Science.gov

Sample records for limited human studies

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

    PubMed Central

    2012-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

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

    SciTech Connect

    Boehnke, M. )

    1994-08-01

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

  4. The retention of balance: an exploratory study into the limits of acceleration the human body can withstand without losing equilibrium.

    PubMed

    de Graaf, B; van Weperen, W

    1997-03-01

    The human limiting values for sudden accelerations we have determined can be used to evaluate specific physical conditions that cause problems in maintaining postural balance. A comparison between the data obtained in the laboratory and the situations occurring during public transport by tram, bus, and metro revealed that both the initial impetus ("jerk") and the level of acceleration found in practice were sufficient to ensure that none of the individuals measured in the laboratory would have been able to retain their balance without extra support. The study suggests that limiting the initial jerk component of the acceleration would help considerably in alleviating the problem. PMID:9302883

  5. 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.

  6. Human exploration mission studies

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.

    1989-01-01

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

  7. Phosphorus: a limiting nutrient for humanity?

    PubMed

    Elser, James J

    2012-12-01

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

  8. Using Symbiotic Relationships with Humans to Help Robots Overcome Limitations

    E-print Network

    Veloso, Manuela M.

    to limitations in perception and execution. To overcome robot limitations and improve robot performance, we takeUsing Symbiotic Relationships with Humans to Help Robots Overcome Limitations Stephanie Rosenthal are interested in task-driven robots in our environments that can communicate with humans. While today's robots

  9. IMMUNOASSAY HUMAN EXPOSURE STUDIES

    EPA Science Inventory

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

  10. Human exploration mission studies

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.

    1990-01-01

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

  11. 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 of replacing humans with computers using artificial intelligence, expert systems, or methods of computational). With the help of expert systems and computational intelligence the role of humans are being steadily eliminated

  12. Limits on the human sentence generator Anthony S. Kroch

    E-print Network

    , however, we will address a different problem; namely, the limits on the capacity of the human language and flexible in their ability to use form to signal meaning and intent. But so long as we assume that human. From the perspective of those of us who would like to develop a computational theory of human language

  13. 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

  14. Teleoperator human factors study

    NASA Technical Reports Server (NTRS)

    Bradford, K. Z.; Schappell, R. T.

    1985-01-01

    The progress made on the Teleoperator Human Factors Study program during the period of September 7, 1985 to October 6, 1985 is discussed. Technical and programmatic problems that were encountered are discussed along with activity planned for the following month. The main portion of the report has been separated into four sections: Work Performed, Future Work, Problems Encountered, and Cost Information.

  15. Introduction Subjective experience is probably not limited to humans

    E-print Network

    Memphis, University of

    Introduction Subjective experience is probably not limited to humans: The evidence from, corresponding effects are found on conscious contents and state, as assessed by reliable reports. In contrast fundamental and phylogenetically ancient. In humans we infer subjective experiences from behavioral and brain

  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. Peptidomics for Studying Limited Proteolysis.

    PubMed

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

    2015-11-01

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

  18. 32 CFR 169a.19 - Study limits.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  19. Optimal Teaching for Limited-Capacity Human Learners

    E-print Network

    Love, Bradley C.

    Optimal Teaching for Limited-Capacity Human Learners Kaustubh Raosaheb Patil Affective Brain Lab University College London l.kopec.12@ucl.ac.uk Bradley C. Love Experimental Psychology University College London b.love@ucl.ac.uk Abstract Basic decisions, such as judging a person as a friend or foe, involve

  20. 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 ...

  1. Limited communication capacity unveils strategies for human interaction

    E-print Network

    Miritello, Giovanna; Cebrián, Manuel; Moro, Esteban

    2013-01-01

    Social connectivity is the key process that characterizes the structural properties of social networks and in turn processes such as navigation, influence or information diffusion. Since time, attention and cognition are inelastic resources, humans should have a predefined strategy to manage their social interactions over time. However, the limited observational length of existing human interaction datasets, together with the bursty nature of dyadic communications have hampered the observation of tie dynamics in social networks. Here we develop a method for the detection of tie activation/deactivation, and apply it to a large longitudinal, cross-sectional communication dataset ($\\approx$ 19 months, $\\approx$ 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 particular we find that men have an overall higher communication capacity than women and that this ...

  2. Limits and patterns of cytomegalovirus genomic diversity in humans

    PubMed Central

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

    2015-01-01

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

  3. 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

  4. The Limits of Human Stereopsis in Space and Time

    PubMed Central

    Kane, David; Guan, Phillip

    2014-01-01

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

  5. Limitations in simulator time-based human reliability analysis methods

    SciTech Connect

    Wreathall, J.

    1989-01-01

    Developments in human reliability analysis (HRA) methods have evolved slowly. Current methods are little changed from those of almost a decade ago, particularly in the use of time-reliability relationships. While these methods were suitable as an interim step, the time (and the need) has come to specify the next evolution of HRA methods. As with any performance-oriented data source, power plant simulator data have no direct connection to HRA models. Errors reported in data are normal deficiencies observed in human performance; failures are events modeled in probabilistic risk assessments (PRAs). Not all errors cause failures; not all failures are caused by errors. Second, the times at which actions are taken provide no measure of the likelihood of failures to act correctly within an accident scenario. Inferences can be made about human reliability, but they must be made with great care. Specific limitations are discussed. Simulator performance data are useful in providing qualitative evidence of the variety of error types and their potential influences on operating systems. More work is required to combine recent developments in the psychology of error with the qualitative data collected at stimulators. Until data become openly available, however, such an advance will not be practical.

  6. 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.

  7. 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).

  8. Humanizing Home Study.

    ERIC Educational Resources Information Center

    Hass, Glen; Fleury, Donna

    The use of correspondence or home study courses for noncredit is a recent development in the field of adult education. The challenge facing the extension worker is to be able to develop and deliver the type of program that not only meets the learning (content) need of the participant but that also meets the learning situation. Unfortunately, the…

  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. 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

  11. 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.

  12. Metabolic profiling in human exposome studies.

    PubMed

    Athersuch, Toby J; Keun, Hector C

    2015-11-01

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

  13. Limited human infection due to recombinant raccoon pox virus

    USGS Publications Warehouse

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

    2004-01-01

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

  14. Evaluating Humane Education: The Jefferson County Study.

    ERIC Educational Resources Information Center

    Fitzgerald, Thomas A., Jr.

    1981-01-01

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

  15. 47 CFR 5.93 - Limited market studies.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

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

  16. How Ideal Are We? Incorporating Human Limitations into Bayesian Models of Word Segmentation*

    E-print Network

    Steyvers, Mark

    for that induction problem, given certain assumptions about the representation of knowledge in the human mindHow Ideal Are We? Incorporating Human Limitations into Bayesian Models of Word Segmentation* Lisa shown that Bayesian model predictions are consistent with human behavior in various cognitive domains

  17. Epidemiological studies in human radiobiology*

    PubMed Central

    1967-01-01

    A meeting on the contribution of epidemiological studies to the better understanding of the effects of radiation on human health was held in Washington, D.C., from 13 to 17 December 1965. This meeting was organized and sponsored by the World Health Organization, with the co-operation of the Division of Radiological Health, Public Health Service, United States Department of Health, Education, and Welfare. The main emphasis of the meeting was on obtaining representative views on the epidemiological studies now in progress and on the possibilities for further studies, but past work was also briefly reviewed under such headings as leukaemia, lung and other tumours, congenital malformations and cytogenetic effects. In addition, information was presented on current concepts of the mechanism of carcinogenesis and life-shortening derived from experimental and theoretical work. Against this background an attempt was made to identify the most essential needs for epidemiological data at present and to consider how such data might be obtained. The text presented below was prepared by Professor L. F. Lamerton of the Department of Biophysics, Institute of Cancer Research (Surrey Branch), Sutton, Surrey, England, and Professor B. MacMahon of the Department of Epidemiology, Harvard University School of Public Health, Boston, Mass., USA. It is a précis of some of the views expressed and of the information and the suggestions made. PMID:20604319

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

    SciTech Connect

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

    1992-01-01

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

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

    PubMed Central

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

    2015-01-01

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

  20. The fanconi anemia pathway limits human papillomavirus replication.

    PubMed

    Hoskins, Elizabeth E; Morreale, Richard J; Werner, Stephen P; Higginbotham, Jennifer M; Laimins, Laimonis A; Lambert, Paul F; Brown, Darron R; Gillison, Maura L; Nuovo, Gerard J; Witte, David P; Kim, Mi-Ok; Davies, Stella M; Mehta, Parinda A; Butsch Kovacic, Melinda; Wikenheiser-Brokamp, Kathryn A; Wells, Susanne I

    2012-08-01

    High-risk human papillomaviruses (HPVs) deregulate epidermal differentiation and cause anogenital and head and neck squamous cell carcinomas (SCCs). The E7 gene is considered the predominant viral oncogene and drives proliferation and genome instability. While the implementation of routine screens has greatly reduced the incidence of cervical cancers which are almost exclusively HPV positive, the proportion of HPV-positive head and neck SCCs is on the rise. High levels of HPV oncogene expression and genome load are linked to disease progression, but genetic risk factors that regulate oncogene abundance and/or genome amplification remain poorly understood. Fanconi anemia (FA) is a genome instability syndrome characterized at least in part by extreme susceptibility to SCCs. FA results from mutations in one of 15 genes in the FA pathway, whose protein products assemble in the nucleus and play important roles in DNA damage repair. We report here that loss of FA pathway components FANCA and FANCD2 stimulates E7 protein accumulation in human keratinocytes and causes increased epithelial proliferation and basal cell layer expansion in the HPV-positive epidermis. Additionally, FANCD2 loss stimulates HPV genome amplification in differentiating cells, demonstrating that the intact FA pathway functions to restrict the HPV life cycle. These findings raise the possibility that FA genes suppress HPV infection and disease and suggest possible mechanism(s) for reported associations of HPV with an FA cohort in Brazil and for allelic variation of FA genes with HPV persistence in the general population. PMID:22623785

  1. 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…

  2. 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

  3. 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.

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

    NASA Technical Reports Server (NTRS)

    Bishop, Phillip A.; Greenisen, Mike

    1992-01-01

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

  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. Superior reproductive success on human blood without sugar is not limited to highly anthropophilic mosquito

    E-print Network

    Juliano, Steven A.

    Superior reproductive success on human blood without sugar is not limited to highly anthropophilic superior reproductive success on human blood when sugar is not available. Life-table experiments were conducted with Aedes albopictus Skuse and Ae. aegypti to compare the effects of sugar availabil- ity on age

  7. Determination of torque-limits for human and cat lumbar spine specimens during displacement-controlled physiological motions

    PubMed Central

    Ianuzzi, Allyson; Pickar, Joel G.; Khalsa, Partap S.

    2009-01-01

    Background Context Quadruped animal models have been validated and utilized as biomechanical models for the lumbar spine. The biomechanics of the cat lumbar spine has not been well characterized, even though it is a common model used in neuromechanical studies. Purpose Compare the physiological ranges of motion and determine torque-limits for cat and human lumbar spine specimens during physiological motions. Study Design/Setting Biomechanics study. Patient Sample Cat and human lumbar spine specimens. Outcome measures Intervertebral angle (IVA), joint moment, yield point, torque-limit, correlation coefficients. Methods Cat (L2-sacrum) and human (T12-sacrum) lumbar spine specimens were mechanically tested to failure during displacement-controlled extension, lateral bending, and axial rotation. Single trials consisted of 10 cycles (10mm/s or 5°/s) to a target displacement where the magnitude of the target displacement was increased for subsequent trials until failure occurred. Whole-lumbar stiffness, torque at yield point, and joint stiffness were determined. Scaling relationships were established using equations analogous to those that describe the load response of elliptically-shaped beams. Results IVA magnitudes for cat and human lumbar spines were similar during physiological motions. Human whole-lumbar and joint stiffness magnitudes were significantly greater than those for cat spine specimens (p<0.05). Torque-limits were also greater for humans compared to cats. Scaling relationships with high correlation (R2>0.77) were established during later lateral bending and axial rotation. Conclusions The current study defined “physiological ranges of movement” for human and cat lumbar spine specimens during displacement-controlled testing, and should be observed in future biomechanical studies conducted under displacement control. PMID:17983845

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

    NASA Astrophysics Data System (ADS)

    Coates, Andrew J.

    2001-11-01

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

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

    PubMed

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

    2015-08-01

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

  10. Humanized Mice to Study Human T Cell Development.

    PubMed

    Bonte, Sarah; Snauwaert, Sylvia; Vanhee, Stijn; Dolens, Anne-Catherine; Taghon, Tom; Vandekerckhove, Bart; Kerre, Tessa

    2016-01-01

    While in vitro models exist to study human T cell development, they still lack the precise environmental stimuli, such as the exact combination and levels of cytokines and chemokines, that are present in vivo. Moreover, studying the homing of hematopoietic stem (HSC) and progenitor (HPC) cells to the thymus can only be done using in vivo models. Although species-specific differences exist, "humanized" models are generated to circumvent these issues. In this chapter, we focus on the humanized mouse models that can be used to study early T cell development. Models that study solely mature T cells, such as the SCID-PBL (Tary-Lehmann et al., Immunol Today 16:529-533) are therefore not discussed here, but have recently been reviewed (Shultz et al., Nat Rev Immunol 12:786-798). PMID:26294414

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

    PubMed

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

    2015-09-01

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

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

    PubMed Central

    Hanna, Elizabeth G.; Tait, Peter W.

    2015-01-01

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

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

    PubMed

    Hanna, Elizabeth G; Tait, Peter W

    2015-07-01

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

  14. 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.

  15. Rabbit Models for Studying Human Infectious Diseases.

    PubMed

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

    2015-01-01

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

  16. 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

  17. 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.

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

    SciTech Connect

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

    1994-10-01

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

  19. Approaches to Study Human T Cell Development.

    PubMed

    Dolens, Anne-Catherine; Van de Walle, Inge; Taghon, Tom

    2016-01-01

    Not only is human T cell development characterized by unique changes in surface marker expression, but it also requires specific growth factors and conditions to mimic and study T cell development in vitro. In this chapter, we provide an overview of the specific aspects that need attention when performing T cell differentiation cultures with human progenitors. PMID:26294413

  20. Technological advances for studying human behavior

    NASA Technical Reports Server (NTRS)

    Roske-Hofstrand, Renate J.

    1990-01-01

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

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

    SciTech Connect

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

    1995-10-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

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

    PubMed

    Rapmund, Garrison

    2002-05-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2012-01-01

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

  7. Gender Studies School of Arts and Humanities

    E-print Network

    Little, Tony

    MSc/MLitt Gender Studies (Applied) School of Arts and Humanities http://stir.ac.uk/fi #12;Why Gender Studies? The MSc/MLitt in Gender Studies (Applied) at the University of Stirling aims to equip students with theoretical and practical skills in gender analysis and research. Developed by colleagues who

  8. 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…

  9. 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 influence the pineal gland is still unsolved. The pineal gland is likely to sense EMFs as light but

  10. 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.

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

    PubMed

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

    2015-10-01

    The objective of this study was to characterize the mechanics of maximal running sprint acceleration in high-level athletes. Four elite (100-m best time 9.95-10.29?s) and five sub-elite (10.40-10.60?s) sprinters performed seven sprints in overground conditions. A single virtual 40-m sprint was reconstructed and kinetics parameters were calculated for each step using a force platform system and video analyses. Anteroposterior force (FY), power (PY), and the ratio of the horizontal force component to the resultant (total) force (RF, which reflects the orientation of the resultant ground reaction force for each support phase) were computed as a function of velocity (V). FY-V, RF-V, and PY-V relationships were well described by significant linear (mean R(2) of 0.892?±?0.049 and 0.950?±?0.023) and quadratic (mean R(2)?=?0.732?±?0.114) models, respectively. The current study allows a better understanding of the mechanics of the sprint acceleration notably by modeling the relationships between the forward velocity and the main mechanical key variables of the sprint. As these findings partly concern world-class sprinters tested in overground conditions, they give new insights into some aspects of the biomechanical limits of human locomotion. PMID:25640466

  12. 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

  13. EVA Health and Human Performance Benchmarking Study

    NASA Technical Reports Server (NTRS)

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

    2016-01-01

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

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

    E-print Network

    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

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

    PubMed

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

    2015-08-01

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

  16. The Limits to Growth: Background and Exercise Suggestions The Limits to Growth (Figure 1) describes the prospects for growth in human population and

    E-print Network

    Ford, Andrew

    the prospects for growth in human population and industrial production in a global system over the next century understanding of the challenges of dealing with population and industrial growth in a finite world. Figure 1The Limits to Growth: Background and Exercise Suggestions The Limits to Growth (Figure 1) describes

  17. HUMAN RIGHTS AND BORDER STUDIES Anthropology Professors

    E-print Network

    Watkins, Joseph C.

    HUMAN RIGHTS AND BORDER STUDIES Anthropology Professors Diane Austin Linda Green Mark Nichter and Development ANTH 395B An Anthropology of Migration: The Borderlands of the American Southwest (regularly course related details. Please remember to select "ANTH - Anthropology Main" as the subject code. #12

  18. Postdisciplinary Liaisons: Science Studies and the Humanities

    E-print Network

    the future of the humanities and science studies has evolved significantly since this essay was presented of Industry and Academia, ed. Henry Etzkowitz et al. (Albany, N.Y., 1998); Academic Capitalism: Politics and the Dynamics of Inclusion since World War II, ed. David A. Hollinger (Baltimore, 2006). Critical Inquiry 35

  19. 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.

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

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  1. Genomic approaches to studying the human microbiota

    PubMed Central

    Weinstock, George M.

    2013-01-01

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

  2. 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

  3. 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

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

    SciTech Connect

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

    2008-04-15

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

  5. Requirements for segmented correctors for diffraction-limited performance in the human eye

    NASA Astrophysics Data System (ADS)

    Miller, Donald T.; Thibos, Larry N.; Hong, Xin

    2005-01-01

    Wavefront correctors have yet to provide diffraction-limited imaging through the human eye's ocular media for large pupils (? 6 mm).To guide future improvements in corrector designs that might enable such imaging, we have modeled the performance of segmented piston correctors in conjunction with measured wave aberration data of normal human eyes (mean=34.2 yr; stdev= 10.6 yr). The model included the effects of pupil size and wavelength in addition to dispersion, phase wrapping, and number and arrangement of facets in the corrector. Results indicate that ? 100x100 facets are needed to reach diffraction-limited performance for pupils up to 8 mm (extrapolated) at 0.6 ?m wavelength. Required facet density for the eye was found to be substantially higher at the pupil's edge than at its center, which is in stark contrast to the requirements for correcting atmospheric turbulence. Substantially more facets are required at shorter wavelengths with performance highly sensitive to facet fill. In polychromatic light, the performance of segmented correctors based on liquid crystal technology was limited by the naturally occurring longitudinal chromatic aberration of the eye rather than phase wrapping and dispersion of the liquid crystal. Required facets to correct defocus alone was found highly sensitive to pupil size and decentration.

  6. 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...

  7. 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...

  8. 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...

  9. 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...

  10. Monoamine oxidase: Radiotracer chemistry and human studies

    SciTech Connect

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

    2015-03-01

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

  11. Monoamine oxidase: Radiotracer chemistry and human studies

    DOE PAGESBeta

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

    2015-03-01

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

  12. Brain, mind and limitations of a scientific theory of human consciousness.

    PubMed

    Gierer, Alfred

    2008-05-01

    In biological terms, human consciousness appears as a feature associated with the functioning of the human brain. The corresponding activities of the neural network occur strictly in accord with physical laws; however, this fact does not necessarily imply that there can be a comprehensive scientific theory of consciousness, despite all the progress in neurobiology, neuropsychology and neurocomputation. Predictions of the extent to which such a theory may become possible vary widely in the scientific community. There are basic reasons-not only practical but also epistemological-why the brain-mind relation may never be fully "decodable" by general finite procedures. In particular self-referential features of consciousness, such as self-representations involved in strategic thought and dispositions, may not be resolvable in all their essential aspects by brain analysis. Assuming that such limitations exist, objective analysis by the methods of natural science cannot, in principle, fully encompass subjective, mental experience. PMID:18404733

  13. 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...

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

    PubMed Central

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

    2013-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2013-01-01

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

  16. Human studies of cannabinoids and medicinal cannabis.

    PubMed

    Robson, P

    2005-01-01

    Cannabis has been known as a medicine for several thousand years across many cultures. It reached a position of prominence within Western medicine in the nineteenth century but became mired in disrepute and legal controls early in the twentieth century. Despite unremitting world-wide suppression, recreational cannabis exploded into popular culture in the 1960s and has remained easily obtainable on the black market in most countries ever since. This ready availability has allowed many thousands of patients to rediscover the apparent power of the drug to alleviate symptoms of some of the most cruel and refractory diseases known to humankind. Pioneering clinical research in the last quarter of the twentieth century has given some support to these anecdotal reports, but the methodological challenges to human research involving a pariah drug are formidable. Studies have tended to be small, imperfectly controlled, and have often incorporated unsatisfactory synthetic cannabinoid analogues or smoked herbal material of uncertain composition and irregular bioavailability. As a result, the scientific evaluation of medicinal cannabis in humans is still in its infancy. New possibilities in human research have been opened up by the discovery of the endocannabinoid system, a rapidly expanding knowledge of cannabinoid pharmacology, and a more sympathetic political environment in several countries. More and more scientists and clinicians are becoming interested in exploring the potential of cannabis-based medicines. Future targets will extend beyond symptom relief into disease modification, and already cannabinoids seem to offer particular promise in the treatment of certain inflammatory and neurodegenerative conditions. This chapter will begin with an outline of the development and current status of legal controls pertaining to cannabis, following which the existing human research will be reviewed. Some key safety issues will then be considered, and the chapter will conclude with some suggestions as to future directions for human research. PMID:16596794

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

    PubMed

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

    2015-07-01

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

  18. Limitations in the process of transcription and translation inhibit recombinant human chorionic gonadotropin expression in CHO cells.

    PubMed

    Liu, Yang; Yi, Xiaoping; Zhuang, Yingping; Zhang, Siliang

    2015-06-20

    Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer with a ? subunit and ? subunit assembled together with disulfide bridges. This hormone plays an important role in the detection of ovulation induction and in the treatment of certain diseases that cause female infertility. The effects of transcription, subunit expression, assembling and secretion on recombinant hCG expression in CHO cells were studied using stable high-producing and low-producing cell lines generated by the FLP-In™ system. The results indicated that the mRNA and polypeptide levels of the ? subunit were always higher than those of the ? subunit. Further study confirmed that the differences were caused by the transcription rate rather than by mRNA stability. In the high-producing cell lines, there was obvious transcription level limitation of the ? subunit in contrast to the ? subunit. In addition, there was obvious limitation of the synthetic steps from mRNA to polypeptide for both the ? subunit and the ? subunit, especially the ? subunit. Significant limitations of the assembly and secretion levels were not observed in this research. This study presents a research methodology for double subunit protein expression and provides valuable evidence for the enhancement of recombinant hCG productivity. PMID:25529346

  19. 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

  20. 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.

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

    PubMed Central

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

    2013-01-01

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

  2. Breakdown Limit Studies in High-Rate Gaseous Detectors

    NASA Technical Reports Server (NTRS)

    Ivaniouchenkov, Yu; Fonte, P.; Peskov, V.; Ramsey, B. D.

    1999-01-01

    We report results from a systematic study of breakdown limits for novel high-rate gaseous detectors: MICROMEGAS, CAT and GEM, together with more conventional devices such as thin-gap parallel-mesh chambers and high-rate wire chambers. It was found that for all these detectors, the maximum achievable pin, before breakdown appears, drops dramatically with incident flux, and is sometimes inversely proportional to it. Further, in the presence of alpha particles, typical of the breakgrounds in high-energy experiments, additional gain drops of 1-2 orders of magnitude were observed for many detectors. It was found that breakdowns at high rates occur through what we have termed an "accumulative" mechanism, which does not seem to have been previously reported in the literature. Results of these studies may help in choosing the optimum detector for given experimental conditions.

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

    ERIC Educational Resources Information Center

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

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

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

    ERIC Educational Resources Information Center

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

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

  5. 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

  6. 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.

  7. 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

    Ausubel, Frederick M.

    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

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

    PubMed

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

    2016-01-01

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

  9. 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.

  10. Drosophila melanogaster in the Study of Human Neurodegeneration

    PubMed Central

    Hirth, Frank

    2010-01-01

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

  11. The Humanized NOD/SCID Mouse as a Preclinical Model to Study the Fate of Encapsulated Human Islets

    PubMed Central

    Vaithilingam, Vijayaganapathy; Oberholzer, Jose; Guillemin, Gilles J.; Tuch, Bernard E.

    2010-01-01

    Despite encouraging results in animal models, the transplantation of microencapsulated islets into humans has not yet reached the therapeutic level. Recent clinical trials using microencapsulated human islets in barium alginate showed the presence of dense fibrotic overgrowth around the microcapsules with no viable islets. The major reason for this is limited understanding of what occurs when encapsulated human islets are allografted. This warrants the need for a suitable small animal model. In this study, we investigated the usefulness of NOD/SCID mice reconstituted with human PBMCs (called humanized NOD/SCID mice) as a preclinical model. In this model, human T cell engraftment could be achieved, and CD45+ cells were observed in the spleen and peripheral blood. Though the engrafted T cells caused a small fibrotic overgrowth around the microencapsulated human islets, this failed to stop the encapsulated islets from functioning in the diabetic recipient mice. The ability of encapsulated islets to survive in this mouse model might partly be attributed to the presence of Th2 cytokines IL-4 and IL-10, which are known to induce graft tolerance. In conclusion, this study showed that the hu-NOD/SCID mouse is not a suitable preclinical model to study the allograft rejection mechanisms of encapsulated human islets. As another result, the maintained viability of transplanted islets on the NOD/SCID background emphasized a critical role of protective mechanisms in autoimmune diabetes transplanted subjects due to specific immunoregulatory effects provided by IL-4 and IL-10. PMID:20703439

  12. 40 CFR 26.1607 - Human Studies Review Board review of completed human research.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  13. 40 CFR 26.1607 - Human Studies Review Board review of completed human research.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  14. 40 CFR 26.1606 - Human Studies Review Board review of proposed human research.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  15. 40 CFR 26.1606 - Human Studies Review Board review of proposed human research.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  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. 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

  19. Ultrahigh pressure liquid chromatography-(tandem) mass spectrometry in human sports drug testing: possibilities and limitations.

    PubMed

    Thevis, Mario; Thomas, Andreas; Pop, Valentin; Schänzer, Wilhelm

    2013-05-31

    Doping control analytical laboratories for human sports predominantly employ nowadays chromatographic-mass spectrometric test methods for routine, high throughput screening and confirmation assays concerning low and high molecular mass analytes. Liquid chromatography-(tandem) mass spectrometry [(LC-MS(/MS)] and particularly ultrahigh pressure liquid chromatography (UHPLC)-MS/MS instruments have become devices of choice due to their indispensable capabilities that compensate for limitations inherent to other commonly used strategies such as immunological and gas chromatography-(tandem) mass spectrometry [(GC-MS(/MS)]-based detection methods. UHPLC-MS/MS-based assays at low mass spectrometric resolution have been established allowing for fast and sensitive targeted analyses focusing on pre-selected target analytes with diagnostic precursor-product ion pairs. Combining UHPLC to high resolution/high accuracy MS(/MS) further expanded the targeted approach (i.e., plotting extracted ion chromatograms of protonated or deprotonated molecules as well as product ions measured with accurate masses) toward non-targeted analyses enabling also retrospective data mining. In this review, recent applications of UHPLC-MS/MS in sports drug testing procedures published between 2008 and 2012 are presented and advantages as well as limitations in a short- and long-term perspective are discussed. PMID:23332783

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

    PubMed

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

    2005-07-01

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

  1. Studies of Inorganic Crystals in Biological Tissue: Magnetite in Human

    E-print Network

    Kirschvink, Joseph L.

    Studies of Inorganic Crystals in Biological Tissue: Magnetite in Human Tumor Atsuko Kobayashi Metallurgy 44 (1997 ), 294 #12;294 Studies of Inorganic Crystals in Biological Tissue: Magnetite in Human Tumor Atsuko Kobayashi*', Naoichi Yamamoto*l and Joseph Kirschvink*2 *1 Graduate School of Human

  2. Department: Human Development and Family Studies Course No: 1070 [190

    E-print Network

    Alpay, S. Pamir

    Department: Human Development and Family Studies Course No: 1070 [190] Credits: 3 Title: Individual. The course is designed as an introduction to the field of Human Development and Family Studies. The course and Family Development (Formerly offered as HDFR 190.) Either semester. Three credits. Human development

  3. Information in the Study of Human Interaction Keith Devlin

    E-print Network

    Devlin, Keith

    from human interaction.) The "analyst" here may be a professional social scientist (as is the caseInformation in the Study of Human Interaction Keith Devlin and Duska Rosenberg May, 2006 -- may be used (by an analyst, as a tool) in a study of human interaction. (Actually, most of what we say

  4. Characterizing human retinotopic mapping with conformal geometry: A preliminary study

    E-print Network

    Wang, Yalin

    Characterizing human retinotopic mapping with conformal geometry: A preliminary study Duyan Taa visual system and the development of human cerebral cortex. They also hold great promises to further our helped us to understand the human cortical structure and early vision process. Previous studies have

  5. The Humanities and the Human Sciences: The Guide Hermeneutics Gives to the Study of Human Experience.

    ERIC Educational Resources Information Center

    Overvold, Gary E.

    1985-01-01

    A curriculum design that focuses on the human sciences, the disciplines that concern themselves with the social and individual activities that are distinctively human, would be a better approach than the current separation of the humanities and social sciences. (MSE)

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-12-01

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

  8. 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

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

    SciTech Connect

    Samei, E.; Kearfott, K.J.

    1995-12-01

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

  10. 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...

  11. 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.

  12. 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.

  13. Meta-Analytic Approaches for Multistressor Dose-Response Function Development: Strengths, Limitations, and Case Studies.

    PubMed

    Levy, Jonathan I; Fabian, M Patricia; Peters, Junenette L

    2015-06-01

    For many policy analyses, including but not limited to cumulative risk assessments, it is important to characterize the individual and joint health effects of multiple stressors. With an increasing focus on psychosocial and other nonchemical stressors, this often includes epidemiological meta-analysis. Meta-analysis has limitations if epidemiological studies do not include all of the stressors of interest or do not provide multivariable outputs in a format necessary for risk assessment. Given these limitations, novel analytical methods are often needed to synthesize the published literature or to build upon available evidence. In this article, we discuss three recent case studies that highlight the strengths and limitations of meta-analytic approaches and other research synthesis techniques for human health risk assessment applications. First, a literature-based meta-analysis within a risk assessment context informed the design of a new epidemiological investigation of the differential toxicity of fine particulate matter constituents. Second, a literature synthesis for an effects-based cumulative risk assessment of hypertension risk factors led to a decision to develop new epidemiological associations using structural equation modeling. Third, discrete event simulation modeling was used to simulate the impact of changes in the built environment on environmental exposures and associated asthma outcomes, linking literature meta-analyses for key associations with a simulation model to synthesize all of the model components. These case studies emphasize the importance of conducting epidemiology with a risk assessment application in mind, the need for interdisciplinary collaboration, and the value of advanced analytical methods to synthesize epidemiological and other evidence for risk assessment applications. PMID:24724810

  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. 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;

  16. Oxidative Damage to RPA Limits the Nucleotide Excision Repair Capacity of Human Cells.

    PubMed

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

    2015-11-01

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

  17. Optical limiting and thermal lensing studies in C60 S. S. Harilal,a)

    E-print Network

    Harilal, S. S.

    Optical limiting and thermal lensing studies in C60 S. S. Harilal,a) C. V. Bindhu, V. P. N 1999 Optical limiting and thermo-optic properties of C60 in toluene are studied using 532 nm, 9 ns pulses from a frequency-doubled Nd:YAG laser. Optical limiting studies in these fullerene molecules lead

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  19. Studying Risk Factors Associated with Human Leptospirosis

    PubMed Central

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

    2014-01-01

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

  20. 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…

  1. October 19, 2009 Team to study human effect on watershed

    E-print Network

    Sparks, Donald L.

    October 19, 2009 Team to study human effect on watershed Research will chart carbon cycle in 565 in a watershed," Aufdenkampe said. "Specifically, how is human erosion affecting the carbon cycle?" Six studies and Christina River watersheds, is one of six areas in the United States where scientists will study watersheds

  2. Limitations of tpi and bg genes sub-genotyping for characterization of human Giardia duodenalis isolates.

    PubMed

    Bonhomme, Julie; Le Goff, Laetitia; Lemée, Véronique; Gargala, Gilles; Ballet, Jean-Jacques; Favennec, Loïc

    2011-09-01

    The intestinal protozoan Giardia duodenalis includes 2 genetically distinct assemblages, A and B, which are responsible for human infections. Little is known so far on the genotypes of G. duodenalis human isolates in France. The present characterization of 19 French clinical isolates was aimed at determining their genotype patterns and associations with clinical symptoms, and in vivo metronidazole resistance, respectively. Based on both triose-phosphate isomerase (tpi) and ?-giardin (bg) gene sequences, twelve isolates were identified as assemblage A, and 7 as assemblage B for the 2 gene loci. Sub-genotyping heterogeneities were observed in 15/19 isolates attributed to either A or B assemblage. They include frequent mismatches and intra-assemblage discordances and mixed positions, which were found more frequently in tpi than in bg sequences, and in assemblage B than in assemblage A sequences. No association was found between sub-genotypes, clinical symptoms and metronidazole sensitivity. Present data underline the need for improvements in the standardization of G. duodenalis multilocus genotyping approach for further molecular epidemiologic studies of giardiasis. PMID:21627998

  3. 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

  4. 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...

  5. 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.

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

    PubMed Central

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

    2013-01-01

    Perhaps more than any other “-omics” endeavor, the accuracy and level of detail obtained from mapping the major connection pathways in the living human brain with diffusion MRI depends on the capabilities of the imaging technology used. The current tools are remarkable; allowing the formation of an “image” of the water diffusion probability distribution in regions of complex crossing fibers at each of half a million voxels in the brain. Nonetheless our ability to map the connection pathways is limited by the image sensitivity and resolution, and also the contrast and resolution in encoding of the diffusion probability distribution. The goal of our Human Connectome Project (HCP) is to address these limiting factors by re-engineering the scanner from the ground up to optimize the high b-value, high angular resolution diffusion imaging needed for sensitive and accurate mapping of the 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

  7. 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…

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

    NASA Astrophysics Data System (ADS)

    Horneck, G.; Humex Team

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

  9. Human Fetal Behavior: 100 Years of Study.

    ERIC Educational Resources Information Center

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

    1998-01-01

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

  10. 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

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

    PubMed Central

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

    2009-01-01

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

  12. 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.

  13. Updated Simulation Studies of Damage Limit of LHC Tertiary Collimators

    E-print Network

    Quaranta, Elena; Bruce, Roderik; Carra, Federico; Cerutti, Francesco; Gradassi, Paolo; Lechner, Anton; Redaelli, Stefano; Skordis, Eleftherios

    2015-01-01

    The tertiary collimators (TCTs) in the LHC, installed in front of the experiments, in standard operation intercept fractions of 10?3 halo particles. However, they risk to be hit by high-intensity primary beams in case of asynchronous beam dump. TCT damage thresholds were initially inferred from results of destructive tests on a TCT jaw, supported by numerical simulations, assuming simplified impact scenarios with one single bunch hitting the jaw with a given impact parameter. In this paper, more realistic failure conditions, including a train of bunches and taking into account the full collimation hierarchy, are used to derive updated damage limits. The results are used to update the margins in the collimation hierarchy and could thus potentially have an influence on the LHC performance.

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

    SciTech Connect

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

    1993-12-31

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

  15. 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

  16. 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

  17. 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.

  18. 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.

  19. 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

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

    PubMed Central

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

    2012-01-01

    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 CD56bright and CD56dim 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

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

    PubMed Central

    Hogan, Daniel R.; Salomon, Joshua A.

    2005-01-01

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

  2. Human neutrophil elastase modulates platelet function by limited proteolysis of membrane glycoproteins.

    PubMed Central

    Brower, M S; Levin, R I; Garry, K

    1985-01-01

    During blood coagulation human polymorphonuclear leukocytes release elastase in amounts that can exceed 100 nmol/liter. We therefore studied the effect of elastase on platelet structure and function. Physiologic concentrations of elastase specifically inhibited thrombin-induced platelet aggregation and ristocetin-induced agglutination of washed platelets in a time- and dose-dependent manner. This was associated with a decrease in the number of high affinity thrombin binding sites on the platelet surface (analysis by "Ligand" program) from 31 per platelet to 12 per platelet (P less than 0.05). As analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, treatment of 3H-labeled platelets with elastase resulted in a decrease in the percent glycoprotein at 130,000-150,000 Mr = and an increase in the percent protein at Mr = 102,000. The supernatant from elastase-treated platelets contained a Mr = 88,000 glycoprotein not found in the supernatant from untreated platelets. Immunoprecipitation studies with monoclonal antiglycoprotein Ib demonstrated that treatment of whole platelets with physiologic concentrations of elastase resulted in proteolytic cleavage of glycoprotein Ib. Elastase treatment of glycoprotein immunoisolated with monoclonal antiglycoprotein Ib antibody resulted in formation of a glycopeptide with the same electrophoretic mobility as the Mr = 102,000 membrane-related glycopeptide. In contrast, analysis by Western blot technique using antiglycoprotein IIb and IIIa antibodies demonstrated that elastase did not degrade glycoproteins IIb or IIIa. We conclude that elastase inhibition of thrombin-induced platelet stimulation is accompanied by (a) a reduction in the number of thrombin binding sites per platelet and (b) proteolysis of glycoprotein Ib. Images PMID:3156151

  3. 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.

  4. 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

  5. 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

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

    ERIC Educational Resources Information Center

    Nickels, Martin

    1998-01-01

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

  7. 78 FR 35031 - Human Studies Review Board Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-11

    ...The U.S. 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 (HSRB) advisory committee. Anticipated vacancies will be filled by September 1, 2013. Sources in addition to this Federal Register Notice may......

  8. What is Communication? Communication is the study of human symbolic

    E-print Network

    Saldin, Dilano

    What is Communication? 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

  9. 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…

  10. Bringing Together Human and Robotic Environment Representations A Pilot Study

    E-print Network

    on the information potential users give to a service robot about its working environment. We further believeBringing Together Human and Robotic Environment Representations ­ A Pilot Study Elin A. Topp, Helge,hehu,hic,kse}@csc.kth.se Abstract-- Human interaction with a service robot requires a shared representation of the environment

  11. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

  12. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  13. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  14. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  15. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

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

    PubMed

    Vermeij, Geerat J

    2012-07-01

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

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

    PubMed Central

    Ben M’Barek, Karim; Regent, Florian; Monville, Christelle

    2015-01-01

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

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

    PubMed

    Namboodiri, K

    1994-01-01

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

  19. 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)

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  1. 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

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

    PubMed Central

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

    2015-01-01

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

  3. Simulation study of PET detector limitations using continuous crystals

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  4. Drosophila as a screening tool to study human neurodegenerative diseases.

    PubMed

    Lenz, Sarah; Karsten, Peter; Schulz, Jörg B; Voigt, Aaron

    2013-11-01

    In an aging society, research involving neurodegenerative disorders is of paramount importance. Over the past few years, research on Alzheimer's and Parkinson's diseases has made tremendous progress. Experimental studies, however, rely mostly on transgenic animal models, preferentially using mice. Although experiments on mice have enormous advantages, they also have some inherent limitations, some of which can be overcome by the use of Drosophila melanogaster as an experimental animal. Among the major advantages of using the fly is its small genome, which can also be modified very easily. The fact that its genome lends itself to diverse alterations (e. g. mutagenesis, transposons) has made the fly a useful organism to perform large-scale and genome-wide screening approaches. This has opened up an entirely new field of experimental research aiming to elucidate genetic interactions and screen for modifiers of disease processes in vivo. Here, we provide a brief overview of how flies can be used to analyze molecular mechanisms underlying human neurodegenerative diseases. PMID:24028575

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

    PubMed

    Hill, D A

    1985-01-01

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

  6. ACCEPTABLE HUMANITIES (HU) COURSES * African American Studies

    E-print Network

    127 Readings in American Literature CAS EN 128 Representing Boston CAS EN 130 Science/Fiction CAS EN Archaeology and Ancient China CAS AR 251 Ancient Maya Civilization Cinema Studies CAS CI 101 History of Global Cinema 1: Origins through 1950s CAS CI 102 History of Global Cinema 2: 1960s to Present Classical Studies

  7. European gas market study sees limited role for LNG imports

    SciTech Connect

    1996-12-31

    An analysis of the Western European gas market published by the European Investment Bank concludes that although the share of imports will grow, existing suppliers Algeria, Russia, and Norway can meet projected demand until and perhaps even beyond 2010. {open_quotes}Alternative sources are not necessary, although Europe might call upon long-distance suppliers to diversify supply sources,{close_quotes} says study author Bertrand Rossert. The gas demand in Western Europe is estimated to grow from 335 bcm in 1995 to 390 bcm by 2000 and 410-450 bcm in 2010, led by the power and residential sectors. Demand in the electricity sector in Belgium, France, Germany, Italy, the Netherlands, Portugal, Spain, and the U.K. should grow rapidly from 40 bcm in 1995 to 70 bcm in 2000 and at a slower rate thereafter. Beyond 2005, the expansion of gas-fired generation will depend on nuclear power policies. (In Eastern Europe, projections are more problematic because of political and economic uncertainties, but could grow from 70 bcm in 1995 to 100 bcm in 2005 and around 110 bcm in 2010).

  8. Human Stem Cell-Derived Neurons: A System to Study Human Tau Function and Dysfunction

    PubMed Central

    Iovino, Mariangela; Patani, Rickie; Watts, Colin; Chandran, Siddharthan; Spillantini, Maria Grazia

    2010-01-01

    Background Intracellular filamentous deposits containing microtubule-associated protein tau constitute a defining characteristic of many neurodegenerative disorders. Current experimental models to study tau pathology in vitro do not usually recapitulate the tau expression pattern characteristic of adult human brain. In this study, we have investigated whether human embryonic stem cell-derived neurons could be a good model to study human tau distribution, function and dysfunction. Methodology/Principal Findings Using RT-PCR, immunohistochemistry, western blotting and cell transfections we have investigated whether all 6 adult human brain tau isoforms are expressed in neurons derived from human embryonic and fetal stem cells and whether 4 repeat tau over-expression alone, or with the F3 tau repeat fragment, (amino acid 258–380 of the 2N4R tau isoform with the ?K280 mutation) affects tau distribution. We found that the shortest 3 repeat tau isoform, similarly to human brain, is the first to be expressed during neuronal differentiation while the other 5 tau isoforms are expressed later. Over expression of tau with 4 repeats affects tau cellular distribution and the short tau F3 fragment appears to increase tau phosphorylation but this effect does not appear to be toxic for the cell. Conclusions Our results indicate that human embryonic stem cell-derived neurons express all 6 tau isoforms and are a good model in which to study tau physiology and pathology. PMID:21085657

  9. RESEARCH ASSISTANT POSITION NEUROPSYCHOLOGICAL STUDIES OF HUMAN MEMORY

    E-print Network

    Patel, Aniruddh D.

    RESEARCH ASSISTANT POSITION NEUROPSYCHOLOGICAL STUDIES OF HUMAN MEMORY The Boston University Memory: assisting in the design and development of experiments; recruiting and scheduling research participants neuropsychological tests and computer-based experiments; maintaining and verifying the accuracy of databases

  10. 76 FR 34703 - Human Studies Review Board Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-14

    ... research (71 FR 24 6138) that called for creating a new, independent human studies review board (i.e., HSRB...; interpersonal, verbal and written communication skills and other attributes that would contribute to the...

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

    EPA Science Inventory

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

  12. A rapid LC-MS/MS method for quantitation of eszopiclone 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 reproducible, specific and cost-effective LC-MS/MS method was developed for simultaneous estimation of eszopiclone (ESZ) with 50 ?L of human plasma using paroxetine as an internal standard (IS). The API-4000 LC-MS/MS was operated under the multiple reaction-monitoring mode using the electrospray ionization technique. A simple liquid-liquid extraction process was used to extract ESZ and IS from human plasma. The total run time was 1.5 min and the elution of ESZ and IS occurred at 0.90 min; this was achieved with a mobile phase consisting of 0.1% formic acid-methanol (15:85, v/v) at a flow rate of 0.50 mL/min on a Discover C(18) (50 × 4.6 mm, 5 µm) column. The developed method was validated in human plasma with a lower limit of quantitation of 0.1 ng/mL for ESZ. A linear response function was established for the range of concentrations 0.10-120 ng/mL (r > 0.998) for ESZ. The intra- and inter-day precision values for ESZ were acceptable as per FDA guidelines. Eszopiclone was stable in the battery of stability studies, viz. bench-top, autosampler and freeze-thaw cycles. The developed assay method was applied to an oral bioequivalence study in humans. PMID:21618564

  13. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  15. 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.

  16. Radioimmunoassay studies of human apolipoprotein E.

    PubMed Central

    Blum, C B; Aron, L; Sciacca, R

    1980-01-01

    This report describes the development and first applications of a sensitive and specific double antibody radioimmunoassay for human apoplipoprotein E (apoE). ApoE was purified from the very low density lipoproteins of hypertriglyceridemic patients by heparin-agarose affinity chromatography, DEAE-cellulose chromatography, and preparative polyacrylamide gel electrophoresis. The purified apoprotein had an amino acid composition characteristic of apoE and resulted in the production of monospecific antisera when injected into rabbits. The radioimmunoassay, which was carried out in the presence of 5 mM sodium decyl sulfate, had a working range of 0.8-12 ng. The withinassay coefficient of variation was 9% and the coefficient of variation for systematic between-assay variability was 3%. Prior delipidation of samples with organic solvents did not alter their immunoreactivity. In 26 normal volunteers, the mean plasma apoE concentration was 36 +/- 13 microgram/ml. Hyperlipidemic patients (n = 68) had higher mean apoE levels. A single patient with type III hyperlipoproteinemia had a plasma apoE level of 664 microgram/ml. The plasma apoE level was independently related to plasma cholesterol and triglyceride levels in a population of 108 normal and nonchylomicronemic hyperlipidemic patients. The multiple correlation coefficient for this relationship was 0.73. Thus, variation in plasma cholesterol and triglyceride concentrations described 53% of the variation in apoE concentrations in this population. The lipoprotein distribution of apoE was investigated by agarose column chromatography and ultracentrifugation of plasma. Agarose column chromatography demonstrated that all or nearly all plasma apoE is associated with lipoproteins. In plasma from normal volunteers and hypercholesterolemic patients, apoE was found in two discrete lipoprotein classes: very low density lipoproteins and a set of lipoprotein particles with size and density characteristics similar to HDL2. In hypertriglyceridemic patients, nearly all apoE was associated with the triglyceride-rich lipoproteins. Images PMID:7440713

  17. Intramolecular Isotope Effects for the Study of Reactions with MassTransfer Limitations 

    E-print Network

    Wagner, Joshua G.

    2010-01-16

    The research presented provides a method to use the comparison of intermolecular isotope effects vs. the intramolecular isotope effects for the study of reactions in which study of the rate limiting step is ambiguous due to interfering mass transfer...

  18. 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.

  19. 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...

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

    ERIC Educational Resources Information Center

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

    2012-01-01

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

  1. 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…

  2. 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…

  3. 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.

  4. 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

  5. ACCEPTABLE HUMANITIES (HU) COURSES * African American Studies

    E-print Network

    in American Literature CAS EN 128 Representing Boston CAS EN 130 Science/Fiction CAS EN 141 Literary Types Archaeology and Ancient China CAS AR 251 Ancient Maya Civilization Art History Any 100-, 200- or 300-level CAS AH course Cinema Studies CAS CI 101 History of Global Cinema 1: Origins through 1950s CAS CI 102

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

    SciTech Connect

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

    2013-04-15

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

  7. 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

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

    PubMed Central

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

    2005-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2014-12-17

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

  11. 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.

  12. 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

  13. 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.

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

    SciTech Connect

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

    2011-03-04

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

  15. The importance of human performance and procedures in limiting severe accident risks

    SciTech Connect

    Higgins, J.C.

    1990-01-01

    Due to the defense in depth concept and redundancy in safety systems utilized, complex industrial plants, such as nuclear power plants (NPPs) can be operated safely. This capability has been demonstrated by many years of safe operation by numerous NPPs in the US and abroad. However, the occurrence of severe accidents has also demonstrated that constant vigilance in a number of areas is necessary to ensure continued safe operation. The areas noted as particularly important are Design, Organization and Management, Maintenance, and Operations (Human Performance). 18 refs.

  16. Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation

    SciTech Connect

    Fabrikant, J.I.

    1982-08-01

    The present review provides an understanding of our current knowledge of the carcinogenic effect of low-dose radiation in man, and surveys the epidemiological studies of human populations exposed to nuclear explosions and medical radiation. Discussion centers on the contributions of quantitative epidemiology to present knowledge, the reliability of the dose-incidence data, and those relevant epidemiological studies that provide the most useful information for risk estimation of cancer-induction in man. Reference is made to dose-incidence relationships from laboratory animal experiments where they may obtain for problems and difficulties in extrapolation from data obtained at high doses to low doses, and from animal data to the human situation. The paper describes the methods of application of such epidemiological data for estimation of excess risk of radiation-induced cancer in exposed human populations, and discusses the strengths and limitations of epidemiology in guiding radiation protection philosophy and public health policy.

  17. 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

  18. Epidemiological studies on radiation carcinogenesis in human populations following acute exposure: nuclear explosions and medical radiation.

    PubMed Central

    Fabrikant, J. I.

    1981-01-01

    The present review provides an understanding of our current knowledge of the carcinogenic effect of low-dose radiation in man, and surveys the epidemiological studies of human populations exposed to nuclear explosions and medical radiation. Discussion centers on the contributions of quantitative epidemiology to present knowledge, the reliability of the dose-incidence data, and those relevant epidemiological studies that provide the most useful information for risk estimation of cancer induction in man. Reference is made to dose-incidence relationships from laboratory animal experiments where they may obtain, for problems and difficulties in extrapolation from data obtained at high doses to low doses, and from animal data to the human situation. The paper describes the methods of application of such epidemiological data for estimation of excess risk of radiation-induced cancer in exposed human populations and discusses the strengths and limitations of epidemiology in guiding radiation protection philosophy and public health policy. PMID:7043913

  19. 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…

  20. Toward a Humane World: Making a Difference with Social Studies.

    ERIC Educational Resources Information Center

    Levy, Tedd

    1999-01-01

    Presents the address delivered by President Tedd Levy at the 78th National Council for Social Studies (NCSS) Annual Conference. Stresses that social studies offers students a place to discuss social-environmental problems the culture is suffering from and gives teachers a chance to promote values inherent in a more humane world. (CMK)

  1. An Experimental Study of the Emergence of Human Communication Systems

    ERIC Educational Resources Information Center

    Galantucci, Bruno

    2005-01-01

    The emergence of human communication systems is typically investigated via 2 approaches with complementary strengths and weaknesses: naturalistic studies and computer simulations. This study was conducted with a method that combines these approaches. Pairs of participants played video games requiring communication. Members of a pair were…

  2. Ecology and Human Values: A Course of Study. (Working Draft).

    ERIC Educational Resources Information Center

    Wisconsin State Dept. of Public Instruction, Madison.

    This interdisciplinary course is designed for senior year high school students in social studies and/or science. Its main thrust is the investigation of human values as they relate to the environment, although rooted in the natural sciences as a means of understanding the complexities inherent in the environment. Use is made of the case study

  3. Emerging Trends in Higher Education Human Resources and Implications for Chief Human Resource Officers: A Delphi Study 

    E-print Network

    Dickens, Brian Keith

    2015-05-11

    education: 1. Social and Digital Media inclusive of, but not limited to, privacy issues, sexting, cyber bullying, depression, relationship depth and breadth, illegal file sharing, access 11 to all human knowledge, validation of information, plagiarism...

  4. 78 FR 57383 - Human Studies Review Board; Notification of a Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ...FRL-9900-98-ORD] Human Studies Review Board; Notification...meeting of the Human Studies Review Board to advise...Agency on the EPA scientific and ethical reviews...2013, EPA's Human Studies Review Board will consider scientific and ethical...

  5. 76 FR 80938 - Human Studies Review Board; Notification of a Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-27

    ...FRL-9611-6] Human Studies Review Board; Notification...meeting of the Human Studies Review Board to advise...Agency on the EPA scientific and ethical reviews...the EPA's Human Studies Review Board will consider scientific and ethical...

  6. 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

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

    PubMed

    Teich, Judith L; Pemberton, Michael R

    2015-01-01

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

  8. Studies of the human c-myb gene and its product in human acute leukemias.

    PubMed

    Slamon, D J; Boone, T C; Murdock, D C; Keith, D E; Press, M F; Larson, R A; Souza, L M

    1986-07-18

    The myb gene is the transforming oncogene of the avian myeloblastosis virus (AMV); its normal cellular homolog, c-myb, is conserved across a broad span of evolution. In humans, c-myb is expressed in malignant hematopoietic cell lines and in primary hematopoietic tumors. Partial complementary DNA clones were generated from blast cells of patients with acute myelogenous leukemia. The sequences of the clones were compared to the c-myb of other species, as well as the v-myb of AMV. In addition, the carboxyl terminal region of human c-myb was placed in an expression vector to obtain protein for the generation of antiserum, which was used to identify the human c-myb gene product. Like v-myb, this protein was found within the nucleus of leukemic cells where it was associated with the nuclear matrix. These studies provide further evidence that c-myb might be involved in human leukemia. PMID:3014652

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

    SciTech Connect

    Price, Paul S. Keenan, Russell E.; Swartout, Jeffrey C.

    2008-11-15

    For most chemicals, the Reference Dose (RfD) is based on data from animal testing. The uncertainty introduced by the use of animal models has been termed interspecies uncertainty. The magnitude of the differences between the toxicity of a chemical in humans and test animals and its uncertainty can be investigated by evaluating the inter-chemical variation in the ratios of the doses associated with similar toxicological endpoints in test animals and humans. This study performs such an evaluation on a data set of 64 anti-neoplastic drugs. The data set provides matched responses in humans and four species of test animals: mice, rats, monkeys, and dogs. While the data have a number of limitations, the data show that when the drugs are evaluated on a body weight basis: 1) toxicity generally increases with a species' body weight; however, humans are not always more sensitive than test animals; 2) the animal to human dose ratios were less than 10 for most, but not all, drugs; 3) the current practice of using data from multiple species when setting RfDs lowers the probability of having a large value for the ratio. These findings provide insight into inter-chemical variation in animal to human extrapolations and suggest the need for additional collection and analysis of matched toxicity data in humans and test animals.

  10. 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

  11. Proc. INTERACT 2005, LNCS 3585, 767-780 RealTourist A Study of Augmenting Human-Human

    E-print Network

    Zhai, Shumin

    to contribute to an empirical foundation of future multimodal human-com- puter interaction systems with eyeProc. INTERACT 2005, LNCS 3585, 767-780 RealTourist A Study of Augmenting Human-Human and Human-Computer Dialogue with Eye-Gaze Overlay Pernilla Qvarfordt1 David Beymer2 Shumin Zhai2 1 Department of Computer

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

    E-print Network

    Stoddard, Angela May

    1994-01-01

    reflect the driver and vehicle population currently on the transportation network. An accident causation study was conducted to determine if roadways with limited stopping sight distance present a safety hazard for the transportation network. Rural two...

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

    PubMed

    Montales, Maria Theresa E; Rahal, Omar M; Nakatani, Hajime; Matsuda, Tsukasa; Simmen, Rosalia C M

    2013-07-01

    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 in rodent breast cancer models. Despite the suggested linkage between obesity and breast cancer, the local influence of bioactive dietary components on mammary adiposity for antitumor effects remains unknown. Herein, we report that post-weaning dietary exposure to soy protein isolate and its bioactive isoflavone genistein (GEN) lowered mammary adiposity and increased mammary tumor suppressor PTEN and E-cadherin expression in female mice, relative to control casein diet. To ascertain GEN's role in mammary adipose deposition that may affect underlying epithelial cell phenotype, we evaluated GEN's effects on SV40-immortalized mouse mammary stromal fibroblast-like (MSF) cells during differentiation into adipocytes. MSF cells cultured in a differentiation medium with 40?nM GEN showed reductions in mature adipocyte numbers, triglyceride accumulation, and Ppar? (Pparg) and fatty acid synthase transcript levels. GEN inhibition of adipose differentiation was accompanied by increased estrogen receptor ? (Er? (Esr2)) gene expression and was modestly recapitulated by ER?-selective agonist 2,3-bis-(4-hydroxyphenyl)-propionitrile (DPN). Reduction of Er? expression by siRNA targeting increased Ppar? transcript levels and stromal fibroblast differentiation into mature adipocytes; the latter was reversed by GEN but not by DPN. Conditioned medium from GEN-treated adipocytes diminished anchorage-independent mammosphere formation of human MCF-7 breast cancer cells. Our results suggest a mechanistic pathway to support direct regulation of mammary adiposity by GEN for breast cancer prevention. PMID:23645249

  14. Literary works as case studies for teaching human experimentation ethics.

    PubMed

    Cassidy, V R

    1996-03-01

    Case studies are widely used as a teaching strategy for a variety of topics in various disciplines. They are particularly valued as a teaching strategy in the teaching of ethics because they provide a context for understanding the complexities of situations involving ethical dilemmas. This article describes the successful use of two literary works as case studies in teaching master's students about the ethical issues in human experimentation. Pygmalion and Flowers for Algernon were selected to exemplify the ethical considerations important in the conduct of research with human subjects. Students found the assignment both personally and professionally stimulating and recommended continued use of the assignment in the course. PMID:8676212

  15. Anterior prefrontal function and the limits of human decision-making.

    PubMed

    Koechlin, Etienne; Hyafil, Alexandre

    2007-10-26

    The frontopolar cortex (FPC), the most anterior part of the frontal lobes, forms the apex of the executive system underlying decision-making. Here, we review empirical evidence showing that the FPC function enables contingent interposition of two concurrent behavioral plans or mental tasks according to respective reward expectations, overcoming the serial constraint that bears upon the control of task execution in the prefrontal cortex. This function is mechanistically explained by interactions between FPC and neighboring prefrontal regions. However, its capacity appears highly limited, which suggests that the FPC is efficient for protecting the execution of long-term mental plans from immediate environmental demands and for generating new, possibly more rewarding, behavioral or cognitive sequences, rather than for complex decision-making and reasoning. PMID:17962551

  16. 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.

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

    PubMed Central

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

    2015-01-01

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

  18. 40 CFR 26.1603 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Operation of the Human Studies Review... PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1603 Operation of the Human Studies Review Board. EPA shall establish and operate a Human Studies Review Board as follows:...

  19. 40 CFR 26.1603 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Operation of the Human Studies Review... PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1603 Operation of the Human Studies Review Board. EPA shall establish and operate a Human Studies Review Board as follows:...

  20. 40 CFR 26.1605 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Operation of the Human Studies Review... PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1605 Operation of the Human Studies Review Board. EPA shall establish and operate a Human Studies Review Board as follows:...

  1. 40 CFR 26.1603 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Operation of the Human Studies Review... PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1603 Operation of the Human Studies Review Board. EPA shall establish and operate a Human Studies Review Board as follows:...

  2. 40 CFR 26.1605 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Operation of the Human Studies Review... PROTECTION OF HUMAN SUBJECTS Review of Proposed and Completed Human Research § 26.1605 Operation of the Human Studies Review Board. EPA shall establish and operate a Human Studies Review Board as follows:...

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

    SciTech Connect

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

    1988-04-01

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

  4. Department of Political Studies The Department of Political Studies at the University of Saskatchewan invites applications for a limited term

    E-print Network

    Saskatchewan, University of

    Department of Political Studies The Department of Political Studies at the University Relations and Global Studies at the rank of Lecturer, for the period July 1, 2015 to June 30, 2016. The College of Arts & Science offers a dynamic combination of programs in the humanities and fine arts

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

    ERIC Educational Resources Information Center

    Adams, Margaret Smolinka

    2013-01-01

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

  6. A Novel Remote Controlled Capsule for Human Drug Absorption studies.

    PubMed

    Xitian, Pi; Xiaolin, Zheng; Chenglin, Peng; Wensheng, Hou; Hongying, Liu

    2005-01-01

    Remote Controlled Capsule (RCC) is a new method to realize non-invasive drug delivery to the selected sites of human gastro-intestinal (GI) tract. With RCC, Human Drug Absorption (HDA) studies are taken easily to obtain data on the intestinal absorption of a drug in humans. In this paper, a new RCC system has been designed based on MEMS technology to provide for the delivery of a wide range of different drug formulations, for example, solution, powder and granulate, into any region of the gut. A magnetic Marker Monitoring (MMM) system was developed to monitor the location of the capsule inside the gut. A novel method to indicating the drug release, called as Indicating System based on Abrupt Movement of Marker (ISAMM), was proposed in this study. High reliability of the RCC system has been proved by animal experiments. PMID:17281385

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

    NASA Astrophysics Data System (ADS)

    Lundquist, Marjorie

    2005-03-01

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

  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. 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

  10. 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

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

    PubMed

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

    2015-06-01

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

  12. Autophagy limits the cytotoxic effects of the AKT inhibitor AZ7328 in human bladder cancer cells

    PubMed Central

    Dickstein, Rian J.; Nitti, Giovanni; Dinney, Colin P.; Davies, Barry R.; Kamat, Ashish M.; McConkey, David J.

    2012-01-01

    Background: Mutations that activate the PI3K/AKT/mTOR pathway are relatively common in urothelial (bladder) cancers, but how these pathway mutations affect AKT dependency is not known. We characterized the relationship between AKT pathway mutational status and sensitivity to the effects of the selective AKT kinase inhibitor AZ7328 using a panel of 12 well-characterized human bladder cancer cell lines. Methods: Sequenome DNA sequencing was performed to identify mutations in a panel of 12 urothelial cancer cell lines. Drug-induced proliferative inhibition and apoptosis were quantified using MTT assays and propidium iodide staining with FACS analyses. Protein activation via phosphorylation was measured by immunoblotting. Autophagy was measured by LC3 immunofluorescence and immunoblotting. Results: AZ7328 inhibited proliferation and AKT substrate phosphorylation in a concentration-dependent manner but had minimal effects on apoptosis. Proliferative inhibition correlated loosely with the presence of activating PIK3CA mutations and was strengthened in combination with the mTOR inhibitor rapamycin. AZ7328 induced autophagy in some of the lines, and in the cells exposed to a combination of AZ7328 and chemical autophagy inhibitors apoptosis was induced. Conclusions: The cytostatic effects of AZ7328 correlate with PIK3CA mutations and are greatly enhanced by dual pathway inhibition using an mTOR inhibitor. Furthermore, AZ7328 can interact with autophagy inhibitors to induce apoptosis in some cell lines. Overall, our results support the further evaluation of combinations of PI3K/AKT/mTOR pathway and autophagy inhibitors in pre-clinical in vivo models and ultimately in patients with PIK3CA mutant bladder cancers. PMID:22895070

  13. USE OF BIOMARKERS OF OXIDATIVE STRESS IN HUMAN STUDIES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In human studies, biomarkers can be employed to reflect environmental pro-oxidant exposures and dietary antioxidant intake or to serve as a surrogate measure of a disease process like carcinogenesis. While a number of challenges must be overcome in using biomarkers to obtain a better understanding ...

  14. Suelo: Human-assisted Sensing for Exploratory Soil Monitoring Studies

    E-print Network

    Kohler, Eddie

    Suelo: Human-assisted Sensing for Exploratory Soil Monitoring Studies Nithya Ramanathan Thomas required to fully un- derstand them. In this paper, we present Suelo, an embed- ded networked sensing system designed for soil monitoring. An important challenge for Suelo is that many soil sensors

  15. 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…

  16. MAJOR: HUMAN DEVELOPMENT & FAMILY STUDIES (HDFS) EMPHASIS: CHILD LIFE

    E-print Network

    Capecchi, Mario R.

    MAJOR: HUMAN DEVELOPMENT & FAMILY STUDIES (HDFS) EMPHASIS: CHILD LIFE Minimum HDFS-CL Major Hours TO FCS 5311: 1- FCS 2610 Understanding Children's Behavior 2- FCS 2620 Child Development Practicum Pre Development (CW if not used as 5311 pre-req 3 SU FCS 5310 Foundation of Child Life Practice if not used

  17. 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...

  18. Moreover, studies of human METH abusers reveal evidence of neurotoxicity

    E-print Network

    Blakely, Randy

    Moreover, studies of human METH abusers reveal evidence of neurotoxicity as indicated by long the contention that METH produces ex- citotoxicity and oxidative damage. Calcium influx through ionotropic). Although, METH increases free radi- cals (Giovanni et al, 1995), only recently has there been evidence

  19. Moral Disengagement in Business and Humanities Majors: An Exploratory Study

    ERIC Educational Resources Information Center

    Cory, Suzanne N.; Hernandez, Abigail R.

    2014-01-01

    This study measures moral disengagement of undergraduate business and humanities students with a focus on differences in moral disengagement between genders. Students completed a survey that consisted of 32 statements and were asked to determine the degree to which they agreed with each, using a 7-point Likert scale. The questions measured moral…

  20. Report of the 90-Day Study on Human Exploration of

    E-print Network

    Rathbun, Julie A.

    Report of the 90-Day Study on Human Exploration of the Moon and Mars November 1989 #12;NOV 20 '89 and one data acurce tor Council consideration of approaches to program, achedule and .technology in the report and also intends to examine a range·of robuet technical alternatives and approachea to mission

  1. Study on Adaptive Kalman Filtering Algorithms in Human Movement Tracking

    E-print Network

    Hu, Huosheng

    Study on Adaptive Kalman Filtering Algorithms in Human Movement Tracking Yi Zhang Huosheng Hu to recover and improve their mobility toward normal life. This paper presents an adaptive Kalman filter and efficiency of the proposed adaptive algorithm is verified by simulation results. Index Terms - Kalman Filter

  2. 40 CFR 26.1603 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...Membership . The Human Studies Review Board shall consist...fields appropriate for the scientific and ethical review of human...Responsibilities . The Human Studies Review Board shall comment on the scientific and ethical aspects of...

  3. 40 CFR 26.1603 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ...Membership . The Human Studies Review Board shall consist...fields appropriate for the scientific and ethical review of human...Responsibilities . The Human Studies Review Board shall comment on the scientific and ethical aspects of...

  4. 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.

  5. IIT Lewis College of Human Sciences Psychology, the scientific study of human behavior and the mind, impacts every

    E-print Network

    Heller, Barbara

    IIT Lewis College of Human Sciences PSYCHOLOGY Psychology, the scientific study of human behavior and the mind, impacts every aspect of our culture and society. How we view our place in the world, make

  6. Simplified detection system for neuroreceptor studies in the human brain

    SciTech Connect

    Bice, A.N.; Wagner, H.N. Jr.; Frost, J.J.; Natarajan, T.K.; Lee, M.C.; Wong, D.F.; Dannals, R.F.; Ravert, H.T.; Wilson, A.A.; Links, J.M.

    1986-02-01

    A simple, inexpensive dual-detector system has been developed for measurement of positronemitting receptor-binding drugs in the human brain. This high efficiency coincidence counting system requires that only a few hundred microcuries of labeled drug be administered to the subject, thereby allowing for multiple studies without an excessive radiation dose. Measurement of the binding of (11C)carfentanil, a high affinity synthetic opiate, to opiate receptors in the presence and in the absence of a competitive opiate antagonist indicates the potential utility of this system for estimating different degrees of receptor occupation in the human brain.

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

    NASA Astrophysics Data System (ADS)

    Horneck, G.

    ESA has recently initiated a study of the human responses, limits and needs with regard to the stress environments of interplanetary and planetary missions. Emphasis was laid on human health and performance care as well as Advanced Life Support Developments including Bioregenerative Life Support Systems and environmental monitoring. The overall study goals were as follows: (i) to define reference scenarios for a European participation in human exploration and to estimate their influence on the Life Sciences and Life Support requirements; (ii) for selected mission scenarios, to critically assess the limiting factors for human health, wellbeing, and performance and to recommend relevant countermeasures; (iii) for selected mission scenarios, to critically assess the potential of Advanced Life Support Developments and to propose a European strategy including terrestrial applications; (iv) to critically assess the feasibility of existing facilities and technologies on ground and in space as testbeds in preparation for human exploratory missions and to develop a test plan for ground and ISS campaigns; (v) to develop a roadmap for a future European strategy towards human exploratory missions, including preparatory activities and terrestrial applications and benefits. A lunar base at the south pole where constant sunlight and potential water ice deposits could be assumed was selected as the moon scenario. the impact on human health, performance and well being has been investigated from the view point of the effects of microgravity (during space travel), reduced gravity (on the Moon) and abrupt gravity changes (during launch and landing), of the effects of cosmic radiation including solar particle events, of psychological issues as well as general health care. Countermeasures as well as necessary research using ground- based testbeds and/or the ISS have been defined. The need for highly intelligent autonomous diagnostic and therapy systems was considered as a driver also for terrestrial applications. Likewise advanced life support systems with a high degree of autonomy and regenerative capacity and synergy effects were considered where bioregenerative life support systems and biodiagnistic systems become essential especially for the long-term Mars scenario. A roadmap for a future European strategy leading to a potential European participation in a cooperative human exploratory mission, either to the Moon or to Mars, was produced. Ref. Horneck et al. HUMEX, study on the Survivability and Adaptation of Humans to Long-Duration Exploratory Missions, ESA SP (in press)

  8. 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

  9. 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.

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  11. 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

  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 human neuron injury model for molecular studies of axonal regeneration.

    PubMed

    Ziegler, Lina; Segal-Ruder, Yael; Coppola, Giovanni; Reis, Arbel; Geschwind, Daniel; Fainzilber, Mike; Goldstein, Ronald S

    2010-05-01

    The enhancement of regeneration of damaged axons in both the peripheral and central nervous systems is a widely pursued goal in clinical medicine. Although some of the molecular mechanisms involved in the intrinsic neurite regeneration program have been elucidated, much additional study is required for development of new therapeutics. The majority of studies in the field of axonal regeneration have utilized animal models due to obvious limitations of the accessibility of human neural tissues. Here we describe the use of human embryonic stem cell (hESC)-derived neurons as a novel model for studying neuronal responses to axonal injury. Neurons were generated using PA6 induction and neurites injured in vitro using trituration or laser microdissection. Lesioned neurons re-extended neurites with distinct growth cones. Expression of proteins associated with regeneration were observed in this human in vitro system, including appearance of importin beta1 in processes after neuritomy. Laser-transected hESC-derived neuronal cultures were analyzed for their transcriptional response to injury using Affymetrix expression microarrays. Profound changes in gene expression were observed over a time course of 2 to 24 hours after lesion. The expression of several genes reported to be involved in axonal injury responses in animal models changed following injury of hESC-derived neurons. Thus, hESC-derived neurons may be a useful in vitro model system for mechanistic studies on human axonal injury and regeneration. PMID:19804775

  15. Modelling Human Regulatory Variation in Mouse: Finding the Function in Genome-Wide Association Studies and Whole-Genome Sequencing

    PubMed Central

    Schmouth, Jean-François; Bonaguro, Russell J.; Corso-Diaz, Ximena; Simpson, Elizabeth M.

    2012-01-01

    An increasing body of literature from genome-wide association studies and human whole-genome sequencing highlights the identification of large numbers of candidate regulatory variants of potential therapeutic interest in numerous diseases. Our relatively poor understanding of the functions of non-coding genomic sequence, and the slow and laborious process of experimental validation of the functional significance of human regulatory variants, limits our ability to fully benefit from this information in our efforts to comprehend human disease. Humanized mouse models (HuMMs), in which human genes are introduced into the mouse, suggest an approach to this problem. In the past, HuMMs have been used successfully to study human disease variants; e.g., the complex genetic condition arising from Down syndrome, common monogenic disorders such as Huntington disease and ?-thalassemia, and cancer susceptibility genes such as BRCA1. In this commentary, we highlight a novel method for high-throughput single-copy site-specific generation of HuMMs entitled High-throughput Human Genes on the X Chromosome (HuGX). This method can be applied to most human genes for which a bacterial artificial chromosome (BAC) construct can be derived and a mouse-null allele exists. This strategy comprises (1) the use of recombineering technology to create a human variant–harbouring BAC, (2) knock-in of this BAC into the mouse genome using Hprt docking technology, and (3) allele comparison by interspecies complementation. We demonstrate the throughput of the HuGX method by generating a series of seven different alleles for the human NR2E1 gene at Hprt. In future challenges, we consider the current limitations of experimental approaches and call for a concerted effort by the genetics community, for both human and mouse, to solve the challenge of the functional analysis of human regulatory variation. PMID:22396661

  16. 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.

  17. 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.

  18. 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.

  19. A validation study of a stochastic model of human interaction

    NASA Astrophysics Data System (ADS)

    Burchfield, Mitchel Talmadge

    The purpose of this dissertation is to validate a stochastic model of human interactions which is part of a developmentalism paradigm. Incorporating elements of ancient and contemporary philosophy and science, developmentalism defines human development as a progression of increasing competence and utilizes compatible theories of developmental psychology, cognitive psychology, educational psychology, social psychology, curriculum development, neurology, psychophysics, and physics. To validate a stochastic model of human interactions, the study addressed four research questions: (a) Does attitude vary over time? (b) What are the distributional assumptions underlying attitudes? (c) Does the stochastic model, {-}N{intlimitssbsp{-infty}{infty}}varphi(chi,tau)\\ Psi(tau)dtau, have utility for the study of attitudinal distributions and dynamics? (d) Are the Maxwell-Boltzmann, Fermi-Dirac, and Bose-Einstein theories applicable to human groups? Approximately 25,000 attitude observations were made using the Semantic Differential Scale. Positions of individuals varied over time and the logistic model predicted observed distributions with correlations between 0.98 and 1.0, with estimated standard errors significantly less than the magnitudes of the parameters. The results bring into question the applicability of Fisherian research designs (Fisher, 1922, 1928, 1938) for behavioral research based on the apparent failure of two fundamental assumptions-the noninteractive nature of the objects being studied and normal distribution of attributes. The findings indicate that individual belief structures are representable in terms of a psychological space which has the same or similar properties as physical space. The psychological space not only has dimension, but individuals interact by force equations similar to those described in theoretical physics models. Nonlinear regression techniques were used to estimate Fermi-Dirac parameters from the data. The model explained a high degree of the variance in each probability distribution. The correlation between predicted and observed probabilities ranged from a low of 0.955 to a high value of 0.998, indicating that humans behave in psychological space as Fermions behave in momentum space.

  20. Utility of a human-mouse xenograft model and in vivo near-infrared fluorescent imaging for studying wound healing.

    PubMed

    Shanmugam, Victoria K; Tassi, Elena; Schmidt, Marcel O; McNish, Sean; Baker, Stephen; Attinger, Christopher; Wang, Hong; Shara, Nawar; Wellstein, Anton

    2015-12-01

    To study the complex cellular interactions involved in wound healing, it is essential to have an animal model that adequately mimics the human wound microenvironment. Currently available murine models are limited because wound contraction introduces bias into wound surface area measurements. The purpose of this study was to demonstrate utility of a human-mouse xenograft model for studying human wound healing. Normal human skin was harvested from elective abdominoplasty surgery, xenografted onto athymic nude (nu/nu) mice, and allowed to engraft for 3 months. The graft was then wounded using a 2-mm punch biopsy. Wounds were harvested on sequential days to allow tissue-based markers of wound healing to be followed sequentially. On the day of wound harvest, mice were injected with XenoLight RediJect cyclooxygenase-2 (COX-2) probe and imaged according to package instructions. Immunohistochemistry confirms that this human-mouse xenograft model is effective for studying human wound healing in vivo. Additionally, in vivo fluorescent imaging for inducible COX-2 demonstrated upregulation from baseline to day 4 (P = 0·03) with return to baseline levels by day 10, paralleling the reepithelialisation of the wound. This human-mouse xenograft model, combined with in vivo fluorescent imaging provides a useful mechanism for studying molecular pathways of human wound healing. PMID:24373153

  1. Activation of NF-?B by Human Papillomavirus 16 E1 Limits E1-Dependent Viral Replication through Degradation of E1

    PubMed Central

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

    2015-01-01

    ABSTRACT NF-?B is a family of transcription factors that regulate gene expression involved in many processes, such as the inflammatory response and cancer progression. Little is known about associations of NF-?B with the human papillomavirus (HPV) life cycle. We have developed a tissue culture system to conditionally induce E1-dependent replication of the human papillomavirus 16 (HPV16) genome in human cervical keratinocytes and found that expression of HPV16 E1, a viral helicase, results in reduction of I?B? and subsequent activation of NF-?B in a manner dependent on helicase activity. Exogenous expression of a degradation-resistant mutant of I?B?, which inhibits the activation of NF-?B, enhanced E1-dependent replication of the viral genome. Wortmannin, a broad inhibitor of phosphoinositide 3-kinases (PI3Ks), and, to a lesser extent, VE-822, an ATR kinase inhibitor, but not KU55933, an ATM kinase inhibitor, suppressed the activation of NF-?B and augmented E1-dependent replication of the HPV16 genome. Interestingly, the enhancement of E1-dependent replication of the viral genome was associated with increased stability of E1 in the presence of wortmannin as well as the I?B? mutant. Collectively, we propose that expression of E1 induces NF-?B activation at least in part through the ATR-dependent DNA damage response and that NF-?B in turn limits E1-dependent replication of HPV16 through degradation of E1, so that E1 and NF-?B may constitute a negative feedback loop. IMPORTANCE A major risk factor in human papillomavirus (HPV)-associated cancers is persistent infection with high-risk HPVs. To eradicate viruses from infected tissue, it is important to understand molecular mechanisms underlying the establishment and maintenance of persistent infection. In this study, we obtained evidence that human papillomavirus 16 (HPV16) E1, a viral DNA helicase essential for amplification of the viral genomes, induces NF-?B activation and that this limits E1-dependent genome replication of HPV16. These results suggest that NF-?B mediates a negative feedback loop to regulate HPV replication and that this feedback loop could be associated with control of the viral copy numbers. We could thus show for the first time that NF-?B activity is involved in the establishment and maintenance of persistent HPV infection. PMID:25717108

  2. Study of Gap Junctions in Human Embryonic Stem Cells.

    PubMed

    Pébay, Alice; Wong, Raymond C B

    2016-01-01

    Gap junctional intercellular communication (GJIC) has been described in different cell types including stem cells and has been involved in different biological events. GJIC is required for mouse embryonic stem cell maintenance and proliferation and various studies suggest that functional GJIC is a common characteristic of human embryonic stem cells (hESC) maintained in different culture conditions. This chapter introduces methods to study gap junctions in hESC, from expression of gap junction proteins to functional study of GJIC in hESC proliferation, apoptosis, colony growth, and pluripotency. PMID:24859928

  3. Study of Light Scattering in the Human Eye

    NASA Astrophysics Data System (ADS)

    Perez, I. Kelly; Bruce, N. C.; Valdos, L. R. Berriel

    2008-04-01

    In this paper we present a numerical model of the human eye to be used in studies of the scattering of light in different components of the eye's optical system. Different parts of the eye are susceptible to produce scattering for different reasons; age, illness or injury. For example, cataracts can appear in the human lens or injuries or fungi can appear on the cornea. The aim of the study is to relate the backscattered light, which is what doctors measure or detect, to the forward scattered light, which is what affects the patient's vision. We present the model to be used, the raytrace procedure and some preliminary results for the image on the retina without scattering.

  4. Sequencing studies in human genetics: design and interpretation

    PubMed Central

    Goldstein, David B.; Allen, Andrew; Keebler, Jonathan; Margulies, Elliott H.; Petrou, Steven; Petrovski, Slavé; Sunyaev, Shamil

    2014-01-01

    Next-gene ration sequencing is becoming the primary discovery tool in human genetics. There have been many clear successes in identifying genes that are responsible for Mendelian diseases, and sequencing approaches are now poised to identify the mutations that cause undiagnosed childhood genetic diseases and those that predispose individuals to more common complex diseases. There are, however, growing concerns that the complexity and magnitude of complete sequence data could lead to an explosion of weakly justified claims of association between genetic variants and disease. Here, we provide an overview of the basic workflow in next-generation sequencing studies and emphasize, where possible, measures and considerations that facilitate accurate inferences from human sequencing studies. PMID:23752795

  5. Noninvasive studies of human visual cortex using neuromagnetic techniques

    SciTech Connect

    Aine, C.J.; George, J.S.; Supek, S. ); Maclin, E.L. . Center for Magnetoencephalography)

    1990-01-01

    The major goals of noninvasive studies of the human visual cortex are: to increase knowledge of the functional organization of cortical visual pathways; and to develop noninvasive clinical tests for the assessment of cortical function. Noninvasive techniques suitable for studies of the structure and function of human visual cortex include magnetic resonance imaging (MRI), positron emission tomography (PET), single photon emission tomography (SPECT), scalp recorded event-related potentials (ERPs), and event-related magnetic fields (ERFs). The primary challenge faced by noninvasive functional measures is to optimize the spatial and temporal resolution of the measurement and analytic techniques in order to effectively characterize the spatial and temporal variations in patterns of neuronal activity. In this paper we review the use of neuromagnetic techniques for this purpose. 8 refs., 3 figs.

  6. IIT Lewis College of Human Sciences In the humanities program at IIT--as you study history, philosophy,

    E-print Network

    Heller, Barbara

    IIT Lewis College of Human Sciences HUMANITIES In the humanities program at IIT--as you study history, philosophy, communication, literature, or art and architectural history--you will also examine to enter the workforce and make a difference for the future. BACHELOR OF SCIENCE IN #12;GET CONNECTED

  7. Establishment of a Reverse Genetics System for Studying Human Bocavirus in Human Airway Epithelia

    PubMed Central

    Cheng, Fang; Luo, Yong; Shen, Weiran; Lei-Butters, Diana C. M.; Chen, Aaron Yun; Li, Yi; Tang, Liang; Söderlund-Venermo, Maria; Engelhardt, John F.; Qiu, Jianming

    2012-01-01

    Human bocavirus 1 (HBoV1) has been identified as one of the etiological agents of wheezing in young children with acute respiratory-tract infections. In this study, we have obtained the sequence of a full-length HBoV1 genome (including both termini) using viral DNA extracted from a nasopharyngeal aspirate of an infected patient, cloned the full-length HBoV1 genome, and demonstrated DNA replication, encapsidation of the ssDNA genome, and release of the HBoV1 virions from human embryonic kidney 293 cells. The HBoV1 virions generated from this cell line-based production system exhibits a typical icosahedral structure of approximately 26 nm in diameter, and is capable of productively infecting polarized primary human airway epithelia (HAE) from the apical surface. Infected HAE showed hallmarks of lung airway-tract injury, including disruption of the tight junction barrier, loss of cilia and epithelial cell hypertrophy. Notably, polarized HAE cultured from an immortalized airway epithelial cell line, CuFi-8 (originally derived from a cystic fibrosis patient), also supported productive infection of HBoV1. Thus, we have established a reverse genetics system and generated the first cell line-based culture system for the study of HBoV1 infection, which will significantly advance the study of HBoV1 replication and pathogenesis. PMID:22956907

  8. The Influences of Genetic and Environmental Factors on Methylome-wide Association Studies for Human Diseases

    PubMed Central

    Sun, Yan V.

    2014-01-01

    DNA methylation (DNAm) is an essential epigenetic mechanism for normal development, and its variation may be associated with diseases. High-throughput technology allows robust measurement of DNA methylome in population studies. Methylome-wide association studies (MWAS) scan DNA methylome to detect new epigenetic loci affecting disease susceptibility. MWAS is an emerging approach to unraveling the mechanism linking genetics, environment, and human diseases. Here I review the recent studies of genetic determinants and environmental modifiers of DNAm, and the concept for partitioning genetic and environmental contribution to DNAm. These studies establish the correlation maps between genome and methylome, and enable the interpretation of epigenetic association with disease traits. Recent findings suggested that MWAS was a promising genomic method to identify epigenetic predictors accounting for unexplained disease risk. However, new study designs, analytical methods and shared resources need to be implemented to address the limitations and challenges in future epigenomic epidemiologic studies. PMID:25422794

  9. Feasibility of a 3D human airway epithelial model to study respiratory absorption.

    PubMed

    Reus, Astrid A; Maas, Wilfred J M; Jansen, Harm T; Constant, Samuel; Staal, Yvonne C M; van Triel, Jos J; Kuper, C Frieke

    2014-03-01

    The respiratory route is an important portal for human exposure to a large variety of substances. Consequently, there is an urgent need for realistic in vitro strategies for evaluation of the absorption of airborne substances with regard to safety and efficacy assessment. The present study investigated feasibility of a 3D human airway epithelial model to study respiratory absorption, in particular to differentiate between low and high absorption of substances. Bronchial epithelial models (MucilAir™), cultured at the air-liquid interface, were exposed to eight radiolabeled model substances via the apical epithelial surface. Absorption was evaluated by measuring radioactivity in the apical compartment, the epithelial cells and the basolateral culture medium. Antipyrine, caffeine, naproxen and propranolol were highly transported across the epithelial cell layer (>5%), whereas atenolol, mannitol, PEG-400 and insulin were limitedly transported (<5%). Results indicate that the 3D human airway epithelial model used in this study is able to differentiate between substances with low and high absorption. The intra-experimental reproducibility of the results was considered adequate based on an average coefficient of variation (CV) of 15%. The inter-experimental reproducibility of highly absorbed compounds was in a similar range (CV of 15%), but this value was considerably higher for those compounds that were limitedly absorbed. No statistical significant differences between different donors and experiments were observed. The present study provides a simple method transposable in any lab, which can be used to rank the absorption of chemicals and pharmaceuticals, and is ready for further validation with respect to reproducibility and capacity of the method to predict respiratory transport in humans. PMID:24216300

  10. Engineered human vaccines

    SciTech Connect

    Sandhu, J.S. . 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. 78 FR 71707 - MAP-21 Comprehensive Truck Size and Weight Limits Study Public Meeting and Outreach Sessions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-29

    ... Federal Highway Administration MAP-21 Comprehensive Truck Size and Weight Limits Study Public Meeting and... Century Act (MAP-21) Comprehensive Truck Size and Weight Limits Study. The Transportation Research Board Committee for Review of the U.S. Department of Transportation (DOT) Truck Size and Weight Limits Study...

  12. Tamoxifen experimental carcinogenicity studies: Implications for human effects

    SciTech Connect

    Williams, G.M.

    1995-02-01

    Tamoxifen is an effective antiestrogen in the treatment of breast cancer and is considered highly safe. In recent years, several trials have been initiated in women to evaluate its potential for the prevention of breast cancer. Such long-term administration of a medication to healthy people requires a substantial degree of safety. This review examines experimental carcinogenicity and mechanistic studies on tamoxifen and the implications for human effects. 25 refs.

  13. Lost in Virtual Space: Studies in Human and Ideal Spatial Navigation

    ERIC Educational Resources Information Center

    Stankiewicz, Brian J.; Legge, Gordon E.; Mansfield, J. Stephen; Schlicht, Erik J.

    2006-01-01

    The authors describe 3 human spatial navigation experiments that investigate how limitations of perception, memory, uncertainty, and decision strategy affect human spatial navigation performance. To better understand the effect of these variables on human navigation performance, the authors developed an ideal-navigator model for indoor navigation…

  14. 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

  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. Experimental study of bioartificial liver with cultured human liver cells

    PubMed Central

    Wang, Ying-Jie; Li, Meng-Dong; Wang, Yu-Ming; Nie, Qing-He; Chen, Guo-Zheng

    1999-01-01

    AIM To establish an extracorporeal bioartificial liver support system (EBLSS) using cultured human liver cells and to study its support effect for fulminant hepatic failure (FHF). METHODS The liver support experiment of EBLSS consisting of aggregates cultured human liver cells, hollow fiber bioreactor, and circulation unit was carried out in dizhepatic dogs. RESULTS The viability of isolated hepatocytes and nonparenchymal liver cells reached 96%. These cells were successfully cultured as multicellular spheroids with synthetic technique. The typical morphological appearance was retained up to the end of the artificial liver experiment. Compared with the control dogs treated with EBLSS without liver cells, the survival time of artificial liver support dogs was significantly prolonged. The changes of blood pressure, heart rate and ECG were slow. Both serum ammonia and lactate levels were significantly lowered at the 3rdh and 5thh. In addition, a good viability of human liver cells was noted after 5h experiment. CONCLUSION EBLSS playing a metabolic role of cultured human hepatocytes, is capable of compensating the function of the liver, and could provide effective artificial liver support and therapy for patients with FHF. PMID:11819412

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

    PubMed Central

    Elwood, J M

    1999-01-01

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

  18. 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...

  19. 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...

  20. 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...

  1. Dietary flavonoid intake and colorectal cancer risk: evidence from human population studies.

    PubMed

    Kocic, B; Kitic, D; Brankovic, S

    2013-01-01

    Flavonoids are biologically active polyphenolic compounds widely distributed in plants. More than 5000 individual flavonoids have been identified, which are classified into at least 10 subgroups according to their chemical structure. Flavonoids of 6 principal subgroups- flavonols, flavones, anthocyanidins, catechins, flavanones, and isoflavones- are relatively common in human diets. Flavonoids are a large and diverse group of phytochemicals and research into their anti-carcinogenic potential with animal and cellular model systems supports a protective role. Whether dietary intake of flavonoids is protective against colorectal cancer in humans cannot be easily extrapolated from cell line and animal findings. Epidemiological assessment of the relationship between dietary flavonoid intake and colorectal cancer is limited, with different case-control and cohort study design investigating different combinations of flavonoids. Epidemiologic studies on flavonoid intake and colorectal cancer risk that were conducted yielded inconsistent results, with positive, inverse, and null associations. Because only a very limited number of epidemiological studies have been conducted to examine the associations of dietary intake of flavonoids with colorectal cancer risk, it is premature to make public health recommendations at this time. However, the data to date are promising and emphasize the need for further investigation of these important bioactive plant compounds. This review summarises the epidemiological evidence from case-control and cohort studies on the associations of dietary flavonoid intake with the risk for colorectal cancer. The difficulties in investigating this topic and possibilities for further research are then discussed. PMID:23613386

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

    ERIC Educational Resources Information Center

    Picasso de Oyague, Alfredo

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

  3. 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...

  4. 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

  5. Permissible Limits of Arm Dimensions for Master-Slave System -Study on Telexistence (LVI)-

    E-print Network

    Tachi, Susumu

    56 Permissible Limits of Arm Dimensions for Master-Slave System -Study on Telexistence (LVI of slave robots in master-slave system, the fact that the dimensions of user does not match the dimensions of slave robot influence on the task performance. In particular, it is important to define analytically

  6. 78 FR 76888 - MAP-21 Comprehensive Truck Size and Weight Limits Study Materials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-19

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

  7. 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…

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

    PubMed

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

    2015-10-15

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

  9. Design, recruitment, and microbiological considerations in human challenge studies.

    PubMed

    Darton, Thomas C; Blohmke, Christoph J; Moorthy, Vasee S; Altmann, Daniel M; Hayden, Frederick G; Clutterbuck, Elizabeth A; Levine, Myron M; Hill, Adrian V S; Pollard, Andrew J

    2015-07-01

    Since the 18th century a wealth of knowledge regarding infectious disease pathogenesis, prevention, and treatment has been accumulated from findings of infection challenges in human beings. Partly because of improvements to ethical and regulatory guidance, human challenge studies-involving the deliberate exposure of participants to infectious substances-have had a resurgence in popularity in the past few years, in particular for the assessment of vaccines. To provide an overview of the potential use of challenge models, we present historical reports and contemporary views from experts in this type of research. A range of challenge models and practical approaches to generate important data exist and are used to expedite vaccine and therapeutic development and to support public health modelling and interventions. Although human challenge studies provide a unique opportunity to address complex research questions, participant and investigator safety is paramount. To increase the collaborative effort and future success of this area of research, we recommend the development of consensus frameworks and sharing of best practices between investigators. Furthermore, standardisation of challenge procedures and regulatory guidance will help with the feasibility for using challenge models in clinical testing of new disease intervention strategies. PMID:26026195

  10. 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.

  11. 76 FR 2107 - Human Studies Review Board; Notice of Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-12

    ...of the Human Studies Review Board...Agency on EPA's scientific and ethical...EPA's Human Studies Review Board will consider scientific and ethical...equipment. The studies were conducted...HSRB on the scientific soundness...

  12. 77 FR 74004 - Human Studies Review Board; Notification of a Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-12-12

    ...meeting of the Human Studies Review Board to advise...Agency on the EPA scientific and ethical reviews...2013, EPA's Human Studies Review Board will consider scientific and ethical issues...a. A completed study report from the...

  13. 77 FR 60116 - Human Studies Review Board; Notification of a Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-02

    ...meeting of the Human Studies Review Board to advise...Agency on the EPA scientific and ethical reviews...2012, EPA's Human Studies Review Board will consider scientific and ethical issues...a. A completed study report from the...

  14. Functional MRI studies of human vision on a clinical imager

    SciTech Connect

    George, J.S.; Lewine, J.D.; Aine, C.J.; van Hulsteyn, D.; Wood, C.C.; Sanders, J.; Maclin, E.; Belliveau, J.W.; Caprihan, A.

    1992-09-01

    During the past decade, Magnetic Resonance Imaging (MRI) has become the method of choice for imaging the anatomy of the human brain. Recently, Belliveau and colleagues have reported the use of echo planar magnetic resonance imaging (EPI) to image patterns of neural activity. Here, we report functional MR imaging in response to visual stimulation without the use of contrast agents, and without the extensive hardware modifications required for EPI. Regions of activity were observed near the expected locations of V1, V2 and possibly V3 and another active region was observed near the parietal-occipital sulcus on the superior surface of the cerebrum. These locations are consistent with sources observed in neuromagnetic studies of the human visual response.

  15. Functional MRI studies of human vision on a clinical imager

    SciTech Connect

    George, J.S.; Lewine, J.D.; Aine, C.J.; van Hulsteyn, D.; Wood, C.C. ); Sanders, J.; Maclin, E. ); Belliveau, J.W. ); Caprihan, A. )

    1992-01-01

    During the past decade, Magnetic Resonance Imaging (MRI) has become the method of choice for imaging the anatomy of the human brain. Recently, Belliveau and colleagues have reported the use of echo planar magnetic resonance imaging (EPI) to image patterns of neural activity. Here, we report functional MR imaging in response to visual stimulation without the use of contrast agents, and without the extensive hardware modifications required for EPI. Regions of activity were observed near the expected locations of V1, V2 and possibly V3 and another active region was observed near the parietal-occipital sulcus on the superior surface of the cerebrum. These locations are consistent with sources observed in neuromagnetic studies of the human visual response.

  16. STUDIES ON THE STABILITY OF THE NORMAL HUMAN FECAL FLORA

    PubMed Central

    Zubrzycki, Leonard; Spaulding, Earle H.

    1962-01-01

    Zubrzycki, Leonard (Temple University, Philadelphia, Pa.) and Earle H. Spaulding. Studies on the stability of the normal human fecal flora. J. Bacteriol. 83:968–974. 1962.—The results of two series of stool cultures show that members of the genus Bacteriodes constitute the most numerous group of bacteria in the normal human adult fecal flora. Together with the enterococci, coliform bacilli, diphtheroids, and lactobacilli, these major components account for more than 99% of the total counts. Wide fluctuations in the number and types of minor organisms observed suggest the probability that they are held in check by these major components which may also possess mechanisms for preventing pathogens from establishing themselves in the large bowel. PMID:16561946

  17. 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.

  18. 78 FR 71707 - MAP-21 Comprehensive Truck Size and Weight Limits Study Public Meeting and Outreach Sessions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-29

    ...operating at or within Federal truck size and weight (TSW) limits and...review of the Comprehensive Truck Size and Weight Limits Study. This...overall synthesis of the preceding body of work. The second peer review...Committee for Review of the DOT Truck Size and Weight Limits Study...

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

    E-print Network

    Bernstein, Michael S.

    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 ...

  20. A Study of Breakdown Limits in Microstrip Gas Counters with Preamplification Structures

    NASA Technical Reports Server (NTRS)

    Fonte, P.; Peskov, V.; Ramsey, B. D.

    1998-01-01

    We have studied the charge and breakdown limits of Microstrip Gas Counters (MSGCs) with 2 different preamplification structures: the Gas Electron Multiplier (GEM) and the Parallel-Plate Avalanche Counter (PPAC). It was found that in both cases the breakdown limit was increased by 1-2 orders of magnitude compared to the bare MSGC that this is due to the spread of the primary electron cloud during pre-amplification. This spreading reduces the charge density in the final MSGC avalanche, permitting much higher total gains before streamers form. The real practical gain limitations in these two-stage detectors arose not from sparking, but from a loss of proportionality due to space charge effects.

  1. 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

  2. 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

  3. Zebrafish as a model for the study of human cancer.

    PubMed

    Etchin, Julia; Kanki, John P; Look, A Thomas

    2011-01-01

    Zebrafish provide an exciting animal model system for the study of human cancers. During the last few years many zebrafish models of cancer have been generated that recapitulate human hematologic malignancies and solid tumors. Concurrent technological advances have significantly improved the genetic tractability and unique advantage of in vivo imaging in zebrafish, providing a means to dissect the molecular pathways underlying tumor initiation, progression and metastasis. Comparisons of cancer-associated gene expression profiles have demonstrated a high degree of similarity in the gene signatures of specific types of tumor cells in fish and humans, indicating that the contributing genetic pathways leading to cancer are evolutionarily conserved. Furthermore, the high fecundity, optical clarity and small embryo size of zebrafish continue to make it particularly amenable to performing whole-organism small molecule screens to identify targets for therapeutic development. This chapter reviews a wide array of these zebrafish cancer models and illustrates the advantages of the zebrafish system for exploring the molecular mechanisms governing cancer-related cellular processes. PMID:21951536

  4. Cornell Roundtable on Environmental Studies Topics The Arrogance of Humanism? : What Is the Role of the Humanities in the Environmental

    E-print Network

    Walter, M.Todd

    Cornell Roundtable on Environmental Studies Topics The Arrogance of Humanism? : What Is the Role of the Humanities in the Environmental Crisis? Michael Smith (Environmental History and Public History, Ithaca College); Nancy Menning (Religious Studies, Ithaca College); Sarah Ensor (English, Cornell); Amy Kohout

  5. Using Genomics to Study Human Biology and Disease

    SciTech Connect

    Myers, Ricard M.

    2005-04-06

    The Human Genome Project culminated in April 2003 with the finished DNA sequence of all of the human chromosomes. This book of information, particularly in conjunction with the genome sequences of many other organisms, has already begun to revolutionize the way that biomedical scientists study our species. The identification of essentially all of our genes has provided a template upon which researchers can discover basic processes that govern cells, organs, and the whole organism, and to understand the fundamental causes of the diseases that occur when something goes wrong with a gene or a set of genes. The Genome Project has already made it possible to identify the genes that are defective in more than 1,000 rare inherited diseases, and these discoveries have helped to understand the mechanisms of the more common forms of these disorders. This understanding of primary defects in diseases - which is translated as mutations in genes that encode proteins that serve specific functions - is transforming the way that biotechnology and pharmaceutical companies identify drug targets, and a few notable cases have already had a striking impact on specific diseases. In addition, it has become clear that the differential response to drugs in human populations is heavily influenced by genes, and a whole field called pharmacogenetics has begun to identify these genetic factors. Such knowledge will allow physicians to prescribe drugs targeted to each individual, with the potential to increase efficacy and decrease side-effects. Determining the DNA sequence of the human genome and identifying the genes has been an exciting endeavor, but we are only just beginning to understand the treasures present in all of our DNA. My presentation will briefly describe the road we took to get the sequence, as well as the tools that we are developing to unlock its secrets.

  6. 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.

  7. Considerations for Comprehensive Analyses of Sporozoite-Based Controlled Human Malaria Infection Studies

    PubMed Central

    Lover, Andrew A.

    2015-01-01

    There has been renewed interest in the use of sporozoite-based approaches for controlled human malaria infections (CHMIs), and several sets of human challenge studies have recently completed. A study undertaken in Tanzania and published in 2014 found dose dependence between 10,000 and 25,000 sporozoite doses, as well as divergent times-to-parasitemia relative to earlier studies in European volunteers, with important implications for planning future studies. Analysis of time-to-event data has had extensive development in recent years, but these methods have had limited exposure outside biostatistics. Expansion of the published analyses to include recent methodological approaches optimized for the types of data used could provide a richer analysis of these studies and may result in alternative findings. Specifically, in a re-analysis of these data using survival analysis techniques, the differences recorded in prepatent periods between the two dosing regimens do not reach statistical significance, and there is no evidence for statistically significant differences in prepatent periods between the Dutch and Tanzanian study sites. Although these findings do not impact the reported safety and tolerability of challange with cryopreserved Plasmodium falciparum sporozoites (PfSPZ), or invalidate the authors' hypotheses regarding naturally acquired immunity and its effect on parasite growth rates and prepatent periods, they highlight important opportunities to more fully use datasets from these trials and related CHMI experiments in the planning of future challenge studies. PMID:26392161

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

    SciTech Connect

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

    2010-02-02

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

  9. 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

  10. Development of myenteric plexus in human foetuses: a quantitative study

    PubMed Central

    Shariff, Ahmadulla; Roy, Tarasankar; Das, Taposh; Rani, Neerja

    2015-01-01

    Maturation of neurons of the myenteric plexus (MP) of human fetal sigmoid colon was studied at various weeks of gestation (WG). There is abundant literature on the development of MP in various segments of the gut but there are fewer reports on the development of MP in human sigmoid colon which is a site of various disorders. Sigmoid colonic segments from 12 aborted foetuses aged 14-23WG were processed for NADPH histochemistry. Stereologic evaluation of the neuronal cell profiles, numerical density, number of neurons per ganglion and myenteric fraction was conducted using using imageJ software. According to gestational age, foetuses were assigned into two groups (group 1 [n=7], less than <17WG and group 2 [n=5], more than >17WG). The overall size of neuronal cell profiles in the MP was significantly increased (P<0.05). The numerical density of neurons decreased in group 2 in comparison to group 1, the number of neurons per ganglion and myenteric fraction were increased in group 2 but all these were not statistically significant. This study revealed that the maturational event increases after 17WG and extensive innervations is established at 23WG. During prenatal life there is an increase in the neuronal cell size from 14-23WG signifying maturational process. Such studies are essential for clinicians and surgeons to correlate the normal and pathologic development of the enteric nervous system. PMID:26140223

  11. Substantial creep in healing human Achilles tendons. A pilot study

    PubMed Central

    Aspenberg, Per; Schepull, Thorsten

    2015-01-01

    Summary Background healing after rupture of the Achilles tendon can be described in terms of mechanical properties of the new-formed tissue, constituting the tendon callus. In previous human studies, the elastic modulus and the density remained almost constant during 3 months after mobilization started, and then improved up to one year. So far, time-dependent deformation of the healing human tendon has not been reported. Methods in a series of 16 patients, operated with Achilles tendon suture, we implanted tantalum beads into the tendon and measured the distance between them repeatedly during 3 min of constant loading, using an ordinary image intensifier. The patients unloaded their leg for 30 min before the test. To avoid bias, all images were investigated in a randomized and blinded order. Results total strain during 3 min of constant loading at 7 weeks post injury amounted to 5%, and at 19 weeks to 3%. About half of the strain, after the loading was applied, occurred during the second and third min. Considerable strain also occurred just before loading, when the patient was told that a load would be applied, but before this was actually done. Conclusion the measurements were crude, and this study should be seen as a pilot. Still, visco-elastic properties seem to dominate the mechanical behavior the healing Achilles tendon from start of mobilization to 19 weeks, at least when tested after 30 min rest. This deserves further studies with more precise methods. PMID:26605187

  12. Diatrizoate CT distribution kinetics: a study of human tissue characterization.

    PubMed

    Oppenheimer, D A; Young, S W

    1983-04-01

    Diatrizoate distribution volume (DDV) is a property of living tissue which characterizes the distribution of diatrizoate contrast material within the tissue. This study compiles DDV and enhancement data from computed tomography (CT) of normal human adults. Tissues examined include liver, spleen, muscle, fat, and renal cortex. Four abnormal tissues, a cirrhotic liver, a liver infiltrated with metastatic colon carcinoma, and two examples of renal malignant lymphoma, were used for comparison. Time-DDV and time-enhancement values were generated for the normal tissues after a bolus of intravenous diatrizoate. The CT-DDV appears to be a potentially reliable indicator of diffuse organ pathology. PMID:6833559

  13. The genomics of preterm birth: from animal models to human studies

    PubMed Central

    2013-01-01

    Preterm birth (delivery at less than 37 weeks of gestation) is the leading cause of infant mortality worldwide. So far, the application of animal models to understand human birth timing has not substantially revealed mechanisms that could be used to prevent prematurity. However, with amassing data implicating an important role for genetics in the timing of the onset of human labor, the use of modern genomic approaches, such as genome-wide association studies, rare variant analyses using whole-exome or genome sequencing, and family-based designs, holds enormous potential. Although some progress has been made in the search for causative genes and variants associated with preterm birth, the major genetic determinants remain to be identified. Here, we review insights from and limitations of animal models for understanding the physiology of parturition, recent human genetic and genomic studies to identify genes involved in preterm birth, and emerging areas that are likely to be informative in future investigations. Further advances in understanding fundamental mechanisms, and the development of preventative measures, will depend upon the acquisition of greater numbers of carefully phenotyped pregnancies, large-scale informatics approaches combining genomic information with information on environmental exposures, and new conceptual models for studying the interaction between the maternal and fetal genomes to personalize therapies for mothers and infants. Information emerging from these advances will help us to identify new biomarkers for earlier detection of preterm labor, develop more effective therapeutic agents, and/or promote prophylactic measures even before conception. PMID:23673148

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

    SciTech Connect

    Rowland, R.E.

    1995-02-10

    This document was originally conceived as a description of the radium studies that took place at Argonne National Laboratory. It soon became evident, however, that to document the widespread use of radium, a brief review of the application of radium in medicine and in the US dial painting industry is required. Further, because the Argonne studies were not the only such efforts, brief overviews of the other radium programs are included. Even so, much material has been omitted. The extensive references included will allow the interested reader to find additional information. The effects of internally deposited radium in humans have been studied in this country for more than 75 years. Some 2,400 subjects have had their body contents of radium measured, and a majority of them have been followed for most of their adult lives, to understand and quantify the effects of radium. Many more individuals acquired radium internally but were never measured. Some of this group have been located and followed until death; in these cases the cause of death is known without a body content measurement. As a consequence of the efforts made to locate, measure, and follow exposed individuals, a great deal of information about the effects of radium is available. Nevertheless, great gaps remain in the knowledge of radium toxicity. The Argonne study is the largest every undertaken of the effects on humans of an internally deposited radioelement, in which the insult has been quantitated by actual measurements of the retained radioisotope. The study has now been terminated, even though more than 1,000 subjects with measured radium burdens are still alive. This document is written as a brief summary of current knowledge accumulated in this incomplete study.

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

    PubMed

    Etzioni, Ruth; Gulati, Roman

    2016-03-01

    Numerous studies have attempted to quantify the number of breast cancers that would never have been diagnosed in the absence of screening. Unfortunately, results are highly variable across studies and there is considerable disagreement about both the frequency of overdiagnosis and the validity of different methodologic approaches. In this Commentary, we review limitations of the two major approaches used in existing studies. Studies that use excess incidence as a proxy for overdiagnosis require a valid estimate of incidence in the absence of screening and sufficient follow-up to ensure the excess excludes relevant (ie, nonoverdiagnosed) cancers detected early. The requirement of sufficient follow-up applies to both population studies and clinical trials, but only certain clinical trial designs have the potential to yield unbiased results. Studies that model disease natural history to infer overdiagnosis must, in addition, examine whether their models produce valid estimates in the presence of nonprogressive cases. In this setting, limited follow-up could lead to a lack of identifiability of the parameters needed to accurately infer overdiagnosis. In a polarized research community, the excess incidence and modeling approaches are generally viewed as competitors, but we argue that they are complementary, with models being more complex but having greater potential to inform about disease natural history and the outcomes of candidate screening policies. Rather than arguing why one approach should be preferred to another, investigators should focus on developing studies that generate reliable estimates of overdiagnosis. Recognizing that both approaches have limitations, which existing studies rarely overcome, is a first step towards reconciling methodologic perspectives and achieving consensus about the real magnitude of the overdiagnosis problem. PMID:26582245

  16. Observation and imitation of actions performed by humans, androids, and robots: an EMG study

    PubMed Central

    Hofree, Galit; Urgen, Burcu A.; Winkielman, Piotr; Saygin, Ayse P.

    2015-01-01

    Understanding others’ actions is essential for functioning in the physical and social world. In the past two decades research has shown that action perception involves the motor system, supporting theories that we understand others’ behavior via embodied motor simulation. Recently, empirical approach to action perception has been facilitated by using well-controlled artificial stimuli, such as robots. One broad question this approach can address is what aspects of similarity between the observer and the observed agent facilitate motor simulation. Since humans have evolved among other humans and animals, using artificial stimuli such as robots allows us to probe whether our social perceptual systems are specifically tuned to process other biological entities. In this study, we used humanoid robots with different degrees of human-likeness in appearance and motion along with electromyography (EMG) to measure muscle activity in participants’ arms while they either observed or imitated videos of three agents produce actions with their right arm. The agents were a Human (biological appearance and motion), a Robot (mechanical appearance and motion), and an Android (biological appearance and mechanical motion). Right arm muscle activity increased when participants imitated all agents. Increased muscle activation was found also in the stationary arm both during imitation and observation. Furthermore, muscle activity was sensitive to motion dynamics: activity was significantly stronger for imitation of the human than both mechanical agents. There was also a relationship between the dynamics of the muscle activity and motion dynamics in stimuli. Overall our data indicate that motor simulation is not limited to observation and imitation of agents with a biological appearance, but is also found for robots. However we also found sensitivity to human motion in the EMG responses. Combining data from multiple methods allows us to obtain a more complete picture of action understanding and the underlying neural computations. PMID:26150782

  17. Observation and imitation of actions performed by humans, androids, and robots: an EMG study.

    PubMed

    Hofree, Galit; Urgen, Burcu A; Winkielman, Piotr; Saygin, Ayse P

    2015-01-01

    Understanding others' actions is essential for functioning in the physical and social world. In the past two decades research has shown that action perception involves the motor system, supporting theories that we understand others' behavior via embodied motor simulation. Recently, empirical approach to action perception has been facilitated by using well-controlled artificial stimuli, such as robots. One broad question this approach can address is what aspects of similarity between the observer and the observed agent facilitate motor simulation. Since humans have evolved among other humans and animals, using artificial stimuli such as robots allows us to probe whether our social perceptual systems are specifically tuned to process other biological entities. In this study, we used humanoid robots with different degrees of human-likeness in appearance and motion along with electromyography (EMG) to measure muscle activity in participants' arms while they either observed or imitated videos of three agents produce actions with their right arm. The agents were a Human (biological appearance and motion), a Robot (mechanical appearance and motion), and an Android (biological appearance and mechanical motion). Right arm muscle activity increased when participants imitated all agents. Increased muscle activation was found also in the stationary arm both during imitation and observation. Furthermore, muscle activity was sensitive to motion dynamics: activity was significantly stronger for imitation of the human than both mechanical agents. There was also a relationship between the dynamics of the muscle activity and motion dynamics in stimuli. Overall our data indicate that motor simulation is not limited to observation and imitation of agents with a biological appearance, but is also found for robots. However we also found sensitivity to human motion in the EMG responses. Combining data from multiple methods allows us to obtain a more complete picture of action understanding and the underlying neural computations. PMID:26150782

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

    PubMed

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

    2015-12-01

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

  19. Studies on the stability of the human cone visual pigments.

    PubMed

    Ramon, Eva; Mao, Xiang; Ridge, Kevin D

    2009-01-01

    The retina of vertebrates contains two kinds of photoreceptor cells, rods and cones, which contain their specific visual pigments that are responsible for scotopic and photopic vision, respectively. In cone photoreceptor cells, there are three types of color pigments: blue, green and red, each with a distinctive absorption maximum. The goal of this investigation was to identify optimal conditions under which these pigments could be obtained and isolated in a stable form, thereby facilitating structural studies using high-resolution approaches. For this purpose, all three human cone opsins were initially expressed in mammalian cells, reconstituted with 11-cis retinal, detergent solubilized, purified and their stability compared with rod rhodopsin. As all three pigments showed dramatically reduced stability relative to rhodopsin, site-directed mutagenesis was used in an attempt to engineer stability into the green cone pigment. The mutations introduced some structural motifs and sites of posttranslational modification present in rhodopsin, as well as amino acid substitutions that have been found to stabilize the rod opsin apo-protein. We also modified the hydrophobic environment of the green cone pigment by varying the detergent and detergent/lipid composition used during solubilization and purification, and compared them with the retinal reconstituted pigment in membranes. Our results show that these changes do not significantly improve the inherent instability of the human cone pigments, and in some cases, lead to a decrease in stability and protein aggregation. We conclude that further efforts are required to stabilize the human cone pigments in a form suitable for high-resolution structural studies. PMID:19192203

  20. 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…

  1. Copyright Freund Publishing House Limited Int J Dis Human Dev 2006;5(2):00-00 Brain-Computer music interface for composition and performance

    E-print Network

    Miranda, Eduardo Reck

    Copyright © Freund Publishing House Limited Int J Dis Human Dev 2006;5(2):00-00 _______________________________________________________________________________________________________________ 00 Brain-Computer music interface for composition and performance Eduardo Reck Miranda, MSc, Ph, United Kingdom Abstract: This paper introduces a new brain-computer interface (BCI) system that uses

  2. Zebrafish as a disease model for studying human hepatocellular carcinoma.

    PubMed

    Lu, Jeng-Wei; Ho, Yi-Jung; Yang, Yi-Ju; Liao, Heng-An; Ciou, Shih-Ci; Lin, Liang-In; Ou, Da-Liang

    2015-11-14

    Liver cancer is one of the world's most common cancers and the second leading cause of cancer deaths. Hepatocellular carcinoma (HCC), a primary hepatic cancer, accounts for 90%-95% of liver cancer cases. The pathogenesis of HCC consists of a stepwise process of liver damage that extends over decades, due to hepatitis, fatty liver, fibrosis, and cirrhosis before developing fully into HCC. Multiple risk factors are highly correlated with HCC, including infection with the hepatitis B or C viruses, alcohol abuse, aflatoxin exposure, and metabolic diseases. Over the last decade, genetic alterations, which include the regulation of multiple oncogenes or tumor suppressor genes and the activation of tumorigenesis-related pathways, have also been identified as important factors in HCC. Recently, zebrafish have become an important living vertebrate model organism, especially for translational medical research. In studies focusing on the biology of cancer, carcinogen induced tumors in zebrafish were found to have many similarities to human tumors. Several zebrafish models have therefore been developed to provide insight into the pathogenesis of liver cancer and the related drug discovery and toxicology, and to enable the evaluation of novel small-molecule inhibitors. This review will focus on illustrative examples involving the application of zebrafish models to the study of human liver disease and HCC, through transgenesis, genome editing technology, xenografts, drug discovery, and drug-induced toxic liver injury. PMID:26576090

  3. Zebrafish as a disease model for studying human hepatocellular carcinoma

    PubMed Central

    Lu, Jeng-Wei; Ho, Yi-Jung; Yang, Yi-Ju; Liao, Heng-An; Ciou, Shih-Ci; Lin, Liang-In; Ou, Da-Liang

    2015-01-01

    Liver cancer is one of the world’s most common cancers and the second leading cause of cancer deaths. Hepatocellular carcinoma (HCC), a primary hepatic cancer, accounts for 90%-95% of liver cancer cases. The pathogenesis of HCC consists of a stepwise process of liver damage that extends over decades, due to hepatitis, fatty liver, fibrosis, and cirrhosis before developing fully into HCC. Multiple risk factors are highly correlated with HCC, including infection with the hepatitis B or C viruses, alcohol abuse, aflatoxin exposure, and metabolic diseases. Over the last decade, genetic alterations, which include the regulation of multiple oncogenes or tumor suppressor genes and the activation of tumorigenesis-related pathways, have also been identified as important factors in HCC. Recently, zebrafish have become an important living vertebrate model organism, especially for translational medical research. In studies focusing on the biology of cancer, carcinogen induced tumors in zebrafish were found to have many similarities to human tumors. Several zebrafish models have therefore been developed to provide insight into the pathogenesis of liver cancer and the related drug discovery and toxicology, and to enable the evaluation of novel small-molecule inhibitors. This review will focus on illustrative examples involving the application of zebrafish models to the study of human liver disease and HCC, through transgenesis, genome editing technology, xenografts, drug discovery, and drug-induced toxic liver injury. PMID:26576090

  4. 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.

  5. 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...

  6. 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

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

    NASA Astrophysics Data System (ADS)

    Kokkinaki, A.; Sleep, B. E.

    2011-12-01

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

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

    PubMed

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

    2015-12-18

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

  9. Keratin film made of human hair as a nail plate model for studying drug permeation.

    PubMed

    Lusiana; Reichl, Stephan; Müller-Goymann, Christel C

    2011-08-01

    The limited source of human nail plate for studying drug permeation inspired us to develop a nail plate model made of human hair keratin. The manufacturing process consisted of keratin extraction, dialysis, molding, solvent evaporation, and curing, producing a water-resistant film. The permeability of the film was examined using three markers: sodium fluorescein, rhodamine B, and fluorescein isothiocyanate-dextran as water-soluble, lipid-soluble, and large molecule models, respectively. Bovine hoof was used for comparison. First investigation showed that keratin films (thickness 120 ?m) resembled hooves (thickness 100 ?m) except that these films were more permeable to rhodamine B compared with hooves (1.8-fold, p<0.01). Subsequent investigations using ungual penetration enhancers (urea, thioglycolic acid, and papain) showed that keratin films were generally more susceptible than hooves. This study revealed that the produced keratin film offers a possibility as a human nail plate substitute. However, inclusion of the penetration enhancer must be carefully interpreted. PMID:21791369

  10. 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

  11. Strong Association Between Human and Animal Brucella Seropositivity in a Linked Study in Kenya, 2012-2013.

    PubMed

    Osoro, Eric Mogaka; Munyua, Peninah; Omulo, Sylvia; Ogola, Eric; Ade, Fredrick; Mbatha, Peter; Mbabu, Murithi; Ng'ang'a, Zipporah; Kairu, Salome; Maritim, Marybeth; Thumbi, Samuel M; Bitek, Austine; Gaichugi, Stella; Rubin, Carol; Njenga, Kariuki; Guerra, Marta

    2015-08-01

    Brucellosis is a common bacterial zoonotic infection but data on the prevalence among humans and animals is limited in Kenya. A cross-sectional survey was conducted in three counties practicing different livestock production systems to simultaneously assess the seroprevalence of, and risk factors for brucellosis among humans and their livestock (cattle, sheep, camels, and goats). A two-stage cluster sampling method with random selection of sublocations and households was conducted. Blood samples were collected from humans and animals and tested for Brucella immunoglobulin G (IgG) antibodies. Human and animal individual seroprevalence was 16% and 8%, respectively. Household and herd seroprevalence ranged from 5% to 73% and 6% to 68%, respectively. There was a 6-fold odds of human seropositivity in households with a seropositive animal compared with those without. Risk factors for human seropositivity included regular ingestion of raw milk (adjusted odds ratio [aOR] = 3.5, 95% confidence interval [CI] = 2.8-4.4), exposure to goats (herding, milking, and feeding) (aOR = 3.1, 95% CI = 2.5-3.8), and handling of animal hides (aOR = 1.8, 95% CI = 1.5-2.2). Attaining at least high school education and above was a protective factor for human seropositivity (aOR = 0.3, 95% CI = 0.3-0.4). This linked study provides evidence of a strong association between human and animal seropositivity at the household level. PMID:26101275

  12. Strong Association between Human and Animal Brucella Seropositivity in a Linked Study in Kenya, 2012–2013

    PubMed Central

    Osoro, Eric Mogaka; Munyua, Peninah; Omulo, Sylvia; Ogola, Eric; Ade, Fredrick; Mbatha, Peter; Mbabu, Murithi; Ng'ang'a, Zipporah; Kairu, Salome; Maritim, Marybeth; Thumbi, Samuel M.; Bitek, Austine; Gaichugi, Stella; Rubin, Carol; Njenga, Kariuki; Guerra, Marta

    2015-01-01

    Brucellosis is a common bacterial zoonotic infection but data on the prevalence among humans and animals is limited in Kenya. A cross-sectional survey was conducted in three counties practicing different livestock production systems to simultaneously assess the seroprevalence of, and risk factors for brucellosis among humans and their livestock (cattle, sheep, camels, and goats). A two-stage cluster sampling method with random selection of sublocations and households was conducted. Blood samples were collected from humans and animals and tested for Brucella immunoglobulin G (IgG) antibodies. Human and animal individual seroprevalence was 16% and 8%, respectively. Household and herd seroprevalence ranged from 5% to 73% and 6% to 68%, respectively. There was a 6-fold odds of human seropositivity in households with a seropositive animal compared with those without. Risk factors for human seropositivity included regular ingestion of raw milk (adjusted odds ratio [aOR] = 3.5, 95% confidence interval [CI] = 2.8–4.4), exposure to goats (herding, milking, and feeding) (aOR = 3.1, 95% CI = 2.5–3.8), and handling of animal hides (aOR = 1.8, 95% CI = 1.5–2.2). Attaining at least high school education and above was a protective factor for human seropositivity (aOR = 0.3, 95% CI = 0.3–0.4). This linked study provides evidence of a strong association between human and animal seropositivity at the household level. PMID:26101275

  13. Case studies addressing human pharmacokinetic uncertainty using a combination of pharmacokinetic simulation and alternative first in human paradigms.

    PubMed

    Harrison, Anthony; Gardner, Iain; Hay, Tanya; Dickins, Maurice; Beaumont, Kevin; Phipps, Alex; Purkins, Lynn; Allan, Gill; Christian, Rachelle; Duckworth, Jonathan; Gurrell, Ian; Kempshall, Sarah; Savage, Mark; Seymour, Mark; Simpson, Marie; Taylor, Louise; Turnpenny, Paul

    2012-01-01

    PF-184298 ((S)-2,3-dichloro-N-isobutyl-N-pyrrolidin-3-ylbenzamide) and PF-4776548 ((3-(4-fluoro-2-methoxy-benzyl)-7-hydroxy-8,9-dihydro-3H,7H-pyrrolo[2,3-c][1,7]naphthyridin-6-one)) are novel compounds which were selected to progress to human studies. Discordant human pharmacokinetic predictions arose from pre-clinical in vivo studies in rat and dog, and from human in vitro studies, resulting in a clearance prediction range of 3 to >20?mL min?¹ kg?¹ for PF-184298, and 5 to >20?mL min?¹ kg?¹ for PF-4776548. A package of work to investigate the discordance for PF-184298 is described. Although ultimately complementary to the human pharmacokinetic data in characterising the disposition of PF-184298 in humans, these data did not provide any further confidence in pharmacokinetic prediction. A fit for purpose human pharmacokinetic study was conducted for each compound, with an oral pharmacologically active dose for PF-184298, and an intravenous and oral microdose for PF-4776548. This provided a relatively low cost, clear decision making approach, resulting in the termination of PF-4776548 and further progression of PF-184298. A retrospective analysis of the data showed that, if the tools had been available at the time, the pharmacokinetics of PF-184298 in human could have been predicted from a population based simulation tool in combination with physicochemical properties and in vitro human intrinsic clearance. PMID:21992032

  14. Microvascularization of the human digit as studied by corrosion casting

    PubMed Central

    Sangiorgi, S; Manelli, A; Congiu, T; Bini, A; Pilato, G; Reguzzoni, M; Raspanti, M

    2004-01-01

    The aim of this study was to describe microcirculation in the human digit, focusing on the vascular patterns of its cutaneous and subcutaneous areas. We injected a functional supranumerary human thumb (Wassel type IV) with a low-viscosity acrylic resin through its digital artery. The tissues around the vessels were then digested in hot alkali and the resulting casts treated for scanning electron microscopy. We concentrated on six different areas: the palmar and dorsal side of the skin, the eponychium, the perionychium, the nail bed and the nail root. On the palmar side, many vascular villi were evident: these capillaries followed the arrangement of the fingerprint lines, whereas on the dorsal side they were scattered irregularly inside the dermal papillae. In the hypodermal layer of the palmar area, vascular supports of sweat glands and many arteriovenous anastomoses were visible, along with glomerular-shaped vessels involved in thermic regulation and tactile function. In the eponychium and perionychium, the vascular villi followed the direction of nail growth. In the face of the eponychium in contact with the nail, a wide-mesh net of capillaries was evident. In the nail bed, the vessels were arranged in many longitudinal trabeculae parallel to the major axis of the digit. In the root of the nail, we found many columnar vessels characterized by multiple angiogenic buttons on their surface. PMID:15032919

  15. 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

  16. Influence of Toxoplasma gondii Infection on Male Fertility: A Pilot Study on Immunocompetent Human Volunteers

    PubMed Central

    COLOSI, Hora?iu Alexandru; JALALI-ZADEH, Babak; COLOSI, Ioana Alina; SIMON, Laura Mihaela; COSTACHE, Carmen Anca

    2015-01-01

    Background: This study was conducted to investigate the influence of Toxoplasma gondii infection on spermatic and hormonal parameters in a pilot sample of immunocompetent human male subjects. Methods: This cross sectional, observational pilot study on 60 immunocompetent human male subjects aged between 18 and 60 yr old was conducted between 2012 -2013. Blind evaluation of serological markers of past T. gondii infection (TOX-IgG, TOX-IgM) was performed, along with individual spermiograms and determinations of follicle-stimulating hormone (FSH) and testosterone serum levels. Results: The overall prevalence of past T. gondii infection in the investigated immunocompetent male subjects was 25%. No statistically significant influence of T. gondii infection on sperm characteristics (ejaculate quantity, sperm count, motility, morphology) and serum levels of FSH or testosterone were found. Among possible predictors of a modified spermiogram studied by multiple logistic regression along with the T. gondii infection (age, smoking, alcohol consumption, fertility influencing malformations, infections, trauma or medication), only the presence of varicocele in the medical history of the studied subjects was found to significantly participate in the prediction of a modified spermiogram (P=0.0154). A necessary sample size of 994 subjects was computed in order to achieve a test power of 0.8 (80%) to discriminate an effect size of 8.89% estimated by our pilot study. Conclusions: Although our investigation did not demonstrate an influence of latent T. gondii infection on spermatic and hormonal parameters of immunocompetent male humans, the absence of such an influence cannot be affirmed, due to the limited sample size of our pilot study. PMID:26622295

  17. An Investigation of Genome-Wide Studies Reported Susceptibility Loci for Ulcerative Colitis Shows Limited Replication in North Indians

    PubMed Central

    Juyal, Garima; Prasad, Pushplata; Senapati, Sabyasachi; Midha, Vandana; Sood, Ajit; Amre, Devendra; Juyal, Ramesh C.; BK, Thelma

    2011-01-01

    Genome-Wide Association studies (GWAS) of both Crohn's Disease (CD) and Ulcerative Colitis (UC) have unearthed over 40 risk conferring variants. Recently, a meta-analysis on UC revealed several loci, most of which were either previously associated with UC or CD susceptibility in populations of European origin. In this study, we attempted to replicate these findings in an ethnically distinct north Indian UC cohort. 648 UC cases and 850 controls were genotyped using Infinium Human 660W-quad. Out of 59 meta-analysis index SNPs, six were not in the SNP array used in the study. Of the remaining 53 SNPs, four were found monomorphic. Association (p<0.05) at 25 SNPs was observed, of which 15 were CD specific. Only five SNPs namely rs2395185 (HLA-DRA), rs3024505 (IL10), rs6426833 (RNF186), rs3763313 (BTNL2) and rs2066843 (NOD2) retained significance after Bonferroni correction. These results (i) reveal limited replication of Caucasian based meta-analysis results; (ii) reiterate overlapping molecular mechanism(s) in UC and CD; (iii) indicate differences in genetic architecture between populations; and (iv) suggest that resources such as HapMap need to be extended to cover diverse ethnic populations. They also suggest a systematic GWAS in this terrain may be insightful for identifying population specific IBD risk conferring loci and thus enable cross-ethnicity fine mapping of disease loci. PMID:21304977

  18. Neurological control of human sexual behaviour: insights from lesion studies

    PubMed Central

    Baird, Amee D; Wilson, Sarah J; Bladin, Peter F; Saling, Michael M; Reutens, David C

    2007-01-01

    We review the human literature examining the effects of neurological insult on human sexual behaviour. We provide a synthesis of the findings to date, and identify key brain regions associated with specific aspects of human sexual behaviour. These include subcortical and cortical regions, with the mesial temporal lobe and the amygdala in particular being a crucial structure in the mediation of human sexual drive. PMID:17189299

  19. A qualitative case study to identify possible barriers that limit effective elementary science education

    NASA Astrophysics Data System (ADS)

    Foster, Donald Carey

    The purpose of this case study was to identify barriers that limit the effectiveness of elementary teachers in the teaching of science. It is of the utmost urgency that barriers be first identified, so that possible solutions can be explored to bring about the improvement of elementary science education. This urgency has been imposed by the scheduled national testing of students in science by 2007, as mandated by the No Child Left Behind Act of 2001. Using qualitative case study methods, the researcher conducted interviews with 8 elementary teachers from two schools within one school district who taught 3rd, 4th, and 5th grade. These interviews were designed to gain insight into barriers these elementary teachers perceived as factors limiting their effectiveness in teaching science and preparing students for high-stakes testing. Barriers in the areas of teacher background, typical teaching day, curriculum, inservices, and legislative influences were explored. This study concluded that the barriers explored do have a substantial negative affect on the teaching and learning of science in the elementary grades. Specifically, the barriers revealed in this study include the limited science background of elementary teachers, inadequate class time devoted to science, non-comprehensive curriculum, ineffective or lack of inservice training, and pressures from legislated mandates. But it is also clear that these barriers are so intertwined that one cannot remove these barriers one at a time. It will take a collective effort from all involved, including legislators, administrators, teachers, parents, and students, to alleviate these barriers and discover effective solutions to improve elementary science education.

  20. Studies of Limits on Uncontrolled Heavy Ion Beam Losses for Allowing Hands-On Maintenance

    SciTech Connect

    Reginald M. Ronningen; Igor Remec

    2010-09-11

    Dose rates from accelerator components activated by 1 W/m beam losses are obtained semiempirically for a 1 GeV proton beam and by use of Monte Carlo transport codes for the proton beam and for 777 MeV/u 3He, 500 MeV/u 48Ca, 86Kr, 136Xe, and 400 MeV/u 238U ions. The dose rate obtained by the semi-empirical method, 0.99 mSv/h (99 mrem/h) at 30 cm, 4 h after 100 d irradiation by a 1-GeV proton beam, is consistent with studies at several accelerator facilities and with adopted hands-on maintenance dose rate limits. Monte Carlo simulations verify this result for protons and extend studies to heavy ion beam losses in drift-tube linac and superconducting linac accelerating structures. The studies indicate that the 1 W/m limit imposed on uncontrolled beam losses for high-energy proton beams might be relaxed for heavy ion beams. These studies further suggest that using the ratio of neutrons produced by a heavy ion beam to neutrons produced by a proton beam along with the dose rate from the proton beam (for thin-target scenarios) should allow an estimate of the dose rates expected from heavy ion beam losses.

  1. Social Studies: Elementary School Guide for Teaching about Human Rights.

    ERIC Educational Resources Information Center

    Frazier, Louise; And Others

    Human rights are those essentials of human existence that are inherent in the species. They are moral claims that satisfy the basic needs of all human beings. Ten major goals and numerous objectives were developed to undergird the Detroit (Michigan) curriculum, and this guide is established around the 10 major goals for teaching students about…

  2. 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…

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

    SciTech Connect

    Cram, L.S.; Stafford, C.

    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.

  4. Ah receptor: relevance of mechanistic studies to human risk assessment

    SciTech Connect

    Cook, J.C.; Gaido, K.W.; Greenlee, W.F.

    1987-12-01

    Studies of the toxic actions of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in numerous animal models and in human and animal cells in culture have established that the most characteristic pathologic lesions produced by this compound results from events initiated by the interaction of TCDD with a specific intracellular receptor protein, the Ah receptor. Although most research on the interaction of TCDD with the Ah receptor has focused on establishing involvement of this receptor complex in specific toxic responses, recent application of modern cell and molecular biology techniques is yielding new insights into the mechanism(s) of signal transduction. Elucidation of these mechanisms is essential for understanding the molecular basis of the cell and species specificity which is a hallmark of TCDD toxicity. This knowledge should provide the framework for development of a more toxicologically relevant risk assessment model.

  5. Preclinical safety studies on autologous cultured human skin fibroblast transplantation.

    PubMed

    Zeng, Wei; Zhang, Shuying; Liu, Dai; Chai, Mi; Wang, Jiaqi; Zhao, Yuming

    2014-01-01

    Recently, FDA approved the clinical use of autologous fibroblasts (LAVIV™) for the improvement of nasolabial fold wrinkles in adults. The use of autologous fibroblasts for the augmentation of dermal and subcutaneous defects represents a potentially exciting natural alternative to the use of other filler materials for its long-term corrective ability and absence of allergic adverse effects proved by clinical application. However, compared to the clinical evidence, preclinical studies are far from enough. In this study, human skin-derived fibroblasts were cultured and expanded for both in vitro and in vivo observations. In vitro, the subcultured fibroblasts were divided into two groups. One set of cells underwent cell cycle and karyotype analysis at passages 5 and 10. The second group of cells was cocultured in medium with different concentrations of human skin extract D for the measurement of collagen concentration and cell count. In vivo, the subcultured fibroblasts were injected into nude mice subcutaneously. Biopsies were taken for morphology observation and specific collagen staining at 1, 2, and 3 months after injection. The results in vitro showed no significant differences in cell cycle distribution between passages 5 and 10. Cell proliferation and secretion were inhibited as the concentration of extract D increased. In vivo, the fibroblasts were remarkably denser on the experimental side with no dysplastic cells. Mitotic cells were easily observed at the end of the first month but were rare at the end of the third month. Type III collagen was detected at the end of the first month, while collagen type I was positive at the end of the second month. The content of both collagens increased as time passed. The above results indicated that the use of the autologous fibroblasts was safe, providing a basic support for clinical use of fibroblasts. PMID:23211390

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

    PubMed Central

    Tomé, Wolfgang A.; Gökhan, ?ölen; Brodin, N. Patrik; Gulinello, Maria E.; Heard, John; Mehler, Mark F.; Guha, Chandan

    2015-01-01

    Cancer patients undergoing cranial irradiation are at risk of developing neurocognitive impairments. Recent evidence suggests that radiation-induced injury to the hippocampi could play an important role in this cognitive decline. As a tool for studying the mechanisms of hippocampal-dependent cognitive decline, we developed a mouse model replicating the results of the recent clinical RTOG 0933 study of hippocampal sparing whole-brain irradiation. We irradiated 16-week-old female C57BL/6J mice to a single dose of 10?Gy using either whole-brain irradiation (WBRT) or hippocampal sparing irradiation (HSI). These animals, as well as sham-irradiated controls, were subjected to behavioral/cognitive assessments distinguishing between hippocampal-dependent and hippocampal-independent functions. Irradiation was well tolerated by all animals and only limited cell death of proliferating cells was found within the generative zones. Animals exposed to WBRT showed significant deficits compared to sham-irradiated controls in the hippocampal-dependent behavioral task. In contrast, HSI mice did not perform significantly different from sham-irradiated mice (control group) and performed significantly better when compared to WBRT mice. This is consistent with the results from the RTOG 0933 clinical trial, and as such this animal model could prove a helpful tool for exploring new strategies for mitigating cognitive decline in cancer patients receiving cranial irradiation. PMID:26399509

  7. Genomic approaches to studying human-specific developmental traits.

    PubMed

    Franchini, Lucía F; Pollard, Katherine S

    2015-09-15

    Changes in developmental regulatory programs drive both disease and phenotypic differences among species. Linking human-specific traits to alterations in development is challenging, because we have lacked the tools to assay and manipulate regulatory networks in human and primate embryonic cells. This field was transformed by the sequencing of hundreds of genomes - human and non-human - that can be compared to discover the regulatory machinery of genes involved in human development. This approach has identified thousands of human-specific genome alterations in developmental genes and their regulatory regions. With recent advances in stem cell techniques, genome engineering, and genomics, we can now test these sequences for effects on developmental gene regulation and downstream phenotypes in human cells and tissues. PMID:26395139

  8. Study on Market Stability and Price Limit of Chinese Stock Index Futures Market: An Agent-Based Modeling Perspective

    PubMed Central

    2015-01-01

    This paper explores a method of managing the risk of the stock index futures market and the cross-market through analyzing the effectiveness of price limits on the Chinese Stock Index 300 futures market. We adopt a cross-market artificial financial market (include the stock market and the stock index futures market) as a platform on which to simulate the operation of the CSI 300 futures market by changing the settings of price limits. After comparing the market stability under different price limits by appropriate liquidity and volatility indicators, we find that enhancing price limits or removing price limits both play a negative impact on market stability. In contrast, a positive impact exists on market stability if the existing price limit is maintained (increase of limit by10%, down by 10%) or it is broadened to a proper extent. Our study provides reasonable advice for a price limit setting and risk management for CSI 300 futures. PMID:26571135

  9. Parasitological and clinical studies on human scabies in Cairo.

    PubMed

    Sarwat, M A; el Okbi, L M; el Sayed, M M; el Okbi, S M; el Deeb, H K

    1993-12-01

    This study is a parasitological and clinical study on human scabies. This study was carried out on 100 patients attending the Dermatology Outpatient Clinic at Ain Shams University Hospitals, including 54 males and 46 females. All patients were subjected to detailed history taking, complete dermatological examination including Skin Scraping Test and Burrow Ink Test. Younger patients attended the dermatology clinic earlier than older patients, who usually delayed their visits until complications occurred. Scratching, erythematous papules and secondary infected lesions were the commonest lesions. The hands, wrist and external genitalia were the most frequently affected sites while the feet, ankles, knees and back were the least affected. Burrows could only be detected in 40% of patients. The most frequent sites were the web spaces, external genitalia, and finger sides. Burrow Ink Test was positive among 85% of patients with burrows while mites could be identified by Skin Scraping Test in 55% of patients. The most frequent clinical manifestations in the parasitologically positive patients were itching, burrows, and papules, and the most frequent sites were the web spaces, and the finger sides. Multiple sites affection was the characteristic feature among the preschool age children who represented 14% of cases. PMID:8308357

  10. Genome-Wide Association Studies of the Human Gut Microbiota

    PubMed Central

    Davenport, Emily R.; Cusanovich, Darren A.; Michelini, Katelyn; Barreiro, Luis B.; Ober, Carole; Gilad, Yoav

    2015-01-01

    The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10?7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut. PMID:26528553

  11. Permeation Studies of Captopril Transdermal Films Through Human Cadaver Skin.

    PubMed

    Nair, Rajesh Sreedharan; Nair, Sujith

    2015-01-01

    Mortality rate due to heart diseases increases dramatically with age. Captopril is an angiotensin converting enzyme inhibitor (ACE) used effectively for the management of hypertension. Due to short elimination half-life of captopril the oral dose is very high. Captopril is prone to oxidation and it has been reported that the oxidation rate of captopril in skin tissues is considerably low when compared to intestinal tissues. All these factors make captopril an ideal drug candidate for transdermal delivery. In this research work an effort was made to formulate transdermal films of captopril by utilizing polyvinylpyrrolidone (PVP) and polyvinyl alcohol (PVA) as film formers and polyethylene glycol 400 (PEG400) as a plasticizer. Dimethyl sulfoxide (DMSO) and dimethylformamide (DMF) were used as permeation enhancers. Physicochemical parameters of the films such as appearance, thickness, weight variation and drug content were evaluated. The invitro permeation studies were carried out through excised human cadaver skin using Franz diffusion cells. The in-vitro permeation studies demonstrated that the film (P4) having the polymer ratio (PVP:PVA = 80:20) with DMSO (10%) resulted a promising drug release of 79.58% at 24 hours with a flux of 70.0 µg/cm(2)/hr. No signs of erythema or oedema were observed on the rabbit skin as a result of skin irritation study by Draize test. Based on the stability report it was confirmed that the films were physically and chemically stable, hence the prepared films are very well suited for transdermal application. PMID:25675336

  12. 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.

  13. Limitations and relative utility of screening assays to assess engineered nanoparticle toxicity in a human cell line

    SciTech Connect

    Monteiro-Riviere, N.A.; Inman, A.O.; Zhang, L.W.

    2009-01-15

    Single-walled carbon nanotubes (SWCNT), fullerenes (C{sub 60}), carbon black (CB), nC{sub 60}, and quantum dots (QD) have been studied in vitro to determine their toxicity in a number of cell types. Here, we report that classical dye-based assays such as MTT and neutral red (NR) that determine cell viability produce invalid results with some NM (nanomaterials) due to NM/dye interactions and/or NM adsorption of the dye/dye products. In this study, human epidermal keratinocytes (HEK) were exposed in vitro to CB, SWCNT, C{sub 60}, nC{sub 60}, and QD to assess viability with calcein AM (CAM), Live/Dead (LD), NR, MTT, Celltiter 96 AQueous One (96 AQ), alamar Blue (aB), Celltiter-Blue (CTB), CytoTox One{sup TM} (CTO), and flow cytometry. In addition, trypan blue (TB) was quantitated by light microscopy. Assay linearity (R{sup 2} value) was determined with HEK plated at concentrations from 0 to 25,000 cells per well in 96-well plates. HEK were treated with serial dilutions of each NM for 24 h and assessed with each of the viability assays. TB, CAM and LD assays, which depend on direct staining of living and/or dead cells, were difficult to interpret due to physical interference of the NM with cells. Results of the dye-based assays varied a great deal, depending on the interactions of the dye/dye product with the carbon nanomaterials (CNM). Results show the optimal high throughput assay for use with carbon and noncarbon NM was 96 AQ. This study shows that, unlike small molecules, CNM interact with assay markers to cause variable results with classical toxicology assays and may not be suitable for assessing nanoparticle cytotoxicity. Therefore, more than one assay may be required when determining nanoparticle toxicity for risk assessment.

  14. Applying systems biology methods to the study of human physiology in extreme environments

    PubMed Central

    2013-01-01

    Systems biology is defined in this review as ‘an iterative process of computational model building and experimental model revision with the aim of understanding or simulating complex biological systems’. We propose that, in practice, systems biology rests on three pillars: computation, the omics disciplines and repeated experimental perturbation of the system of interest. The number of ethical and physiologically relevant perturbations that can be used in experiments on healthy humans is extremely limited and principally comprises exercise, nutrition, infusions (e.g. Intralipid), some drugs and altered environment. Thus, we argue that systems biology and environmental physiology are natural symbionts for those interested in a system-level understanding of human biology. However, despite excellent progress in high-altitude genetics and several proteomics studies, systems biology research into human adaptation to extreme environments is in its infancy. A brief description and overview of systems biology in its current guise is given, followed by a mini review of computational methods used for modelling biological systems. Special attention is given to high-altitude research, metabolic network reconstruction and constraint-based modelling. PMID:23849719

  15. Studying semblances of a true killer: experimental model of human ventricular fibrillation

    PubMed Central

    Nair, K.; Farid, T.; Masse, S.; Umapathy, K.; Watkins, S.; Poku, K.; Asta, J.; Kusha, M.; Sevaptsidis, E.; Jacob, J.; Floras, J. S.

    2012-01-01

    It is unknown whether ventricular fibrillation (VF) studied in experimental models represents in vivo human VF. First, we examined closed chest in vivo VF induced at defibrillation threshold testing (DFT) in four patients with ischemic cardiomyopathy pretransplantation. We examined VF in these same four hearts in an ex vivo human Langendorff posttransplantation. VF from DFT was compared with VF from the electrodes from a similar region in the right ventricular endocardium in the Langendorff using two parameters: the scale distribution width (extracted from continuous wavelet transform) and VF mean cycle length (CL). In a second substudy group where multielectrode phase mapping could be performed, we examined early VF intraoperatively (in vivo open chest condition) in three patients with left ventricular cardiomyopathy. We investigated early VF in the hearts of three patients in an ex vivo Langendorff and compared findings with intraoperative VF using two metrics: dominant frequency (DF) assessed by the Welch periodogram and the number of phase singularities (lasting >480 ms). Wavelet analysis (P = 0.9) and VF CL were similar between the Langendorff and the DFT groups (225 ± 13, 218 ± 24 ms; P = 0.9), indicating that wave characteristics and activation rate of VF was comparable between the two models. Intraoperative DF was slower but comparable with the Langendorff DF over the endocardium (4.6 ± 0.1, 5.0 ± 0.4 Hz; P = 0.9) and the epicardium (4.5 ± 0.2, 5.2 ± 0.4 Hz; P = 0.9). Endocardial phase singularity number (9.6 ± 5, 12.1 ± 1; P = 0.6) was lesser in number but comparable between in vivo and ex vivo VF. VF dynamics in the limited experimental human studies approximates human in vivo VF. PMID:22268105

  16. GC?×?GC-TOFMS and supervised multivariate approaches to study human cadaveric decomposition olfactive signatures.

    PubMed

    Stefanuto, Pierre-Hugues; Perrault, Katelynn A; Stadler, Sonja; Pesesse, Romain; LeBlanc, Helene N; Forbes, Shari L; Focant, Jean-François

    2015-06-01

    In forensic thanato-chemistry, the understanding of the process of soft tissue decomposition is still limited. A better understanding of the decomposition process and the characterization of the associated volatile organic compounds (VOC) can help to improve the training of victim recovery (VR) canines, which are used to search for trapped victims in natural disasters or to locate corpses during criminal investigations. The complexity of matrices and the dynamic nature of this process require the use of comprehensive analytical methods for investigation. Moreover, the variability of the environment and between individuals creates additional difficulties in terms of normalization. The resolution of the complex mixture of VOCs emitted by a decaying corpse can be improved using comprehensive two-dimensional gas chromatography (GC?×?GC), compared to classical single-dimensional gas chromatography (1DGC). This study combines the analytical advantages of GC?×?GC coupled to time-of-flight mass spectrometry (TOFMS) with the data handling robustness of supervised multivariate statistics to investigate the VOC profile of human remains during early stages of decomposition. Various supervised multivariate approaches are compared to interpret the large data set. Moreover, early decomposition stages of pig carcasses (typically used as human surrogates in field studies) are also monitored to obtain a direct comparison of the two VOC profiles and estimate the robustness of this human decomposition analog model. In this research, we demonstrate that pig and human decomposition processes can be described by the same trends for the major compounds produced during the early stages of soft tissue decomposition. PMID:25910882

  17. Human V?2V?2 T cells limit breast cancer growth by modulating cell survival-, apoptosis-related molecules and microenvironment in tumors.

    PubMed

    Aggarwal, Reeva; Lu, Jingwei; Kanji, Suman; Das, Manjusri; Joseph, Matthew; Lustberg, Maryam B; Ray, Alo; Pompili, Vincent J; Shapiro, Charles L; Das, Hiranmoy

    2013-11-01

    Innate immune system has been known to play an important role in inhibiting the malignant transformation, tumor progression and invasion. However, the mechanistic basis remains ambiguous. Despite polyclonality of human ?? T cells, V?2V?2 T cell subset was shown to recognize and limit the growth of various tumors at various degrees. The differential recognition of the tumor cells by V?2V?2 T cells are yet to be defined. Our study reveals that ?? T cells limit in vitro growth of most breast tumor cells, such as SkBr7 (HER2+), MCF7 (ER+) and MDA-MB-231 (ER-) by inhibiting their survival and inducing apoptosis, except BrCa-MZ01 (PR+) cells. To investigate detail mechanisms of antineoplastic effects, we found that cell death was associated with the surface expression levels of MICA/B and ICAM1. Molecular signaling analysis demonstrated that inhibition of cell growth by ?? T cells was associated with the lower expression levels of cell survival-related molecules such as AKT, ERK and concomitant upregulation of apoptosis-related molecules, such as PARP, cleaved caspase 3 and tumor suppressor genes PTEN and P53. However, opposite molecular signaling was observed in the resistant cell line after coculture with ?? T cells. In vivo, antineoplastic effects of ?? T cells were also documented, where tumor growth was inhibited due to the downregulation of survival signals, strong induction of apoptotic molecules, disruption of microvasculature and increased infiltration of tumor associated macrophages. These findings reveal that a complex molecular signaling is involved in ?? T cell-mediated antineoplastic effects. PMID:23595559

  18. Citation Analysis for Collection Development: A Comparative Study of Eight Humanities Fields

    ERIC Educational Resources Information Center

    Knievel, Jennifer E.; Kellsey, Charlene

    2005-01-01

    This study analyzes 9,131 citations from the 2002 volumes of journals in eight humanities fields: art, classics, history, linguistics, literature, music, philosophy, and religion. This study found that citation patterns varied widely among humanities disciplines. Due to these differences, it is important for librarians with humanities collection…

  19. Feb 4, 2014 Postdoctoral positions in human population genomics and association studies

    E-print Network

    Keinan, Alon

    publications from the lab: Neutral genomic regions refine models of recent rapid human population growth in association studies of quantitative traits. PLOS Genetics (2013). Recent explosive human population growth hasFeb 4, 2014 Postdoctoral positions in human population genomics and association studies Two

  20. SAFEgress: A Flexible Platform to Study the Effect of Human and Social Behaviors on Egress Performance

    E-print Network

    Stanford University

    SAFEgress: A Flexible Platform to Study the Effect of Human and Social Behaviors on Egress to incorporate human and social behaviors during evacautions. Simulation results on two scenarios are presented safety. Despite observations and studies about human behaviors during emergencies, most simulation tools

  1. A Study on Quality Metrics vs. Human Perception: Can Visual Measures Help us to

    E-print Network

    it 1/15 A Study on Quality Metrics vs. Human Perception: Can Visual Measures Help us to Filter in visual analysis, if they resemble the human perception. In this work we present a broad study to examine the relation between filtering relevant visualizations based on human perception versus quality metrics

  2. 75 FR 32461 - Human Studies Review Board; Notice of Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-08

    ...persons who conduct or assess human studies, especially studies...comments on the science and ethics issues under discussion, it...scientific and ethical aspects of human subjects research. The major...reports of completed research with human subjects; and (3) how...

  3. 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.

  4. 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.

  5. 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...

  6. 77 FR 43337 - Drugs for Human Use; Drug Efficacy Study Implementation; Certain Prescription Drugs Offered for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-24

    ...DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket Nos. FDA-1975-N-0336...Hydrocortisone Acetate and Pramoxine Hydrochloride] Drugs for Human Use; Drug Efficacy Study Implementation; Certain...

  7. 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 this complex issue. The film screening will be followed by a panel discussion on sexuality and human rights

  8. 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

  9. Modeling aspects of human memory for scientific study.

    SciTech Connect

    Caudell, Thomas P.; Watson, Patrick; McDaniel, Mark A.; Eichenbaum, Howard B.; Cohen, Neal J.; 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.

  10. 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.

  11. Human genetic mapping studies using single sperm typing

    SciTech Connect

    Hubert, R.S.

    1993-01-01

    Sperm typing is a powerful technique that uses the polymerase chain reaction (PCR) to analyze DNA sequences within single sperm cells in order to construct genetic maps. This methodology was used to estimate the recombination fraction between D3S2 and D3S2 which was found to be 0.28 (95% CI = 0.20-0.36). Pedigree analysis was unable to determine genetic distance between these two markers due to their low informativeness. We also showed that dinucleotide and tetranucleotide repeat polymorphisms can be analyzed in single cells without using radioactivity or denaturing gels. This provides a rich new source of DANA polymorphisms for genetic mapping by sperm typing. In addition, an approach that uses the sperm typing methodology is described that can define the physical boundaries of meiotic recombination hotspots. The hotspot at 4p16.3 near the Huntington disease gene was localized to an interval between D4S10 and D4S126. These studies demonstrated the usefulness of sperm typing as a tool for the study of human genetic.

  12. Distribution limits of Batrachochytrium dendrobatidis: a case study in the Rocky Mountains, USA.

    PubMed

    Hossack, Blake R; Muths, Erin; Anderson, Chauncey W; Kirshtein, Julie D; Corn, Paul Stephen

    2009-10-01

    Knowledge of the environmental constraints on a pathogen is critical to predicting its dynamics and effects on populations. Batrachochytrium dendrobatidis (Bd), an aquatic fungus that has been linked with widespread amphibian declines, is ubiquitous in the Rocky Mountains. As part of assessing the distribution limits of Bd in our study area, we sampled the water column and sediments for Bd zoospores in 30 high-elevation water bodies that lacked amphibians. All water bodies were in areas where Bd has been documented from neighboring, lower-elevation areas. We targeted areas lacking amphibians because existence of Bd independent of amphibians would have both ecologic and management implications. We did not detect Bd, which supports the hypothesis that it does not live independently of amphibians. However, assuming a detection sensitivity of 59.5% (based on sampling of water where amphibians tested positive for Bd), we only had 95% confidence of detecting Bd if it was in > or =16% of our sites. Further investigation into potential abiotic reservoirs is needed, but our results provide a strategic step in determining the distributional and environmental limitations of Bd in our study region. PMID:19901397

  13. Low power optical limiting studies of copper doped lithium tetraborate nanoparticles

    NASA Astrophysics Data System (ADS)

    Dhanuskodi, S.; Mohandoss, R.; Vinitha, G.; Pathinettam Padiyan, D.

    2015-04-01

    The copper doped lithium tetraborate (LTB:Cu) nanoparticles were synthesized by sol-gel method and characterized by XRD (tetragonal structure) and by FESEM (sphere-like nanoparticle). UV-Vis studies show that there is no strong absorption in the visible region. In the luminescence spectrum, the emission peak at 370 nm reveals the presence of Cu+ in LTB lattice. The relative powder second harmonic generation efficiency of pure and doped LTB is equal to the standard NLO material, KDP. The nonlinear optical parameters of LTB:Cu nanoparticles say, nonlinear refractive index, nonlinear absorption coefficient and third order nonlinear optical susceptibility were determined to be of the order of 10-8 cm2/W, 10-2 cm/W and 10-5 esu, respectively. The optical power limiting behavior of the samples were studied by Z-scan technique with (532 nm, 50 mW) Nd:YAG laser and the limiting threshold values are found to be 22.7 mW for 0.01 M and 24.9 mW for 0.03 and 0.05 M LTB:Cu nanoparticles.

  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. Low power optical limiting studies of copper doped lithium tetraborate nanoparticles.

    PubMed

    Dhanuskodi, S; Mohandoss, R; Vinitha, G; Pathinettam Padiyan, D

    2015-04-01

    The copper doped lithium tetraborate (LTB:Cu) nanoparticles were synthesized by sol-gel method and characterized by XRD (tetragonal structure) and by FESEM (sphere-like nanoparticle). UV-Vis studies show that there is no strong absorption in the visible region. In the luminescence spectrum, the emission peak at 370 nm reveals the presence of Cu+ in LTB lattice. The relative powder second harmonic generation efficiency of pure and doped LTB is equal to the standard NLO material, KDP. The nonlinear optical parameters of LTB:Cu nanoparticles say, nonlinear refractive index, nonlinear absorption coefficient and third order nonlinear optical susceptibility were determined to be of the order of 10(-8)cm2/W, 10(-2) cm/W and 10(-5) esu, respectively. The optical power limiting behavior of the samples were studied by Z-scan technique with (532 nm, 50 mW) Nd:YAG laser and the limiting threshold values are found to be 22.7 mW for 0.01 M and 24.9 mW for 0.03 and 0.05 M LTB:Cu nanoparticles. PMID:25615676

  16. Needles, Burrs, and Bibliographies: Study Resources: Technological Change, Human Values, and the Humanities.

    ERIC Educational Resources Information Center

    Pennsylvania State Univ., University Park. Center for Continuing Liberal Education.

    In the first of four sections of this publication, James H. Stone reviews recent writings on the humanities, citing 299 books, essays, and articles. In the second section, Maxwell H. Goldberg provides definitions of several of the central terms related to technological change and human values (e.g.,…

  17. Needles, Burrs, and Bibliographies; Study Resources: Technological Change, Human Values, and the Humanities.

    ERIC Educational Resources Information Center

    Goldberg, Maxwell H., Ed.

    In the first of four sections of this publication, James H. Stone reviews recent writings on the humanities, citing 299 books, essays, and articles. In the second section, Maxwell H. Goldberg provides definitions of several of the central terms related to technological change and human values (e.g.,…

  18. An immortalized human blood-nerve barrier endothelial cell line for in vitro permeability studies

    PubMed Central

    Yosef, Nejla; Ubogu, Eroboghene E.

    2012-01-01

    Solute and macromolecular transport studies may elucidate nutritional requirements and drug effects in healthy and diseased peripheral nerves. Endoneurial endothelial cells are specialized microvascular cells that form the restrictive blood-nerve barrier (BNB). Primary human endoneurial endothelial cells (pHEndECs) are difficult to isolate, limiting their widespread availability for biomedical research. We developed a simian virus-40 large T-antigen (SV40-LTA) immortalized human BNB cell line via stable transfection of low passage pHEndECs and observed continuous growth in culture for >45 population doublings. As observed with pHEndECs, the immortalized BNB endothelial cells were Ulex Europaeus agglutinin-1 (UEA-1)-positive and endocytosed low density lipoprotein, but lost von Willebrand factor (vWF) expression. Glucose transporter-1 (GLUT-1), P-glycoprotein (P-gp), ?-glutamyl transpeptidase (?-GT), large neutral amino acid transporter-1 (LAT-1), creatine transporter (CRT) and monocarboxylate transporter-1 (MCT-1) mRNA expression were retained at all passages with loss of alkaline phosphatase (AP) expression after passages 16-20. Compared with an SV40-LTA immortalized human blood-brain barrier (BBB) endothelial cell line, there was increased ?-GT protein expression, equivalent expression of organic anion transporting polypeptide-C (OATP-C), organic anion transporter 3 (OAT-3), MCT-1 and LAT-1, and reduced expression of AP, CRT and P-gp by the BNB cell line at passage 20. Further studies demonstrated lower transendothelial electrical resistance (TEER: ~181 ?.cm2 vs. 191 ?.cm2), equivalent permeability to fluoresceinated sodium (4.84% vs. 4.39%) and lower permeability to fluoresceinated high molecular weight (70 kDa) dextran (0.39% vs. 0.52%) by the BNB cell line. This cell line retained essential molecular and biophysical properties suitable for in vitro peripheral nerve permeability studies. PMID:23104242

  19. Hypersensitivity reactions to human papillomavirus vaccine in Australian schoolgirls: retrospective cohort study

    PubMed Central

    2008-01-01

    Objective To describe the outcomes of clinical evaluation, skin testing, and vaccine challenge in adolescent schoolgirls with suspected hypersensitivity to the quadrivalent human papillomavirus vaccine introduced in Australian schools in 2007. Design Retrospective cohort study. Setting Two tertiary paediatric allergy centres in Victoria and South Australia, Australia. Participants 35 schoolgirls aged 12 to 18.9 years with suspected hypersensitivity reactions to the quadrivalent human papillomavirus vaccine. Main outcome measures Clinical review and skin prick and intradermal testing with the quadrivalent vaccine and subsequent challenge with the vaccine. Results 35 schoolgirls with suspected hypersensitivity to the quadrivalent human papillomavirus vaccine were notified to the specialised immunisation services in 2007, after more than 380?000 doses had been administered in schools. Of these 35 schoolgirls, 25 agreed to further evaluation. Twenty three (92%) experienced reactions after the first dose. Thirteen (52%) experienced urticaria or angio-oedema, and of these, two experienced anaphylaxis. Thirteen had generalised rash, one with angio-oedema. The median time to reaction was 90 minutes. Nineteen (76%) underwent skin testing with the quadrivalent vaccine: all were skin prick test negative and one was intradermal test positive. Eighteen (72%) were subsequently challenged with the quadrivalent vaccine and three (12%) elected to receive the bivalent vaccine. Seventeen tolerated the challenge and one reported limited urticaria four hours after the vaccine had been administered. Only three of the 25 schoolgirls were found to have probable hypersensitivity to the quadrivalent vaccine. Conclusion True hypersensitivity to the quadrivalent human papillomavirus vaccine in Australian schoolgirls was uncommon and most tolerated subsequent doses. PMID:19050332

  20. Human enamel structure studied by high resolution electron microscopy

    SciTech Connect

    Wen, S.L. )

    1989-01-01

    Human enamel structural features are characterized by high resolution electron microscopy. The human enamel consists of polycrystals with a structure similar to Ca10(PO4)6(OH)2. This article describes the structural features of human enamel crystal at atomic and nanometer level. Besides the structural description, a great number of high resolution images are included. Research into the carious process in human enamel is very important for human beings. This article firstly describes the initiation of caries in enamel crystal at atomic and unit-cell level and secondly describes the further steps of caries with structural and chemical demineralization. The demineralization in fact, is the origin of caries in human enamel. The remineralization of carious areas in human enamel has drawn more and more attention as its potential application is realized. This process has been revealed by high resolution electron microscopy in detail in this article. On the other hand, the radiation effects on the structure of human enamel are also characterized by high resolution electron microscopy. In order to reveal this phenomenon clearly, a great number of electron micrographs have been shown, and a physical mechanism is proposed. 26 references.

  1. Using the Human Genome: A Case Study in Education

    ERIC Educational Resources Information Center

    Boyle, John A.

    2002-01-01

    The working drafts of the human genome, announced in February 2001, have clearly provided a breakthrough in biochemistry and molecular biology research. The scientific data also provide an opportunity to vary a typical approach to teaching. Advanced graduate students at our university can elect to take a course in molecular genetics. The human

  2. Ovarian surface epitheliectomy in the non-human primate: continued cyclic ovarian function and limited epithelial replacement

    PubMed Central

    Wright, Jay W.; Pejovic, Tanja; Jurevic, Leigh; Bishop, Cecily V.; Hobbs, Theodore; Stouffer, Richard L.

    2011-01-01

    BACKGROUND The fifth leading cause of cancer deaths among women is ovarian cancer (OC), which originates primarily in the ovarian surface epithelium (OSE) that surrounds the ovary. Permanent removal of the OSE could provide a novel strategy to substantially reduce OC risk, while retaining the benefits of ovarian function, including gameto- and steroidogenesis. It must be determined whether ovarian surface epitheliectomy (OSEx) carries deleterious side effects, including loss of menstrual cyclicity, infertility or scarring (e.g. adhesions), prior to any clinical application of this strategy. To achieve this, we selected the non-human primate, rhesus macaque, for long-term (12 month) studies on the effects of OSEx. METHODS Rhesus macaque females underwent OSEx by detergent treatment and were then monitored for menstrual cyclicity (menstruation, steroidogenesis and follicle development) and adverse side effects (tissue scarring or adhesions). Ovaries were collected at 6 or 12 months and examined for evidence of tissue damage, follicle rupture and regression of the corpus luteum. The ovarian surface was examined immunohistologically for signs of epithelial replacement, using markers for OSE and fimbrial epithelium (FE), a possible alternative source of pelvic tumors diagnosed as OC. RESULTS After OSEx, menstrual cycle length, estrogen and progesterone production, follicle rupture and luteal regression appeared normal. No evidence of adhesions was seen. At 6 and 12 months post-OSEx, the ovarian surface was sparsely populated by cells expressing OSE and FE markers. Proliferative activity in this population was notably low. CONCLUSIONS OSEx may provide a novel method to reduce the risk of OC, without sacrificing ovarian function, although the effects on fertility remain to be tested. The absence of epithelial replacement via enhanced proliferation suggests OSEx does not increase malignant potential. Complete and permanent OSEx may be feasible. PMID:21421661

  3. To boil or not to boil -- A study of bubble embryo dormancy limits

    SciTech Connect

    Martin-Dominguez, I.R.; McDonald, T.W.

    1997-12-31

    In the literature, particularly for refrigerants, experimental studies on the superheat required to initiate nucleate boiling tend to be widely scattered, not only among investigators but even for repeated tests by the same investigator. This study provides an explanation of why this occurs and how to avoid such scatter in future tests. With few exceptions, only re-entrant surface cavities are capable of containing dormant vapor bubble embryos. These dormant embryos are essential to initiate nucleate boiling from a cavity. The temperature (wall superheat) range over which an embryo is stable depends upon the cavity shape, neck size, and the fluid surface tension and thermal properties. Above the upper wall-superheat limit, nucleate boiling occurs. Below the lower limit, the embryo will quench (vanish) and cannot be reactivated by increasing the wall superheat. This study makes the following points, for a given cavity shape, fluid, and pressure (1) The larger the cavity neck radius, the smaller the wall-superheat range over which an embryo can exist. (2) Upon cooling any surface, the boiling cavity with the smallest neck radius will be the first to stop boiling but will require the greatest reduction in wall superheat to quench its embryo. (3) Each site that retains a (dormant) vapor embryo will resume boiling at the same wall-superheat at which it ceased boiling. (4) Small cavities can have a shape such that their vapor embryos will always exist, regardless of the wall temperature. Boiling can always be reinitiated from them. (5) Any wall subject to boiling has a memory. The greater the past wall-subcooling, the greater will be the wall-superheat required to initiate boiling. (6) The wall memory can be erased with sufficient wall-superheat and the presence of vapor.

  4. Quantitative imaging of the human upper airway: instrument design and clinical studies

    NASA Astrophysics Data System (ADS)

    Leigh, M. S.; Armstrong, J. J.; Paduch, A.; Sampson, D. D.; Walsh, J. H.; Hillman, D. R.; Eastwood, P. R.

    2006-08-01

    Imaging of the human upper airway is widely used in medicine, in both clinical practice and research. Common imaging modalities include video endoscopy, X-ray CT, and MRI. However, no current modality is both quantitative and safe to use for extended periods of time. Such a capability would be particularly valuable for sleep research, which is inherently reliant on long observation sessions. We have developed an instrument capable of quantitative imaging of the human upper airway, based on endoscopic optical coherence tomography. There are no dose limits for optical techniques, and the minimally invasive imaging probe is safe for use in overnight studies. We report on the design of the instrument and its use in preliminary clinical studies, and we present results from a range of initial experiments. The experiments show that the instrument is capable of imaging during sleep, and that it can record dynamic changes in airway size and shape. This information is useful for research into sleep disorders, and potentially for clinical diagnosis and therapies.

  5. New techniques for positron emission tomography in the study of human neurological disorders

    SciTech Connect

    Kuhl, D.E.

    1989-11-01

    This progress report represents a summary of our performance during the two year period following initial start-up of these research activities at Michigan. Productivity has been excellent; already over 47 papers and abstracts have been published or accepted for publication from this still young program. They represent significant contributions to extending the technology of positron emission tomography in the study of human neurological disorders. Our focus is to develop more cost effective and efficient means for producing new functionally specific tracers and simpler, less expensive, means for acquiring and interpreting quantitative data. These improved processes are required for the future growth of PET as a sophisticated research tool and for the transfer of this technology to clinical use. Our approach concentrates on two separate yet related areas, radiosynthesis and data analysis. In subproject 1, Drs. Jewett and Mulholland have introduced innovative methods for improving 11C and 18F synthetic processes. In Subproject 2, Dr. Hutchins has laid the foundations for an objective analysis of the limitations and opportunities for quantifying regional PET data. In Subproject 3, Dr. Koeppe has extended rapid techniques for parameter estimation in kinetic modeling of new ligands. Finally, in Subproject 4, Dr. Frey has applied kinetic analysis to ligand tracing of the cholinergic neurotransmitter system in animal and human brain. These DOE supported studies have direct impact on clinical research here and elsewhere which is expected to improve diagnosis and treatment of degenerative neurological diseases, mental illness and brain tumors. 47 refs., 7 figs., 4 tabs.

  6. Immunocompetence of normal human appendiceal lymphoid cells: in vitro studies.

    PubMed Central

    Kawanishi, H

    1987-01-01

    In order to study the activity of immunocompetent lymphocytes in normal human adult mucosal lymphoid tissues in the gut, viable mononuclear cells (MNC) from surgically removed appendices were isolated with a rapid and improved technique, and their immune reactivity determined in vitro. Nearly two-thirds of the isolated cells were B cells, composed of sIgM (30%), sIgA (19%) and sIgG (12%), less than one-third of cells being T cells, composed of OKT4+ helper/inducer T cells (18%) and OKT8+ suppressor/cytotoxic T cells (9%). Isolated B cells were responsive to SAC (Cowan type I Staphylococcus aureus) with marked augmentation of IgG production, but not to lipopolysaccharides (LPS). In the presence or absence of pokeweed mitogen (PWM) and protein A, all isotype-specific Ig production was augmented along with increasing ratios of autologous T cells to B cells, whereas in the presence of anti-HLA-DR antibodies the production of IgA and IgM was reduced to a great extent. Finally, in vitro induction of concanavalin A (Con A)-induced suppressor T (Ts) cells was less than that of helper T (Th) cells. Thus, normal adult appendiceal (Ap) lymphocyte reactivity is predominated by helper T (Th) cells; IgA isotype-specific Ig production appears to be largely regulated by the autoreactive Th subset. This responsiveness to exogenous stimuli may play an important role in the gut mucosal immune responsiveness. PMID:3493205

  7. Anatomic study of human laryngeal ganglia: number and distribution.

    PubMed

    Maranillo, Eva; Vazquez, Teresa; Ibanez, Marta; Hurtado, Miguel; Pascual-Font, Aran; McHanwell, Stephen; Valderrama-Canales, Francisco; Sanudo, Jose

    2008-10-01

    We have studied 12 laryngeal nerves: six internal branches of the superior laryngeal nerve (ILN) and six recurrent laryngeal nerves (RLN) from three human adult larynges (two males and one female). After dissection of each individual laryngeal nerve using a surgical microscope, the nerves were preserved in 10% formalin, embedded in paraffin wax, serially sectioned transversely at a thickness of 10 microm and stained with hematoxylin and eosin. We found 2-4 ganglia associated with the ILN. At least two ganglia were always present (six out of six cases), the largest one being associated with the branch of the nerve innervating the vestibule and the smallest one associated with the branch innervating the aryepiglottic fold. Other ganglia were found associated with the branches for the glosso-epiglottic fold and vallecula (four out of six cases) and interarytenoid muscle (three out of six cases). The RLN showed from two to six ganglia, all of them located in its anterior terminal division. Two of the ganglia were located in the part of the nerve between the origin of the branches for the interarytenoid and lateral cricoarytenoid muscles (three out of six cases). The remaining ganglia were located close to or at the origin of the muscular branches innervating the intrinsic laryngeal muscles. The cytology of the ganglia reported suggests that they were all autonomic in nature, probably parasympathetic. PMID:18773473

  8. 7Li NMR study of normal human erythrocytes

    NASA Astrophysics Data System (ADS)

    Pettegrew, J. W.; Post, J. F. M.; Panchalingam, K.; Withers, G.; Woessner, D. E.

    The biological action of lithium is of great interest because of the therapeutic efficacy of the cation in manic-depressive illness. To investigate possible molecular interactions of lithium, 7Li NMR studies were conducted on normal human erythrocytes which had been incubated with lithium chloride. The uptake of lithium ions was followed by 7Li NMR, using a dysprosium, tripolyphosphate shift reagent. Lithium uptake followed single-exponential kinetics with a time constant of 14.7 h. The intracellular lithium relaxation times were T 1 ? 5 s and T 2 ? 0.15 s, which implies a lengthening of the lithium correlation time. It was found that lithium does not interact significantly with hemoglobin, the erythrocyte membrane, or artificial phospholipid membranes. Based on measurements of lithium T1 and T2 in concentrated agar gels, the large difference between T1 and T2 for intracellular lithium ions may be due to diffusion of the hydrated lithium ion through heterogeneous electrostatic field gradients created by the erythrocyte membrane-associated cytoskeletal network. Lithium binding to the membrane-associated cytoskeleton, however, cannot be ruled out. Because of the large differences between T1 and T2 of intracellular lithium ions, 1Li NMR may be a sensitive and promising noninvasive method to probe the intracellular environment.

  9. A study of rechargeable zinc electrodes for alkaline cells requiring anodic limitation

    NASA Astrophysics Data System (ADS)

    Binder, L.; Odar, W.; Kordesch, K.

    1981-07-01

    Problems associated with the cyclic operation of zinc electrodes in rechargeable alkaline cells for which anodic limitation is required are investigated. Experiments were conducted to determine the influence of electrolyte additives and cell construction on the capacity loss of limited zinc electrodes during cycling; current-voltage diagrams for zinc electrodes within the potential range of passivation and of hydrogen evolution were also recorded. In tests of alkaline cells with zinc and MnO2 electrodes, it is found that the addition of ZnO and Zn(CN)2 to the electrolyte or the use of Zn(CN)2 for the electrode gel leads to an increase in cell cycle life up to 70 cycles. Cells with copper powder and PTFE added to the electrode gel are observed to exhibit nearly uniform cycles after a rapid drop in capacity at the second cycle. Passivation studies based on the current-voltage diagrams reveal a peak in current densities needed for passivation at an electrolyte concentration of 7.5 m KOH. Results also confirm the fact that metals including lead, tin and indium increase the hydrogen overvoltage of zinc to the same extent as mercury.

  10. Sub-Kelvin cooler configuration study for the Background Limited Infrared Submillimeter Spectrometer BLISS on SPICA

    NASA Astrophysics Data System (ADS)

    Holmes, W.; Bock, J. J.; Matt Bradford, C.; Chui, T. C. P.; Koch, T. C.; Lamborn, A. U.; Moore, D.; Paine, C. G.; Thelen, M. P.; Yazzie, A.

    2010-09-01

    The Background Limited Infrared Submillimeter Spectrometer (BLISS) is an instrument proposed for the Japanese space borne telescope mission SPICA. The BLISS concept is a suite of grating spectrometers which combine to cover the 40-400 ?m range at resolving power R˜700 with detector sensitivity approaching the natural photon background limits. To achieve the high sensitivity, the BLISS detectors require cooling to 50 mK, well below the 1.7 K cold stage provided on the SPICA spacecraft. We present a thermal architecture for BLISS that includes a thermal intercept stage actively cooled to a temperature in between the 1.7 K cold tip and the detector stage at 50 mK. This architecture requires, essentially, two coolers; one to cool the intercept stage from 1.7 K and one to cool the detectors from the intercept stage temperature to 50 mK. We compared several configurations of flight-heritage coolers to cool the intercept and detector stages. Of the various configurations studied, a continuous adiabatic demagnetization refrigerator (ADR) for each stage has the highest maturity, lowest heat dump at 1.7 K and total mass comparable to other approaches. Other options, such as a Herschel 3He sorption cooler-ADR hybrid and the recently demonstrated closed cycle version of the dilution cooler on Planck are also feasible for BLISS on SPICA.

  11. Studies of [ital WW] and [ital WZ] production and limits on anomalous [ital WW[gamma

    SciTech Connect

    Grinstein, S.; Mostafa, M.; Piegaia, R. ); Alves, G.A.; Carvalho, W.; da Motta, H.; Santoro, A. ); Lima, J.G.; Oguri, V. ); Mao, H.S. ); Gomez, B.; Mooney, P.; Negret, J.P. ); Hoeneisen, B. ); Parua, N. ); Ducros, Y. ); Beri, S.B.; Bhatnagar, V.; Kohli, J.M.; Singh, J.B. ); Shivpuri, R.K. ); Acharya, B.S.; Banerjee, S.; Dugad, S.R.; Gupta, A.; Krishnaswamy, M.R.; Mondal, N.K.; Narasimham, V.S.; Shankar, H.C. (Tata Inst.

    1999-10-01

    Evidence of anomalous WW and WZ production was sought in p[bar p] collisions at a center-of-mass energy of [radical] (s) =1.8 hthinsp;TeV. The final states WW(WZ)[r arrow][mu][nu] jet jet+X, WZ[r arrow][mu][nu]ee+X and WZ[r arrow]e[nu]ee+X were studied using a data sample corresponding to an integrated luminosity of approximately 90 hthinsp;pb[sup [minus]1]. No evidence of anomalous diboson production was found. Limits were set on anomalous WW[gamma] and WWZ couplings and were combined with our previous results. The combined 95[percent] confidence level anomalous coupling limits for [Lambda]=2 hthinsp;TeV are [minus]0.25[le][Delta][kappa][le]0.39 ([lambda]=0) and [minus]0.18[le][lambda][le]0.19 ([Delta][kappa]=0), assuming the WW[gamma] couplings are equal to the WWZ couplings. [copyright] [ital 1999] [ital The American Physical Society

  12. General Human Health Issues For Moon And Mars Missions: Results From The HUMEX Study

    NASA Astrophysics Data System (ADS)

    Horneck, G.; Comet, B.

    Human exploratory missions, such as the establishment of a permanently inhabited lunar base and/or human visits to Mars will add a new dimension to human space flight, concerning the distance of travel, the radiation environment, the gravity lev-els, the duration of the mission, and the level of confinement and isolation the crew will be exposed to. This will raise the significance of several health issues. Besides spaceflight specific risks, such as radiation health, gravity related effects and psy-chological issues, general health issues need to be considered. These individual risks of illness, injury or death are based on general human health statistics. The duration of the mission is the main factor in these considerations. These risk estimations are the base which have to supplemented by the risks related specifically to the nature of the expedition under consideration. Crew health and performance have to be secured during transfer flights, during lunar or Mars surface exploration, including EVAs, and upon return to Earth, as defined within the constraints of safety objectives and mass restrictions of the mission. Within the ESA Study on the Survivability and Adaptation of Humans to Long-Duration Interplanetary and Planetary Environments (so called HUMEX study), we have critically assessed the human responses, limits and needs with regard to the environments of interplanetary and planetary missions. Based on various scenarios, the crew health risks have been evaluated. The main results are as follows: (i) The state of the art shows that bone loss during the long stay in weightlessness, especially during missions to Mars, remains an unacceptable risk. Solutions to control and to prevent this risk shall be developed. (ii) The control of human physical capacity impairment under weightlessness shall be optimized. (iii) Based of the probability of occurrence of diseases and injuries and on the con-straints imposed by exploratory mission scenarios, the crew shall have a full auton-omy in terms of medical and surgical diagnostics and care means and competency. (iv) The control of the toxic and biological risks in a confined environment for a so long exposure shall be carefully analyzed and the technical solutions shall master these risks. A roadmap in the field of health care has been elaborated for a future European participation strategy towards human exploratory missions taking into account preparatory activities, such as analogue situations and ISS opportunities, European positioning and potential terrestrial applications and benefits. References: Horneck G. , R. Facius, M. Reichert, P. Rettberg, W. Seboldt, D. Man-zey, B. Comet, A. Maillet, H. Preiss, L. Schauer, C.G. Dussap, L. Poughon, A. Belyavin, G. Reitz, C. Baumstark-Khan, R. Gerzer (2003) HUMEX, a Study on the Survivability and Adaptation of Humans to Long-Duration Exploratory Missions, ESA SP-1264

  13. Limited transfer of nitrogen between wood decomposing and ectomycorrhizal mycelia when studied in the field.

    PubMed

    Wallander, Håkan; Lindahl, Björn D; Nilsson, Lars Ola

    2006-05-01

    Transfer of (15)N between interacting mycelia of a wood-decomposing fungus (Hypholoma fasciculare) and an ectomycorrhizal fungus (Tomentellopsis submollis) was studied in a mature beech (Fagus sylvatica) forest. The amount of (15)N transferred from the wood decomposer to the ectomycorrhizal fungus was compared to the amount of (15)N released from the wood-decomposing mycelia into the soil solution as (15)N-NH(4). The study was performed in peat-filled plastic containers placed in forest soil in the field. The wood-decomposing mycelium was growing from an inoculated wood piece and the ectomycorrhizal mycelium from an introduced root from a mature tree. The containers were harvested after 41 weeks when physical contact between the two foraging mycelia was established. At harvest, (15)N content was analyzed in the peat (total N and (15)NH(4) (+)) and in the mycorrhizal roots. A limited amount of (15)N was transferred to the ectomycorrhizal fungus and this transfer could be explained by (15)NH(4) (+) released from the wood-decomposing fungus without involving any antagonistic interactions between the two mycelia. Using our approach, it was possible to study nutritional interactions between basidiomycete mycelia under field conditions and this and earlier studies suggest that the outcomes of such interactions are highly species-specific and depend on environmental conditions such as resource availability. PMID:16598505

  14. Tissue microchimerism is increased during pregnancy: a human autopsy study.

    PubMed

    Rijnink, Emilie C; Penning, Marlies E; Wolterbeek, Ron; Wilhelmus, Suzanne; Zandbergen, Malu; van Duinen, Sjoerd G; Schutte, Joke; Bruijn, Jan A; Bajema, Ingeborg M

    2015-11-01

    Microchimerism is the occurrence of small populations of cells with a different genetic background within an individual. Tissue microchimerism is considered to be primarily pregnancy-derived and is often studied relative to female-dominant autoimmune diseases, pregnancy complications, malignancies, response to injury, and transplantation outcomes. A particular distribution pattern of chimeric cells across various organs was recently described in a model of murine pregnancies. Our aim was to determine the frequency and distribution of tissue microchimerism across organs during and after pregnancy in humans. We performed in situ hybridization of the Y chromosome on paraffin-embedded autopsy samples of kidneys, livers, spleens, lungs, hearts and brains that were collected from 26 women who died while pregnant or within 1 month after delivery of a son. Frequencies of chimeric cells in various tissues were compared with those of a control group of non-pregnant women who had delivered sons. Tissue microchimerism occurred significantly more frequently in the lungs, spleens, livers, kidneys and hearts of pregnant women compared with non-pregnant women (all P < 0.01). We showed that some of the chimeric cells were CD3+ or CD34+. After correction for cell density, the lung was most chimeric (470 Y chromosome-positive nuclei per million nuclei scored), followed by the spleen (208 Y+/10(6) nuclei), liver (192 Y+/10(6) nuclei), kidney (135 Y+/10(6) nuclei), brain (85 Y+/10(6) nuclei) and heart (40 Y+/10(6) nuclei). Data from this unique study group of women who died while pregnant or shortly after delivery provide information about the number and physiologic distribution of chimeric cells in organs of pregnant women. We demonstrate that during pregnancy, a boost of chimeric cells is observed in women, with a distribution across organs, that parallels findings in mouse models. PMID:26307194

  15. Biological effects on human health due to radiofrequency/microwave exposure: a synopsis of cohort studies.

    PubMed

    Breckenkamp, Jürgen; Berg, Gabriele; Blettner, Maria

    2003-10-01

    We evaluated the methods and results of nine cohort studies dealing with the biological effects on human health from exposure to radiofrequencies/microwaves, published between 1980 and 2002. The size of the cohorts varied between 304 (3,362 person years) and nearly 200,000 persons (2.7 million person years). As exposures were defined: dielectric heaters in a plastic manufacturing plant, working with radio devices (professional and amateur), production of wireless communication technologies, radar devices of the Canadian police, radar units used by the military as well as artificially produced electromagnetic pulses similar to those after a nuclear explosion. In all studies (except one that used a qualitative job-exposure-matrix) either the duration of occupational work as an approximation to actual exposure was determined or a simple yes/no differentiation was used based on a definition of high-exposed and/or low-exposed (occupational) groups. Either total mortality, cancer mortality, cancer incidence or other outcomes were estimated. In most of the studies, an increased risk for various types of cancer was found in exposed study participants, although in different organs. The overall results were, however, inconsistent. The most important limitations of the studies were the lack of measurements referring to past and current exposures and, thus, the unknown details on actual exposure, the use of possibly biased data as well as the lack of adjustment for potential confounders and the use of indirect standardization techniques. Due to these limitations and the inconsistencies of the results it has to be concluded that the studies give no evidence of high frequency emissions causing cancer. PMID:14508584

  16. 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.

  17. 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.

  18. 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...

  19. Magnetotransport studies of mobility limiting mechanisms in undoped Si/SiGe heterostructures

    NASA Astrophysics Data System (ADS)

    Mi, X.; Hazard, T. M.; Payette, C.; Wang, K.; Zajac, D. M.; Cady, J. V.; Petta, J. R.

    2015-07-01

    We perform detailed magnetotransport studies on two-dimensional electron gases (2DEGs) formed in undoped Si/SiGe heterostructures in order to identify the electron mobility limiting mechanisms. By analyzing data from 26 different heterostructures, we observe a strong correlation between the background oxygen concentration in the Si quantum well and the maximum mobility. The highest-quality wafer supports a 2DEG with mobility ? =160 000 cm 2/Vs at a density n =2.17 ×1011 /cm 2 and exhibits a metal-to-insulator transition at a critical density nc=0.46 ×1011 /cm 2. We extract a valley splitting ?v˜150 ? eV at a magnetic field B =1.8 T. These results provide evidence that undoped Si/SiGe heterostructures are suitable for the fabrication of few-electron quantum dots.

  20. Establishing the Limits of TrueAllele® Casework: A Validation Study.

    PubMed

    Greenspoon, Susan A; Schiermeier-Wood, Lisa; Jenkins, Brad C

    2015-09-01

    The limits of the expert system, TrueAllele® Casework (TA), were explored using challenging mock casework profiles that included 17 single-source and 18 two-, 15 three- and 7 four-person DNA mixtures. The sensitivity (ability to detect a minor contributor) of the TA analysis process was examined by challenging the system with mixture DNA samples that exhibited allelic and locus dropout and other stochastic effects. The specificity (ability to exclude nondonors) was rigorously tested by interrogating TA derived genotypes with 100 nondonor profiles. The accuracy with which TA estimated mixture weights of contributors to the two-person mixtures was examined. Finally, first-degree relatives of donors were used to assess the ability of the system to exclude close relatives. TA demonstrated great accuracy, sensitivity, and specificity. TA correctly assigned mixture weights and excluded nearly all first-degree relatives. This study demonstrates the analysis power of the TrueAllele® Casework system. PMID:26258391

  1. Pedagogy and Human Movement: Theory, Practice, Research. Routledge Studies in Physical Education and Youth Sport

    ERIC Educational Resources Information Center

    Tinning, Richard

    2011-01-01

    Across the full range of human movement studies and their many sub-disciplines, established institutional practices and forms of pedagogy are used to (re)produce valued knowledge about human movement. "Pedagogy and Human Movement" explores this pedagogy in detail to reveal its applications and meanings within individual fields. This unique book…

  2. 75 FR 10261 - Request for Nominations to the EPA Human Studies Review Board

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-05

    ...The U.S. Environmental Protection Agency (EPA or Agency) Office of the Science Advisor (OSA) is soliciting nominations of people qualified in the areas of bioethics, biostatistics, human health risk assessment and human toxicology to serve on the Human Studies Review Board (HSRB). The HSRB is a Federal advisory committee, operating in accordance with the Federal Advisory Committee Act (FACA) 5......

  3. A Multimodal Real-Time Platform for Studying Human-Avatar Interactions

    E-print Network

    Yu, Chen

    A Multimodal Real-Time Platform for Studying Human-Avatar Interactions Hui Zhang, Damian Fricker in real time, and adjust his own behaviors accordingly. Multimodal data streams are collected in human-avatar promising results about the role and functioning of joint attention in human-avatar interactions. Keywords

  4. BIOL330 Human Sexuality Prerequisite for MA in Sexuality Studies WHY IS THERE A BIOLOGY PREREQUISITE?

    E-print Network

    BIOL330 Human Sexuality Prerequisite for MA in Sexuality Studies WHY IS THERE A BIOLOGY foundations of human sexuality. This foundational knowledge is expected for all entering graduate students, and is necessary for the many advanced discussions about human sexuality in the required graduate theory

  5. Study of Pressure Estimation for a Human Circulatory System with a LVAD

    E-print Network

    Wu, Yi

    Study of Pressure Estimation for a Human Circulatory System with a LVAD Yi Wu1 , Paul Allaire2. Based on the state space model of human circulatory system, the mean aortic pressure can be estimated-invasive evaluation of left ventricular function and properties of human circulatory system. Keywords: Cardiovascular

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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, as assessed by RRS, has been suggested as a promising biomarker for use in human studies. This manuscript describes...

  7. Does Bug Prediction Support Human Developers? Findings From a Google Case Study

    E-print Network

    Cortes, Corinna

    Does Bug Prediction Support Human Developers? Findings From a Google Case Study Chris Lewis1 not have a strong idea about whether such algorithms are useful to guide human developers. We deployed in order to be accepted by human developers and truly change how developers evaluate their code. I

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

    PubMed

    Nguyen, Annalee W; Wagner, Ellen K; Laber, Joshua R; Goodfield, Laura L; Smallridge, William E; Harvill, Eric T; Papin, James F; Wolf, Roman F; Padlan, Eduardo A; Bristol, Andy; Kaleko, Michael; Maynard, Jennifer A

    2015-12-01

    Despite widespread vaccination, pertussis rates are rising in industrialized countries and remain high worldwide. With no specific therapeutics to treat disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin is a major contributor to disease, responsible for local and systemic effects including leukocytosis and immunosuppression. We humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human immunoglobulin G1 molecules with no loss of affinity or in vitro neutralization activity. When administered prophylactically to mice as a binary cocktail, antibody treatment completely mitigated the Bordetella pertussis-induced rise in white blood cell counts and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated, but not untreated control animals, experienced a blunted rise in white blood cell counts and accelerated bacterial clearance rates. These preliminary findings support further investigation into the use of these antibodies to treat human neonatal pertussis in conjunction with antibiotics and supportive care. PMID:26631634

  9. Improved Detection Limit in Rapid Detection of Human Enterovirus 71 and Coxsackievirus A16 by a Novel Reverse Transcription–Isothermal Multiple-Self-Matching-Initiated Amplification Assay

    PubMed Central

    Ding, Xiong; Nie, Kai; Shi, Lei; Zhang, Yong; Guan, Li; Zhang, Dan

    2014-01-01

    Rapid detection of human enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) is important in the early phase of hand-foot-and-mouth disease (HFMD). In this study, we developed and evaluated a novel reverse transcription–isothermal multiple-self-matching-initiated amplification (RT-IMSA) assay for the rapid detection of EV71 and CVA16 by use of reverse transcriptase, together with a strand displacement DNA polymerase. Real-time RT-IMSA assays using a turbidimeter and visual RT-IMSA assays to detect EV71 and CVA16 were established and completed in 1 h, and the reported corresponding real-time reverse transcription–loop-mediated isothermal amplification (RT-LAMP) assays targeting the same regions of the VP1 gene were adopted as parallel tests. Through testing VP1 RNAs transcribed in vitro, the real-time RT-IMSA assays exhibited better linearity of quantification, with R2 values of 0.952 (for EV71) and 0.967 (for CVA16), than the real-time RT-LAMP assays, which had R2 values of 0.803 (for EV71) and 0.904 (for CVA16). Additionally, the detection limits of the real-time RT-IMSA assays (approximately 937 for EV71 and 67 for CVA16 copies/reaction) were higher than those of real-time RT-LAMP assays (approximately 3,266 for EV71 and 430 for CVA16 copies/reaction), and similar results were observed in the visual RT-IMSA assays. The new approaches also possess high specificities for the corresponding targets, with no cross-reactivity observed. In clinical assessment, compared to commercial reverse transcription-quantitative PCR (qRT-PCR) kits, the diagnostic sensitivities of the real-time RT-IMSA assays (96.4% for EV71 and 94.6% for CVA16) were higher than those of the real-time RT-LAMP assays (91.1% for EV71 and 90.8% for CVA16). The visual RT-IMSA assays also exhibited the same results. In conclusion, this proof-of-concept study suggests that the novel RT-IMSA assay is superior to the RT-LAMP assay in terms of detection limit and has the potential to rapidly detect EV71 and CVA16 viruses. PMID:24648558

  10. Abstract--In this paper, we study the limitations imposed by the laws of electromagnetism on achievable MIMO channel

    E-print Network

    Loyka, Sergey

    Abstract-- In this paper, we study the limitations imposed by the laws of electromagnetism electromagnetic wave combined with Nyquist sampling theorem in the spatial domain, we show that the laws of electromagnetism limit the minimum antenna spacing to half a wavelength, /2 , (in the case of 1-D antenna apertures

  11. Are Liberal Studies Teachers Ready to Prepare Human Rights Respecting Students? A Portrait of Teachers' Attitudes towards Human Rights

    ERIC Educational Resources Information Center

    Leung, Yan Wing; Lo, Yan Lam

    2012-01-01

    As in most countries, human rights education (HRE) in Hong Kong has never been high on the educational agenda. In 2009, a compulsory subject, Liberal Studies (LS), which could be used as a platform for HRE, was introduced. The Hong Kong Institute of Education launched a research and development project which, as one of its objectives, studied LS…

  12. A standardized approach to study human variability in isometric thermogenesis during low-intensity physical activity

    PubMed Central

    Sarafian, Delphine; Miles-Chan, Jennifer L.; Yepuri, Gayathri; Montani, Jean-Pierre; Schutz, Yves; Dulloo, Abdul G.

    2013-01-01

    Limitations of current methods: The assessment of human variability in various compartments of daily energy expenditure (EE) under standardized conditions is well defined at rest [as basal metabolic rate (BMR) and thermic effect of feeding (TEF)], and currently under validation for assessing the energy cost of low-intensity dynamic work. However, because physical activities of daily life consist of a combination of both dynamic and isometric work, there is also a need to develop standardized tests for assessing human variability in the energy cost of low-intensity isometric work. Experimental objectives: Development of an approach to study human variability in isometric thermogenesis by incorporating a protocol of intermittent leg press exercise of varying low-intensity isometric loads with measurements of EE by indirect calorimetry. Results: EE was measured in the seated position with the subject at rest or while intermittently pressing both legs against a press-platform at 5 low-intensity isometric loads (+5, +10, +15, +20, and +25 kg force), each consisting of a succession of 8 cycles of press (30 s) and rest (30 s). EE, integrated over each 8-min period of the intermittent leg press exercise, was found to increase linearly across the 5 isometric loads with a correlation coefficient (r) > 0.9 for each individual. The slope of this EE-Load relationship, which provides the energy cost of this standardized isometric exercise expressed per kg force applied intermittently (30 s in every min), was found to show good repeatability when assessed in subjects who repeated the same experimental protocol on 3 separate days: its low intra-individual coefficient of variation (CV) of ~ 10% contrasted with its much higher inter-individual CV of 35%; the latter being mass-independent but partly explained by height. Conclusion: This standardized approach to study isometric thermogenesis opens up a new avenue for research in EE phenotyping and metabolic predisposition to obesity. PMID:23847539

  13. Structural studies of the human polymeric immunoglobulin receptor

    E-print Network

    Hamburger, Agnes Eva, 1976-

    2005-01-01

    The human polymeric immunoglobulin receptor, pIgR, is a glycosylated type I transmembrane protein expressed on the basolateral surface of secretory epithelial cells. pIgR plays a key role in mucosal immunity and, together ...

  14. 76 FR 34703 - Human Studies Review Board Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-14

    ...a diverse range of qualified candidates with expertise in bioethics and toxicology to be considered for appointment to its Human...EPA is seeking nominations for individuals with expertise in bioethics and toxicology. EPA values and welcomes diversity. In...

  15. Experimental study of Human Adenoviruses interactions with clays

    NASA Astrophysics Data System (ADS)

    Bellou, Maria; Syngouna, Vasiliki; Paparrodopoulos, Spyros; Vantarakis, Apostolos; Chrysikopoulos, Constantinos

    2014-05-01

    Clays are used to establish low permeability liners in landfills, sewage lagoons, water retention ponds, golf course ponds, and hazardous waste sites. Human adenoviruses (HAdVs) are waterborne viruses which have been used as viral indicators of fecal pollution. The objective of this study was to investigate the survival of HAdV in static and dynamic clay systems. The clays used as a model were crystalline aluminosilicates: kaolinite and bentonite. The adsorption and survival of HAdVs onto these clays were characterized at two different controlled temperatures (4 and 25o C) under static and dynamic batch conditions. Control tubes, in the absence of clay, were used to monitor virus inactivation due to factors other than adsorption to clays (e.g. inactivation or sorption onto the tubes walls). For both static and dynamic batch experiments, samples were collected for a maximum period of seven days. This seven day time - period was determined to be sufficient for the virus-clay systems to reach equilibrium. To infer the presence of infectious HAdV particles, all samples were treated with Dnase and the extraction of viral nucleid acid was performed using a commercial viral RNA kit. All samples were analyzed by Real - Time PCR which was used to quantify viral particles in clays. Samples were also tested for virus infectivity by A549 cell cultures. Exposure time intervals in the range of seven days (0.50-144 hours) resulted in a load reduction of 0.74 to 2.96 logs for kaolinite and a reduction of 0.89 to 2.92 for bentonite. Furthermore, virus survival was higher onto bentonite than kaolinite (p

  16. Vascular targets for cannabinoids: animal and human studies

    PubMed Central

    Stanley, Christopher; O'Sullivan, Saoirse E

    2014-01-01

    Application of cannabinoids and endocannabinoids to perfused vascular beds or individual isolated arteries results in changes in vascular resistance. In most cases, the result is vasorelaxation, although vasoconstrictor responses are also observed. Cannabinoids also modulate the actions of vasoactive compounds including acetylcholine, methoxamine, angiotensin II and U46619 (thromboxane mimetic). Numerous mechanisms of action have been proposed including receptor activation, potassium channel activation, calcium channel inhibition and the production of vasoactive mediators such as calcitonin gene-related peptide, prostanoids, NO, endothelial-derived hyperpolarizing factor and hydrogen peroxide. The purpose of this review is to examine the evidence for the range of receptors now known to be activated by cannabinoids. Direct activation by cannabinoids of CB1, CBe, TRPV1 (and potentially other TRP channels) and PPARs in the vasculature has been observed. A potential role for CB2, GPR55 and 5-HT1A has also been identified in some studies. Indirectly, activation of prostanoid receptors (TP, IP, EP1 and EP4) and the CGRP receptor is involved in the vascular responses to cannabinoids. The majority of this evidence has been obtained through animal research, but recent work has confirmed some of these targets in human arteries. Vascular responses to cannabinoids are enhanced in hypertension and cirrhosis, but are reduced in obesity and diabetes, both due to changes in the target sites of action. Much further work is required to establish the extent of vascular actions of cannabinoids and the application of this research in physiological and pathophysiological situations. Linked ArticlesThis article is part of a themed section on Cannabinoids 2013. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue-6 PMID:24329566

  17. 76 FR 59697 - Human Studies Review Board (HSRB); Notification of a Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-27

    ...EPA's Human Studies Review Board will consider scientific and ethical issues...the HSRB on the scientific soundness of this completed study for use to estimate...the HSRB on the scientific soundness of this completed study for use in...

  18. 78 FR 69778 - Adjustments to Limitations on Designated School Official Assignment and Study by F-2 and M-2...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-21

    ...School Official Assignment and Study by F-2 and M-2 Nonimmigrants...increase opportunities for study by spouses and children of...less than a full course of study at SEVP-certified schools...significant effect on the human environment. This proposed rule...

  19. Mummified remains from the Archaeological Museum in Zagreb, Croatia - Reviewing peculiarities and limitations of human and non-human radiological identification and analysis in mummified remains.

    PubMed

    Petaros, Anja; Jankovi?, Ivor; Cavalli, Fabio; Ivanac, Gordana; Brklja?i?, Boris; ?avka, Mislav

    2015-10-01

    Forensic protocols and medico-legal techniques are increasingly being employed in investigations of museological material. The final findings of such investigations may reveal interesting facts on historical figures, customs and habits, as well as provide meaningful data for forensic use. Herein we present a case review where forensic experts were requested to identify taxonomic affinities, stage of preservation and provide skeletal analysis of mummified non-human archaeological remains, and verify whether two mummified hands are human or not. The manuscript offers a short review on the process and particularities of radiological species identification, the impact of post-mortem changes in the analysis and imaging of mummified remains as well as the macroscopical interpretation of trauma, pathology and authenticity in mummified remains, which can all turn useful when dealing with forensic cases. PMID:26344461

  20. Studies on the glucuronidation of dopamine D-1 receptor antagonists, SCH 39166 and SCH 23390, by human liver microsomes.

    PubMed

    Tephly, T R; Coffman, B; Styczynski, P; Rios, G; Charkowski, D M; Vanrollins, M; McQuade, R D; Tedford, C E

    1994-01-01

    Dopamine D-1 receptor antagonists are currently under investigation for use as antipsychotic agents. Two potent and selective D-1 receptor antagonists, SCH 39166 and SCH 23390, have been studied extensively in various experimental animal models. SCH 39166 has a more prolonged duration of action in primates in vivo and a lower rate of in vitro glucuronidation by microsomes from squirrel monkey liver. Because the rate of glucuronidation seems to govern the duration of action and may limit the use of these agents in humans, the glucuronidation of SCH 39166 and SCH 23390 by microsomes isolated from human liver was studied. The rates of glucuronide formation (Vmax) for SCH 39166 were much lower than those of SCH 23390, yet the KM values were similar. Therefore, the average efficiency (Vmax/KM) of SCH 39166 glucuronidation was only 14% that of SCH 23390. These results agree with previous studies in hepatic microsomes from squirrel monkeys. Marked inhibition of SCH 39166 glucuronidation by SCH 23390 and its pharmacologically inactive stereoisomer, SCH 23388, was observed. The inactive stereoisomer of SCH 39166, SCH 39165, was a weak inhibitor. In contrast, substrates for morphine UDP-glucuronosyltransferase (UGT), and p-nitrophenol, an alternative substrate for numerous human hepatic UGTs, did not inhibit SCH 39166 glucuronidation. Further separation of human hepatic UGTs activities using chromatofocusing chromatography indicated that SCH 39166 UGT activity was distinct from human hepatic UGT2B15 and human hepatic pI 6.2 UGT activity. Thus, a unique human hepatic UGT may be involved in SCH 39166 glucuronidation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7835222

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

    SciTech Connect

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

    1994-10-01

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

  2. Comparative study of objective functions to overcome noise and bandwidth limitations in full waveform inversion

    NASA Astrophysics Data System (ADS)

    Jiménez Tejero, C. E.; Dagnino, D.; Sallarès, V.; Ranero, C. R.

    2015-10-01

    Ongoing works on full waveform inversion (FWI) are yielding an increasing number of objective functions as alternative to the traditional L2-waveform. These studies aim at designing more robust functions and inversion strategies to reduce the intrinsic dependence of the FWI results on (1) the initial model and (2) the lowest frequency present in field data. In this work, we perform a comparative study of five objective functions in time domain under a common 2-D-acoustic FWI scheme using the Marmousi model as benchmark. In particular, we compare results obtained with L2-based functions that consider the minimization of different wave attributes; the waveform-based, non-integration-method; instantaneous envelope; a modified version of the wrapped instantaneous phase and an improved version of the cross-correlation travel time (CCTT) method; and hybrid strategies combining some of them. We evaluate the robustness of these functionals as a function of their performance with and without low frequencies in the data and the presence of random white Gaussian noise. Our results reveal promising strategies to invert noisy data with limited low-frequency content (?4 Hz), which is the single strategy using the instantaneous phase objective function followed by the hybrid strategies using the instantaneous phase or CCTT as initial models, in particular the combinations [I. Phase + Waveform], [CCTT + Waveform] and [CCTT + I. Phase].

  3. 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…

  4. A calorimetric study of human CuZn superoxide dismutase.

    PubMed Central

    Biliaderis, C G; Weselake, R J; Petkau, A; Friesen, A D

    1987-01-01

    Structural alterations, as manifested by thermal transitions, caused by removal or binding of metal ions to human and bovine CuZn superoxide dismutases (SODs) were investigated by differential scanning calorimetry. Although holo forms of the two mammalian enzymes exhibited irreversible thermal transitions (delta Hcal. = 27.7 J/g and Td = 104 degrees C for bovine SOD; delta Hcal. = 23.6 J/g and Td = 101 degrees C for human SOD), only the bovine apoenzyme showed the presence of a less thermostable form (delta Hcal. = 10.7 J/g and Td = 63 degrees C). These observations suggested that human apo-SOD had considerably less conformational order than bovine apo-SOD. Reconstitution of human and bovine apoenzymes with Cu2+ and Zn2+ resulted in recovery of thermodynamic parameters and specific activity. Binding of Zn2+ alone to human apo-SOD resulted in the formation of two distinct structural units, detectable by differential scanning calorimetry, which underwent conformational disorder at 82 and 101 degrees C respectively. Saturation of binding sites with both Zn2+ and Cu2+ appeared to stabilize the enzyme structure further as shown by elimination of the low-temperature transition and the appearance of another thermal transition at a higher temperature. PMID:3435496

  5. A calorimetric study of human CuZn superoxide dismutase.

    PubMed

    Biliaderis, C G; Weselake, R J; Petkau, A; Friesen, A D

    1987-12-15

    Structural alterations, as manifested by thermal transitions, caused by removal or binding of metal ions to human and bovine CuZn superoxide dismutases (SODs) were investigated by differential scanning calorimetry. Although holo forms of the two mammalian enzymes exhibited irreversible thermal transitions (delta Hcal. = 27.7 J/g and Td = 104 degrees C for bovine SOD; delta Hcal. = 23.6 J/g and Td = 101 degrees C for human SOD), only the bovine apoenzyme showed the presence of a less thermostable form (delta Hcal. = 10.7 J/g and Td = 63 degrees C). These observations suggested that human apo-SOD had considerably less conformational order than bovine apo-SOD. Reconstitution of human and bovine apoenzymes with Cu2+ and Zn2+ resulted in recovery of thermodynamic parameters and specific activity. Binding of Zn2+ alone to human apo-SOD resulted in the formation of two distinct structural units, detectable by differential scanning calorimetry, which underwent conformational disorder at 82 and 101 degrees C respectively. Saturation of binding sites with both Zn2+ and Cu2+ appeared to stabilize the enzyme structure further as shown by elimination of the low-temperature transition and the appearance of another thermal transition at a higher temperature. PMID:3435496

  6. High-Performance Liquid Chromatographic Determination of Rivastigmine in Human Plasma for Application in Pharmacokinetic Studies

    PubMed Central

    Amini, Hossein; Ahmadiani, Abolhassan

    2010-01-01

    A simple and reproducible HPLC method with spectrophotometric detection was developed for determination of rivastigmine in human plasma. Liquid-liquid extraction of rivastigmine and donepezil (as internal standard) from plasma samples was performed with 1-butanol/n-hexane (2:98 v/v) in alkaline condition followed by back-extraction into diluted acetic acid. Chromatography was carried out using a Silica column (250 mm × 4.6 mm, 5 ?m) under isocratic elution with acetonitrile-50 mM aqueous sodium dihydrogen phosphate (17: 83 v/v, pH 3.1. Analyses were run at a flow-rate of 1.3 mL/min at of 50°C. The recovery was 90.8% and 95.7% for rivastigmine and the internal standard donepezil, respectively. The precision of the method was 2.6% to 9.1% over the concentration range of 0.5-16 ng/mL for rivastigmine in plasma with a linearity greater than 0.999. The method was specific and sensitive, with a quantification limit of 0.5 ng/mL and a detection limit of 0.2 ng/mL in plasma. The method was used for a bioequivalence study in healthy subjects. PMID:24363716

  7. 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

  8. Study of the beam-beam limit in e{sup +}e{sup -} circular colliders

    SciTech Connect

    Ohmi, K.; Tawada, M.; Cai, Y.; Kamada, S.; Oide, K.; Qiang, J.

    2004-04-02

    Beam-beam effects limit the luminosity of circular colliders. Once the bunch population exceeds a threshold, the luminosity increases at a slower rate. This phenomenon is called the beam-beam limit. Onset of the beam-beam limit has been analyzed with various simulation methods based on the weak-strong and strong-strong models. We have observed that an incoherent phenomenon is mainly concerned in the beam-beam limit. The simulation have shown that equilibrium distributions of the two colliding beams are distorted from Gaussians when the luminosity is limited. The beam-beam limit is estimated to be (xi) {approx} 0.1 for a B factory with damping time of several thousand turns.

  9. The Ethics of Using Transgenic Non-Human Primates to Study What Makes Us Human

    PubMed Central

    Coors, Marilyn E.; Glover, Jacqueline J.; Juengst, Eric T.; Sikela, James M.

    2010-01-01

    An ongoing flood of comparative genomic data is identifying human lineage specific (HLS) sequences of unknown function, and there is strong interest in investigating their functional effects. Transgenic apes, our closest evolutionary relative, have the highest potential to express HLS sequences as they are expressed in Homo sapiens and likewise experience harm from such transgenic research. These harms render the conduct of this research ethically unacceptable in apes, justifying regulatory barriers between these species and all other non-human primates for transgenic research. PMID:20717156

  10. 75 FR 18497 - Guidance on Simultaneous Transmission Import Limit Studies for the Northwest Region; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-12

    ...and subsystem files), scaling methodologies, identification of energy transfer limits, transfer distribution factors, OASIS practices, methods to identify available uncommitted generation, application of net area interchange, and alternative...

  11. The Background-Limited Infrared Submillimeter Spectrograph (BLISS) for SPICA: A Design Study

    NASA Astrophysics Data System (ADS)

    Bradford, Charles; BLISS-SPICA Study Team

    2010-05-01

    The far-IR waveband carries half of the photon energy ever produced in galaxies and quasars, evidence of the major role of dust-obscured processes in bringing about the modern Universe. The bulk of this appears to have occurred in the first half of the Universe's history (z>1). We are developing the Background-Limited Infrared-Submillimeter Spectrograph (BLISS) to capitalize on SPICA's cold telescope and provide a breakthrough far-IR spectroscopy capability. BLISS-SPICA is 6 orders of magnitude faster than the spectrometers on Herschel and SOFIA in obtaining full-band spectra, and will observe dust-obscured galaxies at all epochs back to the first billion years after the Big Bang (redshift 6), BLISS-SPICA thus probes the complete history of dust-obscured star formation and black-hole growth. It will also be extremely powerful for studying ice-giant planet formation in protoplanetary disks, with its sensitivity to very small amounts of gas. BLISS covers the 38-433 micron range in five grating-spectrometer bands, with two simultaneous sky positions. The detector package is 4224 silicon-nitride micro-mesh leg-isolated bolometers with superconducting transition-edge-sensed (TES) thermistors, read out with a cryogenic time-domain multiplexer, all cooled to 50mK for optimal sensitivity. All technical elements of BLISS have heritage in mature scientific instruments, and many have flown. We report on our design study in which we are optimizing performance while accommodating SPICA's constraints, including the stringent cryogenic mass budget. We present the science case for BLISS, as well as our progress in all key technical aspects: 1) opto-mechanical instrument architecture, 2) detector and readout approach, and 3) sub-K cooling approach. We thank the NASA for support of the BLISS study.

  12. 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.

  13. A Drosophila genetic resource of mutants to study mechanisms underlying human genetic diseases

    PubMed Central

    Yamamoto, Shinya; Jaiswal, Manish; Charng, Wu-Lin; Gambin, Tomasz; Karaca, Ender; Mirzaa, Ghayda; Wiszniewski, Wojciech; Sandoval, Hector; Haelterman, Nele A.; Xiong, Bo; Zhang, Ke; Bayat, Vafa; David, Gabriela; Li, Tongchao; Chen, Kuchuan; Gala, Upasana; Harel, Tamar; Pehlivan, Davut; Penney, Samantha; Vissers, Lisenka E. L. M.; de Ligt, Joep; Jhangiani, Shalini; Xie, Yajing; Tsang, Stephen H.; Parman, Yesim; Sivaci, Merve; Battaloglu, Esra; Muzny, Donna; Wan, Ying-Wooi; Liu, Zhandong; Lin-Moore, Alexander T.; Clark, Robin D.; Curry, Cynthia J.; Link, Nichole; Schulze, Karen L.; Boerwinkle, Eric; Dobyns, William B.; Allikmets, Rando; Gibbs, Richard A.; Chen, Rui; Lupski, James R.; Wangler, Michael F.; Bellen, Hugo J.

    2014-01-01

    Summary Invertebrate model systems are powerful tools for studying human disease owing to their genetic tractability and ease of screening. We conducted a mosaic genetic screen of lethal mutations on the Drosophila X-chromosome to identify genes required for the development, function, and maintenance of the nervous system. We identified 165 genes, most of whose function has not been studied in vivo. In parallel, we investigated rare variant alleles in 1,929 human exomes from families with unsolved Mendelian disease. Genes that are essential in flies and have multiple human homologs were found to be likely to be associated with human diseases. Merging the human datasets with the fly genes allowed us to identify disease-associated mutations in six families and to provide insights into microcephaly associated with brain dysgenesis. This bidirectional synergism between fly genetics and human genomics facilitates the functional annotation of evolutionarily conserved genes involved in human health. PMID:25259927

  14. Contribution of Human Fc?Rs to Disease with Evidence from Human Polymorphisms and Transgenic Animal Studies.

    PubMed

    Gillis, Caitlin; Gouel-Chéron, Aurélie; Jönsson, Friederike; Bruhns, Pierre

    2014-01-01

    The biological activities of human IgG antibodies predominantly rely on a family of receptors for the Fc portion of IgG, Fc?Rs: Fc?RI, Fc?RIIA, Fc?RIIB, Fc?RIIC, Fc?RIIIA, Fc?RIIIB, FcRL5, FcRn, and TRIM21. All Fc?Rs bind IgG at the cell surface, except FcRn and TRIM21 that bind IgG once internalized. The affinity of Fc?Rs for IgG is determined by polymorphisms of human Fc?Rs and ranges from 2?×?10(4) to 8?×?10(7)?M(-1). The biological functions of Fc?Rs extend from cellular activation or inhibition, IgG-internalization/endocytosis/phagocytosis to IgG transport and recycling. This review focuses on human Fc?Rs and intends to present an overview of the current understanding of how these receptors may contribute to various pathologies. It will define Fc?Rs and their polymorphic variants, their affinity for human IgG subclasses, and review the associations found between Fc?R polymorphisms and human pathologies. It will also describe the human Fc?R-transgenic mice that have been used to study the role of these receptors in autoimmune, inflammatory, and allergic disease models. PMID:24910634

  15. Contribution of Human Fc?Rs to Disease with Evidence from Human Polymorphisms and Transgenic Animal Studies

    PubMed Central

    Gillis, Caitlin; Gouel-Chéron, Aurélie; Jönsson, Friederike; Bruhns, Pierre

    2014-01-01

    The biological activities of human IgG antibodies predominantly rely on a family of receptors for the Fc portion of IgG, Fc?Rs: Fc?RI, Fc?RIIA, Fc?RIIB, Fc?RIIC, Fc?RIIIA, Fc?RIIIB, FcRL5, FcRn, and TRIM21. All Fc?Rs bind IgG at the cell surface, except FcRn and TRIM21 that bind IgG once internalized. The affinity of Fc?Rs for IgG is determined by polymorphisms of human Fc?Rs and ranges from 2?×?104 to 8?×?107?M?1. The biological functions of Fc?Rs extend from cellular activation or inhibition, IgG-internalization/endocytosis/phagocytosis to IgG transport and recycling. This review focuses on human Fc?Rs and intends to present an overview of the current understanding of how these receptors may contribute to various pathologies. It will define Fc?Rs and their polymorphic variants, their affinity for human IgG subclasses, and review the associations found between Fc?R polymorphisms and human pathologies. It will also describe the human Fc?R-transgenic mice that have been used to study the role of these receptors in autoimmune, inflammatory, and allergic disease models. PMID:24910634

  16. Human Exploration Missions Study Launch Window from Earth Orbit

    NASA Technical Reports Server (NTRS)

    Young, Archie

    2001-01-01

    The determination of orbital launch window characteristics is of major importance in the analysis of human interplanetary missions and systems. The orbital launch window characteristics are directly involved in the selection of mission trajectories, the development of orbit operational concepts, and the design of orbital launch systems. The orbital launch window problem arises because of the dynamic nature of the relative geometry between outgoing (departure) asymptote of the hyperbolic escape trajectory and the earth parking orbit. The orientation of the escape hyperbola asymptotic relative to earth is a function of time. The required hyperbola energy level also varies with time. In addition, the inertial orientation of the parking orbit is a function of time because of the perturbations caused by the Earth's oblateness. Thus, a coplanar injection onto the escape hyperbola can be made only at a point in time when the outgoing escape asymptote is contained by the plane of parking orbit. Even though this condition may be planned as a nominal situation, it will not generally represent the more probable injection geometry. The general case of an escape injection maneuver performed at a time other than the coplanar time will involve both a path angle and plane change and, therefore, a Delta(V) penalty. Usually, because of the Delta(V) penalty the actual departure injection window is smaller in duration than that determined by energy requirement alone. This report contains the formulation, characteristics, and test cases for five different launch window modes for Earth orbit. These modes are: (1) One impulsive maneuver from a Low Earth Orbit (LEO), (2) Two impulsive maneuvers from LEO, (3) Three impulsive maneuvers from LEO, (4) One impulsive maneuvers from a Highly Elliptical Orbit (HEO), (5) Two impulsive maneuvers from a Highly Elliptical Orbit (HEO) The formulation of these five different launch window modes provides a rapid means of generating realistic parametric data for space exploration studies. Also the formulation provides vector and geometrical data sufficient for use as a good starting point in detail trajectory analysis based on calculus of variations, steepest descent, or parameter optimization program techniques.

  17. Preclinical studies on the pharmacokinetics, safety, and toxicology of oxfendazole: toward first in human studies.

    PubMed

    Codd, Ellen E; Ng, Hanna H; McFarlane, Claire; Riccio, Edward S; Doppalapudi, Rupa; Mirsalis, Jon C; Horton, R John; Gonzalez, Armando E; Garcia, H Hugo; Gilman, Robert H

    2015-01-01

    A 2-week study in rats identified target organs of oxfendazole toxicity to be bone marrow, epididymis, liver, spleen, testis, and thymus. Female rats had greater oxfendazole exposure and exhibited toxicities at lower doses than did males. Decreased white blood cell levels, a class effect of benzimidazole anthelmintics, returned to normal during the recovery period. The no observed adverse effect level was determined to be >5 but <25 mg/kg/d and the maximum tolerated dose 100 mg/kg/d. The highest dose, 200 mg/kg/d, resulted in significant toxicity and mortality, leading to euthanization of the main study animals in this group after 7 days. Oxfendazole did not exhibit genetic toxicology signals in standard Ames bacterial, mouse lymphoma, or rat micronucleus assays nor did it provoke safety concerns when evaluated for behavioral effects in rats or cardiovascular safety effects in dogs. These results support the transition of oxfendazole to First in Human safety studies preliminary to its evaluation in human helminth diseases. PMID:25701764

  18. HUMEX, a study on the survivability and adaptation of humans to long-duration exploratory missions, part I: lunar missions.

    PubMed

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

    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) to define reference scenarios for a European participation in human exploration and to estimate their influence on the life sciences and life support requirements; (ii) for selected mission scenarios, to critically assess the limiting factors for human health, wellbeing, and performance and to recommend relevant countermeasures; (iii) for selected mission scenarios, to critically assess the potential of advanced life support developments and to propose a European strategy including terrestrial applications; (iv) to critically assess the feasibility of existing facilities and technologies on ground and in space as testbeds in preparation for human exploratory missions and to develop a test plan for ground and space campaigns; (v) to develop a roadmap for a future European strategy towards human exploratory missions, including preparatory activities and terrestrial applications and benefits. This paper covers the part of the HUMEX study dealing with lunar missions. A lunar base at the south pole where long-time sunlight and potential water ice deposits could be assumed was selected as the Moon reference scenario. The impact on human health, performance and well being has been investigated from the view point of the effects of microgravity (during space travel), reduced gravity (on the Moon) and abrupt gravity changes (during launch and landing), of the effects of cosmic radiation including solar particle events, of psychological issues as well as general health care. Countermeasures as well as necessary research using ground-based test beds and/or the International Space Station have been defined. Likewise advanced life support systems with a high degree of autonomy and regenerative capacity and synergy effects were considered where bioregenerative life support systems and biodiagnostic systems become essential. Finally, a European strategy leading to a potential European participation in future human exploratory missions has been recommended. PMID:14696589

  19. HUMEX, a study on the survivability and adaptation of humans to long-duration exploratory missions, part I: lunar missions

    NASA Technical Reports Server (NTRS)

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

    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) to define reference scenarios for a European participation in human exploration and to estimate their influence on the life sciences and life support requirements; (ii) for selected mission scenarios, to critically assess the limiting factors for human health, wellbeing, and performance and to recommend relevant countermeasures; (iii) for selected mission scenarios, to critically assess the potential of advanced life support developments and to propose a European strategy including terrestrial applications; (iv) to critically assess the feasibility of existing facilities and technologies on ground and in space as testbeds in preparation for human exploratory missions and to develop a test plan for ground and space campaigns; (v) to develop a roadmap for a future European strategy towards human exploratory missions, including preparatory activities and terrestrial applications and benefits. This paper covers the part of the HUMEX study dealing with lunar missions. A lunar base at the south pole where long-time sunlight and potential water ice deposits could be assumed was selected as the Moon reference scenario. The impact on human health, performance and well being has been investigated from the view point of the effects of microgravity (during space travel), reduced gravity (on the Moon) and abrupt gravity changes (during launch and landing), of the effects of cosmic radiation including solar particle events, of psychological issues as well as general health care. Countermeasures as well as necessary research using ground-based test beds and/or the International Space Station have been defined. Likewise advanced life support systems with a high degree of autonomy and regenerative capacity and synergy effects were considered where bioregenerative life support systems and biodiagnostic systems become essential. Finally, a European strategy leading to a potential European participation in future human exploratory missions has been recommended. c2003 COSPAR. Published by Elsevier Ltd. All rights reserved.

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

    NASA Astrophysics Data System (ADS)

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

    2003-06-01

    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) to define reference scenarios for a European participation in human exploration and to estimate their influence on the life sciences and life support requirements; (ii) for selected mission scenarios, to critically assess the limiting factors for human health, wellbeing, and performance and to recommend relevant countermeasures; (iii) for selected mission scenarios, to critically assess the potential of advanced life support developments and to propose a European strategy including terrestrial applications; (iv) to critically assess the feasibility of existing facilities and technologies on ground and in space as testbeds in preparation for human exploratory missions and to develop a test plan for ground and space campaigns; (v) to develop a roadmap for a future European strategy towards human exploratory missions, including preparatory activities and terrestrial applications and benefits. This paper covers the part of the HUMEX study dealing with lunar missions. A lunar base at the south pole where long-time sunlight and potential water ice deposits could be assumed was selected as the Moon reference scenario. The impact on human health, performance and well being has been investigated from the view point of the effects of microgravity (during space travel), reduced gravity (on the Moon) and abrupt gravity changes (during launch and landing), of the effects of cosmic radiation including solar particle events, of psychological issues as well as general health care. Countermeasures as well as necessary research using ground-based test beds and/or the International Space Station have been defined. Likewise advanced life support systems with a high degree of autonomy and regenerative capacity and synergy effects were considered where bioregenerative life support systems and biodiagnostic systems become essential. Finally, a European strategy leading to a potential European participation in future human exploratory missions has been recommended.

  1. Treatment-limiting toxicities associated withnucleoside analogue reverse transcriptase inhibitor therapy: A prospective, observational study**

    PubMed Central

    Palacios, Rosario; Santos, Jesús; Camino, Xavier; Arazo, Piedad; Torres Perea, Rafael; Echevarrfa, Santiago; Ribera, Esteban; Sánchez de la Rosa, Rainel; Moreno Guillen, Santiago

    2005-01-01

    Background: The Recover Study is an ongoing, prospective study designed 10 to assess toxicity associated with the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) (stavudine, zidovudine, lamivudine, didanosine, abacavir) in HIV-1-infected patients receiving highly active antiretroviral therapy (HAART) in routine clinical practice. This project is being conducted at 120 HIV units at teaching hospitals across Spain. Objective: The aim of this study was to identify the most common treatment-limiting 10 moderate to severe clinical and laboratory adverse effects (AEs), and the individual NRTIs involved in the development of these effects, in HIV-1-infected patients receiving HAART who discontinued use of an NRTI in the Recover Study. Methods: Patients eligible for participation in the Recover Study are aged10 ?18 years; have virologically documented HIV-1 infection; have sustained viral suppression (viral load <200 cells/mL or stable, heavily experienced [ie, have received ?3 antiretroviral regimens] patients with viral load <5000 cells/mL) for ?6 months; are receiving HAART; are undergoing active follow-up; and have developed 2:1 NRTI-associated AE that, in the opinion of a study investigator and under the conditions of routine clinical practice, justified discontinuation of treatment with the offending drug (principal AE/offending NRTI). The present study included patients recruited for the Recover Study between September 2002 and May 2003. Results: A total of 1391 patients were enrolled (966 men, 425 women; mean 1 age, 42 years [range, 18–67 years]). Five hundred six patients (36.4%) had been diagnosed with AIDS. The mean duration of treatment with the offending NRTI was 74 months (range, 6–156 months). Seven hundred nine patients (51.0%) were receiving fourth-line (or more) therapy. Eight hundred twenty-one patients (59.0%) were receiving nonnucleoside analogues, and 552 patients (39.7%), protease inhibitors, as components of their HAART regimens. The NRTIs with the highest discontinuation rates were stavudine (914 patients [65.7%]) and zidovudine (177 [12.7%]). The most frequent NRTI-related AEs were lipoatrophy (550 patients [39.5%]) and peripheral neuropathy (170 [12.2%]). Lipoatrophy was most commonly associated with stavudine (480/550 cases [87.3%]); periph eral neuropathy, with stavudine and didanosine (107/170 [62.9%] and 48/170 [28.2%] cases, respectively); and anemia, with zidovudine (70/77 cases [90.9%]). Conclusions: The results of this study in patients with HIV-1 recruited in the10 Recover Study and undergoing HAART suggest that long-term treatment with NRTIs is associated with AEs (lipoatrophy, peripheral neuropathy, and lipodystrophy), with morphologic disorders (lipoatrophy, lipodystrophy) being the most common AEs leading to discontinuation. Minimizing these AEs by switching to an NRTI not associated with these AEs (eg, tenofovir) would contribute to adherence and hence efficacy of long-term HAART. PMID:24672118

  2. Teacher's Study Guide on the Biology of Human Populations: Asia.

    ERIC Educational Resources Information Center

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

    Factual and conceptual information dealing with the biology of human populations is offered in this guide for secondary science teachers. Instructional approaches are reviewed and suggestions are offered for use of the problem method approach, the discussion technique, and the project option. Information is organized into an introduction and five…

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

    E-print Network

    Capecchi, Mario R.

    Children's Behavior 3 FCS 2620 Child Development Practicum pre-requisite: FCS 2610 3 FCS 3180 Family Across Cultures (IR) 3 FCS 3630 Intimacy and Love (BF) 3 FCS 5250 Theories of Human Development (CW) 3 choose the ECE emphasis are expected to develop knowledge and skills in child development and learning

  4. The Study of the Noosphere--Contemporary Humanism.

    ERIC Educational Resources Information Center

    Moiseev, Nikita N.

    1989-01-01

    Explains the theory of noosphere developed by Soviet academician Vladimir Ivanovich Vernadsky and Jesuit priest Pierre Teilhard de Chardin. States that this theory is based on a new morality concerning the unity of humanity and its responsibility for the fate of the planet. (GG)

  5. OUTDOOR VS. HUMAN EXPOSURE: NERL PM EXPOSURE PANEL STUDIES

    EPA Science Inventory

    An association has been demonstrated between ambient particulate matter (PM 2.5 and PM 10) concentrations and human morbidity/mortality. However, little is known regarding the most important sources of PM exposure, interpersonal and intrapersonal variability in exposure, and the...

  6. HEMATOLOGIC AND IMMUNOLOGIC STUDIES OF HUMANS EXPOSED TO SO2

    EPA Science Inventory

    Immunologic and hematologic parameters were used to evaluate the effects in humans of a single 2 hour exposure to either clean air or 0.75 ppm SO2. Venous blood Samples were obtained before, immediately after, and 24, 48, and 72 hours following the end of exposure. Parameters stu...

  7. The Study of Radioactive Drugs in Human Subjects

    Cancer.gov

    Basic research for the purpose of advancing scientific knowledge The research is intended to obtain basic information regarding the metabolism of radioactive drugs including kinetics, distribution, dosimetry, and localization OR Obtain basic information regarding human physiology, pathophysiology, and biochemistry of radioactive drugs.

  8. CRYSTALLIZATION NOTE Preliminary Crystallographic Studies of Human Mitochondrial

    E-print Network

    Tong, Liang

    amino acid sequences, suggesting that ME may have important biological functions. The enzymes are generally homo-tetrameric, with monomers having about 550 amino acid residues (60 kDa). The human activity is allosteri- cally controlled with fumarate as an activator and ATP as an inhibitor (Loeber et al

  9. Technical Note Defining the habenula in human neuroimaging studies

    E-print Network

    -human primates have suggested a potentially important role in reinforcement processing, putatively via its- nergic neurons in the median and dorsal raphe nuclei (Herkenham, 1979) and in rats receives a direct cortical projection from prelimbic frontal cortex (Beckstead, 1979). This unique position, as a hub between

  10. A Planning Study for the Billerica Human Service Center.

    ERIC Educational Resources Information Center

    Boston Coll., Chestnut Hill, MA.

    This document discusses the development and implementation of a multiservice center that could offer a variety of human social services in a single location. The paper focuses on seven components of the center's operation: governance, organizational structure, core services, joint funding, joint planning, joint programming, and evaluation. The…

  11. A Comparative Study of Definitions on Limit and Continuity of Functions

    ERIC Educational Resources Information Center

    Shipman, Barbara A.

    2012-01-01

    Differences in definitions of limit and continuity of functions as treated in courses on calculus and in rigorous undergraduate analysis yield contradictory outcomes and unexpected language. There are results about limits in calculus that are false by the definitions of analysis, functions not continuous by one definition and continuous by…

  12. A Study of Limited-Precision, Incremental Elicitation in Alexander Kress

    E-print Network

    Boutilier, Craig

    , we show that incremental limited-precision mecha- nisms offer advantages over fixed, single, limitations of standard approaches to mecha- nism design have been identified, and are starting must interact. For instance, mecha- nisms based on the revelation principle must reveal their type (gen

  13. Limits on quark-lepton compositeness and studies of W asymmetry at the Tevatron collider

    SciTech Connect

    Bodek, A.

    1996-10-01

    Drell-Yan dilepton production at high invariant mass place strong limits on quark substructure. Compositeness limits from CDF Run 1, and expected sensitivity in Run II and TEV33 are presented. The W asymmetry data constrains the slope of the d/u quark distributions and significantly reduces the systematic error on the extracted value of the W mass.

  14. Voice-Activated Lightweight Reacher to Assist with Upper Extremity Movement Limitations: A Case Study.

    PubMed

    Khalid, Umer; Conti, Gerry E; Erlandson, Robert F; Ellis, Richard D; Brown, Vince; Pandya, Abhilash K

    2015-01-01

    The focus of this research was to design a functional and user-friendly reacher for people with spinal cord injuries (SCIs). Engineering advancements have taken assistive robotics to new dimensions. Technologies such as wheelchair robotics and myo-electronically controlled systems have opened up a wide range of new applications to assist people with physical disabilities. Similarly, exo-skeletal limbs and body suits have provided new foundations from which technologies can aid function. Unfortunately, these devices have issues of usability, weight, and discomfort with donning. The Smart Assistive Reacher Arm (SARA) system, developed in this research, is a voice-activated, lightweight, mobile device that can be used when needed. SARA was built to help overcome daily reach challenges faced by individuals with limited arm and hand movement capability, such as people with cervical level 5-6 (C5-6) SCI. This article shows that a functional reacher arm with voice control can be beneficial for this population. Comparison study with healthy participants and an SCI participant shows that, when using SARA, a person with SCI can perform simple reach and grasp tasks independently, without someone else's help. This suggests that the interface is intuitive and can be easily used to a high level of proficiency by a SCI individual. PMID:26132355

  15. Brush cells in the human duodenojejunal junction: an ultrastructural study

    PubMed Central

    Morroni, Manrico; Cangiotti, Angela Maria; Cinti, Saverio

    2007-01-01

    Brush cells have been identified in the respiratory and gastrointestinal tract mucosa of many mammalian species. In humans they are found in the respiratory tract and the gastrointestinal apparatus, in both the stomach and the gallbladder. The function of brush cells is unknown, and most morphological data have been obtained in rodents. To extend our knowledge of human brush cells, we performed an ultrastructural investigation of human small intestine brush cells. Six brush cells identified in five out of more than 300 small intestine biopsies performed for gastrointestinal tract disorders were examined by transmission electron microscopy. Five brush cells were located on the surface epithelium and one in a crypt. The five surface brush cells were characterized by a narrow apical pole from which emerged microvilli that were longer and thicker than those of enterocytes. The filamentous core extended far into the cell body without forming the terminal web. Caveolae were abundant. Filaments were in the form of microfilaments and intermediate filaments. Cytoplasmic projections containing filaments were found on the basolateral surface of brush cells. In a single cell, axons containing vesicles and dense core granules were in close contact both with the basal and the lateral surface of the cell. The crypt brush cell appeared less mature. We concluded that human small intestine brush cells share a similar ultrastructural biology with those of other mammals. They are polarized and well-differentiated cells endowed with a distinctive cytoskeleton. The observation of nerve fibres closely associated with brush cells, never previously described in humans, lends support to the hypothesis of a receptor role for these cells. PMID:17509089

  16. Development of a Human Cranial Bone Surrogate for Impact Studies

    PubMed Central

    Roberts, Jack C.; Merkle, Andrew C.; Carneal, Catherine M.; Voo, Liming M.; Johannes, Matthew S.; Paulson, Jeff M.; Tankard, Sara; Uy, O. Manny

    2013-01-01

    In order to replicate the fracture behavior of the intact human skull under impact it becomes necessary to develop a material having the mechanical properties of cranial bone. The most important properties to replicate in a surrogate human skull were found to be the fracture toughness and tensile strength of the cranial tables as well as the bending strength of the three-layer (inner table-diplöe-outer table) architecture of the human skull. The materials selected to represent the surrogate cranial tables consisted of two different epoxy resins systems with random milled glass fiber to enhance the strength and stiffness and the materials to represent the surrogate diplöe consisted of three low density foams. Forty-one three-point bending fracture toughness tests were performed on nine material combinations. The materials that best represented the fracture toughness of cranial tables were then selected and formed into tensile samples and tested. These materials were then used with the two surrogate diplöe foam materials to create the three-layer surrogate cranial bone samples for three-point bending tests. Drop tower tests were performed on flat samples created from these materials and the fracture patterns were very similar to the linear fractures in pendulum impacts of intact human skulls, previously reported in the literature. The surrogate cranial tables had the quasi-static fracture toughness and tensile strength of 2.5?MPa? m and 53?±?4.9?MPa, respectively, while the same properties of human compact bone were 3.1?±?1.8?MPa? m and 68?±?18?MPa, respectively. The cranial surrogate had a quasi-static bending strength of 68?±?5.7?MPa, while that of cranial bone was 82?±?26?MPa. This material/design is currently being used to construct spherical shell samples for drop tower and ballistic tests. PMID:25023222

  17. 76 FR 3134 - Human Studies Review Board; Notice of Public Meeting; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-19

    ...EPA-HQ-ORD-2010-0970; FRL-9254-7] Human Studies Review Board; Notice of Public...January 26, 2011 public meeting of the Human Studies Review Board. The document contained...Avenue, NW., Washington, DC 20460. Hand Delivery: The EPA/DC Public...

  18. Acute Effects of Cocaine in Lower Human Brain: An FMRI Study P. R. Kufahl1

    E-print Network

    Rowe, Daniel B.

    Acute Effects of Cocaine in Lower Human Brain: An FMRI Study P. R. Kufahl1 , Z. Li1 , R. Risinger1: This FMRI study used controlled doses of cocaine to induce BOLD signal changes in the human orbitofrontal cocaine-induced activation patterns across nine different subjects imaged at 1.5 Tesla. INTRODUCTION

  19. 76 FR 2107 - Human Studies Review Board; Notice of Public Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-12

    ... AGENCY Human Studies Review Board; Notice of Public Meeting AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: The U.S. Environmental Protection Agency (EPA or Agency) Office of the Science Advisor (OSA) announces a public meeting of the Human Studies Review Board (HSRB) to advise the Agency...

  20. Molecular Dynamics Simulation Study and Hybrid Pharmacophore Model Development in Human LTA4H

    E-print Network

    Lee, Keun Woo

    Molecular Dynamics Simulation Study and Hybrid Pharmacophore Model Development in Human LTA4H) Molecular Dynamics Simulation Study and Hybrid Pharmacophore Model Development in Human LTA4H Inhibitor-0081539), and Management of Climate Change Program (2010-0029084) through the National Research Foundation of Korea (NRF

  1. A longitudinal study of the health status of a community of religious sisters: addressing the advantages, challenges, and limitations.

    PubMed

    Gaspar, Phyllis Meyer; Bautch, Judith C; Strodthoff, Caritas M

    2015-01-01

    Longitudinal studies are recognized as contributing to understanding the complexity of aging and generating insights that cannot be gained using other research methods. However, conducting longitudinal studies is recognized as challenging, especially among older adults. The purpose of the current review is to describe how the authors addressed the limitations and challenges of longitudinal studies in a study of the health status of a community of religious sisters. Methods of this specific longitudinal study are presented to provide background to the discussion. Challenges, limitations, and advantages of the current longitudinal study are organized into three categories (i.e., sample, method, and data analysis) that have been addressed in the literature as contributing to the fidelity of longitudinal studies. The unique characteristics of the current study sample, particularly their access to health care, creates a comparison group for the study of older women in general. PMID:25860013

  2. KRAS2 Mutations in Human Pancreatic Acinar-Ductal Metaplastic Lesions are Limited to those with PanIN: Implications for the Human Pancreatic Cancer Cell of Origin

    PubMed Central

    Shi, Chanjuan; Hong, Seung-Mo; Lim, Phillip; Kamiyama, Hirohiko; Khan, Mehtab; Anders, Robert A.; Goggins, Michael; Hruban, Ralph H.

    2009-01-01

    Background Pancreatic intraepithelial neoplasia (PanIN) is a precursor to invasive ductal adenocarcinoma of the pancreas. Observations made in genetically engineered mouse models suggest that the acinar/centroacinar compartment can give rise to ductal neoplasia. In order to integrate findings in mice and men, we examined human acinar cells, acinar-ductal metaplasia (ADM) lesions and PanINs for KRAS2 gene mutations. Methods Surgically resected pancreata were screened for foci of ADM with or without an associated PanIN lesion. Stromal cells, acinar cells, ADMs, and PanINs, were separately isolated using laser capture microdissection. KRAS2 status was analyzed using genomic DNA isolated from the microdissected tissue. Results Twelve of these 31 foci of ADM occurred in isolation, while 19 were in the same lobules as a PanIN lesion. All 31 microdissected foci of acinar cells were KRAS2 gene wild-type, as were all 12 isolated ADM lesions lacking an associated PanIN. KRAS2 gene mutations were present in 14 of 19 (74%) PanIN lesions, and in 12 of the 19 (63%) foci of ADM associated with these PanINs. All ADM lesions with a KRAS2 gene mutation harbored the identical KRAS2 gene mutation found in their associated PanIN lesions. Conclusions Ductal neoplasms of the human pancreas, as defined by KRAS2 gene mutations, do not appear to arise from acinar cells. Isolated AMD lesions are genetically distinct from those associated with PanINs, and the latter may represent retrograde extension of the neoplastic PanIN cells, or less likely are PanIN precursor lesions. PMID:19208745

  3. The challenge of studying parallel behaviors in humans and animal models.

    PubMed

    Stephens, David N; Crombag, Hans S; Duka, Theodora

    2013-01-01

    The use of animal models is essential in carrying out research into clinical phenomena such as addiction. However, the complexity of the clinical condition inevitably means that even the best animal models are inadequate representations of the condition they seek to mimic. Such mismatches may account for apparent inconsistencies between discoveries in animal models, including the identification of potential novel therapies, and the translation of such discoveries to the clinic. We argue that it is overambitious to attempt to model human disorders such as addiction in animals, and especially in rodents, where "validity" of such models is often limited to superficial similarities, referred to as "face validity" that reflect quite different underlying phenomena and biological processes from the clinical situation. Instead, we suggest a more profitable approach may be to identify (a) well-defined intermediate human behavioral phenotypes that reflect defined, limited aspects of the human clinical disorder, and (b) to develop animal models that are homologous with those discrete human behavioral phenotypes in terms of psychological processes, and underlying neurobiological mechanisms. Examples of current weaknesses and suggestions for more limited approaches that may allow better homology between the test animal and human condition are made. PMID:21671191

  4. Essays using military-induced variation to study social interactions, human capital development, and labor markets

    E-print Network

    Lyle, David S. (David Stephen), 1971-

    2003-01-01

    This dissertation consists of four empirical studies, each using military-induced variation to examine various aspects of human capital production and the U.S. labor market. The first two chapters study the effects of ...

  5. Supporting statement for community study of human response to aircraft noise

    NASA Technical Reports Server (NTRS)

    Dempsey, T. K.; Deloach, R.; Stephens, D. G.

    1980-01-01

    A study plan for quantifying the relationship between human annoyance and the noise level of individual aircraft events is studied. The validity of various noise descriptors or noise metrics for quantifying aircraft noise levels are assessed.

  6. A Method for the Study of Human Factors in Aircraft Operations

    NASA Technical Reports Server (NTRS)

    Barnhart, W.; Billings, C.; Cooper, G.; Gilstrap, R.; Lauber, J.; Orlady, H.; Puskas, B.; Stephens, W.

    1975-01-01

    A method for the study of human factors in the aviation environment is described. A conceptual framework is provided within which pilot and other human errors in aircraft operations may be studied with the intent of finding out how, and why, they occurred. An information processing model of human behavior serves as the basis for the acquisition and interpretation of information relating to occurrences which involve human error. A systematic method of collecting such data is presented and discussed. The classification of the data is outlined.

  7. Neural Structures within Human Meniscofemoral Ligaments: A Cadaveric Study

    PubMed Central

    Gupte, Chinmay M.; Shaerf, Daniel A.; Sandison, Ann; Bull, Anthony M. J.; Amis, Andrew A.

    2014-01-01

    Aim. To investigate the existence of neural structures within the meniscofemoral ligaments (MFLs) of the human knee. Methods. The MFLs from 8 human cadaveric knees were harvested. 5??m sections were H&E-stained and examined under light microscopy. The harvested ligaments were then stained using an S100 monoclonal antibody utilising the ABC technique to detect neural components. Further examination was performed on 60–80?nm sections under electron microscopy. Results. Of the 8 knees, 6 were suitable for examination. From these both MFLs existed in 3, only anterior MFLs were present in 2, and an isolated posterior MFL existed in 1. Out of the 9?MFLs, 4 demonstrated neural structures on light and electron microscopy and this was confirmed with S100 staining. The ultrastructure of these neural components was morphologically similar to mechanoreceptors. Conclusion. Neural structures are present in MFLs near to their meniscal attachments. It is likely that the meniscofemoral ligaments contribute not only as passive secondary restraints to posterior draw but more importantly to proprioception and may therefore play an active role in providing a neurosensory feedback loop. This may be particularly important when the primary restraint has reduced function as in the posterior cruciate ligament—deficient human knee. PMID:25938111

  8. Thus mangle ye still the human race: a study in structural navigation 

    E-print Network

    Harden, B. Garrick

    2006-08-16

    -1 THUS MANGLE YE STILL THE HUMAN RACE: A STUDY IN STRUCTURAL NAVIGATION A Thesis by B. GARRICK HARDEN Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for degree of MASTER... OF SCIENCE May 2006 Major Subject: Sociology THUS MANGLE YE STILL THE HUMAN RACE: A STUDY IN STRUCTURAL NAVIGATION A Thesis by B. GARRICK HARDEN Submitted to the Office of Graduate Studies of Texas A&M University in partial...

  9. A Study of the Characteristics of Human-Pilot Control Response to Simulated Aircraft Lateral Motions

    NASA Technical Reports Server (NTRS)

    Cheatham, Donald C

    1954-01-01

    Report presents the results of studies made in an attempt to provide information on the control operations of the human pilot. These studies included an investigation of the ability of pilots to control simulated unstable yawing oscillations, a study of the basic characteristics of human-pilot control response, and a study to determine whether and to what extent pilot control response can be represented in an analytical form.

  10. A statistical study of the geological limits to Advanced Piston Coring: ODP Legs 101-149 

    E-print Network

    Lee, Yir-Der Eddy

    1995-01-01

    The Advanced Piston Corer (APC), a soft sediment coring system developed from the hydraulic piston corer (HPC), allows recovery of ocean sediments with minimal coring disturbance. As a coring too[, the APC system is subject to limitations imposed...

  11. 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.

  12. An In vitro Model to Study Immune Responses of Human Peripheral Blood Mononuclear Cells to Human Respiratory Syncytial Virus Infection

    PubMed Central

    Vissers, Marloes; Habets, Marrit N.; Ahout, Inge M. L.; Jans, Jop; de Jonge, Marien I.; Diavatopoulos, Dimitri A.; Ferwerda, Gerben

    2013-01-01

    Human respiratory syncytial virus (HRSV) infections present a broad spectrum of disease severity, ranging from mild infections to life-threatening bronchiolitis. An important part of the pathogenesis of severe disease is an enhanced immune response leading to immunopathology. Here, we describe a protocol used to investigate the immune response of human immune cells to an HRSV infection. First, we describe methods used for culturing, purification and quantification of HRSV. Subsequently, we describe a human in vitro model in which peripheral blood mononuclear cells (PBMCs) are stimulated with live HRSV. This model system can be used to study multiple parameters that may contribute to disease severity, including the innate and adaptive immune response. These responses can be measured at the transcriptional and translational level. Moreover, viral infection of cells can easily be measured using flow cytometry. Taken together, stimulation of PBMC with live HRSV provides a fast and reproducible model system to examine mechanisms involved in HRSV-induced disease. PMID:24379004

  13. Comparative outcome studies of clinical decision support software: limitations to the practice of evidence-based system acquisition.

    PubMed

    Dhiman, Gaurav Jay; Amber, Kyle T; Goodman, Kenneth W

    2015-04-01

    Clinical decision support systems (CDSSs) assist clinicians with patient diagnosis and treatment. However, inadequate attention has been paid to the process of selecting and buying systems. The diversity of CDSSs, coupled with research obstacles, marketplace limitations, and legal impediments, has thwarted comparative outcome studies and reduced the availability of reliable information and advice for purchasers. We review these limitations and recommend several comparative studies, which were conducted in phases; studies conducted in phases and focused on limited outcomes of safety, efficacy, and implementation in varied clinical settings. Additionally, we recommend the increased availability of guidance tools to assist purchasers with evidence-based purchases. Transparency is necessary in purchasers' reporting of system defects and vendors' disclosure of marketing conflicts of interest to support methodologically sound studies. Taken together, these measures can foster the evolution of evidence-based tools that, in turn, will enable and empower system purchasers to make wise choices and improve the care of patients. PMID:25665704

  14. Further Studies of Accretion onto Hot, Massive, White Dwarfs: The Growth to the Chandrasekhar Limit

    NASA Astrophysics Data System (ADS)

    Starrfield, S.; Timmes, F. X.; Hix, W. R.; Sion, E. M.; Sparks, W. M.; Dwyer, S.

    2004-05-01

    We report on further studies of accretion (Solar Composition material) at a variety of rates onto hot, massive white dwarfs (WDs: Starrfield et al. 2003, Atlanta Meeting, poster 45.10). Our initial models are 1.0 M?, 1.25 M?, and 1.35 M? WDs with luminosities of 30 L?. We have now run evolutionary sequences with mass accretion rates varying from 1.6×10-10 M? yr-1 to 3.5×10-7 M? yr-1 and, in all cases, the WDs grow in mass to near the Chandrasekhar Limit. We use the 1D, hydrodynamic computer code as described in Starrfield et al. (APJS, 127,485, 2000) and have updated the nuclear reaction network, since the calculations reported at Atlanta, to that found at www.cococubed.com/code_pages/net_hhe.shtml. This network combines the pp + hot cno + rp breakout network used previously with an alpha-chain that runs to 56Ni. This will allow us to report on whether or not elements such as Si, S, and Ca are produced in the outer layers during the evolution to explosion so that they do not have to be produced by the explosion. We will also report on simulations done with a lower metallicity for the accreting material - characteristic of that of the LMC. S. Starrfield acknowledges support from NSF and NASA grants to ASU, FXT is supported by the National Security Fellow program at Los Alamos National Laboratory, WRH is partially supported by the National Science Foundation under contracts PHY-0244783 and AST-9877130 and by the Department of Energy, through the Scientific Discovery through Advanced Computing Program. Oak Ridge National Laboratory is managed by UT-Battelle, LLC, for the U.S. Department of Energy under contract DE-AC05-00OR22725. EMS is supported by NASA ADP grant NAG5-11182.

  15. Detection limits and cost comparisons of human- and gull-associated conventional and quantitative PCR assays in artificial and environmental waters.

    PubMed

    Riedel, Timothy E; Zimmer-Faust, Amity G; Thulsiraj, Vanessa; Madi, Tania; Hanley, Kaitlyn T; Ebentier, Darcy L; Byappanahalli, Muruleedhara; Layton, Blythe; Raith, Meredith; Boehm, Alexandria B; Griffith, John F; Holden, Patricia A; Shanks, Orin C; Weisberg, Stephen B; Jay, Jennifer A

    2014-04-01

    Some molecular methods for tracking fecal pollution in environmental waters have both PCR and quantitative PCR (qPCR) assays available for use. To assist managers in deciding whether to implement newer qPCR techniques in routine monitoring programs, we compared detection limits (LODs) and costs of PCR and qPCR assays with identical targets that are relevant to beach water quality assessment. For human-associated assays targeting Bacteroidales HF183 genetic marker, qPCR LODs were 70 times lower and there was no effect of target matrix (artificial freshwater, environmental creek water, and environmental marine water) on PCR or qPCR LODs. The PCR startup and annual costs were the lowest, while the per reaction cost was 62% lower than the Taqman based qPCR and 180% higher than the SYBR based qPCR. For gull-associated assays, there was no significant difference between PCR and qPCR LODs, target matrix did not effect PCR or qPCR LODs, and PCR startup, annual, and per reaction costs were lower. Upgrading to qPCR involves greater startup and annual costs, but this increase may be justified in the case of the human-associated assays with lower detection limits and reduced cost per sample. PMID:24583609

  16. Detection limits and cost comparisons of human- and gull-associated conventional and quantitative PCR assays in artificial and environmental waters

    USGS Publications Warehouse

    Riedel, Timothy E.; Zimmer-Faust, Amity G.; Thulsiraj, Vanessa; Madi, Tania; Hanley, Kaitlyn T.; Ebentier, Darcy L.; Byappanahalli, Muruleedhara N.; Layton, Blythe; Raith, Meredith; Boehm, Alexandria B.; Griffith, John F.; Holden, Patricia A.; Shanks, Orin C.; Weisberg, Stephen B.; Jay, Jennifer A.

    2014-01-01

    Some molecular methods for tracking fecal pollution in environmental waters have both PCR and quantitative PCR (qPCR) assays available for use. To assist managers in deciding whether to implement newer qPCR techniques in routine monitoring programs, we compared detection limits (LODs) and costs of PCR and qPCR assays with identical targets that are relevant to beach water quality assessment. For human-associated assays targeting Bacteroidales HF183 genetic marker, qPCR LODs were 70 times lower and there was no effect of target matrix (artificial freshwater, environmental creek water, and environmental marine water) on PCR or qPCR LODs. The PCR startup and annual costs were the lowest, while the per reaction cost was 62% lower than the Taqman based qPCR and 180% higher than the SYBR based qPCR. For gull-associated assays, there was no significant difference between PCR and qPCR LODs, target matrix did not effect PCR or qPCR LODs, and PCR startup, annual, and per reaction costs were lower. Upgrading to qPCR involves greater startup and annual costs, but this increase may be justified in the case of the human-associated assays with lower detection limits and reduced cost per sample.

  17. 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.

  18. THE USE OF FIRST LANGUAGE TURKISH AS A RESOURCE -A GERMAN CASE STUDY ON CHANCES AND LIMITS

    E-print Network

    Prediger, Susanne

    THE USE OF FIRST LANGUAGE TURKISH AS A RESOURCE - A GERMAN CASE STUDY ON CHANCES AND LIMITS explorative approaches and selected findings of interview studies with students of Turkish origin who deal the suc- cess of multilingual students is concentrated on German language learning in all sub- jects (e

  19. Mental Training Affects Distribution of Limited Brain Resources

    E-print Network

    Lutz, Antoine

    and illustrates the usefulness of systematic mental training in the study of the human mind. Citation: Slagter HAMental Training Affects Distribution of Limited Brain Resources Heleen A. Slagter1 , Antoine Lutz1, Leiden, The Netherlands The information processing capacity of the human mind is limited, as is evidenced

  20. Evaluation of drug-induced QT interval prolongation in animal and human studies: a literature review of concordance

    PubMed Central

    Vargas, Hugo M; Bass, Alan S; Koerner, John; Matis-Mitchell, Sherri; Pugsley, Michael K; Skinner, Matthew; Burnham, Matthew; Bridgland-Taylor, Matthew; Pettit, Syril; Valentin, Jean-Pierre

    2015-01-01

    Evaluating whether a new medication prolongs QT intervals is a critical safety activity that is conducted in a sensitive animal model during non-clinical drug development. The importance of QT liability detection has been reinforced by non-clinical [International Conference on Harmonization (ICH) S7B] and clinical (ICH E14) regulatory guidance from the International Conference on Harmonization. A key challenge for the cardiovascular safety community is to understand how the finding from a non-clinical in vivo?QT assay in animals predicts the outcomes of a clinical QT evaluation in humans. The Health and Environmental Sciences Institute Pro-Arrhythmia Working Group performed a literature search (1960–2011) to identify both human and non-rodent animal studies that assessed QT signal concordance between species and identified drugs that prolonged or did not prolong the QT interval. The main finding was the excellent agreement between QT results in humans and non-rodent animals. Ninety-one percent (21 of 23) of drugs that prolonged the QT interval in humans also did so in animals, and 88% (15 of 17) of drugs that did not prolong the QT interval in humans had no effect on animals. This suggests that QT interval data derived from relevant non-rodent models has a 90% chance of predicting QT findings in humans. Disagreement can occur, but in the limited cases of QT discordance we identified, there appeared to be plausible explanations for the underlying disconnect between the human and non-rodent animal QT outcomes. PMID:26031452