Sample records for limited human studies

  1. APS: Studying the Human Physiological Limits of Exploring Mars

    NSDL National Science Digital Library

    PhD James A Pawelczyk (Pennsylvania State University)

    2009-05-13

    This Web Seminar, developed in collaboration with the National Science Digital Library, took place on Wednesday, May 13, 2009 from 6:30 p.m. to 8:00 p.m. Eastern time. In this seminar, Dr Pawelczyk examined the effects of long-term travel on the human body in outer space.

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

    SciTech Connect

    Boehnke, M. (Univ. of Michigan, Ann Arbor, MI (United States))

    1994-08-01

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

  3. A Probabilistic Approach for Deriving Acceptable Human Intake Limits and Human Health Risks from Toxicological Studies: General Framework

    Microsoft Academic Search

    W. Slob; M. N. Pieters

    1998-01-01

    The use of uncertainty factors in the standard method for deriving acceptable intake or exposure limits for humans, such as the Reference Dose (RfD), may be viewed as a conservative method of taking various uncertainties into account. As an obvious alternative, the use of uncertainty distributions instead of uncertainty factors is gaining attention. This paper presents a comprehensive discussion of

  4. How can human populations be limited?

    E-print Network

    Mitchell, Randall J.

    1 How can human populations be limited? Which of these do you prefer as a means to limit human can human populations be limited? · Ultimate causes: ­ Increase deaths ­ Reduce births Movement out human population · Proximate causes ­ What can be done to change birth and death rates? Global Human

  5. Archive: APS: Studying the Human Physiological Limits of Exploring Mars, May 13, 2009

    NSDL National Science Digital Library

    1900-01-01

    Dr. Jim Pawelczyk, Associate Professor of Physiology, Kinesiology and Medicine at Pennsylvania State University has had extensive experience as an astronaut and researcher on the effects of microgravity on the human body. Missions to Mars would require humans to travel well beyond the current record of 15 months by a Russian astronaut, and doubling that length to nearly 30 months. Factors such as the environment, bone repair and growth, radiation, psychological stamina, and other influences play a critical role towards achieving this goal. Data from previous missions such as the International Space Station and Skylab have helped in determining how to address these challenges, but Pawelczyk points out the need to inspire today's students to realize the solutions and possibilities of such travel since they will be our astronauts, engineers, and scientists of tomorrow. For more information about this web seminar, its presenter(s), read what participants said about it, and to see and download its PowerPoint slides go here .

  6. Limitations of Hairless Mouse Skin as a Model for In Vitro Permeation Studies Through Human Skin: Hydration Damage

    Microsoft Academic Search

    John Russell Bond; Brian William Barry

    1988-01-01

    Hairless mouse skin currently provides a popular model membrane for studies in human percutaneous absorption. Although some similarities between the two skin types have been demonstrated, the effects of prolonged hydration on hairless mouse skin have not previously been rigorously examined. We have measured in vitro the effects of hydration at 31°C on the permeabilities of hairless mouse skin and

  7. Human Rights Watch: Limits of Tolerance

    NSDL National Science Digital Library

    Human Rights Watch has recently posted a new report. "Limits of Tolerance: Freedom of Expression and the Public Debate in Chile," examines the extreme restrictions on freedom of speech and freedom of information in the ostensibly democratic nation of Chile.

  8. Teleoperator Human Factors Study

    NASA Technical Reports Server (NTRS)

    1986-01-01

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

  9. Limits to sustainable human metabolic rate.

    PubMed

    Westerterp, K R

    2001-09-01

    There is a limit to the performance of an organism set by energy intake and energy mobilization. Here, the focus is on humans with unlimited access to food and for whom physical activity can be limited by energy mobilization. The physical activity level (PAL) in the general population, calculated as doubly-labelled-water-assessed average daily metabolic rate as a multiple of basal metabolic rate, has an upper limit of 2.2-2.5. The upper limit of sustainable metabolic rate is approximately twice as high in endurance athletes, mainly because of long-term exercise training with simultaneous consumption of carbohydrate-rich food during exercise. Endurance athletes have an increased fat-free mass and can maintain energy balance at a PAL value of 4.0-5.0. High altitude limits exercise performance as a result of combined effects on nutrient supply and the capacity to process nutrients. Thus, trained subjects climbing Mount Everest reached PAL values of 2.0-2.7, well below the observed upper limit at sea level. PMID:11581332

  10. Phosphorus: a limiting nutrient for humanity?

    PubMed

    Elser, James J

    2012-12-01

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

  11. Intractable Limits to a Sustainable Human Population

    Microsoft Academic Search

    Andrew RB Ferguson

    2005-01-01

    The pressing need for a much smaller world population arises for two reasons. Humans are emitting about two and a half times as much carbon as the maximum permissible to achieve stabilisation of carbon in the atmosphere. Today's six billion humans, in striving to enjoy at least a basic quality of life, are damaging many vital ecological systems and causing

  12. Limiting Reactants: Industrial Case Study

    NSDL National Science Digital Library

    Dave Blackburn

    An exercise in which students apply limiting reactants, mass ratios and percent yields to suggest an optimum industrial process. Cost figures are provided but students are told to come up with, and defend, their own criteria for their recommendation.

  13. Human factor and computational intelligence limitations in resilient control systems

    E-print Network

    Wilamowski, Bogdan Maciej

    Human factor and computational intelligence limitations in resilient control systems Bogdan M. Wilamowski Auburn University Abstract - Humans are very capable of solving many scientific and engineering problems, but during the solution process they have a tendency to make mistakes. For example, humans

  14. Environmental thermodynamic limitations on global human population

    Microsoft Academic Search

    Viorel Badescu; Richard B. Cathcart

    2006-01-01

    This paper examines, from a thermodynamic point of view, how many people the Earth can support. The maximum human population allowed by the natural earth ranges from 300 million millions to 1,700 million millions and will not exceed 1,300 million millions if an ambient temperature of 300 K is accepted. A further increase in population number is obtained for macro-engineered

  15. 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

  16. 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.

  17. Study Abroad in Humanities

    E-print Network

    Heller, Barbara

    Study Abroad in Humanities Studying abroad is increasingly important for social science majors gained are critical to the companies' success. Why should I go abroad? Studying abroad is an opportunity your studies and career. Some of the potential benefits of going abroad include: Experience another

  18. Studies on the dynamics of limited filaments

    E-print Network

    Bonde, Jeffrey David

    2010-01-01

    A study on the dynamics of filaments in the presence of a diagnostic, conductive limiter is presented. Plasma filaments are coherent structures present in many fusion devices and transport a significant amount of particles ...

  19. 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

  20. Pumped-limiter study for Alcator DCT

    SciTech Connect

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

    1983-06-01

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

  1. Effects of band-limited noise on human observer performance

    NASA Astrophysics Data System (ADS)

    Salem, Salem; Jacobs, Eddie; Moore, Richard; Hogervorst, Maarten; Bijl, Piet; Halford, Carl

    2007-04-01

    Perception tests establish the effects of spatially band-limited noise and blur on human observer performance. Previously, Bijl showed that the contrast threshold of a target image with spatially band-limited noise is a function of noise spatial frequency. He used the method of adjustment to find the contrast thresholds for each noise frequency band. A noise band exists in which the target contrast threshold reaches a peak relative to the threshold for higher- or lower-noise frequencies. Bijl also showed that the peak of this noise band shifts as high frequency information is removed from the target images. To further establish these results, we performed forced-choice experiments. First, a Night Vision and Electronics Sensors Directorate (NVESD) twelve (12)-target infrared tracked vehicle image set identification (ID) experiment, second, a bar-pattern resolving experiment, and third, a Triangle Orientation Discrimination (TOD) experiment. In all of the experiments, the test images were first spatially blurred, then spatially band-limited noise was added. The noise center spatial frequency was varied in half-octave increments over seven octaves. Observers were shown images of varying target-to-noise contrasts, and a contrast threshold was calculated for each spatial noise band. Finally, we compared the Targeting Task Performance (TTP) human observer model predictions for performance in the presence of spatially band-limited noise with these experimental results.

  2. Human endothelial dihydrofolate reductase low activity limits vascular tetrahydrobiopterin recycling.

    PubMed

    Whitsett, Jennifer; Rangel Filho, Artur; Sethumadhavan, Savitha; Celinska, Joanna; Widlansky, Michael; Vasquez-Vivar, Jeannette

    2013-10-01

    Tetrahydrobiopterin (BH?) is required for NO synthesis and inhibition of superoxide release from endothelial NO synthase. Clinical trials using BH? to treat endothelial dysfunction have produced mixed results. Poor outcomes may be explained by the rapid systemic and cellular oxidation of BH?. One of the oxidation products of BH?, 7,8-dihydrobiopterin (7,8-BH?), is recycled back to BH? by dihydrofolate reductase (DHFR). This enzyme is ubiquitously distributed and shows a wide range of activity depending on species-specific factors and cell type. Information about the kinetics and efficiency of BH4 recycling in human endothelial cells receiving BH? treatment is lacking. To characterize this reaction, we applied a novel multielectrode coulometric HPLC method that enabled the direct quantification of 7,8-BH? and BH?, which is not possible with fluorescence-based methodologies. We found that basal untreated BH? and 7,8-BH? concentrations in human endothelial cells (ECs) are lower than in bovine and murine endothelioma cells. Treatment of human ECs with BH? transiently increased intracellular BH? while accumulating the more stable 7,8-BH?. This was different from bovine or murine ECs, which resulted in preferential BH? increase. Using BH? diastereomers, 6S-BH? and 6R-BH?, the narrow contribution of enzymatic DHFR recycling to total intracellular BH? was demonstrated. Reduction of 7,8-BH? to BH? occurs at very slow rates in cells and needs supraphysiological levels of 7,8-BH?, indicating this reaction is kinetically limited. Activity assays verified that human DHFR has very low affinity for 7,8-BH? (DHF7,8-BH?) and folic acid inhibits 7,8-BH? recycling. We conclude that low activity of endothelial DHFR is an important factor limiting the benefits of BH4 therapies, which may be further aggravated by folate supplements. PMID:23707606

  3. Limitations on the Analysis of Relaxation Studies

    NASA Astrophysics Data System (ADS)

    Snyder, Chad; Mopsik, Frederick

    1998-03-01

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

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

    PubMed Central

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

    2014-01-01

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

  5. PINEAL MELATONIN LEVEL DISRUPTION IN HUMANS DUE TO ELECTROMAGNETIC FIELDS AND ICNIRP LIMITS

    E-print Network

    Halgamuge, Malka N.

    PINEAL MELATONIN LEVEL DISRUPTION IN HUMANS DUE TO ELECTROMAGNETIC FIELDS AND ICNIRP LIMITS Malka N to power-frequency (50 or 60 Hz) EMFs is unavoidable. Melatonin is a natural hormone produced by pineal, as a consequence, may decrease the melatonin production. In this study, more than one hundred experimental data

  6. STUDIES ON HUMAN ANTIBODIES

    PubMed Central

    Moreno, Carlos; Kabat, Elvin A.

    1969-01-01

    Human antibodies to blood group A substance were purified by absorption on columns of insoluble polyleucyl hog blood group A + H substance and eluted first with N-acetylgalactosamine and then with an A active reduced pentasaccharide ARL0.52. The ?M and ?G antibodies in these eluates were separated by density gradient centrifugation. The antibodies were studied for their relative capacities to be inhibited by various blood group A active oligosaccharides. Antibodies eluted by the N-acetylgalactosamine could be inhibited by N-acetylgalactosamine, as well as by lower concentrations of A active tri- and pentasaccharides, while those eluted by the pentasaccharide ARL0.52 could only be inhibited by the two oligosaccharides, but not by N-acetylgalactosamine, indicating that the N-acetylgalactosamine eluate had more antibodies with smaller size combining sites than the ARL0.52 eluate. Measurements by equilibrium dialysis gave values ranging from 2 x 103 to 1 x 105 M–1 and the values obtained with the ARL0.52 eluate were somewhat higher than those with the GalNAc eluate. Only one of three anti-A sera had ?M anti-A in the ARL0.52 eluate, while all three had ?M in the N-acetylgalactosamine eluate. Data on the precipitating, hemagglutinating, complement fixing, hemolytic properties of the eluted antibodies, and of their content of ? and ? light chains are given. PMID:5778788

  7. HUMAN DEVELOPMENT Program of Study

    E-print Network

    Thomas, Andrew

    HUMAN DEVELOPMENT Program of Study Financial Aid Students Applying Correspondence The graduate program in Human Development is designed to provide advanced training, with special emphasis on child development and family relations. This program is designed for those interested in working in the human

  8. Limited communication capacity unveils strategies for human interaction

    PubMed Central

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

    2013-01-01

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

  9. Limited communication capacity unveils strategies for human interaction

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  10. 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

  11. Endothelial human dihydrofolate reductase low activity limits vascular tetrahydrobiopterin recycling

    PubMed Central

    Whitsett, Jennifer; Filho, Artur Rangel; Sethumadhavan, Savitha; Celinska, Joanna; Widlansky, Michael; Vásquez-Vivar, Jeannette

    2013-01-01

    Tetrahydrobiopterin (BH4) is required for NO synthesis and inhibition of superoxide release from eNOS. Clinical trials using BH4 to treat endothelial dysfunction have produced mixed results. Poor outcomes may be explained by the rapid systemic and cellular oxidation of BH4. One of the oxidation products of BH4, 7,8-dihydrobiopterin (7,8-BH2), is recycled back to BH4 by dihydrofolate reductase (DHFR). This enzyme is ubiquitously distributed and shows a wide range of activity depending on species-specific factors and cell type. Information about the kinetics and efficiency of BH4 recycling in human endothelial cells receiving BH4 treatment is lacking. To characterize this reaction, we applied a novel multi-electrode coulometric HPLC method that enabled the direct quantification of 7,8-BH2 and BH4 which is not possible with fluorescent-based methodologies. We found that basal untreated BH4 and 7,8-BH2 concentrations in human ECs is lower than bovine and murine endothelioma cells. Treatment of human ECs with BH4 transiently increased intracellular BH4 while accumulating the more stable 7,8-BH2. This was different from bovine or murine ECs that resulted in preferential BH4 increase. Using BH4 diastereomers, 6S-BH4 and 6R-BH4, the narrow contribution of enzymatic DHFR recycling to total intracellular BH4 was demonstrated. Reduction of 7,8-BH2 to BH4 occurs at very slow rates in cells and needs supra-physiological levels of 7,8-BH2, indicating this reaction is kinetically limited. Activity assays verified that hDHFR has very low affinity for 7,8-BH2 (DHF7,8-BH2) and folic acid inhibits 7,8-BH2 recycling. We conclude that low activity of endothelial DHFR is an important factor limiting the benefits of BH4 therapies which may be further aggravated by folate supplements. PMID:23707606

  12. Studies That Observe Humans

    MedlinePLUS

    ... may also be called a follow-up or longitudinal study.) A cohort study usually observes groups and compares ... factors affect their outcomes. Cohort studies can be prospective , meaning that the researchers select a group and ...

  13. Physiology for High School - Human Physiological Limits to Exploring Mars

    NSDL National Science Digital Library

    PhD James A Pawelczyk (Pennsylvania State University)

    2008-04-05

    The keynote presentation from EB 2008's Physiology for Life Science High School Teachers and Students Workshop. This powerpoint presentation discusses the possibility of human exploration on Mars, specifically, how space flight and life on mars would effect human physiology.

  14. Challenge studies of human volunteers: ethical issues

    PubMed Central

    Hope, T; McMillan, J

    2004-01-01

    There is a long history of medical research that involves intentionally infecting healthy people in order to study diseases and their treatments. Such research—what might be called "human challenge studies"—are an important strand of much current research—for example, in the development of vaccinations. The many international and national guidelines about the proper conduct of medical research do not specifically address human challenge studies. In this paper we review the guidelines on the risk of harm that healthy volunteers may be exposed to in the course of medical research. We examine the ethical arguments that are implicit or explicit in these guidelines. We then ask whether there is reason for limiting such studies on grounds independent of risk of harm. We conclude that the major ethical concern with challenge studies is that of risk of harm and that the fact that a study is a challenge study is not a wrong in itself. PMID:14872087

  15. Limiting disproportionate disaccommodation in design for human variability.

    PubMed

    de Vries, Charlotte; Parkinson, Matthew B

    2014-01-01

    In the design of artefacts, tasks and environments for human use, the body dimensions of the target population are a critical element in spatial optimisation of the design. This study examines how the choices designers make affect the ability of different user groups to safely and effectively interact with a designed artefact. Due to the variability in body size and shape across different demographic groups, heterogeneous user populations are unlikely to experience uniform levels of performance. The associated variability in the rate of unacceptable user conditions is referred to here as disproportionate disaccommodation. This is both an ethical and a performance concern that can partially be addressed through improved design practice. Three methods for incorporating the consideration of user demographics and the corresponding variability in body size and shape are presented. They are compared with a baseline strategy in terms of accommodation and cost. PMID:24206449

  16. 237Poverty and Human Capability Studies Poverty and Human

    E-print Network

    Dresden, Gregory

    237Poverty and Human Capability Studies Poverty and Human CaPability StudieS (Pov) Core Fa and Human Capability offers a cur- ricular and cocurricular program of study that enriches any major to establish a decent minimum of human development for all people. Students complet- ing designated

  17. 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.

  18. Genetic mouse models for bone studies—Strengths and limitations

    PubMed Central

    Elefteriou, Florent; Yang, Xiangli

    2012-01-01

    Mice have become a preferred model system for bone research because of their genetic and pathophysiological similarities to humans: a relatively short reproductive period, leading to relatively low cost of maintenance and the availability of the entire mouse genome sequence information. The success in producing the first transgenic mouse line that expressed rabbit ?-globin protein in mouse erythrocytes three decades ago marked the beginning of the use of genetically engineered mice as model system to study human diseases. Soon afterward the development of cultured pluripotent embryonic stem cells provided the possibility of gene replacement or gene deletion in mice. These technologies have been critical to identify new genes involved in bone development, growth, remodeling, repair, and diseases, but like many other approaches, they have limitations. This review will introduce the approaches that allow the generation of transgenic mice and global or conditional (tissue-specific and inducible) mutant mice. A list of the various promoters used to achieve bone-specific gene deletion or overexpression is included. The limitations of these approaches are discussed, and general guidelines related to the analysis of genetic mouse models are provided. PMID:21907838

  19. Genetic mouse models for bone studies--strengths and limitations.

    PubMed

    Elefteriou, Florent; Yang, Xiangli

    2011-12-01

    Mice have become a preferred model system for bone research because of their genetic and pathophysiological similarities to humans: a relatively short reproductive period, leading to relatively low cost of maintenance and the availability of the entire mouse genome sequence information. The success in producing the first transgenic mouse line that expressed rabbit ?-globin protein in mouse erythrocytes three decades ago marked the beginning of the use of genetically engineered mice as model system to study human diseases. Soon afterward the development of cultured pluripotent embryonic stem cells provided the possibility of gene replacement or gene deletion in mice. These technologies have been critical to identify new genes involved in bone development, growth, remodeling, repair, and diseases, but like many other approaches, they have limitations. This review will introduce the approaches that allow the generation of transgenic mice and global or conditional (tissue-specific and inducible) mutant mice. A list of the various promoters used to achieve bone-specific gene deletion or overexpression is included. The limitations of these approaches are discussed, and general guidelines related to the analysis of genetic mouse models are provided. PMID:21907838

  20. Receivers limit the prevalence of deception in humans: evidence from diving behaviour in soccer players.

    PubMed

    David, Gwendolyn K; Condon, Catriona H; Bywater, Candice L; Ortiz-Barrientos, Daniel; Wilson, Robbie S

    2011-01-01

    Deception remains a hotly debated topic in evolutionary and behavioural research. Our understanding of what impedes or facilitates the use and detection of deceptive signals in humans is still largely limited to studies of verbal deception under laboratory conditions. Recent theoretical models of non-human behaviour have suggested that the potential outcome for deceivers and the ability of receivers to discriminate signals can effectively maintain their honesty. In this paper, we empirically test these predictions in a real-world case of human deception, simulation in soccer. In support of theoretical predictions in signalling theory, we show that cost-free deceit by soccer players decreases as the potential outcome for the signaller becomes more costly. We further show that the ability of receivers (referees) to detect deceptive signals may limit the prevalence of deception by soccer players. Our study provides empirical support to recent theoretical models in signalling theory, and identifies conditions that may facilitate human deception and hinder its detection. PMID:21998745

  1. 227Poverty and Human Capability Studies Poverty AND HUMAN

    E-print Network

    Dresden, Gregory

    227Poverty and Human Capability Studies Poverty AND HUMAN CAPABILIty StUDIeS (Pov) Core FACULty and Human Capability offers a cur- ricularandcocurricularprogramofstudythatenrichesany major. Sustained and establishing a decent minimum of human development for all people. Students completing desig- nated

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

    Microsoft Academic Search

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

    1992-01-01

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

  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. A mathematical model for a limited sociologically structured human community

    Microsoft Academic Search

    V. Skakauskas

    2000-01-01

    A model for a pair formation in the age-sex and religion-structured human community whose vital rates depend on the total\\u000a population is presented. The model describes the dynamics of interacting religions, which tolerate both uniconfessional pairs\\u000a and those with different religions. Two special cases of vital rates are considered, and existence and uniqueness theorems\\u000a are proved.

  5. 47 CFR 5.93 - Limited market studies.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...or receiving equipment used in the study shall be owned by the licensee...the Commission shall establish on a case-by-case basis. If the Commission subsequently determines that a market study is not so limited, the study...

  6. 47 CFR 5.93 - Limited market studies.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...or receiving equipment used in the study shall be owned by the licensee...the Commission shall establish on a case-by-case basis. If the Commission subsequently determines that a market study is not so limited, the study...

  7. 47 CFR 5.93 - Limited market studies.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...or receiving equipment used in the study shall be owned by the licensee...the Commission shall establish on a case-by-case basis. If the Commission subsequently determines that a market study is not so limited, the study...

  8. 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…

  9. Limiter

    DOEpatents

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

    1986-01-01

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

  10. Pulmonary system limitations to endurance exercise performance in humans.

    PubMed

    Amann, Markus

    2012-03-01

    Accumulating evidence over the past 25 years depicts the healthy pulmonary system as a limiting factor of whole-body endurance exercise performance. This brief overview emphasizes three respiratory system-related mechanisms which impair O(2) transport to the locomotor musculature [arterial O(2) content (C(aO(2))) × leg blood flow (Q(L))], i.e. the key determinant of an individual's aerobic capacity and ability to resist fatigue. First, the respiratory system often fails to prevent arterial desaturation substantially below resting values and thus compromises C(aO(2)). Especially susceptible to this threat to convective O(2) transport are well-trained endurance athletes characterized by high metabolic and ventilatory demands and, probably due to anatomical and morphological gender differences, active women. Second, fatiguing respiratory muscle work (W(resp)) associated with strenuous exercise elicits sympathetically mediated vasoconstriction in limb-muscle vasculature, which compromises Q(L). This impact on limb O(2) transport is independent of fitness level and affects all individuals, but only during sustained, high-intensity endurance exercise performed above ?85% maximal oxygen uptake. Third, excessive fluctuations in intrathoracic pressures accompanying W(resp) can limit cardiac output and therefore Q(L). Exposure to altitude exacerbates the respiratory system limitations observed at sea level, further reducing C(aO(2)) and substantially increasing exercise-induced W(resp). Taken together, the intact pulmonary system of healthy endurance athletes impairs locomotor muscle O(2) transport during strenuous exercise by failing to ensure optimal arterial oxygenation and compromising Q(L). This respiratory system-related impact exacerbates the exercise-induced development of fatigue and compromises endurance performance. PMID:22125308

  11. Limits

    NSDL National Science Digital Library

    2013-06-21

    Students will see how the idea of a limit can be presented both in formal epsilon-delta-style terms, and using corresponding animations. After calculating a limit for a simple example function, we point out that limits do not always exist.

  12. Embodied storytellers: disability studies and medical humanities.

    PubMed

    Holmes, Martha Stoddard

    2015-03-01

    Rereading a canonic book in medical humanities can generate an immediate sense of how much has changed in the larger conversations still circulating around the issues that book broached in significant ways. The appearance in 2013 of the second edition of Arthur Frank's The Wounded Storyteller, first published in 1995, prompted me to review what has happened in the field of body studies in the intervening decades. Some developments point to the continuing importance of Frank's book, and others raise productive questions about its limitations. PMID:25739776

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. Population and prehistory II: space-limited human populations in constant environments.

    PubMed

    Puleston, Cedric O; Tuljapurkar, Shripad

    2008-09-01

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

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

    PubMed Central

    Puleston, Cedric O.; Tuljapurkar, Shripad

    2010-01-01

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

  2. 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. [Pacific Northwest Lab., Richland, WA (United States)

    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.

  3. Limitations of quasi-static estimation of human joint loading during locomotion.

    PubMed

    Wu, G; Ladin, Z

    1996-11-01

    The forces and moments at the ankle, knee and hip joints of the human lower limbs are divided into static and inertial components. They are calculated for various activities ranging from slow walking to running. The relative roles of these two components in the 'total' joint loads are studied, and the limitations of using a quasi-static analysis approach for joint load approximation are discussed. The results indicate that the static loads only reflect the gravitational and external reactions between the body and the environment, whereas the inertial loads provide dynamic information on each body segment involved. The effect of the inertial forces and moments becomes more important as the speed of locomotion increases; where the more proximal joints in the human lower extremity are concerned; and where the shear components of the force and moment are of interest. On the other hand, it seems that most of the joint moments in the lower extremity during walking and even running could reasonably be approximated by static components. PMID:9039751

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

    PubMed Central

    Grivel, Jean-Charles; Margolis, Leonid

    2012-01-01

    The study of human cell–cell and cell–pathogen interactions that occur in the context of complex tissue cytoarchitecture is critical for deciphering the mechanisms of many normal and pathogenic processes. This protocol describes methods for culturing and infecting explants of human tissues to study the pathogenesis of human infectious agents and their local interactions. The protocol relies on the use of fresh human tissues dissected into small blocks or biopsies that are cultured at the liquid–air interface on collagen rafts. These tissue blocks retain their cytoarchitecture and support productive infection of various pathogens without exogenous stimulation. Experimental details for setting up cultures of human tonsils, lymph nodes and cervicovaginal and rectosigmoid tissues, including protocols for their infection with HIV-1 and other pathogens, are described here. Using this protocol, culture and infections can be set up in 3–6 h and be maintained for 2–3 weeks, depending on the tissue used. PMID:19197269

  5. 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.

  6. Rational Peptide Selection To Detect Human Immunodeficiency Virus Type 1Specific T-Cell Responses under Resource-Limited Conditions

    Microsoft Academic Search

    C. B. Willberg; S. K. Pillai; E. R. Sharp; M. G. Rosenberg; J. D. Agudelo; J. D. Barbour; D. F. Nixon

    2007-01-01

    Understanding human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T-lymphocyte responses is important for the development of vaccines and therapies. We describe a novel method for the rational selection of peptides that target stable regions of the HIV-1 genome, rich in epitopes specifically recognized by the study population. This method will be of particular use under resource\\/sample-limited conditions. Understanding the fine

  7. Human occupational and performance limits under stress: the thermal environment as a prototypical example

    Microsoft Academic Search

    P. A. HANCOCK; IOANNIS VASMATZIDIS

    1998-01-01

    The authors wish to challenge the contemporary stress limits for workers exposed to adverse thermal conditions. Further, they wish to challenge the basis upon which all such occupational stress exposures are founded. It is their contention that task performance level should be the primary criterion for exposure. Change in behavioural performance efficiency is the most sensitive reflection of human response

  8. Meta-Profiles of Gene Expression during Aging: Limited Similarities between Mouse and Human and an

    E-print Network

    Bulyk, Martha L.

    Meta-Profiles of Gene Expression during Aging: Limited Similarities between Mouse and Human and an Unexpectedly Decreased Inflammatory Signature William R. Swindell1 *, Andrew Johnston2 , Liou Sun3 , Xianying Background: Skin aging is associated with intrinsic processes that compromise the structure

  9. study abroad STUDY ABROADFOR HUMAN DEVELOPMENT AND FAMILY SCIENCES MAJORS

    E-print Network

    John, Lizy Kurian

    study abroad STUDY ABROADFOR HUMAN DEVELOPMENT AND FAMILY SCIENCES MAJORS #12;WHY YOU SHOULD STUDY ABROAD 2 STUDY ABROAD FOR HUMAN DEVELOPMENT AND FAMILY SCIENCES MAJORS Study abroad programs provide. "Studying abroad is a life-changing opportunity because it allows you to experience firsthand other cultural

  10. 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

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

    Microsoft Academic Search

    G. Horneck

    2004-01-01

    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

  12. Practical Limits On Software Dependability: A Case Study

    E-print Network

    Batson, Alan

    implemented software for a specimen life-critical medical device and a developed a rigorous argument showingPractical Limits On Software Dependability: A Case Study Patrick J. Graydon, John C. Knight, there is still no complete so- lution to building software for critical systems in which every aspect of software

  13. A Case Study on Exploring the Performance Limits of PRISM

    E-print Network

    Schneider, Carsten

    A Case Study on Exploring the Performance Limits of PRISM Wolfgang Schreiner Research Institute on a simple system model the range of applicability of the prob- abilistic model checker PRISM. In particular, and of other settings on the time and memory required for the analysis of the model by PRISM. The results

  14. CEW Research Models: Animal and Human Studies

    Microsoft Academic Search

    Theodore C. Chan; Gary M. Vilke

    \\u000a Research on CEWs has involved both animals and humans. Multiple investigators have conducted extensive, detailed and complex\\u000a experimental studies on animal models, as well as human volunteer subjects to measure, monitor, and determine the physiologic\\u000a effects of CEWs. The findings and results of these animal and human experimental studies have varied and, as a result, the\\u000a conclusions drawn by investigators

  15. 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.

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

    Microsoft Academic Search

    J. C. Stephens; D. Briscoe

    1994-01-01

    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

  17. Human hypertrophic and keloid scar models: principles, limitations and future challenges from a tissue engineering perspective

    PubMed Central

    van den Broek, Lenie J; Limandjaja, Grace C; Niessen, Frank B; Gibbs, Susan

    2014-01-01

    Most cutaneous wounds heal with scar formation. Ideally, an inconspicuous normotrophic scar is formed, but an abnormal scar (hypertrophic scar or keloid) can also develop. A major challenge to scientists and physicians is to prevent adverse scar formation after severe trauma (e.g. burn injury) and understand why some individuals will form adverse scars even after relatively minor injury. Currently, many different models exist to study scar formation, ranging from simple monolayer cell culture to 3D tissue-engineered models even to humanized mouse models. Currently, these high-/medium-throughput test models avoid the main questions referring to why an adverse scar forms instead of a normotrophic scar and what causes a hypertrophic scar to form rather than a keloid scar and also, how is the genetic predisposition of the individual and the immune system involved. This information is essential if we are to identify new drug targets and develop optimal strategies in the future to prevent adverse scar formation. This viewpoint review summarizes the progress on in vitro and animal scar models, stresses the limitations in the current models and identifies the future challenges if scar-free healing is to be achieved in the future. PMID:24750541

  18. Biofuels: Efficiency, Ethics, and Limits to Human Appropriation of Ecosystem Services

    Microsoft Academic Search

    Tiziano GomieroMaurizio; Maurizio G. Paoletti; David Pimentel

    2010-01-01

    Biofuels have lately been indicated as a promising source of cheap and sustainable energy. In this paper we argue that some\\u000a important ethical and environmental issues have also to be addressed: (1) the conflict between biofuels production and global\\u000a food security, particularly in developing countries, and (2) the limits of the Human Appropriation of ecosystem services and\\u000a Net Primary Productivity.

  19. Optical limiting and nonlinear optical studies of ferrocenyl substituted calixarenes

    NASA Astrophysics Data System (ADS)

    Singh, C. P.; Sharma, Rekha; Shukla, V.; Khundrakpam, P.; Misra, Rajneesh; Bindra, K. S.; Chari, Rama

    2014-11-01

    Optical limiting behavior of three ferrocenyl substituted calixarenes (FSCs) where ferrocenyl group is attached via ethynyl(a), meta-(b) and para-(c) ethynyl phenyl spacers studied with nanosecond pulses at 532 nm is in the order c > a > b. While, with femtosecond laser pulses at 800 nm strength of nonlinearity is in the order c > b > a. Largest nonlinear refraction (n2 = 9.5 × 10-16 cm2/W) is estimated for the FSC c. Nonlinear absorption in these FSCs is attributed to three-photon absorption. Optical limiting behavior with nanosecond laser pulses is mainly due to thermal nonlinearity and reverse saturable absorption, whereas, with femtosecond laser pulses mainly intrinsic electronic nonlinearity contributes.

  20. 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

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

    PubMed

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

    2015-03-01

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

  2. 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...

  3. Peptide Promotes Overcoming of the Division Limit in Human Somatic Cell

    Microsoft Academic Search

    V. Kh. Khavinson; I. E. Bondarev; A. A. Butyugov; T. D. Smirnova

    2004-01-01

    We previously showed that treatment of normal human diploid cells with Epithalon (Ala-Glu-Asp-Gly) induced expression of telomerase catalytic subunit, its enzymatic activity, and elongation of telomeres. Here we studied the effect of this peptide on proliferative potential of human fetal fibroblasts. Primary pulmonary fibroblasts derived from a 24-week fetus lost the proliferative potential at the 34th passage. The mean size

  4. 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…

  5. Hispanic Studies The School of Humanities

    E-print Network

    Richards-Kortum, Rebecca

    , which tests students'competence in Hispanic literature and linguistics · Take SPAN 507 Teaching College Majors--Students majoring in Hispanic studies must complete at least 30 semester hours in upper181 Hispanic Studies The School of Humanities Degrees Offered: BA and MA in Hispanic Studies

  6. Hispanic Studies The School of Humanities

    E-print Network

    Richards-Kortum, Rebecca

    , which tests students'competence in Hispanic literature and linguistics · Take SPAN 507 Teaching College Majors--Students majoring in Hispanic studies must complete at least 30 semester hours in upper179 Hispanic Studies The School of Humanities Degrees Offered: BA and MA in Hispanic Studies

  7. Expression of Human nPTB Is Limited by Extreme Suboptimal Codon Content

    PubMed Central

    Robinson, Fiona; Jackson, Richard J.; Smith, Christopher W. J.

    2008-01-01

    Background The frequency of synonymous codon usage varies widely between organisms. Suboptimal codon content limits expression of viral, experimental or therapeutic heterologous proteins due to limiting cognate tRNAs. Codon content is therefore often adjusted to match codon bias of the host organism. Codon content also varies between genes within individual mammalian species. However, little attention has been paid to the consequences of codon content upon translation of host proteins. Methodology/Principal Findings In comparing the splicing repressor activities of transfected human PTB and its two tissue-restricted paralogs–nPTB and ROD1–we found that the three proteins were expressed at widely varying levels. nPTB was expressed at 1–3% the level of PTB despite similar levels of mRNA expression and 74% amino acid identity. The low nPTB expression was due to the high proportion of codons with A or U at the third codon position, which are suboptimal in human mRNAs. Optimization of the nPTB codon content, akin to the “humanization” of foreign ORFs, allowed efficient translation in vivo and in vitro to levels comparable with PTB. We were then able to demonstrate that all three proteins act as splicing repressors. Conclusions/Significance Our results provide a striking illustration of the importance of mRNA codon content in determining levels of protein expression, even within cells of the natural host species. PMID:18335065

  8. Human Root Caries: Microbiota of a Limited Number of Root Caries Lesions

    Microsoft Academic Search

    P. Schüpbach; V. Osterwalder; B. Guggenheim

    1996-01-01

    The microbiota of root caries lesions of different grades of severity were studied. Fourteen lesions were examined. The experimental design of the study allowed correlation of histopathologically distinguishable stages with specific and distinct microbial populations. Dentin samples were ground in a sterile mortar and cultured anaerobically on nonselective Columbia blood agar plates supplemented with 5% hemolyzed human blood and on

  9. Study of human bone tumor slice by SRXRF microprobe

    NASA Astrophysics Data System (ADS)

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

    2001-07-01

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

  10. 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 feedback systems towards a collection of higher quality data, an increase in the capacity of studying disasters and improved risk management systems.

  11. 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.

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

    PubMed Central

    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. PMID:23378896

  13. 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.

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

    PubMed

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

    2011-10-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

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

  16. Postdisciplinary Liaisons: Science Studies and the Humanities

    E-print Network

    innovative trend while "innovation studies" may be in the process of reshaping the institutional ecology by the emergence of the digital humanities and innovation studies, I have chosen not to engage in detail., Ivory Tower and Industrial Innovation: University-Industry Technology Transfer before and after the Bayh

  17. Ash samples exceed toxicity limits EPA characterization study reports

    SciTech Connect

    Engelgau, D.

    1988-02-01

    At least two samples of incinerator ash codisposed with solid waste contained lead levels that exceed the Environmental Protection Agency's acceptable toxicity limits. New ways are needed to dispose of the ash. Metals are in the ash and we need to be sure they don't get into ground water. Samples from municipal landfill, codisposal landfills and monofills were used in the study. Ash samples were analyzed for metals and organics, including polychlorinated biphenyls (PCBs), baseneutral acid extractables (BNAs), polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzo-furans (PCDFs). The samples were subjected to simulated leachability tests, including the EP test, the TCLP test and the Monofilled Waste Extraction Procedure (SW-924) test.

  18. 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

  19. The limits for detection of activated caspases of spermatozoa by western blot in human semen.

    PubMed

    Brugnon, F; Pons-Rejraji, H; Artonne, C; Janny, L; Grizard, G

    2012-08-01

    Detection of activated caspases of spermatozoa could be helpful to evaluate male infertility. Although western blot is validated as a highly specific method to detect the proteins extracted from cells, the ability of this technique to detect activated sperm caspases in human semen may be limited. Indeed, round cells, which potentially contain some activated caspases, may be present in semen and interfere with the detection of activated sperm caspases. Moreover, it is necessary to evaluate the minimum amount of spermatozoa necessary to optimise the detection of activated caspases in semen samples. Our results showed that interference due to round cells contained in semen with activated caspase-3 requires separation of spermatozoa by density migration. This sperm preparation selects a mature sperm population that does not reflect the whole sperm population, and in infertile men with oligoasthenoteratozoospermia, the amount of spermatozoa thus selected is usually low. Moreover, the western blot technique's low detection sensitivity and the low level of caspase enzyme activity in human spermatozoa for activated caspase-3, -8 and -9 mean that large quantities of spermatozoa are needed to detect the expression of the activated caspases. These limitations prevent this method being used for routine analysis in clinical practice. PMID:22292703

  20. HUMEX, a study on the survivability and adaptation of humans to long- duration exploratory missions

    Microsoft Academic Search

    G. Horneck

    2002-01-01

    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

  1. Using electroencephalography to study functional coupling between cortical activity and electromyograms during voluntary contractions in humans

    Microsoft Academic Search

    David M Halliday; Bernard A Conway; Simon F Farmer; Jay R. Rosenberg

    1998-01-01

    Previous studies of neuronal oscillations in sensorimotor cortex in humans and primates have observed rhythmic 15–30 Hz activity, which is correlated with motor output. In humans, this work has been limited to magnetic recordings. In the present study we investigate if similar results can be obtained using electroencephalography (EEG). EEG recordings were made from over the sensorimotor cortex of five

  2. 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

  3. 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

  4. Kinetic investigations of the rate-limiting step in human 12- and 15-lipoxygenase.

    PubMed

    Segraves, Erika N; Holman, Theodore R

    2003-05-13

    Mammalian lipoxygenases have been implicated in several inflammatory disorders; however, the details of the kinetic mechanism are still not well understood. In this paper, human platelet 12-lipoxygenase (12-hLO) and human reticulocyte 15-lipoxygenase-1 (15-hLO) were tested with arachidonic acid (AA) and linoleic acid (LA), respectively, under a variety of changing experimental conditions, such as temperature, dissolved oxygen concentration, and viscosity. The data that are presented show that 12-hLO and 15-hLO have slower rates of product release (k(cat)) than soybean lipoxygenase-1 (sLO-1), but similar or better rates of substrate capture for the fatty acid (k(cat)/K(M)) or molecular oxygen [k(cat)/K(M(O)2)]. The primary, kinetic isotope effect (KIE) for 15-hLO with LA was determined to be temperature-independent and large ((D)k(cat) = 40 +/- 8), over the range of 10-35 degrees C, indicating that C-H bond cleavage is the sole rate-limiting step and proceeds through a tunneling mechanism. The (D)k(cat)/K(M) for 15-hLO, however, was temperature-dependent, consistent with our previous results [Lewis, E. R., Johansen, E., and Holman, T. R. (1999) J. Am. Chem. Soc. 121, 1395-1396], indicating multiple rate-limiting steps. This was confirmed by a temperature-dependent, k(cat)/K(M) solvent isotope effect (SIE), which indicated a hydrogen bond rearrangement step at low temperatures, similar to that of sLO-1 [Glickman, M. H., and Klinman, J. P. (1995) Biochemistry 34, 14077-14092]. The KIE could not be determined for 12-hLO due to its inability to efficiently catalyze LA, but the k(cat)/K(M) SIE was temperature-independent, indicating distinct rate-limiting steps from both 15-hLO and sLO-1. PMID:12731864

  5. Limitations of quantitative research in the study of structural adjustment.

    PubMed

    Lundy, P

    1996-02-01

    Sociologists and, more recently, critical medical anthropologists have been arguing for a refocusing of the analysis of health and health care towards a perspective which considers the broader global political economy. In the context of the debt crisis and IMF/World Bank-inspired structural adjustment policies, the political economy theoretical perspective is becoming even more relevant in the analysis of health underdevelopment in many 'Third World' countries. This study focuses on the direct and indirect effects of the Jamaican debt crisis and structural adjustment programmes on health care services and health standards. In this paper it is argued that there are methodological problems using quantitative data when studying the effects of structural adjustment. In addition to providing a limited account of the effects, it is argued that the basic problem is a matter of the availability and reliability of the quantitative data in many 'Third World' countries. It is argued that some of these problems could be overcome by the application of qualitative micro-level analysis. This type of methodology is important to ascertain the effects of global processes at the grass roots level and to gain insights into what those working in the health sector are experiencing and what they perceive as the effects, if any, of structural adjustment policies. This has often been missing from the impersonal accounts offered by quantitative research on the subject to date. PMID:8658227

  6. Limited role of lipopolysaccharide Lewis antigens in adherence of Helicobacter pylori to the human gastric epithelium

    Microsoft Academic Search

    Jafar Mahdavi; T. Boren; Christina Vandenbroucke-grauls; Ben J. Appelmelk

    2003-01-01

    In vitro and in vivo studies from various groups have suggested that Helicobacter pylori lipopolysaccharide (LPS) Lewis x (Le(x)) antigens mediate bacterial adhesion. We have now reevaluated this hypothesis by studying the adherence in situ of H. pylori strain 11637 and its corresponding Le(x)-negative rfbM mutant to human gastric mucosa from patients (n = 22) with various gastric pathologies. Significant

  7. Taurine supplementation in spontaneously hypertensive rats: Advantages and limitations for human applications

    PubMed Central

    Suwanich, Atchariya; Wyss, J Michael; Roysommuti, Sanya

    2013-01-01

    Taurine (2-aminoethanesulfonic acid) is a ?-amino acid found in many tissues particularly brain, myocardium, and kidney. It plays several physiological roles including cardiac contraction, antioxidation, and blunting of hypertension. Though several lines of evidence indicate that dietary taurine can reduce hypertension in humans and in animal models, evidence that taurine supplementation reduces hypertension in humans has not been conclusive. One reason for the inconclusive nature of past studies may be that taurine having both positive and negative effects on cardiovascular system depending on when it is assessed, some effects may occur early, while others only appear later. Further, other consideration may play a role, e.g., taurine supplementation improves hypertension in spontaneously hypertensive rats on a low salt diet but fails to attenuate hypertension on a high salt diet. In humans, some epidemiologic studies indicate that people with high taurine and low salt diets display lower arterial pressure than those with low taurine and high salt diets. Differences in techniques for measuring arterial pressure, duration of treatment, and animal models likely affect the response in different studies. This review considers both the positive and negative effects of taurine on blood pressure in animal models and their applications for human interventions. PMID:24340138

  8. Virus retrieval studies in human neoplasia.

    PubMed

    Dmochowski, L; Georgiades, J; East, J L; Allen, P T; Bowen, J M

    1975-01-01

    Short- and long-term co-cultures of 49 cases of human osteosarcoma cells with bone marrow or peripheral blood cells of patients with different types of leukemia were studied. Morphological changes were observed in 7 of 13 long-term co-cultures resembling those induced by RNA tumor viruses. The changes were accompanied by appearance of cytoplasmic antigen as shown by fixed immunofluorescence test with sera from patients with osteosarcoma, leukemia, and of some apparently normal blood donors. Absorption with Forssman-like substances, whole human embryo cells or osteosarcoma cells demonstrated the reaction to be due to tumor antigen(s) in co-culture cells showing morphological changes. Electron microscopy showed a few type C virus particles in one co-culture. Cell-free filtrates of fluid from the transformed co-cultures induced morphological changes in 1 of 4 human embryo cultures. Uninoculated embryo cultures or those inoculated with filtrates from parental sarcoma or leukemia cultures showed no morphological changes. Human embryo cell cultures treated with fluid from parental leukemic bone marrow but not from parental sarcoma cultures showed appearance of cytoplasmic antigen by immunofluorescence test with sera of osteosarcoma and leukemia patients and of some apparently normal blood donors. Transformed human co-cultures showed the cytoplasmic antigen with 28 of 48 sera of osteosarcoma and leukemia patients tested, after absorption with Forssman-like material, human embryo, and mycoplasma suspensions. Fourteen of 49 sera of normal donors were also positive with the transformed co-cultures. Similar results were obtained in an earlier series of experiments with human embryonic cultures transformed by fluid from different osteosarcoma-leukemia co-cultures when examined by fixed immunofluorescence tests with sera of patients with osteosarcoma and leukemia. In 2 whole human embryo cell cultures showing morphological changes high molecular weight RNA was found, similar to that of RNA animal tumor viruses and in one of the cultures transient reverse transcriptase was detected. PMID:51629

  9. 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

  10. Cytogenetic studies on human breast carcinomas

    Microsoft Academic Search

    Erich Gebhart; Silke Brtiderlein; Meena Augustus; Erwin Siebert; Joachim Feldner; Wilfried Schmidt

    1986-01-01

    Cytogenetic studies were performed on cell material obtained from surgical specimens of 50 human breast carcinomas and from 61 cancerous effusions of 46 patients. Classical cytogenetic analyses of numerical chromosome changes and marker chromosomes revealed the non-random involvement of chromosomes #X and #22 as monosomics, of chromosomes #3, #7, and #19 as trisomics, and chromosome #1 (particularly p 13 to

  11. The Human Studies Database Project: Federating Human Studies Design Data Using the Ontology of Clinical Research

    PubMed Central

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

    2010-01-01

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

  12. A distinct subset of human CD4+ cells with a limited alloreactive T cell receptor repertoire.

    PubMed

    Morishita, Y; Sao, H; Hansen, J A; Martin, P J

    1989-11-01

    We describe a subset of CD4+/CD3+ human T lymphocytes that demonstrated a remarkably limited TCR repertoire responding to alloantigen stimulation. These cells have been characterized previously by their granular morphology and expression of CD11b but not CD28. Whereas multiple CD28+/CD4+ alloproliferative cloned cell lines generated by culture at limiting dilution immediately after isolation from peripheral blood each had a unique TCR-beta gene rearrangement, 19 of 21 CD11b+/CD4+ clones showed identical TCR-beta, and gamma gene rearrangements. In conventional MLR, the CD11b+/CD4+ cells responded poorly after stimulation with some HLA-class II Ag, and staining with a TCR Id-specific antibody and DNA blot hybridization suggested that the responding CD11b+/CD4+ cells typically contained predominant clonal populations. Clones of CD11b+/CD4+ cells with different TCR gene rearrangements showed closely similar patterns of responses when stimulated by a panel of allogeneic PBMC, but the response pattern did not correspond to that of any known HLA-class II Ag. These findings indicate that CD11b+/CD4+ cells have a limited alloproliferative repertoire characterized by predominant recognition of a limited number of undefined determinants that appear to be expressed in association with multiple distinct HLA-class II Ag. Our results suggest that CD11b+/CD4+ cells are selected for clonal reactivity by processes distinct from those for CD28+/CD4+ cells. PMID:2478624

  13. To define the congruence of human population distribution and P. falciparum transmission we used spatially linked databases of human population, limits of malaria

    E-print Network

    Cai, Long

    spatially linked databases of human population, limits of malaria risk and malaria endemicity within defined the spatial extent of P. falciparum risk by using the mapped global limits of malaria risk on the only available global map of malaria endemicity developed in 1968 (refs 6, 7). This map was part

  14. 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.

  15. 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.

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

    PubMed Central

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

    2014-01-01

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

  17. 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.

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

    PubMed

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

    2015-01-01

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

  19. Genetic studies in human prion diseases.

    PubMed

    Jeong, Byung-Hoon; Kim, Yong-Sun

    2014-05-01

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

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 2014-07-01 2014-07-01 false Human Studies Review Board review of proposed human research. 26.1606 Section 26.1606...PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Review of Proposed and...

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 2013-07-01 2013-07-01 false Human Studies Review Board review of completed human research. 26.1607 Section 26.1607...PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Review of Proposed and...

  3. 40 CFR 26.1606 - Human Studies Review Board review of proposed human research.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 2013-07-01 2013-07-01 false Human Studies Review Board review of proposed human research. 26.1606 Section 26.1606...PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Review of Proposed and...

  4. 40 CFR 26.1607 - Human Studies Review Board review of completed human research.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 2014-07-01 2014-07-01 false Human Studies Review Board review of completed human research. 26.1607 Section 26.1607...PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Review of Proposed and...

  5. The Rational Choice Approach to Human Studies: A Reexamination

    Microsoft Academic Search

    Milan Zafirovski

    2003-01-01

    This article reexamines the rational choice or economic approach to human studies. Its adherents claim that its extension beyond its original domain to “all human behavior” can finally lead to integration of the human studies, especially social theory, and thus their elevation from what they see as a chaotic state. Specifically, they propose grounding human studies on the premise that

  6. 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.

  7. Cubital tunnel release with two limited incisions: a cadaver study

    Microsoft Academic Search

    M. Alp; S. M. Akk?n; L. Yalç?n; T. Marur; M. Babacan

    2004-01-01

    Cubital tunnel syndrome is the second most common compressive neuropathy in the upper extremity. Treatment of cubital tunnel syndrome consists of releasing the compression on the ulnar nerve with conservative or surgical methods. Nerve decompression is an alternative simple and less invasive procedure. We have proposed a “two limited incisions” technique in order to release the cubital tunnel with two

  8. 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)…

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

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

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

    PubMed Central

    Tamber-Rosenau, Benjamin J.; Dux, Paul E.

    2013-01-01

    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. PMID:24198320

  11. 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-2r??/? (NSG) immune-deficient mice bearing established melanoma tumors was used to compare the effects of the common ? 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

  12. Tea and Health: Studies in Humans

    PubMed Central

    Khan, Naghma; Mukhtar, Hasan

    2014-01-01

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

  13. 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.

  14. The Human Bitumen Study: executive summary.

    PubMed

    Raulf-Heimsoth, Monika; Pesch, Beate; Rühl, Reinhold; Brüning, Thomas

    2011-06-01

    Bitumen has attracted attention from the scientific community and regulating agencies. The debate on health effects of exposure to vapours and aerosols of bitumen during the hot application of bitumen ranges from respiratory and neurological effects to carcinogenicity. In 2000, the German Hazardous Substances Committee (AGS), in collaboration with the German Bitumen Forum, initiated the examination of a group of mastic asphalt workers and a same number of construction workers without exposure bitumen using a cross-shift design. The study was then extended to the Human Bitumen Study, and the recruitment was finished in 2008 after examination of 500 workers on 80 construction sites. Three hundred and twenty workers exposed to vapours and aerosols of bitumen at high processing temperatures and 118 workers at outdoor construction sites were included. In the Human Bitumen Study external exposure to vapours and aerosols of bitumen, internal exposure to PAH by analysing urinary 1-hydroxypyrene, the sum of hydroxyphenanthrenes and the sum of 1- and 2-hydroxynaphthalenes, irritative effects in the upper and lower airways and genotoxic effects in blood cells were investigated. The study turned out to be one of the largest investigations of workers exposed to vapours and aerosols of bitumen under current exposure conditions. The present paper summarizes its background and main topics. PMID:21369765

  15. A cytogenetic study of 53 human gliomas.

    PubMed

    Jenkins, R B; Kimmel, D W; Moertel, C A; Schultz, C G; Scheithauer, B W; Kelly, P J; Dewald, G W

    1989-06-01

    Cytogenetic studies were performed on human glioma samples obtained by stereotactic biopsy, stereotactic craniotomy, or routine craniotomy. Using in situ culture and robotic harvesting techniques, we obtained suitable metaphases in 50 (94%) of 53 tumors, including 28 diffuse astrocytomas, four juvenile pilocytic astrocytomas, two gliosarcomas, three other miscellaneous astrocytomas, eight oligodendrogliomas, four mixed oligodendroglioma-astrocytomas, and four ependymomas. Cytogenetic studies were performed only on primary cultures; the mean culture time was 9.6 days (range 1-31 days). One or more chromosomally abnormal clones were observed in 35 (66%) tumors. Eleven (21%) other specimens had random nonclonal chromosome abnormalities. In four (8%) specimens, no chromosome abnormalities were noted. The results of this study suggest that grade 3 and 4 tumors are more likely to contain an abnormal clone than tumors of grade 1 or 2 (p less than 0.01). The most common numeric chromosome abnormalities were -6, +7, -10, -13, -14, -15, -18, and -Y. The most common structural abnormalities involved 1p, 6q, 7q, 8p, 9p, 11p, 11q, 13q, and 19q. Four tumors had two or more independent clones and ten contained subclones demonstrating karyotype evolution. With in situ culture and robotic harvesting techniques, cytogenetic studies can be successful on nearly all human gliomas, including those derived from small stereotactic biopsies. PMID:2752377

  16. Bioavailability of tocotrienols: evidence in human studies

    PubMed Central

    2014-01-01

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

  17. Molecular interaction networks for the analysis of human disease: utility, limitations, and considerations.

    PubMed

    Schramm, Sarah-Jane; Jayaswal, Vivek; Goel, Apurv; Li, Simone S; Yang, Yee Hwa; Mann, Graham J; Wilkins, Marc R

    2013-12-01

    High-throughput '-omics' data can be combined with large-scale molecular interaction networks, for example, protein-protein interaction networks, to provide a unique framework for the investigation of human molecular biology. Interest in these integrative '-omics' methods is growing rapidly because of their potential to understand complexity and association with disease; such approaches have a focus on associations between phenotype and "network-type." The potential of this research is enticing, yet there remain a series of important considerations. Here, we discuss interaction data selection, data quality, the relative merits of using data from large high-throughput studies versus a meta-database of smaller literature-curated studies, and possible issues of sociological or inspection bias in interaction data. Other work underway, especially international consortia to establish data formats, quality standards and address data redundancy, and the improvements these efforts are making to the field, is also evaluated. We present options for researchers intending to use large-scale molecular interaction networks as a functional context for protein or gene expression data, including microRNAs, especially in the context of human disease. PMID:24166987

  18. 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.

  19. Limited role of lipopolysaccharide Lewis antigens in adherence of Helicobacter pylori to the human gastric epithelium.

    PubMed

    Mahdavi, Jafar; Borén, Thomas; Vandenbroucke-Grauls, Christina; Appelmelk, Ben J

    2003-05-01

    In vitro and in vivo studies from various groups have suggested that Helicobacter pylori lipopolysaccharide (LPS) Lewis x (Le(x)) antigens mediate bacterial adhesion. We have now reevaluated this hypothesis by studying the adherence in situ of H. pylori strain 11637 and its corresponding Le(x)-negative rfbM mutant to human gastric mucosa from patients (n = 22) with various gastric pathologies. Significant binding of the parent strain was observed in only 8 out of 22 sections; in four out of eight patients, the Le(x)-negative mutant bound less well. One of these four patients displayed no gastric abnormalities, and the other three showed dysplasia, metaplasia, and adenocarcinoma, respectively; hence, we are unable to define the circumstances under which LPS-mediated adhesion takes place. We conclude that H. pylori LPS plays a distinct but minor role in adhesion. PMID:12704161

  20. Limited Role of Lipopolysaccharide Lewis Antigens in Adherence of Helicobacter pylori to the Human Gastric Epithelium

    PubMed Central

    Mahdavi, Jafar; Borén, Thomas; Vandenbroucke-Grauls, Christina; Appelmelk, Ben J.

    2003-01-01

    In vitro and in vivo studies from various groups have suggested that Helicobacter pylori lipopolysaccharide (LPS) Lewis x (Lex) antigens mediate bacterial adhesion. We have now reevaluated this hypothesis by studying the adherence in situ of H. pylori strain 11637 and its corresponding Lex-negative rfbM mutant to human gastric mucosa from patients (n = 22) with various gastric pathologies. Significant binding of the parent strain was observed in only 8 out of 22 sections; in four out of eight patients, the Lex-negative mutant bound less well. One of these four patients displayed no gastric abnormalities, and the other three showed dysplasia, metaplasia, and adenocarcinoma, respectively; hence, we are unable to define the circumstances under which LPS-mediated adhesion takes place. We conclude that H. pylori LPS plays a distinct but minor role in adhesion. PMID:12704161

  1. 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.

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

    PubMed Central

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

    2014-01-01

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

  3. 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.

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

    PubMed Central

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

    1984-01-01

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

  5. Tumor promotion by exposure to radiofrequency electromagnetic fields below exposure limits for humans.

    PubMed

    Lerchl, Alexander; Klose, Melanie; Grote, Karen; Wilhelm, Adalbert F X; Spathmann, Oliver; Fiedler, Thomas; Streckert, Joachim; Hansen, Volkert; Clemens, Markus

    2015-04-17

    The vast majority of in vitro and in vivo studies did not find cancerogenic effects of exposure to electromagnetic fields (RF-EMF), i.e. emitted by mobile phones and base stations. Previously published results from a pilot study with carcinogen-treated mice, however, suggested tumor-promoting effects of RF-EMF (Tillmann et al., 2010). We have performed a replication study using higher numbers of animals per group and including two additional exposure levels (0 (sham), 0.04, 0.4 and 2 W/kg SAR). We could confirm and extend the originally reported findings. Numbers of tumors of the lungs and livers in exposed animals were significantly higher than in sham-exposed controls. In addition, lymphomas were also found to be significantly elevated by exposure. A clear dose-response effect is absent. We hypothesize that these tumor-promoting effects may be caused by metabolic changes due to exposure. Since many of the tumor-promoting effects in our study were seen at low to moderate exposure levels (0.04 and 0.4 W/kg SAR), thus well below exposure limits for the users of mobile phones, further studies are warranted to investigate the underlying mechanisms. Our findings may help to understand the repeatedly reported increased incidences of brain tumors in heavy users of mobile phones. PMID:25749340

  6. Blocks of Limited Haplotype Diversity Revealed by High-Resolution Scanning of Human Chromosome 21

    Microsoft Academic Search

    Nila Patil; Anthony J. Berno; David A. Hinds; Wade A. Barrett; Jigna M. Doshi; Coleen R. Hacker; Curtis R. Kautzer; Danny H. Lee; Claire Marjoribanks; David P. McDonough; Bich T. N. Nguyen; Michael C. Norris; John B. Sheehan; Naiping Shen; David Stern; Renee P. Stokowski; Daryl J. Thomas; Mark O. Trulson; Kanan R. Vyas; Kelly A. Frazer; Stephen P. A. Fodor; David R. Cox

    2001-01-01

    Global patterns of human DNA sequence variation (haplotypes) defined by common single nucleotide polymorphisms (SNPs) have important implications for identifying disease associations and human traits. We have used high-density oligonucleotide arrays, in combination with somatic cell genetics, to identify a large fraction of all common human chromosome 21 SNPs and to directly observe the haplotype structure defined by these SNPs.

  7. 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...

  8. 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 achieve a DSI scan in less than 5 min. To augment this accelerated imaging approach we developed a 64-channel, tight-fitting brain array coil and show its performance benefit compared to a commercial 32-channel coil at all locations in the brain for these accelerated acquisitions. The technical challenges of developing the over-all system are discussed as well as results from SNR comparisons, ODF metrics and fiber tracking comparisons. The ultra-high gradients yielded substantial and immediate gains in the sensitivity through reduction of TE and improved signal detection and increased efficiency of the DSI or HARDI acquisition, accuracy and resolution of diffusion tractography, as defined by identification of known structure and fiber crossing. PMID:23707579

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

    PubMed Central

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

    2013-01-01

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

  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. Study on Optical Filter Heating in Background Limited Detector Experiments

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

  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. A cellular study of human testis development.

    PubMed

    Ostrer, H; Huang, H Y; Masch, R J; Shapiro, E

    2007-01-01

    This study catalogs the cellular events underlying the formation of a human testis. These events were identified by immunocytochemistry using antibodies that served as markers for specific cell types, then contrasted with the events occurring in the developing mouse testis. The presence of germ cells in the embryonic gonadal ridge and of coelomic epithelial cells that give rise to Sertoli cells was observed at 7 weeks. This was followed by the appearance of Sertoli cells in testicular tubules and of Leydig cells at 9 weeks and by the appearance of vascular endothelial cells and peritubular myoid cells at 12 weeks. Overall the temporal sequence of events in humans was similar, albeit longer, than what occurs in mice. Notably, Leydig cell differentiation occurs earlier in the sequence of events and germ cell maturation occurs during fetal life. The candidate testis-determining genes, FGF9, GATA4, FOG2, EMX2, and CBX2 were expressed at 7 weeks suggesting a role in early gonadal development, such as that observed in mice. In addition, expression of FGF9 in germ cells following testis determination suggests a role in germ cell maturation. PMID:18391539

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

    NASA Astrophysics Data System (ADS)

    Barbafieri, Meri

    2013-04-01

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

  15. Solution convergence study during launch phase using limited tracking data

    NASA Technical Reports Server (NTRS)

    Premkumar, R. I.

    1988-01-01

    Orbit determination accuracies during critical phases at launch, when data are available from only one station, can be enhanced using angle data with conventional Doppler and range data. A study performed on the forthcoming Japanese ETS-5 mission indicates that this requires correct handling of the angle biases. This was verified using actual tracking data received from the BS-2B launch.

  16. Metabolomic studies of human gastric cancer: Review

    PubMed Central

    Jayavelu, Naresh Doni; Bar, Nadav S

    2014-01-01

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

  17. Scientific limitations and ethical ramifications of a non-representative Human Genome Project: African American response

    Microsoft Academic Search

    Fatimah Jackson

    1998-01-01

    The Human Genome Project (HGP) represents a massive merging of science and technology in the name of all humanity. While the\\u000a disease aspects of HGP-generated data have received the greatest publicity and are the strongest rationale for the project,\\u000a it should be remembered that the HGP has, as its goal the sequencing of all 100,000 human genes and the accurate

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

    E-print Network

    Gabrielse, Gerald

    Improving the Limit on the Electron EDM: Data Acquisition and Systematics Studies in the ACME Gabrielse Paul William Hess Improving the Limit on the Electron EDM: Data Acquisition and Systematics upper limit on the size of the electron's permanent electric dipole moment (EDM). The existence

  19. Association studies including genotype by environment interactions: prospects and limits

    PubMed Central

    2014-01-01

    Background Association mapping studies offer great promise to identify polymorphisms associated with phenotypes and for understanding the genetic basis of quantitative trait variation. To date, almost all association mapping studies based on structured plant populations examined the main effects of genetic factors on the trait but did not deal with interactions between genetic factors and environment. In this paper, we propose a methodological prospect of mixed linear models to analyze genotype by environment interaction effects using association mapping designs. First, we simulated datasets to assess the power of linear mixed models to detect interaction effects. This simulation was based on two association panels composed of 90 inbreds (pearl millet) and 277 inbreds (maize). Results Based on the simulation approach, we reported the impact of effect size, environmental variation, allele frequency, trait heritability, and sample size on the power to detect the main effects of genetic loci and diverse effect of interactions implying these loci. Interaction effects specified in the model included SNP by environment interaction, ancestry by environment interaction, SNP by ancestry interaction and three way interactions. The method was finally used on real datasets from field experiments conducted on the two considered panels. We showed two types of interactions effects contributing to genotype by environment interactions in maize: SNP by environment interaction and ancestry by environment interaction. This last interaction suggests differential response at the population level in function of the environment. Conclusions Our results suggested the suitability of mixed models for the detection of diverse interaction effects. The need of samples larger than that commonly used in current plant association studies is strongly emphasized to ensure rigorous model selection and powerful interaction assessment. The use of ancestry interaction component brought valuable information complementary to other available approaches. PMID:24393630

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

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    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. Human transcriptome array for high-throughput clinical studies

    E-print Network

    Xu, Weihong

    A 6.9 million-feature oligonucleotide array of the human transcriptome [Glue Grant human transcriptome (GG-H array)] has been developed for high-throughput and cost-effective analyses in clinical studies. This array allows ...

  4. 78 FR 35031 - Human Studies Review Board Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-11

    ...Environmental Protection Agency (EPA) invites nominations from a diverse range of qualified candidates with expertise in bioethics, biostatistics and human health risk assessment to be considered for appointment to its Human Studies Review Board...

  5. 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 of reflected light, and highly mitigated using two photodetectors. Using one photodetector, we obtained a piecewise DoI error model with a DoI resolution of 0.4-0.9 mm for a 1.2 AR crystal, and we observed that including a second photodetector or reducing the amount of reflections reduced the DoI bias but did not significantly improve the DoI resolution. Translating the piecewise DoI error model obtained in this study to image reconstruction we obtained a spatial resolution variability of 0.39 mm using 85% of the FoV, compared to 2.59 mm and 1.87 mm without DoI correction or with a dual layer system, respectively. PMID:25884464

  6. Humex, a study on the survivability and adaptation of humans to long-duration exploratory missions, part I: Lunar missions

    Microsoft Academic Search

    G. Horneck; R. Facius; M. Reichert; P. Rettberg; W. Seboldt; D. Manzey; B. Comet; A. Maillet; H. Preiss; L. Schauer; C. G. Dussap; L. Poughon; A. Belyavin; G. Reitz; C. Baumstark-Khan; R. Gerzer

    2003-01-01

    The European Space Agency has recently initiated a study of the human responses, limits and needs with regard to the stress environments of interplanetary and planetary missions. Emphasis has been 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)

  7. 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)

  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. Sex Without Friction: the Limits of Multi-Mediated Human Subjectivity in Cheang Shu Lea's Tech-Porn

    Microsoft Academic Search

    Jian Chen

    2010-01-01

    :Sex Without Friction focuses on Cheang Shu Lea's science fiction porno I.K.U. (2000) as provocation to think through the limitations of social and cultural criticism that is premised on mediation. Directed by Taiwan-born digital nomad Cheang, multimedia film I.K.U. features a gender-morphing human clone, programmed to collect sexual experiences for the future mass production of sex simulation pills. I.K.U. positions

  10. Sex Without Friction: the Limits of Multi-Mediated Human Subjectivity in Cheang Shu Lea's Tech-Porn

    Microsoft Academic Search

    Jian Chen

    2010-01-01

    Sex Without Friction focuses on Cheang Shu Lea's science fiction porno I.K.U. (2000) as provocation to think through the limitations of social and cultural criticism that is premised on mediation. Directed by Taiwan-born digital nomad Cheang, multimedia film I.K.U. features a gender-morphing human clone, programmed to collect sexual experiences for the future mass production of sex simulation pills. I.K.U. positions

  11. 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. PMID:24335492

  12. Subjective Quantitative Studies of Human Agency

    ERIC Educational Resources Information Center

    Alkire, Sabina

    2005-01-01

    Amartya Sen's writings have articulated the importance of human agency, and identified the need for information on agency freedom to inform our evaluation of social arrangements. Many approaches to poverty reduction stress the need for empowerment. This paper reviews "subjective quantitative measures of human agency at the individual level." It…

  13. A Brief History of Soils and Human Health Studies

    NASA Astrophysics Data System (ADS)

    Brevik, Eric C.; Sauer, Thomas J.

    2013-04-01

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

  14. "The CardioRespiratory Human System:The Cardio Respiratory Human System: a simulation study"

    E-print Network

    Grossmann, Ignacio E.

    "The CardioRespiratory Human System:The Cardio Respiratory Human System: a simulation study" "P S t E i i i H Ph i l ""Process System Engineering in Human Physiology" Elisa Montain, Anibal Blanco vascularvascular system,system, ApproachesApproaches includeinclude:: hemodynamichemodynamic modelsmodels ofof

  15. 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.

  16. 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

  17. Melatonin in humans physiological and clinical studies.

    PubMed

    Wetterberg, L

    1978-01-01

    Studies are reported of the variation of melatonin in serum, plasma urine and cerebrospinal fluid in normal subjects and in patients with various diseases. The diurnal variation of plasma and urine melatonin found in healthy controls on a regular dark-sleep pattern persisted when the subjects slept in light. The effect of sleep deprivation and of rapid light exposure at night is reported. There was a correlation between melatonin in morning urine and plasma at 2 a.m. Four hours of extended darkness in the morning as well as a 9-hour shift of sleep and activity cycles following travel affected the melatonin rhythm. The night increase in plasma melatonin preceeded both the cortisol and prolactin rise. A single oral dose of 4.3 X 10(5) nmol of melatonin given to a 44-year-old healthy male gave a peak plasma value of 624 nmol/l after 30 min. Plasma melatonin was not affected by electroconvulsive therapy, TRH-injection, L-Dopa or bromoergocryptine orally. Patients with alcoholism, migraine, postoperative pinealoma, panhypopituitarism, hereditary dystonia and schizophrenics on propranolol exhibited a decreased amplitude of their diurnal rhythm of melatonin. Two patients with pituitary tumors had occasional high levels of plasma melatonin. The change in melatonin secretion in human is apparently controlled by a mechanism which is at least party influenced by environmental lighting conditions, drugs and different disease states. PMID:381589

  18. Human macrophage development: a morphometric study.

    PubMed Central

    Sokol, R J; Hudson, G; James, N T; Frost, I J; Wales, J

    1987-01-01

    The development of macrophages from the blood monocytes of ten normal subjects has been studied at intervals over a six day period. Suspension cultures were used to obtain randomly orientated cells and morphometric measurements were made on electron micrographs. In order to meet the requirements for normality of distribution and homoscedasticity, data were logarithmically transformed. A two-way analysis of variance was then carried out, taking subjects and time intervals as fixed effects, and using a least significant difference procedure to detect variations between culture time intervals. The whole cell and cytoplasmic volumes showed 3-4 fold increases during culture. The cell surface area more than doubled; this was partly attributable to the larger cell volume and partly to increased surface irregularity. The mitochondrial volume also showed a similar significant increase, attributable to an increase in both number and size of mitochondrial profiles, the cytoplasmic volume fraction remaining approximately constant. Although there was a statistically significant increase in nuclear surface area, the nuclear changes were relatively small. The results and the application of appropriate statistical methods have thus provided basic morphometric data for human macrophage development in culture. The experimental system should permit further investigation of factors governing impaired macrophage development in malignant disease. Images Fig. 1 Fig. 2 PMID:3654357

  19. 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. PMID:24718256

  20. Building Rapport between Human and ECA: A Pilot Study

    E-print Network

    Novick, David G.

    Building Rapport between Human and ECA: A Pilot Study David Novick, Iván Gris Department are interested in exploring how ECAs can build rapport with humans. Face-to-face conversation is an ongoing address in this paper is how ECAs can build rapport with humans through behaviors linked to familiarity

  1. 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)

  2. Human Motion in Cooperative Tasks: Moving Object Case Study

    E-print Network

    Paris-Sud XI, Université de

    Human Motion in Cooperative Tasks: Moving Object Case Study Sylvain Miossec AIST/CNRS JRL Email, for a pair of human operators, in moving a handle-shaped object between two predefined locations on a table of human haptics in physical cooperative tasks involving an object intermediary, which we term person

  3. Studies of human breast cancer metastasis using nude mice

    Microsoft Academic Search

    Janet E. Price; Ruo Dan Zhang

    1990-01-01

    Athymic nude mice have been used in recent years to study the biology of human tumors and to assess therapeutic responses in vivo rather than just in vitro. Some human tumors metastasize in nude mice, providing model systems for analyzing various aspects of the metastatic phenotype of human neoplasms. For breast carcinomas, however, the tumor-take rate of surgical specimens is

  4. 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

  5. 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

  6. 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.

  7. 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…

  8. Pharmacokinetic and Chemoprevention Studies on Tea in Humans

    PubMed Central

    Chow, H-H. Sherry; Hakim, Iman A.

    2011-01-01

    Green tea and its major polyphenols constituents, tea catechins, have been shown to have many health benefits including cancer prevention. Tea catechins and tea catechin metabolites/catabolites are bioavailable in the systemic circulation after oral intake of green tea or green tea catechins. The metabolites/catabolites identified in humans include glucuronide/sulfate conjugates, methylated tea catechin conjugates, and microflora-mediated ring fission products and phenolic acid catabolites. Plasma levels of unchanged tea catechins in humans are mostly in the sub-?M or nM concentration range, which is much lower than the effective concentrations determined in most in vitro studies. However, some of the catechin metabolites/catabolites are present in the systemic circulation at levels much higher than those of the parent catechins. The contribution of catechin derived metabolites/catabolites to the biological effects associated with green tea is yet to be defined. A limited number of chemoprevention trials of green tea or green tea catechins have been conducted to date and have observed potential preventive activity for oral, prostate, and colorectal cancer. Emerging data from multiple ongoing intervention trials will further contribute to defining the cancer preventive activity of green tea or green tea catechins. PMID:21624470

  9. Implementing Time-Limited Welfare: Early Experiences in Three States. The Cross-State Study of Time-Limited Welfare.

    ERIC Educational Resources Information Center

    Bloom, Dan; Butler, David

    This report examines time-limited welfare beginning at the broadest level, tracing the rapid emergence of time-limited welfare as a policy approach in part I. Chapter 1 examines the history of time-limited welfare and the key challenges posed by this policy. Part II begins to focus on the three participating states--Florida, Vermont, and…

  10. Toward new understandings of human–animal relationships in sport: a study of Australian jumps racing

    Microsoft Academic Search

    Phil McManus; Daniel Montoya

    2012-01-01

    The importance of studying human–animal relationships and animal subjectivity is increasingly recognised by social and cultural geographers, particularly in agricultural pursuits. Little research, however, has been undertaken on animals in sport, resulting in a limited understanding of the perceptions and treatment of animals in society. To address this concern, we interrogate print media coverage of the construction and positioning of

  11. 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…

  12. Studies on Human Thyroxine-Binding Globulin

    PubMed Central

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

    1972-01-01

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

  13. 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…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2013-01-01

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

  16. SAFETY, IDENTITY AND CONSENT: A LIMITED DEFENSE OF REPRODUCTIVE HUMAN CLONING

    Microsoft Academic Search

    2006-01-01

    ABSTRACTSome 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

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

    NASA Astrophysics Data System (ADS)

    Zelenyi, Lev

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

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

    Microsoft Academic Search

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

    2011-01-01

    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

  19. Limitations of scanned human copresence encounters for modelling proximity-borne malware

    E-print Network

    Voelker, Geoffrey M.

    by scanners. We show that the statistical properties of scanned encounters differ from actual device. In addition to helping us understand the limitations of encounter data gathered by scanners in the field, our for advertisements and crime prevention [3], increasing the risk of such malware threats. In the case

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

    SciTech Connect

    Hsu, Christina M. L. [Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 and Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 (United States); Palmeri, Mark L. [Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Segars, W. Paul [Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 (United States); Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Veress, Alexander I. [Department of Mechanical Engineering, University of Washington, Seattle, Washington 98195 (United States); Dobbins, James T. III [Carl E. Ravin Advanced Imaging Laboratories, Duke University Medical Center, Durham, North Carolina 27705 (United States); Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710 (United States); Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708 (United States); Medical Physics Graduate Program, Duke University, Durham, North Carolina 27705 (United States); Department of Physics, Duke University, Durham, North Carolina 27708 (United States)

    2013-04-15

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

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

    PubMed Central

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

    Halquist, Don

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

  3. Sensitivity Study of Physical Limits on Ground Motion at Yucca Mountain

    E-print Network

    Duan, Benchun

    1 Sensitivity Study of Physical Limits on Ground Motion at Yucca Mountain Benchun Duan1 and Steven investigate physical3 limits at Yucca Mountain, Nevada, and assess sensitivities due to uncertainties in fault (e.g.,28 Bommer, 2002; Bommer et al., 2004).29 The 1998 PSHA for Yucca Mountain, a potential high

  4. 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…

  5. Spatial Genetic Structure Patterns of Phenotype-Limited and Boundary-Limited Expanding Populations: A Simulation Study

    PubMed Central

    Dai, Qiang; Zhan, Xiangjiang; Lu, Bin; Fu, Jinzhong; Wang, Qian; Qi, Dunwu

    2014-01-01

    Range expansions may create a unique spatial genetic pattern characterized by alternate genetically homogeneous domains and allele frequency clines. Previous attempts to model range expansions have mainly focused on the loss of genetic diversity during expansions. Using individual-based models, we examined spatial genetic patterns under two expansion scenarios, boundary-limited range expansions (BLRE) and phenotype-limited range expansions (PhLRE). Our simulation revealed that the genetic diversity within populations lost quickly during the range expansion, while the genetic difference accumulated between populations. Consequently, accompanying the expansions, the overall diversity featured a slow decrease. Specifically, during BLREs, high speed of boundary motion facilitated the maintenance of total genetic diversity and sharpened genetic clines. Very slight constraints on boundary motion of BLREs drastically narrowed the homogeneous domains and increased the allele frequency fluctuations from those levels exhibited by PhLREs. Even stronger constraints, however, surprisingly brought the width of homogeneous domains and the allele frequency fluctuations back to the normal levels of PhLREs. Furthermore, high migration rates maintained a higher total genetic diversity than low ones did during PhLREs. Whereas, the total genetic diversities during BLREs showed a contrary pattern: higher when migration was low than those when migration was high. Besides, the increase of migration rates helped maintain a greater number of homogeneous domains during PhLREs, but their effects on the number of homogeneous domains during BLREs were not monotonous. Previous studies have showed that the homogenous domains can merge to form a few broad domains as the expansion went on, leading to fewer homogeneous domains. Our simulations, meanwhile, revealed that the range expansions could also rebuild homogeneous domains from the clines during the range expansion. It is possible that that the number of homogeneous domains was determined by the interaction of merging and newly emerging homogeneous domains. PMID:24465700

  6. Interindividual variation in the capacity-limited renal glucuronidation of probenecid by humans

    Microsoft Academic Search

    T. B. Vree; E. W. J. Van Ewijk-Beneken Kolmer; E. W. Wuis; Y. A. Hekster; M. M. M. Broekman

    1993-01-01

    A dose of 1,000 mg probenecid was administered orally to 14 human volunteers in order to quantify the maximal rate of formation and excretion of probenecid acyl glucuronide in the urine. Probenecid showed dose-dependent pharmacokinetics. Plasma protein binding of probenecid was high, being somewhat higher in males (90.7±1.4%) than in females (87.9±1.4%; p=0.0019). It was shown that probenecid is metabolized

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

    Microsoft Academic Search

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

    2012-01-01

    BackgroundWest Nile virus (WNV) is a mosquito-borne flavivirus maintained and amplified among birds and tangentially transmitted to humans and horses which may develop terminal neuroinvasive disease. Outbreaks typically have a three-year pattern of silent introduction, rapid amplification and subsidence, followed by intermittent recrudescence. Our hypothesis that amplification to outbreak levels is contingent upon antecedent seroprevalence within maintenance host populations was

  8. 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

  9. 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-? 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-?, 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

  10. Studies of culture conditions and environmental stability of human metapneumovirus

    Microsoft Academic Search

    Sharon J. Tollefson; Reagan G. Cox; John V. Williams

    2010-01-01

    Human metapneumovirus (HMPV) is a paramyxovirus that is a leading cause of acute respiratory disease. HMPV is difficult to cultivate and limited published data describe the in vitro growth characteristics of the virus and its ability to replicate in different cell lines. Stability of HMPV to different temperatures or environmental conditions has not been described. Nosocomial infections due to HMPV

  11. Risk assessment of diesel exhaust and lung cancer: combining human and animal studies after adjustment for biases in epidemiological studies

    PubMed Central

    2011-01-01

    Background Risk assessment requires dose-response data for the evaluation of the relationship between exposure to an environmental stressor and the probability of developing an adverse health effect. Information from human studies is usually limited and additional results from animal studies are often needed for the assessment of risks in humans. Combination of risk estimates requires an assessment and correction of the important biases in the two types of studies. In this paper we aim to illustrate a quantitative approach to combining data from human and animal studies after adjusting for bias in human studies. For our purpose we use the example of the association between exposure to diesel exhaust and occurrence of lung cancer. Methods Firstly, we identify and adjust for the main sources of systematic error in selected human studies of the association between occupational exposure to diesel exhaust and occurrence of lung cancer. Evidence from selected animal studies is also accounted for by extrapolating to average ambient, occupational exposure concentrations of diesel exhaust. In a second stage, the bias adjusted effect estimates are combined in a common effect measure through meta-analysis. Results The random-effects pooled estimate (RR) for exposure to diesel exhaust vs. non-exposure was found 1.37 (95% C.I.: 1.08-1.65) in animal studies and 1.59 (95% C.I.: 1.09-2.10) in human studies, whilst the overall was found equal to 1.49 (95% C.I.: 1.21-1.78) with a greater contribution from human studies. Without bias adjustment in human studies, the pooled effect estimate was 1.59 (95% C.I.: 1.28-1.89). Conclusions Adjustment for the main sources of uncertainty produced lower risk estimates showing that ignoring bias leads to risk estimates potentially biased upwards. PMID:21481231

  12. Roadmap: Human Development and Family Studies Child and Youth Development -

    E-print Network

    Sheridan, Scott

    Roadmap: Human Development and Family Studies ­ Child and Youth Development - Bachelor of Science Child Development 3 See note 1 on page 2 HDFS 24013 Early Adolescence 3 Kent Core Requirements 3 See or upper division) 3 See note 3 on page 3 #12;Roadmap: Human Development and Family Studies ­ Child

  13. The impact of new technologies on human population studies

    Microsoft Academic Search

    Michael D. Waters; James K. Selkirk; Kenneth Olden

    2003-01-01

    Human population studies involve clinical or epidemiological observations that associate environmental exposures with health endpoints and disease. Clearly, these are the most sought after data to support assessments of human health risk from environmental exposures. However, the foundations of many health risk assessments rest on experimental studies in rodents performed at high doses that elicit adverse outcomes, such as organ

  14. Roadmap: Physical Education Human Movement Studies Bachelor of Science

    E-print Network

    Sheridan, Scott

    Roadmap: Physical Education ­ Human Movement Studies ­ Bachelor of Science [EH-BS-PEP-HMS] College of Education, Health and Human Services School of Teaching, Learning and Curriculum Studies Catalog Year: 2013 Introduction to Physical Education, Fitness and Sport 3 US 10097 Destination Kent State: First Year Experience

  15. Roadmap: Physical Education Human Movement Studies Bachelor of Science

    E-print Network

    Sheridan, Scott

    Roadmap: Physical Education ­ Human Movement Studies ­ Bachelor of Science [EH-BS-PEP-HMS] College of Education, Health and Human Services School of Teaching, Learning and Curriculum Studies Catalog Year: 2012 Introduction to Physical Education, Fitness and Sport 3 US 10097 Destination Kent State: First Year Experience

  16. REPORTING NEEDS FOR STUDIES OF ENVIRONMENTAL CHEMICALS IN HUMAN MILK

    E-print Network

    California at Berkeley, University of

    REPORTING NEEDS FOR STUDIES OF ENVIRONMENTAL CHEMICALS IN HUMAN MILK Michael N. Bates School, USA Studies of environmental chemicals in human milk have been carried out in many coun- tries trends in exposure to chemicals, for research into the determinants of environmental chemicals in milk

  17. 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.

  18. Electrophysiological Studies of Face Perception in Humans

    Microsoft Academic Search

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

    1996-01-01

    Event-related potentials (ERPs) associated with face perception were recorded with scalp electrodes from normal volunteers. Subjects performed a visual target detection task in which they mentally counted the number of occurrences of pictorial stimuli from a designated category such as butterflies. In separate experiments, target stimuli were embedded within a series of other stimuli including unfamiliar human faces and isolated

  19. Studies of strontium biokinetics in humans

    Microsoft Academic Search

    Vera Höllriegl; Eckhard Werner; Paul Roth; Peter Schramel; Iris Wendler

    2002-01-01

    The radioactive isotopes of strontium, mainly 90Sr, which are common fission products, may significantly contribute to the internal exposure of the population in case of their accidental release into the environment and transfer to the food chain. For 90Sr, the internal radiation dose is significantly dependent on the fractional absorption of the ingested activity (f1-value). Human data on the absorption

  20. Limited capacity of the nuclear matrix to bind telomere repeat binding factor TRF1 may restrict the proliferation of mortal human fibroblasts.

    PubMed

    Okabe, Jun; Eguchi, Akiko; Wadhwa, Renu; Rakwal, Randeep; Tsukinoki, Rumi; Hayakawa, Takao; Nakanishi, Mahito

    2004-02-01

    The maintenance of telomere integrity is essential for prolonged cell proliferation, and failure in this mechanism is a most consistent manifestation of cellular senescence. In this study, we investigated the role of telomere repeat binding factor (TRF1) in the proliferation of human fibroblasts. TRF1 expression is upregulated in a large variety of immortal human cells and supports de novo telomere formation in a dose-dependent manner. These observations suggest that the suppression of TRF1 might limit telomere maintenance and thus the life span of mortal cells. However, primary fibroblasts ectopically overexpressing TRF1 were unable to avoid senescence. On the other hand, exogenously expressed TRF1 in primary fibroblasts neither supported de novo telomere formation nor bound to the nuclear matrix as tightly as observed in immortal cells that show upregulated TRF1 expression. We present evidence suggesting that mortal human cells lack specific ligand(s) that anchor TRF1 to the nuclear matrix and that this contributes to their limited lifespan. PMID:14681297

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

    SciTech Connect

    Ascenzi, Paolo, E-mail: ascenzi@uniroma3.it [Interdepartmental Laboratory of Electron Microscopy, University Roma Tre, Via della Vasca Navale 79, I-00146 Roma (Italy) [Interdepartmental Laboratory of Electron Microscopy, University Roma Tre, Via della Vasca Navale 79, I-00146 Roma (Italy); National Institute for Infectious Diseases I.R.C.C.S. 'Lazzaro Spallanzani', Via Portuense 292, I-00149 Roma (Italy); Gullotta, Francesca; Gioia, Magda; Coletta, Massimo [Department of Experimental Medicine and Biochemical Sciences, University of Roma 'Tor Vergata', Via Montpellier 1, I-00133 Roma (Italy) [Department of Experimental Medicine and Biochemical Sciences, University of Roma 'Tor Vergata', Via Montpellier 1, I-00133 Roma (Italy); Interuniversity Consortium for the Research on the Chemistry of Metals in Biological Systems, Piazza Umberto I 1, I-87100 Bari (Italy); Fasano, Mauro [Department of Structural and Functional Biology, and Center of Neuroscience, University of Insubria, Via Alberto da Giussano 12a, I-21052 Busto Arsizio, VA (Italy)] [Department of Structural and Functional Biology, and Center of Neuroscience, University of Insubria, Via Alberto da Giussano 12a, I-21052 Busto Arsizio, VA (Italy)

    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.

  2. Accident causation study on roadways with limited sight distance crest vertical curves

    E-print Network

    Stoddard, Angela May

    1994-01-01

    two-lane and multilane study sites with limited stopping sight distance was similar to the percentage of older drivers in all accidents, reported by the National Safety Council. Only 30 of the accident narratives evaluated were large truck accidents...

  3. 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. [Los Alamos National Lab., NM (United States); Supek, S. [Zagreb Univ. (Croatia). Dept. of Physics

    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.

  4. 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.

  5. 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. PMID:24700822

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

    PubMed

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

    2013-01-01

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

  7. Binding of Transmembrane Mucins to Galectin-3 Limits Herpesvirus 1 Infection of Human Corneal Keratinocytes

    PubMed Central

    Woodward, A. M.; Mauris, J.

    2013-01-01

    Epithelial cells lining mucosal surfaces impose multiple barriers to viral infection. At the ocular surface, the carbohydrate-binding protein galectin-3 maintains barrier function by cross-linking transmembrane mucins on the apical glycocalyx. Despite these defense mechanisms, many viruses have evolved to exploit fundamental cellular processes on host cells. Here, we use affinity assays to show that herpes simplex virus type 1 (HSV-1), but not HSV-2, binds human galectin-3. Knockdown of galectin-3 in human corneal keratinocytes by small interfering RNA significantly impaired HSV-1 infection, but not expression of nectin-1, indicating that galectin-3 is a herpesvirus entry mediator. Interestingly, exposure of epithelial cell cultures to transmembrane mucin isolates decreased viral infectivity. Moreover, HSV-1 failed to elute the biological counterreceptor MUC16 from galectin-3 affinity columns, suggesting that association of transmembrane mucins to galectin-3 provides protection against viral infection. Together, these results indicate that HSV-1 exploits galectin-3 to enhance virus attachment to host cells and support a protective role for transmembrane mucins under physiological conditions by masking viral entry mediators on the epithelial glycocalyx. PMID:23487460

  8. Binding of transmembrane mucins to galectin-3 limits herpesvirus 1 infection of human corneal keratinocytes.

    PubMed

    Woodward, A M; Mauris, J; Argüeso, P

    2013-05-01

    Epithelial cells lining mucosal surfaces impose multiple barriers to viral infection. At the ocular surface, the carbohydrate-binding protein galectin-3 maintains barrier function by cross-linking transmembrane mucins on the apical glycocalyx. Despite these defense mechanisms, many viruses have evolved to exploit fundamental cellular processes on host cells. Here, we use affinity assays to show that herpes simplex virus type 1 (HSV-1), but not HSV-2, binds human galectin-3. Knockdown of galectin-3 in human corneal keratinocytes by small interfering RNA significantly impaired HSV-1 infection, but not expression of nectin-1, indicating that galectin-3 is a herpesvirus entry mediator. Interestingly, exposure of epithelial cell cultures to transmembrane mucin isolates decreased viral infectivity. Moreover, HSV-1 failed to elute the biological counterreceptor MUC16 from galectin-3 affinity columns, suggesting that association of transmembrane mucins to galectin-3 provides protection against viral infection. Together, these results indicate that HSV-1 exploits galectin-3 to enhance virus attachment to host cells and support a protective role for transmembrane mucins under physiological conditions by masking viral entry mediators on the epithelial glycocalyx. PMID:23487460

  9. Myocellular limitations of human performance and their modification through genome-dependent responses at altitude.

    PubMed

    Flueck, Martin

    2010-03-01

    Human muscle operates along a continuum of power output, which is set through bioenergetic and anatomical principles. In turn, environmental and intrinsic factors during contractile work exert pronounced control over muscle performance by instructing muscle remodelling. This phenotypic control is specifically indicated with intense exercise at altitude, when extra strain is put on energy supply and the temperature-dependent mechanical efficiency of contraction. While it is classically thought that chronic exposure to hypoxia is maladaptive, repeated short episodes of reduced oxygenation alone or in combination with intense endurance work is now understood to preserve exercise performance when atmospheric oxygen levels are low. Endurance training at moderate altitude exploits the temperature-dependent malleability of energy supply that may maximize metabolic flux at altitude. The contribution of genomic mechanisms is important to the plasticity of metabolic pathways in exercised muscle. This is highlighted by the association of distinct gene polymorphisms in master governors of mitochondrial and vascular growth with exercise phenotypes. Feedforward control of human locomoter muscle by exercise involves the transient upregulation of transcript expression for metabolic processes. The response of the mitochondrial transcriptome to intense exercise is graded with respect to mitochondrial content and deoxygenation during muscle work and reflects exercise-induced mitochondrial biogenesis. This supports the notion that genome-mediated muscle malleability is under feedback control by design constraints of the pathway of oxygen. Thus, activity-dependent and genetic mechanisms contribute to the interindividual difference in the metabolic bottlenecks in athletes performing in exceptional environmental conditions. PMID:19897567

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

    PubMed Central

    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

    2014-01-01

    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. PMID:25100739

  11. 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. PMID:25100739

  12. 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.

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

    PubMed

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

    2013-01-01

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

  14. The role of mean corpuscular haemoglobin concentration in limiting the storage life of human blood.

    PubMed

    Turner, S; Williams, A R; Rees, J M

    1987-01-01

    Human erythrocytes stored for more than 21 days in citrate phosphate dextrose with adenine (CPDA-1) at +4 degrees C had a decreased cell volume, an increased cell density, an elevated mean corpuscular haemoglobin concentration (MCHC) and hence an elevated internal viscosity. These changes are normally masked by the reversible cell swelling which accompanies storage in CPDA-1. Incubation of stored cells for 24 h at 37 degrees C in fresh autologous plasma mimics the effects of reinfusion and causes the artificially swollen cells to shrink to their true volume. Thus, incubated cells which had been stored in CPDA-1 for more than 21 days exhibited a decreased filterability through Nuclepore membranes in vitro, which is apparently correlated with a decreased survival time in vivo. PMID:3604174

  15. 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.

  16. 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

  17. 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

  18. An Interdisciplinary Deer and Human Population Study

    NSDL National Science Digital Library

    William J. Webb

    2009-01-01

    This activity helps the learner answer the question: "What environmental problems arise due to animal and human overpopulation and what might need to be done to combat these problems?" Learners play a game that simulates population sampling in an imaginary state park. After the game is completed, each park must decide if they are at the carrying capacity for their park or out of equilibrium. Learners write a proposal detailing how they plan to correct their deer population problem and present it to the group (the Department of Natural Resources). This lesson is described as an interdisciplinary unit and includes literature and math curriculum connections.

  19. Duckweed (Lemna minor) as a Model Plant System for the Study of Human Microbial Pathogenesis

    Microsoft Academic Search

    Yong Zhang; Yangbo Hu; Baoyu Yang; Fang Ma; Pei Lu; Lamei Li; Chengsong Wan; Simon Rayner; Shiyun Chen; Pere-Joan Cardona

    2010-01-01

    BackgroundPlant infection models provide certain advantages over animal models in the study of pathogenesis. However, current plant models face some limitations, e.g., plant and pathogen cannot co-culture in a contained environment. Development of such a plant model is needed to better illustrate host-pathogen interactions.Methodology\\/Principal FindingsWe describe a novel model plant system for the study of human pathogenic bacterial infection on

  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. The utilization of humanized mouse models for the study of human retroviral infections

    PubMed Central

    Van Duyne, Rachel; Pedati, Caitlin; Guendel, Irene; Carpio, Lawrence; Kehn-Hall, Kylene; Saifuddin, Mohammed; Kashanchi, Fatah

    2009-01-01

    The development of novel techniques and systems to study human infectious diseases in both an in vitro and in vivo settings is always in high demand. Ideally, small animal models are the most efficient method of studying human afflictions. This is especially evident in the study of the human retroviruses, HIV-1 and HTLV-1, in that current simian animal models, though robust, are often expensive and difficult to maintain. Over the past two decades, the construction of humanized animal models through the transplantation and engraftment of human tissues or progenitor cells into immunocompromised mouse strains has allowed for the development of a reconstituted human tissue scaffold in a small animal system. The utilization of small animal models for retroviral studies required expansion of the early CB-17 scid/scid mouse resulting in animals demonstrating improved engraftment efficiency and infectivity. The implantation of uneducated human immune cells and associated tissue provided the basis for the SCID-hu Thy/Liv and hu-PBL-SCID models. Engraftment efficiency of these tissues was further improved through the integration of the non-obese diabetic (NOD) mutation leading to the creation of NODSCID, NOD/Shi-scid IL2r?-/-, and NOD/SCID ?2-microglobulinnull animals. Further efforts at minimizing the response of the innate murine immune system produced the Rag2-/-?c-/- model which marked an important advancement in the use of human CD34+ hematopoietic stem cells. Together, these animal models have revolutionized the investigation of retroviral infections in vivo. PMID:19674458

  2. Study questions: Energy & Environment: Humans & Nature 18 May 2012 Two `Laws' of human nature

    E-print Network

    Study questions: Energy & Environment: Humans & Nature 18 May 2012 Two `Laws' of human nature 1. Jevons' Law, or the law of diminishing marginal utility One of the class (sorry, can't remember who) posted an interesting note on `Jevons' Law'. This would seem to be a danger signal for the hopeful

  3. Adipose circadian rhythms: translating cellular and animal studies to human physiology.

    PubMed

    Johnston, Jonathan D

    2012-02-01

    Emerging links between circadian rhythms and metabolism promise much for the understanding of metabolic physiology and pathophysiology, in which white adipose tissue (WAT) plays a prominent role. Many WAT endocrine molecules, termed adipokines, display rhythmic plasma concentration. Moreover, similar to most other tissues, WAT exhibits widespread 24-h variation in gene expression, with approximately 20% of the murine adipose transcriptome estimated to undergo daily variation. A major limitation to human chronobiology research is the availability of physiologically defined peripheral tissues. To date most analyses of in vivo human peripheral clocks has been limited to blood leucocytes. However, subcutaneous adipose tissue represents a novel opportunity to study peripheral molecular rhythms that are of clearly defined metabolic relevance. This review summarises basic concepts of circadian and metabolic physiology before then comparing alternative protocols used to analyse the rhythmic properties of human adipose tissue. PMID:21664232

  4. 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…

  5. The transmediastinal arteries of the human testis: an anatomical study

    Microsoft Academic Search

    D. Pais; P. Fontoura; J. A. Esperança-Pina

    2004-01-01

    Although the arterial supply of the human testis via the testicular artery is a well-studied subject, the pattern of approach that this vessel takes when reaching the gland is, on the other hand, not as well described. Based on the observation of angiological preparations of 196 adult human testes, the authors describe the presence of transmediastinal testicular vessels in one

  6. Visually controlled spatial stabilisation of the human head: compensation for the eye's limited ability to roll.

    PubMed

    Gresty, M A; Bronstein, A M

    1992-06-01

    During movements of the head in pitch (yes-yes) or in yaw (no-no) the visual scene appears stable whereas rolling the head (ear down to shoulder) induces an apparent swinging of the world in the opposite direction. This visual instability is due to the inadequacy, in the roll plane, of the reflex eye movements which are effective in stabilising the eyes in space during pitch and yaw. We investigated whether head is stabilised in roll to protect against visual instability. Human subjects were fixed in a gimbal with their heads free and were exposed to unpredictable oscillatory movement in pitch and, for comparison roll, about axes aligned with the head. With vision, during roll motion, the head was displaced from upright by approximately half the amplitude of the gimbal motion. In comparison, with eyes closed relying on vestibular and proprioceptive cues and during pitch stimuli with or without vision, the magnitude of head displacement from upright was approximately equal to that to the gimbal. The superior head stability in roll, dependent on a visual frame of reference, compensates for poverty of eye movement in this plane. PMID:1407702

  7. Energy adaptations in human pregnancy: limits and long-term consequences.

    PubMed

    Prentice, A M; Goldberg, G R

    2000-05-01

    The very slow rate of human fetal growth generates a lower incremental energy stress than in any other mammalian species. This creates a situation in which adaptive changes in metabolic rate and in the amount of additional maternal fat stored during gestation can make a profound difference to the overall energy needs of pregnancy. Comparisons of women in affluent and poor countries have recorded mean population energy needs ranging from as high as 520 MJ to as low as -30 MJ per pregnancy. These energy costs are closely correlated with maternal energy status when analyzed both between and within populations, suggesting that they represent functional adaptations that have been selected for their role in protecting fetal growth. Although this metabolic plasticity represents a powerful mechanism for sustaining pregnancy under very marginal nutritional conditions, it must not be construed as a perfect mechanism that obviates the need for optimal nutritional care of pregnant women. The fact that fetal weight represents up to 60% of total pregnancy weight gain in many pregnancies in poor societies (compared with a well-nourished norm of 25%) indicates that the fetus is developing under suboptimal nutritional and physiologic conditions. It has long been recognized that this has immediate consequences for the offspring in terms of increased perinatal mortality. The more recent appreciation that impaired fetal growth may also precipitate longer-term defects in terms of adult susceptibility to noncommunicable and infectious diseases reinforces the view that pregnancy may be the most sensitive period of the life cycle in which nutritional intervention may reap the greatest benefits. PMID:10799395

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

    PubMed Central

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

    2014-01-01

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

  9. Effect of limited proteolysis on the stability and enzymatic activity of human placental S-adenosylhomocysteine hydrolase.

    PubMed Central

    Huang, H.; Yuan, C. S.; Borchardt, R. T.

    1997-01-01

    Human placental S-adenosylhomocysteine (AdoHcy) hydrolase was subjected to limited papain digestion. The multiple cleavage sites in the enzyme were identified to be Lys94-Ala95, Tyr100-Ala101, Glu243-Ile244, Met367-Ala368, Gln369-Ile370, and Gly382-Val383. Despite multiple cleavage sites in the backbone of the protein, the digested enzyme was able to maintain its quaternary structure and retain its full catalytic activity. The enzyme activity of the partially digested AdoHcy hydrolase was essentially identical to that of the native enzyme at several pH values. The thermal stabilities of the native and partially digested enzymes were only slightly different at all temperatures tested. The stability of both native and partially digested enzymes were examined in guanidine hydrochloride and equilibrium unfolding transitions were monitored by CD spectroscopy and tryptophan fluorescence spectroscopy. The results of these experiments can be summarized as follows: (1) CD spectroscopic analysis showed that the overall secondary and tertiary structures of the partially digested enzyme are essentially identical with those of the native enzyme; and (2) tryptophan fluorescence spectroscopic analysis indicated that there are small differences in the environments of surface-exposed tryptophan residues between the partially digested enzyme and the native enzyme under unfolding conditions. The differences in the free energy of unfolding, delta(delta Gu) [delta Gu(native)-delta Gu(digested)], is approximately 1.3 kcal/mol. When NAD+ was removed from the partially digested enzyme, the secondary and tertiary structures of the apo form of the digested AdoHcy hydrolase were completely lost and the enzymatic activity could not be recovered by incubation with excess NAD+. These results suggest that AdoHcy hydrolase exists as a very compact enzyme with extensive intramolecular bonding, which contributes significantly to the overall global protein stabilization. Identification of the surface-exposed peptide bonds, which are susceptible to papain digestion, has provided some constraints on the spatial orientations of subunits of the enzyme. This information, in turn, has provided supplemental data for X-ray crystallographic studies currently ongoing in our laboratories. PMID:9232649

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

    PubMed

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

    2014-12-01

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

  11. How Many Penguins Does it Take? Studying Carrying Capacity and Limiting Factors

    NSDL National Science Digital Library

    Elissa Elliott

    This hands-on activity simulates the process of population fluctuation. Students will learn the terms limiting factors and carrying capacity. Rather than memorize these terms, the students can see the terms come to life in this animated penguin activity. The results clearly show how populations are affected by many things -- one of them being food availability. This particular activity focuses on a penguin population; however, serious debates regarding the human population and the carrying capacity of the earth have been going on for some time. Students will: predict what the carrying capacity of a penguin population of a certain area will be; engage in a hands-on activity, simulating the way carrying capacity works; and explain what the terms carrying capacity and limiting factors mean for a population. Students can do further research on penguins and how they survive the Antarctic cold.

  12. 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...

  13. Mine waste contamination limits soil respiration rates: a case study using quantile regression

    E-print Network

    Rilli, Matthias C.

    Mine waste contamination limits soil respiration rates: a case study using quantile regression an environmental gradient. We quantified in situ soil respiration, pH, and heavy metal concentrations across a mine. Respiration values were monitored at study sites over 2 years. We used QR to show that soil respiration

  14. A Genomic Region Evolving Toward Different GC Contents in Humans and Chimpanzees Indicates a Recent and Regionally Limited Shift in the Mutation Pattern

    Microsoft Academic Search

    Ingo Ebersberger; Matthias Meyer

    2005-01-01

    DNA sequences evolving differently in the human and chimpanzee genomes signal recent and regionally limited changes in the process of DNA sequence evolution. Here we present the comparison of 90 kb from the nonrecombining part of the human Y chromosome to the corresponding part of the chimpanzee genome using gorilla as out-group. Our results reveal a significant difference in the

  15. Foot Pain and Mobility Limitations in Older Adults: The Framingham Foot Study

    PubMed Central

    2013-01-01

    Background. Foot pain is very common in the general population and has been shown to have a detrimental impact on health-related quality of life. This is of particular concern in older people as it may affect activities of daily living and exacerbate problems with balance and gait. The objective of this study is to evaluate the independent relationships between foot pain and mobility limitation in a population of community-dwelling older adults. Methods. Population-based cross-sectional study. Participants (n = 1,544) from the Framingham Foot Study (2002–2008) were assessed for physical performance. Foot pain was documented using the question “On most days, do you have pain, aching, or stiffness in either foot?” Mobility limitation was assessed using the Short Physical Performance Battery, dichotomized using 1–9 as an indicator of mobility limitation and 10–12 as no mobility limitation. Results. Foot pain was reported by 19% of men and 25% of women. After adjusting for age, obesity, smoking status, and depression, foot pain was significantly associated with mobility limitation in both men (odds ratio = 2.00, 95% confidence interval 1.14 – 3.50; p = .016) and women (odds ratio = 1.59, 95% confidence interval 1.03 – 2.46; p = .037). Conclusion. In our study of older adults from the Framingham Foot Study, foot pain was associated with an increased odds of having mobility limitation in both men and women. Clinicians should consider assessment of foot pain in general examinations of older adults who are at risk of mobility limitation. PMID:23704204

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

    EPA Science Inventory

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

  17. Study Humanities and Social Science Abroad General/Most All

    E-print Network

    Maxwell, Bruce D.

    Study Humanities and Social Science Abroad General/Most All Argentina - Pontificia Universidad) Chile - Pontificia Universidad Católica de Valparaíso (ISEP)* Denmark- University of Copenhagen (DEX (CCIS) Botswana- University of Botswana (ISEP) Bulgaria - University of Veliko Turnovo (CCIS) Chile

  18. Human tracking studies involving an actively powered, augmented exoskeleton

    Microsoft Academic Search

    D. W. Repperger; B. O. Hill; C. Hasser; M. Roark; C. A. Phillips

    1996-01-01

    An actively powered, augmented, exoskeleton system is studied within a speed-accuracy performance task framework with human subjects. This system has a dual use in military applications as well as for the rehabilitation of patients with neuromotor disorders

  19. Trend of different molecular markers in the last decades for studying human migrations.

    PubMed

    Kundu, Sharbadeb; Ghosh, Sankar Kumar

    2015-02-10

    Anatomically modern humans are known to have widely migrated throughout history. Different scientific evidences suggest that the entire human population descended from just several thousand African migrants. About 85,000 years ago, the first wave of human migration was out of Africa, that followed the coasts through the Middle East, into Southern Asia via Sri Lanka, and in due course around Indonesia and into Australia. Another wave of migration between 40,000 and 12,000 years ago brought humans northward into Europe. However, the frozen north limited human expansion in Europe, and created a land bridge, "Bering land bridge", connecting Asia with North America about 25,000 years ago. Although fossil data give the most direct information about our past, it has certain anomalies. So, molecular archeologists are now using different molecular markers to trace the "most recent common ancestor" and also the migration pattern of modern humans. In this study, we have studied the trend of molecular markers and also the methodologies implemented in the last decades (2003-2014). From our observation, we can say that D-loop region of mtDNA and Y chromosome based markers are predominant. Nevertheless, mtDNA, especially the D-loop region, has some unique features, which makes it a more effective marker for tracing prehistoric footprints of modern human populations. Although, natural selection should also be taken into account in studying mtDNA based human migration. As per technology is concerned, Sanger sequencing is the major technique that is being used in almost all studies. But, the emergence of different cost-effective-and-easy-to-handle NGS platforms has increased its popularity over Sanger sequencing in studying human migration. PMID:25510397

  20. Religious Studies The School of Humanities

    E-print Network

    Richards-Kortum, Rebecca

    ,andsocioculturalapproachestothestudyofreligion)andreligious traditions (African religions, Buddhism, Christianity, comparative religions, Hinduism,Africanreligion,Buddhism,comparativestudies,cross-cultural studies,Islam,Hinduism,methodologicalstudies,orethics/philosophy ofreligion Honors Program

  1. Relationship between prolonged and self-limited photoparoxysmal responses and seizure incidence: study and review.

    PubMed

    Puglia, J F; Brenner, R P; Soso, M J

    1992-01-01

    Photoparoxysmal responses (PPRs) are generalized epileptiform abnormalities occurring during photic stimulation. Prolonged PPRs, which outlast the stimulus, can be distinguished from self-limited PPRs, which cease spontaneously or when the flashes stop. Reilly and Peters (1973) found a higher incidence of seizures in patients with prolonged, rather than self-limited, PPRs. More recently, Jayakar and Chiappa (1990) reported a similar seizure incidence in the prolonged and self-limited groups. In order to assess these discordant results, we reviewed EEG records performed in our laboratory from 1983 to 1988. Sixty-eight EEGs had PPRs (19 prolonged and 49 self-limited). Patients with PPRs had a significantly higher incidence of seizures than controls (total patients versus controls, p less than 0.001; prolonged subgroup compared to controls, p less than 0.001; self-limited subgroup versus controls, p less than 0.01). Comparing PPR groups, we found that a prolonged PPR was associated with a higher incidence of seizures than a self-limited response (p less than 0.05); however, patients with a prolonged PPR more often had other epileptiform abnormalities than the self-limited group (p less than 0.001). There was no difference in seizure incidence between the PPR groups when comparing patients whose EEGs also contained other epileptiform abnormalities. Meta-analysis suggests apparent differences among the three studies are superficial. PMID:1532400

  2. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-07-01

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

  4. 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.

  5. Hispanic Studies The School of Humanities

    E-print Network

    Richards-Kortum, Rebecca

    Spanish, which tests students' competence in Hispanic literature and linguistics · TakeSPAN507Teaching College communication. Qualified students may undertake independent work. Degree Requirements for BA in Hispanic Studies at Rice University. Single Majors--Students majoring in Hispanic studies must complete at least 30

  6. Medieval Studies The School of Humanities

    E-print Network

    Richards-Kortum, Rebecca

    Literature and Culture of the Middle Ages:Saints and Sinners · MDST 425 Courtly Love in Medieval France Eras · MDST 429 Music in the Middle Ages #12;212 DEPARTMENTS / Medieval Studies Classical Studies MDST of the Medieval Woman MDST 414 Literature and Culture of the Middle Ages: Saints and Sinners MDST 425 Courtly Love

  7. Medieval Studies The School of Humanities

    E-print Network

    Richards-Kortum, Rebecca

    Literature and Culture of the Middle Ages:Saints and Sinners · MDST 425 Courtly Love in Medieval France Eras · MDST 429 Music in the Middle Ages #12;218 DEPARTMENTS / Medieval Studies Classical Studies MDST of the Medieval Woman MDST 414 Literature and Culture of the Middle Ages: Saints and Sinners MDST 425 Courtly Love

  8. 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.

  9. Numerical Study on Stress Concentration Effect in Rapid Evaluation of Fatigue Limit through Temperature Evolution

    NASA Astrophysics Data System (ADS)

    Ly, Hung Anh; Inoue, Hirotsugu; Irie, Yousuke

    The technique for rapid evaluation of fatigue limit using infrared thermography has been developed and paid much attention recently. However, the enhancement of reliability of this technique is demanded for practical application in industries. This study is conducted to verify the effect of stress concentration on fatigue limit evaluation through numerical simulation. Temperature evolutions of stainless steel specimens with different notches are simulated by 3D elasto-plastic finite element analysis. It has been shown that the fatigue limit evaluation based on the temperature evolution is essentially explained by plastic energy dissipation, and that the temperature evolution should be measured after a sufficiently large number of cycles so that plastic shakedown is achieved. It has been remarked that the fatigue limit is overestimated if the spatial resolution of infrared thermography is not fine enough to measure the temperature evolution at the stress concentration site.

  10. Jewish Studies The School of Humanities

    E-print Network

    Richards-Kortum, Rebecca

    is an interdisciplinary field that encompasses the texts, history, languages, philosophy, and culture of Jews and Judaism of studying Judaism because of the interdisciplinary status of JWST which crosses boundaries between Judaism; or RELI 209 Introduction to Judaism

  11. German Studies The School of Humanities

    E-print Network

    Richards-Kortum, Rebecca

    level, as follows: · GERM304German through Cultural Texts · GERM305Enlightenment and Romanticism, 1750 · GERM305Enlightenment and Romanticism, 1750­1850 #12;2 Departments / German Studies · GERM306Realism

  12. German Studies The School of Humanities

    E-print Network

    Richards-Kortum, Rebecca

    Enlightenment and Romanticism, 1750­1850 · GERM306Realism to Modernity, 1850­present · 4German300-levelcoursesGerman through Cultural Texts · GERM305Enlightenment and Romanticism, 1750­1850 #12;German Studies 193

  13. German Studies The School of Humanities

    E-print Network

    Richards-Kortum, Rebecca

    through Cultural Texts · GERM305Enlightenment and Romanticism, 1750­1850 · GERM306Realism to Modernity and Romanticism, 1750­1850 #12;2 Departments / German Studies · GERM306Realism to Modernity, 1850­present · Three

  14. 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

  15. BLT Humanized Mice as Model to Study HIV Vaginal Transmission

    PubMed Central

    Deruaz, Maud; Luster, Andrew D.

    2013-01-01

    The majority of human immunodeficiency virus type 1 (HIV-1) infections occur by sexual exposure, and vaginal transmission accounts for more than half of all newly acquired infections. Studies of vaginal transmission of simian immunodeficiency virus to nonhuman primates (NHPs) have suggested an important role for immune cell trafficking in the establishment of infection as well is in the process of viral dissemination. However, NHP models do not permit the study of HIV transmission and dissemination. The improvement of humanized mouse models with robust human immune cell reconstitution of the female genital tract renders these mice susceptible to intravaginal HIV infection. Thus humanized mouse models of HIV vaginal infection will allow the study of the mechanisms involved in HIV transmission and dissemination in vivo. PMID:24151319

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

    PubMed

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

    2015-03-01

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

  17. Transgenic mice expressing the human growth hormone gene provide a model system to study human growth hormone synthesis and secretion in non-tumor-derived pituitary cells: Differential effects of dexamethasone and thyroid hormone

    Microsoft Academic Search

    Hana Vakili; Yan Jin; James I. Nagy; Peter A. Cattini

    2011-01-01

    Growth hormone (GH) is regulated by pituitary and hypothalamic factors as well as peripheral endocrine factors including glucocorticoids and thyroid hormone. Studies on human GH are limited largely to the assessment of plasma levels in endocrine disorders. Thus, insight into the regulation of synthesis versus secretion has come mainly from studies done on non-human GH and\\/or pituitary tumor cells. However,

  18. 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.

  19. 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…

  20. 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.

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

    PubMed Central

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

    2013-01-01

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

  2. Jewish Studies The School of Humanities

    E-print Network

    Richards-Kortum, Rebecca

    is an interdisciplinary field that encompasses the texts, history, languages, philosophy, and culture of Jews and Judaism of studying Judaism because of the interdisciplinary status of JWST which crosses boundaries between). · Studentsmusttakeatleastoneofthefollowingcorecourses: HART 377 Jews and Art;RELI208or324Secular Judaism; or RELI 209 Introduction to Judaism

  3. 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…

  4. Toward psychological studies of human freedom

    Microsoft Academic Search

    Malcolm R. Westcott

    1978-01-01

    Outlines central positions and controversies concerning liberty and freedom as represented in social and political philosophy. Distinctions of importance to psychologists such as those among negative liberty, positive liberty, opportunities, resources, and accomplishment of acts, are discussed. Psychological concepts and data arising from studies of attribution, reactance, dissonance, personal causation, and psychotherapy are examined. The important distinction between freedom as

  5. Medieval Studies The School of Humanities

    E-print Network

    Richards-Kortum, Rebecca

    of the Middle Ages German Studies MDST 126 Freshman Seminar: The Legend of King Arthur in the Middle Ages MDST 330 Mapping German Culture: Courtship, Love and Marriage in the Age of Chivalry MDST 402 Middle High of France · MDST 425 Courtly Love in Medieval France · MDST 429 Music in the Middle Ages · HIST 359/RELI 358

  6. Functional near-infrared optical imaging: utility and limitations in human brain mapping.

    PubMed

    Hoshi, Yoko

    2003-07-01

    Although near-infrared spectroscopy (NIRS) was developed as a tool for clinical monitoring of tissue oxygenation, it also has potential for neuroimaging. A wide range of different NIRS instruments have been developed, and instruments for continuous intensity measurements with fixed spacing [continuous wave (CW)-type instruments], which are most readily available commercially, allow us to see dynamic changes in regional cerebral blood flow in real time. However, quantification, which is necessary for imaging of brain functions, is impossible with these CW-type instruments. Over the past 20 years, many different approaches to quantification have been tried, and several multichannel time-resolved and frequency-domain instruments are now in common use for imaging. Although there are still many problems with this technique, such as incomplete knowledge of how light propagates through the head, NIRS will not only open a window on brain physiology for subjects who have rarely been examined until now, but also provide a new direction for functional mapping studies. PMID:14570159

  7. STUDY OF THE HUMAN CHRONIC WOUND TISSUE: ADDRESSING LOGISTIC BARRIERS AND PRODUCTIVE USE OF LASER CAPTURE MICRODISSECTION

    PubMed Central

    Roy, Sashwati; Sen, Chandan K

    2015-01-01

    Direct procurement of tissue samples from clinically presented chronic human wounds is a powerful approach to understand mechanism at play in an actual problem wound. While such approach suffers from limitations related to lack of reproducible conditions across wounds, something that we are used to the laboratory while studying wounds on experimental animals, the direct study of human wound tissue helps recognize the right questions to ask in the laboratory. Going back and forth between human wound and experimental animal studies helps steer studies on experimental wounds in a clinically relevant direction. In this article, we describe critical factors that need to be considered prior to planning a study involving human wound samples. In addition, we describe an approach to capture wound hyperproliferative epithelium (HE) from chronic human wound biopsies using laser capture microdissection (LCM). LCM is a new technology applicable to a broad range of clinical research and represents a catalyst of sophisticated translational research. PMID:24029938

  8. High-throughput telomere length quantification by FISH and its application to human population studies

    Microsoft Academic Search

    Andrés Canela; Elsa Vera; Peter Klatt; M. A. Blasco

    2007-01-01

    A major limitation of studies of the relevance of telomere length to cancer and age-related diseases in human populations and to the development of telomere-based therapies has been the lack of suitable high-throughput (HT) assays to measure telomere length. We have developed an automated HT quantitative telomere FISH platform, HT quantitative FISH (Q-FISH), which allows the quantification of telomere length

  9. 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.

  10. Geometric morphometrics and virtual anthropology: advances in human evolutionary studies.

    PubMed

    Rein, Thomas R; Harvati, Katerina

    2014-01-01

    Geometric morphometric methods have been increasingly used in paleoanthropology in the last two decades, lending greater power to the analysis and interpretation of the human fossil record. More recently the advent of the wide use of computed tomography and surface scanning, implemented in combination with geometric morphometrics (GM), characterizes a new approach, termed Virtual Anthropology (VA). These methodological advances have led to a number of developments in human evolutionary studies. We present some recent examples of GM and VA related research in human evolution with an emphasis on work conducted at the University of Tübingen and other German research institutions. PMID:24818438

  11. Reconceptualizing Treatment Goals from Language Impairment to Functional Limitations: A Case Study

    ERIC Educational Resources Information Center

    Skarakis-Doyle, Elizabeth

    2005-01-01

    This case study of a preadolescent boy with severe expressive and receptive language impairments illustrates treatment focused on the functional limitations on the child's daily academic activities and social participation. Treatment goals incorporated language comprehension objectives into the student's reading program and language use objectives…

  12. On the biogeography of salt limitation: A study of ant communities

    E-print Network

    Kaspari, Mike

    On the biogeography of salt limitation: A study of ant communities Michael Kasparia,b,1 , Stephen P). Furthermore, inland ecosystems with high rainfall may experi- ence significant sodium loss through leaching), butterflies (13), and bees (14) often search for ``salt licks'' (15) or resort to cannibalism (16) to maintain

  13. Electromagnetic study of the quality factor of pillar microcavities in the small diameter limit

    E-print Network

    Paris-Sud XI, Université de

    -emitting lasers.1 Micropillars are also well suited to the realization of cavity quantum electrodynamic CQED implements a single quantum dot in a micropillar.3,4 In the small-diameter limit, other CQED ef- fects observed for submicron micropillars, even in the well studied GaAs/AlAs system; this behavior is commonly

  14. 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…

  15. Sensitivity Study of Physical Limits on Ground Motion at Yucca Mountain

    E-print Network

    Duan, Benchun

    Sensitivity Study of Physical Limits on Ground Motion at Yucca Mountain by Benchun Duan and Steven at Yucca Mountain, Nevada, and assess sensitivities due to uncertainties in fault geometry, off-fault rock ground-motion parameters (e.g., Bommer, 2002; Bommer et al., 2004). The 1998 PSHA for Yucca Mountain

  16. A Limit Study of JavaScript Parallelism Emily Fortuna Owen Anderson Luis Ceze Susan Eggers

    E-print Network

    Anderson, Richard

    A Limit Study of JavaScript Parallelism Emily Fortuna Owen Anderson Luis Ceze Susan Eggers Computer on the potential parallelism of JavaScript appli- cations, including popular web pages and standard JavaScript benchmarks. We examine dependency types and looping behavior to better understand the potential for JavaScript

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

    EPA Science Inventory

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

  18. COMPARATIVE KINETIC STUDIES OF NITRATE-LIMITED GROWTH AND NITRATE UPTAKE IN PHYTOPLANKTON IN CONTINUOUS CULTURE

    EPA Science Inventory

    A comparative kinetic study of nitrate-limited growth and nitrate uptake was carried out in chemostat cultures of Ankistrodesmus falcatus, Asterionella formosa, Fragilaria crotonensis. In each species growth rate (microgram) was related to total cell nitrogen or cell quota (q) by...

  19. Human trigeminal ganglionic explants as a model to study alphaherpesvirus reactivation

    PubMed Central

    Azarkh, Yevgeniy; Bos, Nathan; Gilden, Don

    2013-01-01

    Varicella zoster virus (VZV) latency is characterized by limited virus gene expression and the absence of virus DNA replication. Investigations of VZV latency and reactivation have been hindered by the lack of an in vitro model of virus latency. Since VZV is an exclusively human pathogen, we used naturally infected human trigeminal ganglia (TG) obtained at autopsy to study virus latency. Herein, we report optimization of medium to maintain TG integrity as determined by histology and immunohisto-chemistry. Using the optimized culture medium, we also found that both herpes simplex virus-1 (HSV-1) and VZV DNA replicated in TG explants after 5 days in culture. The increase in HSV-1 DNA was fourfold greater than the increase in VZV DNA. Overall, we present a model for alphaherpesvirus latency in human neurons in which the key molecular events leading to virus reactivation can be studied. PMID:22851387

  20. http://www.kyoto-u.ac.jp/ja Integrated Human Studies Integrated Human Studies

    E-print Network

    Takada, Shoji

    Pharmaceutical Sciences Pharmacy ( ) Engineering Global Engineering, Architecture, Engineering Science and Management Science Science Medicine Medical Science ( ) Human Health Sciences Pharmaceutical Sciences, Electrical and Electronic Engineering, Informatics and Mathematical Science, Industrial Chemistry Agriculture

  1. 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.

  2. Measuring cortisol in human psychobiological studies.

    PubMed

    Levine, Ari; Zagoory-Sharon, Orna; Feldman, Ruth; Lewis, John G; Weller, Aron

    2007-01-30

    The steroid cortisol is an extensively studied and important variable in developmental and other behavioral studies. Cortisol has been assayed by various methods using a range of substrates including blood, saliva, and urine. Cortisol in blood exists in two forms. While most is bound to carrier proteins, a small portion exists in a soluble free form. The informed choice of cortisol fraction and measurement method is critical for research. Such choices should be influenced by understanding the characteristics of the various cortisol fractions, along with their binding proteins' biological functions and relationship to the hypothalamic-pituitary-adrenal (HPA) axis. The goal of this paper is to familiarize researchers with key points for evaluating the choice of total and free cortisol in research as well reviewing various options for measuring free cortisol. These points are raised with special emphasis on their significance during pregnancy and the post-partum. Such information may prove useful in informing researcher's cortisol-related protocols and in the interpretation of cortisol data. PMID:17055006

  3. 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

  4. 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

  5. Characterizing interspecies uncertainty using data from studies of anti-neoplastic agents in animals and humans

    SciTech Connect

    Price, Paul S. [Dow Chemical Company, Toxicology and Environmental Research and Consulting, 1803 Building, Midland MI 48674 (United States)], E-mail: pprice@dow.com; Keenan, Russell E. [AMEC Earth and Environmental, 15 Franklin Street, Portland, ME 04101 (United States); Swartout, Jeffrey C. [National Center for Environmental Assessment U.S. Environmental Protection Agency, 26 W. M. L. King Drive, Cincinnati, OH 45268 (United States)

    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.

  6. Anticipated significant work limitation in primary care consulters with osteoarthritis: a prospective cohort study

    PubMed Central

    Wilkie, Ross; Phillipson, Chris; Hay, Elaine M; Pransky, Glenn

    2014-01-01

    Objective To describe the prevalence of expected work limitations (EWL) prior to future retirement age in osteoarthritis consulters, and the associated health, sociodemographic and workplace factors. Design Population-based prospective cohort study. Setting General practices in Staffordshire, England. Participants 297 working adults aged 50–65, who had consulted primary care for osteoarthritis. Outcome EWL was defined using a single question, “Do you think joint pain will limit your ability to work before you reach 69?years old?” Results 51 (17.2%) indicated that joint pain would not limit their ability to work until 69, 79 (26.6%) indicated EWL and 167 (56.2%) did not know if joint pain would limit work before 69. In bivariate analysis, physical function (OR 0.93; 95% CI 0.91 to 0.96), depression (4.51; 1.81 to 11.3), cognitive symptom (3.84; 1.81 to 8.18), current smoker (2.75; 1.02 to 7.38), age (0.69; 0.58 to 0.82), physically demanding job (3.18; 1.50 to 6.72), no opportunities to retrain (3.01; 1.29 to 7.05) and work dissatisfaction (3.69; 1.43 to 9.49) were associated with EWL. The final multivariate model included physical function and age. Conclusions Only one in five osteoarthritis consulters expected that joint pain would not limit their work participation before 69?years of age. Given the expectation for people to work until they are older, the results highlight the increasing need for clinicians to include work participation in their consultation and implement strategies to address work loss/limitation. Targeting pain-related functional limitation and effective communication with employers to manage workplace issues could reduce EWL. PMID:25190616

  7. Modularized study of human calcium signalling pathway.

    PubMed

    Nayak, Losiana; De, Rajat K

    2007-08-01

    Signalling pathways are complex biochemical networks responsible for regulation of numerous cellular functions. These networks function by serial and successive interactions among a large number of vital biomolecules and chemical compounds. For deciphering and analysing the underlying mechanism of such networks,a modularized study is quite helpful. Here we propose an algorithm for modularization of calcium signalling pathway of H. sapiens . The idea that "a node whose function is dependent on maximum number of other nodes tends to be the center of a sub network" is used to divide a large signalling network into smaller sub networks. Inclusion of node(s) into sub networks(s) is dependent on the outdegree of the node(s). Here outdegree of a node refers to the number of relations of the considered node lying outside the constructed sub network. Node(s) having more than c relations lying outside the expanding sub network have to be excluded from it. Here c is a specified variable based on user preference, which is finally fixed during adjustments of created sub networks, so that certain biological significance can be conferred on them. PMID:17914243

  8. DECADE OF STUDIES OF HUMAN EXPOSURE: WHAT HAVE WE LEARNED?

    EPA Science Inventory

    Between 1980 and 1990, EPA's Office of Research and Development carried out four major studies of human exposure to different classes of pollutants. hese are often referred as Total Exposure Assessment Methodology (TEAM) Studies, after the first in the series, which dealt with vo...

  9. 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…

  10. BA in AMERICAN STUDIES (570120) Map Sheet College of Humanities

    E-print Network

    Martinez, Tony R.

    of North America Anthr 345 American Culture Anthr 346 Anthropology of Mormonism Anthr 390R Special Topics & Methods in American Studies Am St 399R Academic Internship (3 hours required) Anthr 317 Native PeoplesBA in AMERICAN STUDIES (570120) Map Sheet College of Humanities For students entering the degree

  11. REPORTING NEEDS FOR STUDIES OF ENVIRONMENTAL CHEMICALS IN HUMAN MILK

    EPA Science Inventory

    Studies of environmental chemicals in human milk have been carried out in many countries, but few have been conducted in the U.S. These studies are useful for monitoring populations trends in exposure to chemiclas, for research in the determinants of environmental chemicals in m...

  12. Perfluorochemicals and Human Semen Quality: The LIFE Study

    PubMed Central

    Chen, Zhen; Schisterman, Enrique F.; Kim, Sungduk; Sweeney, Anne M.; Sundaram, Rajeshwari; Lynch, Courtney D.; Gore-Langton, Robert E.; Barr, Dana Boyd

    2014-01-01

    Background: The relation between persistent environmental chemicals and semen quality is evolving, although limited data exist for men recruited from general populations. Objectives: We examined the relation between perfluorinated chemicals (PFCs) and semen quality among 501 male partners of couples planning pregnancy. Methods: Using population-based sampling strategies, we recruited 501 couples discontinuing contraception from two U.S. geographic regions from 2005 through 2009. Baseline interviews and anthropometric assessments were conducted, followed by blood collection for the quantification of seven serum PFCs (perfluorosulfonates, perfluorocarboxylates, and perfluorosulfonamides) using tandem mass spectrometry. Men collected a baseline semen sample and another approximately 1 month later. Semen samples were shipped with freezer packs, and analyses were performed on the day after collection. We used linear regression to estimate the difference in each semen parameter associated with a one unit increase in the natural log–transformed PFC concentration after adjusting for confounders and modeling repeated semen samples. Sensitivity analyses included optimal Box-Cox transformation of semen quality end points. Results: Six PFCs [2-(N-methyl-perfluorooctane sulfonamido) acetate (Me-PFOSA-AcOH), perfluorodecanoate (PFDeA), perfluorononanoate (PFNA), perfluorooctane sulfonamide (PFOSA), perfluorooctane sulfonate (PFOS), and perfluorooctanoic acid (PFOA)] were associated with 17 semen quality end points before Box-Cox transformation. PFOSA was associated with smaller sperm head area and perimeter, a lower percentage of DNA stainability, and a higher percentage of bicephalic and immature sperm. PFDeA, PFNA, PFOA, and PFOS were associated with a lower percentage of sperm with coiled tails. Conclusions: Select PFCs were associated with certain semen end points, with the most significant associations observed for PFOSA but with results in varying directions. Citation: Buck Louis GM, Chen Z, Schisterman EF, Kim S, Sweeney AM, Sundaram R, Lynch CD, Gore-Langton RE, Barr DB. 2015. Perfluorochemicals and human semen quality: the LIFE Study. Environ Health Perspect 123:57–63;?http://dx.doi.org/10.1289/ehp.1307621 PMID:25127343

  13. Determination of ibudilast in human serum by high-performance liquid chromatography for pharmacokinetic study.

    PubMed

    Yoon, Hwa; Cho, Hea-Young; Lee, Yong-Bok

    2010-03-01

    A simple, accurate, precise and cost effective reversed-phase HPLC method was developed to determine the concentration of ibudilast in human serum. Ibudilast and an internal standard, butyl 4-hydroxybenzoate, were extracted by liquid-liquid extraction with methyl tert-butyl ether. HPLC analysis was carried out under the following conditions: a Luna C(18)(2) 5 microm column, a mobile phase of acetonitrile-0.02% phosphoric acid (50 : 50, v/v, adjusted to pH 6.0 with triethylamine) and a UV detector at 319 nm. The chromatograms showed good resolution and sensitivity as well as no interference from the human serum. The calibration curves were linear over the concentration range, 1-100 ng/mL, for serum with correlation coefficients >0.999. The intra- and inter-day assay precision as well as the accuracy fulfilled the international requirements. The mean absolute recovery for human serum was 101.7 +/- 6.1%. The lower limit of quantitation in human serum was 1 ng/mL, which is sensitive enough for pharmacokinetic studies. Stability studies revealed that ibudilast in human serum was stable during storage as well as during the assay procedure. This method was applied successfully to an examination of the pharmacokinetics of ibudilast in human subjects following a single oral dose of an ibudilast (10 mg) capsule. PMID:19629961

  14. 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

  15. GogB Is an Anti-Inflammatory Effector that Limits Tissue Damage during Salmonella Infection through Interaction with Human FBXO22 and Skp1

    PubMed Central

    Pilar, Ana Victoria C.; Reid-Yu, Sarah A.; Cooper, Colin A.; Mulder, David T.; Coombes, Brian K.

    2012-01-01

    Bacterial pathogens often manipulate host immune pathways to establish acute and chronic infection. Many Gram-negative bacteria do this by secreting effector proteins through a type III secretion system that alter the host response to the pathogen. In this study, we determined that the phage-encoded GogB effector protein in Salmonella targets the host SCF E3 type ubiquitin ligase through an interaction with Skp1 and the human F-box only 22 (FBXO22) protein. Domain mapping and functional knockdown studies indicated that GogB-containing bacteria inhibited I?B degradation and NF?B activation in macrophages, which required Skp1 and a eukaryotic-like F-box motif in the C-terminal domain of GogB. GogB-deficient Salmonella were unable to limit NF?B activation, which lead to increased proinflammatory responses in infected mice accompanied by extensive tissue damage and enhanced colonization in the gut during long-term chronic infections. We conclude that GogB is an anti-inflammatory effector that helps regulate inflammation-enhanced colonization by limiting tissue damage during infection. PMID:22761574

  16. Improving the translation of animal ischemic stroke studies to humans.

    PubMed

    Jickling, Glen C; Sharp, Frank R

    2015-04-01

    Despite testing more than 1,026 therapeutic strategies in models of ischemic stroke and 114 therapies in human ischemic stroke, only one agent tissue plasminogen activator has successfully been translated to clinical practice as a treatment for acute stroke. Though disappointing, this immense body of work has led to a rethinking of animal stroke models and how to better translate therapies to patients with ischemic stroke. Several recommendations have been made, including the STAIR recommendations and statements of RIGOR from the NIH/NINDS. In this commentary we discuss additional aspects that may be important to improve the translational success of ischemic stroke therapies. These include use of tissue plasminogen activator in animal studies; modeling ischemic stroke heterogeneity in terms of infarct size and cause of human stroke; addressing the confounding effect of anesthesia; use of comparable therapeutic dosage between humans and animals based on biological effect; modeling the human immune system; and developing outcome measures in animals comparable to those used in human stroke trials. With additional study and improved animal modeling of factors involved in human ischemic stroke, we are optimistic that new stroke therapies will be developed. PMID:24526567

  17. Ontology-Based Federated Data Access to Human Studies Information

    PubMed Central

    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

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

    SciTech Connect

    Alessio, Morace; Dimitri, Batani; Renato, Redaelli [University of Milano Bicocca (Italy); Alexander, Magunov [General Physical Institute, Russian Academy of Sciences, Moscow (Russian Federation); Claude, Fourment; Jorge, Santos Joao; Gerard, Malka [Universite de Bordeaux-CNRS-CEA, CELIA, Talence (France); Alain, Boscheron [CEA/CESTA Le BARP (France); Alexis, Casner [CEA-DAM, Bruyres-le-Chatel (France); Wigen, Nazarov [University of St. Andrews (United Kingdom); Tommaso, Vinci [CEA, Bruyeres le Chatel (France); Yasuaki, Okano; Yuichi, Inubushi; Hiroaki, Nishimura [Institute of Laser Engineering , Osaka University (Japan); Alessandro, Flacco [LOA, Ecole Polytechnique, Palaiseau (France); Chris, Spindloe; Martin, Tolley [RUTHERFORD Appleton Laboratory (United Kingdom)

    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).

  19. Advantages and limitations of the use of optogenetic approach in studying fast-scale spike encoding.

    PubMed

    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 population encoding of simulated synaptic potentials generated in dendrites at different distances from the soma. PMID:25850004

  20. 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 population encoding of simulated synaptic potentials generated in dendrites at different distances from the soma. PMID:25850004

  1. The Institute for the Interdisciplinary Study of Human & Machine Cognition

    NSDL National Science Digital Library

    The Institute for the Interdisciplinary Study of Human & Machine Cognition (IHMC) is an interdisciplinary research unit of the University of West Florida. Researchers and staff at the IHMC investigate "a broad range of topics related to understanding cognition in both humans and machines with a particular emphasis on building computational tools to leverage and amplify human cognitive and perceptual capacities." Their work advances the study of human-centered computing, which takes a â??systems viewâ? to link human thought and action and technological systems. They are primarily interested in the analysis, design, and evaluation of computational aids or "cognitive prostheses." The website provides an overview of each of their current research areas, which include: knowledge modeling and sharing, adjustable autonomy, advanced interfaces and displays, communication and collaboration, computer-mediated learning systems, intelligent data understanding, software agents, expertise studies, work practice simulation, knowledge representation, and other related areas. They also provide Cmap Tools, a knowledge modeling software kit, which is free to download and "empowers users to construct, navigate, share, and criticize knowledge models represented as Concept Models." This site is also reviewed in the June 3, 2005.

  2. Human immunodeficiency virus infection and human African trypanosomiasis: a case-control study in Côte d'Ivoire.

    PubMed

    Meda, H A; Doua, F; Laveissière, C; Miezan, T W; Gaens, E; Brattegaard, K; de Muynck, A; De Cock, K M

    1995-01-01

    To assess the association between human immunodeficiency virus (HIV) infection and human African trypanosomiasis (HAT) in Côte d'Ivoire, West Africa, a cross-sectional case-control study was conducted on 301 HAT patients recruited in the main foci of the country. For each HAT patient, 3 controls, matched for sex, age and residence, were selected. Data relating to socio-demographic factors and potential risk factors for Trypanosoma brucei gambiense and HIV infections were obtained, and serum samples were collected for HIV-1 and HIV-2 tests. A positive test consisted of enzyme immunoassay reactive to HIV-1, HIV-2 or both and confirmed by a synthetic peptide test or Western blot. Data were analyzed using conditional logistic regression with EGRET software. No statistically significant difference was found between the prevalence of HIV infection in HAT patients and controls (4.3% and 3.5% respectively; crude odds ratio (OR) 1.28, 95% confidence interval (CI) 0.65-2.50). In multivariate analysis, allowance for 5 covariates did not change the association between the 2 infections (adjusted OR 1.27, 95% CI 0.64-2.52). Although this study had limited statistical power, no significant association was found between HIV infection and T.b. gambiense infection in rural Côte d'Ivoire. Studies are needed to determine whether HIV infection influences the clinical course of HAT, a question not addressed in the present study. PMID:8594681

  3. Epigenome-wide association studies for common human diseases

    Microsoft Academic Search

    Thomas A. Down; Vardhman K. Rakyan; David J. Balding; Stephan Beck

    2011-01-01

    Despite the success of genome-wide association studies (GWASs) in identifying loci associated with common diseases, a substantial proportion of the causality remains unexplained. Recent advances in genomic technologies have placed us in a position to initiate large-scale studies of human disease-associated epigenetic variation, specifically variation in DNA methylation. Such epigenome-wide association studies (EWASs) present novel opportunities but also create new

  4. What are the Limits for ace Galactic Cosmic-ray Isotope Studies?

    NASA Astrophysics Data System (ADS)

    Webber, W. R.

    1998-07-01

    The CRIS experiment on ACE, with its excellent charge and mass resolution and a geometrical factor ˜10× that of any previous experiment, holds the promise of rewriting the book on galactic cosmic-ray abundance studies. Translating these measurements into precise cosmic-ray source abundances and using these measurements to determine more accurately the propagation history of cosmic rays is a different matter, however. In many important cases these studies will be limited by the accuracy of the nuclear cross- sections that determine how the cosmic-ray composition is modified as it traverses the interstellar matter. In this paper we will discuss these cross-sections and how well they are known as a function of the energy and the charge and mass of the cosmic-ray nuclei. This will then be used to discuss what new limits can be expected on several contemporary problems of interest in cosmic rays from the CRIS measurements.

  5. A basic study on the dynamic water level limit sensor utilizing acoustic impedance matching

    Microsoft Academic Search

    Cheol-Han Kim; Su-Ho Lee; Geon Sa-Gong; Jun-Hee Lee

    2006-01-01

    In this study, an ultrasonic level limit sensor with a new structure utilizing the acoustic impedance matching is proposed\\u000a in order to check the change of water-level. Two PZT resonators with the same property are bonded directly on a polyethylene\\u000a plate. The first one is for transmitter as an ultrasonic transducer and the other is for a receiver. In this

  6. 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…

  7. 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

  8. 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

  9. 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

  10. 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

  11. Hermeneutic Inquiry in the Study of Human Conduct

    Microsoft Academic Search

    Martin J. Packer

    1985-01-01

    Interest is growing in the hermeneutic or interpretive approach to the study of human conduct. This article draws upon the work of Martin Heidegger to compare hermeneutics with the other major paradigms of inquiry and explanation in psychology: rationalism (cognitivism and structuralism) and empiricism (experimentalism and behaviorism). The comparison is threefold: in terms of their view of the form and

  12. 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…

  13. The Dating Game A Case Study in Human Evolution

    NSDL National Science Digital Library

    Shoshana Tobias

    1999-01-01

    In this role-playing case study, students attempt to determine the identity of a variety of human fossils based on characteristics described during a “quiz show.”  The case was designed to be used in a general biology class for freshman students where the focus is on evolution. It could also be used in an anthropology or paleontology course.

  14. MAJOR: HUMAN DEVELOPMENT & FAMILY STUDIES (HDFS) EMPHASIS: EARLY CHILDHOOD EDCUATION

    E-print Network

    Tipple, Brett

    , SU FCS 2400 Family Relations Across the Life Course (BF) 3 3. EARLY CHILDHOOD EDUCATION CORE (42 with their advisor on a regular basis. Updated 05/15/2013 The Early Childhood Education (ECE) emphasis providesMAJOR: HUMAN DEVELOPMENT & FAMILY STUDIES (HDFS) EMPHASIS: EARLY CHILDHOOD EDCUATION Minimum HDFS

  15. BA in AMERICAN STUDIES (570120) MAP Sheet College of Humanities

    E-print Network

    Olsen Jr., Dan R.

    required) Anthr 317 Native Peoples of North America Anthr 345 American Culture Anthr 346 AnthropologyBA in AMERICAN STUDIES (570120) MAP Sheet College of Humanities For students entering the degree Testament Doctrine and Covenants The Individual and Society Citizenship American Heritage Global & Cultural

  16. BA in AMERICAN STUDIES (570120) MAP Sheet College of Humanities

    E-print Network

    Olsen Jr., Dan R.

    Lecture Series Am St 399R Academic Internship (3 hours required) Anthr 317 Native Peoples of North America Hist 368 Sport, Society, & American Culture Hist 370 Colonial America Hist 371 Revolutionary AmericaBA in AMERICAN STUDIES (570120) MAP Sheet College of Humanities For students entering the degree

  17. Zebrafish: a model system for the study of human disease

    Microsoft Academic Search

    Kimberly Dooley; Leonard I Zon

    2000-01-01

    The zebrafish (Danio rerio) is a powerful model organism for the study of vertebrate biology, being well suited to both developmental and genetic analysis. Large-scale genetic screens have identified hundreds of mutant phenotypes, many of which resemble human clinical disorders. The creation of critical genetic reagents, coupled with the rapid progress of the zebrafish genome initiative directed by the National

  18. Policy and Procedures 1 HUMAN DEVELOPMENT AND FAMILY STUDIES

    E-print Network

    Rock, Chris

    and Policies 9 1. Philosophy of governance 9 2. Definitions 9 3. Decision making authority 9 4. Conduct Students 17 1. Graduate student organization and input into departmental decision making 17 2. Decisions and educators in our core discipline of Human Development and Family Studies; Integrate diversity into every

  19. 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...

  20. 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...

  1. Adult human heart slices are a multicellular system suitable for electrophysiological and pharmacological studies.

    PubMed

    Camelliti, Patrizia; Al-Saud, Sara Abou; Smolenski, Ryszard T; Al-Ayoubi, Samha; Bussek, Alexandra; Wettwer, Erich; Banner, Nicholas R; Bowles, Christopher T; Yacoub, Magdi H; Terracciano, Cesare M

    2011-09-01

    Electrophysiological and pharmacological data from the human heart are limited due to the absence of simple but representative experimental model systems of human myocardium. The aim of this study was to establish and characterise adult human myocardial slices from small patients' heart biopsies as a simple, reproducible and relevant preparation suitable for the study of human cardiac tissue at the multicellular level. Vibratome-cut myocardial slices were prepared from left ventricular biopsies obtained from end-stage heart failure patients undergoing heart transplant or ventricular assist device implantation, and from hearts of normal dogs. Multiple slices were prepared from each biopsy. Regular contractility was observed at a range of stimulation frequencies (0.1-2 Hz), and stable electrical activity, monitored using multi-electrode arrays (MEA), was maintained for at least 8 h from slice preparation. ATP/ADP and phosphocreatine/creatine ratios were comparable to intact organ values, and morphology and gap junction distribution were representative of native myocardium. MEA recordings showed that field potential duration (FPD) and conduction velocity (CV) in human and dog slices were similar to the values previously reported for papillary muscles, ventricular wedges and whole hearts. Longitudinal CV was significantly faster than transversal CV, with an anisotropic ratio of 3:1 for human and 2.3:1 for dog slices. Importantly, slices responded to the application of E-4031, chromanol and 4-aminopyridine, three potassium channel blockers known to affect action potential duration, with an increase in FPD. We conclude that viable myocardial slices with preserved structural, biochemical and electrophysiological properties can be prepared from adult human and canine heart biopsies and offer a novel preparation suitable for the study of heart failure and drug screening. PMID:21740909

  2. Periodontitis is related to lung volumes and airflow limitation: a cross-sectional study.

    PubMed

    Holtfreter, Birte; Richter, Stefanie; Kocher, Thomas; Dörr, Marcus; Völzke, Henry; Ittermann, Till; Obst, Anne; Schäper, Christoph; John, Ulrich; Meisel, Peter; Grotevendt, Anne; Felix, Stephan B; Ewert, Ralf; Gläser, Sven

    2013-12-01

    This study aimed to assess the potential association of periodontal diseases with lung volumes and airflow limitation in a general adult population. Based on a representative population sample of the Study of Health in Pomerania (SHIP), 1463 subjects aged 25-86 years were included. Periodontal status was assessed by clinical attachment loss (CAL), probing depth and number of missing teeth. Lung function was measured using spirometry, body plethysmography and diffusing capacity of the lung for carbon monoxide. Linear regression models using fractional polynomials were used to assess associations between periodontal disease and lung function. Fibrinogen and high-sensitivity C-reactive protein (hs-CRP) were evaluated as potential intermediate factors. After full adjustment for potential confounders mean CAL was significantly associated with variables of mobile dynamic and static lung volumes, airflow limitation and hyperinflation (p<0.05). Including fibrinogen and hs-CRP did not change coefficients of mean CAL; associations remained statistically significant. Mean CAL was not associated with total lung capacity and diffusing capacity of the lung for carbon monoxide. Associations were confirmed for mean probing depth, extent measures of CAL/probing depth and number of missing teeth. Periodontal disease was significantly associated with reduced lung volumes and airflow limitation in this general adult population sample. Systemic inflammation did not provide a mechanism linking both diseases. PMID:23222882

  3. Synthesis and optical limiting studies of Au-doped TiO2 nanoparticles

    NASA Astrophysics Data System (ADS)

    Mani Rahulan, K.; Ganesan, S.; Aruna, P.

    2011-06-01

    A series of Au-doped TiO2 nanoparticles with different Au concentrations were prepared by the sol–gel method using titanium (IV) isopropoxide and tetrachloroaurate (III) trihydrate as precursors. The framework substitution of Au in TiO2 nanoparticles was established by x-ray diffraction (XRD) and Fourier transform infrared (FT-IR) techniques. X-ray diffraction (XRD) and transmission electron microscopy (TEM) image results confirmed the anatase phase and nanocrystalline nature of TiO2–Au. The optical properties revealed an extended tailing of the absorption edge toward the visible region upon Au doping. The incorporation of Au in TiO2 was also confirmed by fluorescence quenching. The increase in Au doping enhanced the 'red-shift' in the UV-Vis absorption spectra. The spectral and nonlinear optical properties were studied using fluence-dependent transmittance measurements in order to reveal the optical limiting mechanism. The nonlinear optical response and optical limiting effects of TiO2–Au nanocomposites dispersed in ethylene glycol were studied at 532?nm using 5?ns Nd:YAG laser pulses. Effective three-photon absorption mechanisms play a major role for good optical limiting characteristics in these nanoparticles and it is seen that the optical nonlinearity enhances with lower threshold as the volume fraction of the Au concentration increased.

  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. [Centro de Tecnologia Mecanica e Automacao, Departamento de Engenharia Mecanica, Universidade de Aveiro, Campus Universitario de Santiago, 3810-193 Aveiro (Portugal); Barata da Rocha, A. [Departamento de Engenharia Mecanica, Universidade do Porto, Rua Dr. Roberto Frias, s/n 4200-465 Porto (Portugal)

    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. A radiographic study of the detection limits of bone-cement remnants in total joint arthroplasty.

    PubMed

    Rauh, Michael A; Bayers-Thering, Mary; Madanagopal, Sudhakar; Krackow, Kenneth A

    2002-12-01

    Management of an infected hip prosthesis typically requires that all associated cement be removed. In the absence of gross mantle loosening, the surgeon frequently resorts to intraoperative radiographs to assess the completeness of removal. For this reason, we undertook a study to determine limits of detection of retained cement by routine radiography. Polymethyl methacrylate bone-cement beads (Simplex-P; Stryker-Howmedica-Osteonics, Allendale, NJ) were fashioned into graduated sizes and placed within cadaver medullary canals using 2 different methods. Standard radiographic images were obtained. Individually and independently, we viewed these images and proposed the limit of resolution to be 2.4 to 3.2 mm. It is difficult to remove all cement based on radiographs alone. These results suggest a need to use techniques that permit visualization of the canal to ensure adequate cement removal. PMID:12478508

  6. Genome-Wide Association Studies and Human Population Obesity

    Microsoft Academic Search

    Ruth J. F. Loos; Tuomas O. Kilpeläinen

    \\u000a In the past 3 years, genome-wide association (GWA) studies have revolutionized the field of obesity genetics by establishing\\u000a at least 15 new genetic-susceptibility loci for common obesity. GWA studies are hypothesis-generating in that they interrogate\\u000a hundreds of thousands of genetic variants across the whole human genome for association with a disease or trait of interest\\u000a without an a priori hypothesis.

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

    PubMed Central

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

    1999-01-01

    Graves' disease (GD) is characterized by the presence of autoantibodies against the TSH-receptor (TSH-R) which are pathogenic and, upon binding to the receptor, trigger intracellular signal transduction. The autoantibodies are oligoclonal and as they are responsible for disease activity, their characterization would lead to a better understanding of the development of GD. Attempts to isolate anti-TSH-R antibodies from patients have proved to be difficult due to the exceedingly low serum levels due to rarity of these B cells, together with difficulties in obtaining purified TSH-R capable of interacting with patients autoantibodies. We employed phage antibody display technology and performed selection with a previously characterized semisynthetic antibody library on the purified extracellular ectodomain of the TSH-R. We report the isolation of six different anti-TSH-R monoclonal phage antibodies (moPhabs) from this library. All the moPhabs recognized TSH-R and its recombinant fragments by Western blotting, but failed to recognize the native TSH-R by flow cytometry. Consequently, the moPhabs did not lead to TSH-R activation. As these were the first moPhabs to TSH-R, they were analysed in terms of nucleotide and amino acid sequence and epitope specificity on the receptor. The moPhabs used immunoglobulin VH1 and VH3 germ line genes, all associated with V?3 genes. Interestingly, the CDR3 regions of all moPhabs were remarkably similar, though not identical. In light of the common CDR3 usage, the epitopes recognized on TSH-R appeared to be restricted to amino acids residues 405–411 and 357–364. In summary, our results show that semisynthetic libraries may be limited in isolating human monoclonal antibodies that resemble pathogenic antithyrotropin receptor autoantibodies present in patients with GD. It is likely that until preparations of purified TSH-R that can be recognized by patients autoantibodies become available, similar to the recently described glycosylphosphatidylinositol (GPI) anchored TSH-R ectodomain, monoclonal antibodies from phage antibody display to TSH-R will be limited for isolating the rare, pathogenic antibodies of GD. PMID:10540180

  8. Reconciling Human Smoking Behavior and Machine Smoking Patterns: Implications for Understanding Smoking Behavior and the Impact on Laboratory Studies

    PubMed Central

    Marian, Catalin; O'Connor, Richard J.; Djordjevic, Mirjana; Rees, Vaughan W.; Hatsukami, Dorothy K.; Shields, Peter G.

    2009-01-01

    Introduction Recent Food and Drug Administration legislation enables the mandating of product performance standards for cigarette smoke and the evaluation of manufacturers’ health claims for modified tobacco products. Laboratory studies used for these evaluations, and also to understand tobacco smoke toxicology, use machines to generate smoke. The goal of this review is to critically evaluate methods to assess human smoking behavior and replicate this in the laboratory. Methods Smoking behavior and smoking machine studies were identified using PubMed and publically available databases for internal tobacco company documents. Results The smoking machine was developed to generate smoke to allow for comparing cigarette tar and nicotine yields. The intent was to infer relative human disease risk, but this concept was flawed because humans tailor their smoking to the product and chemical yields and toxicological effects change with different smoking profiles. While smoking machines also allow for mechanistic assessments of smoking-related diseases, the interpretations also are limited. However, available methods to assess how humans puff could be used to provide better laboratory assessments, but these need to be validated. Separately, the contribution of smoke mouth-holding and inhalation to dose need to be assessed, because these parts of smoking are not captured by the smoking machine. Better comparisons of cigarettes might be done by tailoring human puff profiles to the product based on human studies and comparing results across regimens. Conclusions There are major research gaps that limit the use of smoking machine studies for informing tobacco control regulation and mechanistic studies. PMID:19959678

  9. UH Human Studies Program Policies and Procedures Page 1 University of Hawai`i

    E-print Network

    Olsen, Stephen L.

    UH Human Studies Program Policies and Procedures Page 1 University of Hawai`i Human Studies Program General Policies and Procedures UH Human Studies Program 1960 East-West Road Biomedical Building B-104 Honolulu, HI 96822 Revised April 3, 2012 #12;UH Human Studies Program Policies and Procedures Page 2 UH

  10. Engineered human vaccines

    SciTech Connect

    Sandhu, J.S. (Mount Sinai Hospital, Toronto, Ontario (Canada). Div. of Immunology and Neurobiology)

    1994-01-01

    The limitations of human vaccines in use at present and the design requirements for a new generation of human vaccines are discussed. The progress in engineering of human vaccines for bacteria, viruses, parasites, and cancer is reviewed, and the data from human studies with the engineered vaccines are discussed, especially for cancer and AIDS vaccines. The final section of the review deals with the possible future developments in the field of engineered human vaccines and the requirement for effective new human adjuvants.

  11. 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.

  12. Framework for Human-Automation Collaboration: Conclusions from Four Studies

    SciTech Connect

    Johanna Oxstrand; Katya L. Le Blanc; John O'Hara; Jeffrey C. Joe; April M. Whaley; Heather Medema

    2013-11-01

    The Human Automation Collaboration (HAC) research project is investigating how advanced technologies that are planned for Advanced Small Modular Reactors (AdvSMR) will affect the performance and the reliability of the plant from a human factors and human performance perspective. The HAC research effort investigates the consequences of allocating functions between the operators and automated systems. More specifically, the research team is addressing how to best design the collaboration between the operators and the automated systems in a manner that has the greatest positive impact on overall plant performance and reliability. Oxstrand et al. (2013 - March) describes the efforts conducted by the researchers to identify the research needs for HAC. The research team reviewed the literature on HAC, developed a model of HAC, and identified gaps in the existing knowledge of human-automation collaboration. As described in Oxstrand et al. (2013 – June), the team then prioritized the research topics identified based on the specific needs in the context of AdvSMR. The prioritization was based on two sources of input: 1) The preliminary functions and tasks, and 2) The model of HAC. As a result, three analytical studies were planned and conduced; 1) Models of Teamwork, 2) Standardized HAC Performance Measurement Battery, and 3) Initiators and Triggering Conditions for Adaptive Automation. Additionally, one field study was also conducted at Idaho Falls Power.

  13. An ex vivo model to study hormone action in the human breast.

    PubMed

    Sflomos, George; Shamsheddin, Marie; Brisken, Cathrin

    2015-01-01

    The study of hormone action in the human breast has been hampered by lack of adequate model systems. Upon in vitro culture, primary mammary epithelial cells tend to lose hormone receptor expression. Widely used hormone receptor positive breast cancer cell lines are of limited relevance to the in vivo situation. Here, we describe an ex vivo model to study hormone action in the human breast. Fresh human breast tissue specimens from surgical discard material such as reduction mammoplasties or mammectomies are mechanically and enzymatically digested to obtain tissue fragments containing ducts and lobules and multiple stromal cell types. These tissue microstructures kept in basal medium without growth factors preserve their intercellular contacts, the tissue architecture, and remain hormone responsive for several days. They are readily processed for RNA and protein extraction, histological analysis or stored in freezing medium. Fluorescence activated cell sorting (FACS) can be used to enrich for specific cell populations. This protocol provides a straightforward, standard approach for translational studies with highly complex, varied human specimens. PMID:25590412

  14. Maintenance of therapeutic effects of total sleep deprivation by limitation of subsequent sleep. A pilot study.

    PubMed

    van Bemmel, A L; van den Hoofdakker, R H

    1981-05-01

    In a previous study it was shown that in endogenous depression repeated sleep deprivation (SD) during clomipramine treatment resulted in rapid improvement after each SD. However, except after the first night, relapses were observed after all sleep nights following SD (the "recovery nights"). The present pilot study had a therapeutic aim, namely to prevent these relapses. We were interested in whether limitation of sleep during the recovery nights might prevent these relapses and whether different amounts of sleep would have different effects on the course of mood after recovery sleep. Ten endogenously depressed patients were treated with clomipramine and with three SD's. Five patients slept for approximately 2 h, and the other five for about 5 h during the second and third recovery nights. On average, no relapse was shown by these patients and, in fact, there was some additional improvement after these nights, in contrast to the findings in the previous study, where patients were allowed unlimited sleep. PMID:7032222

  15. Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves

    NASA Astrophysics Data System (ADS)

    Chen, Kun; Fu, Xing; Dorantes-Gonzalez, Dante J.; Lu, Zimo; Li, Tingting; Li, Yanning; Wu, Sen; Hu, Xiaotang

    2014-07-01

    Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAW's are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin.

  16. Simulation study of melanoma detection in human skin tissues by laser-generated surface acoustic waves.

    PubMed

    Chen, Kun; Fu, Xing; Dorantes-Gonzalez, Dante J; Lu, Zimo; Li, Tingting; Li, Yanning; Wu, Sen; Hu, Xiaotang

    2014-01-01

    Air pollution has been correlated to an increasing number of cases of human skin diseases in recent years. However, the investigation of human skin tissues has received only limited attention, to the point that there are not yet satisfactory modern detection technologies to accurately, noninvasively, and rapidly diagnose human skin at epidermis and dermis levels. In order to detect and analyze severe skin diseases such as melanoma, a finite element method (FEM) simulation study of the application of the laser-generated surface acoustic wave (LSAW) technique is developed. A three-layer human skin model is built, where LSAW’s are generated and propagated, and their effects in the skin medium with melanoma are analyzed. Frequency domain analysis is used as a main tool to investigate such issues as minimum detectable size of melanoma, filtering spectra from noise and from computational irregularities, as well as on how the FEM model meshing size and computational capabilities influence the accuracy of the results. Based on the aforementioned aspects, the analysis of the signals under the scrutiny of the phase velocity dispersion curve is verified to be a reliable, a sensitive, and a promising approach for detecting and characterizing melanoma in human skin. PMID:25057963

  17. Thrombopoietin is a major limiting factor for selective outgrowth of human umbilical cord blood cells in non-obese diabetic/severe combined immunodeficient recipient mice.

    PubMed

    Verstegen, Monique M A; Wognum, Albertus W; Wagemaker, Gerard

    2003-09-01

    A single dose (0.3 microg) of recombinant human thrombopoietin (TPO) was injected into sublethal irradiated non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice immediately after transplantation of 1.5 x 10(5) purified CD34+ umbilical cord blood (UCB) cells. Bone marrow (BM) was analysed for human cells by immunophenotyping and colony culture at d 35. TPO treatment produced a two- to sixfold increase in the frequency and number of human CD45+ cells. The lineage distributions among the human cells were similar irrespective of TPO treatment; however, a prominent increase was observed in CD71+GpA- cells, reflecting the proliferative stimulus provided by TPO. The frequency of immature CD34+ cells and human granulocyte-macrophage colony-forming units and erythroid burst-forming units in TPO-treated mice was similar to that of untreated mice, but their absolute numbers had increased proportionally to the increase in human cells. The results demonstrate that human TPO is a major limiting factor for multilineage outgrowth of human UCB cells in NOD/SCID mice and can be conveniently supplemented by single-dose treatment immediately after transplantation. TPO did not affect the survival of mice after transplantation and did not significantly increase the number of immature CD34+CD38- cells; secondary transplantation revealed that TPO administration also had no significant effect on long-term repopulation. The findings demonstrate that human TPO is required for proper outgrowth of human haematopoietic stem cells after transplantation. In addition, a single administration of TPO may improve the efficiency and reproducibility of the NOD/SCID mouse assay for human immature transplantable progenitor cells. PMID:12930398

  18. HUMAN BIOLOGYHUMAN BIOLOGYHUMAN BIOLOGY This major is designed for students seeking a focused course of study in human

    E-print Network

    Rohs, Remo

    HUMAN BIOLOGYHUMAN BIOLOGYHUMAN BIOLOGY This major is designed for students seeking a focused course of study in human anatomy, physiology, metabolism, and/or evolution. The BS degree includes: Applied Physiology, Biomedical Sciences, Nutrition and Metabolism, and Human Evolutionary Biology. The BA

  19. THE MANY FACES OF HUMAN TRAFFICKING The "Many Faces of Human Trafficking" Faculty Study Group, sponsored by the

    E-print Network

    Indiana University

    THE MANY FACES OF HUMAN TRAFFICKING The "Many Faces of Human Trafficking" Faculty Study Group interned with the Indiana Office of the Attorney General in the Consumer Protection Division's Anti-Human Trafficking Unit. Ashik Shah, native of India, worked for the Dalit Welfare Organization and Nepal Child

  20. Raman microspectroscopic approach to the study of human granulocytes.

    PubMed Central

    Puppels, G J; Garritsen, H S; Segers-Nolten, G M; de Mul, F F; Greve, J

    1991-01-01

    A sensitive confocal Raman microspectrometer was employed to record spectra of nuclei and cytoplasmic regions of single living human granulocytes. Conditions were used that ensured cell viability and reproducibility of the spectra. Identical spectra were obtained from the nuclei of neutrophilic, eosinophilic, and basophilic granulocytes, which yield information about DNA and protein secondary structure and DNA-protein ratio. The cytoplasmic Raman spectra of the three cell types are very different. This was found to be mainly due to the abundant presence of peroxidases in the cytoplasmic granules of neutrophilic granulocytes (myeloperoxidase) and eosinophilic granulocytes (eosinophil peroxidase). Strong signal contributions of the active site heme group(s) of these enzymes were found. This paper illustrates the potentials and limitations for Raman spectroscopic analysis of cellular constituents and processes. PMID:1760504

  1. Determination of Actarit from Human Plasma for Bioequivalence Studies

    PubMed Central

    Loya, P.; Saraf, M. N.

    2010-01-01

    An analytical method based on high-performance liquid chromatography with ultraviolet detection (245 nm) was developed for the determination of actarit in human plasma. Coumarin was used as an internal standard. Chromatographic separation was achieved with a C8 column using a mobile phase of methanol: 1% acetic acid (50-50, v/v) with a flow rate of 1.0 ml/min. The calibration curve was linear over the range of 0.1–4.0 ?g/ml (r2 > 0.99) and the lower limit of quantification was 0.1 ?g/ml. The method was validated for sensitivity, accuracy, precision, recovery and stability. The method was used to determine the concentration-time profiles of actarit in the plasma following oral administration of 100 mg actarit tablets. PMID:21969744

  2. Advancing the management and control of typhoid fever: a review of the historical role of human challenge studies.

    PubMed

    Waddington, Claire S; Darton, Thomas C; Woodward, William E; Angus, Brian; Levine, Myron M; Pollard, Andrew J

    2014-05-01

    Typhoid infection causes considerable morbidity and mortality worldwide, particularly in settings where lack of clean water and inadequate sanitation facilitate disease spread through faecal-oral transmission. Improved understanding of the pathogenesis, immune control and microbiology of Salmonella Typhi infection can help accelerate the development of improved vaccines and diagnostic tests necessary for disease control. S. Typhi is a human-restricted pathogen; therefore animal models are limited in their relevance to human infection. During the latter half of the 20th century, induced human infection ("challenge") studies with S. Typhi were used effectively to assess quantitatively the human host response to challenge and to measure directly the efficacy of typhoid vaccines in preventing clinical illness. Here, the findings of these historic challenge studies are reviewed, highlighting the pivotal role that challenge studies have had in improving our understanding of the host-pathogen interaction, and illustrating issues relevant to modern typhoid challenge model design. PMID:24491597

  3. A critical review of epidemiologic studies of radiofrequency exposure and human cancers.

    PubMed Central

    Elwood, J M

    1999-01-01

    This paper reviews studies that have assessed associations between likely exposure to radiofrequency (RF) transmissions and various types of human cancer. These studies include three cluster investigations and five studies relating to general populations; all of these studies consider place of residence at the time of cancer diagnosis in regard to proximity to radio or television transmitters. There are also five relevant occupational cohort studies and several case-control studies of particular types of cancer. These studies assessed a large number of possible associations. Several positive associations suggesting an increased risk of some types of cancer in those who may have had greater exposure to RF emissions have been reported. However, the results are inconsistent: there is no type of cancer that has been consistently associated with RF exposures. The epidemiologic evidence falls short of the strength and consistency of evidence that is required to come to a reasonable conclusion that RF emissions are a likely cause of one or more types of human cancer. The evidence is weak in regard to its inconsistency, the design of the studies, the lack of detail on actual exposures, and the limitations of the studies in their ability to deal with other likely relevant factors. In some studies there may be biases in the data used PMID:10229715

  4. A review of adverse pregnancy outcomes and formaldehyde exposure in human and animal studies.

    PubMed

    Collins, J J; Ness, R; Tyl, R W; Krivanek, N; Esmen, N A; Hall, T A

    2001-08-01

    We examine the potential for reproductive and developmental effects from formaldehyde exposure. Formaldehyde is unlikely to reach the reproductive system in humans in concentrations sufficient to cause damage since it is rapidly metabolized and detoxified upon contact with the respiratory tract. While there are effects seen in in vitro studies or after injection, there is little evidence of reproductive or developmental toxicity in animal studies under exposure levels and routes relevant to humans. Most of the epidemiology studies examined spontaneous abortion and showed some evidence of increased risk (meta-relative risk=1.4, 95% CI 0.9-2.1). We found evidence of reporting biases and publication biases among the epidemiology studies and when these biases were taken into account, we found no evidence of increased risk of spontaneous abortion among workers exposed to formaldehyde (meta-relative risk=0.7, 95% CI 0.5-1.0). The small number of studies on birth defects, low birth weight, and infertility among formaldehyde workers; the limitations in the design of these studies; and the inconsistent findings across these studies make it difficult to draw conclusions from the epidemiology data alone. However, information from experimental studies and studies of metabolism indicate reproductive impacts are unlikely at formaldehyde exposures levels observed in the epidemiology studies. PMID:11502153

  5. 40 CFR 26.1603 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 2012-07-01 false Operation of the Human Studies Review Board. 26.1603 Section...PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1603 Operation of...

  6. 40 CFR 26.1605 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 2013-07-01 false Operation of the Human Studies Review Board. 26.1605 Section...PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1605 Operation of...

  7. 40 CFR 26.1603 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 2011-07-01 false Operation of the Human Studies Review Board. 26.1603 Section...PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1603 Operation of...

  8. 40 CFR 26.1603 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 2010-07-01 false Operation of the Human Studies Review Board. 26.1603 Section...PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1603 Operation of...

  9. 40 CFR 26.1605 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 2014-07-01 false Operation of the Human Studies Review Board. 26.1605 Section...PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1605 Operation of...

  10. Human pharmacological studies of a new transdermal system containing nitroglycerin

    Microsoft Academic Search

    P. Mtiller; P. R. Imhof; F. Burkart; L.-C. Chu; A. Gérardin

    1982-01-01

    Summary  A new transdermal therapeutic system (TTS) for the administration of nitroglycerin (NTG) was tested in human pharmacological\\u000a studies in 26 healthy volunteers. Plasma concentrations and haemodynamic responses were determined after the application of\\u000a the system in different dosages. The concentrations of NTG reached in the plasma were uniform and dose-related, i.e. dependent\\u000a on the drug-release area, and showed only minor

  11. Human colonic biota studied by ribosomal DNA sequence analysis

    Microsoft Academic Search

    KENNETH H. WILSON; R. B. Blitchington

    1996-01-01

    Human colonic biota is a complex microbial ecosystem that serves as a host defense. Unlike most microbial ecosystems, its composition has been studied extensively by relatively efficient culture methods. We have compared an established culture-based method with direct amplification and partial sequencing of cloned 16S rRNAgenesfromahumanfecalspecimen.NinecyclesofPCRwerealsocomparedwith35cycles.Coloniesand clonedampliconswereclassifiedbycomparingtheirribosomalDNA(rDNA;DNAcodingforrRNA)sequences with rDNA sequences of known phylogeny. Quantitative culture recovered 58% of the microscopic

  12. Giant intranuclear granules in human megakaryocytes: A ultrastructural study

    Microsoft Academic Search

    Angel Hernandez; Ignacio Español; Nuria Pujol-Moix

    1998-01-01

    The appearance of “giant perichromatin granules” to date has been considered pathognomonic of nasopharyngeal angiofibroma. We present the finding of giant intranuclear granules in human megakaryocytes. The patient was a 34-year-old woman with a diagnosis of Sebastian platelet syndrome. The bone marrow aspirate showed an increased number of megakaryocytes. Ultrastructural study revealed giant perichromatin-like granules in the nuclei of 80%

  13. 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 370nm 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)cm(2)/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 (532nm, 50mW) Nd:YAG laser and the limiting threshold values are found to be 22.7mW for 0.01M and 24.9mW for 0.03 and 0.05M LTB:Cu nanoparticles. PMID:25615676

  14. 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.

  15. Biocompatibility of electrospun human albumin: a pilot study.

    PubMed

    Noszczyk, B H; Kowalczyk, T; ?y?niak, M; Zembrzycki, K; Miku?owski, G; Wysocki, J; Kawiak, J; Pojda, Z

    2015-01-01

    Albumin is rarely used for electrospinning because it does not form fibres in its native globular form. This paper presents a novel method for electrospinning human albumin from a solution containing pharmaceutical grade protein and 25% polyethylene oxide (PEO) used as the fibre-forming agent. After spontaneous cross-linking at body temperature, with no further chemicals added, the fibres become insoluble and the excess PEO can be washed out. Albumin deposited along the fibres retains its native characteristics, such as its non-adhesiveness to cells and its susceptibility for degradation by macrophages. To demonstrate this we evaluated the mechanical properties, biocompatibility and biodegradability of this novel product. After subcutaneous implantation in mice, albumin mats were completely resorbable within six days and elicited only a limited local inflammatory response. In vitro, the mats suppressed cell attachment and migration. As this product is inexpensive, produced from human pharmaceutical grade albumin without chemical modifications, retains its native protein properties and fulfils the specific requirements for anti-adhesive dressings, its clinical use can be expedited. We believe that it could specifically be used when treating paediatric patients with epidermolysis bullosa, in whom non-healing wounds occur after minor hand injuries which lead to rapid adhesions and devastating contractures. PMID:25727172

  16. An Integrated Simulation System for Human Factors Study Ying Wang, Wei Zhang

    E-print Network

    Paris-Sud XI, Université de

    An Integrated Simulation System for Human Factors Study Ying Wang, Wei Zhang Department reality hardware/software, the system allows natural human-system and/or human-human interaction the quality of the system design in human factors perspective based on the measurement. It can also

  17. 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.

  18. Ten-dimensional anthropomorphic arm control in a human brain-machine interface: difficulties, solutions, and limitations.

    PubMed

    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. PMID:25514320

  19. Predictive value and limitations of animal models for human transplantation: do we need more models for facial transplantation?

    Microsoft Academic Search

    Thomas J. Cahill; Shehan Hettiaratchy; Alex Clarke; Peter E. M. Butler

    2006-01-01

    Animal models have traditionally provided the basis for preliminary investigation of new techniques prior to trials taking place in human subjects. The timing of when to proceed with human trials is difficult, as the accuracy of preclinical models can only be determined with hindsight. This review outlines the progression from transplantation in animal models to man. Now that many transplant

  20. The Werner syndrome protein limits the error-prone 8-oxo-dG lesion bypass activity of human DNA polymerase kappa

    PubMed Central

    Maddukuri, Leena; Ketkar, Amit; Eddy, Sarah; Zafar, Maroof K.; Eoff, Robert L.

    2014-01-01

    Human DNA polymerase kappa (hpol ?) is the only Y-family member to preferentially insert dAMP opposite 7,8-dihydro-8-oxo-2?-deoxyguanosine (8-oxo-dG) during translesion DNA synthesis. We have studied the mechanism of action by which hpol ? activity is modulated by the Werner syndrome protein (WRN), a RecQ helicase known to influence repair of 8-oxo-dG. Here we show that WRN stimulates the 8-oxo-dG bypass activity of hpol ? in vitro by enhancing the correct base insertion opposite the lesion, as well as extension from dC:8-oxo-dG base pairs. Steady-state kinetic analysis reveals that WRN improves hpol ?-catalyzed dCMP insertion opposite 8-oxo-dG ?10-fold and extension from dC:8-oxo-dG by 2.4-fold. Stimulation is primarily due to an increase in the rate constant for polymerization (kpol), as assessed by pre-steady-state kinetics, and it requires the RecQ C-terminal (RQC) domain. In support of the functional data, recombinant WRN and hpol ? were found to physically interact through the exo and RQC domains of WRN, and co-localization of WRN and hpol ? was observed in human cells treated with hydrogen peroxide. Thus, WRN limits the error-prone bypass of 8-oxo-dG by hpol ?, which could influence the sensitivity to oxidative damage that has previously been observed for Werner's syndrome cells. PMID:25294835

  1. [The dog as a model for comparative studies of lymphoma and leukemia in humans].

    PubMed

    Pawlak, Aleksandra; Obmi?ska-Mrukowicz, Bo?ena; Rapak, Andrzej

    2013-01-01

    Dogs have accompanied humankind for thousands of years. They share the same environment, and thus are exposed to the same environmental factors such as air pollution, tobacco smoke, and various chemicals. Recent development of veterinary care has led to a significant extension of dogs' lifespan and allowed the diagnosis and treatment of a growing number of different diseases in this species. Among all diseases in dogs, cancer is considered the main cause of mortality, with lymphoproliferative disorders accounting for up to 30% of all canine cancers. Some of them, such as non-Hodgkin lymphoma (NHL) and lymphocytic leukemia, are very similar in the etiology, pathogenesis and response to treatment to the diseases occurring in humans. Due to anatomical and physiological similarities to humans, the dog is a useful model for the study of new therapeutic strategies for humans. Studies on the canine neoplasia are currently limited by the lack of well-characterized and widely available cell lines; thus, recently obtained canine NHL cell lines may become a valuable model for such studies. Investigation of their sensitivity to the antiproliferative effects of different factors should allow the creation of a database similar to the existing classification of human leukemias and lymphomas. This should enable quick and accurate diagnosis and selection of appropriate treatment based on phenotypic analysis and histopathological examination of clinical samples. The cooperation between human and veterinary oncologists gives the opportunity to use the dog as a model for the study of certain types of cancers presenting a challenge for modern medicine. PMID:23752599

  2. A Novel In vitro Model for Studying the Interactions Between Human Whole Blood and Endothelium

    PubMed Central

    Nordling, Sofia; Nilsson, Bo; Magnusson, Peetra U.

    2014-01-01

    The majority of all known diseases are accompanied by disorders of the cardiovascular system. Studies into the complexity of the interacting pathways activated during cardiovascular pathologies are, however, limited by the lack of robust and physiologically relevant methods. In order to model pathological vascular events we have developed an in vitro assay for studying the interaction between endothelium and whole blood. The assay consists of primary human endothelial cells, which are placed in contact with human whole blood. The method utilizes native blood with no or very little anticoagulant, enabling study of delicate interactions between molecular and cellular components present in a blood vessel. We investigated functionality of the assay by comparing activation of coagulation by different blood volumes incubated with or without human umbilical vein endothelial cells (HUVEC). Whereas a larger blood volume contributed to an increase in the formation of thrombin antithrombin (TAT) complexes, presence of HUVEC resulted in reduced activation of coagulation. Furthermore, we applied image analysis of leukocyte attachment to HUVEC stimulated with tumor necrosis factor (TNF?) and found the presence of CD16+ cells to be significantly higher on TNF? stimulated cells as compared to unstimulated cells after blood contact. In conclusion, the assay may be applied to study vascular pathologies, where interactions between the endothelium and the blood compartment are perturbed. PMID:25489671

  3. A novel in vitro model for studying the interactions between human whole blood and endothelium.

    PubMed

    Nordling, Sofia; Nilsson, Bo; Magnusson, Peetra U

    2014-01-01

    The majority of all known diseases are accompanied by disorders of the cardiovascular system. Studies into the complexity of the interacting pathways activated during cardiovascular pathologies are, however, limited by the lack of robust and physiologically relevant methods. In order to model pathological vascular events we have developed an in vitro assay for studying the interaction between endothelium and whole blood. The assay consists of primary human endothelial cells, which are placed in contact with human whole blood. The method utilizes native blood with no or very little anticoagulant, enabling study of delicate interactions between molecular and cellular components present in a blood vessel. We investigated functionality of the assay by comparing activation of coagulation by different blood volumes incubated with or without human umbilical vein endothelial cells (HUVEC). Whereas a larger blood volume contributed to an increase in the formation of thrombin antithrombin (TAT) complexes, presence of HUVEC resulted in reduced activation of coagulation. Furthermore, we applied image analysis of leukocyte attachment to HUVEC stimulated with tumor necrosis factor (TNF?) and found the presence of CD16(+) cells to be significantly higher on TNF? stimulated cells as compared to unstimulated cells after blood contact. In conclusion, the assay may be applied to study vascular pathologies, where interactions between the endothelium and the blood compartment are perturbed. PMID:25489671

  4. Modification of digital music files for use in human temporary threshold shift studies

    PubMed Central

    Le Prell, C. G.; Yang, Q.; Harris, J. G.

    2011-01-01

    An exposure that is reproducible across clinical?laboratory environments, and appealing to subjects, is described here. Digital music files are level-equated within and across songs such that playlists deliver an exposure that is consistent across time. Modified music is more pleasant to listen to than pure tones or shaped noise, and closely follows music exposures subjects may normally experience. Multiple therapeutics reduce noise-induced hearing loss in animals but human trial design is complicated by limited access to noise-exposed subject populations. The development of standard music exposure parameters for temporary threshold shift studies would allow comparison of protection across agents with real-world relevant stimuli in human subjects. PMID:21974483

  5. FT-Raman spectroscopy study of human breast tissue

    NASA Astrophysics Data System (ADS)

    Bitar Carter, Renata A.; Martin, Airton A.; Netto, Mario M.; Soares, Fernando A.

    2004-07-01

    Optical spectroscopy has been extensively studied as a potential in vivo diagnostic tool to provide information about the chemical and morphologic structure of tissue. Raman Spectroscpy is an inelastic scattering process that can provide a wealth of spectral features that can be related to the specific molecular structure of the sample. This article reports results of an in vitro study of the FT-Raman human breast tissue spectra. An Nd:YAG laser at 1064nm was used as the excitation source in the FT-Raman Spectrometer. The neoplastic human breast samples, both Fibroadenoma and ICD, were obtained during therapeutical routine medical procedures required by the primary disease, and the non-diseased human tissue was obtained in plastic surgery. No sample preparation was needed for the FT-Raman spectra collection. The FT-Raman spectra were recorded from normal, benign (Fibroadenomas) and malignant (IDC-Intraductal Carcinoma) samples, adding up 51 different areas. The main spectral differences of a typical FT-Raman spectra of a Normal (Non-diseased), Fibroadenoma, and Infiltrating Ductal Carcinoma (IDC) breast tissue at the interval of 600 to 1800cm-1, which may differentiate diagnostically the sample, were found in the bands of 1230 to 1295cm-1, 1440 to 1460 cm-1 and 1650 to 1680 cm-1, assigned to the vibrational bands of the carbohydrate-amide III, proteins and lipids, and carbohydrate-amide I, respectively.

  6. OBATOCLAX and ABT-737 Induce ER Stress Responses in Human Melanoma Cells that Limit Induction of Apoptosis

    PubMed Central

    Wroblewski, David; Jiang, Chen Chen; Croft, Amanda; Farrelly, Margaret L.; Zhang, Xu Dong; Hersey, Peter

    2013-01-01

    Anti-apoptotic Bcl-2 family proteins, in particular, Mcl-1, are known to play a critical role in resistance of human melanoma cells to induction of apoptosis by endoplasmic reticulum stress and other agents. The present study examined whether the BH3 mimetics, Obatoclax and ABT-737, which inhibit multiple anti-apoptotic Bcl-2 family proteins, would overcome resistance to apoptosis. We report that both agents induced a strong unfolded protein response (UPR) and that RNAi knockdown of UPR signalling proteins ATF6, IRE1? and XBP-1 inhibited Mcl-1 upregulation and increased sensitivity to the agents. These results demonstrate that inhibition of anti-apoptotic Bcl-2 proteins by Obatoclax and ABT-737 appears to elicit a protective feedback response in melanoma cells, by upregulation of Mcl-1 via induction of the UPR. We also report that Obatoclax, but not ABT-737, strongly induces autophagy, which appears to play a role in determining melanoma sensitivity to the agents. PMID:24367627

  7. Electron trapping in neutron-irradiated silicon studied by space-charge-limited current.

    NASA Technical Reports Server (NTRS)

    Quat, V. T.; Nicolet, M.-A.

    1972-01-01

    The trapping and detrapping of electrons is studied through measurements of space-charge-limited current in the temperature range of 77 to 293 K in high-purity silicon after irradiation with 14-MeV neutrons. A model is developed which describes most of the results quantitatively and self-consistently, including dc characteristics. Two distinct trap levels exist: the fast levels lie at 0.14 (plus or minus 0.005) eV below the conduction band, and the slow levels lie at 0.47 (plus or minus 0.01) eV below the conduction band. At 77 K, injected free electrons are initially captured by the fast 0.14-eV traps and then sink into the deep 0.47-eV traps, predominantly without being reemitted into the band. Above approximately 110 K, the detrapping rate from the shallow traps becomes so fast that the deep traps dominate. The results also offer a direct verification of the simple model of space-charge-limited current dominated by shallow and deep traps.

  8. Epithelial Cell Coculture Models for Studying Infectious Diseases: Benefits and Limitations

    PubMed Central

    Duell, Benjamin L.; Cripps, Allan W.; Schembri, Mark A.; Ulett, Glen C.

    2011-01-01

    Countless in vitro cell culture models based on the use of epithelial cell types of single lineages have been characterized and have provided insight into the mechanisms of infection for various microbial pathogens. Diverse culture models based on disease-relevant mucosal epithelial cell types derived from gastrointestinal, genitourinary, and pulmonary organ systems have delineated many key host-pathogen interactions that underlie viral, parasitic, and bacterial disease pathogenesis. An alternative to single lineage epithelial cell monoculture, which offers more flexibility and can overcome some of the limitations of epithelial cell culture models based on only single cell types, is coculture of epithelial cells with other host cell types. Various coculture models have been described, which incorporate epithelial cell types in culture combination with a wide range of other cell types including neutrophils, eosinophils, monocytes, and lymphocytes. This paper will summarize current models of epithelial cell coculture and will discuss the benefits and limitations of epithelial cell coculture for studying host-pathogen dynamics in infectious diseases. PMID:22007147

  9. Simple instrument for biochemical studies of the living human brain

    SciTech Connect

    Bice, A.N.; Wagner, H.N. Jr.; Lee, M.C.; Frost, J.J.

    1986-09-01

    A simple, relatively inexpensive radiation detection system was developed for measurement of positron-emitting receptor-binding drugs in the human brain. This high-efficiency coincidence counting system requires that only a few hundred microcuries of labeled drug be administered to the subject, thereby allowing for multiple studies without an excessive radiation dose. Measurement of the binding of (/sup 11/C)-carfentanil, a high-affinity synthetic opiate, to opiate receptors in the presence and in the absence of a competitive opiate antagonist exemplifies the use of this system for estimating different degrees of receptor binding of drugs in the human brain. The instrument has also been used for measurement of the transport into the brain of other positron-emitting radiotracers, such as large neutral amino acids.

  10. Resveratrol: A review of preclinical studies for human cancer prevention

    SciTech Connect

    Athar, Mohammad; Back, Jung Ho; Tang Xiuwei [Department of Dermatology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street VC15-204, New York, NY 10032 (United States); Kim, Kwang Ho [Department of Dermatology, Hallym University College of Medicine (Korea, Republic of); Kopelovich, Levy [Division of Cancer Prevention, National Cancer Institute, Bethesda, MD 20892 (United States); Bickers, David R. [Department of Dermatology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street VC15-204, New York, NY 10032 (United States); Kim, Arianna L. [Department of Dermatology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street VC15-204, New York, NY 10032 (United States)], E-mail: ak309@columbia.edu

    2007-11-01

    The search for novel and effective cancer chemopreventive agents has led to the identification of various naturally occurring compounds one of which is resveratrol (trans-3,4',5-trihydroxystilbene), a phytoalexin derived from the skin of grapes and other fruits. Resveratrol is known to have potent anti-inflammatory and antioxidant effects and to inhibit platelet aggregation and the growth of a variety of cancer cells. Its potential chemopreventive and chemotherapeutic activities have been demonstrated in all three stages of carcinogenesis (initiation, promotion, and progression), in both chemically and UVB-induced skin carcinogenesis in mice, as well as in various murine models of human cancers. Evidence from numerous in vitro and in vivo studies has confirmed its ability to modulate various targets and signaling pathways. This review discusses the current preclinical and mechanistic data available and assesses resveratrol's anticancer effects to support its potential as an anticancer agent in human populations.

  11. Morphological and functional studies on microencapsulated human fetal pancreatic tissue.

    PubMed

    Yang, H; Wu, Z G

    1989-10-01

    Fifty human fetal pancreases of 4-6 months gestation obtained from legal abortions were microencapsulated with alginate, poly-lysine after culture for 4-7 days. The microcapsules were studied morphologically and functionally. Immunocytochemical staining for insulin indicated B-cells were morphologically intact at 48 days. Insulin and C-peptide of the culture medium measured with radioimmuno-assay (RIA) showed that the microcapsules still retained the function of insulin secretion after culture for 25 days. There was no statistical difference when compared with noncapsulated tissues. No exocrine function was detected as evidenced by the amylase determination. We conclude that microencapsulated human fetal pancreatic tissues retain viability in culture for more than 25 days and can be used as transplants in the treatment of diabetes mellitus. PMID:2483542

  12. Federal Reserve Bank of Atlanta: Center for Human Capital Studies

    NSDL National Science Digital Library

    Based at the Federal Reserve Bank of Atlanta, the Center for Human Capital Studies "intends to enhance the understanding of human capital development and labor market issues." On its page, visitors can learn about the centerâ??s annual reports, its Jobs Calculator, and various events and symposia. The Jobs Calculator calculates the net employment change needed to achieve a target unemployment rate after a specified number of months. Visitors can start by entering their own metrics to view statewide numbers or consult a list of FAQs for using the calculator. The centerâ??s newsletter and working papers can be found in the Publications area and the podcasts offer another great feature to the site. Podcast topics include "Economic Gardening: A Homegrown Approach to Growth" and "Help for Difficult to Employ Populations: Colocating Jobs and Training Opportunities.â?

  13. Resveratrol and Clinical Trials: The Crossroad from In Vitro Studies to Human Evidence

    PubMed Central

    Tomé-Carneiro, Joao; Larrosa, Mar; González-Sarrías, Antonio; Tomás-Barberán, Francisco A.; García-Conesa, María Teresa; Espín, Juan Carlos

    2013-01-01

    Resveratrol (3,5,4’-trihydroxy-trans-stilbene) is a non-flavonoid polyphenol that may be present in a limited number of food-stuffs such as grapes and red wine. Resveratrol has been reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human diet have drawn the worldwide attention of many research groups over the past twenty years, which has resulted in a huge output of in vitro and animal (preclinical) studies. In line with this expectation, many resveratrol-based nutraceuticals are consumed all over the world with questionable clinical/scientific support. In fact, the confirmation of these benefits in humans through randomized clinical trials is still very limited. The vast majority of preclinical studies have been performed using assay conditions with a questionable extrapolation to humans, i.e. too high concentrations with potential safety concerns (adverse effects and drug interactions), short-term exposures, in vitro tests carried out with non-physiological metabolites and/or concentrations, etc. Unfortunately, all these hypothesis-generating studies have contributed to increased the number of ‘potential’ benefits and mechanisms of resveratrol but confirmation in humans is very limited. Therefore, there are many issues that should be addressed to avoid an apparent endless loop in resveratrol research. The so-called ‘Resveratrol Paradox’, i.e., low bioavailability but high bioactivity, is a conundrum not yet solved in which the final responsible actor (if any) for the exerted effects has not yet been unequivocally identified. It is becoming evident that resveratrol exerts cardioprotective benefits through the improvement of inflammatory markers, atherogenic profile, glucose metabolism and endothelial function. However, safety concerns remain unsolved regarding chronic consumption of high RES doses, specially in medicated people. This review will focus on the currently available evidence regarding resveratrol’s effects on humans obtained from randomized clinical trials. In addition, we will provide a critical outlook for further research on this molecule that is evolving from a minor dietary compound to a possible multi-target therapeutic drug. PMID:23448440

  14. Use of Laboratory Studies for the Design, Explanation, and Validation of Human Micronutrient Intervention Studies123

    PubMed Central

    Ross, A. Catharine

    2012-01-01

    Many micronutrient supplementation trials have led to important new findings relevant to public health, but some outcomes have been unclear or concerning. Can and should laboratory studies and animal models be used more extensively to pretest the proposed designs of human studies? This paper illustrates, as examples, the contributions that animal models have made to several major advances in understanding the biology of the micronutrients vitamin A and carotenoids, and it proposes that animal studies can play a more integrated role in public health nutrition by serving as a first line of interrogation for study designs and thereby as a means of refining the designs of human studies so that large, expensive, and logistically difficult human trials will yield the best possible information. PMID:22090470

  15. Crowdsourcing and Human Computation: Systems, Studies and Platforms

    E-print Network

    Bernstein, Michael

    2011-01-01

    Crowdsourcing and human computation are transforming human-computer interaction, and CHI has led the way. The seminal publication in human computation was initially published in CHI in 2004 [1], and the first paper ...

  16. Effect of thoracic gas compression and bronchodilation on the assessment of expiratory flow limitation during exercise in healthy humans.

    PubMed

    Guenette, Jordan A; Dominelli, Paolo B; Reeve, Sabrina S; Durkin, Christopher M; Eves, Neil D; Sheel, A William

    2010-03-31

    Expiratory flow limitation (EFL) during exercise may be overestimated or falsely detected when superimposing tidal breaths within a pre-exercise maximal expiratory flow volume (MEFV) curve due to thoracic gas compression (TGC) and bronchodilation. Accordingly, the purpose of this study was to determine the effects of TGC and bronchodilation on the assessment of EFL in 35 healthy subjects. A pre-exercise forced vital capacity (FVC) maneuver was performed that did not account for TGC (MEFV(pre)). Subjects then performed graded expirations from total lung capacity to residual volume at different efforts to account for TGC (MEFV(pre-TGC)). Post-exercise FVC (MEFV(post)) and post-exercise graded expirations (MEFV(post-TGC)) were performed to account for bronchodilation and TGC. EFL occurred in 29 subjects when using MEFV(pre). The magnitude of EFL in these subjects was 47+/-23% which was significantly higher than MEFV(pre-TGC) (28+/-28%), MEFV(post) (24+/-27%) and MEFV(post-TGC) (19+/-24%) (P<0.00001). Using the traditional MEFV(pre) curve overestimates and falsely detects EFL since it does not account for TGC and bronchodilation. PMID:20138157

  17. 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.

  18. 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.

  19. Hamiltonian tomography of dissipative systems under limited access: A biomimetic case study

    E-print Network

    Maruyama, Koji; Ishizaki, Akihito; Whaley, K Birgitta; Takui, Takeji

    2011-01-01

    The identification of parameters in the Hamiltonian that describes complex many-body quantum systems is generally a very hard task. Such problems of Hamiltonian tomography for networks formed with two-level systems have recently been studied actively. Pragmatically, however, the effect of decoherence makes the identification task even more difficult, because injected signals are likely to decay before they accumulate sufficient information for parameter estimation. In this paper, we attempt to apply our scheme of Hamiltonian tomography [PRA79, 020305(R) (2009); NJP11, 103019 (2009)] to dissipative systems with a limited set of state preparation and measurement probes. As an example, we consider a network modelling a light harvesting complex, the Fenna-Matthews-Olson complex, whose Hamiltonian recently attracts much interest and is a subject of intensive investigations. We also classify graph properties of networks for which we can and cannot estimate the Hamiltonian under the same conditions on state preparat...

  20. An in vitro study of the effect of mifepristone and ulipristal acetate on human sperm functions.

    PubMed

    Ko, J K Y; Huang, V W; Li, R H W; Yeung, W S B; Ho, P C; Chiu, P C N

    2014-11-01

    Ulipristal acetate (UPA) and mifepristone are currently well-established agents for emergency contraception. Both drugs are selective progestogen receptor modulators which have been shown to have better efficacy than the widely used levonorgestrel in prevention of pregnancy. However, there is only limited information on the action of UPA on sperm function. The present study compared the in vitro biological effects of mifepristone and UPA on human sperm functions. Spermatozoa from semen samples with normal semen parameters were isolated. Capacitated spermatozoa were pre-incubated with 0.04, 0.4, 4 and 40 ?M mifepristone or UPA for 1 h. Sperm motility, viability, DNA integrity, capacitation, spontaneous acrosome reaction, spontaneous hyperactivation, zona pellucida (ZP) binding capability and intracellular calcium concentration ([Ca(2+)]i) were determined. The effects of mifepristone and UPA on progesterone-induced acrosome reaction, hyperactivation and [Ca(2+)]i were also studied. Our results showed that mifepristone and UPA dose-dependently suppressed progesterone-induced acrosome reaction, hyperactivation and [Ca(2+)]i at concentrations ?0.4 ?M in human spermatozoa. Both compounds did not affect sperm motility, viability, DNA integrity, capacitation, spontaneous acrosome reaction, spontaneous hyperactivation, ZP binding capability and [Ca(2+)]i. This study demonstrated that UPA and mifepristone modulate human sperm functions by acting as progesterone antagonists. The results enable us to gain a better understanding of the mechanisms by which mifepristone and UPA work for emergency contraception, and provide a scientific basis for their clinical application. PMID:25168311

  1. Human cardiomyocyte progenitor cells differentiate into functional mature cardiomyocytes: an in vitro model for studying human cardiac physiology and pathophysiology

    Microsoft Academic Search

    Anke M Smits; Patrick van Vliet; Corina H Metz; Tom Korfage; Joost PG Sluijter; Pieter A Doevendans; Marie-José Goumans

    2009-01-01

    To date, there is no suitable in vitro model to study human adult cardiac cell biology. Although embryonic stem cells are able to differentiate into cardiomyocytes in vitro, the efficiency of this process is very low. Other methods to differentiate progenitor cells into beating cardiomyocytes rely on coculturing with rat neonatal cardiomyocytes, making it difficult to study human cardiomyocyte differentiation

  2. Human habitation field study of the Habitat Demonstration Unit (HDU)

    NASA Astrophysics Data System (ADS)

    Litaker, Harry L.; Archer, Ronald D.; Szabo, Richard; Twyford, Evan S.; Conlee, Carl S.; Howard, Robert L.

    2013-10-01

    Landing and supporting a permanent outpost on a planetary surface represents humankind's capability to expand its own horizons and challenge current technology. With this in mind, habitability of these structures becomes more essential given the longer durations of the missions. The purpose of this evaluation was to obtain preliminary human-in-the-loop performance data on the Habitat Demonstration Unit (HDU) in a Pressurized Excursion Module (PEM) configuration during a 14-day simulated lunar exploration field trial and to apply this knowledge to further enhance the habitat's capabilities for forward designs. Human factors engineers at the NASA/Johnson Space Center's Habitability and Human Factors Branch recorded approximately 96 h of crew task performance with four work stations. Human factors measures used during this study included the NASA Task Load Index (TLX) and customized post questionnaires. Overall the volume for the PEM was considered acceptable by the crew; however; the habitat's individual work station volume was constrained when setting up the vehicle for operation, medical operations, and suit maintenance while general maintenance, logistical resupply, and geo science was considered acceptable. Crew workload for each station indicated resupply as being the lowest rated, with medical operations, general maintenance, and geo science tasks as being light, while suit maintenance was considered moderate and general vehicle setup being rated the highest. Stowage was an issue around the habitat with the Space Exploration Vehicle (SEV) resupply stowage located in the center of the habitat as interfering with some work station volumes and activities. Ergonomics of the geo science station was considered a major issue, especially with the overhead touch screens.

  3. Impairment of a pregnant woman's acquired ability to limit Plasmodium falciparum by infection with human immunodeficiency virus type-1.

    PubMed

    Steketee, R W; Wirima, J J; Bloland, P B; Chilima, B; Mermin, J H; Chitsulo, L; Breman, J G

    1996-01-01

    In Africa, the human immunodeficiency virus (HIV) is the most serious emerging infection and Plasmodium falciparum malaria is one of the most prevalent infectious diseases. Both infections have serious consequences in pregnant women, their fetuses, and infants. We examined the association between HIV and P. falciparum in pregnant women enrolled in a malaria chemoprophylaxis study in rural Malawi. Pregnant women (n = 2,946) were enrolled at their first antenatal clinic visit (mean 5.6 months of pregnancy), placed on one of three chloroquine regimens, and followed through delivery. Plasmodium falciparum parasitemia was measured at enrollment, monthly thereafter, at delivery, and 2-6 months postpartum; placental and newborn (umbilical cord blood) infection was measured for hospital-delivered infants. Serum collected during pregnancy was tested for antibodies to HIV by enzyme-linked immunoassay with Western blot confirmation. Parasitemia was detected in 46% of 2,946 women at enrollment and 19.1% at delivery; HIV seroprevalence was 5.5%. The prevalence and geometric mean density (GMPD) of parasitemia at enrollment and at delivery were higher in HIV-seropositive(+) than in HIV-seronegative(-) women (at enrollment: 57% prevalence and a GMPD of 1,558 parasites/mm3 versus 44% and 670/mm3, respectively; P < 0.0001; and at delivery: 35% and 1,589/mm3 versus 18% and 373/mm3; P < 0.0005). Placental infection rates were higher in HIV(+) compared with HIV(-) women, (38% versus 23%; P < 0.0005). This association was strongest in multigravidas. Compared with infants born to HIV(-) women, newborns born to HIV(+) women had higher rates of umbilical cord blood parasitemia. Both HIV(+) and HIV(-) women had similar rates of parasitemia 2-6 months postpartum. The HIV infection diminishes a pregnant woman's capacity to control P. falciparum parasitemia and placental and newborn infection, the major determinants of the impact of P. falciparum on fetal growth and infant survival. PMID:8702036

  4. Human Aspects and Habitat Studies from EuroGeoMars Campaign

    NASA Astrophysics Data System (ADS)

    Boche-Sauvan, L.; Pletser, V.; Foing, B. H.; Eurogeomars Team

    2009-04-01

    Introduction: In a human space mission, the human factor is one of the dominant aspects, which may strongly influence work results and efficiency. To quantify such a difficult and uncontrollable aspect of space missions, it is necessary to reproduce as exactly as possible the environmental and technical conditions in which astronauts may be confronted: limited re-sources, social interactions in an isolated and cramped area… We will take the benefit of the EuroGeoMars campaign in the Mars Desert Research Station (MDRS, Mars Society) in Utah to observe and measure these characteristics. EuroGeoMars campaign: The EuroGeoMars team aims at assessing the development of scientific protocols and techniques in geology and biology research in planetary conditions. In this framework, MRDS simulation constitutes its main achievement. The scientific investigations conducted in MRDS are expected to provide valuable results, beyond the simple reflection on how managing planetary specific conditions. Nevertheless, the different scientific protocols, even tailored for extreme environmental conditions, require an exhaustive analysis to evaluate how the results and their timing may possibly be affected. MDRS: The MDRS habitat will demand the crew members to work in a cramped environment, surrounded by dust and very limited manpower. Moreover, energy power and communication bandwidth will be limited to the crew members. Human aspects and habitat studies: The crewmember will work in an uncomfortable environment in the habitat: dust, cramping and crowd. Moreover, the sustainibility of the mission will relie on an optimal energy and ressources sharing. This will impose a planification of the different investigating activities. The study of the human aspects and habitat will be performed in terms of impact on scientific and technical tasks rather than in terms of crew's comfort. As any astronaut will previously be aware of the daily condition, we want to improve the working conditions in the aim of optimizing the obtaining of scientific results. A mission off the land will be worth only with a real scientific gain. Moreover, as the schedule is focused on the work time, better working conditions will provide better general living resentment. Following this approach, observations and interviews of the crewmembers in the simulation will be done. That will cover several sides: layout, equipment, area, and mostly man-machine interface. This last side will be the most studied in different situation: during daily life, in the laboratory, in the workshop and during the EVA. Indeed, the specifications for such an interface will be different according to the use: easy use in EVA, but with a good layout in the habitat. Acknowledgements: We thank the EuroGeo-Mars teams for their support in this study, and Mars Society for the opportunity of such a campaign.

  5. A morphometric study on human muscle mitochondria in aging

    Microsoft Academic Search

    Carlo Bertoni-Freddari; Patrizia Fattoretti; Ugo Caselli; Belinda Giorgetti; Stefano Albanelli; Francesco Torelli; Giorgio Felzani; Jacopo Vecchiet

    2002-01-01

    Mitochondria are dynamic organelles capable of significant changes of their ultrastructural features according to the tissue-specific\\u000a energy demands. In human biopsies of vastus lateralis and anterior tibialis muscles from young (25.0 ± 4.4 years), middle-aged\\u000a (50.4 ± 7.5 years) and old (75.5±3.9 years) healthy volunteers, we carried out a morphometric study on subsarcolemmal and\\u000a intermyofibrillar mitochondria to assess whether age-related

  6. LIFESTYLE AS RISK FACTOR FOR CANCER: EVIDENCE FROM HUMAN STUDIES

    PubMed Central

    Khan, Naghma; Afaq, Farrukh; Mukhtar, Hasan

    2010-01-01

    It is increasingly appreciated that the chances of developing cancer are significantly affected by the choice of our lifestyle. There are several uncontrollable risk factors which account for the majority of cancers, but we can modify our lifestyle to reduce enhanced threat of cancer. Healthy lifestyle behaviors for cancer risk reduction include a healthy diet, weight management, regular exercise, reduction in alcohol consumption and smoking cessation. In this article, we present evidences on the association between certain lifestyle characteristics and their contribution for developing breast, prostate, lung and colon cancers, using information derived from human studies. PMID:20080335

  7. The dopaminergic basis of human behaviors: a review of molecular imaging studies

    PubMed Central

    Egerton, Alice; Mehta, Mitul A; Montgomery, Andrew J; Lappin, Julia M; Howes, Oliver D; Reeves, Suzanne J; Cunningham, Vincent J; Grasby, Paul M

    2013-01-01

    This systematic review describes human molecular imaging studies which have investigated alterations in extracellular DA levels during performance of behavioral tasks. Whilst heterogeneity in experimental methods limits meta-analysis, we describe the advantages and limitations of different methodological approaches. Interpretation of experimental results may be limited by regional cerebral blood flow (rCBF) changes, head movement and choice of control conditions. We revisit our original study of striatal DA release during video-game playing (Koepp et al., 1998) to illustrate the potentially confounding influences of head movement and alterations in rCBF. Changes in [11C]raclopride binding may be detected in extrastriatal as well as striatal brain regions – however we review evidence which suggests that extrastriatal changes may not be clearly interpreted in terms of DA release. Whilst several investigations have detected increases in striatal extracellular DA concentrations during task components such as motor learning and execution, reward-related processes, stress and cognitive performance, the presence of potentially biasing factors should be carefully considered (and, where possible, accounted for) when designing and interpreting future studies. PMID:19481108

  8. Integrating and mining diverse data in human immunological studies.

    PubMed

    Siebert, Janet C; Wagner, Brandie D; Juarez-Colunga, Elizabeth

    2014-01-01

    Bioanalysts and immunologists can interrogate the immune system with a variety of high-throughput technologies such as gene expression, multiplex bead arrays and flow cytometry. Conceptually, these assays support systems immunology studies, in which phenomena can be measured and correlated across biological compartments. First, however, the resulting high-dimensional data must be combined in a consistent fashion that supports analysis of the data as an integrated whole. Next, analytical methods must be applied to the hundreds or thousands of readouts. We recommend the use of a four-part analytical pipeline, consisting of data integration, hypothesis generation, prediction and hypothesis testing, and validation. We describe a variety of established methods appropriate for these integrated datasets, and highlight their application to human immunological studies. Our goal is to provide bioanalysts, immunologists and data analysts with a valuable perspective with which to approach the multiassay high-dimensional datasets generated by contemporary immunological studies. PMID:24423597

  9. Human Liver Transplantation As A Model To Study HCV Pathogenesis

    PubMed Central

    Hughes, Michael G.; Rosen, Hugo R.

    2010-01-01

    Hepatitis C is a leading etiology of liver cancer and cause for liver transplantation. Although new therapies have improved the rates of sustained response, a large proportion of patients (~50%) fail to respond to antiviral treatment, thus remaining at risk for disease progression. While chimpanzees have been used to study HCV biology and treatments, their cost is quite high and their use is strictly regulated; indeed, the NIH no longer supports the breeding of chimpanzees for study. The development of HCV therapies has been hindered by the relative paucity of small animal models to study HCV pathogenesis. This review presents the strengths of the human liver transplant, highlighting the advances derived from this model, including insights into viral kinetics and quasispecies, viral receptor binding and entry, innate and adaptive immunity. Moreover, consideration is made of current and emerging antiviral therapeutic approaches based on translational research results. PMID:19877210

  10. Informed consent for human genetic and genomic studies: a systematic review.

    PubMed

    Khan, A; Capps, B J; Sum, M Y; Kuswanto, C N; Sim, K

    2014-09-01

    As genetic and genomic studies grow in scale, there are ethical concerns related to the collection and use of genetic information. The emergence of large public databases potentially redefine the terms of participation in genetic and genomic research, and suggests the changing application of traditional ethical principles such as privacy or consent. For this study, we wanted to see whether such developments are reflected in the informed consent processes in human genetic and genomic studies. Therefore, we performed a systematic review of the empirical studies that examined informed consent involving large genetic databases in human genetic and genomic studies, grouped the identified issues related to the different stakeholders (including subjects, researchers, and institutional review boards) and discussed the limitations and implications of these findings. Major themes related to the place of bioethical considerations, procured tissues, people involved, process of informed consent and study procedures. Frequently raised issues included confidentiality of participants, documentation of informed consent, public attitudes, future use of participant samples or data, and disclosure of results. Awareness and attention to these bioethical issues as well as assiduousness in managing these concerns in genetic/genomic research would further strengthen and safeguard the rights, safety and well-being of genetic research participants. PMID:24646408

  11. Yeast Modulation of Human Dendritic Cell Cytokine Secretion: An In Vitro Study

    PubMed Central

    Smith, Ida M.; Christensen, Jeffrey E.; Arneborg, Nils; Jespersen, Lene

    2014-01-01

    Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The concept of individual microorganisms influencing the makeup of T cell subsets via interactions with intestinal dendritic cells (DCs) appears to constitute the foundation for immunoregulatory effects of probiotics, and several studies have reported probiotic strains resulting in reduction of intestinal inflammation through modulation of DC function. Consequent to a focus on Saccharomyces boulardii as the fundamental probiotic yeast, very little is known about hundreds of non-Saccharomyces yeasts in terms of their interaction with the human gastrointestinal immune system. The aim of the present study was to evaluate 170 yeast strains representing 75 diverse species for modulation of inflammatory cytokine secretion by human DCs in vitro, as compared to cytokine responses induced by a S. boulardii reference strain with probiotic properties documented in clinical trials. Furthermore, we investigated whether cytokine inducing interactions between yeasts and human DCs are dependent upon yeast viability or rather a product of membrane interactions regardless of yeast metabolic function. We demonstrate high diversity in yeast induced cytokine profiles and employ multivariate data analysis to reveal distinct clustering of yeasts inducing similar cytokine profiles in DCs, highlighting clear species distinction within specific yeast genera. The observed differences in induced DC cytokine profiles add to the currently very limited knowledge of the cross-talk between yeasts and human immune cells and provide a foundation for selecting yeast strains for further characterization and development toward potentially novel yeast probiotics. Additionally, we present data to support a hypothesis that the interaction between yeasts and human DCs does not solely depend on yeast viability, a concept which may suggest a need for further classifications beyond the current definition of a probiotic. PMID:24816850

  12. Yeast modulation of human dendritic cell cytokine secretion: an in vitro study.

    PubMed

    Smith, Ida M; Christensen, Jeffrey E; Arneborg, Nils; Jespersen, Lene

    2014-01-01

    Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The concept of individual microorganisms influencing the makeup of T cell subsets via interactions with intestinal dendritic cells (DCs) appears to constitute the foundation for immunoregulatory effects of probiotics, and several studies have reported probiotic strains resulting in reduction of intestinal inflammation through modulation of DC function. Consequent to a focus on Saccharomyces boulardii as the fundamental probiotic yeast, very little is known about hundreds of non-Saccharomyces yeasts in terms of their interaction with the human gastrointestinal immune system. The aim of the present study was to evaluate 170 yeast strains representing 75 diverse species for modulation of inflammatory cytokine secretion by human DCs in vitro, as compared to cytokine responses induced by a S. boulardii reference strain with probiotic properties documented in clinical trials. Furthermore, we investigated whether cytokine inducing interactions between yeasts and human DCs are dependent upon yeast viability or rather a product of membrane interactions regardless of yeast metabolic function. We demonstrate high diversity in yeast induced cytokine profiles and employ multivariate data analysis to reveal distinct clustering of yeasts inducing similar cytokine profiles in DCs, highlighting clear species distinction within specific yeast genera. The observed differences in induced DC cytokine profiles add to the currently very limited knowledge of the cross-talk between yeasts and human immune cells and provide a foundation for selecting yeast strains for further characterization and development toward potentially novel yeast probiotics. Additionally, we present data to support a hypothesis that the interaction between yeasts and human DCs does not solely depend on yeast viability, a concept which may suggest a need for further classifications beyond the current definition of a probiotic. PMID:24816850

  13. 006 op: methodological limitations and advances in studying culture and mental health: significance of qualitative approaches.

    PubMed

    Patel, R

    2015-01-01

    Social Epidemiology has had a long standing position in health research and covers distribution and determinants of health-related states in defined populations. The domain investigates patterns and causality, revealing health inequalities which aim to prevent and control health related issues. Understandably this field of research has advanced biological fields in exploring the relevance of social, cultural, environmental and economic factors that also play a fundamental role in ill health which is crucially ignored in biological standpoints. However, the dynamic of current societies is continuously changing and for example some areas in the UK are distinctively culturally diverse. By using my study of exploring reasons behind low reported rates of mental illness within the Gujarati community in Leicester I will argue that Social Epidemiology is limiting as method of studying in particular ethnic groups and mental health. This presentation will firstly, address the current problems with epidemiological studies in this area such as ecological fallacy, cultural stereotypes and validity of official statistics. Secondly, I will argue that qualitative research and sociological approaches are progressive for studying mental health. With reference to interview data I will outline a few current cultural complexities such as religion, language and changing traditions faced by both first and second generation migrants. Finally, I will conclude by proposing to progress mental health provision for ethnic groups there is much to be learnt about the intrinsic relationship culture has on mental health. Both qualitative methods and sociological approaches accommodate this required necessity. Having recognised the significance qualitative research has in health, we are faced with the problem of incorporating this in the universal province of the medical model of health which indeed is tricky and perhaps not one that is welcomed by all. PMID:25869715

  14. Optimization of a mega-ampere spherical tokamak for beta-limit and confinement studies

    SciTech Connect

    McCool, S.C.; Wootton, A.J.; Bravenec, R.V. [and others

    1994-10-01

    Recent favorable results on the START experiment have caused renewed interest in the potential of low aspect ratio tokamaks. To aid in designing a next-step spherical tokamak to study confinement scaling, high beta, and high normalized beta plasmas for minimal cost, the authors have developed a transport scaling and device optimization code. This code STOP, benchmarked against START, includes 10 empirical confinement scaling laws and essential tokamak physics such as stability limits. Parameters are optimized separately for each scaling law and physical goal. Using STOP the authors find for R/a = 1.2 to 2.0 one can achieve {beta}{sub N} = 5, ({beta}) = 31--44%, and easily study predicted confinement degradation with auxiliary heating with just two neutral beams (P{sub NB} < 3.5 MW) for I{sub p} {ge} 0.75 MA, and R{sub 0} {ge} 0.6 m. In contrast, if one insists on using the nominal device parameters, i.e. I{sub p} = 1 MA and R{sub 0} = 0.8 m, with each scaling law, achieving {beta}{sub N} = 5 requires typically P{sub NB} {approx} 7.5 MW. They also conclude that while running D{sup 0} {yields} D{sup +} increases {tau}{sub E} {approx} 25%, with {tau}{sub E} already uncertain by 2--3{times}, one incurs restricted machine access and compromised physics operation.

  15. Virus-Free Human Placental Cell Lines To Study Genetic Functions

    Cancer.gov

    These immortalized virus-free human placental cell lines expressing major proteins of human trophoblasts provide efficient in vitro models to study placental functions, control of tissue-specific gene expression, and other studies.

  16. A Study to Increase Participation of Habitat for Humanity Affiliates in LEED for Homes Certification

    E-print Network

    Rabb, Amy Elizabeth

    2013-04-30

    community, but this study looks at the specific impact and impediments to obtaining LEED certification for Habit for Humanity housing, specifically in Texas. This study assesses Habit for Humanity affiliate’s involvement with LEED and sustainable building...

  17. AN OVERVIEW OF THE NATIONAL HUMAN EXPOSURE ASSESSMENT SURVEY (NHEXAS) PHASE I STUDIES

    EPA Science Inventory

    The National Human Exposure Assessment Survey (NHEXAS) Phase I studies were sponsored by EPA's Office of Research and Development (ORD) to address critical information needs for assessing human exposures to multiple chemicals from multiple pathways and media. These studies were...

  18. Guidelines to Evaluate Human Observational Studies for Quantitative Risk Assessment

    PubMed Central

    Vlaanderen, Jelle; Vermeulen, Roel; Heederik, Dick; Kromhout, Hans

    2008-01-01

    Background Careful evaluation of the quality of human observational studies (HOS) is required to assess the suitability of HOS for quantitative risk assessment (QRA). In particular, the quality of quantitative exposure assessment is a crucial aspect of HOS to be considered for QRA. Objective We aimed to develop guidelines for the evaluation of HOS for QRA and to apply these guidelines to case–control and cohort studies on the relation between exposure to benzene and acute myeloid leukemia (AML). Methods We developed a three-tiered framework specific for the evaluation of HOS for QRA and used it to evaluate HOS on the relation between exposure to benzene and AML. Results The developed framework consists of 20 evaluation criteria. A specific focus of the framework was on the quality of exposure assessment applied in HOS. Seven HOS on the relation of benzene and AML were eligible for evaluation. Of these studies, five were suitable for QRA and were ranked based on the quality of the study design, conduct, and reporting on the study. Conclusion The developed guidelines facilitate a structured evaluation that is transparent in its application and harmonizes the evaluation of HOS for QRA. With the application of the guidelines, it was possible to identify studies suitable for QRA of benzene and AML and rank these studies based on their quality. Application of the guidelines in QRA will be a valuable addition to the assessment of the weight of evidence of HOS for QRA. PMID:19079723

  19. Awards for Sabbatical Study The Oppenheimer Memorial Trust (OMT) awards a limited number of grants each year to support

    E-print Network

    Awards for Sabbatical Study The Oppenheimer Memorial Trust (OMT) awards a limited number of grants with the Trust's reporting procedures. The Manager Oppenheimer Memorial Trust First Floor, No. 9 St. David's Park

  20. Resonance Raman Spectroscopic Evaluation of Skin Carotenoids as a Biomarker of Carotenoid Status for Human Studies

    PubMed Central

    Mayne, Susan T.; Cartmel, Brenda; Scarmo, Stephanie; Jahns, Lisa; Ermakov, Igor V.; Gellermann, Werner

    2013-01-01

    Resonance Raman Spectroscopy (RRS) is a non-invasive method that has been developed to assess carotenoid status in human tissues including human skin in vivo. Skin carotenoid status has been suggested as a promising biomarker for human studies. This manuscript describes research done relevant to the development of this biomarker, including its reproducibility, validity, feasibility for use in field settings, and factors that affect the biomarker such as diet, smoking, and adiposity. Recent studies have evaluated the response of the biomarker to controlled carotenoid interventions, both supplement-based and dietary [e.g., provision of a high-carotenoid fruit and vegetable (F/V)-enriched diet], demonstrating consistent response to intervention. The totality of evidence supports the use of skin carotenoid status as an objective biomarker of F/V intake, although in the cross-sectional setting, diet explains only some of the variation in this biomarker. However, this limitation is also a strength in that skin carotenoids may effectively serve as an integrated biomarker of health, with higher status reflecting greater F/V intake, lack of smoking, and lack of adiposity. Thus, this biomarker holds promise as both a health biomarker and an objective indicator of F/V intake, supporting its further development and utilization for medical and public health purposes. PMID:23823930

  1. Resonance Raman spectroscopic evaluation of skin carotenoids as a biomarker of carotenoid status for human studies.

    PubMed

    Mayne, Susan T; Cartmel, Brenda; Scarmo, Stephanie; Jahns, Lisa; Ermakov, Igor V; Gellermann, Werner

    2013-11-15

    Resonance Raman spectroscopy (RRS) is a non-invasive method that has been developed to assess carotenoid status in human tissues including human skin in vivo. Skin carotenoid status has been suggested as a promising biomarker for human studies. This manuscript describes research done relevant to the development of this biomarker, including its reproducibility, validity, feasibility for use in field settings, and factors that affect the biomarker such as diet, smoking, and adiposity. Recent studies have evaluated the response of the biomarker to controlled carotenoid interventions, both supplement-based and dietary [e.g., provision of a high-carotenoid fruit and vegetable (F/V)-enriched diet], demonstrating consistent response to intervention. The totality of evidence supports the use of skin carotenoid status as an objective biomarker of F/V intake, although in the cross-sectional setting, diet explains only some of the variation in this biomarker. However, this limitation is also a strength in that skin carotenoids may effectively serve as an integrated biomarker of health, with higher status reflecting greater F/V intake, lack of smoking, and lack of adiposity. Thus, this biomarker holds promise as both a health biomarker and an objective indicator of F/V intake, supporting its further development and utilization for medical and public health purposes. PMID:23823930

  2. CENSHARE - Center to Study Human Animal Relationships and Environments

    NSDL National Science Digital Library

    Established in 1981 at the University of Minnesota's School of Public Health, the Center to Study Human Animal Relationships and Environments (CENSHARE) is an umbrella organization that supports groups that aim to educate about the human animal relationship and the environment they share. This mission of this education is to improve the quality of life for both, encourage scientific study of such relationships, and also serve as a resource for the community on these relationships. Visitors should check out the thorough explanation of "Animal Assisted Therapy" (AAT), and learn how it differs from, say, Animal Assisted Activities (AAA). As animal therapy can be stressful on the animal if it is not properly trained for such demanding work, the AAT link gives helpful tips to visitors on how to get an animal ready to be a therapy animal. Visitors will also learn from the AAT link that such animals have been evaluated and registered by national groups that specialize in therapy animals, but are not given the federal protections that specially-trained service dogs are, such as access to public transportation and public buildings. Finally, visitors should check out the "Companion Animals in Care Environments" link. Here they can read a bittersweet story titled "Lessons to be Learned from the Saga of Mae" which addresses the considerations that should be made when deciding whether to allow a resident animal in a care facility.

  3. Humanimalia: A journal of human/animal interface studies

    NSDL National Science Digital Library

    The website for the new journal Humanimalia, published by DePauw University, recently released its first issue. The appeal and importance of the journal goes beyond appearance, as the journal states that the study of the human/animal interface has been a "neglected" area of research. In the "Humanimalifesto" link, a lengthy explanation is given, and it notes that one of the main goals of the journal is "to approach animal/human interfaces without relying on stigmatizing critique of philosophical, political, or cultural antagonists." The first issue consists of articles and reviews, including an article called "Hooters for Neuters: Sexist Transgressive Animal Advocacy Campaign?" and a review of the popular Michael Pollan book, "The Omnivore's Dilemma: A Natural History of Four Meals". Visitors interested in submitting an article to the peer-reviewed, interdisciplinary journal should check out the guidelines in the "Call-for-Papers" link on the left side of the page. The "Notes and Bulletins" link, also on the left side of the page, has a notice of an Animal Studies meeting at NYU, and the "Links" area includes information on upcoming conferences.

  4. [Problems and limitations of conventional and innovative methods for the diagnosis of Toxoplasmosis in humans and animals].

    PubMed

    Piergili Fioretti, D

    2004-06-01

    Diagnosis of toxoplasmosis is useful for human and animal health. Several techniques are employed for the diagnosis in feline and canine population. Coprological tests for the detection of oocysts in cat faeces are of little significance owing to short patency (15 days). Histological examinations of biological samples show a lack of reliability when the animals are infected with few parasites; the mouse inoculation is the most reliable method even if the detection of cysts in mice brain require 40 days. However tachyzoites of virulent strains can be isolated from peritoneal exudate 3-4 days after inoculation. Samples inoculation in cell cultures (VERO, human fibroblasts) requires specialized laboratories and fails if non viable parasites are present due to tissutal autolysis. Serological tests are the most used diagnostic methods; Dye test and IFAT that require intact tachyzoites are more sensitive and specific compared to IHA, LA, ELISA because, during the infection, the first significant increase of IgM and IgG antibodies was observed against cuticolar antigens. A PCR to identify T. gondii DNA in canine and feline biological samples was developed. The B1 PCR performed on blood samples was less sensitive than when it was performed on other biological fluids requiring 100 tachyzoites, instead of 10. Aqueous humor PCR results could be negative if the infection is low grade or is restricted to the posterior segment or the animal was previously treated with anti-Toxoplasma drugs. SNC disease may be also difficult to diagnose because an high serum IgG titer may be associated with locally production or leakage from serum through a compromised blood-CSF barrier. AB1 PCR was successfully applied for the diagnosis of Toxoplasma abortion in ewes requiring only 10 parasites in placental cotyledon samples; the test compared with mouse inoculation showed similar sensitivity. Discrepancies may have been due to a low and focal distribution of parasites in the tissues or to the presence of non viable parasites if the tissues are autolysed. In regard to diagnostic methods adaptable to slaughter testing, several serological tests have been studied (IFAT, ELISA, IHA) for detection of IgG in sheep, pigs, cattle using also recombinant antigens (gene fragments H4 and H11) to lack the cross reactivity. The problem is the antibodies fall to near background levels as the infection became chronic (6-10 months p.-i.). A highly sensitive and specific method (Toxo Taq Man) has been developed to detect and quantitate T. gondii burden in animal tissue samples (0.1 pg of T. gondii genomic DNA, which is equivalent to 1 bradyzoite) using T. gondii ITS1-derived primers and a fluorogenic probe via Real-Time PCR. This assay is compatible with automation technology for potential slaughterhouse use. The diagnosis of acute infection in human pregnancy is difficult since IgM antibodies can be detected for a very long time after the acute phase; an IgA increase is of more diagnostic value because can be detected only for 6-7 months while the short kinetics of IgE can be useful only to date the infection precisely. In addition an IgG seroconversion is essential for the diagnosis. Among the most reliable tests, IgG avidity test is useful when a single serum sample, in the first months of gestation, is available, but low avidity results may persist for as long as 1 year. For this purpose a panel of serologic tests must be performed (ELISA, EIA, ISAGA, IgG avidity, IFAT, Dye test) for IgM, IgA, IgG and IgE. The serological diagnosis of prenatal infection is difficult since maternal IgG are passively transferred in utero to the foetus and caution must be exercised in interpretation of IgM or IgA results. A technique of Western blots of paired maternal and baby sera for evidencing different bands in the blots of two sera was developed for this purpose (specificity 97-100%, sensitivity 96-98%). The most reliable methods for prenatal diagnosis are PCR, mouse inoculation and cultural techniques performed on amniotic fluid, foetal blood and peripheral maternal blood in p

  5. A prospective study of floor surface, shoes, floor cleaning and slipping in US limited-service restaurant workers

    Microsoft Academic Search

    Santosh K Verma; Wen Ruey Chang; Theodore K Courtney; David A Lombardi; Yueng-Hsiang Huang; Melanye J Brennan; Murray A Mittleman; James H Ware; Melissa J Perry

    2010-01-01

    ObjectivesSlips and falls are a leading cause of injury at work. Few studies, however, have systematically examined risk factors of slipping outside the laboratory environment. This study examined the association between floor surface characteristics, slip-resistant shoes, floor cleaning frequency and the risk of slipping in limited-service restaurant workers.Methods475 workers from 36 limited-service restaurants from three major chains in six states

  6. 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.

  7. Preservation of the Myofibroblastic Phenotype of Human Papilloma Virus 16 E6\\/E7 Immortalized Human Bone Marrow Cells Using the Lineage Limited a-Smooth Muscle Actin Promoter1

    Microsoft Academic Search

    Corinne Loeuillet; Luc Douay; Patrick Herve; David E. Chalmers

    The in vitro study of mammalian hematopoiesis is hindered by the lack of immortalized human stromal cell lines that support hematopoiesis. We have immortalized human stromal vascular smooth muscle cells characterized by the expression of the a-smooth muscle (a-SM) actin. This marker is usually down- regulated as a result of oncogenic transformation. To correct this dedifferentiation, we placed the expression

  8. The Limits of Collaboration: A Qualitative Study of Community Ethical Review of Environmental Health Research

    PubMed Central

    Fullilove, Robert E.; Kaufman, Molly Rose; Wallace, Rodrick; Fullilove, Mindy Thompson

    2009-01-01

    Objectives. We assessed the effectiveness of various systems of community participation in ethical review of environmental health research. Methods. We used situation analysis methods and a global workspace theoretical framework to conduct comparative case studies of 3 research organizations at 1 medical center. Results. We found a general institutional commitment to community review as well as personal commitment from some participants in the process. However, difficulty in communicating across divides of knowledge and privilege created serious gaps in implementation, leaving research vulnerable to validity threats (such as misinterpretation of findings) and communities vulnerable to harm. The methods used in each collaboration solved some, but not all, of the problems that hindered communication. Conclusions. Researchers, community spokespersons, and institutional review boards constitute organizational groups with strong internal ties and highly developed cultures. Few cross-linkages and little knowledge of each other cause significant distortion of information and other forms of miscommunication between groups. Our data suggest that organizations designed to protect human volunteers are in the best position to take the lead in implementing community review. PMID:19542033

  9. ?-Cell Generation: Can Rodent Studies Be Translated to Humans?

    PubMed Central

    Carlotti, Françoise; Zaldumbide, Arnaud; Ellenbroek, Johanne H.; Spijker, H. Siebe; Hoeben, Rob C.; de Koning, Eelco J.

    2011-01-01

    ?-cell replacement by allogeneic islet transplantation is a promising approach for patients with type 1 diabetes, but the shortage of organ donors requires new sources of ? cells. Islet regeneration in vivo and generation of ?-cells ex vivo followed by transplantation represent attractive therapeutic alternatives to restore the ?-cell mass. In this paper, we discuss different postnatal cell types that have been envisaged as potential sources for future ?-cell replacement therapy. The ultimate goal being translation to the clinic, a particular attention is given to the discrepancies between findings from studies performed in rodents (both ex vivo on primary cells and in vivo on animal models), when compared with clinical data and studies performed on human cells. PMID:22007286

  10. Remote controlled capsules in human drug absorption (HDA) studies.

    PubMed

    Wilding, Ian R; Prior, David V

    2003-01-01

    The biopharmaceutical complexity of today's new drug candidates provides significant challenges for pharmaceutical scientists in terms of both candidate selection and optimizing subsequent development strategy. In addition, life cycle management of marketed drugs has become an important income stream for pharmaceutical companies, but the selection of least risk/highest benefit strategies is far from simple. The proactive adoption of human drug absorption (HDA) studies using remote controlled capsules offers the pharmaceutical scientist significant guidance for planning a route through the maze of product development. This review examines the position of HDA studies in drug development, using a variety of case histories and an insightful update on remote controlled capsules to achieve site-specific delivery. PMID:14979866

  11. Reverse genetics system for studying human rhinovirus infections.

    PubMed

    Lee, Wai-Ming; Wang, Wensheng; Bochkov, Yury A; Lee, Iris

    2015-01-01

    Human rhinovirus (HRV) contains a 7.2 kb messenger-sense RNA genome which is the template for reproducing progeny viruses after it enters the cytoplasm of a host cell. Reverse genetics refers to the regeneration of progeny viruses from an artificial cDNA copy of the RNA genome of an RNA virus. It has been a powerful molecular genetic tool for studying HRV and other RNA viruses because the artificial DNA stage makes it practical to introduce specific mutations into the viral RNA genome. This chapter uses HRV-16 as the model virus to illustrate the strategy and methods for constructing and cloning the artificial cDNA copy of a full-length HRV genome, identifying the infectious cDNA clone isolates, and selecting the most vigorous cDNA clone isolate to serve as the standard parental clone for future molecular genetic study of the virus. PMID:25261313

  12. Using natural disasters to study prenatal maternal stress in humans.

    PubMed

    King, Suzanne; Laplante, David P

    2015-01-01

    Animal studies of prenatal maternal stress permit random assignment of pregnant animals to stress and no-stress groups, and allow total control of the type, severity, and timing of the stressor in utero. Human studies have obvious constraints that make the use of experimental methods nearly impossible. Studying pregnant women who experience natural disasters during pregnancy, however, approximates the random assignment to groups enjoyed by animal studies, and can characterize the timing of the stressor in utero with great precision. In this chapter, we briefly describe our three ongoing prospective longitudinal studies of children exposed to prenatal maternal stress from natural disasters. We present results from Project Ice Storm in detail, showing effects of prenatal maternal stress on cognitive and neurodevelopment. We contrast these results with preliminary findings from the Iowa Flood Study and introduce the QF2011 Queensland Flood Project. In the "Discussion" section, we present conclusions to date and discuss the relative effects of the severity of maternal objective disaster exposure and maternal subjective distress levels, the moderating effects of fetal sex and the timing of the stressor in utero, and the longevity of the effects. Finally, we discuss some possible mechanisms that may mediate the effects of prenatal maternal stress on the neurodevelopment of children. PMID:25287546

  13. Evolutionary and developmental foundations of human knowledge: a case study of mathematics

    Microsoft Academic Search

    Marc D. Hauser; Elizabeth Spelke

    What are the brain and cognitive systems that allow humans to play baseball, compute square roots, cook soufflés, or navigate the Tokyo subways? It may seem that studies of human infants and of non-human animals will tell us little about these abilities, because only educated, enculturated human adults engage in organized games, formal mathematics, gourmet cooking, or map-reading. In this

  14. For Immediate Release IFI-published study: Human rights mechanisms gaining ground

    E-print Network

    Shihadeh, Alan

    recently in their active engagement with the Human Rights Council's Universal Periodic Review. This shows and declarations, including the entire human rights treaty system, the Human Rights council, and the OutcomeFor Immediate Release IFI-published study: Human rights mechanisms gaining ground in Arab States

  15. The human hepatoma HepaRG cells: a highly differentiated model for studies of liver metabolism and toxicity of xenobiotics.

    PubMed

    Guillouzo, André; Corlu, Anne; Aninat, Caroline; Glaise, Denise; Morel, Fabrice; Guguen-Guillouzo, Christiane

    2007-05-20

    Although they have several important limitations primary human hepatocytes still represent the in vitro gold standard model for xenobiotic metabolism and toxicity studies. The large use of human liver cell lines either from tumoral origin or obtained by oncogenic immortalisation is prevented by the loss of various liver-specific functions, especially many cytochrome P450 (CYP)-related enzyme activities. We review here recent results obtained with a new human hepatoma cell line, named HepaRG, derived from a human hepatocellular carcinoma. These cells exhibit unique features: when seeded at low density they acquire an elongated undifferentiated morphology, actively divided and after having reached confluency formed typical hepatocyte-like colonies surrounded by biliary epithelial-like cells. Moreover contrary to other human hepatoma cell lines including HepG2 cells, HepaRG cells express various CYPs (CYP1A2, 2B6, 2C9, 2E1, 3A4) and the nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR) at levels comparable to those found in cultured primary human hepatocytes. They also express various other functions such phase 2 enzymes, apical and canalicular ABC transporters and basolateral solute carrier transporters, albumin, haptoglobin as well as aldolase B that is a specific marker of adult hepatocytes. HepaRG cells could represent a surrogate to primary human hepatocytes for xenobiotic metabolism and toxicity studies and even more, a unique model system for analysing genotoxic compounds. PMID:17241619

  16. SUGGESTED THREE-YEAR GRADUATION PLAN Human Development and Family Studies Case Management

    E-print Network

    Sheridan, Scott

    SUGGESTED THREE-YEAR GRADUATION PLAN Human Development and Family Studies ­Case Management HDFS 44192 Internship in Human Development and Family Studies: Case Management I 3-6 Offered in fall below #12;SUGGESTED THREE-YEAR GRADUATION PLAN Human Development and Family Studies ­Case Management

  17. Roadmap: Human Development and Family Studies Case Management for Individuals and Families -Bachelor of Science

    E-print Network

    Sheridan, Scott

    Roadmap: Human Development and Family Studies ­ Case Management for Individuals and Families only HDFS 44192 Internship in Human Development and Family Studies: Case Management I 3-6 Offered Internship in Human Development and Family Studies: Case Management II 3-6 Offered in spring only; fulfills

  18. SUGGESTED THREE-YEAR GRADUATION PLAN Human Development and Family Studies Case Management

    E-print Network

    Sheridan, Scott

    SUGGESTED THREE-YEAR GRADUATION PLAN Human Development and Family Studies ­Case Management Internship in Human Development and Family Studies: Case Management I 3-6 Offered in fall only; fulfills THREE-YEAR GRADUATION PLAN Human Development and Family Studies ­Case Management for Individuals

  19. Managerial Leverage Is Limited by the Extent of the Market: Hierarchies, Specialization, and the Utilization of Lawyers' Human Capital

    Microsoft Academic Search

    Luis Garicano

    2007-01-01

    This paper examines the role of hierarchies in the organization of human-capital-intensive production. We develop an equilibrium model of hierarchical organization and provide empirical evidence based on confidential data on thousands of law offices. The equilibrium assignment of individuals to hierarchical positions varies with the degree of field specialization, which increases as the extent of the market increases. As individuals'

  20. 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…

  1. A Large Sample Study of the Life Table and Product Limit Estimates Under Random Censorship

    Microsoft Academic Search

    N. E. Breslow; J. Crowley

    1974-01-01

    Using the model of random censorship, a necessary and sufficient condition for the consistency of the standard (actuarial) life table estimate of a survival distribution is derived. We establish the asymptotic normality of this estimate, showing that Greenwood's variance formula is nearly correct. In the case of a continuous survival distribution we establish limiting normality for the product limit estimate

  2. An experimental study of droplet ignition characteristics near the ignitable limit

    Microsoft Academic Search

    T. Saitoh; S. Ishiguro; T. Niioka

    1982-01-01

    The ignition characteristics of a fuel droplet near the ignitable limit are investigated. The experimental results show that the ignition time increases as the droplet diameter decreases at the region near the ignition limits, and that, over the broad range, ignition occurs more rapidly as the diameter increases if the initial droplet temperature is high. These results are compared with

  3. 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

  4. Functional and association studies on the pig HMGCR gene, a cholesterol-synthesis limiting enzyme.

    PubMed

    Cánovas, A; Quintanilla, R; Gallardo, D; Díaz, I; Noguera, J L; Ramírez, O; Pena, R N

    2010-02-01

    The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the rate-limiting enzyme in the biosynthesis of cholesterol. We have studied the role of the HMGCR gene in pig lipid metabolism by means of expression and structural analysis. We describe here the complete coding region of this gene in pigs and report two synonymous single nucleotide polymorphisms in the coding region. We have, additionally, studied the association of one of these polymorphisms (HMGCR:c.807A>C) with several lipid deposition- and cholesterol-related traits in a half-sib population generated from a commercial Duroc line, showing in some families a positive relationship of HMGCR:c.807A allele with serum low-density lipoprotein (LDL)-bound cholesterol and triglyceride levels, and also with intramuscular fat (IMF) content of gluteus medius muscle. We have also assessed the expression levels in muscle and in liver from 68 Duroc individuals corresponding to the most extreme animals for the analysed traits. Liver HMGCR expression correlated negatively with the serum high-density lipoprotein (HDL) levels, carcass lean percentage and stearic acid content, while muscle expression correlated also negatively with the carcass lean percentage, stearic and linoleic acids content, but showed a positive correlation with the serum lipid cholesterol (HDL, LDL and total cholesterol), IMF and muscle oleic and palmitic fatty acid content. With this information, we have performed an association analysis of expression data with lipid metabolism phenotypic levels and the HMGCR genotype. The results indicate that HMGCR expression levels in muscle are different in the two groups of pigs with extreme values for fat deposition and total cholesterol levels, and also between animals with the different HMGCR genotypes. PMID:22443876

  5. 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…

  6. Photoacoustic FTIR spectroscopic study of undisturbed human cortical bone

    NASA Astrophysics Data System (ADS)

    Gu, Chunju; Katti, Dinesh R.; Katti, Kalpana S.

    2013-02-01

    Chemical pretreatment has been the prevailing sample preparation procedure for infrared (IR) spectroscopic studies on bone. However, experiments have indicated that chemical pretreatment can potentially affect the interactions between the components. Typically the IR techniques have involved transmission experiments. Here we report experimental studies using photoacoustic Fourier transform infrared spectroscopy (PA-FTIR). As a nondestructive technique, PA-FTIR can detect absorbance spectrum from a sample at controllable sampling depth and with little or no sample preparation. Additionally, the coupling inert gas, helium, which is utilized in the PA-FTIR system, can inhibit bacteria growth of bone by displacing oxygen. Therefore, we used this technique to study the undisturbed human cortical bone. It is found that photoacoustic mode (linear-scan, LS-PA-FTIR) can obtain basically similar spectra of bone as compared to the traditional transmission mode, but it seems more sensitive to amide III and ?2 carbonate bands. The ?3 phosphate band is indicative of detailed mineral structure and symmetry of native bone. The PA-FTIR depth profiling experiments on human cortical bone also indicate the influence of water on OH band and the cutting effects on amide I and mineral bands. Our results indicate that phosphate ion geometry appears less symmetric in its undisturbed state as detected by the PA-FTIR as compared to higher symmetry observed using transmission techniques on disturbed samples. Moreover, the PA-FTIR spectra indicate a band at 1747 cm-1 possibly resulting from Cdbnd O stretching of lipids, cholesterol esters, and triglycerides from the arteries. Comparison of the spectra in transverse and longitudinal cross-sections demonstrates that, the surface area of the longitudinal section bone appears to have more organic matrix exposed and with higher mineral stoichiometry.

  7. Cognitive conflict in human-automation interactions: a psychophysiological study.

    PubMed

    Dehais, Frédéric; Causse, Mickaël; Vachon, François; Tremblay, Sébastien

    2012-05-01

    The review of literature in sociology and distributed artificial intelligence reveals that the occurrence of conflict is a remarkable precursor to the disruption of multi-agent systems. The study of this concept could be applied to human factors concerns, as man-system conflict appears to provoke perseveration behavior and to degrade attentional abilities with a trend to excessive focus. Once entangled in such conflicts, the human operator will do anything to succeed in his current goal even if it jeopardizes the mission. In order to confirm these findings, an experimental setup, composed of a real unmanned ground vehicle, a ground station is developed. A scenario involving an authority conflict between the participants and the robot is proposed. Analysis of the effects of the conflict on the participants' cognition and arousal is assessed through heart-rate measurement (reflecting stress level) and eye-tracking techniques (index of attentional focus). Our results clearly show that the occurrence of the conflict leads to perseveration behavior and can induce higher heart rate as well as excessive attentional focus. These results are discussed in terms of task commitment issues and increased arousal. Moreover, our results suggest that individual differences may predict susceptibility to perseveration behavior. PMID:21992968

  8. Neural mechanisms of discourse comprehension: a human lesion study.

    PubMed

    Barbey, Aron K; Colom, Roberto; Grafman, Jordan

    2014-01-01

    Discourse comprehension is a hallmark of human social behaviour and refers to the act of interpreting a written or spoken message by constructing mental representations that integrate incoming language with prior knowledge and experience. Here, we report a human lesion study (n = 145) that investigates the neural mechanisms underlying discourse comprehension (measured by the Discourse Comprehension Test) and systematically examine its relation to a broad range of psychological factors, including psychometric intelligence (measured by the Wechsler Adult Intelligence Scale), emotional intelligence (measured by the Mayer, Salovey, Caruso Emotional Intelligence Test), and personality traits (measured by the Neuroticism-Extraversion-Openness Personality Inventory). Scores obtained from these factors were submitted to voxel-based lesion-symptom mapping to elucidate their neural substrates. Stepwise regression analyses revealed that working memory and extraversion reliably predict individual differences in discourse comprehension: higher working memory scores and lower extraversion levels predict better discourse comprehension performance. Lesion mapping results indicated that these convergent variables depend on a shared network of frontal and parietal regions, including white matter association tracts that bind these areas into a coordinated system. The observed findings motivate an integrative framework for understanding the neural foundations of discourse comprehension, suggesting that core elements of discourse processing emerge from a distributed network of brain regions that support specific competencies for executive and social function. PMID:24293267

  9. Neural mechanisms of discourse comprehension: a human lesion study

    PubMed Central

    Colom, Roberto; Grafman, Jordan

    2014-01-01

    Discourse comprehension is a hallmark of human social behaviour and refers to the act of interpreting a written or spoken message by constructing mental representations that integrate incoming language with prior knowledge and experience. Here, we report a human lesion study (n = 145) that investigates the neural mechanisms underlying discourse comprehension (measured by the Discourse Comprehension Test) and systematically examine its relation to a broad range of psychological factors, including psychometric intelligence (measured by the Wechsler Adult Intelligence Scale), emotional intelligence (measured by the Mayer, Salovey, Caruso Emotional Intelligence Test), and personality traits (measured by the Neuroticism-Extraversion-Openness Personality Inventory). Scores obtained from these factors were submitted to voxel-based lesion-symptom mapping to elucidate their neural substrates. Stepwise regression analyses revealed that working memory and extraversion reliably predict individual differences in discourse comprehension: higher working memory scores and lower extraversion levels predict better discourse comprehension performance. Lesion mapping results indicated that these convergent variables depend on a shared network of frontal and parietal regions, including white matter association tracts that bind these areas into a coordinated system. The observed findings motivate an integrative framework for understanding the neural foundations of discourse comprehension, suggesting that core elements of discourse processing emerge from a distributed network of brain regions that support specific competencies for executive and social function. PMID:24293267

  10. Use of human lung tissue for studies of structural changes associated with chronic ozone exposure: Opportunities and critical issues

    SciTech Connect

    Lippmann, M. [New York Univ. Medical Center, Tuxedo, NY (United States)

    1993-12-01

    Definitive information on the chronic effects of exposure to ozone (O{sub 3}) in humans is not available. There is a strong concern that ozone could produce chronic lung damage in humans on the basis that exposures are ubiquitous at levels that produce transient symptoms, function deficits, and lung inflammation in humans and chronic lung damage in laboratory animals. Both prospective and national population surveys suggest an association between chronic O{sub 3} exposure and reduced lung function, and a pilot investigation of autopsied lungs of accident victims in Los Angeles reported an unexpectedly high incidence of disease in the centriacinar region, the lung region known to receive the highest dose of inhaled O{sub 3}. This paper discusses the advantages and limitations of further studies of structural changes in human lung tissue in relation to chronic O{sub 3} exposure. The major advantages of such studies are that (a) measurable effects may be related to realistic chronic exposures, (b) the effects may be described quantitatively and compared directly to those obtained in chronic animal inhalation exposures, and (c) evidence for chronic effects may be obtained much more rapidly than in prospective studies. The major limitations are the difficulties in obtaining sufficient reliable information on residential history, physical activity out-of-doors, and smoking and other confounding exposures to lung irritants from next of kin, and limited availability of adequate air quality data for determining ambient concentrations at places of residence and/or outdoor exercise. The paper also discusses approaches to minimizing these limitations in the design of specific studies. 15 refs.

  11. A study in human attention to guide computational action recognition

    E-print Network

    Sinai, Sam

    2014-01-01

    Computer vision researchers have a lot to learn from the human visual system. We, as humans, are usually unaware of how enormously difficult it is to watch a scene and summarize its most important events in words. We only ...

  12. A comparative study of theoretical graph models for characterizing structural networks of human brain.

    PubMed

    Li, Xiaojin; Hu, Xintao; Jin, Changfeng; Han, Junwei; Liu, Tianming; Guo, Lei; Hao, Wei; Li, Lingjiang

    2013-01-01

    Previous studies have investigated both structural and functional brain networks via graph-theoretical methods. However, there is an important issue that has not been adequately discussed before: what is the optimal theoretical graph model for describing the structural networks of human brain? In this paper, we perform a comparative study to address this problem. Firstly, large-scale cortical regions of interest (ROIs) are localized by recently developed and validated brain reference system named Dense Individualized Common Connectivity-based Cortical Landmarks (DICCCOL) to address the limitations in the identification of the brain network ROIs in previous studies. Then, we construct structural brain networks based on diffusion tensor imaging (DTI) data. Afterwards, the global and local graph properties of the constructed structural brain networks are measured using the state-of-the-art graph analysis algorithms and tools and are further compared with seven popular theoretical graph models. In addition, we compare the topological properties between two graph models, namely, stickiness-index-based model (STICKY) and scale-free gene duplication model (SF-GD), that have higher similarity with the real structural brain networks in terms of global and local graph properties. Our experimental results suggest that among the seven theoretical graph models compared in this study, STICKY and SF-GD models have better performances in characterizing the structural human brain network. PMID:24369454

  13. Advancing Humanities Studies at Community, Technical, and Junior Colleges.

    ERIC Educational Resources Information Center

    Eisenberg, Diane U.; And Others

    The American Association of Community and Junior Colleges' (AACJC's) two-year Advancing the Humanities Project (AHP) has assisted selected community colleges in promoting the humanities on their campuses. Parts I and II of this report on the AHP present statements by Dale Parnell and Judith Jeffrey Howard about the AACJC's humanities initiatives…

  14. Teacher's Study Guide on the Biology of Human Populations: Africa.

    ERIC Educational Resources Information Center

    United Nations Educational, Scientific, and Cultural Organization, Paris (France).

    This teacher's guide is designed to give background information on current biological subjects not usually treated in student texts. The book is divided into five parts, each representing one of the following topics: (1) evolution of human populations; (2) environment of human populations; (3) dynamics of human populations; (4) reproduction in…

  15. Magnitude of Alloresponses to MHC Class I/II Expressing Human Cardiac Myocytes is Limited by their Intrinsic Ability to Process and Present Antigenic Peptides

    PubMed Central

    Sundstrom, J. Bruce; Jollow, Kimberley C.; Braud, Veronique; Villinger, Francois; McMichael, Andrew J.; Lawrence, E. Clinton; Ades, Edwin W.; Ansari, Aftab A.

    2003-01-01

    In this investigation we have explored the relationship between the weak allogenicity of cardiac myocytes and their capacity to present allo-antigens by examining the ability of a human cardiac myocyte cell line (W-1) to process and present nominal antigens. W-1 cells (HLA-A*0201 and HLA-DR ?1*0301) pulsed with the influenza A matrix 1 (58-66) peptide (M1) were able to serve as targets for the HLA-A*0201 restricted CTL line PG, specific for M1-peptide. However, PG-CTLs were unable to lyse W-1 target cells infected with a recombinant vaccinia virus expressing the M1 protein (M1-VAC). Pretreatment of these M1-VAC targets with IFN-? partially restored their ability to process and present the M1 peptide. However, parallel studies demonstrated that IFN-? pretreated W-1's could not process tetanus toxin (TT) or present the TT(830-843) peptide to HLA-DR3 restricted TT-primed T cells. Semi-quantitative RT-PCR measurements revealed significantly lower constitutive levels of expression for MHC class I, TAP-1/2, and LMP-2/7 genes in W-1s that could be elevated by pretreatment with IFN-? to values equal to or greater than those expressed in EBV-PBLs. However, mRNA levels for the genes encoding MHC class II, Ii, CIITA, and DMA/B were markedly lower in both untreated and IFN-? pretreated W-1s relative to EBV-PBLs. Furthermore, pulse-chase analysis of the corresponding genes revealed significantly lower protein levels and longer half-life expression in W-1s relative to EBV-PBLs. These results suggest that weak allogenicity of cardiac myocytes may be governed by their limited expression of MHC genes and gene products critical for antigen processing and presentation. PMID:14768954

  16. Density limit studies in the tokamak and the reversed-field pinch

    NASA Astrophysics Data System (ADS)

    Spizzo, G.; Pucella, G.; Tudisco, O.; Zuin, M.; Agostini, M.; Alessi, E.; Auriemma, F.; Bin, W.; Buratti, P.; Carraro, L.; Cavazzana, R.; Ciaccio, G.; De Masi, G.; Esposito, B.; Galperti, C.; Garavaglia, S.; Granucci, G.; Marinucci, M.; Marrelli, L.; Martines, E.; Mazzotta, C.; Minelli, D.; Moro, A.; Puiatti, M. E.; Scarin, P.; Sozzi, C.; Spolaore, M.; Schmitz, O.; Vianello, N.; White, R. B.

    2015-04-01

    The ITER scenarios and the project of DEMO involve stable operation above the Greenwald density, which justifies efforts to understand and overcome the density limit, this last observed as a disruptive termination of tokamak discharges and a thermal crash (with no disruption) of stellarator and reversed-field pinch (RFP) ones. Both in the tokamak and the RFP, new findings show that the high density limit is not governed by a unique, theoretically well-determined physical phenomenon, but by a combination of complex mechanisms involving two-fluid effects, electrostatic plasma response to magnetic islands and plasma–wall interaction. In this paper we will show new evidence challenging the traditional picture of the ‘Greenwald limit’, in particular with reference to the role of thermal instabilities and the edge radial electric field Er in the development of this limit.

  17. Visual disruption using the thermal lensing effect in the human eye: pilot study

    NASA Astrophysics Data System (ADS)

    Towle, Erica L.; Garcia, Paul V.; Smith, Peter A.; Thomas, Robert J.; Dunn, Andrew K.; Welch, Ashley J.; Foutch, Brian K.

    2012-10-01

    At select wavelengths, near infrared (IR) light is absorbed in the preretinal media of the eye. This produces small transient increases in temperature that temporarily alter the local index of refraction. If the IR exposure is sufficiently high, a momentary reduction in the focusing power of the eye can be induced through an effect known as thermal lensing. Fundamental optical interaction and safety aspects of this phenomenon have been demonstrated previously in animal and artificial eye models. However, whether the effect will induce an observable visual change in human subjects has not been explored. Here, results of a pilot study are shown where eight human subjects were exposed to an IR laser at levels that were below the safe exposure limit. The exposures did induce a transient visual distortion if sufficiently high levels were used. While the description of the visual change varied between subjects, this experiment was able to determine a general guideline for power needed to induce significant effects in human subjects.

  18. Life Sciences Division and Center for Human Genome Studies 1994

    SciTech Connect

    Cram, L.S.; Stafford, C. [comp.

    1995-09-01

    This report summarizes the research and development activities of the Los Alamos National Laboratory`s Life Sciences Division and the biological aspects of the Center for Human Genome Studies for the calendar year 1994. The technical portion of the report is divided into two parts, (1) selected research highlights and (2) research projects and accomplishments. The research highlights provide a more detailed description of a select set of projects. A technical description of all projects is presented in sufficient detail so that the informed reader will be able to assess the scope and significance of each project. Summaries useful to the casual reader desiring general information have been prepared by the group leaders and appear in each group overview. Investigators on the staff of the Life Sciences Division will be pleased to provide further information.

  19. A study of the effect of posted speed limits on traffic speeds

    E-print Network

    Rowan, Neilon Joyce

    1959-01-01

    was ona of wide-spread disrespect mnong drivers for speed limits and for the police who enforced tham. Tha cause of this condition was attributed to the invariable setting of speed limits by local officials at 20 or 25 miles per hour, regardless..., Ru R, Ru 8, R 8, R Enoscope Enoscope Enoscope Enoscopc Eroscope Enoscope Enoscope. Enoscope Enoscope Enoscupe Enoscope Enoscope Enoscope Radar Enoscope Radar Radar Enoscope Enoscope Enoscope Enoscope Radar Enoscope Radar...

  20. T Cell Expansion Is the Limiting Factor of Virus Control in Mice with Attenuated TCR Signaling: Implications for Human Immunodeficiency.

    PubMed

    Hillen, Kristina M; Gather, Ruth; Enders, Anselm; Pircher, Hanspeter; Aichele, Peter; Fisch, Paul; Blumenthal, Britta; Schamel, Wolfgang W; Straub, Tobias; Goodnow, Christopher C; Ehl, Stephan

    2015-03-15

    Defining the minimal thresholds for effective antiviral T cell immunity is important for clinical decisions in immunodeficient patients. TCR signaling is critical for T cell development, activation, and effector functions. In this article, we analyzed which of these TCR-mediated processes is limiting for antiviral immunity in a mouse strain with reduced expression of SLP-76 (twp mice). Despite severe T cell activation defects in vitro, twp mice generated a normal proportion of antiviral effector T cells postinfection with lymphocytic choriomeningitis virus (LCMV). Twp CD8(+) T cells showed impaired polyfunctional cytokine production, whereas cytotoxicity as the crucial antiviral effector function for LCMV control was normal. The main limiting factor in the antiviral response of twp mice was impaired T cell proliferation and survival, leading to a 5- to 10-fold reduction of antiviral T cells at the peak of the immune response. This was still sufficient to control infection with the LCMV Armstrong strain, but the more rapidly replicating LCMV-WE induced T cell exhaustion and viral persistence. Thus, under conditions of impaired TCR signaling, reduced T cell expansion was the limiting factor in antiviral immunity. These findings have implications for understanding antiviral immunity in patients with T cell deficiencies. PMID:25672755

  1. 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

  2. [Possibilities and limitations of fibroblast cultures in the study of animal aging].

    PubMed

    Van Gansen, P; Van Lerberghe, N

    1987-01-01

    INTRODUCTION. Aging--the effect of time--occurs in every living organism. Senescence is the last period of the lifespan, leading to death. It happens in all animals, with the exception of a few didermic species (Hydras) having a stock of embryonic cells and being immortal. The causes of animal senescence are badly known. They depend both on genetic characters (maximal lifespan of a species) and on medium factors (mean expectation of life of the animals of a species). Animal senescence could depend on cell aging: 1) by senescence and death of the differentiated cells, 2) by modified proliferation and differentiation of the stem cells of differentiated tissues, 3) by alterations in the extracellular matrices, 4) by interactions between factors 1) 2) and 3) in each tissue, 5) by interactions between the several tissues of an organism. This complexity badly impedes the experimental study of animal senescence. Normal mammal cells are aging when they are cultivated (in vitro ageing): their phenotype varies and depends on the cell generation (in vitro differentiation); the last cell-generation doesn't divide anymore and declines until death of the culture (in vitro senescence). Analysis of these artificial but well controlled systems allows an experimental approach of the proliferation, differentiation, senescence and death of the cells and of the extracellular matrix functions. Present literature upon in vitro aging of cultivated human cells is essentially made of papers where proliferation and differentiation characteristics are compared between early ("young") and late ("old") cell-generations of the cultures. FIBROBLASTIC CELLS OF THE MOUSE SKIN. This cell type has been studied in our laboratory, using different systems: 1) Primary cultures isolated from peeled skins of 19 day old mouse embryos, 2) Mouse dermis analyzed in the animals, 3) Cultivated explants of skins, 4) Serial sub-cultures of fibroblasts isolated from these explants, 5) Cells cultivated comparably on plane substrates (glass, plastic, collagen films) and on tridimensional matrices (collagen fibres). Systems 2), 3), 4) and 5) have been obtained either from 19 day old embryos or from 6 groups of animals of different ages (from 1/2 till 25 month). In primary cultures (system 1) all the cell generations have been analyzed, including the last one until death of the culture. We have shown that many characters are varying with cell-generation: cell form and cell mass, rate of DNA replication and cell division, rate of RNA transcription, nature of the accumulated and of the synthetized proteins, organization of the cytoskeletal elements, organization of the extracellular matrix, type of cell death.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3079271

  3. A study on the effects of artifacts on fatigue limit of ductile Cast Iron with ferritic structure

    Microsoft Academic Search

    Jinhak Kim; Mingun Kim

    2000-01-01

    In this study, fatigue tests were performed to examine the effects of micro drill hole on fatigue limit of as cast and austempered\\u000a ductile cast iron (ADI) using the rotary bending fatigue tester. As results, micro drill holes (diameter?0.4mm) did not influence the fatigue limit of ADI, compared to annealed ductile cast iron; the critical defect size of crack initiation,

  4. The Women's Studies Program and the Human Rights Institute present a film screening and panel discussion

    E-print Network

    Holsinger, Kent

    The Women's Studies Program and the Human Rights Institute present a film screening and panel is sponsored by: the Women's Studies Program, the Human Rights Institute, the Institute for Puerto Rican Society Coalition on Human Rights and Constitutional Law, explores the reality that for some LGBTI

  5. The Women's Studies Program and the Human Rights Institute present a film screening and panel discussion

    E-print Network

    Alpay, S. Pamir

    The Women's Studies Program and the Human Rights Institute present a film screening and panel is sponsored by: the Women's Studies Program, the Human Rights Institute, the Institute for Puerto Rican with the Ugandan Civil Society Coalition on Human Rights and Constitutional Law, explores the reality that for some

  6. TUFTS UNIVERSITY Eliot-Pearson Department of Child Study and Human Development

    E-print Network

    Dennett, Daniel

    TUFTS UNIVERSITY Eliot-Pearson Department of Child Study and Human Development ASSISTANT PROFESSOR POSITION IN DEVELOPMENTAL METHODOLOGY THE ELIOT-PEARSON DEPARTMENT OF CHILD STUDY AND HUMAN DEVELOPMENT or in one of the fields associated with developmental science (e.g., human development, child development

  7. Improved Imaged-derived Input Function for Study of Human Brain FDG-PET

    E-print Network

    Renaut, Rosemary

    Improved Imaged-derived Input Function for Study of Human Brain FDG-PET Hongbin Guo, Rosemary Improved Imaged-derived Input Function for Study of Human Brain FDG-PET I. INTRODUCTION Positron emission-invasive image-derived input function is validated for human [18 F]-fluoro deoxyglucose (FDG) positron emission

  8. What Can We Learn from Biological Vision Studies for Human Motion Segmentation?

    Microsoft Academic Search

    Cheng Chen; Guoliang Fan

    2006-01-01

    We review recent biological vision studies that are related to human motion segmentation. Our goal is to develop a practically plau- sible computational framework that is guided by recent cognitive and psychological studies on the human visual system for the segmentation of human body in a video sequence. Specically , we discuss the roles and interactions of bottom-up and top-down

  9. Development and validation of a highly sensitive LC-MS/MS method for quantitation of dexlansoprazole in human plasma: application to a human pharmacokinetic study.

    PubMed

    Hotha, Kishore Kumar; Vijaya Bharathi, D; Jagadeesh, B; Ravindranath, L K; Jaya Veera, K N; Venkateswarulu, V

    2012-02-01

    A highly sensitive, specific and simple LC-MS/MS method was developed for the simultaneous estimation of dexlansoprazole (DEX) with 50 ?L of human plasma using omeprazole as an internal standard (IS). The API-4000 LC-MS/MS was operated under multiple reaction-monitoring mode using electrospray ionization. A simple liquid-liquid extraction process was used to extract DEX and IS from human plasma. The total run time was 2.00 min and the elution of DEX and IS occurred at 1.20 min. This was achieved with a mobile phase consisting of 0.2% ammonia-acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on an X-terra RP 18 (50 × 4.6 mm, 5 µm) column. The developed method was validated in human plasma with a lower limit of quantitation of 2 ng/mL for DEX. A linear response function was established for the range of concentrations 2.00-2500.0 ng/mL (r > 0.998) for DEX. The intra- and inter-day precision values for DEX met the acceptance criteria as per FDA guidelines. DEX was stable in the battery of stability studies, viz. bench-top, auto-sampler and freeze-thaw cycles. The developed assay method was applied to an oral bioequivalence study in humans. PMID:21618562

  10. Theranostic Studies of Human Sodium Iodide Symporter Imaging and Therapy Using 188Re: A Human Glioma Study in Mice

    PubMed Central

    Guo, Rui; Zhang, M.; Xi, Yun; Ma, Yufei; Liang, Sheng; Shi, Shuo; Miao, Ying; Li, Biao

    2014-01-01

    Objective To investigate the role of 188Re in human sodium iodide symporter (hNIS) theranostic gene-mediated human glioma imaging and therapy in model mice. Methods The human glioma cell line U87 was transfected with recombinant lentivirus encoding the hNIS gene under the control of cytomegalovirus promoter (U87-hNIS). The uptake and efflux of 188Re were determined after incubating the cells with 188Re. 188Re uptake experiments in the presence of various concentrations of sodium perchlorate were carried out. In vitro cell killing tests with 188Re were performed. U87-hNIS mediated 188Re distribution, imaging and therapy in nude mice were also tested. Results U87-hNIS cell line was successfully established. The uptake of 188Re in U87-hNIS cells increased up to 26-fold compared to control cells, but was released rapidly with a half-life of approximately 4 minutes. Sodium perchlorate reduced hNIS-mediated 188Re uptake to levels of control cell lines. U87-hNIS cells were selectively killed following exposure to 188Re, with a survival of 21.4%, while control cells had a survival of 92.1%. Unlike in vitro studies, U87-hNIS tumor showed a markedly increased 188Re retention even 48 hours after 188Re injection. In the therapy study, there was a significant difference in tumor size between U87-hNIS mice (317±67 mm3) and control mice (861±153 mm3) treated with 188Re for 4 weeks (P<0.01). Conclusion The results indicate that inserting the hNIS gene into U87 cells is sufficient to induce specific 188Re uptake, which has a cell killing effect both in vitro and in vivo. Moreover, our study, based on the function of hNIS as a theranostic gene allowing noninvasive imaging of hNIS expression by 188Re scintigraphy, provides detailed characterization of in vivo vector biodistribution and level, localization, essential prerequisites for precise planning and monitoring of clinical gene therapy that aims to individualize gene therapy concept. PMID:25000403

  11. Alaska Humans Factors Safety Study: The Southern Coastal Area

    NASA Technical Reports Server (NTRS)

    Chappell, Sheryl L.; Reynard, William (Technical Monitor)

    1995-01-01

    At the request of the Alaska Air Carriers Association, researchers from the NASA Aviation Safety Reporting System, at NASA Ames Research Center, conducted a study on aspects of safety in Alaskan Part 135 air taxi operations. An interview form on human factors safety issues was created by a representative team from the FAA-Alaska, NTSB-Alaska, NASA-ASRS, and representatives of the Alaska Air Carriers Association which was subsequently used in the interviews of pilots and managers. Because of the climate and operational differences, the study was broken into two geographical areas, the southern coastal areas and the northern portion of the state. This presentation addresses the southern coastal areas, specifically: Anchorage, Dillingham, King Salmon, Kodiak, Cold Bay, Juneau, and Ketchikan. The interview questions dealt with many of the potential pressures on pilots and managers associated with the daily air taxi operations in Alaska. The impact of the environmental factors such as the lack of available communication, navigation and weather information systems was evaluated. The results of this study will be used by government and industry working in Alaska. These findings will contribute important information on specific Alaska safety issues for eventual incorporation into training materials and policies that will help to assure the safe conduct of air taxi flights in Alaska.

  12. Alaska Humans Factors Safety Study: The Northern Area

    NASA Technical Reports Server (NTRS)

    Connell, Linda; Reynard, William (Technical Monitor)

    1995-01-01

    At the request of the Alaska Air Carriers Association, researchers from the NASA Aviation Safety Reporting System, at NASA Ames Research Center, conducted a study on aspects of safety in Alaskan Part 135 air taxi operations. An interview form on human factors safety issues was created by a representative team from the FAA-Alaska, NTSB-Alaska, NASAASRS, and representatives of the Alaska Air Carriers Association which was subsequently used in the interviews of pilots and managers. Because of the climate and operational differences, the study was broken into two geographical areas, the southern coastal areas and the northern portion of the state. This presentation addresses the northern area, specifically: Bethel, Fairbanks, Nome, Kotzebue, and Barrow. The interview questions dealt with many of the potential pressures on pilots and managers associated with the daily air taxi operations in Alaska. The impact of the environmental factors such as the lack of available communication, navigation and weather information systems was evaluated. The results of this study will be used by government and industry working in Alaska. These findings will contribute important information on specific Alaska safety issues for eventual incorporation into training materials and policies that will help to assure the safe conduct of air taxi flights in Alaska.

  13. A Human Full-Skin Culture System for Interventional Studies

    PubMed Central

    Steinstraesser, Lars; Rittig, Andrea; Gevers, Kai; Sorkin, Michael; Hirsch, Tobias; Kesting, Marco; Sand, Michael; Al-Benna, Sammy; Langer, Stefan; Steinau, Hans-Ulrich; Jacobsen, Frank

    2009-01-01

    Objective: Novel approaches to bridge the gap between clinical studies and experimental basic research of skin physiology are urgently needed. The aim of this study was to develop an effective surrogate model in which ex vivo full-thickness organ culture experiments may be performed. Methods: Human full skin from patients was placed into a stainless steel chamber and cultured at an air-liquid interphase for 4 weeks. Samples were evaluated every week by HE-staining and immunohistochemical characterization. Epidermal gene transfer kinetics was performed as an interventional study. Results: This ex vivo chamber model maintained the physiologic and histologic properties of the skin explants for 4 weeks. This indicated the model's acceptable ex vivo physiologic validity. No epidermolysis was observed, and both basal lamina and blood vessels were detected within all tissue samples. Transgene expression was demonstrated to be time dependent. Conclusion: This model chamber presents a convenient, easy-to-use, and robust model in which ex vivo full-thickness organ culture experiments may be performed. PMID:19198642

  14. Binding of amifostine to human serum albumin: A biophysical study.

    PubMed

    Sun, Yifu; Wu, Han; Zhao, Guoqing; Shi, Ying

    2015-02-01

    The aim of this present work is to investigate the interaction between amifostine and human serum albumin (HSA) in simulated physiological conditions by spectroscopic methods to reveal potential toxic effects of the drug. The results reflected that amifostine caused fluorescence quenching of HSA through a static quenching process, which was further confirmed by the electrochemical experiments. The binding constants at 290, 297 and 304?K were obtained as 2.53?×?10(5) /M, 8.13?×?10(4) /M and 3.59?×?10(4) /M, respectively. There may be one binding site of amifostine on HSA. The thermodynamic parameters indicated that the interaction between amifostine and HSA was driven mainly by hydrogen bonding and electrostatic forces. Synchronous fluorescence spectra, circular dichroism and Fourier transform infrared spectroscopy results showed amifostine binding slightly changed the conformation of HSA with secondary structural content changes. Förster resonance energy transfer study revealed high possibility of energy transfer with amifostine-Trp-214 distance of 3.48?nm. The results of the present study may provide valuable information for studying the distribution, toxicological and pharmacological mechanisms of amifostine in vivo. Copyright © 2014 John Wiley & Sons, Ltd. PMID:24962599

  15. Keyhole limpet haemocyanin - a model antigen for human immunotoxicological studies.

    PubMed

    Swaminathan, Ashwin; Lucas, Robyn M; Dear, Keith; McMichael, Anthony J

    2014-11-01

    Immunization with a T-cell dependent antigen has been promoted as a reliable and sensitive tool for assessing the influence of putative immunotoxic exposures or agents on immune function. Keyhole limpet haemocyanin (KLH) is a very large, copper-containing protein molecule derived from the haemolymph of the inedible mollusc, Megathura crenulata. KLH is a highly immunogenic T-cell dependent antigen that is used increasingly in immunotoxicological studies, particularly in those involving animals. This report systematically reviews the human clinical studies that have used trans-cutaneous KLH immunization for assessment of the influence of various physiological and disease states and exposures on immune function over the last 20 years (1994-2013). These studies varied in their immunization protocols, formulation of KLH, dose, site and route of administration and immunoassay platforms developed to assess KLH-specific responses. KLH immunization has been well tolerated with only mild to moderate adverse effects reported. Though very promising as a model antigen candidate in immunotoxicology research, more work on standardizing immunization and immunoassay protocols is required. PMID:24833186

  16. Apoptosis induced by human cytomegalovirus infection can be enhanced by cytokines to limit the spread of virus.

    PubMed

    Chaudhuri, A R; St Jeor, S; Maciejewski, J P

    1999-07-01

    Fas-mediated apoptosis is one of the immune effector pathways leading to the elimination of virus infected cells. In vivo, apoptotic signals are delivered to virus infected cells by Fas-L and other cytokines secreted by specific T lymphocytes. Cellular immune response appears to be essential in prevention of human cytomegalovirus (HCMV) disease. We have hypothesized that HCMV infection might directly or indirectly result in upregulation of Fas receptor and in the presence of Fas ligand, lead to apoptosis of infected cells. We show that infection of human fibroblasts with HCMV is associated with upmodulation of Fas-R process that could be further potentiated by interferon (IFN-gamma). Using DNA agarose gel electrophoresis, terminal dideoxy transferase reaction, and annexin assay, we demonstrated that in a productive HCMV infection of human fibroblasts, loss of cell viability was not only due to virus-mediated cell lysis but also to due to apoptosis. IFN-gamma induced relative HCMV resistance and prevented loss in cell viability. In contrast, anti-Fas monoclonal antibody CH11, serving as Fas agonist, resulted in an accelerated loss in viability of infected cells. IFN-gamma in combination with CH11 further increased the rate of apoptosis and compared to cultures with CH11 only, this effect was not restricted to only infected cells. While IFN-gamma did not affect the number of cells expressing immediate early antigen, it markedly reduced structural protein expression. IFN-gamma in combination with CH11, decreased the expression of HCMV matrix protein pp65, reduced the amount of HCMV DNA and infectious virus produced. Our results are consistent with the theory that cells infected with HCMV can be eliminated by immune effector cells via Fas-mediated apoptosis. IFN-gamma, in addition to its intrinsic antiviral activity, primes HCMV infected cells to the action of Fas ligand and Fas-mediated apoptosis. PMID:10390195

  17. How to measure thermal effects of personal cooling systems: human, thermal manikin and human simulator study.

    PubMed

    Bogerd, N; Psikuta, A; Daanen, H A M; Rossi, R M

    2010-09-01

    Thermal effects, such as cooling power and thermophysiological responses initiated upon application of a personal cooling system, can be assessed with (i) humans, (ii) a thermal manikin and (iii) a thermophysiological human simulator. In order to compare these methods, a cooling shirt (mild cooling) and an ice vest (strong cooling) were measured using human participants and a thermal manikin. Under all conditions, cooling was provided for 45 min, while resting at a room temperature of 24.6-25.0 degrees C and a relative humidity of 22-24%. Subsequently, the thermophysiological human simulator was used under the same conditions to provide data on thermophysiological responses such as skin and rectal temperatures. The cooling power determined using the thermal manikin was 2 times higher for the cooling shirt and 1.5 times higher for the ice vest compared to the cooling power determined using human participants. For the thermophysiological human simulator, the cooling power of the cooling shirt was similar to that obtained using human participants. However, it was 2 times lower for the ice vest when using the thermophysiological human simulator. The thermophysiological human simulator is shown to be a useful tool to predict thermophysiological responses, especially upon application of mild cooling intensity. However, the thermophysiological human simulator needs to be further improved for strong cooling intensities under heterogeneous conditions. PMID:20664163

  18. 77 FR 12310 - Drugs for Human Use; Drug Efficacy Study Implementation; Prescription Drugs That Contained...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-29

    ...DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-1978-N-0441] (formerly 78N-0324); DESI 10392] Drugs for Human Use; Drug Efficacy Study Implementation; Prescription...

  19. Communication is the study of human symbolic behavior. Communication courses train students to communicate

    E-print Network

    Saldin, Dilano

    Communication is the study of human symbolic behavior. Communication courses train students to communicate more effectively; to understand and use various formats of communication including oral, written, nonverbal and visual; and to analyze human communication patterns in educational, interpersonal, inter

  20. TRANSLATIONAL STEM CELL STUDIES Consensus Guidance for Banking and Supply of Human

    E-print Network

    Zandstra, Peter W.

    TRANSLATIONAL STEM CELL STUDIES Consensus Guidance for Banking and Supply of Human Embryonic Stem Cell Lines for Research Purposes The International Stem Cell Banking Initiative # Humana Press 2009 Keywords Human embryonic stem cells . Cell banking . Standardisation . Microbiological testing

  1. A numerical study of the small dispersion limit of the Korteweg-de Vries equation and asymptotic solutions

    NASA Astrophysics Data System (ADS)

    Grava, T.; Klein, C.

    2012-12-01

    We study numerically the small dispersion limit for the Korteweg-de Vries (KdV) equation ut+6uux+?2uxxx=0 for ??1 and give a quantitative comparison of the numerical solution with various asymptotic formulae for small ? in the whole (x,t)-plane. The matching of the asymptotic solutions is studied numerically.

  2. A study of a program for limited English proficient (LEP) students in the St Thomas\\/St John School District

    Microsoft Academic Search

    Joyce M. Thomas

    1992-01-01

    This study examined an alternative education program on the elementary school level named Project Up-grade (PUG). The influx of limited English proficient students entering the Virgin Islands public schools from Eastern Caribbean countries created the need to provide them with an adequate education. The purposes of the study were: (1) to identify reading and math levels of PUG students who

  3. 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.

  4. 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.

  5. A limited upstream region of the human sucrase-isomaltase gene confers glucose-regulated expression on a heterologous gene.

    PubMed Central

    Rodolosse, A; Chantret, I; Lacasa, M; Chevalier, G; Zweibaum, A; Swallow, D; Rousset, M

    1996-01-01

    We have previously shown that glucose can exert a repressive effect on the transcription of the sucrase-isomaltase (SI) gene in the differentiated enterocyte-like human colon carcinoma cell lines HT-29 and Caco-2. To characterize the region through which glucose exerts this effect, three different-length fragments of the 5'-flanking region of the human SI gene were linked to the reporter gene luciferase in an episomal vector carrying a hygromycin resistance gene. These fragments were used for transfection into a clone of the Caco-2 cell line, PF11, which has high glucose consumption and only expresses SI at high levels when cultured in the presence of a low supply of glucose. By using the stably transformed PF11 cells grown either in standard high glucose (25 mM) or in low glucose (1 mM) it was possible to show that the smallest fragment of the SI promoter, extending from bases -370 to +30, contains all the information required for the glucose repression of the reporter gene luciferase. PMID:8670122

  6. Limited Applicability of GW9662 to Elucidate PPAR?-Mediated Fatty Acid Effects in Primary Human T-Helper Cells

    PubMed Central

    Jaudszus, Anke; Gruen, Michael; Roth, Alexander; Jahreis, Gerhard

    2014-01-01

    Synthetic antagonists of the nuclear receptor PPAR? such as GW9662 are widely used to elucidate receptor-mediated ligand effects. In addition and complementary to recent work, we examined whether GW9662 is suitable to serve for mechanistic investigation in T-helper cells. Human peripheral blood mononuclear cells (PBMC) were preincubated with increasing concentrations of GW9662 (0, 0.4, 2, and 10??mol/L) 30?min before adding the c9,t11-isomer of conjugated linoleic acid (c9,t11-CLA) as representative of PPAR?-activating fatty acids with immunomodulatory properties. Corresponding cultures were incubated with GW9662 in the absence of the fatty acid. After 19?h, cells were mitogen stimulated for further 5?h. Subsequently, intracellular IL-2 was measured in CD3+CD4+ lymphocytes by means of flow cytometry. 100??mol/L c9,t11-CLA reduced the number of T-helper cells expressing IL-2 by 68%. GW9662 failed to abrogate this fatty acid effect, likely due to the fact that the compound exerted an own inhibitory effect on IL-2 production. Moreover, GW9662 dose-dependently induced cell death in human leukocytes. These results suggest that application of GW9662 is not conducive in this experimental setting. PMID:25054074

  7. Synchrotron Study of Strontium in Modern and Ancient Human Bones

    NASA Astrophysics Data System (ADS)

    Pingitore, N. E.; Cruz-Jimenez, G.

    2001-05-01

    Archaeologists use the strontium in human bone to reconstruct diet and migration in ancient populations. Because mammals discriminate against strontium relative to calcium, carnivores show lower bone Sr/Ca ratios than herbivores. Thus, in a single population, bone Sr/Ca ratios can discriminate a meat-rich from a vegetarian diet. Also, the ratio of 87-Sr to 86-Sr in soils varies with the underlying geology; incorporated into the food chain, this local signature becomes embedded in our bones. The Sr isotopic ratio in the bones of individuals or populations which migrate to a different geologic terrane will gradually change as bone remodels. In contrast, the isotopic ratio of tooth enamel is fixed at an early age and is not altered later in life. Addition of Sr to bone during post-mortem residence in moist soil or sediment compromises application of the Sr/Ca or Sr-isotope techniques. If this post-mortem Sr resides in a different atomic environment than the Sr deposited in vivo, x-ray absorption spectroscopy could allow us to distinguish pristine from contaminated, and thus unreliable, samples. Initial examination of a suite of modern and ancient human and animal bones by extended x-ray absorption fine structure (EXAFS) showed no obvious differences between the fresh and buried materials. We note, with obvious concern, that the actual location of Sr in modern bone is controversial: there is evidence both that Sr substitutes for Ca and that Sr is sorbed on the surfaces of bone crystallites. Additional material is being studied.

  8. Characterizing human retinotopic mapping with conformal geometry: a preliminary study

    NASA Astrophysics Data System (ADS)

    Ta, Duyan; Shi, Jie; Barton, Brian; Brewer, Alyssa; Lu, Zhong-Lin; Wang, Yalin

    2014-03-01

    Functional magnetic resonance imaging (fMRI) has been widely used to measure the retinotopic organization of early visual cortex in the human brain. Previous studies have identified multiple visual field maps (VFMs) based on statistical analysis of fMRI signals, but the resulting geometry has not been fully characterized with mathematical models. Here we test whether VFMs V1 and V2 obey the least restrictive of all geometric mappings; that is, whether they are anglepreserving and therefore maintain conformal mapping. We measured retinotopic organization in individual subjects using standard traveling-wave fMRI methods. Visual stimuli consisted of black and white, drifting checkerboards comprising rotating wedges and expanding rings to measure the cortical representations of polar angle and eccentricity, respectively. These representations were then projected onto a 3D cortical mesh of each hemisphere. By generating a mapped unit disk that is conformal of the VFMs using spherical stereographic projection and computing the parameterized coordinates of the eccentricity and polar angle gradients, we computed Beltrami coefficients to check whether the mapping from the visual field to the V1 and V2 cortical representations is conformal. We find that V1 and V2 exhibit local conformality. Our analysis of the Beltrami coefficient shows that selected regions of V1 and V2 that contain reasonably smooth eccentricity and polar angle gradients do show significant local conformality, warranting further investigation of this approach for analysis of early and higher visual cortex. These results suggest that such a mathematical model can be used to characterize the early VFMs in human visual cortex.

  9. A study of the feasibility of limited shelters for physical education

    E-print Network

    Wagner, William Grant

    1963-01-01

    regarding its degree of in- fluence on human comfort. Only in recent years has a unit of measure been defined that rates the thermal properties of a particular combina- t Ion of clothing. This unit of measure, called a "clo" was defined by Gagge, Burton...

  10. Studies of the Transferrin Receptor on both Human Reticulocytes and Nucleated Human Cells in Culture

    PubMed Central

    Frazier, Janet L.; Caskey, Jennifer H.; Yoffe, Mark; Seligman, Paul A.

    1982-01-01

    The transferrin receptor, present on reticulocytes and nucleated cells in tissue culture, has been measured with both immunoassay techniques and transferrin binding studies. The total cellular immunoreactive receptor is rapidly lost from erythrocytes during the process of reticulocyte maturation (from as many as 400,000 molecules to <20,000 molecules/reticulocyte). This event parallels the loss of cell surface transferrin binding sites and RNA content, and correlates with previous studies that have measured the decline in hemoglobin synthesis. Nonhemoglobin-producing normal human fibroblasts, which appear to have a much lower iron requirement than reticulocytes, contain similar numbers of immunoreactive receptors per cell (400,000 receptor molecules), when in an active state of proliferation. Although receptor density on fibroblasts is directly related to cell proliferation, our studies demonstrate that nonproliferating fibroblasts still retain significant numbers of immunoreactive receptors (150,000 molecules/cell) and transferrin binding sites. Since additional studies indicate that proliferating cells have increased iron uptake, a simple hypothesis would predict that the parallel increase in transferrin binding sites and total cellular immunoreactive receptor associated with proliferation is related to an increased cellular iron requirement. However, the number of immunoreactive receptor molecules and transferrin binding sites is not changed when cells are grown in iron-deficient media, or in media with added transferrin-iron. This result and the lack of marked differences in receptor number on both hemoglobin-producing and nonhemoglobin-producing cells indicate that other factors besides receptor density play major roles in the regulation of cellular iron uptake, retention, and loss. Images PMID:6804495

  11. Modeling aspects of human memory for scientific study.

    SciTech Connect

    Caudell, Thomas P. (University of New Mexico); Watson, Patrick (University of Illinois - Champaign-Urbana Beckman Institute); McDaniel, Mark A. (Washington University); Eichenbaum, Howard B. (Boston University); Cohen, Neal J. (University of Illinois - Champaign-Urbana Beckman Institute); Vineyard, Craig Michael; Taylor, Shawn Ellis; Bernard, Michael Lewis; Morrow, James Dan; Verzi, Stephen J.

    2009-10-01

    Working with leading experts in the field of cognitive neuroscience and computational intelligence, SNL has developed a computational architecture that represents neurocognitive mechanisms associated with how humans remember experiences in their past. The architecture represents how knowledge is organized and updated through information from individual experiences (episodes) via the cortical-hippocampal declarative memory system. We compared the simulated behavioral characteristics with those of humans measured under well established experimental standards, controlling for unmodeled aspects of human processing, such as perception. We used this knowledge to create robust simulations of & human memory behaviors that should help move the scientific community closer to understanding how humans remember information. These behaviors were experimentally validated against actual human subjects, which was published. An important outcome of the validation process will be the joining of specific experimental testing procedures from the field of neuroscience with computational representations from the field of cognitive modeling and simulation.

  12. Human factors and medication errors: a case study.

    PubMed

    Gluyas, Heather; Morrison, Paul

    2014-12-15

    Human beings are error prone. A significant component of human error is flaws inherent in human cognitive processes, which are exacerbated by situations in which the individual making the error is distracted, stressed or overloaded, or does not have sufficient knowledge to undertake an action correctly. The scientific discipline of human factors deals with environmental, organisational and job factors, as well as human and individual characteristics, which influence behaviour at work in a way that potentially gives rise to human error. This article discusses how cognitive processing is related to medication errors. The case of a coronial inquest into the death of a nursing home resident is used to highlight the way people think and process information, and how such thinking and processing may lead to medication errors. PMID:25492790

  13. Indications, limitations and pitfalls in the determination of human growth hormone, IGF-I and their binding proteins.

    PubMed

    Laron, Zvi; Bidlingmaier, Martin; Strasburger, Christian Joseph

    2007-10-01

    Deviations from normal growth are a major part of Pediatric Endocrinology. The principal post-natal growth promoting hormones are pituitary growth hormone (GH) and insulin-like growth factor-I (IGF-I). The GH-IGF-I axis has many links and portals, the secrets of which have been disclosed in recent years by scientific advances (genetic and biochemical technologies). In this article, we describe the players in the GH axis, the auxological indications for performing GH evaluation tests, enumerate the most frequently used tests and discuss the laboratory tests which help to define the pathological entities along the GH axis. Emphasis is put on the limitations of methods used, lack of standards, norms and the possible errors in diagnosis and treatment indications that may evolve. As both hGH and IGF-I immunoassay measurements represent cornerstones in the diagnosis and monitoring of the different etiological entities presenting with short stature, clinicians must have an insight into the variability and limitations of these analytical techniques. Interpretation of biochemical results without proper reference data and without knowledge of the assay-inherent characteristics inevitably leads to misdiagnosis, unnecessary further testing and treatment and imposes a burden on the child, family and the health care system. PMID:18167466

  14. Placental Glucose Transfer: A Human In Vivo Study

    PubMed Central

    Holme, Ane M.; Roland, Marie Cecilie P.; Lorentzen, Bjørg; Michelsen, Trond M.; Henriksen, Tore

    2015-01-01

    Objectives The placental transfer of nutrients is influenced by maternal metabolic state, placenta function and fetal demands. Human in vivo studies of this interplay are scarce and challenging. We aimed to establish a method to study placental nutrient transfer in humans. Focusing on glucose, we tested a hypothesis that maternal glucose concentrations and uteroplacental arterio-venous difference (reflecting maternal supply) determines the fetal venous-arterial glucose difference (reflecting fetal consumption). Methods Cross-sectional in vivo study of 40 healthy women with uncomplicated term pregnancies undergoing planned caesarean section. Glucose and insulin were measured in plasma from maternal and fetal sides of the placenta, at the incoming (radial artery and umbilical vein) and outgoing vessels (uterine vein and umbilical artery). Results There were significant mean (SD) uteroplacental arterio-venous 0.29 (0.23) mmol/L and fetal venous-arterial 0.38 (0.31) mmol/L glucose differences. The transplacental maternal-fetal glucose gradient was 1.22 (0.42) mmol/L. The maternal arterial glucose concentration was correlated to the fetal venous glucose concentration (r = 0.86, p<0.001), but not to the fetal venous-arterial glucose difference. The uteroplacental arterio-venous glucose difference was neither correlated to the level of glucose in the umbilical vein, nor fetal venous-arterial glucose difference. The maternal-fetal gradient was correlated to fetal venous-arterial glucose difference (r = 0.8, p<0.001) and the glucose concentration in the umbilical artery (r = ?0.45, p = 0.004). Glucose and insulin concentrations were correlated in the mother (r = 0.52, p = 0.001), but not significantly in the fetus. We found no significant correlation between maternal and fetal insulin values. Conclusions We did not find a relation between indicators of maternal glucose supply and the fetal venous-arterial glucose difference. Our findings indicate that the maternal-fetal glucose gradient is significantly influenced by the fetal venous-arterial difference and not merely dependent on maternal glucose concentration or the arterio-venous difference on the maternal side of the placenta. PMID:25680194

  15. 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 rates are fast relative to stream-water velocity and all solute is exchanged with the storage zone over the experimental reach. As DaI increases, tracer dispersion caused by hyporheic exchange eventually reaches an equilibrium condition and storage-zone exchange parameters become essentially nonidentifiable.

  16. Zn-K edge EXAFS study of human nails

    NASA Astrophysics Data System (ADS)

    Katsikini, M.; Mavromati, E.; Pinakidou, F.; Paloura, E. C.; Gioulekas, D.

    2009-11-01

    Extended X-ray absorption fine structure (EXAFS) spectroscopy at the Zn - K edge is applied for the study of the bonding geometry of Zn in human nails. The studied nail clippings belong to healthy donors and donors who suffer from lung diseases. Fitting of the first nearest neighboring shell of Zn reveals that it is bonded with N and S, at distances that take values in the ranges 2.00-2.04 Å and 2.23-2.28Å, respectively. Zn is four - fold coordinated and the ratio of the number of sulfur and nitrogen atoms (NS/NN) in the first coordination shell ranges from 0.52 to 1. The sample that belongs to the donor who suffers from lung fibrosis, a condition that is related to keratinization of the lung tissue, is characterized by the highest number of NS/NN. Simulation, using the FEFF8 code, of the Zn - K edge EXAFS spectra with models of tetrahedrally coordinated Zn with 1 (or 2) cysteine and 3 (or 2) histidines is satisfactory.

  17. The Introduction of New Cockpit Technology: A Human Factors Study

    NASA Technical Reports Server (NTRS)

    Curry, R. E.

    1985-01-01

    A joint Airline/NASA field study of B-767 training and operations was conducted during the period this aircraft was being introduced into line service. The objectives of the study were: (1) to identify any adverse reactions to the new technology; (2) to provide a clearing house of information for the airlines and pilots during the introductory period; (3) to provide feedback on airline training programs for the new aircraft; and (4) to provide field data to NASA and other researchers to help them develop principles of human interaction with automated systems. It is concluded that: (1) a large majority of pilots enjoy flying the B-767 more than the older aircraft; (2) pilots accept new cockpit technology and find it useful; (3) pilots are aware of the potential loss of flying skills because of automation, and take steps to prevent this from happening; (4) autopilot/autothrottle interactions and FMS operations were sometimes confusing or surprising to pilots, and they desired more training in this area; and (5) highly automated cockpits can result in a loss of effective monitoring performance.

  18. Study of evoked potentials in human African trypanosomiasis.

    PubMed

    Tabaraud, F; Hugon, J; Tapie, P; Buguet, A; Lonsdorfer, A; Gati, R; Doua, F; Dumas, M

    1992-08-01

    Human African trypanosomiasis or sleeping sickness has a stage of neurological involvement characterized by the onset of diffuse meningoencephalitis with sleep disturbances and decreased wakefulness. The pathogenesis of this disease is not well understood. We studied auditory, visual, sensory, and motor evoked potentials in 16 patients with trypanosomiasis in the early stage of meningoencephalitis. In all patients, the brain-stem auditory evoked response (BAER) and the pattern-reversal visual evoked response (PVER) were normal. On the other hand, abnormalities of the somatosensory evoked response (SSER) or the motor evoked response (MER) were found in only five cases; however, their relationship to the illness could not be definitely confirmed. The study results indicate that the evaluated pathways were essentially intact, in particular at the level of the brain-stem in the early stage of the disease. Sleep disturbances and decreased wakefulness noted at this stage were thus linked more closely to functional involvement at the level of the sleep centres than to any detectable specific anatomic lesion. PMID:1495120

  19. Mine waste contamination limits soil respiration rates: a case study using quantile regression

    Microsoft Academic Search

    Philip W. Ramsey; Matthias C. Rillig; Kevin P. Feris; Johnnie N. Moore; James E. Gannon

    2005-01-01

    We present an application of a statistical approach, quantile regression (QR), which identifies trends in soil processes otherwise masked by spatial and temporal variability. QR identifies limits on processes and changes in the variance of a response along an environmental gradient. We quantified in situ soil respiration, pH, and heavy metal concentrations across a mine waste contamination gradient that spanned

  20. In the Death Zone: A study of limits in the 1996 Mount Everest disaster

    Microsoft Academic Search

    Sue Tempest; Ken Starkey; Christine Ennew

    2007-01-01

    This article examines the May 1996 Everest disaster through the lens of limits and liminality to provide an alternative interpretation of the significance of the event as a counterpoint to existing accounts. The Everest disaster is an example of management under the most extreme conditions and also an example of a common managerial mindset that is prevalent in the literature