Science.gov

Sample records for limited human studies

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  2. Overcoming Current Limitations in Humanized Mouse Research

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

    2011-01-01

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

  4. The detection limits for estimates of infection intensity in schistosomiasis mansoni established by a study in non-human primates.

    PubMed

    Alan Wilson, R; van Dam, Govert J; Kariuki, Thomas M; Farah, Idle O; Deelder, André M; Coulson, Patricia S

    2006-10-01

    In human schistosomiasis mansoni, it is impossible to directly determine worm burden and hence infection intensity, so surrogates must be used. Studies on non-human primates revealed a linear relationship between worm burden and three surrogates, faecal egg output, circulating anodic and circulating cathodic antigens. By regression, the thresholds of detection were determined as 40, 24 and 47 worms, respectively. These observations provide a quantitative basis for the contention that low intensity infections in humans are being missed. The significance for estimates of disease prevalence, evaluation of the effects of chemotherapy and the implementation of vaccine trials is emphasised. PMID:16930605

  5. Limit cycle oscillations in standing human posture.

    PubMed

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

    2016-05-01

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

  6. Limits to sustainable human metabolic rate.

    PubMed

    Westerterp, K R

    2001-09-01

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

  7. Teleoperator Human Factors Study

    NASA Technical Reports Server (NTRS)

    1986-01-01

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

  8. Circular-dichroism and electron-microscopy studies of human subcomponent C1q before and after limited proteolysis by pepsin.

    PubMed Central

    Brodsky-Doyle, B; Leonard, K R; Reid, K B

    1976-01-01

    1. A fragment of human subcomponent C1q was prepared by limited proteolysis with pepsin at 37 degrees C for 20 h, and at pH4.4, followed by gel filtration on Sephadex G-200. This fragment was shown to contain all the collagen-like features known to be present in the intact molecule [Reid (1976) Biochem. J. 155, 5-17]. 2. Circular-dichroism studies showed the presence of positive bands at 230 and 223 nm in the intact subcomponent C1q and pepsin fragment respectively, compared with a positive band at 220 nm obtained for lathyritic rat skin collagen. These bands were abolished by collagenase treatment, which suggested that there may some collagen-like triple-helical structure in subcomponent C1q and that this structure resides in the pepsin-resistant portion of the molecule. However, the 230 and 223 nm bands had a substantially lower magnitude than that obtained for the unaggregated single fibres of totally triple-helical collagen. 3. Thermal-transition temperatures obtained for subcomponent C1q, the pepsin fragment and the reduced and alkylated pepsin fragment were 48 degrees, 48 degrees and 39 degrees C respectively, compared with a value of 38 degrees C obtained for lathyritic rat skin collagen. 4. Only the unreduced pepsin fragment regained significant amounts (up to 60%) of collagen-like structure, after heat denaturation and cooling, as estimated by circular-dichroism measurements. 5. Electron-microscopy studies of subcomponent C1q and the collagen-like pepsin-resistant fragment of subcomponent C1q showed that the six peripheral globular regions of the molecule were fragmented by pepsin leaving the six collagen-like connecting strands and fibril-like central portion intact. Images PLATE 1 PLATE 2 PMID:187173

  9. Human exploration mission studies

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.

    1989-01-01

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

  10. Studying the Human Microbiota.

    PubMed

    Walker, Alan W

    2016-01-01

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

  11. 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

  12. Limited Diversity among Human Isolates of Bartonella henselae

    PubMed Central

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

    2002-01-01

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

  13. Human exposure limits to hypergolic fuels

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  14. Approaching the limit of predictability in human mobility.

    PubMed

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

    2013-01-01

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

  15. Approaching the Limit of Predictability in Human Mobility

    PubMed Central

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

    2013-01-01

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

  16. 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...

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  18. IMMUNOASSAY HUMAN EXPOSURE STUDIES

    EPA Science Inventory

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

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

    PubMed Central

    Woods, Angela

    2014-01-01

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

  20. The limits of narrative: provocations for the medical humanities.

    PubMed

    Woods, Angela

    2011-12-01

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

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

    ERIC Educational Resources Information Center

    Ryan, James

    1994-01-01

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

  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. Effects of band-limited noise on human observer performance

    NASA Astrophysics Data System (ADS)

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

    2007-04-01

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

  4. 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.

  5. Independent Human Studies.

    ERIC Educational Resources Information Center

    Kaplan, Suzanne; Wilson, Gordon

    1978-01-01

    The Independent Human Studies program at Schoolcraft College offers an alternative method of earning academic credits. Students delineate an area of study, pose research questions, gather resources, synthesize the information, state the thesis, choose the method of presentation, set schedules, and take responsibility for meeting deadlines. (MB)

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

    NASA Astrophysics Data System (ADS)

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

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

  7. Density limit studies on DIII-D

    SciTech Connect

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

    1998-08-01

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

  8. 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

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

    NASA Astrophysics Data System (ADS)

    Smith, A. G.

    1981-09-01

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

  10. Limited communication capacity unveils strategies for human interaction

    NASA Astrophysics Data System (ADS)

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

    2013-06-01

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

  11. Limited communication capacity unveils strategies for human interaction

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  13. Urinary tract infection of mice to model human disease: Practicalities, implications and limitations.

    PubMed

    Carey, Alison J; Tan, Chee K; Ipe, Deepak S; Sullivan, Matthew J; Cripps, Allan W; Schembri, Mark A; Ulett, Glen C

    2016-09-01

    Urinary tract infections (UTIs) are among the most common bacterial infections in humans. Murine models of human UTI are vital experimental tools that have helped to elucidate UTI pathogenesis and advance knowledge of potential treatment and infection prevention strategies. Fundamentally, several variables are inherent in different murine models, and understanding the limitations of these variables provides an opportunity to understand how models may be best applied to research aimed at mimicking human disease. In this review, we discuss variables inherent in murine UTI model studies and how these affect model usage, data analysis and data interpretation. We examine recent studies that have elucidated UTI host-pathogen interactions from the perspective of gene expression, and review new studies of biofilm and UTI preventative approaches. We also consider potential standards for variables inherent in murine UTI models and discuss how these might expand the utility of models for mimicking human disease and uncovering new aspects of pathogenesis. PMID:26006172

  14. Limited Trabecular Bone Density Heterogeneity in the Human Skeleton

    PubMed Central

    Chirchir, Habiba

    2016-01-01

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

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

    ERIC Educational Resources Information Center

    de Oliveira, Thiago Ranniery Moreira; Lopes, Danielle Bastos

    2016-01-01

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

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

    PubMed

    Eser, Albin; Koch, Hans-Georg

    2004-01-01

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

  17. [Principles and juridical limits to human embryo research].

    PubMed

    de Sá, Maria de Fátima

    2003-01-01

    This work intends to provide a wide scope of the legal situation in Brazil referred to Human Embryos and how it has been developed through the 20th century. Across the last century, the human being got the possibility of making genetic experiments with human embryos. Our main goal is to assume the future responsibility of these actions through a juridical and ethical point of view. PMID:15032101

  18. 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.

  19. 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.

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

    NASA Technical Reports Server (NTRS)

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

    1961-01-01

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

  1. Limiter

    DOEpatents

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

    1986-01-01

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

  2. 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...

  3. 47 CFR 5.93 - Limited market studies.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Limited market studies. 5.93 Section 5.93...) Applications and Licenses § 5.93 Limited market studies. Unless otherwise stated in the instrument of authorization, licenses granted for the purpose of limited market studies pursuant to § 5.3(j) of this part...

  4. 47 CFR 5.93 - Limited market studies.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false Limited market studies. 5.93 Section 5.93...) Applications and Licenses § 5.93 Limited market studies. Unless otherwise stated in the instrument of authorization, licenses granted for the purpose of limited market studies pursuant to § 5.3(j) of this part...

  5. Limitation of using synthetic human odours to test mosquito repellents

    PubMed Central

    Okumu, Fredros O; Titus, Emmanuel; Mbeyela, Edgar; Killeen, Gerry F; Moore, Sarah J

    2009-01-01

    Background Gold-standard tests of mosquito repellents involve exposing human volunteers to host-seeking mosquitoes, to assess the protective efficacy of the repellents. These techniques are not exposure-free and cannot be performed prior to toxicological evaluation. It is postulated that synthetic lures could provide a useful assay that mimics in-vivo conditions for use in high-throughput screening for mosquito repellents. Methods This paper reports on a semi-field evaluation of repellents using a synthetic blend of human derived attractants for the malaria vector, Anopheles gambiae sensu stricto Different concentrations of known repellents, N, N diethyl-3-methylbenzamide (deet) and Para-methane-3, 8, diol (PMD) were added into traps baited with the synthetic blend, and resulting changes in mosquito catches were measured. Results All test concentrations of deet (0.001% to 100%) reduced the attractiveness of the synthetic blend. However, PMD was repellent only at 0.25%. Above this concentration, it significantly increased the attractiveness of the blend. There was no relationship between the repellent concentrations and the change in mosquito catches when either deet (r2 = 0.033, P = 0.302) or PMD (r2 = 0.020, P = 0.578) was used. Conclusion It is concluded that while some repellents may reduce the attractiveness of synthetic human odours, others may instead increase their attractiveness. Such inconsistencies indicate that even though the synthetic attractants may provide exposure-free and consistent test media for repellents, careful selection and multiple-repellent tests are necessary to ascertain their suitability for use in repellent screening. The synthetic odour blend tested here is not yet sufficiently refined to serve as replacement for humans in repellent testing, but may be developed further and evaluated in different formats for exposure free repellent testing purposes. PMID:19583848

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

    PubMed

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

    2015-01-01

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

  7. A highly selective telomerase inhibitor limiting human cancer cell proliferation

    PubMed Central

    Damm, Klaus; Hemmann, Ulrike; Garin-Chesa, Pilar; Hauel, Norbert; Kauffmann, Iris; Priepke, Henning; Niestroj, Claudia; Daiber, Christine; Enenkel, Barbara; Guilliard, Bernd; Lauritsch, Ines; Müller, Elfriede; Pascolo, Emanuelle; Sauter, Gabriele; Pantic, Milena; Martens, Uwe M.; Wenz, Christian; Lingner, Joachim; Kraut, Norbert; Rettig, Wolfgang J.; Schnapp, Andreas

    2001-01-01

    Telomerase, the ribonucleoprotein enzyme maintaining the telomeres of eukaryotic chromosomes, is active in most human cancers and in germline cells but, with few exceptions, not in normal human somatic tissues. Telomere maintenance is essential to the replicative potential of malignant cells and the inhibition of telomerase can lead to telomere shortening and cessation of unrestrained proliferation. We describe novel chemical compounds which selectively inhibit telomerase in vitro and in vivo. Treatment of cancer cells with these inhibitors leads to progressive telomere shortening, with no acute cytotoxicity, but a proliferation arrest after a characteristic lag period with hallmarks of senescence, including morphological, mitotic and chromosomal aberrations and altered patterns of gene expression. Telomerase inhibition and telomere shortening also result in a marked reduction of the tumorigenic potential of drug-treated tumour cells in a mouse xenograft model. This model was also used to demonstrate in vivo efficacy with no adverse side effects and uncomplicated oral administration of the inhibitor. These findings indicate that potent and selective, non-nucleosidic telomerase inhibitors can be designed as novel cancer treatment modalities. PMID:11742973

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

    PubMed

    Bays, Paul M

    2016-09-01

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

  9. 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.

  10. 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…

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

    PubMed Central

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

    2013-01-01

    The species-specific determinants of repolarization are poorly understood. This study compared the contribution of various currents to cardiac repolarization in canine and human ventricle. Conventional microelectrode, whole-cell patch-clamp, molecular biological and mathematical modelling techniques were used. Selective IKr block (50–100 nmol l−1 dofetilide) lengthened AP duration at 90% of repolarization (APD90) >3-fold more in human than dog, suggesting smaller repolarization reserve in humans. Selective IK1 block (10 μmol l−1 BaCl2) and IKs block (1 μmol l−1 HMR-1556) increased APD90 more in canine than human right ventricular papillary muscle. Ion current measurements in isolated cardiomyocytes showed that IK1 and IKs densities were 3- and 4.5-fold larger in dogs than humans, respectively. IKr density and kinetics were similar in human versus dog. ICa and Ito were respectively ∼30% larger and ∼29% smaller in human, and Na+–Ca2+ exchange current was comparable. Cardiac mRNA levels for the main IK1 ion channel subunit Kir2.1 and the IKs accessory subunit minK were significantly lower, but mRNA expression of ERG and KvLQT1 (IKr and IKsα-subunits) were not significantly different, in human versus dog. Immunostaining suggested lower Kir2.1 and minK, and higher KvLQT1 protein expression in human versus canine cardiomyocytes. IK1 and IKs inhibition increased the APD-prolonging effect of IKr block more in dog (by 56% and 49%, respectively) than human (34 and 16%), indicating that both currents contribute to increased repolarization reserve in the dog. A mathematical model incorporating observed human–canine ion current differences confirmed the role of IK1 and IKs in repolarization reserve differences. Thus, humans show greater repolarization-delaying effects of IKr block than dogs, because of lower repolarization reserve contributions from IK1 and IKs, emphasizing species-specific determinants of repolarization and the limitations of animal models

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

    PubMed

    Fenyvesi, É; Vikmon, M; Szente, L

    2016-09-01

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

  13. Cdc45 is limiting for replication initiation in humans

    PubMed Central

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

    2016-01-01

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

  14. 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…

  15. 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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Halgamuge, Malka N

    2013-05-01

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

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

    PubMed Central

    Sariol, Carlos A.; White, Laura J.

    2014-01-01

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

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

    PubMed Central

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

    2006-01-01

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

  20. Mapping by admixture linkage disequilibrium in human populations: limits and guidelines.

    PubMed Central

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

    1994-01-01

    Certain human hereditary conditions, notably those with low penetrance and those which require an environmental event such as infectious disease exposure, are difficult to localize in pedigree analysis, because of uncertainty in the phenotype of an affected patient's relatives. An approach to locating these genes in human cohort studies would be to use association analysis, which depends on linkage disequilibrium 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 > or = .3 between admixed parent populations) to produce an efficient approach (> 95% ascertainment) for locating genes not easily tracked in human pedigrees. PMID:7942858

  1. 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.

  2. 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.

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

    PubMed

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

    2016-02-01

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

  4. Measuring human locomotor control using EMG and EEG: Current knowledge, limitations and future considerations.

    PubMed

    Enders, Hendrik; Nigg, Benno M

    2016-06-01

    Electrical signals encoding different forms of information can be observed at multiple levels of the human nervous system. Typically, these signals have been recorded in a rather isolated fashion with little overlap between the static recordings of electroencephalography (EEG) commonly used in neuroscience and the typical surface electromyography (EMG) recordings used in biomechanics. However, within the last decade, there has been an emerging need to link the electrical activation patterns of brain areas during movement to the behavior of the musculoskeletal system. This review discusses some of the most recent studies using the EEG and/or EMG to study the neural control of movement and human locomotion as well as studies quantifying the connectivity between brain and muscles. The focus is on rhythmic locomotor-type activities; however, results are discussed within the framework of initial work that has been done in upper and lower limbs during static and dynamic contractions. Limitations and current challenges as well as the possibility and functional interpretation of studying the connectivity between the cortex and skeletal muscles using a measure of coherence are discussed. The manuscript is geared toward scientists interested in the application of EEG in the field of locomotion, sports and exercise. PMID:26238032

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

    PubMed Central

    Mushak, P

    1998-01-01

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

  6. Why study human limb malformations?

    PubMed Central

    Wilkie, Andrew OM

    2003-01-01

    Congenital limb malformations occur in 1 in 500 to 1 in 1000 human live births and include both gross reduction defects and more subtle alterations in the number, length and anatomy of the digits. The major causes of limb malformations are abnormal genetic programming and intra-uterine disruption to development. The identification of causative gene mutations is important for genetic counselling and also provides insights into the mechanisms controlling limb development. This article illustrates some of the lessons learnt from the study of human limb malformation, organized into seven categories. These are: (1) identification of novel genes, (2) allelic mutation series, (3) pleiotropy, (4) qualitative or (5) quantitative differences between mouse and human development, (6) physical and teratogenic disruption, and (7) unusual biological phenomena. PMID:12587917

  7. 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

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

    PubMed

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

    2015-09-01

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

  10. 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

  11. 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

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

    PubMed Central

    Wang, Qi; Taylor, John E.

    2016-01-01

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

  13. 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

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

    NASA Astrophysics Data System (ADS)

    Mattigiri, S.; Warty, C.

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

  15. 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.

  16. 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

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

    PubMed

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

    2009-05-10

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

  18. 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.

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

    PubMed

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

    2016-06-15

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

  20. 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.

  1. 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

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

    SciTech Connect

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

    2012-12-21

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

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

    ERIC Educational Resources Information Center

    Gordon, Malcolm; And Others

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

  4. Study of radiation limits in fusion reactor scenarios

    NASA Astrophysics Data System (ADS)

    Becker, G.

    1999-07-01

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

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

    PubMed

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

    2015-10-01

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

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

    PubMed

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

    2016-01-01

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

  7. Conditioned Medium From Human Amniotic Mesenchymal Stromal Cells Limits Infarct Size and Enhances Angiogenesis

    PubMed Central

    Danieli, Patrizia; Malpasso, Giuseppe; Ciuffreda, Maria Chiara; Cervio, Elisabetta; Calvillo, Laura; Copes, Francesco; Pisano, Federica; Mura, Manuela; Kleijn, Lennaert; de Boer, Rudolf A.; Viarengo, Gianluca; Rosti, Vittorio; Spinillo, Arsenio; Roccio, Marianna

    2015-01-01

    The paracrine properties of human amniotic membrane-derived mesenchymal stromal cells (hAMCs) have not been fully elucidated. The goal of the present study was to elucidate whether hAMCs can exert beneficial paracrine effects on infarcted rat hearts, in particular through cardioprotection and angiogenesis. Moreover, we aimed to identify the putative active paracrine mediators. hAMCs were isolated, expanded, and characterized. In vitro, conditioned medium from hAMC (hAMC-CM) exhibited cytoprotective and proangiogenic properties. In vivo, injection of hAMC-CM into infarcted rat hearts limited the infarct size, reduced cardiomyocyte apoptosis and ventricular remodeling, and strongly promoted capillary formation at the infarct border zone. Gene array analysis led to the identification of 32 genes encoding for the secreted factors overexpressed by hAMCs. Among these, midkine and secreted protein acidic and rich in cysteine were also upregulated at the protein level. Furthermore, high amounts of several proangiogenic factors were detected in hAMC-CM by cytokine array. Our results strongly support the concept that the administration of hAMC-CM favors the repair process after acute myocardial infarction. PMID:25824141

  8. Conditioned medium from human amniotic mesenchymal stromal cells limits infarct size and enhances angiogenesis.

    PubMed

    Danieli, Patrizia; Malpasso, Giuseppe; Ciuffreda, Maria Chiara; Cervio, Elisabetta; Calvillo, Laura; Copes, Francesco; Pisano, Federica; Mura, Manuela; Kleijn, Lennaert; de Boer, Rudolf A; Viarengo, Gianluca; Rosti, Vittorio; Spinillo, Arsenio; Roccio, Marianna; Gnecchi, Massimiliano

    2015-05-01

    The paracrine properties of human amniotic membrane-derived mesenchymal stromal cells (hAMCs) have not been fully elucidated. The goal of the present study was to elucidate whether hAMCs can exert beneficial paracrine effects on infarcted rat hearts, in particular through cardioprotection and angiogenesis. Moreover, we aimed to identify the putative active paracrine mediators. hAMCs were isolated, expanded, and characterized. In vitro, conditioned medium from hAMC (hAMC-CM) exhibited cytoprotective and proangiogenic properties. In vivo, injection of hAMC-CM into infarcted rat hearts limited the infarct size, reduced cardiomyocyte apoptosis and ventricular remodeling, and strongly promoted capillary formation at the infarct border zone. Gene array analysis led to the identification of 32 genes encoding for the secreted factors overexpressed by hAMCs. Among these, midkine and secreted protein acidic and rich in cysteine were also upregulated at the protein level. Furthermore, high amounts of several proangiogenic factors were detected in hAMC-CM by cytokine array. Our results strongly support the concept that the administration of hAMC-CM favors the repair process after acute myocardial infarction. PMID:25824141

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

    PubMed Central

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

    1968-01-01

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

  10. 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

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

    PubMed Central

    Melican, Keira; Aubey, Flore; Duménil, Guillaume

    2014-01-01

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

  12. 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.

  13. 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

  14. Recent advances in human viruses imaging studies.

    PubMed

    Florian, Paula Ecaterina; Rouillé, Yves; Ruta, Simona; Nichita, Norica; Roseanu, Anca

    2016-06-01

    Microscopy techniques are often exploited by virologists to investigate molecular details of critical steps in viruses' life cycles such as host cell recognition and entry, genome replication, intracellular trafficking, and release of mature virions. Fluorescence microscopy is the most attractive tool employed to detect intracellular localizations of various stages of the viral infection and monitor the pathogen-host interactions associated with them. Super-resolution microscopy techniques have overcome the technical limitations of conventional microscopy and offered new exciting insights into the formation and trafficking of human viruses. In addition, the development of state-of-the art electron microscopy techniques has become particularly important in studying virus morphogenesis by revealing ground-braking ultrastructural details of this process. This review provides recent advances in human viruses imaging in both, in vitro cell culture systems and in vivo, in the animal models recently developed. The newly available imaging technologies bring a major contribution to our understanding of virus pathogenesis and will become an important tool in early diagnosis of viral infection and the development of novel therapeutics to combat the disease. PMID:27059598

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

    NASA Astrophysics Data System (ADS)

    Soto Gomez, A.

    2012-12-01

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

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

    PubMed

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

    2013-01-01

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

  17. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2004-11-01

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

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

    PubMed

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

    2011-10-01

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

  20. Haplotype-based banking of human pluripotent stem cells for transplantation: potential and limitations.

    PubMed

    Zimmermann, Anna; Preynat-Seauve, Olivier; Tiercy, Jean-Marie; Krause, Karl-Heinz; Villard, Jean

    2012-09-01

    High expectations surround the area of stem cells therapeutics. However, the cells' source-adult or embryonic-and the cells' origin-patient-derived autologous or healthy donor genetically unrelated-remain subjects of debate. Autologous origins have the advantage of a theoretical absence of immune rejection by the recipient. However, this approach has several limitations with regard to the disease of the recipient and to potential problems with the generation, expansion, and manipulation of autologous induced pluripotent stem cells (iPS cells) preparation. An alternative to using autologous cells is the establishment of a bank of well-characterized adult cells that would be used to generate iPS cells and their derivatives. In the context of transplantation, such cells would come from genetically unrelated donors and the immune system of the recipient would reject the graft without immunosuppressive therapy. To minimize the risk of rejection, human leukocyte antigen (HLA) compatibility is certainly the best option, and the establishment of an HLA-organized bank would mean having a limited number of stem cells that would be sufficient for a large number of recipients. The concept of haplobanking with HLA homozygous cell lines would also limit the number of HLA mismatches, but such an approach will not necessarily be less immunogenic in terms of selection criteria, because of the limited number of HLA-compatible loci and the level of HLA typing resolution. PMID:22559254

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

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

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

  2. Studies of retroviral infection in humanized mice

    PubMed Central

    Marsden, Matthew D.; Zack, Jerome A.

    2015-01-01

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

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

    PubMed

    McKechnie, Claire Charlotte

    2014-12-01

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

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

    PubMed Central

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

    2008-01-01

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

  5. 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

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

    PubMed Central

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

    2016-01-01

    Background In 2009, Ghana adopted the Strengthening Laboratory Management Toward Accreditation (SLMTA) programme in order to improve laboratory quality. The programme was implemented successfully with limited donor funding and local human resources. Objectives To demonstrate how Ghana, which received very limited PEPFAR funding, was able to achieve marked quality improvement using local human resources. Method Local partners led the SLMTA implementation and local mentors were embedded in each laboratory. An in-country training-of-trainers workshop was conducted in order to increase the pool of local SLMTA implementers. Three laboratory cohorts were enrolled in SLMTA in 2011, 2012 and 2013. Participants from each cohort attended in a series of three workshops interspersed with improvement projects and mentorship. Supplemental training on internal audit was provided. Baseline, exit and follow-up audits were conducted using the Stepwise Laboratory Quality Improvement Process Towards Accreditation (SLIPTA) checklist. In November 2013, four laboratories underwent official SLIPTA audits by the African Society for Laboratory Medicine (ASLM). Results The local SLMTA team successfully implemented three cohorts of SLMTA in 15 laboratories. Seven out of the nine laboratories that underwent follow-up audits have reached at least one star. Three out of the four laboratories that underwent official ASLM audits were awarded four stars. Patient satisfaction increased from 25% to 70% and sample rejection rates decreased from 32% to 10%. On average, $40 000 was spent per laboratory to cover mentors' salaries, SLMTA training and improvement project support. Conclusion Building in-country capacity through local partners is a sustainable model for improving service quality in resource-constrained countries such as Ghana. Such models promote country ownership, capacity building and the use of local human resources for the expansion of SLMTA. PMID:26937417

  7. Studies on the human choroid plexus in vitro.

    PubMed

    Redzic, Zoran B

    2013-01-01

    The role of human choroid plexus (CP) epithelium in the transport of solutes between the blood and the cerebrospinal fluid and/or in secretion processes may be studied by employing several experimental approaches. There are a number of in vitro techniques for human CP epithelium (CPE) and all have limitations that do not exclude them a priori, but that should be carefully taken into consideration. Developmental and morphological studies have been largely performed on human choroid plexus samples of either embryonic or post-mortem origin. Functional uptake studies may be performed on pathologically unaltered CP samples obtained during surgical removal of choroid plexus tumors. This approach can be used to explore transport processes mainly across the apical side of the CPE, but cannot be used to study vectorial transport across the CPE. Also, these samples have limited viability. A monolayer of CPE in culture, grown on permeable supports, provides the best available tool to study transport processes or polarized secretion by the CP, but thus far only limited attempts to culture these cells have been published and they mainly include data from neoplastic CPE. A study that used a human papilloma-derived cell line in culture showed that it forms a monolayer with barrier properties, although the cells express pleomorphic and neoplastic features and lack contact inhibition. Other cell cultures express some CPE markers but do not develop tight junctions/barrier properties. This article reviews the main characteristics and limitations of available in vitro methods to study human CPE, which could help researchers choose an appropriate experimental approach for a particular study. PMID:23391221

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

    PubMed

    de Rham, Casimir; Villard, Jean

    2014-01-01

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

  9. 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

  10. Exploring the Limits to Observational Diffuse Interstellar Band Studies

    NASA Astrophysics Data System (ADS)

    Foing, B. H.

    2014-02-01

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

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

    PubMed Central

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

    2016-01-01

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

  12. Rabbit Models for Studying Human Infectious Diseases

    PubMed Central

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

    2015-01-01

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

  13. Rabbit Models for Studying Human Infectious Diseases.

    PubMed

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

    2015-12-01

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

  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. Explaining human movements and actions: children's understanding of the limits of psychological explanation.

    PubMed

    Schult, C A; Wellman, H M

    1997-03-01

    Human actions and movements can be caused by psychological states (e.g. beliefs and desires), physical forces (e.g. gravity) and biological processes (e.g. reflexes). In three studies we explored young children's understanding of the causes of human movements in order to examine their ability to differentiate and coordinate psychological, physical and biological reasoning to account for the activities of one single entity--a human being. In Study 1, 4-year-olds explained characters' voluntary actions, mistakes, physically-caused and biologically-caused behaviors and movements. Children gave psychological explanations for the intended actions and mistakes, but biological and physical explanations for the biologically-caused and physically-caused movements. Studies 2 and 3 extended the investigation to younger children (3-year-olds), encompassed a greater variety of items, and used several converging methods in order to examine children's judgments and explanations. Consistently, 3- and 4-year-olds gave appropriately different responses and explanations to the different item types. These findings show that far from viewing people in strictly psychological terms, young children evidence multiple causal-explanatory construals of human behavior. We discuss the implications of these findings for children's everyday psychological, physical, and biological theories. One implication of the findings is that young children do not assume a match between entities and theories (persons-psychology, objects-physics). If they do not, this raises the question of what information they use to decide which explanatory system fits which events. PMID:9187061

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

    PubMed Central

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

    2013-01-01

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

  17. 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 α subunit and β 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 β subunit were always higher than those of the α 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 α subunit in contrast to the β subunit. In addition, there was obvious limitation of the synthetic steps from mRNA to polypeptide for both the α subunit and the β subunit, especially the β 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

  18. 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

  19. 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.

  20. The Acceptability Limit in Food Shelf Life Studies.

    PubMed

    Manzocco, Lara

    2016-07-26

    Despite its apparently intuitive nature, the acceptability limit is probably the most difficult parameter to be defined when developing a shelf life test. Although it dramatically affects the final shelf life value, it is surprising that discussion on its nature has been largely neglected in the literature and only rare indications about the possible methodologies for its determination are available in the literature. This is due to the fact that the definition of this parameter is a consumer- and market-oriented issue, requiring a rational evaluation of the potential negative consequences of food unacceptability in the actual market scenario. This paper critically analyzes the features of the acceptability limit and the role of the decision maker. The methodologies supporting the choice of the acceptability limit as well as acceptability limit values proposed in the literature to calculate shelf life of different foods are reviewed. PMID:26593702

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

    PubMed Central

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

    2014-01-01

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

  2. Study of viral pathogenesis in humanized mice.

    PubMed

    Gaska, Jenna M; Ploss, Alexander

    2015-04-01

    Many of the viral pathogens that cause infectious diseases in humans have a highly restricted species tropism, making the study of their pathogenesis and the development of clinical therapies difficult. The improvement of humanized mouse models over the past 30 years has greatly facilitated researchers' abilities to study host responses to viral infections in a cost effective and ethical manner. From HIV to hepatotropic viruses to Middle East Respiratory Syndrome coronavirus, humanized mice have led to the identification of factors crucial to the viral life cycle, served as an outlet for testing candidate therapies, and improved our abilities to analyze human immune responses to infection. In tackling both new and old viruses as they emerge, humanized mice will continue to be an indispensable tool. PMID:25618248

  3. 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...

  4. Studies of human mutation rates

    SciTech Connect

    Neel, J.V.

    1990-01-01

    November 1989, marked the beginning of a new three-year cycle of DOE grant support, in connection with which the program underwent a major reorganization. This document presents the progress on the three objectives of the present program which are: to isolate by the technique of two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), proteins of special interest because of the relative mutability of the corresponding gene, establish the identity of the protein, and, for selected proteins, move to a characterization of the corresponding gene; to develop a more efficient approach, based on 2-D PAGE, for the detection of variants in DNA, with special reference to the identification of mutations in the parents of the individual whose DNA is being examined; and, to continue an effective interface with the genetic studies on the children of atomic bomb survivors in Japan, with reference to both the planning and implementation of new studies at the molecular level.

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

    PubMed Central

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

    2008-01-01

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

  6. Initial ALT-I pump limiter studies on TEXOR

    SciTech Connect

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

    1984-05-01

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

  7. 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.

  8. Predicting Nursing Human Resources: An Exploratory Study

    PubMed Central

    Squires, Allison; Beltrán-Sánchez, Hiram

    2010-01-01

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

  9. 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...

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

    ERIC Educational Resources Information Center

    Romm, Joseph

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

  11. 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.

  12. 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…

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Ting, T Y

    1984-09-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

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

    2014-01-01

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

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

    ERIC Educational Resources Information Center

    Eastmond, J. Nicholls, Jr.; And Others

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

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

    PubMed Central

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

    2015-01-01

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

  19. Enrollment of sudden cardiac death victims into a limited cardiac autopsy study in the emergency department.

    PubMed Central

    Denninghoff, K. R.

    2000-01-01

    The lack of balanced recruitment for racial and ethnic groups in research protocols is an important ethical issue. African Americans have a history of forced participation, unethical research, and unwilling human dissection/demonstration that leads to a lack of participation in clinical research. We have embarked on a study of the pathophysiology of sudden death among African Americans which requires a limited autopsy of the heart. Our objective was to improve the recruitment rate in this study when compared with historical rates seen in clinical research and organ donation. We have screened 14 and enrolled 10 African Americans with sudden death (95% CI 0.41-0.91). By addressing the concerns of the African-American community and involving qualified input in the planning stages of the study we have been able to significantly improve the recruitment rate for this important population subgroup. PMID:10800285

  20. 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

  1. 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

  2. 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.

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

    SciTech Connect

    Gilbert, E.S.

    1984-10-01

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

  4. 75 FR 359 - Guidance on Simultaneous Transmission Import Limit Studies; Notice Allowing Post-Technical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-05

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

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

    PubMed Central

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

    1984-01-01

    obtained by bronchoalveolar lavage represents the total in vivo population of alveolar macrophages, although normal human macrophages are capable of IL-1 release, they are relatively limited in this ability, and this limitation seems to be linked to the maturational state of the mononuclear phagocyte. These observations may explain, in part, the ability of alveolar macrophages to clear the airspaces of foreign antigens without extensive activation of other pulmonary inflammatory and immune effector cells. Images PMID:6334697

  6. Subcellular fractionation of human liver reveals limits in global proteomic quantification from isolated fractions.

    PubMed

    Wiśniewski, Jacek R; Wegler, Christine; Artursson, Per

    2016-09-15

    The liver plays an important role in metabolism and elimination of xenobiotics, including drugs. Determination of concentrations of proteins involved in uptake, distribution, metabolism, and excretion of xenobiotics is required to understand and predict elimination mechanisms in this tissue. In this work, we have fractionated homogenates of snap-frozen human liver by differential centrifugation and performed quantitative mass spectrometry-based proteomic analysis of each fraction. Concentrations of proteins were calculated by the "total protein approach". A total of 4586 proteins were identified by at least five peptides and were quantified in all fractions. We found that the xenobiotics transporters of the canalicular and basolateral membranes were differentially enriched in the subcellular fractions and that phase I and II metabolizing enzymes, the cytochrome P450s and the UDP-glucuronyl transferases, have complex subcellular distributions. These findings show that there is no simple way to scale the data from measurements in arbitrarily selected membrane fractions using a single scaling factor for all the proteins of interest. This study also provides the first absolute quantitative subcellular catalog of human liver proteins obtained from frozen tissue specimens. Our data provide quantitative insights into the subcellular distribution of proteins and can be used as a guide for development of fractionation procedures. PMID:27311553

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

    PubMed Central

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

    2014-01-01

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

  8. 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

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

    PubMed Central

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

    2013-01-01

    Perhaps more than any other “-omics” endeavor, the accuracy and level of detail obtained from mapping the major connection pathways in the living human brain with diffusion MRI depends on the capabilities of the imaging technology used. The current tools are remarkable; allowing the formation of an “image” of the water diffusion probability distribution in regions of complex crossing fibers at each of half a million voxels in the brain. Nonetheless our ability to map the connection pathways is limited by the image sensitivity and resolution, and also the contrast and resolution in encoding of the diffusion probability distribution. The goal of our Human Connectome Project (HCP) is to address these limiting factors by re-engineering the scanner from the ground up to optimize the high b-value, high angular resolution diffusion imaging needed for sensitive and accurate mapping of the brain’s structural connections. Our efforts were directed based on the relative contributions of each scanner component. The gradient subsection was a major focus since gradient amplitude is central to determining the diffusion contrast, the amount of T2 signal loss, and the blurring of the water PDF over the course of the diffusion time. By implementing a novel 4-port drive geometry and optimizing size and linearity for the brain, we demonstrate a whole-body sized scanner with Gmax = 300mT/m on each axis capable of the sustained duty cycle needed for diffusion imaging. The system is capable of slewing the gradient at a rate of 200 T/m/s as needed for the EPI image encoding. In order to enhance the efficiency of the diffusion sequence we implemented a FOV shifting approach to Simultaneous MultiSlice (SMS) EPI capable of unaliasing 3 slices excited simultaneously with a modest g-factor penalty allowing us to diffusion encode whole brain volumes with low TR and TE. Finally we combine the multi-slice approach with a compressive sampling reconstruction to sufficiently undersample q

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

    PubMed

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

    2013-10-15

    Perhaps more than any other "-omics" endeavor, the accuracy and level of detail obtained from mapping the major connection pathways in the living human brain with diffusion MRI depend on the capabilities of the imaging technology used. The current tools are remarkable; allowing the formation of an "image" of the water diffusion probability distribution in regions of complex crossing fibers at each of half a million voxels in the brain. Nonetheless our ability to map the connection pathways is limited by the image sensitivity and resolution, and also the contrast and resolution in encoding of the diffusion probability distribution. The goal of our Human Connectome Project (HCP) is to address these limiting factors by re-engineering the scanner from the ground up to optimize the high b-value, high angular resolution diffusion imaging needed for sensitive and accurate mapping of the brain's structural connections. Our efforts were directed based on the relative contributions of each scanner component. The gradient subsection was a major focus since gradient amplitude is central to determining the diffusion contrast, the amount of T2 signal loss, and the blurring of the water PDF over the course of the diffusion time. By implementing a novel 4-port drive geometry and optimizing size and linearity for the brain, we demonstrate a whole-body sized scanner with G(max) = 300 mT/m on each axis capable of the sustained duty cycle needed for diffusion imaging. The system is capable of slewing the gradient at a rate of 200 T/m/s as needed for the EPI image encoding. In order to enhance the efficiency of the diffusion sequence we implemented a FOV shifting approach to Simultaneous MultiSlice (SMS) EPI capable of unaliasing 3 slices excited simultaneously with a modest g-factor penalty allowing us to diffusion encode whole brain volumes with low TR and TE. Finally we combine the multi-slice approach with a compressive sampling reconstruction to sufficiently undersample q-space to

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

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

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

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

    PubMed

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

    2016-08-15

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

  13. 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.

  14. Studies of Human Memory and Language Processing.

    ERIC Educational Resources Information Center

    Collins, Allan M.

    The purposes of this study were to determine the nature of human semantic memory and to obtain knowledge usable in the future development of computer systems that can converse with people. The work was based on a computer model which is designed to comprehend English text, relating the text to information stored in a semantic data base that is…

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

    NASA Astrophysics Data System (ADS)

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

    2013-04-01

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

  16. 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

  17. 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.

  18. 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.

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

    NASA Astrophysics Data System (ADS)

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

    1993-10-01

    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 Astrophysics Data System (ADS)

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

    1993-10-01

    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. Study made of ductility limitations of aluminum-silicon alloys

    NASA Technical Reports Server (NTRS)

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

    1967-01-01

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

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

    ERIC Educational Resources Information Center

    Carey, Michelle

    2015-01-01

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

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

    PubMed

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

    2010-01-01

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

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

    PubMed

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

    2016-07-01

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

  5. 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...

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

    PubMed

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

    2013-03-12

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

  7. Limitations of Levothyroxine Bioequivalence Evaluation: Analysis of An Attempted Study.

    PubMed

    Mayor, Gilbert H.; Orlando, Tony; Kurtz, Neil M.

    1995-06-01

    The relative bioavailability and therapeutic comparability of four levothyroxine products (two proprietary and two nonbranded) were determined in an open-label, block-randomized, four-way crossover trial with no washout periods in 24 presumed hypothyroid ambulatory care patients who were considered euthyroid while on 100 &mgr;g or 150 &mgr;g of oral levothyroxine daily for at least 3 months. Patients randomly received each of the four levothyroxine products for 6 weeks at the same dosage as their prestudy regimen. Area under the serum concentration versus time curve (AUC), maximum change in serum concentration (C(max)), and time to peak serum concentration (T(max)) were calculated for total thyroxine (TT(4)), total triiodothyronine (TT(3)), free thyroxine index (FT(4)I), and thyrotropin (TSH) for each product, with and without baseline correction and normalization for tablet potency differences. Ninety-percent confidence intervals were determined for each paired treatment comparison. Using the response variable of values uncorrected for baseline (Hour 0), 90% confidence intervals for paired treatment comparisons of nonlogarithmically transformed AUC and C(max) (TT(4), TT(3), and FT(4)I) were within the range of 80% to 120%. However, using the response variable of baseline corrected values, no confidence intervals for TT(4) or TT(3) AUC or TT(3) C(max) were within the range of 80% to 120%. Confidence intervals for TSH AUC and C(max) based on both baseline corrected and uncorrected values were outside the 80--120% range. Results were similar when AUC and C(max) were normalized for tablet potency. Thus, results both within and between response variables were conflicting. Further, results normalized for potency using either response variable also failed to demonstrate bioequivalence, pointing to the serious difficulties inherent in levothyroxine bioequivalence studies. Independent consultant review of study design, execution, and data analysis was used to identify

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

    PubMed Central

    2014-01-01

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

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

    PubMed

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

    2016-01-15

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

  10. Evidence that diffusion limitation determines oxygen uptake kinetics during exercise in humans.

    PubMed Central

    Koike, A; Wasserman, K; McKenzie, D K; Zanconato, S; Weiler-Ravell, D

    1990-01-01

    To determine the role of arterial O2 content on the mechanism of muscle O2 utilization, we studied the effect of 2, 11, and 20% carboxyhemoglobin (COHb) on O2 uptake (VO2), and CO2 output (VCO2) kinetics in response to 6 min of constant moderate- and heavy-intensity cycle exercise in 10 subjects. Increased COHb did not affect resting heart rate, VO2 or VCO2. Also, the COHb did not affect the asymptotic VO2 in response to exercise. However, VO2 and VCO2 kinetics were affected differently. The time constant (TC) of VO2 significantly increased with increased COHb for both moderate and heavy work intensities. VO2 TC was positively correlated with blood lactate. In contrast, VCO2 TC was negatively correlated with increased COHb for the moderate but unchanged for the heavy work intensity. The gas exchange ratio reflected a smaller increase in CO2 stores and faster VCO2 kinetics relative to VO2 with increased COHb. These changes can be explained by compensatory cardiac output (heart rate) increase in response to reduced arterial O2 content. The selective slowing of VO2 kinetics, with decreased blood O2 content and increased cardiac output, suggests that O2 is diffusion limited at the levels of exercise studied. PMID:2122982

  11. 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

  12. 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

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  15. Human studies on polyglycerol polyricinoleate (PGPR).

    PubMed

    Wilson, R; Smith, M

    1998-01-01

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

  16. Studies in human skin epithelial cell carcinogenesis

    SciTech Connect

    Lehman, T.A.

    1987-01-01

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

  17. 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

  18. 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.

  19. 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

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

    PubMed Central

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

    2016-01-01

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

  1. Technological Change and Human Dignity. A Study in Human Values.

    ERIC Educational Resources Information Center

    Goldberg, Maxwell H.; Kochanek, Patricia

    The purpose of this text of questions and readings and of the project CCLE-IBM Humanities Project on Technological Change from which it emerged, is to aid the participant-reader become habituated to coping with a complex environment by actively responding to technological change in a way that enhances his own sense of personal and human dignity.…

  2. Human fertility studies under field conditions. Introduction.

    PubMed

    Harrison, G A

    1992-07-01

    Human fertility is part of biological anthropology embracing human population biology devoted to the analysis of the nature, caused, origin, and development of human variation at molecular, cellular, and whole body levels. The successful outcome of human fertility depends on the interactions of biochemical, physiological, and psychological processes whose disturbance results in slight variations in behavior and even total infertility. The Hutterites in the US have the highest average fertility with over 11 live births/women. Hunter-gatherer groups rarely have more than 4 children/woman. The case of a woman who gave birth to 67 children was recorded. Total infertility often occurs even in noncontracepting societies. The most important factor that determines the character of genetic variation within the human species seems to be comparative population growth, as this was the factor determining which populations spread and which became extinct. The study of the determinants of female fertility has attracted attention recently because pregnancy and motherhood affect daily life, and in turn, reproduction is also affected by daily life. Lactational amenorrhea plays a vital role in child spacing, but the mechanism of breast feeding is complex with factors of duration, frequency, milk production, and suckling frequency interwoven. Female reproduction comprises whole body function, nutrition, body composition (the recent debate on fat stores affecting the onset of fertility), physical work, and mental health all influencing the endocrinological state. Heavy physical labor and intensive training by sportswomen can result in amenorrhea. Beta-endorphins also play a role in lactational amenorrhea along with nutrition and body composition. Infectious and venereal diseases particularly affect fertility, yet genetics protect the placenta against falciparum malaria in sickle-cell trait women. PMID:1634557

  3. 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

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

    PubMed

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

    2013-11-01

    West Nile Virus (WNV) is a mosquito-borne pathogen that impacts the health of its passerine bird hosts as well as incidentally infected humans in the United States. Intensive enzootic activity among the hosts and vectors does not always lead to human outbreaks, as is the situation throughout much of the southeastern United States. In Georgia, substantial yearly evidence of WNV in the mosquito vectors and avian hosts since 2001 has only led to 324 human cases. Although virus has been consistently isolated from mosquitoes trapped in Atlanta, GA, little is known about viral activity among the passerine hosts. A possible reason for the suppression of WNV spillover to humans is that viremic birds are absent from high human-use areas of the city. To test this hypothesis, multiseason, multihabitat, longitudinal WNV surveillance for active WNV viremia was conducted within the avian host community of urban Atlanta by collection of blood samples from wild passerine birds in five urban microhabitats. WNV was isolated from the serum of six blood samples collected from 630 (0.95%) wild passerine birds in Atlanta during 2010-2012, a proportion similar to that found in the Chicago, IL, area in 2005, when over 200 human cases were reported. Most of the viremic birds were Northern Cardinals, suggesting they may be of particular importance to the WNV transmission cycle in Georgia. Results indicated active WNV transmission in all microhabitats of urban Atlanta, except in the old-growth forest patches. The number of viremic birds was highest in Zoo Atlanta, where 3.5% of samples were viremic. Although not significant, these observations may suggest a possible transmission reduction effect of urban old-growth forests and a potential role in WNV amplification for Zoo Atlanta. Overall, spillover to humans remains a rare occurrence in urban Atlanta settings despite active WNV transmission in the avian population. PMID:24107200

  5. 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

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

    PubMed

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

    2015-01-01

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

  7. 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

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

    PubMed Central

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

    2013-01-01

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

  9. 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...

  10. 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…

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

    PubMed

    Grimm, Herwig; Hartnack, Sonja

    2013-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1993-01-01

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

  13. 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.

  14. Bioavailability of tocotrienols: evidence in human studies

    PubMed Central

    2014-01-01

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

  15. 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.

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

    PubMed

    Egerth, Martin; Pump, Stefan; Graf, Jürgen

    2013-06-01

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

  17. 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…

  18. 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…

  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. Limited predictability of postmortem human brain tissue quality by RNA integrity numbers.

    PubMed

    Sonntag, Kai-C; Tejada, George; Subburaju, Sivan; Berretta, Sabina; Benes, Francine M; Woo, Tsung-Ung W

    2016-07-01

    The RNA integrity number (RIN) is often considered to be a critical measure of the quality of postmortem human brains. However, it has been suggested that RINs do not necessarily reflect the availability of intact mRNA. Using the Agilent bioanalyzer and qRT-PCR, we explored whether RINs provide a meaningful way of assessing mRNA degradation and integrity in human brain samples by evaluating the expression of 3'-5' mRNA sequences of the cytochrome C-1 (CYC1) gene. Analysis of electropherograms showed that RINs were not consistently correlated with RNA or cDNA profiles and appeared to be poor predictors of overall cDNA quality. Cycle thresholds from qRT-PCR analysis to quantify the amount of CYC1 mRNA revealed positive correlations of RINs with amplification of full-length transcripts, despite the variable degree of linear degradation along the 3'-5' sequence. These data demonstrate that in postmortem human brain tissue the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Quality assessment of postmortem human brains by RNA integrity numbers (RINs) may be misleading, as they do not measure intact mRNAs. We show that the RIN is an indicator of mRNA quantity independent of degradation, but does not predict mRNA integrity, suggesting that RINs provide an incomplete measure of brain tissue quality. Our results resolve controversial assumption on interpreting quality assessments of human postmortem brains by RINs. PMID:27062510

  1. 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.

  2. Sorption studies of human keratinized tissues

    NASA Astrophysics Data System (ADS)

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

    2010-04-01

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

  3. Preliminary neutron crystallographic study of human transthyretin

    PubMed Central

    Haupt, Melina; Blakeley, Matthew P.; Teixeira, Susana C. M.; Mason, Sax A.; Mitchell, Edward P.; Cooper, Jonathan B.; Forsyth, V. Trevor

    2011-01-01

    Preliminary studies of perdeuterated crystals of human transthyretin (TTR) have been carried out using the LADI-III and D19 diffractometers at the Institut Laue–Langevin in Grenoble. The results demonstrate the feasibility of a full crystallographic analysis to a resolution of 2.0 Å using Laue diffraction and also illustrate the potential of using monochromatic instruments such as D19 for higher resolution studies where larger crystals having smaller unit cells are available. This study will yield important information on hydrogen bonding, amino-acid protonation states and hydration in the protein. Such information will be of general interest for an understanding of the factors that stabilize/destabilize TTR and for the design of ligands that may be used to counter TTR amyloid fibrillogenesis. PMID:22102249

  4. A study of the relation between the limit of detection and the limit of quantitation in inductively coupled plasma spectrochemistry

    NASA Astrophysics Data System (ADS)

    Carré, M.; Excoffier, S.; Mermet, J. M.

    1997-12-01

    The limit of quantitation based on a repeatability threshold concept is compared with the limit of detection in induction coupled plasma atomic emission spectrometry (ICP-AES) and induction coupled plasma mass spectrometry (ICP-MS). A 5%-based limit of quantitation would normally correspond to 10 times the 3-σ based limit of detection. However, because of a possible lack of linearity of the calibration graph at low concentrations, some additional noise not taken into consideration and the possible use of time-correlated multichannel detection, this ratio of 10 cannot be used in every case. It is suggested that a suitable way of determining the limit of quantitation is to establish the plot of the percentage relative standard deviation (RSD) of the net signal as a function of the concentration in a range from the limit of detection to 50 times this limit.

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

    PubMed

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

    2016-01-01

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

  6. 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

  7. The basic N-terminal domain of TRF2 limits recombination endonuclease action at human telomeres.

    PubMed

    Saint-Léger, Adélaïde; Koelblen, Melanie; Civitelli, Livia; Bah, Amadou; Djerbi, Nadir; Giraud-Panis, Marie-Josèphe; Londoño-Vallejo, Arturo; Ascenzioni, Fiorentina; Gilson, Eric

    2014-01-01

    The stability of mammalian telomeres depends upon TRF2, which prevents inappropriate repair and checkpoint activation. By using a plasmid integration assay in yeasts carrying humanized telomeres, we demonstrated that TRF2 possesses the intrinsic property to both stimulate initial homologous recombination events and to prevent their resolution via its basic N-terminal domain. In human cells, we further showed that this TRF2 domain prevents telomere shortening mediated by the resolvase-associated protein SLX4 as well as GEN1 and MUS81, 2 different types of endonucleases with resolvase activities. We propose that various types of resolvase activities are kept in check by the basic N-terminal domain of TRF2 in order to favor an accurate repair of the stalled forks that occur during telomere replication. PMID:25483196

  8. Human Laboratory Studies on Cannabinoids and Psychosis.

    PubMed

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

    2016-04-01

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

  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. 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

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

    PubMed Central

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

    2015-01-01

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

  12. Spatial genetic structure patterns of phenotype-limited and boundary-limited expanding populations: a simulation study.

    PubMed

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

    2014-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  14. 75 FR 18497 - Guidance on Simultaneous Transmission Import Limit Studies for the Northwest Region; Notice of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-12

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

  15. 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)

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

    Frost, Ginger

    2011-01-01

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

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

    PubMed

    Bermes, C

    2015-01-01

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

  20. Features and limitations of digital human models--a new German guideline.

    PubMed

    Zülch, Gert

    2012-01-01

    In 2008 the Association of German Engineers (VDI) published the first part of the VDI 4499 guideline for methods and tools for the digital factory. Part 1 of this guideline deals with the fundamentals of the system and will be expanded by the addition of further parts on specific topics within the digital factory. Soon to be published is Part 4 which covers human models as tools of the digital factory. It describes the state of the art of current digital human models with regards to the methods and procedures implemented in German speaking countries. The structure of this part of the guideline is based on the different sections of engineering mechanics and outlines the opportunities for ergonomic assessments and the evaluation of work systems. During the writing of the guideline, the restrictions of the existing procedures also became evident thus showing the requirement for further development of such procedures. This is illustrated in this paper using examples from commercial software systems. PMID:22317050

  1. Senescence occurs with hTERT repression and limited telomere shortening in human oral keratinocytes cultured with feeder cells.

    PubMed

    Kang, Mo K; Kameta, Ayako; Shin, Ki-Hyuk; Baluda, Marcel A; Park, No-Hee

    2004-06-01

    We investigated the phenotypic and molecular alterations in normal human oral keratinocytes (NHOK) during in vitro replication in two different culture conditions. The cells were cultured either in chemically defined Keratinocyte Growth Medium (KGM) without feeder layers or in serum-containing flavin-adenine dinucleotide (FAD) medium with feeder layers. Primary NHOK underwent 22 +/- 3 population doublings (PDs) in KGM and 42 +/- 4 PDs in FAD medium, reflecting 52% increase in replication capacity with feeder layers. In both culture conditions, exponentially replicating NHOK demonstrated telomerase activity and expression of human telomerase reverse transcriptase (hTERT) gene. Telomerase activity and hTERT expression were rapidly diminished in senescing NHOK, which exhibited small decrease of telomere length for the remaining limited cellular replications until the complete arrest of cell division. However, telomere length in senescent NHOK was 6.7 +/- 0.5 kilobase pairs (kbps), significantly longer than that (5.12 kbps) of senescent human fibroblasts. The onset of senescence was accompanied with marked induction of p16(INK4A), and this occurred in both culture systems using either KGM or FAD medium. These results indicate that replicative senescence of NHOK is associated with loss of telomerase activity followed by limited telomere shortening. PMID:15095283

  2. 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

  3. 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

  4. 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

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. Metabolomic studies of human gastric cancer: review.

    PubMed

    Jayavelu, Naresh Doni; Bar, Nadav S

    2014-07-01

    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

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

    PubMed

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

    2015-05-01

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

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

    PubMed Central

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

    2015-01-01

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

  12. ERBS human factors analysis: A case study

    NASA Technical Reports Server (NTRS)

    Moe, K. L.; Weger, C.

    1983-01-01

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

  13. The utility and limitations of glycosylated human CD133 epitopes in defining cancer stem cells

    PubMed Central

    Bidlingmaier, Scott; Zhu, Xiaodong; Liu, Bin

    2008-01-01

    Human CD133 (human prominin-1), a five transmembrane domain glycoprotein, was originally identified as a cell surface antigen present on CD34+ hematopoietic stem cells. Although the biological function of CD133 is not well understood, antibodies to CD133 epitopes have been widely used to purify hematopoietic stem and progenitor cells. The cancer stem cell (CSC) hypothesis postulates that a rare population of tumor cells possessing increased capacities for self-renewal and tumor initiation is responsible for maintaining the growth of neoplastic tissue. The expression of the CD133 epitopes, AC133 and AC141, has been shown to define a subpopulation of brain tumor cells with significantly increased capacity for tumor initiation in xenograft models. Following the discovery of the AC133/AC141+ population of brain tumor stem cells, the AC133 and AC141 epitopes have been extensively used as markers for purifying CSCs in other solid tumors. There are, however, several issues associated with the use of the AC133 and AC141 CD133 epitopes as markers for CSCs. The antibodies routinely used for purification of AC133 and AC141-positive cells target poorly characterized glycosylated epitopes of uncertain specificity. Discordant expression of the AC133 and AC141 epitopes has been observed, and the epitopes can be absent despite the presence of CD133 protein. In addition, CD133 expression has recently been shown to be modulated by oxygen levels. These factors, in combination with the uncertain biological role of CD133, suggest that the use of CD133 expression as a marker for CSCs should be critically evaluated in each new experimental system and highlight the need for additional CSC surface markers that are directly involved in maintaining CSC properties. PMID:18535813

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

    PubMed Central

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

    2012-01-01

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

  15. Passwords usage and human memory limitations: a survey across age and educational background.

    PubMed

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

    2012-01-01

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

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

    SciTech Connect

    Ascenzi, Paolo; Gullotta, Francesca; Gioia, Magda; Coletta, Massimo; Fasano, Mauro

    2011-03-04

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

  17. 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…

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

    ERIC Educational Resources Information Center

    Anderson, James A.; Meyer, Timothy P.

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

  19. Study of human sperm motility post cryopreservation

    PubMed Central

    Oberoi, Bhavni; Kumar, Sushil; Talwar, Pankaj

    2014-01-01

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

  20. A Brief History of Soils and Human Health Studies

    NASA Astrophysics Data System (ADS)

    Brevik, Eric C.; Sauer, Thomas J.

    2013-04-01

    scientist to date to be awarded a Nobel Prize. In the 1940s and 50s William Albrecht of the University of Missouri became interested in links between soils and human health, an interest that lead to the publication of several papers. Albrecht's works focused on links between soil fertility and dental health, with a particular focus on the relationships between soil fertility and dental cavities. However, Albrecht did extend the relationships between soil fertility and human health out to broader, more general health issues in some of his writings as well. Well-known figures such as Sir Albert Howard and J.I. Rodale also published works in the 1940s that included soils and human health components. Then André Voisin published "Soil, Grass, and Cancer" in 1959. Much of Voisin's work focused on nutrient content in soils, including both nutrient deficiencies and imbalances, and how that influences nutrient status in plants and animals that are in turn consumed by humans. Several health problems are discussed, including but not limited to birth defects, goiter, mental illness, diabetes, and cancer. Voisin concluded that the medical profession had largely ignored soils in their efforts to improve human health, but that soil science should be the foundation of preventative medicine. Soils and human health studies continued in the later part of the 20th Century. The health effects of exposures to radioactive elements in soils received considerable attention after the 1986 Chernobyl incident, however, even prior to Chernobyl radionuclides in the soil and how they may affect human health were receiving attention. Investigations into the effects of heavy metals in soils became a common theme as did organic chemicals in soils and the effects of trace elements on human health. Following up on the discovery of antibiotics, soil organisms received increased attention as they related to human health. By the end of the 1900s, M.A. Oliver (1997) noted that "… there is a dearth of

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

    PubMed

    Gresty, M A; Bronstein, A M

    1992-06-01

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

  2. 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].

  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. 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.

  5. Subjective Quantitative Studies of Human Agency

    ERIC Educational Resources Information Center

    Alkire, Sabina

    2005-01-01

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

  6. 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

  7. 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.

  8. A Histoenzymatic Study of Human Intracranial Atherosclerosis

    PubMed Central

    Hoff, Henry F.

    1972-01-01

    A light microscopy study on the localization of enzyme activity within atherosclerotic human intracranial arteries was performed on autopsy material obtained within 4 hours of death. The data suggests that the atherosclerotic process first goes through a proliferative phase and then a degenerative phase culminating in the formation of a plaque. In the proliferative phase, smooth muscle cell proliferation has formed a thickened intima. Tetrazolium reductase, adenosine triphosphatase (ATPase) and adenosine monophosphatase (AMPase) activities are present in these cells, while all dehydrogenases and acid phosphatase activities were weak or not present. As the degenerative phase commences, an area of necrosis, lipid and macrophage accumulation is formed on the lumen side of the elastica. This area increases in size until a plaque is formed. Unsaturated polar and nonpolar lipid, cholesterol, α-glycerophosphate dehydrogenase, acid phosphatase, and AMPase activities are associated with these areas and in foam cells, which are often found in the thickened intima of the proliferative phase. Tetrazolium reductase and ATPase activities decrease in the thickened intima as the area of necrosis increases in size, while dehydrogenase activity, except that for α-glycerophosphate, remains low or not present. Patterns of enzyme alterations for various stages of the disease process in intracranial arteries, the aorta and coronary arteries suggest a similar, if not identical, progression of the atherosclerotic process, irrespective of known differences in the prevalence of atherosclerosis. ImagesFig 2Fig 3Fig 5Fig 1Fig 4 PMID:4260721

  9. Detecting directional coupling in the human epileptic brain: Limitations and potential pitfalls

    NASA Astrophysics Data System (ADS)

    Osterhage, Hannes; Mormann, Florian; Wagner, Tobias; Lehnertz, Klaus

    2008-01-01

    We study directional relationships—in the driver-responder sense—in networks of coupled nonlinear oscillators using a phase modeling approach. Specifically, we focus on the identification of drivers in clusters with varying levels of synchrony, mimicking dynamical interactions between the seizure generating region (epileptic focus) and other brain structures. We demonstrate numerically that such an identification is not always possible in a reliable manner. Using the same analysis techniques as in model systems, we study multichannel electroencephalographic recordings from two patients suffering from focal epilepsy. Our findings demonstrate that—depending on the degree of intracluster synchrony—certain subsystems can spuriously appear to be driving others, which should be taken into account when analyzing field data with unknown underlying dynamics.

  10. 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.