E7 oncogenes of high-risk papillomaviruses were shown to be able to transform normal human melanocytes in vitro experiments. Thus, we can assume the presence of the association of melanoma with oncogenic HPV. The clinical significance of this problem is indisputable under the conditions of the steady increase in melanoma incidence and mortality rates in Russia and abroad. The problem requires further study. PMID:27522713

  7. [Melanoma and Human Papillomaviruses: Is There an Outlook for Study?].

    PubMed

    Volgareva, G M; Mikhaylova, I N; Golovina, D A

    2016-01-01

    Melanoma is one of the most aggressive human malignant tumors. Its incidence and mortality are growing steadily. Ultraviolet irradiation is the main risk factor for melanoma involved in melanomagenesis. The probability of viral etiology of melanoma has been discussed. Human papillomaviruses (HPV) have been mentioned among candidates for its etiologic agents because some HPV types are the powerful carcinogens causing cervical cancer and other cancers. The review analyses the literature data on the association of melanoma with HPV Several groupsfound HPVin skin melanomas as well as in mucosa; viruses of high oncogenic risk were detected in some cases. For some organs the etiological role of high-risk HPV as inducers of invasive carcinomas is confirmed. These organs require special mention: cervix uteri, vulva, vagina, penis, anal region, and oral cavity. However in the majority of the studies in which viral DNA-positive melanomas were found, testing for viral genome expression was not done while this is the fact of primary importance. HPVare found in normal skin and mucous membranes thus creating justifiable threat of tumor specimen contamination with viral DNA in vivo. There are limited data on aggravation of the disease prognosis in papillomavirus-positive melanomas. However, any systematic observation of a sizeable patient group distinguished by that tumor type has not been performed yet. Viral E6 and E7 oncogenes of high-risk papillomaviruses were shown to be able to transform normal human melanocytes in vitro experiments. Thus, we can assume the presence of the association of melanoma with oncogenic HPV. The clinical significance of this problem is indisputable under the conditions of the steady increase in melanoma incidence and mortality rates in Russia and abroad. The problem requires further study.

  8. 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...

  9. 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

  10. 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…

  11. A Study of Mainstreamed Limited English Proficient Handicapped Students in Bilingual Education.

    ERIC Educational Resources Information Center

    Nuttall, Ena Vazquez; And Others

    The study examined mainstreaming efforts for limited English proficient (LEP) handicapped students in a sample of 21 Local Education Agencies (LEAs). Directors and teachers from both the bilingual education and special education departments were interviewed, programs were visited and documents examined. The focus was on three main areas:…

  12. 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…

  13. Effect of Teacher Specialized Training on Limited English Speaking Students' Assessment Outcomes: Quantitative Study

    ERIC Educational Resources Information Center

    Palaroan, Michelle A.

    2009-01-01

    The quantitative study was a comparison of Limited English Proficient (LEP) students' assessment outcomes when taught by a teacher with specialized training and when taught by teachers with no specialized training. The comparison of 2007-2008 Northern Nevada LEP third grade student scores in the content areas of English language arts and…

  14. The Uses and Limitations of Eye-Movement Studies of Reading.

    ERIC Educational Resources Information Center

    Tinker, Miles A.

    Uses and limitations of eye-movement records as measures of reading performance are discussed. Research studies and findings are cited, standards for reliability and validity are given, and types of eye-movement measures are described. Research has demonstrated that eye movements are not causes but symptoms of reading proficiency; therefore,…

  15. 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…

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

    PubMed

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

    2014-09-01

    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.

  17. 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

  18. We "Must" Integrate Human Rights into the Social Studies.

    ERIC Educational Resources Information Center

    O'Brien, Ed

    1999-01-01

    Asserts that educators need to teach about human rights issues, such as social and economic rights, in the social studies curriculum because these issues are disregarded throughout the country. Defines human rights, discusses the importance of the Universal Declaration of Human Rights (UDHR), and provides two lessons. (CMK)

  19. Preliminary Study of Ideal Operational MHD Beta Limit in HL-2A Tokamak Plasmas

    NASA Astrophysics Data System (ADS)

    Shen, Yong; Dong, Jiaqi; He, Hongda; D. Turnbull, A.

    2009-04-01

    Magnetohydrodynamic (MHD) n = 1 kink mode with n the toroidal mode number is studied and the operational beta limit, constrained by the mode, is calculated for the equilibrium of HL-2A by using the GATO code. Approximately the same beta limit is obtained for configurations with a value of the axial safety factor q0 both larger and less than 1. Without the stabilization of the conducting wall, the beta limit is found to be 0.821% corresponding to a normalized beta value of βcN = 2.56 for a typical HL-2A discharge with a plasma current Ip = 0.245 MA, and the scaling of βcN ~constant is confirmed.

  20. 78 FR 71707 - MAP-21 Comprehensive Truck Size and Weight Limits Study Public Meeting and Outreach Sessions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-29

    ... Federal Highway Administration MAP-21 Comprehensive Truck Size and Weight Limits Study Public Meeting and... Century Act (MAP-21) Comprehensive Truck Size and Weight Limits Study. The Transportation Research Board... MAP-21 Comprehensive Truck Size and Weight Limits Study. The DOT will hold a second public...

  1. 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…

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

    NASA Astrophysics Data System (ADS)

    Aslam; Pejović-Milić, 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 4π 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 26Mg(n,γ)27Mg reaction produces γ-rays of 0.843 MeV from the decay of 27Mg, which interfere with the 0.847 MeV γ-rays from the decay of 56Mn, produced by the 55Mn(n,γ)56Mn 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 µg/g Ca. It

  3. 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…

  4. Study of the use of a nonlinear, rate limited, filter on pilot control signals

    NASA Technical Reports Server (NTRS)

    Adams, J. J.

    1977-01-01

    The use of a filter on the pilot's control output could improve the performance of the pilot-aircraft system. What is needed is a filter with a sharp high frequency cut-off, no resonance peak, and a minimum of lag at low frequencies. The present investigation studies the usefulness of a nonlinear, rate limited, filter in performing the needed function. The nonlinear filter is compared with a linear, first order filter, and no filter. An analytical study using pilot models and a simulation study using experienced test pilots was performed. The results showed that the nonlinear filter does promote quick, steady maneuvering. It is shown that the nonlinear filter attenuates the high frequency remnant and adds less phase lag to the low frequency signal than does the linear filter. It is also shown that the rate limit in the nonlinear filter can be set to be too restrictive, causing an unstable pilot-aircraft system response.

  5. Study of target heating induced by fast electrons in mass limited targets

    NASA Astrophysics Data System (ADS)

    Alessio, Morace; Alexander, Magunov; Dimitri, Batani; Renato, Redaelli; Claude, Fourment; Jorge, Santos Joao; Gerard, Malka; Alain, Boscheron; Alexis, Casner; Wigen, Nazarov; Tommaso, Vinci; Yasuaki, Okano; Yuichi, Inubushi; Hiroaki, Nishimura; Alessandro, Flacco; Chris, Spindloe; Martin, Tolley

    2010-02-01

    We studied the induced plasma heating in three different kind of targets: mass limited, foam targets and large mass targets. The experiment was performed at Alisé laser facility of CEA/CESTA. The laser system emitted a ˜1-ps pulse with ˜10 J energy at a wavelength of ˜1 μm. Mass limited targets had three layers with thickness 10 μm C8H8, 1 μm C8H7Cl, 10 μm C8H8 with size 100 μm×100 μm. Detailed spectroscopic analysis of X-rays emitted from the Cl tracer showed that it was possible to heat up the plasma mass limited targets to a temperature ˜250 eV with density ˜1021 cm-3. The plasma heating is only produced by fast electron transport in the target, being the 10 μm C8H8 overcoating thick enough to prevent any possible direct irradiation of the tracer layer even taking into account mass-ablation due to the pre-pulse. These results demonstrate that with mass limited targets is possible to generate a plasma heated up to several hundreds eV. It is also very important for research concerning high energy density phenomena and for fast ignition (in particular for the study of fast electrons transport and induced heating).

  6. Study of target heating induced by fast electrons in mass limited targets

    SciTech Connect

    Alessio, Morace; Dimitri, Batani; Renato, Redaelli; Alexander, Magunov; Claude, Fourment; Jorge, Santos Joao; Gerard, Malka; Alain, Boscheron; Wigen, Nazarov; Tommaso, Vinci; Yasuaki, Okano; Yuichi, Inubushi; Hiroaki, Nishimura; Alessandro, Flacco; Chris, Spindloe; Martin, Tolley

    2010-02-02

    We studied the induced plasma heating in three different kind of targets: mass limited, foam targets and large mass targets. The experiment was performed at Alise laser facility of CEA/CESTA. The laser system emitted a {approx}1-ps pulse with {approx}10 J energy at a wavelength of {approx}1 {mu}m. Mass limited targets had three layers with thickness 10 {mu}m C{sub 8}H{sub 8}, 1 {mu}m C{sub 8}H{sub 7}Cl, 10 {mu}m C{sub 8}H{sub 8} with size 100 {mu}mx100 {mu}m. Detailed spectroscopic analysis of X-rays emitted from the Cl tracer showed that it was possible to heat up the plasma mass limited targets to a temperature {approx}250 eV with density {approx}10{sup 21} cm{sup -3}. The plasma heating is only produced by fast electron transport in the target, being the 10 {mu}m C{sub 8}H{sub 8} overcoating thick enough to prevent any possible direct irradiation of the tracer layer even taking into account mass-ablation due to the pre-pulse. These results demonstrate that with mass limited targets is possible to generate a plasma heated up to several hundreds eV. It is also very important for research concerning high energy density phenomena and for fast ignition (in particular for the study of fast electrons transport and induced heating).

  7. Advantages and Limitations of the Use of Optogenetic Approach in Studying Fast-Scale Spike Encoding

    PubMed Central

    Malyshev, Aleksey; Goz, Roman; LoTurco, Joseph J.; Volgushev, Maxim

    2015-01-01

    Understanding single-neuron computations and encoding performed by spike-generation mechanisms of cortical neurons is one of the central challenges for cell electrophysiology and computational neuroscience. An established paradigm to study spike encoding in controlled conditions in vitro uses intracellular injection of a mixture of signals with fluctuating currents that mimic in vivo-like background activity. However this technique has two serious limitations: it uses current injection, while synaptic activation leads to changes of conductance, and current injection is technically most feasible in the soma, while the vast majority of synaptic inputs are located on the dendrites. Recent progress in optogenetics provides an opportunity to circumvent these limitations. Transgenic expression of light-activated ionic channels, such as Channelrhodopsin2 (ChR2), allows induction of controlled conductance changes even in thin distant dendrites. Here we show that photostimulation provides a useful extension of the tools to study neuronal encoding, but it has its own limitations. Optically induced fluctuating currents have a low cutoff (~70Hz), thus limiting the dynamic range of frequency response of cortical neurons. This leads to severe underestimation of the ability of neurons to phase-lock their firing to high frequency components of the input. This limitation could be worked around by using short (2 ms) light stimuli which produce membrane potential responses resembling EPSPs by their fast onset and prolonged decay kinetics. We show that combining application of short light stimuli to different parts of dendritic tree for mimicking distant EPSCs with somatic injection of fluctuating current that mimics fluctuations of membrane potential in vivo, allowed us to study fast encoding of artificial EPSPs photoinduced at different distances from the soma. We conclude that dendritic photostimulation of ChR2 with short light pulses provides a powerful tool to investigate

  8. 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…

  9. 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

  10. Activation of NF-κB by Human Papillomavirus 16 E1 Limits E1-Dependent Viral Replication through Degradation of E1

    PubMed Central

    Nakahara, Tomomi; Tanaka, Katsuyuki; Ohno, Shin-ichi; Egawa, Nagayasu; Yugawa, Takashi

    2015-01-01

    ABSTRACT NF-κB is a family of transcription factors that regulate gene expression involved in many processes, such as the inflammatory response and cancer progression. Little is known about associations of NF-κB with the human papillomavirus (HPV) life cycle. We have developed a tissue culture system to conditionally induce E1-dependent replication of the human papillomavirus 16 (HPV16) genome in human cervical keratinocytes and found that expression of HPV16 E1, a viral helicase, results in reduction of IκBα and subsequent activation of NF-κB in a manner dependent on helicase activity. Exogenous expression of a degradation-resistant mutant of IκBα, which inhibits the activation of NF-κB, enhanced E1-dependent replication of the viral genome. Wortmannin, a broad inhibitor of phosphoinositide 3-kinases (PI3Ks), and, to a lesser extent, VE-822, an ATR kinase inhibitor, but not KU55933, an ATM kinase inhibitor, suppressed the activation of NF-κB and augmented E1-dependent replication of the HPV16 genome. Interestingly, the enhancement of E1-dependent replication of the viral genome was associated with increased stability of E1 in the presence of wortmannin as well as the IκBα mutant. Collectively, we propose that expression of E1 induces NF-κB activation at least in part through the ATR-dependent DNA damage response and that NF-κB in turn limits E1-dependent replication of HPV16 through degradation of E1, so that E1 and NF-κB may constitute a negative feedback loop. IMPORTANCE A major risk factor in human papillomavirus (HPV)-associated cancers is persistent infection with high-risk HPVs. To eradicate viruses from infected tissue, it is important to understand molecular mechanisms underlying the establishment and maintenance of persistent infection. In this study, we obtained evidence that human papillomavirus 16 (HPV16) E1, a viral DNA helicase essential for amplification of the viral genomes, induces NF-κB activation and that this limits E1-dependent

  11. 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.

  12. Preliminary Study of Open Quotient in an Ex-Vivo Perfused Human Larynx Model

    PubMed Central

    Mendelsohn, Abie H.; Zhang, Zhaoyan; Luegmair, Georg; Orestes, Michael; Berke, Gerald S.

    2016-01-01

    Importance Scientific understanding human voice production to date is a product of indirect investigations including animal models, cadaveric tissue study, or computational modeling. Due to its invasive nature, direct experimentation of human voice production has previously not been possible. The feasibility of an ex-vivo perfused human phonatory model has recently allowed systematic investigation in virtually living human larynges with parametric laryngeal muscle stimulation. Objective In this study, the relationship between adductor muscle group stimulation and the open quotient (OQ) of vocal fold vibration was investigated using an ex-vivo perfused human larynx. Design Human perfused tissue study. Setting Physiology Laboratory. Participants Human larynx is recovered from research-consented organ donors within two hours of cardiac death. Interventions, Main Outcomes and Measures Perfusion with donated human blood is re-established shortly after cardiac death. Human perfused phonation is achieved by providing subglottal airflow under graded neuromuscular electrical stimulation bilaterally to the intrinsic adductor groups and cricothyroid muscles. The phonation resulting from the graded states of neuromuscular stimulations are evaluated through high-speed vibratory imaging. OQ is derived through digital kymography and glottal area waveform analysis. Results Under constant glottal flow, step-wise increase in adductor muscle group stimulation decreased OQ. Quantitatively, OQ values reached a lower limit of 0.42. Increased stimulation above maximal muscle deformation was unable to affect OQ beyond this lower limit. Conclusions and Relevance For the first time in a neuromuscularly activated human larynx, a negative relationship between adductor muscle group stimulation and phonatory OQ was demonstrated. Further experience with the ex-vivo perfused human phonatory model will work to systematically define this causal relationship. PMID:26181642

  13. 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.

  14. 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.

  15. Picosecond optical limiting in reverse saturable absorbers: a theoretical and experimental study

    NASA Astrophysics Data System (ADS)

    Lepkowicz, Richard; Kobyakov, Andrey; Hagan, David J.; van Stryland, Eric W.

    2002-01-01

    We theoretically and experimentally study absorption of picosecond laser pulses in materials described by a four-level system that exhibit reverse saturable absorption (RSA). Using an approximate solution to the rate equations, we derive, analyze, and verify, numerically and experimentally, a single dynamical equation for the spatial evolution of the pulse fluence that includes both the rate equations and the propagation equation. This analytical approach considerably simplifies the study of optical limiting with picosecond pulses and helps to predict the behavior of the nonlinear transmittance, the level of output signal clamping, and a possible turnover from RSA to saturable absorption that restricts the performance of optical limiters based on RSA. The results obtained can also be used to characterize RSA materials by the pump-probe technique.

  16. Load transmission characteristics of limited carpal fusions: a two-dimensional finite element study.

    PubMed

    Bicen, A C; Gokdemir, H; Seber, S; Aydin, R; Gunal, I

    2015-02-01

    Although limited carpal fusion is a choice of treatment in several wrist disorders, little is known about the biomechanics of these procedures, especially the loads carried by the ligaments. In a finite element study, four types of limited carpal fusions (scaphotrapeziotrapezoid, capitohamate, four corner fusion with and without scaphoid excision) were simulated and the loads carried by the ligaments were recorded. Measurements were repeated with and without implantation. The load transmission through the ligaments varied by the type of the fusion but, radioscaphoid and long radiolunate ligaments carried significantly more loads if not excised during the operation. Implantation did not affect the results in most cases. The model of the present study may be useful in preoperative planning.

  17. Recognizing the Limitations of Cancer Overdiagnosis Studies: A First Step Towards Overcoming Them.

    PubMed

    Etzioni, Ruth; Gulati, Roman

    2016-03-01

    Numerous studies have attempted to quantify the number of breast cancers that would never have been diagnosed in the absence of screening. Unfortunately, results are highly variable across studies and there is considerable disagreement about both the frequency of overdiagnosis and the validity of different methodologic approaches. In this Commentary, we review limitations of the two major approaches used in existing studies. Studies that use excess incidence as a proxy for overdiagnosis require a valid estimate of incidence in the absence of screening and sufficient follow-up to ensure the excess excludes relevant (ie, nonoverdiagnosed) cancers detected early. The requirement of sufficient follow-up applies to both population studies and clinical trials, but only certain clinical trial designs have the potential to yield unbiased results. Studies that model disease natural history to infer overdiagnosis must, in addition, examine whether their models produce valid estimates in the presence of nonprogressive cases. In this setting, limited follow-up could lead to a lack of identifiability of the parameters needed to accurately infer overdiagnosis. In a polarized research community, the excess incidence and modeling approaches are generally viewed as competitors, but we argue that they are complementary, with models being more complex but having greater potential to inform about disease natural history and the outcomes of candidate screening policies. Rather than arguing why one approach should be preferred to another, investigators should focus on developing studies that generate reliable estimates of overdiagnosis. Recognizing that both approaches have limitations, which existing studies rarely overcome, is a first step towards reconciling methodologic perspectives and achieving consensus about the real magnitude of the overdiagnosis problem.

  18. 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…

  19. 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.

  20. 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

  1. 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

  2. Application of chimeric mice with humanized liver for study of human-specific drug metabolism.

    PubMed

    Bateman, Thomas J; Reddy, Vijay G B; Kakuni, Masakazu; Morikawa, Yoshio; Kumar, Sanjeev

    2014-06-01

    Human-specific or disproportionately abundant human metabolites of drug candidates that are not adequately formed and qualified in preclinical safety assessment species pose an important drug development challenge. Furthermore, the overall metabolic profile of drug candidates in humans is an important determinant of their drug-drug interaction susceptibility. These risks can be effectively assessed and/or mitigated if human metabolic profile of the drug candidate could reliably be determined in early development. However, currently available in vitro human models (e.g., liver microsomes, hepatocytes) are often inadequate in this regard. Furthermore, the conduct of definitive radiolabeled human ADME studies is an expensive and time-consuming endeavor that is more suited for later in development when the risk of failure has been reduced. We evaluated a recently developed chimeric mouse model with humanized liver on uPA/SCID background for its ability to predict human disposition of four model drugs (lamotrigine, diclofenac, MRK-A, and propafenone) that are known to exhibit human-specific metabolism. The results from these studies demonstrate that chimeric mice were able to reproduce the human-specific metabolite profile for lamotrigine, diclofenac, and MRK-A. In the case of propafenone, however, the human-specific metabolism was not detected as a predominant pathway, and the metabolite profiles in native and humanized mice were similar; this was attributed to the presence of residual highly active propafenone-metabolizing mouse enzymes in chimeric mice. Overall, the data indicate that the chimeric mice with humanized liver have the potential to be a useful tool for the prediction of human-specific metabolism of xenobiotics and warrant further investigation.

  3. Studies of human pancreatic elastase treatment of rabbit and human vein rings to predict human therapeutic doses.

    PubMed

    Burke, Steven K; Bunton, David; Bingham, Karen; Moss, Emma; Bland, Kimberly S; Starcher, Barry; Wong, Marco D; Franano, F Nicholas

    2016-06-01

    Vascular tissue contains abundant elastic fibers that contribute to vessel elasticity. Vonapanitase (formerly PRT-201) is a recombinant human chymotrypsin-like elastase family member 1 (CELA1) shown to cleave the elastin component of elastic fibers, resulting in increased vessel diameter. The purpose of these current studies was to determine vein diameter, wall thickness, elastin content, and vonapanitase potency in veins used in a model of arteriovenous fistula (AVF) and in patients undergoing AVF creation for hemodialysis access to guide dose selection for human trials. Rabbit linguofacial, maxillary, and external jugular veins, and human basilic and upper and lower arm cephalic veins were dissected postmortem and sectioned into 2 mm length rings. Rings were incubated in vonapanitase at 37°C at varying concentrations and times. Elastin content was estimated histologically and by quantifying desmosine, a protein cross-link unique to elastin. Rabbit veins were substantially thinner and contained less elastin than human veins. In human veins, elastin content was greatest in basilic and least in lower arm cephalic. Vonapanitase removed elastin in a time- and concentration-dependent manner in all vein types. A lower concentration of vonapanitase was required to remove elastin from rabbit relative to human veins. In summary, vonapanitase reduced the elastin content of rabbit and human veins but did so at a lower concentration in the rabbit veins. Rabbit models may overestimate the potency of vonapanitase in humans. These results indicate that human dose selection should be guided by human vein ring experiments. PMID:27433340

  4. Muscle pain: animal and human experimental and clinical studies.

    PubMed

    Marchettini, P

    1993-10-01

    The search for the identification of the sensory apparatus encoding muscle pain sensation in humans is recounted. Basic neurophysiologic animal studies, leading to a description of slowly conducting afferent from muscle and definition of high threshold polymodal muscle nociceptors, and pioneer psychophysic human studies together with recent microneurographic experiments in humans are described. The phenomena of muscle pain broad localization and distant referral are discussed, and clinical implications are extrapolated to interpret muscle pain as a localizing sign of mononeuropathy or radiculopathy. The identification of human muscle nociceptors has defined the scientific standard to test emerging clinical descriptions having muscle pain as a symptom.

  5. 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.

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

    PubMed

    Dillmann, Christina; Ringel, Christian; Ringleb, Julia; Mora, Javier; Olesch, Catherine; Fink, Annika F; Roberts, Edward; Brüne, 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-α 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-α production. This is antagonized by S1PR4 signaling, thus decreasing TLR-induced IFN-α secretion. At a functional level, attenuated IFN-α 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-γ) 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-α production. PMID:26783340

  7. The background-limited infrared-submillimeter spectrograph (BLISS) for SPICA: a design study

    NASA Astrophysics Data System (ADS)

    Bradford, C. M.; Bock, James; Holmes, Warren; Kenyon, M.; Beyer, A.; Werner, M.; Rud, M.; Prouvé, T.; Echternach, P.; Irwin, K.; Cho, S.; Harwit, M.; Stacey, G.; Helou, G.; Armus, L.; Appleton, P.; Smith, J. D.; Gorti, U.; Rieke, G.; Egami, E.; Lester, D.; Glenn, J.; Malkan, M.; Dale, D.

    2010-07-01

    We are developing the Background-Limited Infrared-Submillimeter Spectrograph (BLISS) for SPICA to provide a breakthrough capability for far-IR survey spectroscopy. SPICAs large cold aperture allows mid-IR to submm observations which are limited only by the natural backgrounds, and BLISS is designed to operate near this fundamental limit. BLISS-SPICA is 6 orders of magnitude faster than the spectrometers on Herschel and SOFIA in obtaining full-band spectra. It enables spectroscopy of dust-obscured galaxies at all epochs back to the rst billion years after the Big Bang (redshift 6), and study of all stages of planet formation in circumstellar disks. BLISS covers 35 - 433 microns range in ve or six wavelength bands, and couples two 2 sky positions simultaneously. The instrument is cooled to 50 mK for optimal sensitivity with an on-board refrigerators. 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 technical elements of BLISS have heritage in mature scientic instruments, and many have own. We report on our design study in which we are optimizing performance while accommodating SPICAs constraints, including the stringent cryogenic mass budget. In particular, we present our progress in the optical design and waveguide spectrometer prototyping. A companion paper in Conference 7741 (Beyer et al.) discusses in greater detail the progress in the BLISS TES bolometer development.

  8. 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

  9. A study of nonflammable gas mixtures for limited streamer tubes in the VENUS detector at TRISTAN

    NASA Astrophysics Data System (ADS)

    Uebayashi, T.; Haba, J.; Kamitani, T.; Kanematsu, N.; Nagashima, Y.; Osabe, H.; Sakamoto, S.; Sugimoto, S.; Suzuki, Y.; Tsukamoto, A.; Yamashita, Y.; Sumiyoshi, T.; Takasaki, F.; Homma, Y.; Hojyo, Y.; Sakae, H.

    1988-03-01

    Performances of limited streamer tubes operated with nonflammable gas mixtures composed of argon (Ar), carbon-dioxide (CO2) and isobutane (i-C4H10) with ratios of 1:1.5:0.15, 1:2:0.2, 1:3:0.3, 1:4:0.4 and 1:6:0.6 were studied. It was found that these mixtures were very suitable for the VENUS detector. The charge spectra exhibited very sharp distributions and indicated the possibility for the limited streamer tubes to be applied to calorimetry use. A mixture of 1:2:0.2 was chosen for the VENUS streamer tubes because of its moderate gain and long efficiency plateau.

  10. A study of nonflammable gas mixtures for limited streamer tubes in the VENUS detector at TRISTAN

    NASA Astrophysics Data System (ADS)

    Uebayashi, T.; Haba, J.; Kamitani, T.; Kanematsu, N.; Nagashima, Y.; Osabe, H.; Sakamoto, S.; Sugimoto, S.; Suzuki, Y.; Tsukamoto, A.; Yamashita, Y.; Sumiyoshi, T.; Takasaki, F.; Homma, Y.; Hojyo, Y.; Sakae, H.

    1998-03-01

    Performances of limited streamer tubes operated with nonflammable gas mixtures composed of argon (Ar), carbon-dioxide (CO2) and isobutane (i-C4H10) with ratios of 1:1.5:0.15, 1:2:0.2, 1:3:0.3, 1:4:0.4 and 1:6:0.6 were studied. It was found that these mixtures were very suitable for the VENUS detector. The charge spectra exhibited very sharp distributions and indicated the possibility for the limited streamer tubes to be applied to calorimetry use. A mixture of 1:2:0.2 was chosen for the VENUS streamer tubes because of its moderate gain and long efficiency plateau.

  11. Studies on the tolerance limit of fluoride in food in China

    SciTech Connect

    Chen, S.L.; Gong, Y.J.; Fu, Y.G. )

    1988-10-01

    To estimate the appropriate tolerance limit of fluoride in food in China, fluoride-related endemic diseases, background levels of fluoride in foods, and daily total intake of fluoride per capita were studied in addition to the subchronic toxicity test of fluoride in rats. In the general population, the daily total intake of fluoride from food, water, and air is 1.45-3.15 mg per capita. On the basis of these results and other information, it is suggested that the ADI of fluoride in the Chinese population should be 3.5 mg per capita, or 0.058 mg/kg body wt, and the tolerance limit of fluoride should be 1.0 ppm in rice, wheat flour, vegetables, and freshwater fish.

  12. Exploring the limits of trigonometric functions: results and reflections from a pilot study

    NASA Astrophysics Data System (ADS)

    Man, Yiu-Kwong; Poon, Kin-Keung

    2014-02-01

    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 basic concepts of limits, but had room for further improvement in those that required them to explain their answers. An analysis of the students' performances in the tests by using the APOS (i.e. action-process-object-schema) theory framework is reported. Reflections and suggestions on how to teach the topic more effectively are provided.

  13. 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

  14. Limited Protection from a Pathogenic Chimeric Simian-Human Immunodeficiency Virus Challenge following Immunization with Attenuated Simian Immunodeficiency Virus

    PubMed Central

    Lewis, Mark G.; Yalley-Ogunro, Jake; Greenhouse, Jack J.; Brennan, Terry P.; Jiang, Jennifer Bo; VanCott, Thomas C.; Lu, Yichen; Eddy, Gerald A.; Birx, Deborah L.

    1999-01-01

    Two live attenuated single-deletion mutant simian immunodeficiency virus (SIV) constructs, SIV239Δnef and SIVPBj6.6Δnef, were tested for their abilities to stimulate protective immunity in macaques. During the immunization period the animals were examined for specific immune responses and virus growth. Each construct generated high levels of specific immunity in all of the immunized animals. The SIV239Δnef construct was found to grow to high levels in all immunized animals, with some animals remaining positive for virus isolation and plasma RNA throughout the immunization period. The SIVPBj6.6Δnef was effectively controlled by all of the immunized animals, with virus mostly isolated only during the first few months following immunization and plasma RNA never detected. Following an extended period of immunization of over 80 weeks, the animals were challenged with a pathogenic simian-human immunodeficiency virus (SHIV) isolate, SIV89.6PD, by intravenous injection. All of the SIV239Δnef-immunized animals became infected with the SHIV isolate; two of five animals eventually controlled the challenge and three of five animals, which failed to check the immunizing virus, progressed to disease state before the unvaccinated controls. One of five animals immunized with SIVPBj6.6Δnef totally resisted infection by the challenge virus, while three others limited its growth and the remaining animal became persistently infected and eventually died of a pulmonary thrombus. These data indicate that vaccination with attenuated SIV can protect macaques from disease and in some cases from infection by a divergent SHIV. However, if animals are unable to control the immunizing virus, potential damage that can accelerate the disease course of a pathogenic challenge virus may occur. PMID:9882330

  15. Alterations in Gene Expression of Proprotein Convertases in Human Lung Cancer Have a Limited Number of Scenarios

    PubMed Central

    Demidyuk, Ilya V.; Shubin, Andrey V.; Gasanov, Eugene V.; Kurinov, Alexander M.; Demkin, Vladimir V.; Vinogradova, Tatyana V.; Zinovyeva, Marina V.; Sass, Alexander V.; Zborovskaya, Irina B.; Kostrov, Sergey V.

    2013-01-01

    Proprotein convertases (PCs) is a protein family which includes nine highly specific subtilisin-like serine endopeptidases in mammals. The system of PCs is involved in carcinogenesis and levels of PC mRNAs alter in cancer, which suggests expression status of PCs as a possible marker for cancer typing and prognosis. The goal of this work was to assess the information value of expression profiling of PC genes. Quantitative polymerase chain reaction was used for the first time to analyze mRNA levels of all PC genes as well as matrix metalloproteinase genes MMP2 and MMP14, which are substrates of PCs, in 30 matched pairs of samples of human lung cancer tumor and adjacent tissues without pathology. Significant changes in the expression of PCs have been revealed in tumor tissues: increased FURIN mRNA level (p<0.00005) and decreased mRNA levels of PCSK2 (p<0.007), PCSK5 (p<0.0002), PCSK7 (p<0.002), PCSK9 (p<0.00008), and MBTPS1 (p<0.00004) as well as a tendency to increase in the level of PCSK1 mRNA. Four distinct groups of samples have been identified by cluster analysis of the expression patterns of PC genes in tumor vs. normal tissue. Three of these groups covering 80% of samples feature a strong elevation in the expression of a single gene in cancer: FURIN, PCSK1, or PCSK6. Thus, the changes in the expression of PC genes have a limited number of scenarios, which may reflect different pathways of tumor development and cryptic features of tumors. This finding allows to consider the mRNAs of PC genes as potentially important tumor markers. PMID:23409034

  16. 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 baclofen’s 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, baclofen’s effects to increase alcohol sedation and to reduce alcohol consumption were limited to those individuals with DRD4 ≥7 repeats (DRD4L). Yet, baclofen’s effects on alcohol consumption were also moderated by 5-HTTLPR LL genotype. In conclusion, baclofen’s 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

  17. A comparative study of the trabecular bony architecture of the talus in humans, non-human primates, and Australopithecus.

    PubMed

    DeSilva, Jeremy M; Devlin, Maureen J

    2012-09-01

    This study tested the hypothesis that talar trabecular microarchitecture reflects the loading patterns in the primate ankle joint, to determine whether talar trabecular morphology might be useful for inferring locomotor behavior in fossil hominins. Trabecular microarchitecture was quantified in the anteromedial, anterolateral, posteromedial, and posterolateral quadrants of the talar body in humans and non-human primates using micro-computed tomography. Trabecular bone parameters, including bone volume fraction, trabecular number and thickness, and degree of anisotropy differed between primates, but not in a manner entirely consistent with hypotheses derived from locomotor kinematics. Humans have highly organized trabecular struts across the entirety of the talus, consistent with the compressive loads incurred during bipedal walking. Chimpanzees possess a high bone volume fraction, consisting of plate-like trabecular struts. Orangutan tali are filled with a high number of thin, connected trabeculae, particularly in the anterior portion of the talus. Gorillas and baboons have strikingly similar internal architecture of the talus. Intraspecific analyses revealed no regional differences in trabecular architecture unique to bipedal humans. Of the 22 statistically significant regional differences in the human talus, all can also be found in other primates. Trabecular thickness, number, spacing, and connectivity density had the same regional relationship in the talus of humans, chimpanzees, gorillas, and baboons, suggesting a deeply conserved architecture in the primate talus. Australopithecus tali are human-like in most respects, differing most notably in having more oriented struts in the posteromedial quadrant of the body compared with the posterolateral quadrant. Though this result could mean that australopiths loaded their ankles in a unique manner during bipedal gait, the regional variation in degree of anisotropy was similar in humans, chimpanzees, and gorillas

  18. 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.

  19. Intratumoral spread of wild-type adenovirus is limited after local injection of human xenograft tumors: virus persists and spreads systemically at late time points.

    PubMed

    Sauthoff, Harald; Hu, Jing; Maca, Cielo; Goldman, Michael; Heitner, Sheila; Yee, Herman; Pipiya, Teona; Rom, William N; Hay, John G

    2003-03-20

    Oncolytic replicating adenoviruses are a promising new modality for the treatment of cancer. Despite the assumed biologic advantage of continued viral replication and spread from infected to uninfected cancer cells, early clinical trials demonstrate that the efficacy of current vectors is limited. In xenograft tumor models using immune-incompetent mice, wild-type adenovirus is also rarely able to eradicate established tumors. This suggests that innate immune mechanisms may clear the virus or that barriers within the tumor prevent viral spread. The aim of this study was to evaluate the kinetics of viral distribution and spread after intratumoral injection of virus in a human tumor xenograft model. After intratumoral injection of wild-type virus, high levels of titratable virus persisted within the xenograft tumors for at least 8 weeks. Virus distribution within the tumors as determined by immunohistochemistry was patchy, and virus-infected cells appeared to be flanked by tumor necrosis and connective tissue. The close proximity of virus-infected cells to the tumor-supporting structure, which is of murine origin, was clearly demonstrated using a DNA probe that specifically hybridizes to the B1 murine DNA repeat. Importantly, although virus was cleared from the circulation 6 hr after intratumoral injection, after 4 weeks systemic spread of virus was detected. In addition, vessels of infected tumors were surrounded by necrosis and an advancing rim of virus-infected tumor cells, suggesting reinfection of the xenograft tumor through the vasculature. These data suggest that human adenoviral spread within tumor xenografts is impaired by murine tumor-supporting structures. In addition, there is evidence for continued viral replication within the tumor, with subsequent systemic dissemination and reinfection of tumors via the tumor vasculature. Despite the limitations of immune-incompetent models, an understanding of the interactions between the virus and the tumor

  20. 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…

  1. Lack of blood formate accumulation in humans following exposure to methanol vapor at the current permissible exposure limit of 200 ppm

    SciTech Connect

    Lee, E.W.; Terzo, T.S.; D'Arcy, J.B.; Gross, K.B.; Schreck, R.M. )

    1992-02-01

    Accumulation of formate, the putative toxic metabolite of methanol, in the blood and the relationship between pulmonary intake and blood methanol concentration were investigated in six human volunteers following a 6-hr exposure to 200 ppm methanol (the current Occupational Safety and Health Administration 8-hr time-weighted average permissible exposure limit). At the end of a 6-hr exposure to 200 ppm methanol at rest, the blood methanol concentration was increased from a mean of 1.8 micrograms/mL to 7.0 micrograms/mL. Under light exercise, the total amount of methanol inhaled during the 6-hr exposure period was 1.8 times that inhaled at rest. However, no statistically significant increase in blood methanol concentration was observed under exercise: the concentrations averaged 8.1 micrograms/mL. Formate did not accumulate in the blood above its background level following the 6-hr exposures to 200 ppm methanol whether subjects were exposed at rest or during exercise. Unlike the data collected from epidemiologic studies, the authors' results were obtained under well-controlled methanol exposure conditions and by using appropriate dietary restrictions. The data show that (1) the biological load of methanol would be the same regardless of whether workers are engaged in light physical activity when they are exposed to methanol vapors below 200 ppm and (2) the formate that is associated with acute methanol toxicities in humans does not accumulate in blood when methanol exposure concentrations are below 200 ppm.

  2. Comparative study of limited intentional normovolaemic haemodilution in patients with left main coronary artery stenosis.

    PubMed

    Herregods, L; Foubert, L; Moerman, A; François, K; Rolly, G

    1995-11-01

    Intentional normovolaemic haemodilution is a blood saving technique which can be performed when major blood loss is expected. Severe coronary artery disease and particularly left main stenosis are considered a contraindication for intentional normovolaemic haemodilution. The effects and complications of limited intentional normovolaemic haemodilution in patients with left main coronary artery stenosis scheduled for coronary artery bypass grafting were evaluated. Patients were randomly allocated to two groups: group A (n = 15) underwent limited intentional normovolaemic haemodilution to a haematocrit of 34%; group B (n = 15), no intentional normovolaemic haemodilution was performed. In both groups succinyl-linked gelatin was used to maintain normovolaemia. Haemodynamic parameters were kept as constant as possible. In group A, a mean (SD) volume of 785 (250) ml of blood was withdrawn [range 500-1200 ml]. ST segment changes occurred on the ECG in three patients in each group. There were no statistically significant differences for frequency, maximum deflection and duration of ST-segment changes. Limited intentional normovolaemic haemodilution can be performed safely in patients with left main coronary artery stenosis. In this study it was not associated with increased frequency, severity or duration of ST-segment changes, or with arrhythmias or haemodynamic instability.

  3. The studies on radiological limits of color-glazed tiles used in home decoration.

    PubMed

    Yahong, Mao; Yigang, Liu; Guang, Zhang; Xiaolei, Hu

    2002-04-01

    This study was carried out to lay down the radiological limits of color-glazed tiles used in home decoration. The activity concentrations of various end products and raw materials as well as processed materials were measured using gamma spectroscopy. 222Rn exhalation rates from the surface of color-glazed tiles were measured using charcoal canister method. Levels of exposure to alpha ray and beta ray from the surface of glazed tiles were measured by surface alpha and beta contaminant instrument. The results show a great difference between the radioactive levels of the surface glaze and the matrix of color-glazed tiles. The 222Rn exhalation rates from the surface of color-glazed tiles are in the range of 10(-3) - 10(-4) Bq m(-2) s(-1). The concentrations of some natural radionuclides in glaze exceed the exempt limits of International Basic Safety Standards for Protection against Ionizing Radiation Sources (IAEA 1997). The limits for color-glazed tiles were deduced according to these data and the theory of UNSCEAR (1993). The activity concentration of 226Ra (Bq kg(-1)) in the glaze of color-glazed tiles should be in the range of A(226Ra) < or = 1,000 (Bq kg(-1)), and, at the same time, the specific activity of the natural radionuclides (Bq kg(-1)) should be in the range of A(232Th)/230 + A(226Ra)/310 + A(40K)/3,500 < or = 1. PMID:11906139

  4. 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.

  5. 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.

  6. Capability and limitation study of the DDT passive-active neutron waste assay instrument

    SciTech Connect

    Nicholas, N.J.; Coop, K.L.; Estep, R.J.

    1992-05-01

    The differential-dieaway-technique passive-active neutron assay system is widely used by transuranic waste generators to certify their drummed waste for eventual shipment to the Waste Isolation Pilot Plant (WIPP). Stricter criteria being established for waste emplacement at the WIPP site has led to a renewed interest in improvements to and a better understanding of current nondestructive assay (NDA) techniques. Our study includes the effects of source position, extreme matrices, high neutron backgrounds, and source self-shielding to explore the system`s capabilities and limitations and to establish a basis for comparison with other NDA systems. 11 refs.

  7. Capability and limitation study of the DDT passive-active neutron waste assay instrument

    SciTech Connect

    Nicholas, N.J.; Coop, K.L.; Estep, R.J.

    1992-05-01

    The differential-dieaway-technique passive-active neutron assay system is widely used by transuranic waste generators to certify their drummed waste for eventual shipment to the Waste Isolation Pilot Plant (WIPP). Stricter criteria being established for waste emplacement at the WIPP site has led to a renewed interest in improvements to and a better understanding of current nondestructive assay (NDA) techniques. Our study includes the effects of source position, extreme matrices, high neutron backgrounds, and source self-shielding to explore the system's capabilities and limitations and to establish a basis for comparison with other NDA systems. 11 refs.

  8. 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...

  9. 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...

  10. 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...

  11. 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...

  12. 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...

  13. 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…

  14. 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.…

  15. Quantitative detection of RT activity by PERT assay: feasibility and limits to a standardized screening assay for human vaccines.

    PubMed

    André, M; Morgeaux, S; Fuchs, F

    2000-06-01

    The detection of adventitious retroviruses has always been critical for assessing the safety concerns associated with viral vaccines. Assays for the enzymatic activity of reverse transcriptase (RT) are used as general methods for the detection of both known and unknown retroviruses. Several studies using newly-developed ultrasensitive PCR-based RT assays reported RT activity in viral vaccines grown in chicken cells. Here, we have assessed the performances of such a PCR-based RT assay--PERT assay--for the quantitative detection of RT activity in vaccines. Sensitivity, linearity and reproducibility of the method were studied on purified RT and viral vaccines treated to release RT from potentially contaminant retroviruses. The level of RT activity detected in chicken cell-derived vaccines was higher for live attenuated vaccines compared to inactivated ones. Contrary to other studies, RT activity was found in some mammalian cell-derived vaccines. AZT-TP sensitivity of RT activities detected in these vaccines and discrimination between retroviral and RT-like activities was further investigated. Feasibility and limits of PERT assay as a broad-spectrum retroviruses detection method in vaccines are discussed.

  16. All humanity is my ingroup: a measure and studies of identification with all humanity.

    PubMed

    McFarland, Sam; Webb, Matthew; Brown, Derek

    2012-11-01

    To psychologists Adler (1927/1954) and Maslow (1954), fully mature individuals care deeply for all humanity, not just for their own ingroups. This paper reports a series of studies with a new measure of that caring, the Identification With All Humanity Scale (IWAH). These studies together show that identification with all humanity is more than an absence of ethnocentrism and its correlates and more than the presence of dispositional empathy, moral reasoning, moral identity, and the value of universalism. Across these studies, the IWAH predicted concern for global human rights and humanitarian needs (Studies 1 and 2), was temporally stable (Study 3), and correlated with how close others see one as being (Study 4). The IWAH strongly distinguished members of 2 known groups from a general adult sample (Study 5). It predicted valuing the lives of ingroup and outgroup members equally (Study 7), knowledge of global humanitarian concerns (Study 8) and choosing to learn about these concerns (Study 9), and a willingness to contribute to international humanitarian relief (Study 10). In regression analyses, it predicted these results beyond related constructs. Although psychologists have focused extensively upon negative qualities such as ethnocentrism and its roots, we suggest that the positive quality of identification with all humanity also merits extensive study. PMID:22708625

  17. 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

  18. 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

  19. 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.

  20. 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

  1. A Phylogenetic Comparative Study of Bantu Kinship Terminology Finds Limited Support for Its Co-Evolution with Social Organisation.

    PubMed

    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.

  2. A Phylogenetic Comparative Study of Bantu Kinship Terminology Finds Limited Support for Its Co-Evolution with Social Organisation.

    PubMed

    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

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

    PubMed Central

    Ben M’Barek, 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

  4. Relevance of non-human animal studies to the understanding of human sexuality.

    PubMed

    Agmo, Anders; Ellingsen, Ellinor

    2003-07-01

    There are several reasons for studying sexual behavior in animals other than the human. Prominent among these is probably the use of sexual behavior as a model system for analyzing hormone actions on the brain. In this kind of study, lordosis behavior in the female rat has frequently been used as the behavioral end-point. Recently, the mouse has become a popular subject because of the availability of strains lacking estrogen or progesterone receptors. Animal sexual behavior is also studied for its own sake by biologists, by agricultural scientists and by those interested in the management of wildlife resources. Finally, there are some researchers interested in human sexual behavior who prefer to approach their problems through studies in non-human subjects, as they thereby gain access to techniques of experimentation impossible in human subjects. This is particularly important when the neurobiological basis of sexual behavior is the subject of study. Two striking similarities between humans and other mammals are the hormone dependency of sexual motivation and the fundamentally bisexual organization of the nervous system. In addition, animal studies have revealed how learning with sexual reinforcement can be an important determinant of sexual behavior. The role of learning has been largely ignored in human studies, and this has led to many misconceptions. Paramount among these is the idea that sexual behavior is associated with reproduction. PMID:12914594

  5. 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…

  6. Introduction to Environmental Studies, Human Ecological Problems.

    ERIC Educational Resources Information Center

    Wang, J. Y.

    This introductory text of general readings for environmental studies is specifically prepared for undergraduate college students although useful also as a reference book for graduate students and instructors and as an information resource for the general public. The book is problem oriented emphasizing the interaction and interdependence of man…

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. Creation of “Humanized” Mice to Study Human Immunity

    PubMed Central

    Pearson, Todd; Greiner, Dale L.; Shultz, Leonard D.

    2010-01-01

    “Humanized” mice are a promising translational model for studying human hematopoiesis and immunity. Their utility has been enhanced by the development of new stocks of immunodeficient hosts, most notably mouse strains such as NOD-scid IL2rγ null mice that lack the IL-2 receptor common gamma chain. These stocks of mice lack adaptive immune function, display multiple defects in innate immunity, and support heightened levels of human hematolymphoid engraftment. Humanized mice can support studies in many areas of immunology, including autoimmunity, transplantation, infectious diseases, and cancer. These models are particularly valuable in experimentation where there is no appropriate small animal model of the human disease, as in the case of certain viral infections. This unit details the creation of humanized mice by engraftment of immunodeficient mice with hematopoietic stem cells or peripheral blood mononuclear cells, provides methods for evaluating engraftment, and discusses considerations for choosing the appropriate model system to meet specific goals. PMID:18491294

  13. A mouse model replicating hippocampal sparing cranial irradiation in humans: A tool for identifying new strategies to limit neurocognitive decline.

    PubMed

    Tomé, Wolfgang A; Gökhan, Şölen; 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

  14. A mouse model replicating hippocampal sparing cranial irradiation in humans: A tool for identifying new strategies to limit neurocognitive decline

    PubMed Central

    Tomé, Wolfgang A.; Gökhan, Şölen; 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

  15. 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…

  16. 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

  17. 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.

  18. 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

  19. 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...

  20. 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

  1. A guide to studying human hair follicle cycling in vivo

    PubMed Central

    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

    2015-01-01

    Hair follicles (HFs) undergo life-long cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative “quiescence” (telogen). Since 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. While available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. Here, 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 sub-optimally 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Comparative studies of color fields, visual acuity fields, and movement perception limits among varsity athletes and non-varsity groups.

    PubMed

    Mizusawa, K; Sweeting, R L; Knouse, S B

    1983-06-01

    This paper examined effects of sports practice on patterns of color fields, limits of peripheral movement perception, and visual acuity field by comparing varsity ball players and non-varsity control groups. The first study measured extent of color fields and limits of horizontal and vertical meridians for peripheral movement perception of 139 college students. The second study tested visual acuity fields of female and male basketball players and female and male controls. The first study indicated that athletes had wider limits for horizontal movement perception, while the non-athletes had better vertical movement perception limits. Basketball players demonstrated color fields and limits for peripheral movement perception superior to those of soccer players. In the second study, athletes did not have any wider visual acuity fields than non-athletes, but their movement-perception limits were significantly wider than those of non-athletes.

  7. Chemostat Studies of TCE-Dehalogenating Anaerobic Consortia under Excess and Limited Electron Donor Addition

    NASA Astrophysics Data System (ADS)

    Semprini, L.; Azizian, M.; Green, J.; Mayer-Blackwell, K.; Spormann, A. M.

    2015-12-01

    Two cultures - the Victoria Strain (VS) and the Evanite Strain (EV), enriched with the organohalide respiring bacteria Dehalococcoides mccartyi - were grown in chemostats for more than 4 years at a mean cell residence time of 50 days. The slow doubling rate represents growth likely experienced in the subsurface. The chemostats were fed formate as an electron donor and trichloroethene (TCE) as the terminal electron acceptor. Under excess formate conditions, stable operation was observed with respect to TCE transformation, steady-state hydrogen (H2) concentrations (40 nM), and the structure of the dehalogenating community. Both cultures completely transformed TCE to ethene, with minor amounts of vinyl chloride (VC) observed, along with acetate formation. When formate was limited, TCE was transformed incompletely to ethene (40-60%) and VC (60- 40%), and H2 concentrations ranged from 1 to 3 nM. The acetate concentration dropped below detection. Batch kinetic studies of TCE transformation with chemostat harvested cells found transformation rates of c-DCE and VC were greatly reduced when the cells were grown with limited formate. Upon increasing formate addition to the chemostats, from limited to excess, essentially complete transformation of TCE to ethene was achieved. The increase in formate was associated with an increase in H2 concentration and the production of acetate. Results of batch kinetic tests showed increases in transformation rates for TCE and c-DCE by factors of 3.5 and 2.5, respectively, while VC rates increased by factors of 33 to 500, over a six month period. Molecular analysis of chemostat samples is being performed to quantify the changes in copy numbers of reductase genes and to determine whether shifts in the strains of Dehalococcoides mccartyi where responsible for the observed rate increases. The results demonstrate the importance of electron donor supply for successful in-situ remediation.

  8. 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

  9. Human Studies of Angiogenic Gene Therapy

    PubMed Central

    Gupta, Rajesh; Tongers, Jörn; 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

  10. 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.

  11. 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.

  12. An assessment of the dietary uptake of di-2-(ethylhexyl) adipate (DEHA) in a limited population study.

    PubMed

    Loftus, N J; Woollen, B H; Steel, G T; Wilks, M F; Castle, L

    1994-01-01

    The plasticizer di-2-(ethylhexyl) adipate (DEHA), which may be present in food-contact films, can migrate into certain foodstuffs. Results from plasticizer migration studies into food have enabled an indirect estimate of the maximum daily dietary intake of DEHA. A previous study of the metabolism and pharmacokinetics of DEHA in humans identified the urinary metabolite 2-ethylhexanoic acid (EHA) as a useful marker metabolite for assessing DEHA intake. The present study was designed to investigate urinary EHA concentrations following a controlled dose of DEHA presented with food, and to assess the average daily intake of DEHA in a limited population survey. The urinary elimination profile of EHA, following a dose of DEHA in food, showed that in order to extrapolate DEHA intake from EHA measurements, a 24-hr urine sample was required. In the survey the elimination of EHA was determined in 24-hr urine samples in 112 individuals from five different geographical locations in the UK. No restrictions were placed on age or gender. Estimates of daily intake of DEHA show a skewed distribution with a median value of 2.7 mg. This is similar to an estimated maximum daily intake of 8.2 mg/day, derived using an indirect method by the UK Ministry of Agriculture, Fisheries and Food.

  13. Study of Forming Limit for Rotational Incremental Sheet Forming of Magnesium Alloy Sheet

    NASA Astrophysics Data System (ADS)

    Park, Jingee; Kim, Jeounghan; Park, Nhokwang; Kim, Youngsuk

    2010-01-01

    As a lightweight material, magnesium is being increasingly used for automotive parts. However, due to a hexagonal-closed-packed (hcp) crystal structure, in which only the basal plane can move, magnesium alloy sheets exhibit a low ductility and formability at room temperature. Press forming of magnesium alloy sheets is conventionally performed at elevated temperatures of 200 °C to 250 °C and thus is known as energy consumed forming. Therefore, in view of an energy saving forming technology, we study magnesium alloy sheet forming by a rotational incremental sheet forming (RISF) at room temperature, where the rotational tool generates local heat of specimen enough to accelerate plastic deformation. The flow curves of the magnesium alloy sheet are obtained and calculated at elevated temperatures, while the yield loci of the magnesium alloy sheet are measured at room temperature. Using RISF, a square cup of 80-mm width, 80-mm length, and 25-mm height is then formed from a magnesium alloy sheet at room temperature. In addition, the strain distribution is obtained and compared with the forming limit curve (FLC) by considering the effect of the tool radius and is found to effectively predict the forming limit of a magnesium alloy sheet in RISF.

  14. Interferon gamma-activated human monocytes downregulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron.

    PubMed Central

    Byrd, T F; Horwitz, M A

    1989-01-01

    We have investigated the role of iron in the intracellular biology of Legionella pneumophila in human monocytes and in the effector arm of cell-mediated immune defense against this intracellular bacterial pathogen. To determine if L. pneumophila intracellular multiplication is iron dependent, we studied the effect of the iron chelator deferoxamine on L. pneumophila infection of monocytes. Deferoxamine at 15 microM completely inhibited L. pneumophila intracellular multiplication. The inhibitory effect of deferoxamine was reversed with equimolar iron-saturated transferrin but not apotransferrin. To examine the potential role of iron in monocyte activation, we investigated the influence of iron-saturated transferrin on L. pneumophila multiplication in IFN gamma-activated monocytes. Iron transferrin, but not apotransferrin, neutralized the capacity of activated monocytes to inhibit L. pneumophila multiplication. To explore a potential mechanism by which activated monocytes might limit the availability of intracellular iron, we examined transferrin receptor expression on nonactivated and activated monocytes cultured in vitro for 5 d. By fluorescence-activated flow cytometry, activated monocytes exhibited markedly fewer transferrin receptors than nonactivated monocytes. By Scatchard analysis of 125I-transferrin binding to monocytes, nonactivated monocytes had 38,300 +/- 12,700 (mean +/- SE) transferrin binding sites, whereas activated monocytes had 10,300 +/- 1,600, a reduction of 73%. Activated and nonactivated monocytes had a similar mean Kd (1.8 +/- 0.2 nM). This study demonstrates that (a) L. pneumophila intracellular multiplication is iron dependent; (b) activated monocytes inhibit L. pneumophila multiplication by limiting the availability of intracellular iron; and (c) transferrin receptors are downregulated on IFN gamma-activated monocytes. Images PMID:2496141

  15. Nelfinavir is effective against human cervical cancer cells in vivo: a potential treatment modality in resource-limited settings

    PubMed Central

    Davis, Mitzie-Ann; Delaney, Joe R; Patel, Chandni B; Storgard, Ryan; Stupack, Dwayne G

    2016-01-01

    Objective The standard treatment for cervical cancer in developed countries includes surgery and chemoradiation, with standard of care lagging in developing countries. Even in the former case, treatment frequently yields recalcitrant tumors and women succumb to disease. Here we examine the impact of nelfinavir, an off-patent viral protease inhibitor, which has shown promise as an antineoplastic agent. Methods We evaluated the morphological and proliferative effects of the autophagy-stressing drug nelfinavir in normal and cisplatin-resistant cervical cancer cells. Immunofluorescent validation of autophagy markers was performed and the impact of nelfinavir in an in vivo model of tumor growth was determined. Results Nelfinavir exhibits cytotoxicity against both cisplatin-sensitive and -resistant ME-180 human cervical cancer cells in vitro and in vivo. Immunoblotting and immunofluorescence showed an expression of the autophagy marker LC3-II in response to nelfinavir treatment. Conclusion Nelfinavir, now available as an inexpensive generic orally dosed agent (Nelvir), is cytotoxic against cervical cancer cells. It acts by burdening the autophagy pathway to impair tumor cell survival and a modest induction of apoptosis. While further studies are needed to elucidate the optimal method of application of nelfinavir, it may represent an appealing global option for the treatment of cervical cancer. PMID:27330277

  16. Human Mars Entry, Descent, and Landing Architecture Study Overview

    NASA Technical Reports Server (NTRS)

    Cianciolo, Alicia D.; Polsgrove, Tara T.

    2016-01-01

    The Entry, Descent, and Landing (EDL) Architecture Study is a multi-NASA center activity to analyze candidate EDL systems as they apply to human Mars landing in the context of the Evolvable Mars Campaign. The study, led by the Space Technology Mission Directorate (STMD), is performed in conjunction with the NASA's Science Mission Directorate and the Human Architecture Team, sponsored by NASA's Human Exploration and Operations Mission Directorate. The primary objective is to prioritize future STMD EDL technology investments by (1) generating Phase A-level designs for selected concepts to deliver 20 t human class payloads, (2) developing a parameterized mass model for each concept capable of examining payloads between 5 and 40 t, and (3) evaluating integrated system performance using trajectory simulations. This paper summarizes the initial study results.

  17. A clinicopathological study of human yellow fever*

    PubMed Central

    Francis, T. I.; Moore, D. L.; Edington, G. M.; Smith, J. A.

    1972-01-01

    During an epidemic of yellow fever in the Jos Plateau area of Nigeria, 9 adult males with clinically diagnosed yellow fever were studied by haematological, biochemical, virological, serological, and liver biopsy methods. The ages of the patients ranged from 20 to 55 years and the duration of illness was 3-62 days. No virus was isolated from any patient but all patients should biochemical evidence of severe hepatocellular damage. Leucopenia was a feature of the late acute stage of the disease. Five sera had antibodies to yellow fever at titres greater than 1: 32, 3 of them being monospecific for yellow fever. The classical histological features of yellow fever were present only in the acute or late acute stages, when complement-fixation tests may be negative. With convalescence and the production of complement-fixing antibodies in high titres, the histological features resembled those of a persisting nonspecific hepatitis. In an endemic area, the histological features of yellow fever will depend on the stage of the disease and a picture of nonspecific hepatitis would not exclude yellow fever in the absence of confirmation from serological tests. ImagesFig. 1Fig. 2AFig. 2BFig. 3Fig. 4Fig. 5Fig. 6 PMID:4538039

  18. Activity Limitations among Young Adults with Developmental Disabilities: A Population-Based Follow-Up Study

    ERIC Educational Resources Information Center

    Braun, Kim Van Naarden; Yeargin-Allsopp, Marshalyn; Lollar, Donald

    2009-01-01

    Developmental disabilities are a heterogeneous group of chronic conditions that may result in substantial activity limitations. The type and number of limitations may vary by impairment characteristics. Economic and social constraints may impact activity limitations beyond those attributable to their impairment. Using the International…

  19. 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, Bogusław

    2015-05-06

    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.

  20. 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…

  1. Animal models are reliably mimicking human diseases? A morphological study that compares animal with human NAFLD.

    PubMed

    Solinas, Paola; Isola, Michela; Lilliu, Maria Alberta; Conti, Gabriele; Civolani, Alberto; Demelia, Luigi; Loy, Francesco; Isola, Raffaella

    2014-10-01

    Non-alcoholic fatty liver disease (NAFLD) is a clinical-pathological syndrome that includes a wide spectrum of morphological alterations. In research, animal models are crucial in evaluating not only the pathogenesis of NAFLD and its progression, but also the therapeutic effects of various agents. Investigations on the ultrastructural features of NAFLD in humans are not copious, due to the difficulty to obtain human samples and to the long time of NAFLD to evolve. Translational comparative studies on the reliability of animal models in representing the histopathologic picture as seen in humans are missing. To overcome this lack of investigations, we compared the ultrastructural NAFLD features of an animal model versus human. Sprague-Dawley rats were fed with a high fat diet (HFD) for 1-4 weeks, while control rats were fed with a standard diet. Human specimens were collected from patients with diagnosed fatty liver disease, undergoing liver biopsies or surgery. Rat and human samples were examined by light microscopy and by transmission and high resolution scanning electron microscopy. The present work demonstrated that NAFLD in animal model and in human, share overlapping ultrastructural features. In conclusion, animal HFD represent an appropriate tool in studying the pathogenesis of NAFLD.

  2. Stratosphere and troposphere (S-T) studies at Millstone Hill. Recent results, capabilities and limitations

    NASA Technical Reports Server (NTRS)

    Rastogi, P. K.

    1983-01-01

    The 440-MHz incoherent-scatter radar at Millstone Hill has been used in recent years for studies of the troposphere and lower stratosphere with a fully steerable 150' antenna. The configuration of the radar system is briefly outlined. Clear-air returns are received over an altitude range 4 to 25 km. The power spectra of these returns can be measured with a range resolution of up to 300 m and a Doppler resolution of up to 4 cm/sec. Due to the lack of a natural shield around the radar, the ground clutter at Millstone is more severe than at other installations. With the use of a fine Doppler resolution, however, the atmospheric returns are readily discriminated from the clutter. Observations of turbulence structures, spatial inhomogeneity of turbulence, and enhanced turbulence associated with convective phenomena are described. Capabilities and limitations of the Millstone S-T radar are pointed out.

  3. 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.

  4. 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.

  5. Absorbed dose thresholds and absorbed dose rate limitations for studies of electron radiation effects on polyetherimides

    NASA Technical Reports Server (NTRS)

    Long, Edward R., Jr.; Long, Sheila Ann T.; Gray, Stephanie L.; Collins, William D.

    1989-01-01

    The threshold values of total absorbed dose for causing changes in tensile properties of a polyetherimide film and the limitations of the absorbed dose rate for accelerated-exposure evaluation of the effects of electron radiation in geosynchronous orbit were studied. Total absorbed doses from 1 kGy to 100 MGy and absorbed dose rates from 0.01 MGy/hr to 100 MGy/hr were investigated, where 1 Gy equals 100 rads. Total doses less than 2.5 MGy did not significantly change the tensile properties of the film whereas doses higher than 2.5 MGy significantly reduced elongation-to-failure. There was no measurable effect of the dose rate on the tensile properties for accelerated electron exposures.

  6. Third order optical nonlinearity and optical limiting studies of propane hydrazides

    NASA Astrophysics Data System (ADS)

    Naseema, K.; Manjunatha, K. B.; Sujith, K. V.; Umesh, G.; Kalluraya, Balakrishna; Rao, Vijayalakshmi

    2012-09-01

    Four hydrazones, 2-(4-isobutylphenyl)-N'-[phenylmethylene] propanehydrazide (P1), 2-(4-isobutylphenyl)-N'-[(4- tolyl)methylene] propane hydrazide (P2), 2-(4-isobutylphenyl)-N'-[1-(4- chlorophenyl)ethylidene] propanehydrazide (P3) and 2-(4-isobutylphenyl)-N'-[1-(4-Nitrrophenyl)ethylidene] propane hydrazide (P4) were synthesized and their third order nonlinear optical properties have been investigated using a single beam Z-scan technique with nanosecond laser pulses at 532 nm. The measurement on the compound-P1 is not reported as there is no detectable nonlinear response. Open aperture data of the other three compounds indicate two photon absorption at this wavelength. The nonlinear refractive index n2, nonlinear absorption coefficient β, magnitude of effective third order susceptibility χ(3), the second order hyperpolarizability γh and the coupling factor ρ have been estimated. The values obtained are comparable with the values obtained for 4-methoxy chalcone derivatives and dibenzylideneacetone derivatives. The experimentally determined values of β, n2, Re χ(3) and Im χ(3), γh and ρ of the compound-P4 are 1.42 cm/GW, -0.619 × 10-11 esu, -0.663 × 10-13 esu, 0.22 × 10-13 esu, 0.34 × 10-32 esu and 0.33 respectively. Further the compound-P4 exhibited the best optical power limiting behavior at 532 nm among the compounds studied. Our studies suggest that compounds P2, P3 and P4 are potential candidates for the optical device applications such as optical limiters and optical switches.

  7. Convergent integration of animal model and human studies of bipolar disorder (manic-depressive illness).

    PubMed

    Le-Niculescu, Helen; Patel, Sagar D; Niculescu, Alexander B

    2010-10-01

    Animal models and human studies of bipolar disorder and other psychiatric disorders are becoming increasingly integrated, prompted by recent successes. Particularly for genomics, the convergence and integration of data across species, experimental modalities and technical platforms is providing a fit-to-disease way of extracting reproducible and biologically important signal, in sharp contrast to the fit-to-cohort effect, disappointing findings to date, and limited reproducibility of human genetic analyses alone. Such work in psychiatry can provide an example of how to address other genetically complex disorders, and in turn will benefit by incorporating concepts from other areas, such as cancer biology and diabetes.

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

    PubMed Central

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

    2016-01-01

    ABSTRACT 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

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. Studies on the nucleic acid of human bladder carcinoma

    SciTech Connect

    Nabih, I.; Mantawy, M.M.; Abdel-Hamid, A.Z. )

    1990-01-01

    DNA was isolated from different histopathologic types and grades of human bladder carcinoma. The isolated DNA was submitted to quantitative determination and base composition analysis. A pilot study was done on the effect of gamma irradiation as a physical mutagen on characteristics of DNA in the examined tissues. Identity in the genetic components in the urinary bilharziasis snails and the human bladder cancer was observed. The same was observed in both intestinal bilharziasis snails and the cancerous intestinal tissues.

  14. Brain banks: benefits, limitations and cautions concerning the use of post-mortem brain tissue for molecular studies.

    PubMed

    Ferrer, Isidre; Martinez, Anna; Boluda, Susana; Parchi, Piero; Barrachina, Marta

    2008-09-01

    Brain banks are facilities providing an interface between generous donation of nervous tissues and research laboratories devoted to increase our understanding of the diseases of the nervous system, discover new diagnostic targets, and develop new strategies. Considering this crucial role, it is important to learn about the suitabilities, limitations and proper handling of individual brain samples for particular studies. Several factors may interfere with preservation of DNA, RNA, proteins and lipids, and, therefore, special care must be taken first to detect sub-optimally preserved tissues and second to provide adequate material for each specific purpose. Basic aspects related with DNA, RNA and protein preservation include agonal state, post-mortem delay, temperature of storage and procedures of tissue preservation. Examination of DNA and RNA preservation is best done by using bioanalyzer technologies instead of less sensitive methods such as agarose gels. Adequate RNA preservation is mandatory in RNA microarray studies and adequate controls are necessary for proper PCR validation. Like for RNA, the preservation of proteins is not homogeneous since some molecules are more vulnerable than others. This aspect is crucial in the study of proteins including expression levels and possible post-translational modifications. Similarly, the reliability of functional and enzymatic studies in human post-mortem brain largely depends on protein preservation. Much less is known about other aspects, such as the effects of putative deleterious factors on epigenetic events such as methylation of CpGs in gene promoters, nucleosome preservation, histone modifications, and conservation of microRNA species. Most brains are appropriate for morphological approaches but not all brains are useful for certain biochemical and molecular studies.

  15. Maximum Parsimony and the Skewness Test: A Simulation Study of the Limits of Applicability

    PubMed Central

    Määttä, Jussi; Roos, Teemu

    2016-01-01

    The maximum parsimony (MP) method for inferring phylogenies is widely used, but little is known about its limitations in non-asymptotic situations. This study employs large-scale computations with simulated phylogenetic data to estimate the probability that MP succeeds in finding the true phylogeny for up to twelve taxa and 256 characters. The set of candidate phylogenies are taken to be unrooted binary trees; for each simulated data set, the tree lengths of all (2n − 5)!! candidates are computed to evaluate quantities related to the performance of MP, such as the probability of finding the true phylogeny, the probability that the tree with the shortest length is unique, the probability that the true phylogeny has the shortest tree length, and the expected inverse of the number of trees sharing the shortest length. The tree length distributions are also used to evaluate and extend the skewness test of Hillis for distinguishing between random and phylogenetic data. The results indicate, for example, that the critical point after which MP achieves a success probability of at least 0.9 is roughly around 128 characters. The skewness test is found to perform well on simulated data and the study extends its scope to up to twelve taxa. PMID:27035667

  16. 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.

  17. Maximum Parsimony and the Skewness Test: A Simulation Study of the Limits of Applicability.

    PubMed

    Määttä, Jussi; Roos, Teemu

    2016-01-01

    The maximum parsimony (MP) method for inferring phylogenies is widely used, but little is known about its limitations in non-asymptotic situations. This study employs large-scale computations with simulated phylogenetic data to estimate the probability that MP succeeds in finding the true phylogeny for up to twelve taxa and 256 characters. The set of candidate phylogenies are taken to be unrooted binary trees; for each simulated data set, the tree lengths of all (2n - 5)!! candidates are computed to evaluate quantities related to the performance of MP, such as the probability of finding the true phylogeny, the probability that the tree with the shortest length is unique, the probability that the true phylogeny has the shortest tree length, and the expected inverse of the number of trees sharing the shortest length. The tree length distributions are also used to evaluate and extend the skewness test of Hillis for distinguishing between random and phylogenetic data. The results indicate, for example, that the critical point after which MP achieves a success probability of at least 0.9 is roughly around 128 characters. The skewness test is found to perform well on simulated data and the study extends its scope to up to twelve taxa. PMID:27035667

  18. Advantages and limitations of OM, SEM, TEM and AFM in the study of ancient decorated pottery

    NASA Astrophysics Data System (ADS)

    Arenas-Alatorre, J.; Silva-Velazquez, Y.; Alva Medina, A.; Rivera, M.

    2010-03-01

    This paper presents results from the study of two fragments of pre-Hispanic pottery, decorated with red pigment, using Optical Microscopy (OM), Scanning Electron Microscopy (SEM), High Resolution Transmission Electron Microscopy (HRTEM), Atomic Force Microscopy (AFM) and Magnetic Force Microscopy (MFM). Capabilities and limitations of these techniques in the analysis of archaeological material are highlighted with special emphasis on TEM, AFM and MFM due to their contribution in the study of the pigment layer at micro and nano scale. The analyzed samples come from the archaeological sites of El Tajin and Xochicalco, both in Mexico. Results of conventional TEM and HRTEM analysis of the red pigment showed nanometric Fe2O3 particles in both samples but different particle shape and size distributions: specimen from El Tajin presented irregular particles between 50-100 nm while that from Xochicalco exhibited semispherical shapes in the 3-25 nm range. AFM images showed the topography of the pigments, which are related to the texture of their surface and thus to the production process. Finally, MFM showed different contrast regions suggesting the presence of ferromagnetic elements forming clusters and domain orientations on the color layer.

  19. 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

  20. 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.

  1. 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…

  2. Human Lesion Studies in the 21st Century.

    PubMed

    Adolphs, Ralph

    2016-06-15

    The study of patients with brain lesions has made major historical contributions to cognitive neuroscience. Here I argue for an increased investment in modern lesion mapping, complementing fMRI studies and laying the conceptual and analytic foundations for future techniques that could experimentally manipulate human brain function. PMID:27311080

  3. 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.

  4. [Decisions on limiting treatment in critically-ill neonates: a multicenter study].

    PubMed

    2002-12-01

    Backgrounds Some patients with a poor prognosis cause serious doubts about the real benefit of life-sustaining treatment. In some cases the possibility of limiting those treatments is raised. Such end-of-life decisions provoke ethical dilemmas and questions about procedure.ObjectivesTwo determine the frequency of end-of-life decisions in neonates, patient characteristics, and the criteria used by those taking decisions.Patients and methodsWe performed a multicenter, descriptive, prospective study. Neonates from 15 neonatal intensive care units who died during their stay in the hospital between 1999 and 2000, as well as those in whom end-of-life decisions were taken, were included. End-of-life decisions were defined as clinical decisions to withhold or withdraw life-sustaining treatment.ResultsA total of 330 patients were included. End-of-life decisions were taken in 171 (52 %); of these, 169 (98.8 %) died. The remaining 159 patients (48.2 %) died without treatment limitation. The main disorders involving end-of-life decisions were congenital malformation (47 %), neurologic disorders secondary to perinatal asphyxia and intracranial hemorrhage-periventricular leukomalacia (37 %). Of the 171 neonates, treatment was withheld in 80 and vital support was withdrawn in 91. The most frequently withdrawn life-sustaining treatment was mechanical ventilation (68 %). The criteria most commonly used in end-of-life decisions were poor vital prognosis (79.5 %), and current and future quality of life (37 % and 48 % respectively). The patient's external factors such as unfavorable family environment or possible negative consequences for familial equilibrium were a factor in 5 % of decisions.ConclusionsThe present study, the first of this type performed in Spain, reveals little-known aspects about the clinical practice of withholding and/or withdrawing life-sustaining treatment in critically ill neonates. End-of-life decisions were frequent (52 %) and were followed by death in most

  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. 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

    2016-02-17

    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.

  7. [Studies on mode of human infection with Echinochasmus liliputanus].

    PubMed

    Xiao, X; Lu, D; Wang, T; Gao, J; Zhu, C; Zhang, B; An, J; Pong, H; Xu, M; Wu, W

    1995-01-01

    Epidemiological survey and experimental studies on the mode of human infection with Echinochasmus liliputanus were carried out in Chenqiaozhou Village, Hexian County, Anhui Province in 1992. The results showed that humans could be infected through drinking unboiled water containing E.liliputanus cercaria or eating raw fish containing the metacercaria. The infection rates of E. liliputanus were 1.5% in the inhabitants who did not drink raw water, and 20.1% in those who used to drink raw water. It was only the cercaria, not the metacercaria that was detected in the water from ponds of this village. None of the investigated inhabitants ate uncooked fish. The results indicated that drinking raw water containing E.liliputanus cercaria was a major way through which a humans were infected and eating food containing the metacercaria was a minor mode of human infection.

  8. Stable carbon isotopes and the study of prehistoric human diet.

    PubMed

    Boutton, T W; Lynott, M J; Bumsted, M P

    1991-01-01

    Mass spectrometric analysis of the stable carbon isotope composition (13C/12C or delta 13C) of bone collagen from human remains recovered at archaeological sites provides a direct chemical method for investigating dietary patterns of prehistoric human populations. This methodology is based on the facts that (1) different food items within the human diet have distinct delta 13C values, and (2) the delta 13C value of human bone collagen is determined by the delta 13C value of the diet. Studies of the development of subsistence patterns based on corn agriculture, one of the most significant developments in North American prehistory, can benefit from the use of stable carbon isotope techniques because corn has a high delta 13C value relative to other components of the human diet. Measurements of delta 13C of bone collagen from prehistoric human skeletal remains from southeastern Missouri and northeastern Arkansas indicate that intensive corn agriculture began in this region around A.D. 1000, that the incorporation of corn into the human diet was a rapid phenomenon, and that 35 to 77% of the human diet from A.D. 1000 to A.D. 1600 consisted of corn. Results from an isochronous population in southeastern South Dakota (A.D. 1400) suggest that 78 to 90% of the diet of this group consisted of corn, with no difference between males and females. Coupled with more traditional archaeological methods, stable carbon isotope analysis of bone collagen can significantly enhance reconstruction of dietary patterns of prehistoric humans.

  9. 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.

  10. Images of the Limit of Function Formed in the Course of Mathematical Studies at the University

    ERIC Educational Resources Information Center

    Przenioslo, Malgorzata

    2004-01-01

    The paper is based on extensive research carried out on students of mathematics who had completed a university course of calculus. The basic purpose of the research was to determine the students' images of the concept of limit, that is to find out their associations, conceptions and intuitions connected with limits and to determine the degree of…

  11. 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…

  12. Enhanced Transmural Fiber Rotation and Connexin 43 Heterogeneity Are Associated With an Increased Upper Limit of Vulnerability in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy

    PubMed Central

    Ripplinger, Crystal M.; Li, Wenwen; Hadley, Jennifer; Chen, Junjie; Rothenberg, Florence; Lombardi, Raffaella; Wickline, Samuel A.; Marian, Ali J.; Efimov, Igor R.

    2008-01-01

    Human hypertrophic cardiomyopathy, characterized by cardiac hypertrophy and myocyte disarray, is the most common cause of sudden cardiac death in the young. Hypertrophic cardiomyopathy is often caused by mutations in sarcomeric genes. We sought to determine arrhythmia propensity and underlying mechanisms contributing to arrhythmia in a transgenic (TG) rabbit model (β-myosin heavy chain–Q403) of human hypertrophic cardiomyopathy. Langendorff-perfused hearts from TG (n = 6) and wild-type (WT) rabbits (n = 6) were optically mapped. The upper and lower limits of vulnerability, action potential duration (APD) restitution, and conduction velocity were measured. The transmural fiber angle shift was determined using diffusion tensor MRI. The transmural distribution of connexin 43 was quantified with immunohistochemistry. The upper limit of vulnerability was significantly increased in TG versus WT hearts (13.3 ± 2.1 versus 7.4 ± 2.3 V/cm; P = 3.2e−5), whereas the lower limits of vulnerability were similar. APD restitution, conduction velocities, and anisotropy were also similar. Left ventricular transmural fiber rotation was significantly higher in TG versus WT hearts (95.6 ± 10.9° versus 79.2 ± 7.8°; P = 0.039). The connexin 43 density was significantly increased in the mid-myocardium of TG hearts compared with WT (5.46 ± 2.44% versus 2.68 ± 0.77%; P = 0.024), and similar densities were observed in the endo- and epicardium. Because a nearly 2-fold increase in upper limit of vulnerability was observed in the TG hearts without significant changes in APD restitution, conduction velocity, or the anisotropy ratio, we conclude that structural remodeling may underlie the elevated upper limit of vulnerability in human hypertrophic cardiomyopathy. PMID:17885214

  13. 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

  14. Insights from human studies into the host defense against candidiasis.

    PubMed

    Filler, Scott G

    2012-04-01

    Candida spp. are the most common cause of mucosal and disseminated fungal infections in humans. Studies using mutant strains of mice have provided initial information about the roles of dectin-1, CARD9, and Th17 cytokines in the host defense against candidiasis. Recent technological advances have resulted in the identification of mutations in specific genes that predispose humans to develop candidal infection. The analysis of individuals with these mutations demonstrates that dectin-1 is critical for the host defense against vulvovaginal candidiasis and candidal colonization of the gastrointestinal tract. They also indicate that CARD9 is important for preventing both mucosal and disseminated candidiasis, whereas the Th17 response is necessary for the defense against mucocutaneous candidiasis. This article reviews the recent studies of genetic defects in humans that result in an increased susceptibility to candidiasis and discusses how these studies provide new insight into the host defense against different types of candidal infections.

  15. 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.

  16. 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…

  17. 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.

  18. 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.

  19. Ecologic studies of rodent reservoirs: their relevance for human health.

    PubMed Central

    Mills, J. N.; Childs, J. E.

    1998-01-01

    Within the past few years, the number of "new" human diseases associated with small-mammal reservoirs has increased dramatically, stimulating renewed interest in reservoir ecology research. A consistent, integrative approach to such research allows direct comparisons between studies, contributes to the efficient use of resources and data, and increases investigator safety. We outline steps directed toward understanding vertebrate host ecology as it relates to human disease and illustrate the relevance of each step by using examples from studies of hosts associated with rodent-borne hemorrhagic fever viruses. PMID:9866729

  20. Experimental Study of RF Sheath Formation on a Fast Wave Antenna and Limiter in the LAPD

    NASA Astrophysics Data System (ADS)

    Martin, Michael; Gekelman, Walter; Pribyl, Patrick; van Compernolle, Bart; Carter, Troy

    2015-11-01

    Ion cyclotron resonance heating (ICRH) will be an essential component of heating power in ITER. During ICRH, radio frequency (RF) sheaths may form both at the exciting antenna and further away, e.g. in the divertor region, and may cause wall material sputtering and decreased RF power coupling to the plasma. It is important to do detailed laboratory experiments that fully diagnose the sheaths and wave fields. This is not possible in fusion devices. A new RF system has recently been constructed for performing such studies in the LAPD plasma column (ne ~1012 -1013cm-3 , Te ~ 1 - 10 eV ,B0 ~ 400 - 2000 G , diameter ~ 60cm , length ~ 18 m) . The RF system is capable of pulsing at the 1 Hz rep. rate of the LAPD plasma and operating between 2-6 MHz (1st - 9th harmonic of fci in H) with a power output of 200 kW. First results of this system driving a single-strap fast wave antenna will be presented. Emissive and Langmuir probe measurements in the vicinity of both the antenna and a remote limiter and wave coupling measured by magnetic pickup loops will be presented.

  1. Self-assembly of high molecular weight polypeptide copolymers studied via diffusion limited aggregation.

    PubMed

    Meier, Christoph; Wu, Yuzhou; Pramanik, Goutam; Weil, Tanja

    2014-01-13

    The assembly of high molecular weight polypeptides into complex architectures exhibiting structural complexity ranging from the nano- to the mesoscale is of fundamental importance for various protein-related diseases but also hold great promise for various nano- and biotechnological applications. Here, the aggregation of partially unfolded high molecular weight polypeptides into multiscale fractal structures is investigated by means of diffusion limited aggregation and atomic force microscopy. The zeta potential, the hydrodynamic radius, and the obtained fractal morphologies were correlated with the conformation of the polypeptide backbones as obtained from circular dichroism measurements. The polypeptides are modified with polyethylene oxide side chains to stabilize the polypeptides and to normalize intermolecular interactions. The modification with the hydrophobic thioctic acid alters the folding of the polypeptide backbone, resulting in a change in solution aggregation and fractal morphology. We found that a more compact folding results in dense and highly branched structures, whereas a less compact folded polypeptide chain yields a more directional assembly. Our results provide first evidence for the role of compactness of polypeptide folding on aggregation. Furthermore, the mesoscale-structured biofilms were used to achieve a hierarchical protein assembly, which is demonstrated by deposition of Rhodamine-labeled HSA with the preassembled fractal structures. These results contribute important insights to the fundamental understanding of the aggregation of high molecular weight polypeptides in general and provide opportunities to study nanostructure-related effects on biological systems such as adhesion, proliferation, and the development of, for example, neuronal cells. PMID:24354281

  2. 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

  3. [HBSC Study as an Instrument for Health Reporting among Children and Adolescents - Potential and Limitations].

    PubMed

    Bucksch, J; Hilitzer, U; Gohres, H; Kolip, P

    2016-07-01

    Prevention and health promotion have to target children and adolescents. Health reporting significantly contributes to assess the needs in terms of intervention planning in children and adolescents and to plan interventions of the highest priority. In Germany, reporting on children and adolescent's health takes place at federal, federal state and regional levels. Health reporting is based on surveys or monitoring, official statistics or on other data provided by institutions and stakeholders in the health system. The nationally representative Health Behaviour in School-Aged Children (HBSC) survey under the auspices of the WHO - which has been conducted every 4 years since 1982, is a further database in Germany that is representative for the 11-15-year olds girls and boys from general educational schools. In this paper, the HBSC survey will be located within the canon of the German health reporting system. A special emphasis is to describe the potential and limitations of HBSC study for health reporting and to highlight the additional value for health reporting in Germany.

  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).

  5. Self-assembly of high molecular weight polypeptide copolymers studied via diffusion limited aggregation.

    PubMed

    Meier, Christoph; Wu, Yuzhou; Pramanik, Goutam; Weil, Tanja

    2014-01-13

    The assembly of high molecular weight polypeptides into complex architectures exhibiting structural complexity ranging from the nano- to the mesoscale is of fundamental importance for various protein-related diseases but also hold great promise for various nano- and biotechnological applications. Here, the aggregation of partially unfolded high molecular weight polypeptides into multiscale fractal structures is investigated by means of diffusion limited aggregation and atomic force microscopy. The zeta potential, the hydrodynamic radius, and the obtained fractal morphologies were correlated with the conformation of the polypeptide backbones as obtained from circular dichroism measurements. The polypeptides are modified with polyethylene oxide side chains to stabilize the polypeptides and to normalize intermolecular interactions. The modification with the hydrophobic thioctic acid alters the folding of the polypeptide backbone, resulting in a change in solution aggregation and fractal morphology. We found that a more compact folding results in dense and highly branched structures, whereas a less compact folded polypeptide chain yields a more directional assembly. Our results provide first evidence for the role of compactness of polypeptide folding on aggregation. Furthermore, the mesoscale-structured biofilms were used to achieve a hierarchical protein assembly, which is demonstrated by deposition of Rhodamine-labeled HSA with the preassembled fractal structures. These results contribute important insights to the fundamental understanding of the aggregation of high molecular weight polypeptides in general and provide opportunities to study nanostructure-related effects on biological systems such as adhesion, proliferation, and the development of, for example, neuronal cells.

  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

  7. Global Retrieval of Roughness Length from EOS-Terra Satellite Products and Limited Field Study Data

    NASA Astrophysics Data System (ADS)

    Schaudt, K. J.; Dickinson, R. E.

    2003-12-01

    Global and regional retrievals, which illustrate the seasonality, of roughness length will be presented. Roughness length is a key factor in estimating the sensible and latent heat fluxes in climate models. In the past the lack of observations made it necessary for most climate models to use relatively crude estimates for roughness length. Typically the roughness length was assigned a constant value for each of the land cover classifications. In reality roughness length depends upon the average height, shape, density and Leaf Area Index (LAI) of the vegetation present. The retrievals presented here depend on these four variables, and they represent a significant improvement over past approaches. The parameterization of roughness length in terms of the four variables (average height, shape, density and LAI) is based on the work of Raupach and Lindroth. The roughness length is formulated in such a way that roughness length can be found either by remote sensing or by variables used in climate models with interactive canopies. The EOS-Terra satellite products used are the overstory plant density and LAI for the seven treed IGBP land cover classes (evergreen and deciduous needle-leaf, evergreen and deciduous broad-leaf and mixed forests, savannah and woody savannah). The tree crown shape (the canopy height-to-width ratio) is based on field studies; it depends on the tree's basic shape (conical or elliptical) and on latitude. At present, the height is of all the vegetation is the average height for the various land cover classifications found in numerous field studies. Limitations of the current retrieval and future improvements will be discussed.

  8. Limited Generalizability of Registration Trials in Hepatitis C: A Nationwide Cohort Study

    PubMed Central

    de Knegt, Robert J.; Blokzijl, Hans; Kuiken, Sjoerd D.; van Erpecum, Karel J. L.; Willemse, Sophie B.; den Hollander, Jan; van Vonderen, Marit G. A.; Friederich, Pieter; van Hoek, Bart; van Nieuwkerk, Carin M. J.; Drenth, Joost P. H.; Kievit, Wietske

    2016-01-01

    Background Approval of drugs in chronic hepatitis C is supported by registration trials. These trials might have limited generalizability through use of strict eligibility criteria. We compared effectiveness and safety of real world hepatitis C patients eligible and ineligible for registration trials. Methods We performed a nationwide, multicenter, retrospective cohort study of chronic hepatitis C patients treated in the real world. We applied a combined set of inclusion and exclusion criteria of registration trials to our cohort to determine eligibility. We compared effectiveness and safety in eligible vs. ineligible patients, and performed sensitivity analyses with strict criteria. Further, we used log binomial regression to assess relative risks of criteria on outcomes. Results In this cohort (n = 467) 47% of patients would have been ineligible for registration trials. Main exclusion criteria were related to hepatic decompensation and co-morbidity (cardiac disease, anemia, malignancy and neutropenia), and were associated with an increased risk for serious adverse events (RR 1.45–2.31). Ineligible patients developed significantly more serious adverse events than eligible patients (27% vs. 11%, p< 0.001). Effectiveness was decreased if strict criteria were used. Conclusions Nearly half of real world hepatitis C patients would have been excluded from registration trials, and these patients are at increased risk to develop serious adverse events. Hepatic decompensation and co-morbidity were important exclusion criteria, and were related to toxicity. Therefore, new drugs should also be studied in these patients, to genuinely assess benefits and risk of therapy in the real world population. PMID:27598789

  9. The human component of sustainability: a study for assessing "human performances" of energy efficient construction blocks.

    PubMed

    Attaianese, Erminia; Duca, Gabriella

    2012-01-01

    This paper presents an applied research aimed at understanding the relevance and the applicability of human related criteria in sustainability assessment of construction materials. Under a theoretical perspective, human factors consideration is strongly encouraged by building sustainability assessment methods, but the practice demonstrates that current models for building sustainability assessment neglect ergonomic issues, especially those ones concerning the construction phase. The study starts from the observation that new construction techniques for high energy efficient external walls are characterized by elements generally heavier and bigger than traditional materials. In this case, high sustainability performances connected with energy saving could be reached only consuming high, and then not very much sustainable, human efforts during setting-up operations. The paper illustrates a practical approach for encompassing human factors in sustainability assessment of four block types for energy efficient external walls. Research steps, from block selections to bricklaying task analysis, human factors indicators and metrics formulation, data gathering and final assessment are going to be presented. Finally, open issues and further possible generalizations from the particular case study will be discussed.

  10. 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.

  11. American Studies: Humanities. Curriculum Study and Improvement Project.

    ERIC Educational Resources Information Center

    1971

    Designed for eleventh grade students, this guide incorporates the four disciplines of art, music, literature, and history. The objectives are for students to apply knowledge gained from the study of past problems toward the problems of contemporary society; to develop an understanding of cultural and societal patterns; to trace personal values of…

  12. 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

  13. 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.

  14. A cocktail of humanized anti-pertussis toxin antibodies limits disease in murine and baboon models of whooping cough

    PubMed Central

    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.

    2016-01-01

    In spite of wide-spread vaccination, pertussis rates are rising in industrialized countries and remain high world-wide. 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. Here, we humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human IgG1 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 B. pertussis-induced rise in white blood cell count and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated but not control animals experienced a blunted rise in white blood cell count 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

  15. Meta-analyses of studies of the human microbiota.

    PubMed

    Lozupone, Catherine A; Stombaugh, Jesse; Gonzalez, Antonio; Ackermann, Gail; Wendel, Doug; Vázquez-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. Meta-analyses of studies of the human microbiota

    PubMed Central

    Lozupone, Catherine A.; Stombaugh, Jesse; Gonzalez, Antonio; Ackermann, Gail; Wendel, Doug; Vázquez-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

  17. In Vitro and In Vivo Models for the Study of Human Polyomavirus Infection

    PubMed Central

    Barth, Heidi; Solis, Morgane; Kack-Kack, Wallys; Soulier, Eric; Velay, Aurélie; Fafi-Kremer, Samira

    2016-01-01

    Developments of genome amplification techniques have rapidly expanded the family of human polyomaviruses (PyV). Following infection early in life, PyV persist in their hosts and are generally of no clinical consequence. High-level replication of PyV can occur in patients under immunosuppressive or immunomodulatory therapy and causes severe clinical entities, such as progressive multifocal leukoencephalopathy, polyomavirus-associated nephropathy or Merkel cell carcinoma. The characterization of known and newly-discovered human PyV, their relationship to human health, and the mechanisms underlying pathogenesis remain to be elucidated. Here, we summarize the most widely-used in vitro and in vivo models to study the PyV-host interaction, pathogenesis and anti-viral drug screening. We discuss the strengths and limitations of the different models and the lessons learned. PMID:27782080

  18. 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...

  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. 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... shall fully disclose, among other financial interests, the candidate's employment, stocks and bonds, and..., EPA will evaluate each candidate to assess whether there is any conflict of financial...

  1. 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...

  2. 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,"…

  3. Has untargeted sexual health promotion for young people reached its limit? A quasi-experimental study

    PubMed Central

    Elliott, Lawrie; Henderson, Marion; Nixon, Catherine; Wight, Daniel

    2013-01-01

    Background Theoretically, there may be benefit in augmenting school-based sexual health education with sexual health services, but the outcomes are poorly understood. Healthy Respect 2 (HR2) combined sex education with youth-friendly sexual health services, media campaigns and branding, and encouraged joint working between health services, local government and the voluntary sector. This study examined whether HR2: (1) improved young people's sexual health knowledge, attitudes, behaviour and use of sexual health services and (2) reduced socioeconomic inequalities in sexual health. Methods A quasi-experiment in which the intervention and comparison areas were matched for teenage pregnancy and terminations, and schools were matched by social deprivation. 5283 pupils aged 15–16 years (2269 intervention, 3014 comparison) were recruited to cross-sectional surveys in 2007, 2008 and 2009. Results The intervention improved males’ and, to a lesser extent, females’ sexual health knowledge. Males’ intention to use condoms, and reported use of condoms, was unaffected, compared with a reduction in both among males in the comparison arm. Although females exposed to the intervention became less accepting of condoms, there was no change in their intention to use condoms and reported condom use. Pupils became more tolerant of sexual coercion in both the intervention and comparison arms. Attitudes towards same-sex relationships remained largely unaffected. More pupils in the HR2 area used sexual health services, including those from lower socioeconomic backgrounds. This aside, sexual health inequalities remained. Conclusions Combining school-based sex education and sexual health clinics has a limited impact. Interventions that address the upstream causes of poor sexual health, such as a detrimental sociocultural environment, represent promising alternatives. These should prioritise the most vulnerable young people. PMID:23427206

  4. Topology of sarcoplasmic reticulum Ca2+-ATPase: an infrared study of thermal denaturation and limited proteolysis.

    PubMed

    Echabe, I; Dornberger, U; Prado, A; Goñi, F M; Arrondo, J L

    1998-05-01

    Sarcoplasmic reticulum Ca2+-ATPase structure and organization in the membrane has been studied by infrared spectroscopy by decomposition of the amide I band. Besides the component bands assignable to secondary structure elements such as alpha-helix, beta-sheet, etc...., two unusual bands, one at 1,645 cm(-1) in H2O buffer and the other at 1,625 cm(-1) in D2O buffer are present. By perturbing the protein using temperature and limited proteolysis, the band at 1,645 cm(-1) is tentatively assigned to alpha-helical segments located in the cytoplasmic domain and coupled to beta-sheet structure, whereas the band at 1,625 cm(-1) arises probably from monomer-monomer contacts in the native oligomeric protein. The secondary structure obtained is 33% alpha-helical segments in the transmembrane plus stalk domain; 20% alpha-helix and 22% beta-sheet in the cytoplasmic domain plus 19% turns and 6% unordered structure. Thermal unfolding of Ca2+-ATPase is a complex process that cannot be described as a two-state denaturation. The results obtained are compatible with the idea that the protein is an oligomer at room temperature. The loss of the 1,625 cm(-1) band upon heating would be consistent with a disruption of the oligomers in a process that later gives rise to aggregates (appearance of the 1,618 cm(-1) band). This picture would also be compatible with early results suggesting that processes governing Ca2+ accumulation and ATPase activity are uncoupled at temperatures above 37 degrees C, so that while ATPase activity proceeds at high rates, Ca2+ accumulation is inhibited.

  5. Topology of sarcoplasmic reticulum Ca2+-ATPase: an infrared study of thermal denaturation and limited proteolysis.

    PubMed Central

    Echabe, I.; Dornberger, U.; Prado, A.; Goñi, F. M.; Arrondo, J. L.

    1998-01-01

    Sarcoplasmic reticulum Ca2+-ATPase structure and organization in the membrane has been studied by infrared spectroscopy by decomposition of the amide I band. Besides the component bands assignable to secondary structure elements such as alpha-helix, beta-sheet, etc...., two unusual bands, one at 1,645 cm(-1) in H2O buffer and the other at 1,625 cm(-1) in D2O buffer are present. By perturbing the protein using temperature and limited proteolysis, the band at 1,645 cm(-1) is tentatively assigned to alpha-helical segments located in the cytoplasmic domain and coupled to beta-sheet structure, whereas the band at 1,625 cm(-1) arises probably from monomer-monomer contacts in the native oligomeric protein. The secondary structure obtained is 33% alpha-helical segments in the transmembrane plus stalk domain; 20% alpha-helix and 22% beta-sheet in the cytoplasmic domain plus 19% turns and 6% unordered structure. Thermal unfolding of Ca2+-ATPase is a complex process that cannot be described as a two-state denaturation. The results obtained are compatible with the idea that the protein is an oligomer at room temperature. The loss of the 1,625 cm(-1) band upon heating would be consistent with a disruption of the oligomers in a process that later gives rise to aggregates (appearance of the 1,618 cm(-1) band). This picture would also be compatible with early results suggesting that processes governing Ca2+ accumulation and ATPase activity are uncoupled at temperatures above 37 degrees C, so that while ATPase activity proceeds at high rates, Ca2+ accumulation is inhibited. PMID:9605321

  6. 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

  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.

  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.

  9. 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

  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. Study on Recovery Performance of High Tc Superconducting Tapes for Resistive Type Superconducting Fault Current Limiter Applications

    NASA Astrophysics Data System (ADS)

    kar, Soumen; Kulkarni, Sandeep; Dixit, Manglesh; Singh, Kuwar Pal; Gupta, Alok; Balasubramanyam, P. V.; Sarangi, S. K.; Rao, V. V.

    Recent advances in reliable production of long length high temperature superconducting (HTS) tapes have resulted in commercial application of superconducting fault current limiters (SFCLs) in electrical utility networks. SFCL gives excellent technical performance when compared to conventional fault current limiters. The fast self-recovery from normal state to superconducting state immediately after the fault removal is an essential criterion for resistive type SFCL operation. In this paper, results on AC over-current testing of 1st generation (1G) Bi2223 tapes and 2nd generation (2G) YBCO coated conductors operating at 77 K are reported. From these results, the recovery time is estimated for different available HTS tapes in the market. The current limiting tests have also been performed to study the effective current limitation. Further, the recovery characteristics after the current limitation are quantitatively discussed for repetitive faults for different time intervals in the range of 100 ms to few seconds.

  12. Local confidence limits for IMRT and VMAT techniques: a study based on TG119 test suite.

    PubMed

    Thomas, M; Chandroth, M

    2014-03-01

    The aim of this study was to generate a local confidence limit (CL) for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques used at Waikato Regional Cancer Centre. This work was carried out based on the American Association of Physicists in Medicine (AAPM) Task Group (TG) 119 report. The AAPM TG 119 report recommends CLs as a bench mark for IMRT commissioning and delivery based on its multiple institutions planning and dosimetry comparisons. In this study the locally obtained CLs were compared to TG119 benchmarks. Furthermore, the same bench mark was used to test the capabilities and quality of the VMAT technique in our clinic. The TG 119 test suite consists of two primary and four clinical tests for evaluating the accuracy of IMRT planning and dose delivery systems. Pre defined structure sets contoured on computed tomography images were downloaded from AAPM website and were transferred to a locally designed phantom. For each test case two plans were generated using IMRT and VMAT optimisation. Dose prescriptions and planning objectives recommended by TG119 report were followed to generate the test plans in Eclipse Treatment Planning System. For each plan the point dose measurements were done using an ion chamber at high dose and low dose regions. The planar dose distribution was analysed for percentage of points passing the gamma criteria of 3%/3 mm, for both the composite plan and individual fields of each plan. The CLs were generated based on the results from the gamma analysis and point dose measurements. For IMRT plans, the CLs obtained were (1) from point dose measurements: 2.49% at high dose region and 2.95% for the low dose region (2) from gamma analysis: 2.12% for individual fields and 5.9% for the composite plan. For VMAT plans, the CLs obtained were (1) from point dose measurements: 2.56% at high dose region and 2.6% for the low dose region (2) from gamma analysis: 1.46% for individual fields and 0.8% for

  13. Operating limit study for the proposed solid waste landfill at Paducah Gaseous Diffusion Plant

    SciTech Connect

    Lee, D.W.; Wang, J.C.; Kocher, D.C.

    1995-06-01

    A proposed solid waste landfill at Paducah Gaseous Diffusion Plant (PGDP) would accept wastes generated during normal operations that are identified as non-radioactive. These wastes may include small amounts of radioactive material from incidental contamination during plant operations. A site-specific analysis of the new solid waste landfill is presented to determine a proposed operating limit that will allow for waste disposal operations to occur such that protection of public health and the environment from the presence of incidentally contaminated waste materials can be assured. Performance objectives for disposal were defined from existing regulatory guidance to establish reasonable dose limits for protection of public health and the environment. Waste concentration limits were determined consistent with these performance objectives for the protection of off-site individuals and inadvertent intruders who might be directly exposed to disposed wastes. Exposures of off-site individuals were estimated using a conservative, site-specific model of the groundwater transport of contamination from the wastes. Direct intrusion was analyzed using an agricultural homesteader scenario. The most limiting concentrations from direct intrusion or groundwater transport were used to establish the concentration limits for radionuclides likely to be present in PGDP wastes.

  14. Improving the Limit on the Electron EDM: Data Acquisition and Systematics Studies in the ACME Experiment

    NASA Astrophysics Data System (ADS)

    Hess, Paul William

    The ACME collaboration has completed a measurement setting a new upper limit on the size of the electron's permanent electric dipole moment (EDM). The existence of the EDM is well motivated by theories extending the standard model of particle physics, with predicted sizes very close to the current experimental limit. The new limit was set by measuring spin precession within the metastable H state of the polar molecule thorium monoxide (ThO). A particular focus here is on the automated data acquisition system developed to search for a precession phase odd under internal and external reversal of the electric field. Automated switching of many different experimental controls allowed a rapid diagnosis of major systematics, including the dominant systematic caused by non-reversing electric fields and laser polarization gradients. Polarimetry measurements made it possible to quantify and minimize the polarization gradients in our state preparation and probe lasers. Three separate measurements were used to determine the electric field that did not reverse when we tried to switch the field direction. The new bound of | de| < 8.7 x 10--29 e·cm is over an order of magnitude smaller than previous limits, and strongly limits T-violating physics at TeV energy scales.

  15. Western Zika Virus in Human Fetal Neural Progenitors Persists Long Term with Partial Cytopathic and Limited Immunogenic Effects.

    PubMed

    Hanners, Natasha W; Eitson, Jennifer L; Usui, Noriyoshi; Richardson, R Blake; Wexler, Eric M; Konopka, Genevieve; Schoggins, John W

    2016-06-14

    The recent Zika virus (ZIKV) outbreak in the Western hemisphere is associated with severe pathology in newborns, including microcephaly and brain damage. The mechanisms underlying these outcomes are under intense investigation. Here, we show that a 2015 ZIKV isolate replicates in multiple cell types, including primary human fetal neural progenitors (hNPs). In immortalized cells, ZIKV is cytopathic and grossly rearranges endoplasmic reticulum membranes similar to other flaviviruses. In hNPs, ZIKV infection has a partial cytopathic phase characterized by cell rounding, pyknosis, and activation of caspase 3. Despite notable cell death, ZIKV did not activate a cytokine response in hNPs. This lack of cell intrinsic immunity to ZIKV is consistent with our observation that virus replication persists in hNPs for at least 28 days. These findings, supported by published fetal neuropathology, establish a proof-of-concept that neural progenitors in the developing human fetus can be direct targets of detrimental ZIKV-induced pathology.

  16. 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

  17. 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:...

  18. 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:...

  19. 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:...

  20. 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:...

  1. 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:...

  2. Human Mars Entry, Descent and Landing Architectures Study Overview

    NASA Technical Reports Server (NTRS)

    Polsgrove, Tara T.; Dwyer Cianciolo, Alicia

    2016-01-01

    Landing humans on Mars will require entry, descent and landing (EDL) capability beyond the current state of the art. Nearly twenty times more delivered payload and an order of magnitude improvement in precision landing capability will be necessary. Several EDL technologies capable of meeting the human class payload delivery requirements are being considered. The EDL technologies considered include low lift-to-drag vehicles like Hypersonic Inflatable Aerodynamic Decelerators (HIAD), Adaptable Deployable Entry and Placement Technology (ADEPT), and mid range lift-to-drag vehicles like rigid aeroshell configurations. To better assess EDL technology options and sensitivities to future human mission design variations, a series of design studies has been conducted. The design studies incorporate EDL technologies with conceptual payload arrangements defined by the Evolvable Mars Campaign to evaluate the integrated system with higher fidelity than have been performed to date. This paper describes the results of the design studies for a lander design using the HIAD, ADEPT and rigid shell entry technologies and includes system and subsystem design details including mass and power estimates. This paper will review the point design for three entry configurations capable of delivering a 20 t human class payload to the surface of Mars.

  3. 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

  4. Covalent ligation studies on the human telomere quadruplex

    PubMed Central

    Qi, Jianying; Shafer, Richard H.

    2005-01-01

    Recent X-ray crystallographic studies on the human telomere sequence d[AGGG(TTAGGG)3] revealed a unimolecular, parallel quadruplex structure in the presence of potassium ions, while earlier NMR results in the presence of sodium ions indicated a unimolecular, antiparallel quadruplex. In an effort to identify and isolate the parallel form in solution, we have successfully ligated into circular products the single-stranded human telomere and several modified human telomere sequences in potassium-containing solutions. Using these sequences with one or two terminal phosphates, we have made chemically ligated products via creation of an additional loop. Circular products have been identified by polyacrylamide gel electrophoresis, enzymatic digestion with exonuclease VII and electrospray mass spectrometry in negative ion mode. Optimum pH for the ligation reaction of the human telomere sequence ranges from 4.5 to 6.0. Several buffers were also examined, with MES yielding the greatest ligation efficiency. Human telomere sequences with two phosphate groups, one each at the 3′ and 5′ ends, were more efficient at ligation, via pyrophosphate bond formation, than the corresponding sequences with only one phosphate group, at the 5′ end. Circular dichroism spectra showed that the ligation product was derived from an antiparallel, single-stranded guanine quadruplex rather than a parallel single-stranded guanine quadruplex structure. PMID:15933211

  5. Study and Analysis of Heat Transfer Limitation of Separated Heat Pipe

    NASA Astrophysics Data System (ADS)

    Mou, Qizheng; Mou, Kai

    2002-01-01

    satellite and spacecraft. evaporator, heat isolation and condenser along the axial direction. The working fluid absorbs heat and evaporates in evaporator, and then the vapor flows to condenser and gives out heat. The condensed liquid is pumped to evaporator by wick. By the circulation, the heat can by transferred continuously. heat pipe as follow: - Vapor-liquid two phase flow inside pipe; - The manner of latent heat to transfer heat; - Automatic circulation by working fluid flowing - A certain extent of vacuum. and the traditional heat pipe, that is, the vapor fluid and liquid fluid flow along the same direction. So it is obviously that the separated heat pipe has special internal heat transfer characteristic and crisis. This paper has regard for the heat transfer crisis of the separated heat pipe, and meanwhile relevant calculation and analysis have been done. 1. FLOW TYPE OF THE WORKING FLUID IN SEPARATED HEAT PIPE 2. HEAT TRANSFER CRISIS IN THE EVAPORATOR 3. CARRYING PHENOMENON INSIDE SEPARATED HEAT PIPE 4. THE STAGNANT FLOW PHENOMENON AND THE BACKWARD FLOW PHENOMENON IN EVAPORATOR CONCLUSION transfer limitation of location burn-out, and the heat transfer limitation of flow unconventionality in erective pipe. The carrying phenomenon can occurs not only in evaporator but also in condenser of separated heat pipe. It is in the evaporator that should take place the heat transfer limitation of liquid film dry-out at first. Then with the increasing of heat flux, the heat transfer limitation of location burn-out would happen. In order to avoid the heat transfer limitation of flow unconventionality in erective pipe, the length and diameter of the outflow tube and inflow tube must be reasonably calculated to control the flow velocity of the working fluid inside pipe. Key words:Separated Heat PipeHeat Transfer LimitationDry-OutCarryingStagnancy

  6. 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

  7. Reminiscences of a journeyman scientist: studies of thermoregulation in non-human primates and humans.

    PubMed

    Adair, Eleanor Reed

    2008-12-01

    After graduating from Mount Holyoke College in 1948 where I majored in experimental psychology I worked at the College for 2 years with the Johns Hopkins Thermophysiological Unit. My graduate work later at the University of Wisconsin, centering on sensory psychology, culminated in my 1955 PhD thesis on human dark adaptation. I continued work in sensory psychology later with Neal Miller at Yale and then moved to the John B. Pierce Foundation--a Yale affiliate--where I began the studies of thermoregulation that constitute the center of my scientific career. Those studies were largely--later wholly--conducted using microwave energy as a thermal load and were thus published in Bioelectromagnetics even as I played an active role in the Bioelectromagnetics Society. In the beginning this work was centered on the responses of Squirrel Monkeys to thermal loads. Later, serving as Senior Scientist at the Air Force Research Laboratory at San Antonio, I completed an extensive analysis of thermal regulation in humans. I consider this work of special note inasmuch as the extraordinary human thermoregulatory ability was surely among the attributes that were paramount in initially separating humans from the other anthropoid primates.

  8. Animal-free toxicology: the use of human tissue to replace the use of animals - examples from human biomonitoring and human placental transport studies.

    PubMed

    Knudsen, Lisbeth E

    2013-12-01

    Human data on exposure and adverse effects are the most appropriate for human risk assessment, and modern toxicology focuses on human pathway analysis and the development of human biomarkers. Human biomonitoring and human placental transport studies provide necessary information for human risk assessment, in accordance with the legislation on chemical, medicine and food safety. Toxicology studies based on human mechanistic and exposure information can replace animal studies. These animal-free approaches can be further supplemented by new in silico methods and chemical structure-activity relationships. The inclusion of replacement expertise in the international Three Rs centres, the ongoing exploration of alternatives to animal research, and the improvement of conditions for research animals, all imply the beginning of a paradigm shift in toxicology research toward the use of human data.

  9. Experimental design for estimating parameters of rate-limited mass transfer: Analysis of stream tracer studies

    NASA Astrophysics Data System (ADS)

    Wagner, Brian J.; Harvey, Judson W.

    Tracer experiments are valuable tools for analyzing the transport characteristics of streams and their interactions with shallow groundwater. The focus of this work is the design of tracer studies in high-gradient stream systems subject to advection, dispersion, groundwater inflow, and exchange between the active channel and zones in surface or subsurface water where flow is stagnant or slow moving. We present a methodology for (1) evaluating and comparing alternative stream tracer experiment designs and (2) identifying those combinations of stream transport properties that pose limitations to parameter estimation and therefore a challenge to tracer test design. The methodology uses the concept of global parameter uncertainty analysis, which couples solute transport simulation with parameter uncertainty analysis in a Monte Carlo framework. Two general conclusions resulted from this work. First, the solute injection and sampling strategy has an important effect on the reliability of transport parameter estimates. We found that constant injection with sampling through concentration rise, plateau, and fall provided considerably more reliable parameter estimates than a pulse injection across the spectrum of transport scenarios likely encountered in high-gradient streams. Second, for a given tracer test design, the uncertainties in mass transfer and storage-zone parameter estimates are strongly dependent on the experimental Damkohler number, DaI, which is a dimensionless combination of the rates of exchange between the stream and storage zones, the stream-water velocity, and the stream reach length of the experiment. Parameter uncertainties are lowest at DaI values on the order of 1.0. When DaI values are much less than 1.0 (owing to high velocity, long exchange timescale, and/or short reach length), parameter uncertainties are high because only a small amount of tracer interacts with storage zones in the reach. For the opposite conditions (DaI>>1.0), solute exchange

  10. Experimental design for estimating parameters of rate-limited mass transfer: Analysis of stream tracer studies

    USGS Publications Warehouse

    Wagner, B.J.; Harvey, J.W.

    1997-01-01

    Tracer experiments are valuable tools for analyzing the transport characteristics of streams and their interactions with shallow groundwater. The focus of this work is the design of tracer studies in high-gradient stream systems subject to advection, dispersion, groundwater inflow, and exchange between the active channel and zones in surface or subsurface water where flow is stagnant or slow moving. We present a methodology for (1) evaluating and comparing alternative stream tracer experiment designs and (2) identifying those combinations of stream transport properties that pose limitations to parameter estimation and therefore a challenge to tracer test design. The methodology uses the concept of global parameter uncertainty analysis, which couples solute transport simulation with parameter uncertainty analysis in a Monte Carlo framework. Two general conclusions resulted from this work. First, the solute injection and sampling strategy has an important effect on the reliability of transport parameter estimates. We found that constant injection with sampling through concentration rise, plateau, and fall provided considerably more reliable parameter estimates than a pulse injection across the spectrum of transport scenarios likely encountered in high-gradient streams. Second, for a given tracer test design, the uncertainties in mass transfer and storage-zone parameter estimates are strongly dependent on the experimental Damkohler number, DaI, which is a dimensionless combination of the rates of exchange between the stream and storage zones, the stream-water velocity, and the stream reach length of the experiment. Parameter uncertainties are lowest at DaI values on the order of 1.0. When DaI values are much less than 1.0 (owing to high velocity, long exchange timescale, and/or short reach length), parameter uncertainties are high because only a small amount of tracer interacts with storage zones in the reach. For the opposite conditions (DaI >> 1.0), solute exchange

  11. Human population studies and the World Health Organization.

    PubMed

    de Chadarevian, Soraya

    2015-01-01

    This essay draws attention to the role of the WHO in shaping research agendas in the biomedical sciences in the postwar era. It considers in particular the genetic studies of human populations that were pursued under the aegis of the WHO from the late 1950s to 1970s. The study provides insights into how human and medical genetics entered the agenda of the WHO. At the same time, the population studies become a focus for tracking changing notions of international relations, cooperation, and development and their impact on research in biology and medicine in the post-World War I era. After a brief discussion of the early history of the WHO and its position in Cold War politics, the essay considers the WHO program in radiation protection and heredity and how the genetic study of "vanishing" human populations and a world-wide genetic study of newborns fitted this broader agenda. It then considers in more detail the kind of support offered by the WHO for these projects. The essay highlights the role of single individuals in taking advantage of WHO support for pushing their research agendas while establishing a trend towards cooperative international projects in biology.

  12. 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.

  13. Human population studies and the World Health Organization.

    PubMed

    de Chadarevian, Soraya

    2015-01-01

    This essay draws attention to the role of the WHO in shaping research agendas in the biomedical sciences in the postwar era. It considers in particular the genetic studies of human populations that were pursued under the aegis of the WHO from the late 1950s to 1970s. The study provides insights into how human and medical genetics entered the agenda of the WHO. At the same time, the population studies become a focus for tracking changing notions of international relations, cooperation, and development and their impact on research in biology and medicine in the post-World War I era. After a brief discussion of the early history of the WHO and its position in Cold War politics, the essay considers the WHO program in radiation protection and heredity and how the genetic study of "vanishing" human populations and a world-wide genetic study of newborns fitted this broader agenda. It then considers in more detail the kind of support offered by the WHO for these projects. The essay highlights the role of single individuals in taking advantage of WHO support for pushing their research agendas while establishing a trend towards cooperative international projects in biology. PMID:26775433

  14. Understanding the Limits of Marxist Approaches to Sociocultural Studies of Science Education

    ERIC Educational Resources Information Center

    Lima, Paulo, Jr.; Ostermann, Fernanda; Rezende, Flavia

    2014-01-01

    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…

  15. Redundant Manipulator Self-Motion Topology Under Joint Limits with an 8-DOF Case Study

    NASA Technical Reports Server (NTRS)

    Luck, C. L.; Lee, S.

    1993-01-01

    This paper investigates the topology of self-motion manifolds for serial redundant manipulators with revolute joints in the presence of joint limits. It is known that the preimages of singular taskpoints divide the configuration space into regions where self-motion manifolds are homotopic.

  16. High-Stakes Testing, High School Graduation, and Limited English Proficient Students: A Case Study

    ERIC Educational Resources Information Center

    Giambo, Debra A.

    2010-01-01

    The educational accountability systems of both the No Child Left Behind (NCLB) Act of 2001 and the state of Florida (as of 1999) were modeled after Texas' system, despite its flaws. NCLB reaches for all students to achieve academic proficiency and designates students with limited English proficiency (LEP) as an important subgroup. As we work with…

  17. 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.

  18. 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

  19. Additional road markings as an indication of speed limits: results of a field experiment and a driving simulator study.

    PubMed

    Daniels, Stijn; Vanrie, Jan; Dreesen, An; Brijs, Tom

    2010-05-01

    Although speed limits are indicated by road signs, road users are not always aware, while driving, of the actual speed limit on a given road segment. The Roads and Traffic Agency developed additional road markings in order to support driver decisions on speed on 70 km/h roads in Flanders-Belgium. In this paper the results are presented of two evaluation studies, both a field study and a simulator study, on the effects of the additional road markings on speed behaviour. The results of the field study showed no substantial effect of the markings on speed behaviour. Neither did the simulator study, with slightly different stimuli. Nevertheless an effect on lateral position was noticed in the simulator study, showing at least some effect of the markings. The role of conspicuity of design elements and expectations towards traffic environments is discussed. Both studies illustrate well some strengths and weaknesses of observational field studies compared to experimental simulator studies.

  20. Voluntary limit setting and player choice in most intense online gamblers: an empirical study of gambling behaviour.

    PubMed

    Auer, Michael; Griffiths, Mark D

    2013-12-01

    Social responsibility in gambling has become a major issue for the gaming industry. The possibility for online gamblers to set voluntary time and money limits are a social responsibility practice that is now widespread among online gaming operators. The main issue concerns whether the voluntary setting of such limits has any positive impact on subsequent gambling behaviour and whether such measures are of help to problem gamblers. In this paper, this issue is examined through data collected from a representative random sample of 100,000 players who gambled on the win2day gambling website. When opening an account at the win2day site, there is a mandatory requirement for all players to set time and cash-in limits (that cannot exceed 800 per week). During a 3-month period, all voluntary time and/or money limit setting behaviour by a subsample of online gamblers (n = 5,000) within this mandatory framework was tracked and recorded for subsequent data analysis. From the 5,000 gamblers, the 10 % most intense players (as measured by theoretical loss) were further investigated. Voluntary spending limits had the highest significant effect on subsequent monetary spending among casino and lottery gamblers. Monetary spending among poker players significantly decreased after setting a voluntary time limit. The highest significant decrease in playing duration was among poker players after setting a voluntary playing duration limit. The results of the study demonstrated that voluntary limit setting had a specific and significant effect on the studied gamblers. Therefore, voluntary limits appear to show an appropriate effect in the desired target group (i.e., the most gaming intense players).