Science.gov

Sample records for limited human studies

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

    PubMed

    Murray, Andrew; Costa, Ricardo J S

    2012-07-19

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-05-01

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

  3. Limitations of functionally determined joint centers for the analysis of athletic human movement: a case study of the upper limb.

    PubMed

    Roosen, Andy; Pain, Matthew T G; Begon, Mickaël

    2009-11-01

    Much research is ongoing into improving the accuracy of functional algorithms to determine joint centers (JC), but there has been limited testing using human movement data. This paper is in three parts: Part 1, errors in determining JCs from real human movement data using the SCoRE method; Part 2, variability of marker combinations during a punch; Part 3, variability in the JC due to reconstruction. Results indicate determining the JC of the shoulder or elbow with a triad of markers per segment with an accuracy greater than 20 mm is unlikely. Part 2 suggests conducting a pilot study with abundant markers to obtain triads, which are most stable due to differences of 300-400% in variability between triads. Variability due to the choice of reference frame for reconstruction during the punch ranged from 2.5 to 13.8 mm for the shoulder and 1.5 to 21.1 mm for the elbow. It would appear more pertinent to enhance the practical methods in situ than to further improve theoretical accuracy of functional methods.

  4. Estimating limits for natural human embryo mortality.

    PubMed

    Jarvis, Gavin E

    2016-01-01

    Natural human embryonic mortality is generally considered to be high. Values of 70% and higher are widely cited. However, it is difficult to determine accurately owing to an absence of direct data quantifying embryo loss between fertilisation and implantation. The best available data for quantifying pregnancy loss come from three published prospective studies (Wilcox, Zinaman and Wang) with daily cycle by cycle monitoring of human chorionic gonadotrophin (hCG) in women attempting to conceive. Declining conception rates cycle by cycle in these studies indicate that a proportion of the study participants were sub-fertile. Hence, estimates of fecundability and pre-implantation embryo mortality obtained from the whole study cohort will inevitably be biased. This new re-analysis of aggregate data from these studies confirms the impression that discrete fertile and sub-fertile sub-cohorts were present. The proportion of sub-fertile women in the three studies was estimated as 28.1% (Wilcox), 22.8% (Zinaman) and 6.0% (Wang). The probability of conceiving an hCG pregnancy (indicating embryo implantation) was, respectively, 43.2%, 38.1% and 46.2% among normally fertile women, and 7.6%, 2.5% and 4.7% among sub-fertile women. Pre-implantation loss is impossible to calculate directly from available data although plausible limits can be estimated. Based on this new analysis and a model for evaluating reproductive success and failure it is proposed that a plausible range for normal human embryo and fetal mortality from fertilisation to birth is 40-60%.

  5. Limited caspase cleavage of human BAP31.

    PubMed

    Määttä, J; Hallikas, O; Welti, S; Hildén, P; Schröder, J; Kuismanen, E

    2000-11-10

    Human BAP31 was cleaved at both of its two identical caspase cleavage sites in two previously reported models of apoptosis. We show here that only the most carboxy-terminal site is cleaved during apoptosis induced in HeLa cells by tunicamycin, tumor necrosis factor and cycloheximide, or staurosporine. Similar results were obtained in HL-60 cells using Fas/APO-1 antibodies, or cycloheximide. This limited cleavage, which is inhibited by several caspase inhibitors, removes eight amino acids from human BAP31 including the KKXX coat protein I binding motif. Ectopic expression of the resulting cleavage product induces redistribution of mannosidase II from the Golgi and prevents endoplasmic reticulum to Golgi transport of virus glycoproteins.

  6. Deep Sequencing of Influenza A Virus from a Human Challenge Study Reveals a Selective Bottleneck and Only Limited Intrahost Genetic Diversification

    PubMed Central

    McClain, Micah T.; Smith, Gavin J. D.; Wentworth, David E.; Halpin, Rebecca A.; Lin, Xudong; Ransier, Amy; Gilbert, Anthony S.; Lambkin-Williams, Robert; Ginsburg, Geoffrey S.; Woods, Christopher W.; Koelle, Katia

    2016-01-01

    ABSTRACT Knowledge of influenza virus evolution at the point of transmission and at the intrahost level remains limited, particularly for human hosts. Here, we analyze a unique viral data set of next-generation sequencing (NGS) samples generated from a human influenza challenge study wherein 17 healthy subjects were inoculated with cell- and egg-passaged virus. Nasal wash samples collected from 7 of these subjects were successfully deep sequenced. From these, we characterized changes in the subjects' viral populations during infection and identified differences between the virus in these samples and the viral stock used to inoculate the subjects. We first calculated pairwise genetic distances between the subjects' nasal wash samples, the viral stock, and the influenza virus A/Wisconsin/67/2005 (H3N2) reference strain used to generate the stock virus. These distances revealed that considerable viral evolution occurred at various points in the human challenge study. Further quantitative analyses indicated that (i) the viral stock contained genetic variants that originated and likely were selected for during the passaging process, (ii) direct intranasal inoculation with the viral stock resulted in a selective bottleneck that reduced nonsynonymous genetic diversity in the viral hemagglutinin and nucleoprotein, and (iii) intrahost viral evolution continued over the course of infection. These intrahost evolutionary dynamics were dominated by purifying selection. Our findings indicate that rapid viral evolution can occur during acute influenza infection in otherwise healthy human hosts when the founding population size of the virus is large, as is the case with direct intranasal inoculation. IMPORTANCE Influenza viruses circulating among humans are known to rapidly evolve over time. However, little is known about how influenza virus evolves across single transmission events and over the course of a single infection. To address these issues, we analyze influenza virus

  7. The limits of agency in walking humans.

    PubMed

    Kannape, O A; Schwabe, L; Tadi, T; Blanke, O

    2010-05-01

    An important principle of human ethics is that individuals are not responsible for actions performed when unconscious. Recent research found that the generation of an action and the building of a conscious experience of that action (agency) are distinct processes and crucial mechanisms for self-consciousness. Yet, previous agency studies have focussed on actions of a finger or hand. Here, we investigate how agents consciously monitor actions of the entire body in space during locomotion. This was motivated by previous work revealing that (1) a fundamental aspect of self-consciousness concerns a single and coherent representation of the entire spatially situated body and (2) clinical instances of human behaviour without consciousness occur in rare neurological conditions such as sleepwalking or epileptic nocturnal wandering. Merging techniques from virtual reality, full-body tracking, and cognitive science of conscious action monitoring, we report experimental data about consciousness during locomotion in healthy participants. We find that agents consciously monitor the location of their entire body and its locomotion only with low precision and report that while precision remains low it can be systematically modulated in several experimental conditions. This shows that conscious action monitoring in locomoting agents can be studied in a fine-grained manner. We argue that the study of the mechanisms of agency for a person's full body may help to refine our scientific criteria of self-hood and discuss sleepwalking and related conditions as alterations in neural systems encoding motor awareness in walking humans.

  8. Teleoperator Human Factors Study

    NASA Technical Reports Server (NTRS)

    1986-01-01

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

  9. Human 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.

  10. 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.

  11. Approaching the Limit of Predictability in Human Mobility

    NASA Astrophysics Data System (ADS)

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

    2013-10-01

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

  12. Limits to human locomotor performance: phylogenetic origins and comparative perspectives.

    PubMed

    Dudley, R

    2001-09-01

    Studies of human exercise physiology have been conducted from a largely ahistorical perspective. This approach usefully elucidates proximate limits to locomotor performance, but ignores potential sources of biomechanical and physiological variation that derive from adaptation to ancestral environments. Phylogenetic reconstruction suggests that multiple hominoid lineages, including that leading to Homo sapiens, evolved in African highlands at altitudes of 1000-2000 m. The evolution of human locomotor physiology therefore occurred under conditions of hypobaric hypoxia. In contrast to present-day humans running on treadmills or exercising in otherwise rectilinear trajectories, ancestral patterns of hominid locomotion probably involved intermittent knuckle-walking over variable terrain, occasional bouts of arboreality and an evolving capacity for bipedalism. All such factors represent potential axes of locomotor variation at present unstudied in extant hominoid taxa. As with humans, hummingbirds evolved in mid-montane contexts but pose an extreme contrast with respect to body size, locomotor mode and metabolic capacity. Substantial biomechanical and physiological challenges are associated with flight in hypobaria. Nonetheless, hummingbird lineages demonstrate a progressive invasion of higher elevations and a remarkable tolerance to hypoxia during hovering. Upregulation of aerobic capacity and parallel resistance to hypoxia may represent coupled evolutionary adaptations to flight under high-altitude conditions.

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

  16. 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...

  17. Limits to running speed in dogs, horses and humans.

    PubMed

    Denny, Mark W

    2008-12-01

    Are there absolute limits to the speed at which animals can run? If so, how close are present-day individuals to these limits? I approach these questions by using three statistical models and data from competitive races to estimate maximum running speeds for greyhounds, thoroughbred horses and elite human athletes. In each case, an absolute speed limit is definable, and the current record approaches that predicted maximum. While all such extrapolations must be used cautiously, these data suggest that there are limits to the ability of either natural or artificial selection to produce ever faster dogs, horses and humans. Quantification of the limits to running speed may aid in formulating and testing models of locomotion.

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

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Study limits. 169a.19 Section 169a.19 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING COMMERCIAL ACTIVITIES PROGRAM PROCEDURES Procedures § 169a.19 Study limits. No DoD funds shall be available to perform any...

  19. Human Memory Limitations in Multi-Object Tracking.

    DTIC Science & Technology

    1982-06-01

    Atkinson , R. C., & Shiffrin , R. M. Human memory : A proposed system and its control processes. In K. W. Spence & J. T. Spence (eds.), The psychology of...side It tv~eae .mE fdmrntiIr bY Week n..mbar) Human performance measurement -.get tracking Visual memory Hum, memory limitations Mathematical models of...performance and may be traded off in a complex manner. A family of mathematical models of human memory that focus on the encoding, learning, and rehearsal

  20. The Limitation of Human Population: A Natural History

    ERIC Educational Resources Information Center

    Dumond, Don E.

    1975-01-01

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

  1. 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

  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. 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...

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

    PubMed

    Binder, Andreas

    2016-02-01

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

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

    PubMed

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

    2013-10-01

    Tetrahydrobiopterin (BH₄) is required for NO synthesis and inhibition of superoxide release from endothelial NO synthase. 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 multielectrode coulometric HPLC method that enabled the direct quantification of 7,8-BH₂ and BH₄, which is not possible with fluorescence-based methodologies. We found that basal untreated BH₄ and 7,8-BH₂ concentrations in human endothelial cells (ECs) are lower than in 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, which 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 supraphysiological levels of 7,8-BH₂, indicating this reaction is kinetically limited. Activity assays verified that human DHFR 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.

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

    PubMed Central

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

    2014-01-01

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

  7. The limits of human stereopsis in space and time.

    PubMed

    Kane, David; Guan, Phillip; Banks, Martin S

    2014-01-22

    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.

  8. Limits to genetic intervention in humans: somatic and germline.

    PubMed

    Davis, B D

    1990-01-01

    The promise of somatic cell gene therapy is likely to be limited to a narrow range of monogenic hereditary defects. This therapy raises few moral issues. However, extension to the 'improvement' of a normal trait might raise problems, similar to the use of hormones in sports. Another danger is uses that result, like heroic measures to save the premature newborn, in the prolongation of misery and in intolerable expense. The genetic alteration of germline cells, which can already be accomplished in animals, is in principle applicable to all monogenic diseases. Its use in humans is much less acceptable than somatic cell therapy. The objection that it tampers with human evolution is widely cited. However, more important may be the risk of producing a new defect, for risk is much less acceptable in a yet unborn person than in an already ill individual. In addition, the goal of germline therapy could almost always be accomplished more simply and safely by prenatal diagnosis and selective abortion. The highly polygenic nature of the most interesting traits, both behavioural and physical, makes it unlikely that we shall be able to modify them usefully in the foreseeable future by either somatic or germline intervention. Despite this delivery from temptation, public fear of future 'blueprinting' of humans no doubt contributes to a multi-faceted antiscience movement.

  9. 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.

  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. Master Athletes Are Extending the Limits of Human Endurance

    PubMed Central

    Lepers, Romuald; Stapley, Paul J.

    2016-01-01

    The increased participation of master athletes (i.e., >40 years old) in endurance and ultra-endurance events (>6 h duration) over the past few decades has been accompanied by an improvement in their performances at a much faster rate than their younger counterparts. Aging does however result in a decrease in overall endurance performance. Such age-related declines in performance depend upon the modes of locomotion, event duration, and gender of the participant. For example, smaller age-related declines in cycling performance than in running and swimming have been documented. The relative stability of gender differences observed across the ages suggests that the age-related declines in physiological function did not differ between males and females. Among the main physiological determinants of endurance performance, the maximal oxygen consumption (VO2max) appears to be the parameter that is most altered by age. Exercise economy and the exercise intensity at which a high fraction of VO2max can be sustained (i.e., lactate threshold), seem to decline to a lesser extent with advancing age. The ability to maintain a high exercise-training stimulus with advancing age is emerging as the single most important means of limiting the rate of decline in endurance performance. By constantly extending the limits of (ultra)-endurance, master athletes therefore represent an important insight into the ability of humans to maintain physical performance and physiological function with advancing age. PMID:28018241

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

    PubMed

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

    2014-07-01

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

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

    PubMed

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

    2011-01-01

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

  14. 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

  15. 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.

  16. 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

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

    PubMed

    Post, S G

    1991-01-01

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

  18. 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…

  19. Limiting disproportionate disaccommodation in design for human variability.

    PubMed

    de Vries, Charlotte; Parkinson, Matthew B

    2014-01-01

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

  20. 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.

  1. [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.

  2. A Limited Number of Globin Genes in Human DNA

    PubMed Central

    Gambino, Roberto; Kacian, Daniel; O'Donnell, Joyce; Ramirez, Francesco; Marks, Paul A.; Bank, Arthur

    1974-01-01

    The number of globin genes in human cells was determined by hybridizing DNA from human spleens to 3H-labeled DNA complementary to human globin mRNA. Assuming the rates of reannealing of complementary DNA and cellular DNA are similar, the extent of hybridization of complementary DNA at various ratios of cellular DNA to complementary DNA indicate that there are fewer than 10 globin gene copies per haploid human genome. An alternative analysis of the data, which introduces no assumptions concerning the relative rates of reaction of complementary DNA and cellular DNA, indicates fewer than 20 globin gene copies are present. DNA isolated from the spleen of a patient with β+ thalassemia contained a number of globin gene copies similar to that of normal DNA. PMID:4530276

  3. 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.

  4. 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...

  5. 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...

  6. 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...

  7. 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.

  8. Gaia limits for brown dwarf studies.

    NASA Astrophysics Data System (ADS)

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

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

  9. The limits of discipline: towards interdisciplinary food studies.

    PubMed

    Wilk, Richard

    2012-11-05

    While the number of scholars working on the broad topic of food has never been greater, the topic is still divided among numerous disciplines and specialists who do not often communicate with each other. This paper discusses some of the deep differences between disciplinary approaches, and concludes that food scientists differ in some of their basic assumptions about human nature. After outlining some of the institutional issues standing in the way of interdisciplinary work, the paper argues for a more synthetic and empirical approach, grounded in the study of everyday life. True interdisciplinary collaboration will have to go beyond assembling multidisciplinary teams. Instead we must accept the limitations of the classic disciplinary paradigms, and be willing to question and test our methods and assumptions.

  10. 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.

  11. The fanconi anemia pathway limits human papillomavirus replication.

    PubMed

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

    2012-08-01

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

  12. Human exploration mission studies

    NASA Technical Reports Server (NTRS)

    Cataldo, Robert L.

    1989-01-01

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

  13. A signature of neural coding at human perceptual limits

    PubMed Central

    Bays, Paul M.

    2016-01-01

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

  14. At the Limit: Introducing Energy with Human Senses

    NASA Astrophysics Data System (ADS)

    Stinken, Lisa; Heusler, Stefan; Carmesin, Hans-Otto

    2016-12-01

    Energy belongs to the core ideas of the physics curriculum. But at the same time, energy is one of the most complex topics in science education since it occurs in multiple ways, such as motion, sound, light, and thermal energy. It can neither be destroyed nor created, but only converted. Due to the variety of relevant scales and abstractness of the term energy, the question arises how to introduce energy at the introductory physics level. The aim of this article is to demonstrate how the concept of energy can become meaningful in the context of the human senses. Three simple experiments to investigate the minimal amount of energy that is required to generate a sensory perception are presented. In this way students can learn that even different sensory perceptions can be compared by using energy as the unifying concept.

  15. 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…

  16. 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

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

    PubMed

    Fenyvesi, É; Vikmon, M; Szente, L

    2016-09-09

    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.

  18. Limitations of Reliability for Long-Endurance Human Spaceflight

    NASA Technical Reports Server (NTRS)

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

    2016-01-01

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

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

    PubMed

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

    2015-07-10

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

  20. Network model of human aging: Frailty limits and information measures

    NASA Astrophysics Data System (ADS)

    Farrell, Spencer G.; Mitnitski, Arnold B.; Rockwood, Kenneth; Rutenberg, Andrew D.

    2016-11-01

    Aging is associated with the accumulation of damage throughout a persons life. Individual health can be assessed by the Frailty Index (FI). The FI is calculated simply as the proportion f of accumulated age-related deficits relative to the total, leading to a theoretical maximum of f ≤1 . Observational studies have generally reported a much more stringent bound, with f ≤fmax<1 . The value of fmax in observational studies appears to be nonuniversal, but fmax≈0.7 is often reported. A previously developed network model of individual aging was unable to recover fmax<1 while retaining the other observed phenomenology of increasing f and mortality rates with age. We have developed a computationally accelerated network model that also allows us to tune the scale-free network exponent α . The network exponent α significantly affects the growth of mortality rates with age. However, we are only able to recover fmax by also introducing a deficit sensitivity parameter 1 -q , which is equivalent to a false-negative rate q . Our value of q =0.3 is comparable to finite sensitivities of age-related deficits with respect to mortality that are often reported in the literature. In light of nonzero q , we use mutual information I to provide a nonparametric measure of the predictive value of the FI with respect to individual mortality. We find that I is only modestly degraded by q <1 , and this degradation is mitigated when increasing number of deficits are included in the FI. We also find that the information spectrum, i.e., the mutual information of individual deficits versus connectivity, has an approximately power-law dependence that depends on the network exponent α . Mutual information I is therefore a useful tool for characterizing the network topology of aging populations.

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

    PubMed

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

    2008-10-01

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

  2. 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…

  3. 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.

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

    NASA Technical Reports Server (NTRS)

    Bishop, Phillip A.; Greenisen, Mike

    1992-01-01

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

  5. 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.

  6. Molecular characterization showed limited genetic diversity among Salmonella Enteritidis isolated from humans and animals in Malaysia.

    PubMed

    Ngoi, Soo Tein; Thong, Kwai Lin

    2013-12-01

    Salmonella enterica serovar Enteritidis (S. Enteritidis) is the most common causative agent of non-typhoidal salmonellosis in Malaysia. We aimed to characterize S. Enteritidis isolated from humans and animals by analyzing their antimicrobial resistance profiles and genotypes. A total of 111 strains were characterized using multiple-locus variable-number tandem repeat analysis, pulsed-field gel electrophoresis, and antimicrobial susceptibility testing. Both typing methods revealed that genetically similar S. Enteritidis strains had persisted among human and animal populations within the period of study (2003-2008). Only 39% of the strains were multi-drug resistant (i.e., resistant to 3 or more classes of antimicrobial agents), with a majority (73%) of these in low-risk phase (multiple antibiotic resistant index <0.20). Limited genetic diversity among clinical and zoonotic S. Enteritidis suggested that animals are possible sources of human salmonellosis. The degree of multi-drug resistance among the strains was generally low during the study period.

  7. A Dual Reporter Mouse Model of the Human β-Globin Locus: Applications and Limitations

    PubMed Central

    Papadopoulos, Petros; Gutiérrez, Laura; van der Linden, Reinier; Kong-A-San, John; Maas, Alex; Drabek, Dubravka; Patrinos, George P.; Philipsen, Sjaak; Grosveld, Frank

    2012-01-01

    The human β-globin locus contains the β-like globin genes (i.e. fetal γ-globin and adult β-globin), which heterotetramerize with α-globin subunits to form fetal or adult hemoglobin. Thalassemia is one of the commonest inherited disorders in the world, which results in quantitative defects of the globins, based on a number of genome variations found in the globin gene clusters. Hereditary persistence of fetal hemoglobin (HPFH) also caused by similar types of genomic alterations can compensate for the loss of adult hemoglobin. Understanding the regulation of the human γ-globin gene expression is a challenge for the treatment of thalassemia. A mouse model that facilitates high-throughput assays would simplify such studies. We have generated a transgenic dual reporter mouse model by tagging the γ- and β-globin genes with GFP and DsRed fluorescent proteins respectively in the endogenous human β-globin locus. Erythroid cell lines derived from this mouse model were tested for their capacity to reactivate the γ-globin gene. Here, we discuss the applications and limitations of this fluorescent reporter model to study the genetic basis of red blood cell disorders and the potential use of such model systems in high-throughput screens for hemoglobinopathies therapeutics. PMID:23272095

  8. Cyclooxygenase-2 Inhibition Limits Angiotensin II-Induced DNA Oxidation and Protein Nitration in Humans

    PubMed Central

    Pialoux, Vincent; Poulin, Marc J.; Hemmelgarn, Brenda R.; Muruve, Daniel A.; Chirico, Erica N.; Faes, Camille; Sola, Darlene Y.; Ahmed, Sofia B.

    2017-01-01

    Compared to other cyclooxygenase-2 inhibitors, celecoxib is associated with a lower cardiovascular risk, though the mechanism remains unclear. Angiotensin II is an important mediator of oxidative stress in the pathophysiology of vascular disease. Cyclooxygenase-2 may modify the effects of angiotensin II though this has never been studied in humans. The purpose of the study was to test the effects of selective cyclooxygenase-2 inhibition on plasma measures of oxidative stress, the vasoconstrictor endothelin-1, and nitric oxide metabolites, both at baseline and in respose to Angiotensin II challenge in healthy humans. Measures of 8-hydroxydeoxyguanosine, advanced oxidation protein products, nitrotyrosine, endothelin-1, and nitric oxide metabolites were assessed from plasma samples drawn at baseline and in response to graded angiotensin II infusion (3 ng/kg/min × 30 min, 6 ng/kg/min × 30 min) before and after 14 days of cyclooxygenase-2 inhibition in 14 healthy subjects (eight male, six female) in high salt balance, a state of maximal renin angiotensin system suppression. Angiotensin II infusion significantly increased plasma oxidative stress compared to baseline (8-hydroxydeoxyguanosine; +17%; advanced oxidation protein products; +16%), nitrotyrosine (+76%). Furthermore, levels of endothelin-1 levels were significantly increased (+115%) and nitric oxide metabolites were significantly decreased (−20%). Cycloxygenase-2 inhibition significantly limited the increase in 8-hydroxydeoxyguanosine, nitrotyrosine and the decrease in nitric oxide metabolites induced by angiotensin II infusion, though no changes in advanced oxidation protein products and endothelin-1 concentrations were observed. Cyclooxygenase-2 inhibition with celecoxib partially limited the angiotensin II-mediated increases in markers of oxidative stress in humans, offering a potential physiological pathway for the improved cardiovascular risk profile of this drug. PMID:28344559

  9. Challenge studies of human volunteers: ethical issues

    PubMed Central

    Hope, T; McMillan, J

    2004-01-01

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

  10. 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

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

    PubMed Central

    Stanton, Bruce A.

    2015-01-01

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

  12. 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.

  13. Limited Immunogenicity of Human Induced Pluripotent Stem Cell-Derived Cartilages

    PubMed Central

    Kimura, Takeshi; Yamashita, Akihiro; Ozono, Keiichi

    2016-01-01

    Articular cartilage damage does not spontaneously heal and could ultimately result in a loss of joint function. Damaged cartilage can be repaired with cell/tissue sources that are transplanted, however, autologous chondrocytes are limited in number as a cell source. Induced pluripotent stem cells (iPSCs) are a relatively new and abundant cell source and can be made from the patient, but at a considerable cost. Because cartilage is immunoprivileged tissue, allogeneic cartilages have been transplanted effectively without matching for human leukocyte antigen (HLA), but are difficult to acquire due to scarcity of donors. In this study, we examined the immunogenicity of human iPSC-derived cartilages (hiPS-Carts) in vitro to evaluate whether allogeneic hiPS-Carts can be a new cell/tissue source. The cells in hiPS-Carts expressed limited amounts of major histocompatibility complex (MHC) class I (HLA-ABC) and MHC class II (HLA-DRDQDP). Treatment with interferon γ (IFNγ) induced the expression of MHC class I, but not MHC class II in hiPS-Carts. A mixed lymphocyte reaction assay showed that hiPS-Carts stimulated the proliferation of neither T cells nor the activation of NK cells. Furthermore, hiPS-Carts suppressed the proliferation of T cells stimulated with interleukin 2 and phytohemagglutinin (PHA). Together with previously reported findings, these results suggest that hiPS-Carts are no more antigenic than human cartilage. Additionally, in combination with the fact that iPSCs are unlimitedly expandable and thus can supply unlimited amounts of iPS-Carts from even one iPSC line, they suggest that allogeneic hiPS-Carts are a candidate source for transplantation to treat articular cartilage damage. PMID:27762664

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

    PubMed

    Hanna, Elizabeth G; Tait, Peter W

    2015-07-15

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

  15. 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

  16. The effective rate of influenza reassortment is limited during human infection.

    PubMed

    Sobel Leonard, Ashley; McClain, Micah T; Smith, Gavin J D; Wentworth, David E; Halpin, Rebecca A; Lin, Xudong; Ransier, Amy; Stockwell, Timothy B; Das, Suman R; Gilbert, Anthony S; Lambkin-Williams, Rob; Ginsburg, Geoffrey S; Woods, Christopher W; Koelle, Katia; Illingworth, Christopher J R

    2017-02-01

    We characterise the evolutionary dynamics of influenza infection described by viral sequence data collected from two challenge studies conducted in human hosts. Viral sequence data were collected at regular intervals from infected hosts. Changes in the sequence data observed across time show that the within-host evolution of the virus was driven by the reversion of variants acquired during previous passaging of the virus. Treatment of some patients with oseltamivir on the first day of infection did not lead to the emergence of drug resistance variants in patients. Using an evolutionary model, we inferred the effective rate of reassortment between viral segments, measuring the extent to which randomly chosen viruses within the host exchange genetic material. We find strong evidence that the rate of effective reassortment is low, such that genetic associations between polymorphic loci in different segments are preserved during the course of an infection in a manner not compatible with epistasis. Combining our evidence with that of previous studies we suggest that spatial heterogeneity in the viral population may reduce the extent to which reassortment is observed. Our results do not contradict previous findings of high rates of viral reassortment in vitro and in small animal studies, but indicate that in human hosts the effective rate of reassortment may be substantially more limited.

  17. The effective rate of influenza reassortment is limited during human infection

    PubMed Central

    Sobel Leonard, Ashley; McClain, Micah T.; Wentworth, David E.; Halpin, Rebecca A.; Lin, Xudong; Ransier, Amy; Gilbert, Anthony S.; Woods, Christopher W.; Koelle, Katia

    2017-01-01

    We characterise the evolutionary dynamics of influenza infection described by viral sequence data collected from two challenge studies conducted in human hosts. Viral sequence data were collected at regular intervals from infected hosts. Changes in the sequence data observed across time show that the within-host evolution of the virus was driven by the reversion of variants acquired during previous passaging of the virus. Treatment of some patients with oseltamivir on the first day of infection did not lead to the emergence of drug resistance variants in patients. Using an evolutionary model, we inferred the effective rate of reassortment between viral segments, measuring the extent to which randomly chosen viruses within the host exchange genetic material. We find strong evidence that the rate of effective reassortment is low, such that genetic associations between polymorphic loci in different segments are preserved during the course of an infection in a manner not compatible with epistasis. Combining our evidence with that of previous studies we suggest that spatial heterogeneity in the viral population may reduce the extent to which reassortment is observed. Our results do not contradict previous findings of high rates of viral reassortment in vitro and in small animal studies, but indicate that in human hosts the effective rate of reassortment may be substantially more limited. PMID:28170438

  18. Limit velocities of lamb waves: Analytic and numerical studies

    NASA Astrophysics Data System (ADS)

    Avershieva, A. V.; Goldstein, R. V.; Kuznetsov, S. V.

    2016-09-01

    The Lamb wave propagation in elastic isotropic and orthotropic layers is studied by numerical and analytic methods. An analytic solution is obtained by using the Cauchy formalism for the entire frequency range. Numerical solutions are obtained in a neighborhood of the second limit velocity corresponding to very small frequencies. The influence of variations in the layer geometry on the dispersion curves is studied.

  19. 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

  20. Dietary bioactive peptides: Human studies.

    PubMed

    Bouglé, Dominique; Bouhallab, Saïd

    2017-01-22

    Current opinion strongly links nutrition and health. Among nutrients, proteins, and peptides which are encrypted in their sequences and released during digestion could play a key role in improving health. These peptides have been claimed to be active on a wide spectrum of biological functions or diseases, including blood pressure and metabolic risk factors (coagulation, obesity, lipoprotein metabolism, and peroxidation), gut and neurological functions, immunity, cancer, dental health, and mineral metabolism. A majority of studies involved dairy peptides, but the properties of vegetal, animal, and sea products were also assessed. However, these allegations are mainly based on in vitro and experimental studies which are seldom confirmed in humans. This review focused on molecules which were tested in humans, and on the mechanisms explaining discrepancies between experimental and human studies.

  1. 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

  2. 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

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

    SciTech Connect

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

    1994-10-01

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

  4. 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.

  5. 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.

  6. Limits for antibody affinity maturation and repertoire diversification in hypervaccinated humans.

    PubMed

    Poulsen, Tine Rugh; Jensen, Allan; Haurum, John S; Andersen, Peter S

    2011-10-15

    The immune system is known to generate a diverse panel of high-affinity Abs by adaptively improving the recognition of pathogens during ongoing immune responses. In this study, we report the biological limits for Ag-driven affinity maturation and repertoire diversification by analyzing Ab repertoires in two adult volunteers after each of three consecutive booster vaccinations with tetanus toxoid. Maturation of on-rates and off-rates occurred independently, indicating a kinetically controlled affinity maturation process. The third vaccination induced no significant changes in the distribution of somatic mutations and binding rate constants implying that the limits for affinity maturation and repertoire diversification had been reached. These fully matured Ab repertoires remained similar in size, genetically diverse, and dynamic. Somatic mutations and kinetic rate constants showed normal and log-normal distribution profiles, respectively. Mean values can therefore be considered as biological constants defining the observed boundaries. At physiological temperature, affinity maturation peaked at k(on) = 1.6 × 10(4) M(-1) s(-1) and k(off) = 1.7 × 10(-4) s(-1) leading to a maximum mean affinity of K(D) = 1.0 × 10(-9) M. At ambient temperature, the average affinity increased to K(D) = 3.4 × 10(-10) M mainly due to slower off-rates. This experimentally determined set of constants can be used as a benchmark for analysis of the maturation level of human Abs and Ab responses.

  7. 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.

  8. Evidence that calcineurin is rate-limiting for primary human lymphocyte activation.

    PubMed Central

    Batiuk, T D; Kung, L; Halloran, P F

    1997-01-01

    Cyclosporine (CsA) is both a clinical immunosuppressive drug and a probe to dissect intracellular signaling pathways. In vitro, CsA inhibits lymphocyte gene activation by inhibiting the phosphatase activity of calcineurin (CN). In clinical use, CsA treatment inhibits 50-75% of CN activity in circulating leukocytes. We modeled this degree of CN inhibition in primary human leukocytes in vitro in order to study the effect of partial CN inhibition on the downstream signaling events that lead to gene activation. In CsA-treated leukocytes stimulated by calcium ionophore, the degree of reduction in CN activity was accompanied by a similar degree of inhibition of each event tested: dephosphorylation of nuclear factor of activated T cell proteins, nuclear DNA binding, activation of a transfected reporter gene construct, IFN-gamma and IL-2 mRNA accumulation, and IFN-gamma production. Furthermore, the degree of CN inhibition was reflected by a similar degree of reduction in lymphocyte proliferation and IFN-gamma production in the allogeneic mixed lymphocyte cultures. These data support the conclusion that CN activity is rate-limiting for the activation of primary human T lymphocytes. Thus, the reduction of CN activity observed in CsA-treated patients is accompanied by a similar degree of reduction in lymphocyte gene activation, and accounts for the immunosuppression observed. PMID:9312192

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

    NASA Astrophysics Data System (ADS)

    Duan, Zhe; Qin, Qing

    2016-01-01

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

  10. Using diagnostic radiology in human evolutionary studies

    PubMed Central

    SPOOR, FRED; JEFFERY, NATHAN; ZONNEVELD, FRANS

    2000-01-01

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

  11. 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.

  12. 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.

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

    PubMed

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

    2012-10-01

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

  14. Human locomotion through a multiple obstacle environment: strategy changes as a result of visual field limitation.

    PubMed

    Jansen, Sander E M; Toet, Alexander; Werkhoven, Peter J

    2011-07-01

    This study investigated how human locomotion through an obstacle environment is influenced by visual field limitation. Participants were asked to walk at a comfortable pace to a target location while avoiding multiple vertical objects. During this task, they wore goggles restricting their visual field to small (S: 40°×25°), medium (M: 80°×60°), large (L: 115°×90°), or unlimited (U) visual field sizes. Full-body motion capture was used to extract for each trial the mean speed, pathlength, mean step width, magnitude of head rotation and head mean angular speed. The results show that compared with the U condition, the M and L conditions caused participants to select a wider path around the obstacles without slowing down or altering step width. However, the S condition did slow down the participants, and increased both their step width and path length. We conclude that only for the S condition, balancing problems were substantial enough to spend more energy associated with increased step width. In all cases, participants choose to optimize safety (collision avoidance) at the cost of spending more energy.

  15. 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.

  16. Human CD133+ Renal Progenitor Cells Induce Erythropoietin Production and Limit Fibrosis After Acute Tubular Injury

    PubMed Central

    Aggarwal, Shikhar; Grange, Cristina; Iampietro, Corinne; Camussi, Giovanni; Bussolati, Benedetta

    2016-01-01

    Persistent alterations of the renal tissue due to maladaptive repair characterize the outcome of acute kidney injury (AKI), despite a clinical recovery. Acute damage may also limit the renal production of erythropoietin, with impairment of the hemopoietic response to ischemia and possible lack of its reno-protective action. We aimed to evaluate the effect of a cell therapy using human CD133+ renal progenitor cells on maladaptive repair and fibrosis following AKI in a model of glycerol-induced rhabdomyolysis. In parallel, we evaluated the effect of CD133+ cells on erythropoietin production. Administration of CD133+ cells promoted the restoration of the renal tissue, limiting the presence of markers of injury and pro-inflammatory molecules. In addition, it promoted angiogenesis and protected against fibrosis up to day 60. No effect of dermal fibroblasts was observed. Treatment with CD133+ cells, but not with PBS or fibroblasts, limited anemia and increased erythropoietin levels both in renal tissue and in circulation. Finally, CD133+ cells contributed to the local production of erythropoietin, as observed by detection of circulating human erythropoietin. CD133+ cells appear therefore an effective source for cell repair, able to restore renal functions, including erythropoietin release, and to limit long term maldifferentiation and fibrosis. PMID:27853265

  17. Breakdown Limit Studies in High-Rate Gaseous Detectors

    NASA Technical Reports Server (NTRS)

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

    1999-01-01

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

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

    PubMed

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

    2015-08-01

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

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

    PubMed Central

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

    2015-01-01

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

  20. The limitations of case-control studies in the detection of environmental carcinogens.

    PubMed Central

    Crombie, I K

    1981-01-01

    The ability of the case-control study to detect human carcinogens has been investigated theoretically for varying fractions of the population exposed to hazards carrying different relative risks. The method is shown to be useful for the investigation of factors to which exposure is widespread (for example, common foods or beverages) but it is of limited use for the study of uncommon types of exposure, such as those associated with occupation. The case-control study is unable to detect very small relative risks (less than 1.5) even where exposure is widespread and large numbers of cases of cancer are occurring in the population. The principal limitation of the method is the maximum number of cases which can be recruited and analysed. It will only be through large-scale collaborative multicentre or international studies that important risk factors will be detected. PMID:7338704

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2015-11-01

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

  3. 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.

  4. 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

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

    PubMed

    Braks, M A H; Juliano, S A; Lounibos, L P

    2006-03-01

    Anthropophilic mosquitoes such as Aedes aegypti L. (Diptera: Culicidae) have been shown to have superior reproductive success on human blood when sugar is not available. Life-table experiments were conducted with Aedes albopictus Skuse and Ae. aegypti to compare the effects of sugar availability on age-specific survivorship, lifetime and daily fecundity, and blood-feeding frequency when offered human blood daily. There were no significant interactions between the effects of sugar availability and mosquito species for these four variables, indicating similar effects of sugar availability for both species. Lifetime fecundity was not significantly affected by sugar availability, but sugar-deprived females had significantly reduced age-specific survivorship than did sugar-fed females. In absence of sugar, females took bloodmeals twice as often, resulting in a higher daily fecundity. The results indicate that superior reproductive success on human blood without sugar does not seem to be limited to highly anthropophilic mosquito species, such as Ae. aegypti. We conclude that evolution of a highly anthropophilic feeding strategy is not an inevitable result of the ability to thrive on human blood alone.

  6. 75 FR 359 - Guidance on Simultaneous Transmission Import Limit Studies; Notice Allowing Post-Technical...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-05

    ... on Simultaneous Transmission Import Limit Studies; Notice Allowing Post-Technical Conference Comments... Simultaneous Transmission Import Limit (SIL) studies. All interested persons are invited to file...

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

    NASA Astrophysics Data System (ADS)

    Lemu, H. G.

    2012-04-01

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

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

    PubMed

    Lundy, P

    1996-02-01

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

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

    PubMed Central

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

    2016-01-01

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

  10. 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

  11. 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.

  12. Nitrogen limited biobarriers remove atrazine from contaminated water: laboratory studies.

    PubMed

    Hunter, William J; Shaner, Dale L

    2009-01-07

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

  13. 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

  14. 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.

  15. Studies on Human Platelet Gangliosides

    PubMed Central

    Marcus, Aaron J.; Ullman, Harris L.; Safier, Lenore B.

    1972-01-01

    Gangliosides, glycosphingolipids which contain sialic acid, were studied in human platelets. They represented 0.5% of the platelet lipids and accounted for 6% of the total neuraminic acid content of platelets. Three major ganglioside fractions were identified and characterized. Ganglioside I was hematoside (G6) and comprised 92% of the platelet gangliosides. It contained glucose, galactose, and sialic acid in molar ratios of 1:1:1 and no hexosamine. The major fatty acid was behenate (22:0). Ganglioside I was also identified in isolated platelet granules and membranes. Ganglioside II (5%) contained glucose, galactose, sialic acid, and hexosamines (molar ratios 1:2:1:1). The hexosamines were glucosamine (72%) and galactosamine (28%). It was therefore designated as ganglioside lacto-N-neotetraose. Ganglioside III (2%) contained disialosyllactosyl ceramide (G3A) as well as two other gangliosides which could not be precisely characterized. Gangliosides I, II, and III were susceptible to the action of Clostridium perfringens neuraminidase as evidenced by full recovery of sialic acid in its free form after incubation. Neutral platelet glycolipids were qualitatively examined by thin-layer chromatography. The major component was lactosyl ceramide. Interactions of gangliosides I and III and serotonin-14C were examined in an equilibrium dialysis system at 4°C. The gangliosides bound serotonin-14C in relatively small quantities, whereas control lipids were negative. The binding was essentially unchanged by reverse dialysis, ultracentrifugation and subsequent thin-layer chromatography. The results are comparable to the previously observed nonmetabolic interactions between whole platelets and serotonin in the cold. It is suggested that the orientation and specific distribution of platelet membrane glycolipids may be important determinants of the unique surface properties of platelets. Images PMID:4341436

  16. 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.

  17. 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

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

    PubMed

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

    2015-06-20

    Human chorionic gonadotropin (hCG) is a glycoprotein hormone that exists as a heterodimer with a 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.

  19. Study of Limited-view Tomography Algorithms for Plasma Diagnostics

    NASA Astrophysics Data System (ADS)

    Wan, Xiong; Gao, Yiqing; Yu, Shenglin

    2002-09-01

    Optical Computed Tomography is a useful tool for plasma diagnostics. But in plasma physics, viewing access is very limited, which leads a highly undetermined inversion problem. Two major approaches to this problem are compared in this paper: Maximum Entropy (ME) method and Simultaneous Iterative Reconstruction Technique (SIRT). The results of numerical simulation and experiments illustrate that both two algorithms can yield good qualities of reconstruction with limited views when some prior information has incorporated into calculation. Especially, in the case of two views, with prior information, a good result can even be achieved by ME algorithm.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    ERIC Educational Resources Information Center

    Romm, Joseph

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

  2. Fetal tolerance in human pregnancy--a crucial balance between acceptance and limitation of trophoblast invasion.

    PubMed

    von Rango, Ulrike

    2008-01-15

    During human pregnancy the semi-allogeneic/allogeneic fetal graft is normally accepted by the mother's immune system. Initially the contact between maternal and fetal cells is restricted to the decidua but during the 2nd trimester it is extended to the entire body. Two contrary requirements influence the extent of invasion of extravillous fetal trophoblast cells (EVT) in the maternal decidua: anchorage of the placenta to ensure fetal nutrition and protection of the uterine wall against over-invasion. To establish the crucial balance between tolerance of the EVT and its limitation, recognition of the semi-allogeneic/allogeneic fetal cell by maternal leukocytes is prerequisite. A key mechanism to limit EVT invasion is induction of EVT apoptosis. Apoptotic bodies are phagocytosed by antigen-presenting cells (APC). Peptides from apoptotic cells are presented by APC cells and induce an antigen-specific tolerance against the foreign antigens on EVT cells. These pathways, including up-regulation of the expression of IDO, IFNgamma and CTLA-4 as well as the induction of T(regulatory) cells, are general immunological mechanisms which have developed to maintain peripheral tolerance to self-antigens. Together these data suggest that the mother extends her "definition of self" for 9 months on the foreign antigens of the fetus.

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

    PubMed

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

    2011-07-06

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

  4. Expanding the Limits of Human Blood Metabolite Quantitation Using NMR Spectroscopy

    PubMed Central

    2015-01-01

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

  5. 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

  6. Limited transmission of bla(CTX-M-9)-type-positive Escherichia coli between humans and poultry in Vietnam.

    PubMed

    Ueda, Shuhei; Ngan, Bui Thi Kim; Huong, Bui Thi Mai; Hirai, Itaru; Tuyen, Le Danh; Yamamoto, Yoshimasa

    2015-01-01

    We examined whether Escherichia coli isolates that produce CTX-M-9-type extended-spectrum β-lactamases (ESBL) are transferred between humans and chickens in a Vietnamese community. The phylogenetic group compositions, sequence types, antimicrobial resistance profiles, the prevalence of plasmid antibiotic resistance genes, and the plasmid replicon types generally differed between the human and chicken E. coli isolates. Our results suggest that transmission of the bla(CTX-M-9)-positive E. coli between humans and poultry was limited.

  7. Air Sanctuaries in Limited War: A Korean War Case Study.

    DTIC Science & Technology

    1986-03-01

    these restrictions, however, FEAF managed to maintain air superiority throughout Korea for the duration of the war. It routinely bombed North Korean air...and National Policy. Vol III, The Korean War, part 2. Washington, Mar 1979. 555p. PERIODICALS Foot, Rosemary. The Sino American Conflict in Korea : The...A07 844 AlR SANCTUARIES IN LIMITED WAR. A KOREAN WAR CASE STWJY i/I (UJ) AIR WAR COLL MAXMd LL AFB AL C M HINKLE MAR 8 AUJ-AWC-86-898

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

    PubMed Central

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

    2016-01-01

    Abstract 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 chainnull (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

  9. 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.

  10. Lactational Stage of Pasteurized Human Donor Milk Contributes to Nutrient Limitations for Infants

    PubMed Central

    Valentine, Christina J.; Morrow, Georgia; Reisinger, Amanda; Dingess, Kelly A.; Morrow, Ardythe L.; Rogers, Lynette K.

    2017-01-01

    Background. Mother’s own milk is the first choice for feeding preterm infants, but when not available, pasteurized human donor milk (PDM) is often used. Infants fed PDM have difficulties maintaining appropriate growth velocities. To assess the most basic elements of nutrition, we tested the hypotheses that fatty acid and amino acid composition of PDM is highly variable and standard pooling practices attenuate variability; however, total nutrients may be limiting without supplementation due to late lactational stage of the milk. Methods. A prospective cross-sectional sampling of milk was obtained from five donor milk banks located in Ohio, Michigan, Colorado, Texas-Ft Worth, and California. Milk samples were collected after Institutional Review Board (#07-0035) approval and informed consent. Fatty acid and amino acid contents were measured in milk from individual donors and donor pools (pooled per Human Milk Banking Association of North America guidelines). Statistical comparisons were performed using Kruskal–Wallis, Spearman’s, or Multivariate Regression analyses with center as the fixed factor and lactational stage as co-variate. Results. Ten of the fourteen fatty acids and seventeen of the nineteen amino acids analyzed differed across Banks in the individual milk samples. Pooling minimized these differences in amino acid and fatty acid contents. Concentrations of lysine and docosahexaenoic acid (DHA) were not different across Banks, but concentrations were low compared to recommended levels. Conclusions. Individual donor milk fatty acid and amino acid contents are highly variable. Standardized pooling practice reduces this variability. Lysine and DHA concentrations were consistently low across geographic regions in North America due to lactational stage of the milk, and thus not adequately addressed by pooling. Targeted supplementation is needed to optimize PDM, especially for the preterm or volume restricted infant. PMID:28335478

  11. 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…

  12. 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.

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

    PubMed

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

    2015-06-01

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

  14. 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

  15. 78 FR 76888 - MAP-21 Comprehensive Truck Size and Weight Limits Study Materials

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-19

    ... Federal Highway Administration MAP-21 Comprehensive Truck Size and Weight Limits Study Materials AGENCY... for Progress in the 21st Century Act (MAP-21) Comprehensive Truck Size and Weight Limits Study, which... public meetings on the MAP-21 Comprehensive Truck Size and Weight Limits Study and to announce...

  16. Glutamine pretreatment reduces IL-8 production in human intestinal epithelial cells by limiting IkappaBalpha ubiquitination.

    PubMed

    Hubert-Buron, Aurélie; Leblond, Jonathan; Jacquot, Arnaud; Ducrotté, Philippe; Déchelotte, Pierre; Coëffier, Moïse

    2006-06-01

    Glutamine, the most abundant amino acid in the human body, plays several important roles in the intestine. Recent studies showed that glutamine regulates protein metabolism and intestinal inflammation among other mechanisms by reducing proinflammatory cytokine release. Because regulation of the inflammatory response was shown to be linked to proteolysis regulation, we hypothesized that glutamine pretreatment could act on IL-8 production in human intestinal epithelial cells through the regulation of inhibitor kappaB (IkappaB) ubiquitination. The HCT-8 cells were pretreated for 24 h with 0.6, 2, or 10 mmol/L glutamine. IL-8 concentration and IkappaB (free and ubiquitinated) expressions were assessed by ELISA and immunoblotting, respectively. A pretreatment with 10 mmol/L glutamine decreased IL-8 production under both basal and proinflammatory conditions (both P < 0.05). In the presence of a proteasome inhibitor (MG132), the ubiquitin-IkappaBalpha complex expression was not significantly modified by glutamine under basal conditions but decreased significantly under proinflammatory conditions (P < 0.05). After the addition of 10 mmol/L of glutamine, the free IkappaBalpha expression increased under basal and stimulated conditions (both P < 0.05). A glutamine pretreatment of 10 mmol/L did not affect ubiquitin expression or proteasome activity. This study indicates that glutamine pretreatment may reduce the intestinal inflammatory response by limiting the proteolysis of IkappaBalpha.

  17. 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

  18. 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

  19. 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...

  20. 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.

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

    NASA Technical Reports Server (NTRS)

    Premkumar, R. I.

    1988-01-01

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

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

    PubMed

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

    2015-04-17

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

  4. 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

  5. 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

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

    PubMed Central

    Wakeling, James M.

    2015-01-01

    This study investigated the influence of cycle frequency and workload on muscle coordination and the ensuing relationship with mechanical efficiency and power output of human limb movement. Eleven trained cyclists completed an array of cycle frequency (cadence)-power output conditions while excitation from 10 leg muscles and power output were recorded. Mechanical efficiency was maximized at increasing cadences for increasing power outputs and corresponded to muscle coordination and muscle fiber type recruitment that minimized both the total muscle excitation across all muscles and the ineffective pedal forces. Also, maximum efficiency was characterized by muscle coordination at the top and bottom of the pedal cycle and progressive excitation through the uniarticulate knee, hip, and ankle muscles. Inefficiencies were characterized by excessive excitation of biarticulate muscles and larger duty cycles. Power output and efficiency were limited by the duration of muscle excitation beyond a critical cadence (120–140 rpm), with larger duty cycles and disproportionate increases in muscle excitation suggesting deteriorating muscle coordination and limitations of the activation-deactivation capabilities. Most muscles displayed systematic phase shifts of the muscle excitation relative to the pedal cycle that were dependent on cadence and, to a lesser extent, power output. Phase shifts were different for each muscle, thereby altering their mechanical contribution to the pedaling action. This study shows that muscle coordination is a key determinant of mechanical efficiency and power output of limb movement across a wide range of mechanical demands and that the excitation and coordination of the muscles is limited at very high cycle frequencies. PMID:26445873

  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. Aging in mouse and human systems: a comparative study.

    PubMed

    Demetrius, Lloyd

    2006-05-01

    This article discusses the significance of mouse models as a basis for elucidating the aging process in humans. We identify certain parallels between mouse and human systems and review the theoretical and empirical support for the claim that the large divergence in the rate of aging between the two species resides in differences in the stability of their metabolic networks. We will show that these differences in metabolic stability have their origin in the different ecological constraints the species experience during their evolutionary history. We exploit these ideas to compare the effect of caloric restriction on murine and human systems. The studies predict that the large increases in mean life span and maximum life-span potential observed in laboratory rodents subject to caloric restriction will not obtain in human populations. We predict that, in view of the different metabolic stability of the two systems, caloric restriction will have no effect on the maximum life-span potential of humans, and a relatively minor effect on the mean life span of nonobese populations. This article thus points to certain intrinsic limitations in the use of mouse models in elucidating the aging process in humans. We furthermore contend the view that these limitations can be mitigated by considering the metabolic stability of the two species.

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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...

  15. Equilibrium intakes of calcium and magnesium within an adequate and limited range of sodium intake in human.

    PubMed

    Nishimuta, Mamoru; Kodama, Naoko; Morikuni, Eiko; Yoshioka, Yayoi H; Matsuzaki, Nobue; Takeyama, Hidemaro; Yamada, Hideaki; Kitajima, Hideaki

    2006-12-01

    In the previous analysis of our human mineral balance studies, we demonstrated positive correlations between the balances of calcium (Ca) and magnesium (Mg) and sodium (Na) intake in the range of 3.06 and 4.06 g/d or 43.71 and 96.40 mg/kg body weight (BW)/d, but there was no correlation between Na intake and Na balance. This suggested that the balances of Ca and Mg are affected by Na intake. Therefore, in the current study, we recalculated equilibrium intakes for Ca and Mg when balances of their intakes and outputs were equal to zero within the above Na range to reduce the effects of Na intake. From 1986 to 2000, 90 volunteers (10 male, 80 female; age 18 to 28 y) took part in 9 mineral balance studies. The balance periods ranged from 8 to 12 d, with adaptation periods of 2 to 4 d. The dietary intakes of Ca and Mg ranged from 294 to 719 and 154 to 334 mg/d, or from 4.83 to 15.07 and 2.44 to 6.42 mg/kg BW/d, respectively. Intake of Ca significantly correlated with Ca balance (r2 = 0.268; p < 0.0001). When the balance was equal to zero, the mean value and upper limit of the 95% confidence interval for the regression equation between intake vs. balance were 10.072 and 10.660 mg/kg BW/d, respectively. Mg intake correlated significantly with Mg balance (r2 = 0.141, p = 0.003). When the balance was equal to zero, the mean value and upper limit of the 95% confidence interval for the regression equation between intake and balance were 4.078 and 4.287 mg/kg BW/d, respectively.

  16. Natural experiments to study the effects of early experience: progress and limitations.

    PubMed

    O'Connor, Thomas G

    2003-01-01

    Questions concerning the long-term effects of early experience on psychological development in humans continue to stir up controversy. There are, at present, great diversity and contradictions among extant conceptual models and inadequate data to resolve these differences. Limited opportunities to use experimental approaches and the inherent restrictions of observational approaches in research on humans implies that alternative research designs are needed. This article examines the use of "natural experiments" as a method for testing hypotheses concerning the effects of early experience on psychological development. The benefits and limitations of using natural experiments are reviewed and several case illustrations are considered.

  17. 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.

  18. Substrate availability limits human skeletal muscle oxidative ATP regeneration at the onset of ischemic exercise.

    PubMed Central

    Timmons, J A; Gustafsson, T; Sundberg, C J; Jansson, E; Hultman, E; Kaijser, L; Chwalbinska-Moneta, J; Constantin-Teodosiu, D; Macdonald, I A; Greenhaff, P L

    1998-01-01

    We have demonstrated previously that dichloroacetate can attenuate skeletal muscle fatigue by up to 35% in a canine model of peripheral ischemia (Timmons, J.A., S.M. Poucher, D. Constantin-Teodosiu, V. Worrall, I.A. Macdonald, and P.L. Greenhaff. 1996. J. Clin. Invest. 97:879-883). This was thought to be a consequence of dichloroacetate increasing acetyl group availability early during contraction. In this study we characterized the metabolic effects of dichloroacetate in a human model of peripheral muscle ischemia. On two separate occasions (control-saline or dichloroacetate infusion), nine subjects performed 8 min of single-leg knee extension exercise at an intensity aimed at achieving volitional exhaustion in approximately 8 min. During exercise each subject's lower limbs were exposed to 50 mmHg of positive pressure, which reduces blood flow by approximately 20%. Dichloroacetate increased resting muscle pyruvate dehydrogenase complex activation status by threefold and elevated acetylcarnitine concentration by fivefold. After 3 min of exercise, phosphocreatine degradation and lactate accumulation were both reduced by approximately 50% after dichloroacetate pretreatment, when compared with control conditions. However, after 8 min of exercise no differences existed between treatments. Therefore, it would appear that dichloroacetate can delay the accumulation of metabolites which lead to the development of skeletal muscle fatigue during ischemia but does not alter the metabolic profile when a maximal effort is approached. PMID:9421469

  19. 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

  20. Denervated muscles in humans: limitations and problems of currently used functional electrical stimulation training protocols.

    PubMed

    Kern, Helmut; Hofer, Christian; Mödlin, Michaela; Forstner, Claudia; Raschka-Högler, Doris; Mayr, Winfried; Stöhr, Hans

    2002-03-01

    Prior clinical work showed that electrical stimulation therapy with exponential current is able to slow down atrophy and maintain the muscle during nonpermanent flaccid paralysis. However, exponential currents are not sufficient for long-term therapy of denervated degenerated muscles (DDMs). We initiated a European research project investigating the rehabilitation strategies in humans, but also studying the underlying basic scientific knowledge of muscle regeneration from satellite cells or myoblast activity in animal experiments. In our prior study, we were able to show that high-intensity stimulation of DDMs is possible. At the beginning of training, only single muscle twitches can be elicited by biphasic pulses with durations of 120-150 ms. Later, tetanic contraction of the muscle with special stimulation parameters (pulse duration of 30-50 ms, stimulation frequency of 16-25 Hz, pulse amplitudes of up to 250 mA) can improve the structural and metabolic state of the DDMs. Because there are no nerve endings for conduction of stimuli, large-size, anatomically shaped electrodes are used. This ensures an even contraction of the whole muscle. Contrary to the current clinical knowledge, we were able to stimulate and train denervated muscle 15-20 years after denervation. The estimated amount of muscle fibers that have to be restored is about 2-4 million fibers in each m. quadriceps. To rebuild such a large number of muscle fibers takes up to 3-4 years. Despite constant stimulation parameters and training protocols, there is a high variation in the developed contraction force and fatigue resistance of the muscle during the first years of functional electrical stimulation.

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

    PubMed

    Vermeij, Geerat J

    2012-07-01

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

  2. Rapid increase in human life expectancy: will it soon be limited by the aging of elastin?

    PubMed

    Robert, L; Robert, A M; Fülöp, T

    2008-04-01

    The postponement of the most frequent age-related diseases stimulated speculations of the possibility of "dying of old age". The selective decline of individual physiological functions-aging in spare-parts-indicates however the potential limitation of the life-span by the rapid decline of some of the vital parameters. We explored a possibility of such a limitation of maximal life-span by the age-related alteration of elastin, consisting in Ca-accumulation, lipid deposition and elastolytic degradation. The quantitative evaluation of these processes suggests an approximative upper limit for the elastic properties of the cardio-respiratory system of about 100-120 years, at least, as far as elastin is involved. This process, age-related alterations of elastic fibers, is however not the only one limiting the functional value of the cardiovascular system. Crosslinking of collagen fibers by advanced glycation end-products certainly contributes also to the age-dependent rigidification of the cardiovascular system. Therefore the answer to the initial question, can age-dependent alterations of a single matrix macromolecule be limiting such vital functions as the cardio-respiratory system-is a cautious yes, with however the caveat that other, independent mechanisms, such as the Maillard reaction, can also interfere with and limit further the functional value of such vital physiological functions.

  3. A model-based method for flow limitation analysis in the heterogeneous human lung.

    PubMed

    Polak, Adam G

    2008-02-01

    Flow limitation in the airways is a fundamental process constituting the maximal expiratory flow-volume curve. Its location is referred to as the choke point. In this work, expressions enabling the calculation of critical flows in the case of wave-speed, turbulent or viscous limitation were derived. Then a computational model for the forced expiration from the heterogeneous lung was used to analyse the regime and degree of flow limitation as well as movement and arrangement of the choke points. The conclusion is that flow limitation begins at similar time in every branch of the bronchial tree developing a parallel arrangement of the choke points. A serial configuration of flow-limiting sites is possible for short time periods in the case of increased airway heterogeneity. The most probable locations of choke points are the regions of airway junctions. The wave-speed mechanism is responsible for flow choking over most of vital capacity and viscous dissipation of pressure for the last part of the test. Turbulent dissipation, however, may play a significant role as a supporting factor in transition between wave-speed and viscous flow limitation.

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

    PubMed

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

    2004-07-29

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

  5. 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

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

    PubMed

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

    2014-07-01

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

  7. 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

  8. 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.

  9. 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

  10. Genomic approaches to studying the human microbiota

    PubMed Central

    Weinstock, George M.

    2013-01-01

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

  11. 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.

  12. 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.

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

    PubMed

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

    2014-01-01

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

  14. [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.

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

    PubMed Central

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

    Bessant, Judith

    2009-01-01

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

  17. 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...

  18. 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…

  19. 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.

  20. Collaborative study to establish human immunoglobulin BRP batch 3 and human immunoglobulin (molecular size) BRP batch 1.

    PubMed

    Sandberg, E; Daas, A; Behr-Gross, M-E

    2006-11-01

    A study was carried out by the European Directorate for the Quality of Medicines (EDQM) as part of the joint Biological Standardisation Programme of the Council of Europe and the European Commission with the aim to establish replacement batches of the European Pharmacopoeia (Ph. Eur.) human immunoglobulin Biological Reference Preparation (BRP) batch 2. Twenty-eight laboratories participated in this study. The suitability of the candidate reference preparations to serve as working references in the tests for distribution of the molecular size, anticomplementary activity and Fc function, in accordance with the specifications of the Ph. Eur. monographs Human normal immunoglobulin for intravenous administration (0918), Human normal immunoglobulin (0338) and Anti-T lymphocyte immunoglobulin for human use, animal (1928) was demonstrated. The candidates were therefore established as human immunoglobulin BRP batch 3 and Human immunoglobulin (molecular size) BRP batch 1. The prescribed use of the latter BRP is limited to the test for distribution of molecular size.

  1. 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

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

    USGS Publications Warehouse

    Cobb, Ernest D.

    1986-01-01

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

  3. Microdosing studies in humans: the role of positron emission tomography.

    PubMed

    Bauer, Martin; Wagner, Claudia Christina; Langer, Oliver

    2008-01-01

    Positron emission tomography (PET)-microdosing comprises the administration of a carbon-11- or fluorine-18-labelled drug candidate to human subjects in order to describe the drug's concentration-time profile in body tissues targeted for treatment. As PET microdosing involves the administration of only microgram amounts of unlabelled drug, the potential toxicological risk to human subjects is very limited. Consequently, regulatory authorities require reduced preclinical safety testing as compared with conventional phase 1 studies. Microdose studies are gaining increasing importance in clinical drug research as they have the potential to shorten time-lines and cut costs along the critical path of drug development. Current applications of PET in anticancer, anti-infective and CNS system drug research are reviewed.

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

    PubMed

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

    2014-06-26

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

  5. Monoamine oxidase: Radiotracer chemistry and human studies

    DOE PAGES

    Fowler, Joanna S.; Logan, Jean; Shumay, Elena; ...

    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

  6. 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.

  7. Monitoring antiretroviral therapy in resource-limited settings: balancing clinical care, technology, and human resources.

    PubMed

    Hosseinipour, Mina C; Schechter, Mauro

    2010-08-01

    Due to the rapid expansion of first-line antiretroviral therapy in resource-limited settings (RLS), increasing numbers of people are living with HIV for prolonged periods of time. Treatment programs must now decide how to balance monitoring costs necessary to maximize health benefits for those already on treatment with the continued demand to initiate more patients on first-line treatment. We review currently available evidence related to monitoring strategies in RLS and discuss their implications on timing of switching to second-line treatment, development of HIV resistance, and clinical outcome.

  8. [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.

  9. Mechanisms of interaction of laser radiation with ocular tissues: implications for human exposure limits

    NASA Astrophysics Data System (ADS)

    Sliney, D. H.

    1981-12-01

    Many investigations of laser injury to the eye have been carried out over the past 15 years in order to set standards for safe exposure of the human eye to laser radiation. A review of this extensive body of mainly experimental data suggests that there are at least three dominant mechanisms of injury which are well accepted. However, other effects cannot be ruled out. In particular, several results suggest that the time evolution of injury and repair processes as well as the physical aspects of the interaction of biological tissue with optical radiation must be considered.

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

    ERIC Educational Resources Information Center

    Reynolds, Jack; And Others

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

  11. 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

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

    PubMed Central

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

    2013-01-01

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

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

    EPA Science Inventory

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

  14. 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

  15. Microdosing for early biokinetic studies in humans.

    PubMed

    Stenström, K; Sydoff, M; Mattsson, S

    2010-01-01

    Microdosing is a new concept in drug development that--if implemented in the pharmaceutical industry--would mean that new drugs can be tested earlier in humans than done today. The human microdosing concept--or 'Phase 0'--may offer improved candidate selection, reduced failure rates in the drug development line and a reduction in the use of laboratory animals in early drug development, factors which will help to speed up drug development and also reduce the costs. Microdosing utilises sub-pharmacological amounts of the substance to open opportunities for early studies in man. Three technologies are used for microdosing: accelerator mass spectrometry (AMS), positron emission tomography and liquid chromatography-tandem mass spectrometry. This paper focuses on the principle of AMS and discusses the current status of microdosing with AMS.

  16. Experimental studies of the charge limit phenomenon in GaAs photocathodes

    SciTech Connect

    Tang, H.; Alley, R.; Aoyagi, H.; Clendenin, J.; Saez, P.; Schultz, D.; Turner, J.

    1993-10-01

    GaAs photocathodes have been in use for generating high intensity polarized electron beams (up to a peak current of 6 A in 2 ns pulses) for the SLC high energy physics program. If the quantum efficiency (measured at low light intensities) of a GaAs photocathode is below a certain level, the maximum photoemitted charge is found to be limited by the intrinsic properties of the cathode instead of by the space charge limit. We have studied this charge limit phenomenon in a variety of GaAs photocathodes. The effects of the quantum efficiency, excitation laser wavelength, and extraction electric field on the charge limit have been examined. The temporal behavior of the charge limit as manifested in both intrapulse and interpulse effects has also been studied. These results will be discussed in light of possible mechanisms.

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

    PubMed

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

    2007-02-01

    In healthy subjects expiratory flow limitation (EFL) during exercise can lower O(2) delivery to the working muscles. We hypothesized that if this affects exercise performance it should influence O(2) kinetics at the end of exercise when the O(2) debt is repaid. We performed an incremental exercise test on six healthy males with a Starling resistor in the expiratory line limiting expiratory flow to approximately 1 l s(-1) to determine maximal EFL exercise workload (W (max)). In two more square-wave exercise runs subjects exercised with and without EFL at W (max) for 6 min, while measuring arterial O(2) saturation (% SaO(2)), end-tidal pressure of CO(2) (P (ET)CO(2)) and breath-by-breath O(2) consumption VO2 taking into account changes in O(2) stored in the lungs. Over the last minute of EFL exercise, mean P (ET)CO(2) (54.7 +/- 9.9 mmHg) was significantly higher (P < 0.05) compared to control (41.4 +/- 3.9 mmHg). At the end of EFL exercise %SaO(2) fell significantly by 4 +/- 3%. When exercise stopped, EFL was removed, and we continued to measure VO2. During recovery, there was an immediate step increase in [Formula: see text] so that repayment of EFL O(2) debt started at a higher VO2 than control. Recovery VO2 kinetics after EFL exercise was best characterized by a double-exponential function with fundamental and slow time constants of 27 +/- 11 and 1,020 +/- 305 s, compared to control values of 41 +/- 10 and 1,358 +/- 320 s, respectively. EFL O(2) debt was 52 +/- 22% greater than control (2.19 +/- 0.58 vs. 1.49 +/- 0.38 l). We conclude that EFL exercise increases the O(2) debt and leads to hypoxemia in part due to hypercapnia.

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

    PubMed

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

    2013-06-01

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

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

    PubMed

    Lane, Robert

    2006-06-01

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

  20. Endotoxin responsiveness of human airway epithelia is limited by low expression of MD-2.

    PubMed

    Jia, Hong Peng; Kline, Joel N; Penisten, Andrea; Apicella, Michael A; Gioannini, Theresa L; Weiss, Jerrold; McCray, Paul B

    2004-08-01

    The expression of inducible antimicrobial peptides, such as human beta-defensin-2 (HBD-2) by epithelia, comprises a component of innate pulmonary defenses. We hypothesized that HBD-2 induction in airway epithelia is linked to pattern recognition receptors such as the Toll-like receptors (TLRs). We found that primary cultures of well-differentiated human airway epithelia express the mRNA for TLR-4, but little or no MD-2 mRNA, and display little HBD-2 expression in response to treatment with purified endotoxin +/- LPS binding protein (LBP) and soluble CD14. Expression of endogenous MD-2 by transduction of airway epithelial cells with an adenoviral vector encoding MD-2 or extracellular addition of recombinant MD-2 both increased the responses of airway epithelia to endotoxin + LBP and sCD14 by >100-fold, as measured by NF-kappaB-luciferase activity and HBD-2 mRNA expression. MD-2 mRNA could be induced in airway epithelia by exposure of these cells to specific bacterial or host products (e.g., killed Haemophilus influenzae, the P6 outer membrane protein from H. influenzae, or TNF-alpha + IFN-gamma). These findings suggest that MD-2, either coexpressed with TLR-4 or secreted when produced in excess of TLR-4 from neighboring cells, is required for airway epithelia to respond sensitively to endotoxin. The regulation of MD-2 expression in airway epithelia and pulmonary macrophages may serve as a means to modify endotoxin responsiveness in the airway.

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

    PubMed

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

    2013-07-01

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

  2. 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.

  3. A critical review of biomarkers used for monitoring human exposure to lead: advantages, limitations, and future needs.

    PubMed

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

    2005-12-01

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

  4. 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.

  5. 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.

  6. 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

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

    SciTech Connect

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

    2011-03-04

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

  8. 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.

  9. 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…

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

    PubMed

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

    2015-09-01

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

  11. Integrative genomic analysis implicates limited peripheral adipose storage capacity in the pathogenesis of human insulin resistance.

    PubMed

    Lotta, Luca A; Gulati, Pawan; Day, Felix R; Payne, Felicity; Ongen, Halit; van de Bunt, Martijn; Gaulton, Kyle J; Eicher, John D; Sharp, Stephen J; Luan, Jian'an; De Lucia Rolfe, Emanuella; Stewart, Isobel D; Wheeler, Eleanor; Willems, Sara M; Adams, Claire; Yaghootkar, Hanieh; Forouhi, Nita G; Khaw, Kay-Tee; Johnson, Andrew D; Semple, Robert K; Frayling, Timothy; Perry, John R B; Dermitzakis, Emmanouil; McCarthy, Mark I; Barroso, Inês; Wareham, Nicholas J; Savage, David B; Langenberg, Claudia; O'Rahilly, Stephen; Scott, Robert A

    2017-01-01

    Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.

  12. Testing paradigm for prediction of development-limiting barriers and human drug toxicity.

    PubMed

    Sasseville, V G; Lane, J H; Kadambi, V J; Bouchard, P; Lee, F W; Balani, S K; Miwa, G T; Smith, P F; Alden, C L

    2004-11-01

    The financial investment grows exponentially as a new chemical entity advances through each stage of discovery and development. The opportunity exists for the modern toxicologist to significantly impact expenditures by the early prediction of potential toxicity/side effect barriers to development by aggressive evaluation of development-limiting liabilities early in drug discovery. Improved efficiency in pharmaceutical research and development lies both in leveraging "best in class" technology and integration with pharmacologic activities during hit-to-lead and early lead optimization stages. To meet this challenge, a discovery assay by stage (DABS) paradigm should be adopted. The DABS clearly delineates to discovery project teams the timing and type of assay required for advancement of compounds to each subsequent level of discovery and development. An integrative core pathology function unifying Drug Safety Evaluation, Molecular Technologies and Clinical Research groups that effectively spans all phases of drug discovery and development is encouraged to drive the DABS. The ultimate goal of such improved efficiency being the accurate prediction of toxicity and side effects that would occur in development before commitment of the large prerequisite resource. Good justification of this approach is that every reduction of development attrition by 10% results in an estimated increase in net present value by $100 million.

  13. Human Immunodeficiency Virus and Leprosy Coinfection: Challenges in Resource-Limited Setups

    PubMed Central

    Kwobah, Charles M.; Wools-Kaloustian, Kara K.; Gitau, Jane N.; Siika, Abraham M.

    2012-01-01

    Mycobacteria leprae(leprosy) and HIV coinfection are rare in Kenya. This is likely related to the low prevalence (1 per 10,000 of population) of leprosy. Because leprosy is no longer a public health challenge there is generally a low index of suspicion amongst clinicians for its diagnosis. Management of a HIV-1-leprosy-coinfected individual in a resource-constrained setting is challenging. Some of these challenges include difficulties in establishing a diagnosis of leprosy; the high pill burden of cotreatment with both antileprosy and antiretroviral drugs (ARVs); medications' side effects; drug interactions; scarcity of drug choices for both diseases. This challenge is more profound when managing a patient who requires second-line antiretroviral therapy (ART). We present an adult male patient coinfected with HIV and leprosy, who failed first-line antiretroviral therapy (ART) and required second-line treatment. Due to limited choices in antileprosy drugs available, the patient received monthly rifampicin and daily lopinavir-/ritonavir-based antileprosy and ART regimens, respectively. Six months into his cotreatment, he seemed to have adequate virological control. This case report highlights the challenges of managing such a patient. PMID:22649458

  14. 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.

  15. Experimental studies of the charge limit phenomenon in NEA GaAs photocathodes

    SciTech Connect

    Tang, H.; Alley, R.K.; Aoyagi, H.; Clendenin, J.E.; Frisch, J.C.; Mulhollan, G.A.; Saez, P.J.; Schultz, D.C.; Turner, J.L.

    1994-06-01

    Negative electron affinity GaAs photocathodes have been in continuous use at SLAC for generating polarized electron beams since early 1992. If the quantum efficiency of a GaAs cathode is below a critical value, the maximum photoemitted charge with photons of energies close to the band gap in a 2-ns pulse is found to be limited by the intrinsic properties of the cathode instead of by the space charge limit. We have studied this novel charge limit phenomenon in a variety of GaAs photocathodes of different structures and doping densities. We find that the charge limit is strongly dependent on the cathode`s quantum efficiency and the extraction electric field, and to a lesser degree on the excitation laser wavelength. In addition, we show that the temporal behavior of the charge limit depends critically on the doping density.

  16. Influence of expiratory flow-limitation during exercise on systemic oxygen delivery in humans.

    PubMed

    Aliverti, A; Dellacà, R L; Lotti, P; Bertini, S; Duranti, R; Scano, G; Heyman, J; Lo Mauro, A; Pedotti, A; Macklem, P T

    2005-10-01

    To determine the effects of exercise with expiratory flow-limitation (EFL) on systemic O(2) delivery, seven normal subjects performed incremental exercise with and without EFL at approximately 0.8 l s(-1) (imposed by a Starling resistor in the expiratory line) to determine maximal power output under control (W'(max,c)) and EFL (W'(max,e)) conditions. W'(max,e) was 62.5% of W'(max,c), and EFL exercise caused a significant fall in the ventilatory threshold. In a third test, after exercising at W'(max,e) without EFL for 4 min, EFL was imposed; exercise continued for 4 more minutes or until exhaustion. O(2) consumption (V'(O)(2)) was measured breath-by-breath for the last 90 s of control, and for the first 90 s of EFL exercise. Assuming that the arterio-mixed venous O(2) content remained constant immediately after EFL imposition, we used V'(O)(2) as a measure of cardiac output (Q'(c)). Q'(c) was also calculated by the pulse contour method with blood pressure measured continuously by a photo-plethysmographic device. Both sets of data showed a decrease of Q'(c) due to a decrease in stroke volume by 10% (p < 0.001 for V'(O)(2)) with EFL and remained decreased for the full 90 s. Concurrently, arterial O(2) saturation decreased by 5%, abdominal, pleural and alveolar pressures increased, and duty cycle decreased by 43%. We conclude that this combination of events led to a decrease in venous return secondary to high expiratory pressures, and a decreased duty cycle which decreased O(2) delivery to working muscles by approximately 15%.

  17. Limitations to vasodilatory capacity and .VO2 max in trained human skeletal muscle.

    PubMed

    Barden, Jeremy; Lawrenson, Lesley; Poole, Jennifer G; Kim, Jeannie; Wray, D Walter; Bailey, Damian M; Richardson, Russell S

    2007-05-01

    To further explore the limitations to maximal O(2) consumption (.VO(2 max)) in exercise-trained skeletal muscle, six cyclists performed graded knee-extensor exercise to maximum work rate (WR(max)) in hypoxia (12% O(2)), hyperoxia (100% O(2)), and hyperoxia + femoral arterial infusion of adenosine (ADO) at 80% WR(max). Arterial and venous blood sampling and thermodilution blood flow measurements allowed the determination of muscle O(2) delivery and O(2) consumption. At WR(max), O(2) delivery rose progressively from hypoxia (1.0 +/- 0.04 l/min) to hyperoxia (1.20 +/- 0.09 l/min) and hyperoxia + ADO (1.33 +/- 0.05 l/min). Leg .VO(2 max) varied with O(2) availability (0.81 +/- 0.05 and 0.97 +/- 0.07 l/min in hypoxia and hyperoxia, respectively) but did not improve with ADO-mediated vasodilation (0.80 +/- 0.09 l/min in hyperoxia + ADO). Although a vasodilatory reserve in the maximally working quadriceps muscle group may have been evidenced by increased leg vascular conductance after ADO infusion beyond that observed in hyperoxia (increased blood flow but no change in blood pressure), we recognize the possibility that the ADO infusion may have provoked vasodilation in nonexercising tissue of this limb. Together, these findings imply that maximally exercising skeletal muscle may maintain some vasodilatory capacity, but the lack of improvement in leg .VO(2 max) with significantly increased O(2) delivery (hyperoxia + ADO), with a degree of uncertainty as to the site of this dilation, suggests an ADO-induced mismatch between O(2) consumption and blood flow in the exercising limb.

  18. COMPARISON OF AMPLITUDE RECOVERY DYNAMICS OF TWO LIMIT CYCLE OSCILLATOR MODELS OF THE HUMAN CIRCADIAN PACEMAKER

    PubMed Central

    Indic, Premananda; Forger, Daniel B.; St. Hilaire, Melissa A.; Dean, Dennis A.; Brown, Emery N.; Kronauer, Richard E.; Klerman, Elizabeth B.; Jewett, Megan E.

    2013-01-01

    At an organism level, the mammalian circadian pacemaker is a two-dimensional system. For these two dimensions, phase (relative timing) and amplitude of the circadian pacemaker are commonly used. Both the phase and the amplitude (A) of the human circadian pacemaker can be observed within multiple physiological measures—including plasma cortisol, plasma melatonin, and core body temperature (CBT)—all of which are also used as markers of the circadian system. Although most previous work has concentrated on changes in phase of the circadian system, critically timed light exposure can significantly reduce the amplitude of the pacemaker. The rate at which the amplitude recovers to its equilibrium level after reduction can have physiological significance. Two mathematical models that describe the phase and amplitude dynamics of the pacemaker have been reported. These models are essentially equivalent in predictions of phase and in predictions of amplitude recovery for small changes from an equilibrium value (A = 1), but are markedly different in the prediction of recovery rates when A < 0.6. To determine which dynamic model best describes the amplitude recovery observed in experimental data; both models were fit to CBT data using a maximum likelihood procedure and compared using Akaike’s Information Criterion (AIC). For all subjects, the model with the lower recovery rate provided a better fit to data in terms of AIC, supporting evidence that the amplitude recovery of the endogenous pacemaker is slow at low amplitudes. Experiments derived from model predictions are proposed to test the influence of low amplitude recovery on the physiological and neurobehavioral functions. PMID:16147894

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

    ERIC Educational Resources Information Center

    Adams, Margaret Smolinka

    2013-01-01

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

  20. 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

  1. 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.

  2. 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

  3. Morphometric Study of Pancreas in Human Fetuses

    PubMed Central

    Dhende, Abhijeet S.; Joshi, Deepak S.

    2016-01-01

    Introduction The pancreas arises from the endoderm as a dorsal and a ventral bud which fuse together to form the single organ. It extends transversely across the posterior abdominal wall from the duodenum to the spleen. Functionally, it is endocrine and exocrine. Aim This study was undertaken to study the morphometry of human pancreas at different gestational age groups of normal, still born fetuses. Materials and Methods Forty aborted human fetuses (25 male and 15 female) of 12-40 weeks gestational age with no obvious congenital abnormality were obtained. The fetuses were dissected and pancreas was removed. The length and weight of the pancreas as well as height of its head were noted. Results It was observed that there was increase in body weight and crown rump length with increasing gestational age. The average length of pancreas was 1.80 cm in 12th week and 4.70 cm in 40th week of gestation. The average height of pancreas head was 0.80 cm in the 12th and 2.70 cm in 40th week of gestation. Conclusion The knowledge of development of pancreas helps in planning new therapeutic interventions in the treatment of various congenital and functional pancreatic anomalies. PMID:28050352

  4. 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.

  5. Metabolic Phenotyping Guidelines: studying eating behaviour in humans.

    PubMed

    Gibbons, Catherine; Finlayson, Graham; Dalton, Michelle; Caudwell, Phillipa; Blundell, John E

    2014-08-01

    The study of human appetite and eating behaviour has become increasingly important in recent years due to the rise in body weight dysregulation through both obesity and eating disorders. Adequate control over appetite is paramount for the control of body weight and in order to understand appetite, it is necessary to measure eating behaviour accurately. So far, research in this field has revealed that no single experimental design can answer all research questions. Each research question posed will require a specific study design that will limit the findings of that study to those particular conditions. For example, choices will be made among the use of laboratory or free-living studies, time period for examination, specific measurement techniques and investigative methodologies employed. It is important that these represent informed decisions about what design and which methodology will provide the most meaningful outcomes. This review will examine some of the 'gold standard' study designs and methodologies currently employed in the study of human appetite and eating behaviour.

  6. 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.

  7. 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

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

    PubMed

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

    2015-08-01

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

  9. Drosophila melanogaster in the Study of Human Neurodegeneration

    PubMed Central

    Hirth, Frank

    2010-01-01

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

  10. Consolidated Human Activity Database (CHAD) for use in human exposure and health studies and predictive models

    EPA Pesticide Factsheets

    EPA scientists have compiled detailed data on human behavior from 22 separate exposure and time-use studies into CHAD. The database includes more than 54,000 individual study days of detailed human behavior.

  11. 2012 North Plains research field 12-200 limited irrigation corn production study

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

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

    2014-12-06

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

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

    PubMed Central

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

    2014-01-01

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

  15. 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...

  16. 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...

  17. 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...

  18. 40 CFR 26.1606 - Human Studies Review Board review of proposed human research.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

  19. Electron Microscope Studies of the Human Epidermis

    PubMed Central

    Hibbs, Richard G.; Clark, Wallace H.

    1959-01-01

    The thin skin of the left upper quadrant of the human abdomen has been studied by electron microscopy. Tissue removed with a high speed rotary punch was fixed in osmium tetroxide or potassium permanganate. The latter fixative in our preparations is superior to osmium for the demonstration of epidermal cell membranes and certain other membranous structures of the epidermis. The cytoplasmic membranes of basal cells and cells of the stratum granulosum have been found to be relatively straight, while those of most spinous cells are sharply scalloped. The deep cells of the stratum spinosum in the rete ridge area show cell membranes and cytoplasmic structure intermediate between true basal cells and most cells of the stratum spinosum. The extracellular material of the desmosome has been found to consist of alternate dark and light laminae similar to those described by Odland (13) and Horstmann and Knoop (7). PMID:13673050

  20. 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.

  1. 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

  2. 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

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

    PubMed Central

    Stevenson, Richard J.; Attuquayefio, Tuki

    2013-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1998-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

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

  6. Implications of limits of detection of various methods for Bacillus anthracis in computing risks to human health.

    PubMed

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

    2009-10-01

    Used for decades for biological warfare, Bacillus anthracis (category A agent) has proven to be highly stable and lethal. Quantitative risk assessment modeling requires descriptive statistics of the limit of detection to assist in defining the exposure. Furthermore, the sensitivities of various detection methods in environmental matrices are vital information for first responders. A literature review of peer-reviewed journal articles related to methods for detection of B. anthracis was undertaken. Articles focused on the development or evaluation of various detection approaches, such as PCR, real-time PCR, immunoassay, etc. Real-time PCR and PCR were the most sensitive methods for the detection of B. anthracis, with median instrument limits of detection of 430 and 440 cells/ml, respectively. There were very few peer-reviewed articles on the detection methods for B. anthracis in the environment. The most sensitive limits of detection for the environmental samples were 0.1 CFU/g for soil using PCR-enzyme-linked immunosorbent assay (ELISA), 17 CFU/liter for air using an ELISA-biochip system, 1 CFU/liter for water using cultivation, and 1 CFU/cm(2) for stainless steel fomites using cultivation. An exponential dose-response model for the inhalation of B. anthracis estimates of risk at concentrations equal to the environmental limit of detection determined the probability of death if untreated to be as high as 0.520. Though more data on the environmental limit of detection would improve the assumptions made for the risk assessment, this study's quantification of the risk posed by current limitations in the knowledge of detection methods should be considered when employing those methods in environmental monitoring and cleanup strategies.

  7. Synergistic COX2 Induction by IFNγ and TNFα Self-Limits Type-1 Immunity in the Human Tumor Microenvironment.

    PubMed

    Wong, Jeffrey L; Obermajer, Nataša; Odunsi, Kunle; Edwards, Robert P; Kalinski, Pawel

    2016-04-01

    Maintenance of CTL-, Th1-, and NK cell-mediated type-1 immunity is essential for effective antitumor responses. Unexpectedly, we observed that the critical soluble mediators of type-1 immune effector cells, IFNγ and TNFα, synergize in the induction of cyclooxygenase 2 (COX2), the key enzyme in prostaglandin (PG)E2 synthesis, and the subsequent hyperactivation of myeloid-derived suppressor cells (MDSC) within the tumor microenvironment (TME) of ovarian cancer patients. MDSC hyperactivation by type-1 immunity and the resultant overexpression of indoleamine 2,3-dioxygenase (IDO), inducible nitric oxide synthase (iNOS/NOS2), IL10, and additional COX2 result in strong feedback suppression of type-1 immune responses. This paradoxical immune suppression driven by type-1 immune cell activation was found to depend on the synergistic action of IFNγ and TNFα, and could not be reproduced by either of these factors alone. Importantly, from a therapeutic standpoint, these negative feedback limiting type-1 responses could be eliminated by COX2 blockade, allowing amplification of type-1 immunity in the ovarian cancer TME. Our data demonstrate a new mechanism underlying the self-limiting nature of type-1 immunity in the human TME, driven by the synergistic induction of COX2 by IFNγ and TNFα, and provide a rationale for targeting the COX2-PGE2 axis to enhance the effectiveness of cancer immunotherapies.

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

    PubMed

    Genuis, Stephen J; Lane, Kevin; Birkholz, Detlef

    2016-01-01

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

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

    PubMed Central

    Lane, Kevin; Birkholz, Detlef

    2016-01-01

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

  10. Acute inhibition of iron bioavailability by zinc: studies in humans.

    PubMed

    Olivares, Manuel; Pizarro, Fernando; Ruz, Manuel; de Romaña, Daniel López

    2012-08-01

    Iron (Fe) and zinc (Zn) deficiencies constitute two of the most important nutritional and public health problems affecting developing countries. Combined supplementation or fortification with Zn and Fe are strategies that can be used to improve the Zn and Fe status of a population. However, there is concern about potential negative interactions between these two micronutrients due to a competitive binding to DMT1 and Zip14 transporter. Studies performed in humans have shown an inhibitory effect of Zn on Fe absorption when both minerals are given together as a solution in fasting conditions. We found that at low doses of iron (0.5 mg) the threshold for the inhibition of iron bioavailability was at a Zn:Fe wt/wt ratio ≥5.9:1, whereas at higher doses of Fe (10 mg) this inhibition occurred at 1:1 Zn:Fe wt/wt ratio. This differential response could be explained by the variation in the abundance of both cations as they compete for a limited number of shared transporters at the enterocyte. Conflicting results have been obtained when this interaction was studied in different food matrices. A negative interaction was not observed when Fe and Zn were provided in a composite hamburger meal, premature formula, human milk, or cow milk. A decrease on Fe absorption was observed in only 1 of 3 studies when Fe and Zn were supplied in wheat flour. The possibility of a negative interaction should be considered for supplementation or fortification programs with both microminerals.

  11. Options and limitations in studies of successive pregnancy outcomes: an overview.

    PubMed

    Basso, Olga

    2007-07-01

    This paper provides a brief overview of options and limitations in studies of successive pregnancy outcomes, largely derived from the author's personal experience on Danish registries. The issues discussed here by no means constitute an exhaustive list, but aim at providing an introduction for researchers interested in this topic.

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

    ERIC Educational Resources Information Center

    Tinker, Miles A.

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

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

    ERIC Educational Resources Information Center

    Picasso de Oyague, Alfredo

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

  14. The Texas Successful Schools Study: Quality Education for Limited English Proficient Students.

    ERIC Educational Resources Information Center

    Texas Education Agency, Austin.

    A study by the Texas Education Agency examined the variables contributing to the academic success of economically disadvantaged and language minority students. Data were collected from seven high-achieving elementary schools with high poverty rates and high percentages of limited English proficient (LEP) students via teacher questionnaires;…

  15. 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

    ... Import Limit Studies (SIL) required as part of their updated market power analyses associated with their market based rate authorizations, which are due in June 2010. Participants are encouraged to review the... their pending updated market power analyses. Interested persons planning to participate in the...

  16. Delivery of radiation therapy in resource-limited settings: A pilot quality assessment study.

    PubMed

    Power-Hays, Alexandra; Friedrich, Paola; Fernandez, Gretchen; Cruz, Naly A; Marcus, Karen; Rodriguez-Galindo, Carlos; Collado, Luisa

    2017-02-22

    Progress has been made in resource-limited countries in treating acute lymphoblastic leukemia, but advances in solid malignancies have been slower. Multidisciplinary care coordination is challenging, assessing adherence to guidelines through quality improvement initiatives is essential. We characterized deviations from guidelines in the delivery of radiation in a middle-income country program as a pilot for evaluating adequacy of local control and as surrogate for integration of multidisciplinary care. One-third of patients for whom it was indicated did not receive radiation. Of the patients who received radiation, 95% had a deviation. This study underscores the importance of quality assessment in resource-limited settings.

  17. Human intestinal lipoproteins. Studies in chyluric subjects.

    PubMed

    Green, P H; Glickman, R M; Saudek, C D; Blum, C B; Tall, A R

    1979-07-01

    To explore the role of the human intestine as a source of apolipoproteins, we have studied intestinal lipoproteins and apoprotein secretion in two subjects with chyluria (mesenteric lymphatic-urinary fistulae). After oral corn oil, apolipoprotein A-I (apoA-I) and apolipoprotein A-II (apoA-II) output in urine increased in parallel to urinary triglyceride. One subject, on two occasions, after 40 g of corn oil, excreted 8.4 and 8.6 g of triglyceride together with 196 and 199 mg apoA-I and on one occasion, 56 mg apoA-II. The other subject, after 40 g corn oil, excreted 0.3 g triglyceride and 17.5 mg apoA-I, and, after 100 g of corn oil, excreted 44.8 mg apoA-I and 5.8 mg apoA-II. 14.5+/-2.1% of apoA-I and 17.7+/-4.3% of apoA-II in chylous urine was in the d < 1.006 fraction (chylomicrons and very low density lipoprotein). Calculations based on the amount of apoA-I and apoA-II excreted on triglyceride-rich lipoproteins revealed that for these lipid loads, intestinal secretion could account for 50 and 33% of the calculated daily synthetic rate of apoA-I and apoA-II, respectively. Similarly, subject 2 excreted 48-70% and 14% of the calculated daily synthetic rate of apoA-I and apoA-II, respectively. Chylous urine contained chylomicrons, very low density lipoproteins and high density lipoproteins, all of which contained apoA-I. Chylomicrons and very low density lipoproteins contained a previously unreported human apoprotein of 46,000 mol wt. We have called this apoprotein apoA-IV because of the similarity of its molecular weight and amino acid composition to rat apoA-IV. In sodium dodecyl sulfate gels, chylomicron apoproteins consisted of apoB 3.4+/-0.7%, apoA-IV 10.0+/-3.3%, apoE 4.4+/-0.3%, apoA-I 15.0+/-1.8%, and apoC and apoA-II 43.3+/-11.3%. Very low density lipoprotein contained more apoB and apoA-IV and less apoC than chylomicrons. Ouchterlony immunodiffusion of chylomicron apoproteins revealed the presence of apoC-I, apoC-II, and apoC-III. In contrast, plasma

  18. 76 FR 34703 - Human Studies Review Board Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-14

    ... AGENCY Human Studies Review Board Advisory Committee AGENCY: Environmental Protection Agency (EPA). ACTION: Request for Nominations to the Human Studies Review Board (HSRB) Advisory Committee. SUMMARY: The... candidates with expertise in bioethics and toxicology to be considered for appointment to its Human...

  19. 78 FR 35031 - Human Studies Review Board Advisory Committee

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-11

    ... AGENCY Human Studies Review Board Advisory Committee AGENCY: Environmental Protection Agency (EPA). ACTION: Request for Nominations to the Human Studies Review Board (HSRB) Advisory Committee. SUMMARY: The... candidates with expertise in bioethics, biostatistics and human health risk assessment to be considered...

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

    PubMed

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

    2014-07-07

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

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

    NASA Astrophysics Data System (ADS)

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

    2009-04-01

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

  2. RECENT STUDIES ON THE CURRENT LIMITATIONS OF STATE-OF-THE-ART Nb3Sn CAVITIES

    SciTech Connect

    Hall, Daniel Leslie; Liepe, Matthias; Maniscalco, J. T.; Posen, Sam; Proslier, T.

    2015-01-01

    Recent advances in the study of Nb3Sn at Cornell University have yielded single-cell cavities that show excellent performance without the limiting Q-slope seen in previous work. This performance has been shown to be repeatable across multiple cavities. However, they are still limited by a quench field of approximately 16 MV/m, as well as residual resistance. In this work we present results quantifying the impact of ambient magnetic fields on Nb3Sn cavities, as well as discuss the impact of cavity cooldown procedures on cavity performance. Finally, we will briefly discuss XRD results that shed light on the composition of the Nb3Sn layer and how this relates to the current limits of these cavities.

  3. 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.

  4. Studying Food Reward and Motivation in Humans

    PubMed Central

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

    2014-01-01

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

  5. 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

  6. Studying food reward and motivation in humans.

    PubMed

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

    2014-03-19

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

  7. AD Hoc Study on Human Robot Interface Issues

    DTIC Science & Technology

    2002-09-01

    ARMY SCIENCE BOARD AD HOC STUDY ON HUMAN ROBOT INTERFACE ISSUES FINAL REPORT SEPTEMBER 2002 Distribution: Approved for...conclusions contained in this report are those of the 2002 Ad Hoc Study Panel on “Human- Robot Interface Issues” and do not necessarily reflect the official...DATES COVERED Army Science Board – 2002 Ad Hoc Study 4. TITLE AND SUBTITLE AD HOC STUDY ON HUMAN ROBOT INTERFACE ISSUES 6. AUTHOR(S) Study

  8. 78 FR 71707 - MAP-21 Comprehensive Truck Size and Weight Limits Study Public Meeting and Outreach Sessions

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-29

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

  9. Molecular Genetic Study of Human Esophageal Carcinoma

    DTIC Science & Technology

    1991-07-16

    activating transmembrane mutations in the c- erbB2 proto-oncogene in human breast cancer. Oncogene, 5:237-239, 1990. Levine, A.J., & Monard, J. Tumor...have demonstrated susceptibility to mutations in different types of neoplasia. In the present investigation, two approaches were undertaken in the...search for such genes which might be mutated during the development of esophageal carcinoma. In the first, the human HER2 oncogene, encoding a

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

    PubMed

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

    2016-01-01

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

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

    ERIC Educational Resources Information Center

    Fredman, Nick

    2014-01-01

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

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

    EPA Science Inventory

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

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

    PubMed

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

    2014-09-01

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

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

    ERIC Educational Resources Information Center

    Man, Yiu-Kwong; Poon, Kin-Keung

    2014-01-01

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

  15. Cellular systems for studying human oral squamous cell carcinomas.

    PubMed

    Patel, Vyomesh; Iglesias-Bartolome, Ramiro; Siegele, Bradford; Marsh, Christina A; Leelahavanichkul, Kantima; Molinolo, Alfredo A; Gutkind, J Silvio

    2011-01-01

    The human oral squamous epithelium plays an important role in maintaining a barrier function against mechanical, physical, and pathological injury. However, the self-renewing cells residing on the basement membrane of the epithelium can give rise to oral squamous cell carcinomas (OSCC), now the sixth most common cancer in the developed world, which is still associated with poor prognosis. This is due, in part, to the limited availability of well-defined culture systems for studying oral epithelial cell biology, which could advance our understanding of the molecular basis of OSCC. Here, we describe methods to successfully isolate large cultures of human oral epithelial cells and fibroblasts from small pieces of donor tissues for use in techniques such as three-dimensional cultures and animal grafts to validate genes suspected of playing a role in OSCC development and progression. Finally, the use of isolated oral epithelial cells in generating iPS cells is discussed which holds promise in the field of oral regenerative medicine.

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

    ERIC Educational Resources Information Center

    O'Brien, Ed

    1999-01-01

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

  17. A novel SCID mouse model for studying spontaneous metastasis of human lung cancer to human tissue.

    PubMed

    Teraoka, S; Kyoizumi, S; Seyama, T; Yamakido, M; Akiyama, M

    1995-05-01

    We established a novel severe combined immunodeficient (SCID) mouse model for the study of human lung cancer metastasis to human lung. Implantation of both human fetal and adult lung tissue into mammary fat pads of SCID mice showed a 100% rate of engraftment, but only fetal lung implants revealed normal morphology of human lung tissue. Using these chimeric mice, we analyzed human lung cancer metastasis to both mouse and human lungs by subcutaneous inoculation of human squamous cell carcinoma and adenocarcinoma cell lines into the mice. In 60 to 70% of SCID mice injected with human-lung squamous-cell carcinoma, RERF-LC-AI, cancer cells were found to have metastasized to both mouse lungs and human fetal lung implants but not to human adult lung implants 80 days after cancer inoculation. Furthermore, human-lung adenocarcinoma cells, RERF-LC-KJ, metastasized to the human lung implants within 90 days in about 40% of SCID mice, whereas there were no metastases to the lungs of the mice. These results demonstrate the potential of this model for the in vivo study of human lung cancer metastasis.

  18. A Limited Group of Class I Histone Deacetylases Acts To Repress Human Immunodeficiency Virus Type 1 Expression▿

    PubMed Central

    Keedy, Kara S.; Archin, Nancie M.; Gates, Adam T.; Espeseth, Amy; Hazuda, Daria J.; Margolis, David M.

    2009-01-01

    Silencing of the integrated human immunodeficiency virus type 1 (HIV-1) genome in resting CD4+ T cells is a significant contributor to the persistence of infection, allowing the virus to evade both immune detection and pharmaceutical attack. Nonselective histone deacetylase (HDAC) inhibitors are capable of inducing expression of quiescent HIV-1 in latently infected cells. However, potent global HDAC inhibition can induce host toxicity. To determine the specific HDACs that regulate HIV-1 transcription, we evaluated HDAC1 to HDAC11 RNA expression and protein expression and compartmentalization in the resting CD4+ T cells of HIV-1-positive, aviremic patients. HDAC1, -3, and -7 had the highest mRNA expression levels in these cells. Although all HDACs were detected in resting CD4+ T cells by Western blot analysis, HDAC5, -8, and -11 were primarily sequestered in the cytoplasm. Using chromatin immunoprecipitation assays, we detected HDAC1, -2, and -3 at the HIV-1 promoter in Jurkat J89GFP cells. Targeted inhibition of HDACs by small interfering RNA demonstrated that HDAC2 and HDAC3 contribute to repression of HIV-1 long terminal repeat expression in the HeLa P4/R5 cell line model of latency. Together, these results suggest that HDAC inhibitors specific for a limited number of class I HDACs may offer a targeted approach to the disruption of persistent HIV-1 infection. PMID:19279091

  19. Human search with a limited field of view: effects of scan speed, aperture size, and target conspicuity

    NASA Astrophysics Data System (ADS)

    Hogervorst, Maarten A.; Toet, Alexander; Bijl, Piet

    2013-04-01

    We investigate how human visual search performance with field of view (FOV) restrictions depends on scan speed, zoom factor, target location, and conspicuity. First, observers search a FOV that moves at a constant speed along a predefined path over a visual search scene (the field of regard, or FOR), and we measure the effects of scan speed, zoom factor, FOV size, target location, and conspicuity on search performance (detection time and probability). Then observers search either visual or thermal scenes by freely moving a joystick-controlled FOV over the FOR, while freely selecting the zoom factor in some conditions, and we measure the effects of the scan path characteristics and the use of different strategies on search performance. Search performance depends on the effective FOV size (the area where targets are expected to occur), but is largely independent of the display area. Both for visual and thermal imagery, various search performance measures correlate with target conspicuity. The results of both experiments suggest that observers can optimize their performance by adjusting their scanning behavior both to their visual limitations and to the expected target conspicuity. We present the outlines of a simple search model based on these current findings.

  20. A Case Study of Habitat for Humanity

    DTIC Science & Technology

    1994-01-01

    of reference 3). 4.2.1 Precedence Method using Primavera Proiect Planner (p3. The p3 software system was initially chosen because it is so...I ! I, B-8I I APPENDIX C INITIAL TABULAR SCHEDULE PRINTOUT ALACHUA HABITAT FOR HU1ANITY PRIMAVERA PROJECT PLANNER HABITAT FOR NANITY GENEIIC REPORT...HABITAT FOR HUMANITY PRIMAVERA PROJECT PLANNER HABITAT FOR HUMANITY GENERIC SCNED REPORT DATE 15JUL94 RUN NO. 21 START DATE 30OCT93 FIN DATE 27JAN94 11

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

    NASA Astrophysics Data System (ADS)

    Kokkinaki, A.; Sleep, B. E.

    2011-12-01

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

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

    NASA Astrophysics Data System (ADS)

    Aslam; Pejović-Milić, A.; Chettle, D. R.; McNeill, F. E.

    2008-08-01

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

  3. An epidemiologic study of the human bite.

    PubMed Central

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

    1979-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2010-07-01

    We are developing the Background-Limited Infrared-Submillimeter Spectrograph (BLISS) for SPICA to provide a breakthrough capability for far-IR survey spectroscopy. SPICAs large cold aperture allows mid-IR to submm observations which are limited only by the natural backgrounds, and BLISS is designed to operate near this fundamental limit. BLISS-SPICA is 6 orders of magnitude faster than the spectrometers on Herschel and SOFIA in obtaining full-band spectra. It enables spectroscopy of dust-obscured galaxies at all epochs back to the rst billion years after the Big Bang (redshift 6), and study of all stages of planet formation in circumstellar disks. BLISS covers 35 - 433 microns range in ve or six wavelength bands, and couples two 2 sky positions simultaneously. The instrument is cooled to 50 mK for optimal sensitivity with an on-board refrigerators. The detector package is 4224 silicon-nitride micro-mesh leg-isolated bolometers with superconducting transition-edge-sensed (TES) thermistors, read out with a cryogenic time-domain multiplexer. All technical elements of BLISS have heritage in mature scientic instruments, and many have own. We report on our design study in which we are optimizing performance while accommodating SPICAs constraints, including the stringent cryogenic mass budget. In particular, we present our progress in the optical design and waveguide spectrometer prototyping. A companion paper in Conference 7741 (Beyer et al.) discusses in greater detail the progress in the BLISS TES bolometer development.

  5. Parsimonious modeling of vegetation dynamics for ecohydrologic studies of water-limited ecosystems

    NASA Astrophysics Data System (ADS)

    Montaldo, Nicola; Rondena, Roberta; Albertson, John D.; Mancini, Marco

    2005-10-01

    The structure and function of vegetation regulate fluxes across the biosphere-atmosphere interface with large effects in water-limited ecosystems. Vegetation dynamics are often neglected in hydrological modeling except for simple prescriptions of seasonal phenology. However, changes in vegetation densities, influencing the partitioning of incoming solar energy into sensible and latent heat fluxes, can result in long-term changes in both local and global climates with resulting feedbacks on vegetation growth. This paper seeks a simple vegetation dynamics model (VDM) for simulation of the leaf area index (LAI) dynamics in hydrologic models. Five variants of a VDM are employed, with a range of model complexities. The VDMs are coupled to a land surface model (LSM), with the VDM providing the LAI evolution through time and the LSM using this to compute the land surface fluxes and update the soil water contents. We explore the models through case studies of water-limited grass fields in California (United States) and North Carolina (United States). Results show that a simple VDM, simulating only the living aboveground green biomass (i.e., with low parameterization), is able to accurately simulate the LAI. Results also highlight the importance of including the VDM in the LSM when studying the climate-soil-vegetation interactions over moderate to long timescales. The inclusion of the VDM in the LSM is demonstrated to be essential for assessing the impact of interannual rainfall variability on the water budget of a water limited region.

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

    ERIC Educational Resources Information Center

    Quamen, Harvey

    2006-01-01

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

  7. Teacher Leader Human Relations Skills: A Comparative Study

    ERIC Educational Resources Information Center

    Roby, Douglas E.

    2012-01-01

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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2013-01-01

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

  11. Studies of WW and WZ production and limits on anomalous WWγ and WWZ couplings

    NASA Astrophysics Data System (ADS)

    Abbott, B.; Abolins, M.; Abramov, V.; Acharya, B. S.; Adam, I.; Adams, D. L.; Adams, M.; Ahn, S.; Akimov, V.; Alves, G. A.; Amos, N.; Anderson, E. W.; Baarmand, M. M.; Babintsev, V. V.; Babukhadia, L.; Baden, A.; Baldin, B.; Banerjee, S.; Bantly, J.; Barberis, E.; Baringer, P.; Bartlett, J. F.; Belyaev, A.; Beri, S. B.; Bertram, I.; Bezzubov, V. A.; Bhat, P. C.; Bhatnagar, V.; Bhattacharjee, M.; Biswas, N.; Blazey, G.; Blessing, S.; Bloom, P.; Boehnlein, A.; Bojko, N. I.; Borcherding, F.; Boswell, C.; Brandt, A.; Breedon, R.; Briskin, G.; Brock, R.; Bross, A.; Buchholz, D.; Burtovoi, V. S.; Butler, J. M.; Carvalho, W.; Casey, D.; Casilum, Z.; Castilla-Valdez, H.; Chakraborty, D.; Chekulaev, S. V.; Chen, W.; Choi, S.; Chopra, S.; Choudhary, B. C.; Christenson, J. H.; Chung, M.; Claes, D.; Clark, A. R.; Cobau, W. G.; Cochran, J.; Coney, L.; Cooper, W. E.; Coppage, D.; Cretsinger, C.; Cullen-Vidal, D.; Cummings, M. A.; Cutts, D.; Dahl, O. I.; Davis, K.; de, K.; del Signore, K.; Demarteau, M.; Denisov, D.; Denisov, S. P.; Diehl, H. T.; Diesburg, M.; di Loreto, G.; Draper, P.; Ducros, Y.; Dudko, L. V.; Dugad, S. R.; Dyshkant, A.; Edmunds, D.; Ellison, J.; Elvira, V. D.; Engelmann, R.; Eno, S.; Eppley, G.; Ermolov, P.; Eroshin, O. V.; Evans, H.; Evdokimov, V. N.; Fahland, T.; Fatyga, M. K.; Feher, S.; Fein, D.; Ferbel, T.; Fisk, H. E.; Fisyak, Y.; Flattum, E.; Forden, G. E.; Fortner, M.; Frame, K. C.; Fuess, S.; Gallas, E.; Galyaev, A. N.; Gartung, P.; Gavrilov, V.; Geld, T. L.; Genik, R. J.; Genser, K.; Gerber, C. E.; Gershtein, Y.; Gibbard, B.; Gobbi, B.; Gómez, B.; Gómez, G.; Goncharov, P. I.; González Solís, J. L.; Gordon, H.; Goss, L. T.; Gounder, K.; Goussiou, A.; Graf, N.; Grannis, P. D.; Green, D. R.; Green, J. A.; Greenlee, H.; Grinstein, S.; Grudberg, P.; Grünendahl, S.; Guglielmo, G.; Guida, J. A.; Guida, J. M.; Gupta, A.; Gurzhiev, S. N.; Gutierrez, G.; Gutierrez, P.; Hadley, N. J.; Haggerty, H.; Hagopian, S.; Hagopian, V.; Hahn, K. S.; Hall, R. E.; Hanlet, P.; Hansen, S.; Hauptman, J. M.; Hays, C.; Hebert, C.; Hedin, D.; Heinson, A. P.; Heintz, U.; Hernández-Montoya, R.; Heuring, T.; Hirosky, R.; Hobbs, J. D.; Hoeneisen, B.; Hoftun, J. S.; Hsieh, F.; Hu, Tong; Ito, A. S.; Jerger, S. A.; Jesik, R.; Joffe-Minor, T.; Johns, K.; Johnson, M.; Jonckheere, A.; Jones, M.; Jöstlein, H.; Jun, S. Y.; Jung, C. K.; Kahn, S.; Karmanov, D.; Karmgard, D.; Kehoe, R.; Kim, S. K.; Klima, B.; Klopfenstein, C.; Ko, W.; Kohli, J. M.; Koltick, D.; Kostritskiy, A. V.; Kotcher, J.; Kotwal, A. V.; Kozelov, A. V.; Kozlovsky, E. A.; Krane, J.; Krishnaswamy, M. R.; Krzywdzinski, S.; Kubantsev, M.; Kuleshov, S.; Kulik, Y.; Kunori, S.; Landry, F.; Landsberg, G.; Leflat, A.; Li, J.; Li, Q. Z.; Lima, J. G.; Lincoln, D.; Linn, S. L.; Linnemann, J.; Lipton, R.; Lucotte, A.; Lueking, L.; Lyon, A. L.; Maciel, A. K.; Madaras, R. J.; Madden, R.; Magaña-Mendoza, L.; Manankov, V.; Mani, S.; Mao, H. S.; Markeloff, R.; Marshall, T.; Martin, M. I.; Martin, R. D.; Mauritz, K. M.; May, B.; Mayorov, A. A.; McCarthy, R.; McDonald, J.; McKibben, T.; McKinley, J.; McMahon, T.; Melanson, H. L.; Merkin, M.; Merritt, K. W.; Miao, C.; Miettinen, H.; Mincer, A.; Mishra, C. S.; Mokhov, N.; Mondal, N. K.; Montgomery, H. E.; Mooney, P.; Mostafa, M.; da Motta, H.; Murphy, C.; Nang, F.; Narain, M.; Narasimham, V. S.; Narayanan, A.; Neal, H. A.; Negret, J. P.; Nemethy, P.; Norman, D.; Oesch, L.; Oguri, V.; Oshima, N.; Owen, D.; Padley, P.; Para, A.; Parashar, N.; Park, Y. M.; Partridge, R.; Parua, N.; Paterno, M.; Pawlik, B.; Perkins, J.; Peters, M.; Piegaia, R.; Piekarz, H.; Pischalnikov, Y.; Pope, B. G.; Prosper, H. B.; Protopopescu, S.; Qian, J.; Quintas, P. Z.; Raja, R.; Rajagopalan, S.; Ramirez, O.; Reay, N. W.; Reucroft, S.; Rijssenbeek, M.; Rockwell, T.; Roco, M.; Rubinov, P.; Ruchti, R.; Rutherfoord, J.; Sánchez-Hernández, A.; Santoro, A.; Sawyer, L.; Schamberger, R. D.; Schellman, H.; Sculli, J.; Shabalina, E.; Shaffer, C.; Shankar, H. C.; Shivpuri, R. K.; Shpakov, D.; Shupe, M.; Sidwell, R. A.; Singh, H.; Singh, J. B.; Sirotenko, V.; Smith, E.; Smith, R. P.; Snihur, R.; Snow, G. R.; Snow, J.; Snyder, S.; Solomon, J.; Sosebee, M.; Sotnikova, N.; Souza, M.; Stanton, N. R.; Steinbrück, G.; Stephens, R. W.; Stevenson, M. L.; Stichelbaut, F.; Stoker, D.; Stolin, V.; Stoyanova, D. A.; Strauss, M.; Streets, K.; Strovink, M.; Sznajder, A.; Tamburello, P.; Tarazi, J.; Tartaglia, M.; Thomas, T. L.; Thompson, J.; Toback, D.; Trippe, T. G.; Tuts, P. M.; Vaniev, V.; Varelas, N.; Varnes, E. W.; Volkov, A. A.; Vorobiev, A. P.; Wahl, H. D.; Wang, G.; Warchol, J.; Watts, G.; Wayne, M.; Weerts, H.; White, A.; White, J. T.; Wightman, J. A.; Willis, S.; Wimpenny, S. J.; Wirjawan, J. V.; Womersley, J.; Wood, D. R.; Yamada, R.; Yamin, P.; Yasuda, T.

    1999-10-01

    Evidence of anomalous WW and WZ production was sought in pp¯ collisions at a center-of-mass energy of s=1.8 TeV. The final states WW(WZ)-->μν jet jet+X, WZ-->μνee+X and WZ-->eνee+X were studied using a data sample corresponding to an integrated luminosity of approximately 90 pb-1. No evidence of anomalous diboson production was found. Limits were set on anomalous WWγ and WWZ couplings and were combined with our previous results. The combined 95% confidence level anomalous coupling limits for Λ=2 TeV are -0.25<=Δκ<=0.39 (λ=0) and -0.18<=λ<=0.19 (Δκ=0), assuming the WWγ couplings are equal to the WWZ couplings.

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

    NASA Astrophysics Data System (ADS)

    Man, Yiu-Kwong; Poon, Kin-Keung

    2014-02-01

    In this paper, we report a pilot study on engaging a group of undergraduate students to explore the limits of sin(x)/x and tan(x)/x as x approaches to 0, with the use of non-graphic scientific calculators. By comparing the results in the pretest and the post-test, we found that the students had improvements in the tested items, which involved the basic concepts of limits, but had room for further improvement in those that required them to explain their answers. An analysis of the students' performances in the tests by using the APOS (i.e. action-process-object-schema) theory framework is reported. Reflections and suggestions on how to teach the topic more effectively are provided.

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

    SciTech Connect

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

    1988-10-01

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

  14. Study on the limiting factor of critical current in Ag-Bi2223 tapes

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Ding, S. Y.; Luo, H.; Leng, X.; Lin, J. W.

    2003-04-01

    The silver sheathed tapes of Ag-Bi 2- xPb xSr 2Ca 2-Cu 3O 7- y (Ag-Bi2223) were fabricated by usual process. The limiting factor of the critical current density jc of the tapes was studied. V- I characteristic was performed for the tapes immersed in liquid nitrogen with and without magnetic fields. Hysteresis loop of V- I curve was observed. A model based on polycrystalline superconductors was proposed to account for this kind of hysteresis. The result shows that in our Ag-Bi2223 tapes the weak link is the key factor limiting the global critical current. The measurement of V- I loop can be an effective method to check whether there exist harmful weak links in polycrystalline samples.

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

    NASA Astrophysics Data System (ADS)

    Horneck, G.; Humex Team

    ESA has recently initiated a study of the human responses, limits and needs with regard to the stress environments of interplanetary and planetary missions. Emphasis was laid on human health and performance care as well as Advanced Life Support Developments including Bioregenerative Life Support Systems and environmental monitoring. The overall study goals were as follows: (i) to define reference scenarios for a European participation in human exploration and to estimate their influence on the Life Sciences and Life Support requirements; (ii) for selected mission scenarios, to critically assess the limiting factors for human health, wellbeing, and performance and to recommend relevant countermeasures; (iii) for selected mission scenarios, to critically assess the potential of Advanced Life Support Developments and to pro-pose a European strategy including terrestrial applications; (iv) to critically assess the feasibility of existing facilities and technologies on ground and in space as test-beds in preparation for human exploratory missions and to develop a test plan for ground and ISS campaigns; (v) to develop a roadmap for a future European strategy towards human exploratory missions, including preparatory activities and terrestrial applications and benefits. Two scenarios for a Mars mission were selected: (i) with a 30 days stay on Mars, and (ii) with about 500 days stay on Mars. The impact on human health, perform-ance and well being has been investigated from the view point of (i) the effects of microgravity (during space travel), reduced gravity (on Mars) and abrupt gravity changes (during launch and landing), (ii) the effects of cosmic radiation including solar particle events, (iii) psychological issues as well as general health care. Coun-termeasures as well as necessary research using ground-based testbeds and/or the ISS have been defined. The need for highly intelligent autonomous diagnostic and therapy systems was emphasized. Advanced life support

  16. Widespread GLI expression but limited canonical hedgehog signaling restricted to the ductular reaction in human chronic liver disease

    PubMed Central

    Tirnitz-Parker, Janina Elke Eleonore; Hamson, Elizabeth Jane; Warren, Alessandra; Maneck, Bharvi; Chen, Jinbiao; Patkunanathan, Bramilla; Boland, Jade; Cheng, Robert; Shackel, Nicholas Adam; Seth, Devanshi; Bowen, David Geoffrey; Martelotto, Luciano Gastón; Watkins, D. Neil; McCaughan, Geoffrey William

    2017-01-01

    Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations. This study extends these observations to human liver tissue, and analyses the effect of GLI inhibition on LPC viability/gene expression. Human donor and cirrhotic liver tissue specimens were evaluated for SHH, GLI2 and Pc expression using immunofluorescence and qRT-PCR. Changes to viability and gene expression in LPCs in vitro were assessed following GLI inhibition. Identification of Pc (as a marker of canonical Hh signaling) in human cirrhosis was predominantly confined to the ductular reaction and LPCs. In contrast, GLI2 was expressed in multiple cell populations including Pc-ve endothelium, hepatocytes, and leukocytes. HSCs/myofibroblasts (>99%) expressed GLI2, with only 1.92% displaying Pc. In vitro GLI signals maintained proliferation/viability within LPCs and GLI inhibition affected the expression of genes related to stemness, hepatocyte/biliary differentiation and Hh/Wnt signaling. At least two mechanisms of GLI signaling (Pc/SMO-dependent and Pc/SMO-independent) mediate chronic liver disease pathogenesis. This may have significant ramifications for the choice of Hh inhibitor (anti-SMO or anti-GLI) suitable for clinical trials. We also postulate GLI delivers a pro-survival signal to LPCs whilst maintaining stemness. PMID:28187190

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

    NASA Astrophysics Data System (ADS)

    Foster, Donald Carey

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

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

    PubMed

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

    2013-01-01

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

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

    SciTech Connect

    Rowland, R.E.

    1994-09-01

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

  20. Empirical study on human acupuncture point network

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

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

  1. Comparative study of limited-range wavelength conversion policies for asynchronous optical packet switching

    NASA Astrophysics Data System (ADS)

    Dogan, Kaan; Gunalay, Yavuz; Akar, Nail

    2007-02-01

    We study an asynchronous optical packet (OP)-switching node equipped with a number of limited range (LR) wavelength converters shared per output link. We study both circular and noncircular LR-wavelength-conversion schemes. A wavelength conversion policy governs the selection of the outgoing wavelength for an OP if the incoming wavelength is in use. Through simulations, we show that the so-called far-conversion policy for which the OP is switched onto the farthest available wavelength in the tuning range, outperforms the other policies we studied. We point out the clustering effect in the use of wavelengths to explain this phenomenon. We also provide an approximate analytical method to find the packet-blocking probability in circular-type LR-wavelength-conversion systems. Based on the simulation results, the approximate method appears to lead to a lower bound for blocking probabilities for all the conversion policies we study.

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

    SciTech Connect

    Reginald M. Ronningen; Igor Remec

    2010-09-11

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

  3. Predicting the limits of the endoscopic endonasal approach in children: a radiological anatomical study.

    PubMed

    Youssef, Carl A; Smotherman, Carmen R; Kraemer, Dale F; Aldana, Philipp R

    2016-04-01

    OBJECT The endoscopic endonasal approach (EEA) has been established as an alternative approach to craniovertebral junction (CVJ) pathology in adults. The authors have previously described the nasoaxial line (NAxL) as an accurate predictor of the lower limit of the EEA to the CVJ in adults. The surgical anatomy limiting the EEA to the pediatric CVJ has not been well studied. Furthermore, predicting the lower limit of the EEA in various pediatric age groups is important in surgical planning. To better understand the anatomy affecting the EEA to the CVJ, the authors examined the skull base anatomy relevant to the EEA in children of different age groups and used the NAxL to predict the EEA lower limit in children. METHODS Axial brain CT scans of 39 children with normal skull base anatomy were reconstructed sagittally. Children were divided into 4 groups according to age: 3-6, 7-10, 11-14, and 15-18 years old. The intersection of the NAxL with the odontoid process of C-2 was described for each group. Analyses of variance were used to estimate the effect of age, sex, interaction between age and sex on different anatomical parameters relevant to the endonasal corridor (including the length of the hard palate [HPLe]), dimensions of choana and piriform aperture, and the length of the NAxL to C-2. The effect of the HPLe on the working distance of NAxL to the odontoid was also estimated using analysis of covariance, controlling for age, sex, and their interaction. RESULTS The NAxL extended to the odontoid process in 38 of the 39 children. Among the 39 children, the NAxL intersected the upper third of the odontoid process in 25 while intersecting the middle third in the remaining 13 children. The measurements of the inferior limits did not differ with age, varying between 9 and 11 mm below the hard palate line at the ventral surface of C-2. Significant increases in the size of the piriform aperture and choana and the HPLe were observed after age 10. The HPLe predicted the

  4. Complex-shaped hardened parts fatigue limit prediction according to the witness sample study results

    NASA Astrophysics Data System (ADS)

    Surgutanova, Yu N.; Mikushev, N. N.; Surgutanov, N. A.; Kiselev, P. E.; Shlyapnikov, P. A.; Meshcheryakova, A. A.

    2016-11-01

    The aim of this study is to investigate the possibility of assessment of the effect of preparatory surface plastic deformation by hydraulic shot blasting on the fatigue strength of cylindrical parts of different diameters (10-40 mm) of D16T alloy with circular notches of semicircular section, based on measurements of residual stress (initial deformations) of a witness sample. The residual stresses of smooth parts were used to calculate the residual stresses of parts with stress raisers. These were used to predict the increment of these parts fatigue limit caused by hardening hydraulic shot blasting. It was found that the highest compressive residual stresses in the smooth parts obtained through calculations differ from the observed values not more than by 7%, and in notched parts by 8%. Using the criterion of mean integral residual stresses, we calculate the increments of the fatigue limit of parts due to superficial hardening. The discrepancy between the experimental and calculated increment values of the fatigue limit of hardened parts with raisers does not exceed 17%.

  5. Alterations in gene expression of proprotein convertases in human lung cancer have a limited number of scenarios.

    PubMed

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

    2013-01-01

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

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

    PubMed Central

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

    2015-01-01

    Peptide immunotherapy (PIT) is a targeted therapeutic approach, involving administration of disease-associated peptides, with the aim of restoring antigen-specific immunological tolerance without generalized immunosuppression. In type 1 diabetes, proinsulin is a primary antigen targeted by the autoimmune response, and is therefore a strong candidate for exploitation via PIT in this setting. To elucidate the optimal conditions for proinsulin-based PIT and explore mechanisms of action, we developed a preclinical model of proinsulin autoimmunity in a humanized HLA-DRB1*0401 transgenic HLA-DR4 Tg mouse. Once proinsulin-specific tolerance is broken, HLA-DR4 Tg mice develop autoinflammatory responses, including proinsulin-specific T cell proliferation, interferon (IFN)-γ and autoantibody production. These are preventable and quenchable by pre- and post-induction treatment, respectively, using intradermal proinsulin-PIT injections. Intradermal proinsulin-PIT enhances proliferation of regulatory [forkhead box protein 3 (FoxP3+)CD25high] CD4 T cells, including those capable of proinsulin-specific regulation, suggesting this as its main mode of action. In contrast, peptide delivered intradermally on the surface of vitamin D3-modulated (tolerogenic) dendritic cells, controls autoimmunity in association with proinsulin-specific IL-10 production, but no change in regulatory CD4 T cells. These studies define a humanized, translational model for in vivo optimization of PIT to control autoimmunity in type 1 diabetes and indicate that dominant mechanisms of action differ according to mode of peptide delivery. PMID:26206289

  7. Development of an ex vivo human-porcine respiratory model for preclinical studies

    PubMed Central

    Perinel, Sophie; Pourchez, Jérémie; Leclerc, Lara; Avet, John; Durand, Marc; Prévôt, Nathalie; Cottier, Michèle; Vergnon, Jean M.

    2017-01-01

    Anatomical models to study aerosol delivery impose huge limitations and extrapolation to humans remains controversial. This study aimed to develop and validate an ex vivo human-like respiratory tract model easy to use and relevant to compare to in vivo human data. A human plastinated head is connected to an ex vivo porcine pulmonary tract ventilated artificially by passive expansion. A physiological study measures “pleural” depressions, tidal volumes, and minute ventilation for the respiratory rates chosen (10, 15, and 20 per minute) with three inspiratory/expiratory ratios (1/1, 1/2, and 1/3). Scintigraphy with 81mKrypton assesses the homogeneity of the ventilation. Forty different experiments were set for validation, with 36 (90%) ventilating successfully. At a respiratory rate of 15/minute with inspiratory/expiratory ratio of 1/2, the tidal volume average was 824 mL (standard deviation, 207 mL). The scintigraphy performed on 16 ex vivo models (44.4%), showed homogenous ventilation with great similarity to human physiological studies. Ratio of the peripheral to central count rates were equally correlated with human data published in the literature. This new model, combining research feasibility and human physiology likeness, provides a realistic approach to human inhalation and therefore can be an interesting tool in aerosol regional deposition studies. PMID:28233793

  8. Development of an ex vivo human-porcine respiratory model for preclinical studies.

    PubMed

    Perinel, Sophie; Pourchez, Jérémie; Leclerc, Lara; Avet, John; Durand, Marc; Prévôt, Nathalie; Cottier, Michèle; Vergnon, Jean M

    2017-02-24

    Anatomical models to study aerosol delivery impose huge limitations and extrapolation to humans remains controversial. This study aimed to develop and validate an ex vivo human-like respiratory tract model easy to use and relevant to compare to in vivo human data. A human plastinated head is connected to an ex vivo porcine pulmonary tract ventilated artificially by passive expansion. A physiological study measures "pleural" depressions, tidal volumes, and minute ventilation for the respiratory rates chosen (10, 15, and 20 per minute) with three inspiratory/expiratory ratios (1/1, 1/2, and 1/3). Scintigraphy with (81m)Krypton assesses the homogeneity of the ventilation. Forty different experiments were set for validation, with 36 (90%) ventilating successfully. At a respiratory rate of 15/minute with inspiratory/expiratory ratio of 1/2, the tidal volume average was 824 mL (standard deviation, 207 mL). The scintigraphy performed on 16 ex vivo models (44.4%), showed homogenous ventilation with great similarity to human physiological studies. Ratio of the peripheral to central count rates were equally correlated with human data published in the literature. This new model, combining research feasibility and human physiology likeness, provides a realistic approach to human inhalation and therefore can be an interesting tool in aerosol regional deposition studies.

  9. A Comparative Study Between Strain And Stress Based Forming Limit Analysis By Applying Several Phenomenological Yield Criteria

    SciTech Connect

    Butuc, Marilena C.; Vincze, Gabriela T.; Gracio, Jose J.; Barata da Rocha, A.

    2005-08-05

    The present work aims at analyzing a comparative study between the strain-based forming limit criterion (FLD) and the stress-based forming limit criterion (FLSD), under linear and complex strain paths. The selected material is an AA5182-0 aluminium alloy. Some relevant remarks about stress-based forming limit criterion concept are presented.

  10. Vestibular schwannoma and cell-phones. Results, limits and perspectives of clinical studies.

    PubMed

    Mornet, E; Kania, R; Sauvaget, E; Herman, P; Tran Ba Huy, P

    2013-11-01

    The widespread development of cell-phones entails novel user exposure to electromagnetic fields. Health impact is a public health issue and a source of anxiety in the population. Some clinical studies reported an association between cell and cordless phone use and vestibular schwannoma; others found none. A systematic review was performed of all published clinical studies (cohort, registry, case-control and validation studies), with analysis of results, to determine the nature of the association and the level of evidence. Cohort studies were inconclusive due to short exposure durations and poor representativeness. Registry studies showed no correlation between evolution of cell-phone use and incidence of vestibular schwannoma. Case-control studies reported contradictory results, with methodological flaws. Only a small number of subjects were included in long-term studies (>10 years), and these failed to demonstrate any indisputable causal relationship. Exposure assessment methods were debatable, and long-term assessment was lacking. An on-going prospective study should determine any major effect of electromagnetic fields; schwannoma being a rare pathology, absence of association will be difficult to prove. No clinical association has been demonstrated between cell and cordless phone use and vestibular schwannoma. Existing studies are limited by their retrospective assessment of exposure.

  11. [Dopamine beta hydroxylase. Value and limits of its study in neurology].

    PubMed

    Miras Portugal, M T; Aunis, D; Mandel, P; Warter, J M; Coquillat, G; Collard, M; Rohmer, F

    1976-06-01

    Plasma dopamine-beta-hydroxylase was studied in 96 subjects, 33 of them controls and 63 of them patients (Parkinson's disease, chronic chorea, torsion dystonia, postural tremor and epilepsy). Only the epileptics showed a significant decrease in the average level of dopamine-beta-hydroxylase activity in comparison with the controls. During the cold test, DBH did not vary except in one case. On the other hand, during epileptic attacks, DBH activity underwent considerable fluctuations. Therefore, except in special pathological conditions, such as epileptic attacks, measurement of plasma or serum DBH activity is of limited value for neurological pathology and is not a good indication of the activity of the sympathetic nervous system.

  12. Fluorescence confocal endomicroscopy of the cervix: pilot study on the potential and limitations for clinical implementation

    NASA Astrophysics Data System (ADS)

    Schlosser, Colin; Bodenschatz, Nico; Lam, Sylvia; Lee, Marette; McAlpine, Jessica N.; Miller, Dianne M.; Van Niekerk, Dirk J. T.; Follen, Michele; Guillaud, Martial; MacAulay, Calum E.; Lane, Pierre M.

    2016-12-01

    Current diagnostic capabilities and limitations of fluorescence endomicroscopy in the cervix are assessed by qualitative and quantitative image analysis. Four cervical tissue types are investigated: normal columnar epithelium, normal and precancerous squamous epithelium, and stromal tissue. This study focuses on the perceived variability within and the subtle differences between the four tissue groups in the context of endomicroscopic in vivo pathology. Conclusions are drawn on the general ability to distinguish and diagnose tissue types, on the need for imaging depth control to enhance differentiation, and on the possible risks for diagnostic misinterpretations.

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

    SciTech Connect

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

    1992-02-01

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

  14. Cell death of gamma interferon-stimulated human fibroblasts upon Toxoplasma gondii infection induces early parasite egress and limits parasite replication.

    PubMed

    Niedelman, Wendy; Sprokholt, Joris K; Clough, Barbara; Frickel, Eva-Maria; Saeij, Jeroen P J

    2013-12-01

    The intracellular protozoan parasite Toxoplasma gondii is a major food-borne illness and opportunistic infection for the immunosuppressed. Resistance to Toxoplasma is dependent on gamma interferon (IFN-γ) activation of both hematopoietic and nonhematopoietic cells. Although IFN-γ-induced innate immunity in nonhematopoietic cells has been extensively studied in mice, it remains unclear what resistance mechanisms are relied on in nonhematopoietic human cells. Here, we report an IFN-γ-induced mechanism of resistance to Toxoplasma in primary human foreskin fibroblasts (HFFs) that does not depend on the deprivation of tryptophan or iron. In addition, infection is still controlled in HFFs deficient in the p65 guanylate binding proteins GBP1 or GBP2 and the autophagic protein ATG5. Resistance is coincident with host cell death that is not dependent on the necroptosis mediator RIPK3 or caspases and is correlated with early egress of the parasite before replication. This IFN-γ-induced cell death and early egress limits replication in HFFs and could promote clearance of the parasite by immune cells.

  15. On the averaging area for incident power density for human exposure limits at frequencies over 6 GHz.

    PubMed

    Hashimoto, Yota; Hirata, Akimasa; Morimoto, Ryota; Aonuma, Shinta; Laakso, Ilkka; Jokela, Kari; Foster, Kenneth R

    2017-02-08

    Incident power density is used as the dosimetric quantity to specify the restrictions on human exposure to electromagnetic fields at frequencies above 3 or 10 GHz in order to prevent excessive temperature elevation at the body surface. However, international standards and guidelines have different definitions for the size of the area over which the power density should be averaged. This study reports computational evaluation of the relationship between the size of the area over which incident power density is averaged and the local peak temperature elevation in a multi-layer model simulating a human body. Three wave sources are considered in the frequency range from 3 to 300 GHz: an ideal beam, a half-wave dipole antenna, and an antenna array. 1D analysis shows that averaging area of 20 mm  ×  20 mm is a good measure to correlate with the local peak temperature elevation when the field distribution is nearly uniform in that area. The averaging area is different from recommendations in the current international standards/guidelines, and not dependent on the frequency. For a non-uniform field distribution, such as a beam with small diameter, the incident power density should be compensated by multiplying a factor that can be derived from the ratio of the effective beam area to the averaging area. The findings in the present study suggest that the relationship obtained using the 1D approximation is applicable for deriving the relationship between the incident power density and the local temperature elevation.

  16. On the averaging area for incident power density for human exposure limits at frequencies over 6 GHz

    NASA Astrophysics Data System (ADS)

    Hashimoto, Yota; Hirata, Akimasa; Morimoto, Ryota; Aonuma, Shinta; Laakso, Ilkka; Jokela, Kari; Foster, Kenneth R.

    2017-04-01

    Incident power density is used as the dosimetric quantity to specify the restrictions on human exposure to electromagnetic fields at frequencies above 3 or 10 GHz in order to prevent excessive temperature elevation at the body surface. However, international standards and guidelines have different definitions for the size of the area over which the power density should be averaged. This study reports computational evaluation of the relationship between the size of the area over which incident power density is averaged and the local peak temperature elevation in a multi-layer model simulating a human body. Three wave sources are considered in the frequency range from 3 to 300 GHz: an ideal beam, a half-wave dipole antenna, and an antenna array. 1D analysis shows that averaging area of 20 mm  ×  20 mm is a good measure to correlate with the local peak temperature elevation when the field distribution is nearly uniform in that area. The averaging area is different from recommendations in the current international standards/guidelines, and not dependent on the frequency. For a non-uniform field distribution, such as a beam with small diameter, the incident power density should be compensated by multiplying a factor that can be derived from the ratio of the effective beam area to the averaging area. The findings in the present study suggest that the relationship obtained using the 1D approximation is applicable for deriving the relationship between the incident power density and the local temperature elevation.

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

    PubMed

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

    2014-06-01

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

  18. Potential Utility and Limitations of Thyroid Cancer Cell Lines as Models for Studying Thyroid Cancer

    PubMed Central

    Pilli, Tania; Prasad, Kanteti V.; Jayarama, Shankar; Pacini, Furio

    2009-01-01

    Background Tumor-derived cell lines are widely used to study the mechanisms involved in thyroid carcinogenesis but recent studies have reported redundancy among thyroid cancer cell lines and identification of some “thyroid cell lines” that are likely not of thyroid origin. Summary In this review, we have summarized the uses, the limitations, and the existing problems associated with the available follicular cell-derived thyroid cancer cell lines. There are some limitations to the use of cell lines as a model to “mimic” in vivo tumors. Based on the gene expression profiles of thyroid cell lines originating from tumors of different types it has become apparent that some of the cell lines are closely related to each other and to those of undifferentiated carcinomas. Further, many cell lines have lost the expression of thyroid-specific genes and have altered karyotypes, while they exhibit activation of several oncogenes (BRAF, v-raf murine sarcoma viral oncogene homolog B1; RAS, rat sarcoma; and RET/PTC, rearranged in transformation/papillary thyroid carcinoma) and inactivation of tumor suppressor gene (TP53) which is known to be important for thyroid tumorigenesis. Conclusions A careful selection of thyroid cancer cell lines that reflect the major characteristics of a particular type of thyroid cancer being investigated could be used as a good model system to analyze the signaling pathways that may be important in thyroid carcinogenesis. Further, the review of literature also suggests that some of the limitations can be overcome by using multiple cell lines derived from the same type of tumor. PMID:20001716

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

    PubMed

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

    2015-02-01

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

  20. Animal model for study of human hepatitis viruses.

    PubMed

    Chayama, Kazuaki; Hayes, C Nelson; Hiraga, Nobuhiko; Abe, Hiromi; Tsuge, Masataka; Imamura, Michio

    2011-01-01

    Human hepatitis B virus (HBV) and hepatitis C virus (HCV) infect only chimpanzees and humans. Analysis of both viruses has long been hampered by the absence of a small animal model. The recent development of human hepatocyte chimeric mice has enabled us to carry out studies on viral replication and cellular changes induced by replication of human hepatitis viruses. Various therapeutic agents have also been tested using this model. In the present review, we summarize published studies using chimeric mice and discuss the merits and shortcomings of this model.

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

    SciTech Connect

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

    1993-12-31

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

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

    PubMed

    Guillon, Myrtille; Mace, Ruth

    2016-01-01

    The classification of kin into structured groups is a diverse phenomenon which is ubiquitous in human culture. For populations which are organized into large agropastoral groupings of sedentary residence but not governed within the context of a centralised state, such as our study sample of 83 historical Bantu-speaking groups of sub-Saharan Africa, cultural kinship norms guide all aspects of everyday life and social organization. Such rules operate in part through the use of differing terminological referential systems of familial organization. Although the cross-cultural study of kinship terminology was foundational in Anthropology, few modern studies have made use of statistical advances to further our sparse understanding of the structuring and diversification of terminological systems of kinship over time. In this study we use Bayesian Markov Chain Monte Carlo methods of phylogenetic comparison to investigate the evolution of Bantu kinship terminology and reconstruct the ancestral state and diversification of cousin terminology in this family of sub-Saharan ethnolinguistic groups. Using a phylogenetic tree of Bantu languages, we then test the prominent hypothesis that structured variation in systems of cousin terminology has co-evolved alongside adaptive change in patterns of descent organization, as well as rules of residence. We find limited support for this hypothesis, and argue that the shaping of systems of kinship terminology is a multifactorial process, concluding with possible avenues of future research.

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

    PubMed Central

    Guillon, Myrtille; Mace, Ruth

    2016-01-01

    The classification of kin into structured groups is a diverse phenomenon which is ubiquitous in human culture. For populations which are organized into large agropastoral groupings of sedentary residence but not governed within the context of a centralised state, such as our study sample of 83 historical Bantu-speaking groups of sub-Saharan Africa, cultural kinship norms guide all aspects of everyday life and social organization. Such rules operate in part through the use of differing terminological referential systems of familial organization. Although the cross-cultural study of kinship terminology was foundational in Anthropology, few modern studies have made use of statistical advances to further our sparse understanding of the structuring and diversification of terminological systems of kinship over time. In this study we use Bayesian Markov Chain Monte Carlo methods of phylogenetic comparison to investigate the evolution of Bantu kinship terminology and reconstruct the ancestral state and diversification of cousin terminology in this family of sub-Saharan ethnolinguistic groups. Using a phylogenetic tree of Bantu languages, we then test the prominent hypothesis that structured variation in systems of cousin terminology has co-evolved alongside adaptive change in patterns of descent organization, as well as rules of residence. We find limited support for this hypothesis, and argue that the shaping of systems of kinship terminology is a multifactorial process, concluding with possible avenues of future research. PMID:27008364

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

    PubMed

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

    2009-10-01

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

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

    USGS Publications Warehouse

    Hossack, B.R.; Muths, E.; Anderson, C.W.; Kirshtein, J.D.; Corn, P.S.

    2009-01-01

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

  6. Passive optical limiting studies of nanostructured Cu doped ZnO-PVA composite thin films

    NASA Astrophysics Data System (ADS)

    Tamgadge, Y. S.; Sunatkari, A. L.; Talwatkar, S. S.; Pahurkar, V. G.; Muley, G. G.

    2016-01-01

    We prepared undoped and Cu doped ZnO semiconducting nanoparticles (NPs) by chemical co-precipitation method and obtained Cu doped ZnO-polyvinyl alcohol (PVA) nanocomposite thin films by spin coating to investigate third order nonlinear optical and optical limiting properties under cw laser excitation. Powder samples of NPs were characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), energy dispersive spectroscopy, transmission electron microscopy, ultraviolet-visible (UV-vis) and Fourier transform infrared spectroscopy. XRD pattern and FE-SEM micrograph revealed the presence of hexagonal wurtzite phase ZnO NPs having uniform morphology with average particle size of 20 nm. The presence of excitons and absorption peaks in the range 343-360 nm, revealed by UV-vis study, were attributed to excitons in n = 1 quantum state. Third order NLO properties of all composite thin films were investigated by He-Ne continuous wave (cw) laser of wavelength 632.8 nm using Z-scan technique. Thermally stimulated enhanced values of nonlinear refraction and absorption coefficients were obtained which may be attributed to self-defocusing effect, reverse saturable absorption, weak free carrier absorption and surface states properties originated from thermo optic effect. Optical limiting properties have been studied using cw diode laser of wavelength 808 nm and results are presented.

  7. HCV Sensing by Human Trophoblasts Induces Innate Immune Responses and Recruitment of Maternal NK Cells: Potential Implications for Limiting Vertical Transmission

    PubMed Central

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

    2015-01-01

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

  8. Retinal electrophysiology for toxicology studies: applications and limits of ERG in animals and ex vivo recordings.

    PubMed

    Rosolen, Serge Georges; Kolomiets, Bogdan; Varela, Oscar; Picaud, Serge

    2008-06-01

    Assessing retinal drug toxicity is becoming increasingly important as different molecules are now developed for the treatment of neurodegenerative diseases and vascular disorders. In pharmacology and toxicology, the electroretinogram (ERG) and the multielectrode array (MEA) recording techniques can be used to quantify the possible side effects of retino-active xenobiotics. Toxicity testing requires the use of rodent as well as non-rodent models for extrapolation to the human model when determining risk and safety. Animal species differ in their retinal anatomo-physiology: most rodents used in toxicology studies are essentially nocturnal species, whereas the non-rodent laboratory species normally used (e.g. dogs, pigs and monkeys) are diurnal. The ratio between the photoreceptor populations which varies from species to species, should be considered when designing the experiment protocol and the interpretation. The described ERG procedures are designed to comply with all applicable good laboratory practice standards. Use of these procedures should yield an acceptable level of intra- and inter-subject variability for compiling a historical database, and for detecting possible retinal toxicity in animal studies. They could therefore be used as specific and standardized tools for screening of potential retinotoxic molecules in drug discovery and development in order to compare methods and results with those obtained in human electrophysiological assessments. Recording of ganglion cell light responses on ex vivo retina with the MEA technique can further demonstrate how retino-active xenobiotics affect retinal visual information processing by eliminating potential obstacles related to bioavailability and blood barrier permeability.

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

    PubMed

    Xiong, Xiong; Nan, Ding; Yang, Yang; Yongjie, Zhang

    2015-01-01

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

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

    PubMed Central

    2015-01-01

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

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

    PubMed Central

    2011-01-01

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

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

    PubMed

    DeSilva, Jeremy M; Devlin, Maureen J

    2012-09-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-12-01

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

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

    PubMed

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

    2015-09-24

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

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

    PubMed

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

    2013-01-01

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

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

    ERIC Educational Resources Information Center

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

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

  17. Chronic illness and functional limitation in Ontario children: findings of the Ontario Child Health Study.

    PubMed Central

    Cadman, D; Boyle, M H; Offord, D R; Szatmari, P; Rae-Grant, N I; Crawford, J; Byles, J

    1986-01-01

    The Ontario Child Health Study (OCHS) was based on interviews of 1869 Ontario families who were selected by means of a stratified, multistaged sampling method from the 1981 census of Canada. Its primary purpose was to determine the prevalence and distribution of mental health problems in Ontario children aged 4 to 16 years and their families, but it also allowed an estimate of other significant medical conditions and provided an overview of these children's use of health care, education and social services. Our results are based on questionnaire responses concerning 3294 children. Limitation of function without a chronic illness or medical condition was reported in 1.9%, the converse in 14.0%, and a chronic illness or medical condition with limitation of function in 3.7%. When the three groups are considered together, 19.6% of Ontario children had a chronic health problem. Children of lower socioeconomic status were much more likely to have chronic health problems. Overall, children with chronic health problems were more likely to use physician, special education, social and mental health services. These findings have implications for those who provide services for children, plan community programs or train professionals in caring for children. PMID:3756702

  18. A qualitative study of limited access permit dental hygienists in Oregon.

    PubMed

    Battrell, Ann M; Gadbury-Amyot, Cynthia C; Overman, Pamela R

    2008-03-01

    Many states have adopted alternative oral health care delivery systems that include expanded roles for dental hygienists. This qualitative study was designed to evaluate the impact of the Limited Access Permit (LAP) legislation in Oregon and to understand the relationship between dental hygienists and dentists within this delivery system. The snowball sampling technique was used to identify LAP dental hygienists and collaborating dentists. The snowball sampling technique begins with the identification of a known expert in the field who serves as the initial "sampling unit." Subsequent individuals are then recommended, or nominated, to the investigator by the initial study participant and are selected based upon the need to fill in or extend information. The final sample consisted of seven LAP dental hygienists and two collaborating dentists. Interviews, field observations, and document analysis were utilized for data collection. Factors that led to the creation of LAP dental hygiene practice, current LAP practice, personal characteristics, relationships between LAP dental hygienists and dentists, and the impact that LAP dental hygienists have had on access to oral health care were explored. Data revealed that the Oregon legislature twice expanded the LAP scope of practice to increase access to oral health care services. LAP dental hygienists practice in community and school-based settings. Common characteristics of LAP dental hygienists include entrepreneurship, lifelong learning, and a commitment to underserved populations. The findings from this study indicate that LAP dental hygienists and collaborating dentists have positive relationships. No evidence of lower quality of care in unsupervised dental hygiene practices was found. However, the impact of the LAP legislation is still unknown due to the limited numbers of LAP dental hygienists and the early nature of the LAP practice.

  19. Human skull translucency: post mortem studies

    PubMed Central

    Sawosz, P.; Wojtkiewicz, S.; Kacprzak, M.; Weigl, W.; Borowska-Solonynko, A.; Krajewski, P.; Bejm, K.; Milej, D.; Ciszek, B.; Maniewski, R.; Liebert, A.

    2016-01-01

    Measurements of optical translucency of human skulls were carried out. An incandescent light source and a CCD camera were used to measure the distribution of light transmitted through the skull in 10 subjects post-mortem. We noticed that intra-individual differences in optical translucency may be up to 100 times but inter-individual translucency differences across the skull reach 105 times. Based on the measurement results, a “theoretical” experiment was simulated. Monte-Carlo calculations were used in order to evaluate the influence of the differences in optical translucency of the skull on results of NIRS measurements. In these calculations a functional stimulation was done, in which the oxyhemoglobin and deoxyhemoglobin concentrations in the brain cortex change by 5μM and −5μM respectively. The maximal discrepancies between assumed hemoglobin concentration changes and hemoglobin concentration changes estimated with Monte-Carlo simulation may reach 50% depending of the translucency of the skull. PMID:28018721

  20. Human Ecology. Study Guide and Course Outline.

    ERIC Educational Resources Information Center

    Zaki, Gamal

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

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

    PubMed

    Hill, D A

    1985-01-01

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

  2. Thulium laser in interventional endoscopy: animal and human studies.

    PubMed

    Tontini, Gian E; Neumann, Helmut; Pastorelli, Luca; Spina, Luisa; Cavallaro, Flaminia; Soriani, Paola; Rimondi, Alessandro; Bruni, Barbara; Clemente, Claudio; Fagnani, Filippo; Lagoussis, Pavlos; Carmignani, Luca; Vecchi, Maurizio

    2017-01-20

    Background and study aims The thulium laser system (TLS) is an emerging surgical tool. The 2-μm wavelength provides a confined coagulation depth (0.2 - 0.4 mm) to reduce the potential for inadvertent injuries. For the first time ever, we assessed TLS feasibility for endoscopic hemostasis ex vivo in pigs. In addition, we performed the first in vivo hemostatic treatments in humans. Patients and methods Tissue damage induced by TLS using different settings and optical fibers was compared to that from argon plasma coagulation (APC) in established ex vivo animal models. Three consecutive patients with complex nonvariceal upper gastrointestinal bleedings were treated and followed up. Results No deep submucosal injury was observed in animal models. The TLS showed a progressive penetration depth with increased power outputs and tissue exposures but very limited vertical tissue injury (0.1 - 2.0 mm) and lateral spreading damage (0.1 - 0.3 mm and 0.2 - 0.7 mm using the 365-µm and 550-µm fibers, respectively). In vivo, endoscopic hemostasis with TLS was always successful without complications. Conclusions The TLS has proven to be very precise and easy to use. This novel technique appears to be a promising tool for advanced interventional endoscopy.

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

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  4. Development of a new humanized mouse model to study acute inflammatory arthritis

    PubMed Central

    2012-01-01

    Background Substantial advances have been generated in understanding the pathogenesis of rheumatoid arthritis (RA). Current murine models of RA-like disease have provided great insights into the molecular mechanism of inflammatory arthritis due to the use of genetically deficient or transgenic mice. However, these studies are limited by differences that exist between human and murine immune systems. Thus, the development of an animal model that utilizes human immune cells, will afford the opportunity to study their function in the initiation and propagation of inflammatory arthritis. Methods One to two-day old irradiated NOD-scid IL2rγnull (NSG) mice were reconstituted with human CD34+ cord blood stem cells. Leukocytes were analyzed by flow cytometry and circulating antibodies were determined by ELISA. Arthritis was induced by injecting complete Freund’s adjuvant into knee or ankle joints. Mice were also treated with the TNF inhibitor, Etanercept, or PBS and joints were analyzed histologically. Results Humanized mice were established with high reconstitution rates and were able to spontaneously produce human immunoglobulins as well as specific IgG in response to immunization. Intraperitoneal injection of thioglycolate or injection of complete Freund’s adjuvant into joints resulted in migration of human immune cells to the injected sites. Arthritic humanized mice treated with Etanercept had markedly less inflammation, which was associated with decreased total numbers of human CD45+ cells, including human lymphocytes and neutrophils. Conclusions The humanized mouse model is a new model to study inflammatory arthritis disease using human leukocytes without rejection of engrafted tissue. Future studies may adapt this system to incorporate RA patient cord blood and develop a chimeric animal model of inflammatory arthritis using genetically predisposed immune cells. PMID:22974474

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

    PubMed

    Johnston, Jonathan D

    2012-02-05

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

  6. Human Rights and History Education: An Australian Study

    ERIC Educational Resources Information Center

    Burridge Nina; Buchanan, John; Chodkiewicz, Andrew

    2014-01-01

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

  7. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  8. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  9. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

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

    NASA Astrophysics Data System (ADS)

    Wodlinger, B.; Downey, J. E.; Tyler-Kabara, E. C.; Schwartz, A. B.; Boninger, M. L.; Collinger, J. L.

    2015-02-01

    Objective. In a previous study we demonstrated continuous translation, orientation and one-dimensional grasping control of a prosthetic limb (seven degrees of freedom) by a human subject with tetraplegia using a brain-machine interface (BMI). The current study, in the same subject, immediately followed the previous work and expanded the scope of the control signal by also extracting hand-shape commands from the two 96-channel intracortical electrode arrays implanted in the subject’s left motor cortex. Approach. Four new control signals, dictating prosthetic hand shape, replaced the one-dimensional grasping in the previous study, allowing the subject to control the prosthetic limb with ten degrees of freedom (three-dimensional (3D) translation, 3D orientation, four-dimensional hand shaping) simultaneously. Main results. Robust neural tuning to hand shaping was found, leading to ten-dimensional (10D) performance well above chance levels in all tests. Neural unit preferred directions were broadly distributed through the 10D space, with the majority of units significantly tuned to all ten dimensions, instead of being restricted to isolated domains (e.g. translation, orientation or hand shape). The addition of hand shaping emphasized object-interaction behavior. A fundamental component of BMIs is the calibration used to associate neural activity to intended movement. We found that the presence of an object during calibration enhanced successful shaping of the prosthetic hand as it closed around the object during grasping. Significance. Our results show that individual motor cortical neurons encode many parameters of movement, that object interaction is an important factor when extracting these signals, and that high-dimensional operation of prosthetic devices can be achieved with simple decoding algorithms. ClinicalTrials.gov Identifier: NCT01364480.

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

    SciTech Connect

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

    2009-01-15

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

  12. Motion Sickness: A Study of Its Effects on Human Physiology.

    DTIC Science & Technology

    1987-12-01

    SICKNESS: A STUDY OF ITS EFFECTS ON HUMAN PHYSIOLOGY THESIS Pierre J. Gaudreault Captain, USAF AFIT/GE/ENG/87D- 2 0 TO STEC TEo VN;FB 1 0 1988...ENG/87D-20 MOTION SICKNESS: A STUDY OF ITS EFFECTS ON HUMAN PHYSIOLOGY THESIS Pierre J. Gaudreault Captain, USAF AFIT/GE/ENG/87D-20 Approved for public...SICKNESS: A STUDY OF ITS EFFECTS ON HUMAN PHYSIOLOGY THESIS Presented to the Faculty of the School of Engineering of the Air Force Institute of Technology

  13. Structural studies of human urinary kallikrein (urokallikrein).

    PubMed

    ole-MoiYoi, O K; Spragg, J; Austen, K F

    1979-07-01

    Human urinary kallikrein (urokallikrein) has been purified by affinity chromatography with aprotinin coupled to CH-Sepharose and by gel filtration. The isolation procedure, which was performed under mild conditions, was completed in a 36-hr period and yielded an overall recovery of more than 75% and a purification of 1727-fold. Homogeneity of the urokallikrein was demonstrated by three criteria: the coincidence of the stained protein band and functional urokallikrein in duplicate gels after alkaline disc gel electrophoresis; the appearance of a single stained band of molecular weight 48,000 on sodium dodecyl sulfate/polyacrylamide gel electrophoresis of reduced and unreduced enzyme; and the finding of a single amino-terminal residue, namely alanine after dansylation and acid hydrolysis of purified enzyme. The Km of urokallikrein on N alpha-p-tosyl-L-arginine methyl ester was 400 microM, and the Vmax was 194 mumol/min per mg of protein, which is higher than that observed with any previous preparations. The molecular weight of 48,700 determined on gel filtration and the molecular weight of 48,000 observed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis are in good agreement with the molecular weight of 48,213 calculated from the amino acid composition. The finding of a molecular weight higher than those previously reported, namely 27,000-43,500, the increased functional activity on tosylarginine methyl ester, and the detection of a single amino-terminal residue are consistent with the isolation of a more native protein by the procedure described in this paper.

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

    PubMed

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

    2006-05-01

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

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

    NASA Technical Reports Server (NTRS)

    Rastogi, P. K.

    1983-01-01

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

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

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

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

  17. Nitrogen Limitation of Terrestrial Net Primary Production: Global Patterns From Field Studies with Nitrogen Fertilization

    NASA Astrophysics Data System (ADS)

    Lebauer, D. S.; Treseder, K. K.

    2006-12-01

    Net primary production (NPP) transfers carbon from the atmospheric CO2 pool into the biosphere. Experimental evidence demonstrates that NPP is often limited by nitrogen availability. Hence, accelerated nitrogen availability due to fertilizer production, fossil fuel use, and biomass burning could stimulate global NPP. Over the next century, these nitrogen sources are expected to both increase in strength and expand from their current concentration in the temperate regions of Europe and the United States into the tropical regions of South America, Southeast Asia, and India. In order to predict future carbon budgets, it is necessary to quantify the impact of nitrogen on NPP. Currently there is no synthesis of ecosystem scale experiments that evaluates responses among biomes and across environmental gradients. The aim of this investigation is to test the prediction that nitrogen limitation is widespread, and to evaluate global patterns of NPP response to nitrogen. The present study compiles results from field-based nitrogen addition experiments in a comprehensive meta-analysis. Published studies were obtained through key word searches and referenced articles. A response metric was derived from each study based on measurements of plant growth under ambient nitrogen deposition (control) and experimental nitrogen addition (treatment). This metric is the response ratio (R): the ratio of mean growth in treatment divided by control plots. Therefore, a positive effect of nitrogen results in R>1. A meta-analysis was performed on ln(R) weighted by within-study variance. We found that most ecosystems are nitrogen limited (P<0.0001) and that average growth response to nitrogen was 32%. However, response was not uniform across biomes. Significant responses were observed in grasslands and forests (P<0.0001), but not wetlands and tundra (P=0.08 and P=0.16). While mean annual precipitation (MAP) was significantly correlated to R overall (P<0.0001), the direction of the effect varied

  18. Understanding the limits of Marxist approaches to sociocultural studies of science education

    NASA Astrophysics Data System (ADS)

    Lima, Paulo; Ostermann, Fernanda; Rezende, Flavia

    2014-12-01

    In the first three sections of this paper we comment on some of the ideas developed in the forum papers, pointing out possible misunderstandings and constructing new explanations that clarify arguments we made in the original article. In the last section we expand the discussion raised in the original paper, elaborating on the limits of the use of Marxist approaches to sociocultural studies of science education. Following insights suggested by Loxley et al. (Cult Stud Sci Educ. doi: 10.1007/s11422-013-9554-z, 2013) and detailed by Zuss (Cult Stud Sci Educ. doi: 10.1007/s11422-013-9555-y, 2014) on the commodification of knowledge, we sketch an analysis of how knowledge is transformed into capital to understand why contemporary scholars are likely to be engaged in a relation of production that resembles capitalist exploitation.

  19. Understanding the limits of Marxist approaches to sociocultural studies of science education

    NASA Astrophysics Data System (ADS)

    Lima Junior, Paulo; Ostermann, Fernanda; Rezende, Flavia

    2014-09-01

    In the first three sections of this paper we comment on some of the ideas developed in the forum papers, pointing out possible misunderstandings and constructing new explanations that clarify arguments we made in the original article. In the last section we expand the discussion raised in the original paper, elaborating on the limits of the use of Marxist approaches to sociocultural studies of science education. Following insights suggested by Loxley et al. (Cult Stud Sci Edu. doi: 10.1007/s11422-013-9554-z, 2013) and detailed by Zuss (Cult Stud Sci Edu, 2014) on the commodification of knowledge, we sketch an analysis of how knowledge is transformed into capital to understand why contemporary scholars are likely to be engaged in a relation of production that resembles capitalist exploitation.

  20. Comparative study of the extracellular proteome of Sulfolobus species reveals limited secretion.

    PubMed

    Ellen, Albert F; Albers, Sonja-Verena; Driessen, Arnold J M

    2010-01-01

    Although a large number of potentially secreted proteins can be predicted on the basis of genomic distribution of signal sequence-bearing proteins, protein secretion in Archaea has barely been studied. A proteomic inventory and comparison of the growth medium proteins in three hyperthermoacidophiles, i.e., Sulfolobus solfataricus, S. acidocaldarius and S. tokodaii, indicates that only few proteins are freely secreted into the growth medium and that the majority originates from cell envelope bound forms. In S. acidocaldarius both cell-associated and secreted alpha-amylase activities are detected. Inactivation of the amyA gene resulted in a complete loss of activity, suggesting that the same protein is responsible for the a-amylase activity at both locations. It is concluded that protein secretion in Sulfolobus is a limited process, and it is suggested that the S-layer may act as a barrier for the free diffusion of folded proteins into the medium.

  1. Study of the art: canine olfaction used for cancer detection on the basis of breath odour. Perspectives and limitations.

    PubMed

    Jezierski, Tadeusz; Walczak, Marta; Ligor, Tomasz; Rudnicka, Joanna; Buszewski, Bogusław

    2015-05-06

    Experimental studies using trained dogs to identify breath odour markers of human cancer, published in the recent decade, have been analyzed and compared with the authors' own results. Particular published studies differ as regards the experimental setup, kind of odour samples (breath, urine, tumor tissue, serum), sample collection methods, dogs' characteristics and dog training methods as well as in results presented in terms of detection sensitivity and specificity. Generally it can be stated that trained dogs are able to distinguish breath odour samples typical for patients with lung cancer and other cancers from samples typical for healthy humans at a 'better than by chance' rate. Dogs' indications were positively correlated with content of 2-pentanone and ethyl acetate (r = 0.97 and r = 0.85 respectively) and negatively correlated with 1-propanol and propanal in breath samples (r = -0.98 and -0.87 respectively). The canine method has some advantages as a potential cancer-screening method, due to its non-invasiveness, simplicity of odour sampling and storage, ease of testing and interpretation of results and relatively low costs. Disadvantages and limitations of this method are related to the fact that it is still not known exactly to which chemical compounds and/or their combinations the dogs react. So far it could not be confirmed that dogs are able to sniff out early preclinical cancer stages with approximately the same accuracy as already diagnosed cases. The detection accuracy may vary due to failure in conditioning of dogs, decreasing motivation or confounding factors. The dogs' performance should be systematically checked in rigorous double-blind procedures. Recommendations for methodological standardization have been proposed.

  2. Analysis of human brain exposure to low-frequency magnetic fields: a numerical assessment of spatially averaged electric fields and exposure limits.

    PubMed

    Chen, Xi-Lin; Benkler, Stefan; Chavannes, Nicholas; De Santis, Valerio; Bakker, Jurriaan; van Rhoon, Gerard; Mosig, Juan; Kuster, Niels

    2013-07-01

    Compliance with the established exposure limits for the electric field (E-field) induced in the human brain due to low-frequency magnetic field (B-field) induction is demonstrated by numerical dosimetry. The objective of this study is to investigate the dependency of dosimetric compliance assessments on the applied methodology and segmentations. The dependency of the discretization uncertainty (i.e., staircasing and field singularity) on the spatially averaged peak E-field values is first determined using canonical and anatomical models. Because spatial averaging with a grid size of 0.5 mm or smaller sufficiently reduces the impact of artifacts regardless of tissue size, it is a superior approach to other proposed methods such as the 99th percentile or smearing of conductivity contrast. Through a canonical model, it is demonstrated that under the same uniform B-field exposure condition, the peak spatially averaged E-fields in a heterogeneous model can be significantly underestimated by a homogeneous model. The frequency scaling technique is found to introduce substantial error if the relative change in tissue conductivity is significant in the investigated frequency range. Lastly, the peak induced E-fields in the brain tissues of five high-resolution anatomically realistic models exposed to a uniform B-field at ICNIRP and IEEE reference levels in the frequency range of 10 Hz to 100 kHz show that the reference levels are not always compliant with the basic restrictions. Based on the results of this study, a revision is recommended for the guidelines/standards to achieve technically sound exposure limits that can be applied without ambiguity.

  3. A study of the human decomposition sequence in central Texas.

    PubMed

    Parks, Connie L

    2011-01-01

    Decomposition studies utilizing nonhuman subjects as human analogues are well established, but fewer studies utilizing intact human remains exist. This study provides data from a controlled decomposition study involving human remains in Central Texas. A 63.5-kg unmodified cadaver was placed in an open-air site and observed over a 10-week period from April 11 through June 19, 2008. A wire enclosure restricted scavenger access. State of decomposition and environmental conditions were recorded daily for the first 36 days and then every 2 weeks thereafter. Results indicated a high degree of correlation with other decomposition studies originating in the southwestern United States, although slight deviations for the average duration of early events were noted. The data were also utilized to test a quantitative method for estimating the postmortem interval. Results indicated preliminary support for a quantitative approach. Additional research is encouraged to further establish the human decomposition data set for Central Texas.

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

    PubMed

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

    2012-05-01

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

  5. Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

    PubMed Central

    Atkinson, Stuart P.; Quiñonero, Alicia; Martínez, Sebastián; Pellicer, Antonio; Simón, Carlos

    2012-01-01

    Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expression of tissue remodeling enzymes and activity of human endometrial stromal cells (hESCs) related to trophoblast invasion control. Treatment of hESCs with the HDAC inhibitor trichostatin A (TSA) increased the expression of TIMP-1 and TIMP-3 while decreased MMP-2, MMP-9 and uPA and have an inhibitory effect on trophoblast invasion. Moreover, histone acetylation is detected at the promoters of TIMP-1 and TIMP-3 genes in TSA-treated. In addition, in an in vitro decidualized hESCs model, the increase of TIMP-1 and TIMP-3 expression is associated with histone acetylation at the promoters of these genes. Our results demonstrate that histone acetylation disrupt the balance of ECM modulators provoking a restrain of trophoblast invasion. These findings are important as an epigenetic mechanism that can be used to control trophoblast invasion. PMID:22291969

  6. Space station human productivity study, volume 1

    NASA Technical Reports Server (NTRS)

    1985-01-01

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

  7. A rapid LC-MS/MS method for quantitation of eszopiclone in human plasma: application to a human pharmacokinetic study.

    PubMed

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

    2012-02-01

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

  8. Chamber studies of SOA formation from aromatic hydrocarbons: observation of limited glyoxal uptake

    NASA Astrophysics Data System (ADS)

    Nakao, S.; Liu, Y.; Tang, P.; Chen, C.-L.; Zhang, J.; Cocker, D. R., III

    2012-05-01

    This study evaluates the significance of glyoxal acting as an intermediate species leading to secondary organic aerosol (SOA) formation from aromatic hydrocarbon photooxidation under humid conditions. Rapid SOA formation from glyoxal uptake onto aqueous (NH4)2SO4 seed particles is observed in agreement with previous studies; however, glyoxal did not partition significantly to SOA (with or without aqueous seed) during aromatic hydrocarbon photooxidation within an environmental chamber (RH less than 80%). Rather, glyoxal influences SOA formation by raising hydroxyl (OH) radical concentrations. Four experimental approaches supporting this conclusion are presented in this paper: (1) increased SOA formation and decreased SOA volatility in the toluene + NOx photooxidation system with additional glyoxal was reproduced by matching OH radical concentrations through H2O2 addition; (2) glyoxal addition to SOA seed formed from toluene + NOx photooxidation did not increase SOA volume under dark; (3) SOA formation from toluene + NOx photooxidation with and without deliquesced (NH4)2SO4 seed resulted in similar SOA growth, consistent with a minor contribution from glyoxal uptake onto deliquesced seed and organic coatings; and (4) the fraction of a C4H9+ fragment (observed by Aerodyne High Resolution Time-of-Flight Aerosol Mass Spectrometer, HR-ToF-AMS) in SOA from 2-tert-butylphenol (BP) oxidation was unchanged in the presence of additional glyoxal despite enhanced SOA formation. This study suggests that glyoxal uptake onto aerosol during the oxidation of aromatic hydrocarbons is more limited than previously thought.

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

    ERIC Educational Resources Information Center

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

    2015-01-01

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

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

    EPA Science Inventory

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

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

    EPA Science Inventory

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

  12. Webinar Presentation: Assessing Neurodevelopment in Parallel Animal and Human Studies

    EPA Pesticide Factsheets

    This presentation, Assessing Neurodevelopment in Parallel Animal and Human Studies, was given at the NIEHS/EPA Children's Centers 2015 Webinar Series: Interdisciplinary Approaches to Neurodevelopment held on Sept. 9, 2015.

  13. Comparison of methods for imputing limited-range variables: a simulation study

    PubMed Central

    2014-01-01

    Background Multiple imputation (MI) was developed as a method to enable valid inferences to be obtained in the presence of missing data rather than to re-create the missing values. Within the applied setting, it remains unclear how important it is that imputed values should be plausible for individual observations. One variable type for which MI may lead to implausible values is a limited-range variable, where imputed values may fall outside the observable range. The aim of this work was to compare methods for imputing limited-range variables, with a focus on those that restrict the range of the imputed values. Methods Using data from a study of adolescent health, we consider three variables based on responses to the General Health Questionnaire (GHQ), a tool for detecting minor psychiatric illness. These variables, based on different scoring methods for the GHQ, resulted in three continuous distributions with mild, moderate and severe positive skewness. In an otherwise complete dataset, we set 33% of the GHQ observations to missing completely at random or missing at random; repeating this process to create 1000 datasets with incomplete data for each scenario. For each dataset, we imputed values on the raw scale and following a zero-skewness log transformation using: univariate regression with no rounding; post-imputation rounding; truncated normal regression; and predictive mean matching. We estimated the marginal mean of the GHQ and the association between the GHQ and a fully observed binary outcome, comparing the results with complete data statistics. Results Imputation with no rounding performed well when applied to data on the raw scale. Post-imputation rounding and imputation using truncated normal regression produced higher marginal means than the complete data estimate when data had a moderate or severe skew, and this was associated with under-coverage of the complete data estimate. Predictive mean matching also produced under-coverage of the complete data

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

    PubMed

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

    2016-01-01

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

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

    SciTech Connect

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

    1989-05-01

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

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

    PubMed Central

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

    2015-01-01

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

  17. Fatigue studies of high-palladium dental casting alloys: Part I. Fatigue limits and fracture characteristics.

    PubMed

    Li, D; Brantley, W A; Mitchell, J C; Daehn, G S; Monaghan, P; Papazoglou, E

    2002-04-01

    The fatigue limits and fracture characteristics for a Pd-Cu-Ga alloy and a Pd-Ga alloy were studied. The alloys were cast into tensile test bars with gauge diameter of 3 mm and gauge length of 15 mm, and the surfaces of the castings were neither air-abraded nor polished after removal from the investment. Specimens were prepared from all-new metal (not previously melted), a combination of 50% new metal and 50% old metal (previously melted one time) and 100% old metal. The cast bars were subjected to heat treatment simulating the complete firing cycles for dental porcelain, and fatigued in air at room temperature under uniaxial tension-compression stress at 10 Hz and a ratio of tensile stress amplitude to compressive stress amplitude (R-ratio) of -1. The alloy microstructures and fracture surfaces were examined with a scanning electron microscope (SEM). Results showed that the fatigue limits at 2 x 10(6)cycles of the Pd-Cu-Ga and Pd-Ga alloys were approximately 0.20 and 0.15 of their 0.1% yield strength (YS) in tension, respectively. The fatigue resistance for specimens from both alloys containing 50% old metal and 50% new metal was comparable to that of specimens containing all-new metal, although this decreased dramatically for Pd-Cu-Ga alloy specimens containing all-old metal. The fatigue resistance of the Pd-Cu-Ga alloy subjected to heat treatment simulating the porcelain firing cycles was not adversely affected by remnants of the original as-cast dendritic microstructure that remained in the relatively large test specimens. A longer heat treatment than recommended by the manufacturer for the porcelain firing cycles is needed to completely eliminate the as-cast dendritic structure in these specimens. The Pd-Cu-Ga alloy exhibited superior fatigue resistance to the Pd-Ga alloy, which has an equiaxed-grain microstructure and lower yield strength.

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

    NASA Astrophysics Data System (ADS)

    Tsui, Lap-Chee

    2003-04-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  20. The study of human mutation rates

    SciTech Connect

    Neel, J.V.

    1992-01-01

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

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

    PubMed

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

    2008-09-01

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

  2. Limited value of PCR for detection of Toxoplasma gondii in blood from human immunodeficiency virus-infected patients.

    PubMed Central

    Franzen, C; Altfeld, M; Hegener, P; Hartmann, P; Arendt, G; Jablonowski, H; Rockstroh, J; Diehl, V; Salzberger, B; Fätkenheuer, G

    1997-01-01

    Cerebral toxoplasmosis is a common, opportunistic, and often life-threatening disease in HIV-infected patients. Diagnosis is supported mainly by clinical evidence and computerized tomography or magnetic resonance imaging scans, but brain images may share features with other brain diseases occurring in HIV-infected patients. To determine the diagnostic value of PCR for the detection of Toxoplasma gondii in blood from HIV-infected patients, we examined 89 blood samples from 59 HIV-infected patients. PCR and Southern blot hybridization were done with DNA extracted from blood samples from 20 patients with confirmed cerebral toxoplasmosis and from 10 patients with suspected but not confirmed cerebral toxoplasmosis. The samples were taken before and 7 to 10 days after the beginning of antiparasitic therapy. For 9 patients who suffered from cerebral toxoplasmosis more than 6 months prior to the study and for 20 patients without any evidence for toxoplasmosis only one blood sample per patient was examined. PCR gave positive results with 5 of the 20 blood samples from patients who suffered from cerebral toxoplasmosis. After 7 to 10 days of therapy PCR results became negative in all these five cases. No amplification was seen with DNA from blood samples from the other 54 patients as the target. The results presented here show that PCR testing of blood samples from HIV-infected patients is of limited value for the diagnosis of cerebral toxoplasmosis. The sensitivity was only 25%, but the specificity was very high (100%), so this technique may be useful for discriminating between cerebral toxoplasmosis and other brain diseases which may be mistaken for toxoplasmosis. PMID:9316922

  3. Cannabis and psychosis/schizophrenia: human studies

    PubMed Central

    Sewell, Richard Andrew; Ranganathan, Mohini

    2010-01-01

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

  4. Cannabis and psychosis/schizophrenia: human studies.

    PubMed

    D'Souza, Deepak Cyril; Sewell, Richard Andrew; Ranganathan, Mohini

    2009-10-01

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

  5. Human Studies of Angiogenic Gene Therapy

    PubMed Central

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

    2009-01-01

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

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

    PubMed Central

    Määttä, Jussi; Roos, Teemu

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

  8. An experimental study of secondary electron emission in the limit of low electron energy

    NASA Astrophysics Data System (ADS)

    Demidov, V. I.; Kaganovich, I. D.; Koepke, M. E.

    2013-09-01

    Study of secondary electron emission (SEE) from solid surfaces is important for many areas of science and technology, including but not limited to the formation of electron clouds in particle accelerators, plasma measurements by electrostatic probes and operation of Hall plasma thrusters. The measurements at low incident electron energy below 2eV are very challenging. The goal of this work is to measure SEE coefficient for molybdenum surface in contact with plasmas. In this study nearly mono-energetic electrons arising in plasma-chemical reactions like pair collisions of metastable atoms have been used for the measurements. Variation of the target voltage and measurement of the corresponding electron current from the mono-energetic electrons allows us to obtain the SEE coefficient. It is experimentally demonstrated that the coefficient is close to zero (less than 0.1) for clean targets and may have much higher value for contaminated targets with some absorbed gas on the surface. This work has been supported by DoE contract No. DE-SC0001939 and SPbGU.

  9. Shedding new light on viruses: super-resolution microscopy for studying human immunodeficiency virus.

    PubMed

    Müller, Barbara; Heilemann, Mike

    2013-10-01

    For more than 70 years electron microscopy (EM) techniques have played an important role in investigating structures of enveloped viruses. By contrast, use of fluorescence microscopy (FM) methods for this purpose was limited by the fact that the size of virus particles is generally around or below the diffraction limit of light microscopy. Various super-resolution (SR) fluorescence imaging techniques developed over the past two decades bypass the diffraction limit of light microscopy, allowing visualization of subviral details and bridging the gap between conventional FM and EM methods. We summarize here findings on human immunodeficiency virus (HIV-1) obtained using SR-FM techniques. Although the number of published studies is currently limited and some of the pioneering analyses also covered methodological or descriptive aspects, recent publications clearly indicate the potential to approach open questions in HIV-1 replication from a new angle.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-10-29

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

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

    NASA Technical Reports Server (NTRS)

    Cianciolo, Alicia D.; Polsgrove, Tara T.

    2016-01-01

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

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

    PubMed

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

    2015-03-01

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

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

    PubMed

    2002-12-01

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

  15. Human factors in resuscitation: Lessons learned from simulator studies

    PubMed Central

    Hunziker, S; Tschan, F; Semmer, N K; Howell, M D; Marsch, S

    2010-01-01

    Medical algorithms, technical skills, and repeated training are the classical cornerstones for successful cardiopulmonary resuscitation (CPR). Increasing evidence suggests that human factors, including team interaction, communication, and leadership, also influence the performance of CPR. Guidelines, however, do not yet include these human factors, partly because of the difficulties of their measurement in real-life cardiac arrest. Recently, clinical studies of cardiac arrest scenarios with high-fidelity video-assisted simulations have provided opportunities to better delineate the influence of human factors on resuscitation team performance. This review focuses on evidence from simulator studies that focus on human factors and their influence on the performance of resuscitation teams. Similar to studies in real patients, simulated cardiac arrest scenarios revealed many unnecessary interruptions of CPR as well as significant delays in defibrillation. These studies also showed that human factors play a major role in these shortcomings and that the medical performance depends on the quality of leadership and team-structuring. Moreover, simulated video-taped medical emergencies revealed that a substantial part of information transfer during communication is erroneous. Understanding the impact of human factors on the performance of a complex medical intervention like resuscitation requires detailed, second-by-second, analysis of factors involving the patient, resuscitative equipment such as the defibrillator, and all team members. Thus, high-fidelity simulator studies provide an important research method in this challenging field. PMID:21063563

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

    ERIC Educational Resources Information Center

    Shipman, Barbara A.

    2012-01-01

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

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

    SciTech Connect

    Bodek, A.

    1996-10-01

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

  18. Study of the N=∞ limit of quantized chiral models in one dimension

    NASA Astrophysics Data System (ADS)

    Ogielski, A. T.

    1982-05-01

    A systematic analysis of the N=∞ limit of quantized one-dimensional chiral models on the sphere SN and on the unitary group U(N) is presented. The theory of projective limits of probability spaces is used to investigate the N=∞ limit of Hilbert spaces, Hamiltonians, energy eigenstates, and correlation functions for both models. The results are as follows: Quantum mechanics of the SN model in the limit is isomorphic to that of a harmonic oscillator in infinite-dimensional Euclidean space. Although all N2 degrees of freedom are nontrivially involved in the matrix U(N) model and the situation is more complex here, its limit is essentially equivalent to the tensor product of an infinite-dimensional harmonic oscillator and the U(1) model. A separate analysis is devoted to the central sector of the U(N) model. In the case of the SU(N) group the U(1) factor is absent.

  19. 40 CFR 159.170 - Human epidemiological and exposure studies.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... studies. 159.170 Section 159.170 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns any study that a person described in § 159.158(a) has concluded, or might reasonably conclude,...

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

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... studies. 159.170 Section 159.170 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED... Information § 159.170 Human epidemiological and exposure studies. Information must be submitted which concerns any study that a person described in § 159.158(a) has concluded, or might reasonably conclude,...

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

    PubMed

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

    2015-12-02

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

  2. Polarization and charge limit studies of strained GaAs photocathodes

    SciTech Connect

    Saez, P.J.

    1997-03-01

    This thesis presents studies on the polarization and charge limit behavior of electron beams produced by strained GaAs photocathodes. These photocathodes are the source of high-intensity, high-polarization electron beams used for a variety of high-energy physics experiments at the Stanford Linear Accelerator Center. Recent developments on P-type, biaxially-strained GaAs photocathodes have produced longitudinal polarization in excess of 80% while yielding beam intensities of {approximately} 2.5 A/cm{sup 2} at an operating voltage of 120 kV. The SLAC Gun Test Laboratory, which has a replica of the SLAC injector, was upgraded with a Mott polarimeter to study the polarization properties of photocathodes operating in a high-voltage DC gun. Both the maximum beam polarization and the maximum charge obtainable from these photocathodes have shown a strong dependence on the wavelength of illumination, on the doping concentration, and on the negative electron affinity levels. The experiments performed for this thesis included studying the effects of temperature, cesiation, quantum efficiency, and laser intensity on the polarization of high-intensity beams. It was found that, although low temperatures have been shown to reduce the spin relaxation rate in bulk semiconductors, they don`t have a large impact on the polarization of thin photocathodes. It seems that the short active region in thin photocathodes does not allow spin relaxation mechanisms enough time to cause depolarization. Previous observations that lower QE areas on the photocathode yield higher polarization beams were confirmed. In addition, high-intensity, small-area laser pulses were shown to produce lower polarization beams. Based on these results, together with some findings in the existing literature, a new proposal for a high-intensity, high-polarization photocathode is given. It is hoped that the results of this thesis will promote further investigation on the properties of GaAs photocathodes.

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

    PubMed

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

    2010-10-01

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

  4. HUMEX. A study on the survivability and adaptation of humans to long-duration exploratory missions

    NASA Astrophysics Data System (ADS)

    Harris, Robert A.

    2003-11-01

    After the realisation of the International Space Station (ISS), human exploratory missions to the Moon or Mars, i.e. beyond low Earth orbit (LEO), are widely considered as the next logical step in worldwide peaceful cooperation in space. The HUMEX study has concentrated on human health related aspects: it provides a critical assessment of the human responses, limits and needs with regard to the stress environments of interplanetary and planetary missions. Emphasis has been put on human health, well-being and performance care, such as radiation health issues, adaptation to microgravity and reduced gravity, psychology issues and health, well-being and performance care, such as radiation health issues, adaptation to microgravity and reduced gravity, psychology issues and health maintenance and on advanced life support developments. The overall study goals are: to define reference scenarios for European participation in human exploration and to estimate their influence on the Life Sciences and Life Support requirements; for selected mission scenarios, to critically assess the limiting factors for human health, well-being, and performance and to recommend relevant countermeasures; for selected mission scenarios, to critically assess the potential of advanced life support developments and to propose a European strategy for this field, including terrestrial applications; to critically assess the applicability of existing facilities and technologies on the ground and in space as test beds for human exploratory missions and to develop a test plan for ground and ISS campaigns; to develop a roadmap for future European activities, in preparation for human exploratory missions, including preparatory activities and terrestrial applications and benefits.

  5. Quantifying altitude of human habitation in studies of human health using geographical name server data.

    PubMed

    Thielke, Stephen; Slatore, Christopher G; Banks, William A

    2016-11-21

    Almost all studies examining the effects of altitude on human health have estimated the geographical altitude of defined regions, yet the primary interest lies in where people live, not the land around them. Populations are not homogenously distributed across altitudes. We propose a straightforward and computationally simple method for estimating the average altitude of habitation within the regional units for which health statistics are typically reported (such as counties). The United States Board on Geographical Names database contains records for over 2.7 million places, which can be processed to select places that are associated with human habitation. These points can easily be averaged by region yielding a representative altitude of human habitation within city, county, state regions, or by longitude and latitude zones. We provide an example of using this approach in a study of human health, and compare it with three other previously used methods of estimating altitude for counties.

  6. Suicide in the Greek penal system and the problem of various limitations in relevant studies.

    PubMed

    Themeli, Olga

    2006-01-01

    Suicides in prison are not merely self-destructive acts or a "cry for help." They reflect the inherent need for freedom and the repercussions of imprisonment. SPACE statistics on suicides in prison reveal a rate above 10 per 10,000 in 10 European countries, 4 of which have a rate above 20. Greek data do not appear in all SPACE statistics. This fact has stimulated the present paper. Unpublished data obtained from the Greek Ministry of Justice reveal that Greece belongs to the group of countries with a rate below 10 in 1995 (the year of SPACE statistics). However, the suicide rates fluctuated widely in Greece from a low rate of 3.2 per 10,000 prisoners (convicted, on remand, or hospitalized) in 1982 to the incredibly high rate of nearly 40 in the year 1979 (11 suicides, 10 of which occurred in prison hospitals). A review of the literature indicates that various limitations mentioned in relevant studies lie in the unreliability of data (doubts about the validity of official statistics, missing data in archives, missing files on the victims, suicide in juvenile institutions not always recorded separately, etc.). The research emphasizes the importance of improving suicide statistics (recording, clearing up the incidents of deaths that are recorded without specification of cause, etc.) in order to plan and enforce suicide prevention and intervention strategies that seem to "work" in a particular milieu and are not debatable (e.g., the use of "suicide proof" cells).

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

  8. Limitations on Recently Suggested Atom Interferometry Mission Concepts for Gravitational Wave Studies

    NASA Astrophysics Data System (ADS)

    Bender, Peter L.

    2012-03-01

    In late 2011, suggestions were made of two new atom interferometry mission concepts for gravitational wave studies. [A presentation by B. N. Saif on these concepts is available on the NASA Physics of the Cosmos website under ``Workshop on Gravitational Wave Mission Architectural Concepts'' (Dec. 20-21, 2011)]. The concepts were for measurements between atom clouds separated by distances of L=500 m or L=500 km. At GW frequencies of 0.1 to 10 Hz, sinusoidal variations in the separations dX between two parts of the atom wavefunctions would be induced by motion of the nulls in the optical potential, using the Bloch oscillation approach. But some apparent limitations of this approach are as follows: the S/N required for achieving the strain sensitivities shown appears to be much higher than the value given in the example in the presentation; the large sinusoidal variations required in the control laser frequency make it difficult to use high finesse cavity mode-cleaners to reduce the effects of laser wavefront aberration fluctuations; very small fluctuations in the temperature or size of the atom clouds would cause serious additional noise, particularly for the L=500 m case; and for the L=500 mission concept, the 10-20 W suggested laser power does not seem to permit keeping the spontaneous emission rate low. However, the main issue is that the required atom interferometry systems appear to be far more complex than the gravitational reference sensors that they would replace.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2009-01-01

    The development of novel techniques and systems to study human infectious diseases in both an in vitro and in vivo settings is always in high demand. Ideally, small animal models are the most efficient method of studying human afflictions. This is especially evident in the study of the human retroviruses, HIV-1 and HTLV-1, in that current simian animal models, though robust, are often expensive and difficult to maintain. Over the past two decades, the construction of humanized animal models through the transplantation and engraftment of human tissues or progenitor cells into immunocompromised mouse strains has allowed for the development of a reconstituted human tissue scaffold in a small animal system. The utilization of small animal models for retroviral studies required expansion of the early CB-17 scid/scid mouse resulting in animals demonstrating improved engraftment efficiency and infectivity. The implantation of uneducated human immune cells and associated tissue provided the basis for the SCID-hu Thy/Liv and hu-PBL-SCID models. Engraftment efficiency of these tissues was further improved through the integration of the non-obese diabetic (NOD) mutation leading to the creation of NODSCID, NOD/Shi-scid IL2rγ-/-, and NOD/SCID β2-microglobulinnull animals. Further efforts at minimizing the response of the innate murine immune system produced the Rag2-/-γc-/- model which marked an important advancement in the use of human CD34+ hematopoietic stem cells. Together, these animal models have revolutionized the investigation of retroviral infections in vivo. PMID:19674458

  11. Integrative Review of the Literature on Adults with Limited Education and Skills and the Implications for Human Resource Development

    ERIC Educational Resources Information Center

    Hamilton, David W.; Torraco, Richard J.

    2013-01-01

    Adults with limited education and skills--those who lack the education and skills needed for full participation in U.S. culture and economy--are increasing in numbers. However, the knowledge base addressing this population and their educational needs is fragmented across the literature of several disciplines. A comprehensive review and critique of…

  12. Exploring the damage limitation possibilities of mineral fibres for future integrated solutions: an in vitro study.

    PubMed

    Gabbanelli, F; Mattioli-Belmonte, M; Giantomassi, F; Rimondini, L; Viticchi, C; Biagini, G; Torricelli, P; Gualtieri, A F; Lesci, I G; Giardino, R

    2003-01-01

    Owing to their possible carcinogenic effect, asbestos and other silica derivatives have been identified as priority substances for risk reduction and prevention of pollution. Neutralisation procedures have thus become a topical research subject in many European and American countries. In the present study, silica derivatives (asbestos-containing and asbestos substitutes like slag wool, rock wool, cement asbestos) were fully impregnated with an epoxy resin according to the procedure used for the in situ impregnation with viscous polymeric media, which penetrate and cement the fibres in place and reduce the risk of their dispersion in air. Untreated and treated samples were used to investigate their in vitro interaction with a human continuous epithelial cell line (NCTC 2544 keratinocytes) and test the resin's efficiency in passivating the surface activity of the fibrous particulate. SEM and morpho-quantitative data evidenced that impregnation with the epoxy resin modifies the mineral fibres' bioactivity (reduction of cell adhesion and decreased spread/round cell ratio) and demonstrated the value of in vitro cell testing after passivation as a risk-assessment procedure. These tests could be used for the rapid determination of the level of passivation of new synthetic mineral fibrous materials subjected to resin impregnation.

  13. Identifying selective inhibitors against the human cytosolic sialidase NEU2 by substrate specificity studies.

    PubMed

    Li, Yanhong; Cao, Hongzhi; Yu, Hai; Chen, Yi; Lau, Kam; Qu, Jingyao; Thon, Vireak; Sugiarto, Go; Chen, Xi

    2011-04-01

    Aberrant expression of human sialidases has been shown to associate with various pathological conditions. Despite the effort in the sialidase inhibitor design, less attention has been paid to designing specific inhibitors against human sialidases and characterizing the substrate specificity of different sialidases regarding diverse terminal sialic acid forms and sialyl linkages. This is mainly due to the lack of sialoside probes and efficient screening methods, as well as limited access to human sialidases. A low cellular expression level of the human sialidase NEU2 hampers its functional and inhibitory studies. Here we report the successful cloning and expression of the human sialidase NEU2 in E. coli. About 11 mg of soluble active NEU2 was routinely obtained from 1 L of E. coli cell culture. Substrate specificity studies of the recombinant human NEU2 using twenty p-nitrophenol (pNP)-tagged α2-3- or α2-6-linked sialyl galactosides containing different terminal sialic acid forms including common N-acetylneuraminic acid (Neu5Ac), non-human N-glycolylneuraminic acid (Neu5Gc), 2-keto-3-deoxy-D-glycero-D-galacto-nonulosonic acid (Kdn), or their C5-derivatives in a microtiter plate-based high-throughput colorimetric assay identified a unique structural feature specifically recognized by the human NEU2 but not two bacterial sialidases. The results obtained from substrate specificity studies were used to guide the design of a sialidase inhibitor that was selective against human NEU2. The selectivity of the inhibitor was revealed by the comparison of sialidase crystal structures and inhibitor docking studies.

  14. Machine Learning for Big Data: A Study to Understand Limits at Scale

    SciTech Connect

    Sukumar, Sreenivas R.; Del-Castillo-Negrete, Carlos Emilio

    2015-12-21

    This report aims to empirically understand the limits of machine learning when applied to Big Data. We observe that recent innovations in being able to collect, access, organize, integrate, and query massive amounts of data from a wide variety of data sources have brought statistical data mining and machine learning under more scrutiny, evaluation and application for gleaning insights from the data than ever before. Much is expected from algorithms without understanding their limitations at scale while dealing with massive datasets. In that context, we pose and address the following questions How does a machine learning algorithm perform on measures such as accuracy and execution time with increasing sample size and feature dimensionality? Does training with more samples guarantee better accuracy? How many features to compute for a given problem? Do more features guarantee better accuracy? Do efforts to derive and calculate more features and train on larger samples worth the effort? As problems become more complex and traditional binary classification algorithms are replaced with multi-task, multi-class categorization algorithms do parallel learners perform better? What happens to the accuracy of the learning algorithm when trained to categorize multiple classes within the same feature space? Towards finding answers to these questions, we describe the design of an empirical study and present the results. We conclude with the following observations (i) accuracy of the learning algorithm increases with increasing sample size but saturates at a point, beyond which more samples do not contribute to better accuracy/learning, (ii) the richness of the feature space dictates performance - both accuracy and training time, (iii) increased dimensionality often reflected in better performance (higher accuracy in spite of longer training times) but the improvements are not commensurate the efforts for feature computation and training and (iv) accuracy of the learning algorithms

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

    NASA Astrophysics Data System (ADS)

    Wang, Feng; Uematsu, Haruyuki; Otani, Nobuo

    2007-12-01

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

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

    PubMed Central

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

    2005-01-01

    Background: The Recover Study is an ongoing, prospective study designed 10 to assess toxicity associated with the use of nucleoside analogue reverse transcriptase inhibitors (NRTIs) (stavudine, zidovudine, lamivudine, didanosine, abacavir) in HIV-1-infected patients receiving highly active antiretroviral therapy (HAART) in routine clinical practice. This project is being conducted at 120 HIV units at teaching hospitals across Spain. Objective: The aim of this study was to identify the most common treatment-limiting 10 moderate to severe clinical and laboratory adverse effects (AEs), and the individual NRTIs involved in the development of these effects, in HIV-1-infected patients receiving HAART who discontinued use of an NRTI in the Recover Study. Methods: Patients eligible for participation in the Recover Study are aged10 ≥18 years; have virologically documented HIV-1 infection; have sustained viral suppression (viral load <200 cells/mL or stable, heavily experienced [ie, have received ≥3 antiretroviral regimens] patients with viral load <5000 cells/mL) for ≥6 months; are receiving HAART; are undergoing active follow-up; and have developed 2:1 NRTI-associated AE that, in the opinion of a study investigator and under the conditions of routine clinical practice, justified discontinuation of treatment with the offending drug (principal AE/offending NRTI). The present study included patients recruited for the Recover Study between September 2002 and May 2003. Results: A total of 1391 patients were enrolled (966 men, 425 women; mean 1 age, 42 years [range, 18–67 years]). Five hundred six patients (36.4%) had been diagnosed with AIDS. The mean duration of treatment with the offending NRTI was 74 months (range, 6–156 months). Seven hundred nine patients (51.0%) were receiving fourth-line (or more) therapy. Eight hundred twenty-one patients (59.0%) were receiving nonnucleoside analogues, and 552 patients (39.7%), protease inhibitors, as components of their HAART

  17. Perfluorochemicals and Human Semen Quality: The LIFE Study

    PubMed Central

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

    2014-01-01

    : Buck Louis GM, Chen Z, Schisterman EF, Kim S, Sweeney AM, Sundaram R, Lynch CD, Gore-Langton RE, Barr DB. 2015. Perfluorochemicals and human semen quality: the LIFE Study. Environ Health Perspect 123:57–63; http://dx.doi.org/10.1289/ehp.1307621 PMID:25127343

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

    PubMed Central

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

    2016-01-01

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

  19. Applications and limitations of inflammatory biomarkers for studies on neurocognitive impairment in HIV infection.

    PubMed

    Cassol, Edana; Misra, Vikas; Morgello, Susan; Gabuzda, Dana

    2013-12-01

    Despite reduced prevalence of severe forms of HIV-associated neurocognitive disorders (HAND) on current antiretroviral therapy (ART) regimens, milder forms of neurocognitive impairment (NCI) remain prevalent in HIV-infected populations. These mild forms of HAND consist of subtypes, probably reflecting distinct, though possibly overlapping, pathophysiological mechanisms. Factors associated with HAND in HIV patients with prolonged viral suppression on ART include older age, low nadir CD4, active HCV co-infection, and cardiovascular risk factors, but underlying mechanisms and their relationship to innate immune activation, chronic inflammation, and other features of systemic disease are poorly understood. In this article, we discuss applications and limitations of plasma inflammatory biomarkers for studies on HAND in HIV patients on ART and describe an analysis pipeline to reduce common sources of noise and increase likelihood of identifying relevant inflammatory biomarkers. Clinical covariates and comorbidities that influence inflammatory biomarkers, such as aging, obesity, metabolic abnormalities, HCV co-infection, and substance abuse, are also reviewed. As an example for using this analytic pipeline, we present an exploratory study of 22 plasma inflammatory biomarkers (IFN-α 2b and -γ, 16 cytokines/chemokines, sIL-2R, sCD14, HA, and YKL-40) in a cohort of HIV-infected individuals with advanced disease, frequent HCV co-infection, and viral suppression on ART. The identification of inflammatory biomarkers associated with HAND in HIV+ patients on ART may be useful to distinguish between HAND subtypes with distinct pathophysiology, and is important for achieving a systems-level understanding of the biology of these disorders, developing effective therapies, and evaluating therapeutic outcomes.

  20. Human herpesvirus 6A (HHV-6A) exhibits restrictive propagation with limited activation of PKR-eIF2α stress pathway.

    PubMed

    Sharon, Eyal; Frenkel, Niza

    2017-02-15

    The eIF2α protein plays a critical role in the regulation of translation. The production of dsRNA during viral replication can activate protein kinase R (PKR) which phosphorylates the eIF2α, leading to inhibition of the initial step of translation. Many viruses have evolved gene products targeting PKR-eIF2a pathway, indicating its importance in antiviral defense. In the present study we focus on alternations of PKR-eIF2a pathway along HHV-6A infection while monitoring viral gene expression and infectious viral yields. We have found increased phosphorylated PKR as well as phosphorylated eIF2α coincidental with accumulation of the late gp82-105 viral protein. The level of total PKR was relatively constant, but it decreased by 144 hours post infection. The phosphorylation of eIF2a led to a moderate increase in ATF4 accumulation, indicating moderate inhibition of protein translation during HHV-6A infection. The overexpression of PKR led to decreased viral propagation coincidental with increased accumulation of phosphorylated PKR and phosphorylated eIF2a. Moreover, addition of dominant-negative PKR mutant resulted in a moderate increase in viral replication. HHV-6A exhibits relatively low propagation efficiency of progeny virus secreted into the culture media. This study suggests that the replicative strategy of HHV-6A involves a mild infection over lengthy life cycle in culture, while preventing severe activation of the PKR-eIF2α pathway.IMPORTANCE Human herpesvirus 6A (HHV-6A) and HHV-6B are common, wildly prevalent viruses, causing from mild to severe disease. Our study focuses on the PKR-eIF2α stress pathway that limits viral replication. The HHV-6 genome encodes multiple genes transcribed from the two strands predicting accumulation of dsRNAs which can activates PKR and inhibition of protein synthesis. We report that HHV-6A induced the accumulation of phosphorylated PKR, phosphorylated eIF2α and a moderate increase of the activating transcription factor 4

  1. The blp Locus of Streptococcus pneumoniae Plays a Limited Role in the Selection of Strains That Can Cocolonize the Human Nasopharynx

    PubMed Central

    Valente, Carina; Dawid, Suzanne; Pinto, Francisco R.; Hinds, Jason; Simões, Alexandra S.; Gould, Katherine A.; Mendes, Luís A.; de Lencastre, Hermínia

    2016-01-01

    ABSTRACT Nasopharyngeal colonization is important for Streptococcus pneumoniae evolution, providing the opportunity for horizontal gene transfer when multiple strains co-occur. Although colonization with more than one strain of pneumococcus is common, the factors that influence the ability of strains to coexist are not known. A highly variable blp (bacteriocin-like peptide) locus has been identified in all sequenced strains of S. pneumoniae. This locus controls the regulation and secretion of bacteriocins, small peptides that target other bacteria. In this study, we analyzed a series of cocolonizing isolates to evaluate the impact of the blp locus on human colonization to determine whether competitive phenotypes of bacteriocin secretion restrict cocolonization. We identified a collection of 135 nasopharyngeal samples cocolonized with two or more strains, totaling 285 isolates. The blp locus of all strains was characterized genetically with regard to pheromone type, bacteriocin/immunity content, and potential for locus functionality. Inhibitory phenotypes of bacteriocin secretion and locus activity were assessed through overlay assays. Isolates from single colonizations (n = 298) were characterized for comparison. Cocolonizing strains had a high diversity of blp cassettes; approximately one-third displayed an inhibitory phenotype in vitro. Despite in vitro evidence of competition, pneumococci cocolonized the subjects independently of blp pheromone type (P = 0.577), bacteriocin/immunity content, blp locus activity (P = 0.798), and inhibitory phenotype (P = 0.716). In addition, no significant differences were observed when single and cocolonizing strains were compared. Despite clear evidence of blp-mediated competition in experimental models, the results of our study suggest that the blp locus plays a limited role in restricting pneumococcal cocolonization in humans. IMPORTANCE Nasopharyngeal colonization with Streptococcus pneumoniae (pneumococcus) is important for

  2. Tea and cancer prevention: studies in animals and humans.

    PubMed

    Chung, Fung-Lung; Schwartz, Joel; Herzog, Christopher R; Yang, Yang-Ming

    2003-10-01

    The role of tea in protection against cancer has been supported by ample evidence from studies in cell culture and animal models. However, epidemiological studies have generated inconsistent results, some of which associated tea with reduced risk of cancer, whereas others found that tea lacks protective activity against certain human cancers. These results raise questions about the actual role of tea in human cancer that needs to be addressed. This article is intended to provide a better perspective on this controversy by summarizing the laboratory studies in animals and humans with emphasis on animal tumor bioassays on skin, lung, mammary glands and colon, and the molecular and cellular mechanisms affected by tea. Finally, a recent small pilot intervention study with green tea in smokers is presented.

  3. Overview of the epidemiology methods and applications: strengths and limitations of observational study designs.

    PubMed

    Colditz, Graham A

    2010-01-01

    process and the range of nutrient intakes in the population. In retrospective case-control studies, recall bias of past diet is an additional issue with which to contend. Unlike smoking or screening tests in which the exposure is finite and can be completely stopped and started, one's diet, physical activity, and weight change cannot go to zero for prolonged periods and sustain life. The range of nutrient intake is a major issue when enrolling participants into prevention trials and observational studies. Health-conscious volunteers are more often identified and screened as eligible for a trial. The epidemiology of diet and colon cancer has been extensively studied. For example, Cho et al. (2004) conducted a combined analysis of prospective dietary studies of calcium and vitamin D intake data from 10 cohorts. The dose-response relationship for calcium showed that the greatest benefit for increasing calcium intake was for those participants who had a reported daily intake below 1000 mg/d. Increasing the intake of those individuals with low intake to the level of 1000 mg/day would yield a 20% reduction in risk. Beyond this level of intake, there was little additional reduction in the risk of colon cancer. In the Women's Health Initiative, participants had a mean calcium intake of 1150 mg/d at baseline and increased this intake in the intervention arm to 2250 mg/d on average. This magnitude of increase was of limited association in the combined, prospective, cohort studies and was not related to risk in the randomized trial (Wactawski-Wende et al., 2006). Similar findings apply to the interpretation of the vitamin D intervention and highlight the role of dietary intake at randomization when evaluating dietary components. Returning to the time frame of exposure in the carcinogenic process, the null randomized, controlled trials of fiber (Alberts et al., 2000) and fruit and vegetables (Schatzkin et al., 2000) for the prevention of polyp recurrence amply illustrate Zelen

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

    SciTech Connect

    Fabrikant, J.I.

    1982-08-01

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

  5. T cell expansion is the limiting factor of virus control in mice with attenuated TCR signaling: implications for human immunodeficiency.

    PubMed

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

    2015-03-15

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

  6. Limitations to Work-Related Functioning of People with Persistent "Medically Unexplained" Physical Symptoms: A Modified Delphi Study Among Physicians.

    PubMed

    Weerdesteijn, K H N; Schaafsma, F G; van der Beek, A J; Anema, J R

    2016-10-19

    Purpose The purpose of this study was to obtain consensus among physicians of several medical specialties on the level of limitations to work-related functioning of people with persistent "medically unexplained" physical symptoms (PPS). Methods A modified Delphi study was conducted with 15 physicians of five different medical specialties. The study involved two email rounds and one meeting. In each round, the physicians prioritized the level of limitations in 78 work-related functioning items for four different PPS cases. These items were based on the Dutch Functional Ability List, national guidelines and scientific literature regarding the International Classification of Functioning. Results In all four cases, the physicians reached consensus on the level of limitations to work-related functioning in 49 items. The physicians reported the highest number and level of limitations for PPS of the back and lower extremities, but they reported hardly any limitations for PPS of the abdomen and genitals. For PPS of the head, they reported mainly limitations to personal and social functioning; for PPS of the neck, back and upper or lower extremities, they reported mainly limitations to dynamic movements and static postures. The physicians could not reach consensus on limitations in the category of working hours. Conclusion Physicians reached consensus on the level of limitations in a substantial part of work-related functioning items for PPS. There was a difference in the number and severity of limitations between different cases of PPS. The assessment of functioning seems to be based more on the specific impairment than on the disease.

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

    PubMed Central

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

    2016-01-01

    In spite of wide-spread vaccination, pertussis rates are rising in industrialized countries and remain high world-wide. With no specific therapeutics to treat disease, pertussis continues to cause considerable infant morbidity and mortality. The pertussis toxin is a major contributor to disease, responsible for local and systemic effects including leukocytosis and immunosuppression. Here, we humanized two murine monoclonal antibodies that neutralize pertussis toxin and expressed them as human IgG1 molecules with no loss of affinity or in vitro neutralization activity. When administered prophylactically to mice as a binary cocktail, antibody treatment completely mitigated the B. pertussis-induced rise in white blood cell count and decreased bacterial colonization. When administered therapeutically to baboons, antibody-treated but not control animals experienced a blunted rise in white blood cell count and accelerated bacterial clearance rates. These preliminary findings support further investigation into the use of these antibodies to treat human neonatal pertussis in conjunction with antibiotics and supportive care. PMID:26631634

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

    ERIC Educational Resources Information Center

    Galantucci, Bruno

    2005-01-01

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

  9. Study of the critical behavior of the driven lattice gas model with limited nonequilibrium dynamics

    NASA Astrophysics Data System (ADS)

    Saracco, Gustavo P.; Rubio Puzzo, M. Leticia; Bab, Marisa A.

    2017-02-01

    In this paper the nonequilibrium critical behavior is investigated using a variant of the well-known two-dimensional driven lattice gas (DLG) model, called modified driven lattice gas (MDLG). In this model, the application of the external field is regulated by a parameter p ɛ [ 0 , 1 ] in such a way that if p = 0, the field is not applied, and it becomes the Ising model, while if p = 1, the DLG model is recovered. The behavior of the model is investigated for several values of p by studying the dynamic evolution of the system within the short-time regime in the neighborhood of a phase transition. It is found that the system experiences second-order phase transitions in all the interval of p for the density of particles ρ = 0.5. The determined critical temperatures Tc(p) are greater than the critical temperature of the Ising model TcI, and increase with p up to the critical temperature of the DLG model in the limit of infinite driving fields. The dependence of Tc(p) on p is compatible with a power-law behavior whose exponent is ψ = 0.27(3) . Furthermore, the complete set of the critical and the anisotropic exponents is estimated. For the smallest value of p, the ​dynamics and β exponents are close to that calculated for the Ising model, and the anisotropic exponent Δ is near zero. As p is increased, the exponents and Δ change, meaning that the anisotropy effects increase. For the largest value investigated, the set of exponents approaches to that reported by the most recent theoretical framework developed for the DLG model.

  10. Strengths and Limitations of Model Systems for the Study of Urinary Tract Infections and Related Pathologies

    PubMed Central

    Barber, Amelia E.; Norton, J. Paul; Wiles, Travis J.

    2016-01-01

    SUMMARY Urinary tract infections (UTIs) are some of the most common bacterial infections worldwide and are a source of substantial morbidity among otherwise healthy women. UTIs can be caused by a variety of microbes, but the predominant etiologic agent of these infections is uropathogenic Escherichia coli (UPEC). An especially troubling feature of UPEC-associated UTIs is their high rate of recurrence. This problem is compounded by the drastic increase in the global incidence of antibiotic-resistant UPEC strains over the past 15 years. The need for more-effective treatments for UTIs is driving research aimed at bettering our understanding of the virulence mechanisms and host-pathogen interactions that occur during the course of these infections. Surrogate models of human infection, including cell culture systems and the use of murine, porcine, avian, teleost (zebrafish), and nematode hosts, are being employed to define host and bacterial factors that modulate the pathogenesis of UTIs. These model systems are revealing how UPEC strains can avoid or overcome host defenses and acquire scarce nutrients while also providing insight into the virulence mechanisms used by UPEC within compromised individuals, such as catheterized patients. Here, we summarize our current understanding of UTI pathogenesis while also giving an overview of the model systems used to study the initiation, persistence, and recurrence of UTIs and life-threatening sequelae like urosepsis. Although we focus on UPEC, the experimental systems described here can also provide valuable insight into the disease processes associated with other bacterial pathogens both within the urinary tract and elsewhere within the host. PMID:26935136

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

    SciTech Connect

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

    2008-11-15

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

  12. Fraud Detection by Human Agents: A Pilot Study

    NASA Astrophysics Data System (ADS)

    Almendra, Vinicius; Schwabe, Daniel

    Fraud is a constant problem for online auction sites. Besides failures in detecting fraudsters, the currently employed methods yield many false positives: bona fide sellers that end up harassed by the auction site as suspects. We advocate the use of human computation (also called crowdsourcing) to improve precision and recall of current fraud detection techniques. To examine the feasibility of our proposal, we did a pilot study with a set of human subjects, testing whether they could distinguish fraudsters from common sellers before negative feedback arrived and looking just at a snapshot of seller profiles. Here we present the methodology used and the obtained results, in terms of precision and recall of human classifiers, showing positive evidence that detecting fraudsters with human computation is viable.

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

    SciTech Connect

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

    1995-06-01

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

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

    PubMed Central

    Sim, Ida; Carini, Simona; Tu, Samson W.; Detwiler, Landon T.; Brinkley, James; Mollah, Shamim A.; Burke, Karl; Lehmann, Harold P.; Chakraborty, Swati; Wittkowski, Knut M.; Pollock, Brad H.; Johnson, Thomas M.; Huser, Vojtech

    2012-01-01

    Human studies are one of the most valuable sources of knowledge in biomedical research, but data about their design and results are currently widely dispersed in siloed systems. Federation of these data is needed to facilitate large-scale data analysis to realize the goals of evidence-based medicine. The Human Studies Database project has developed an informatics infrastructure for federated query of human studies databases, using a generalizable approach to ontology-based data access. Our approach has three main components. First, the Ontology of Clinical Research (OCRe) provides the reference semantics. Second, a data model, automatically derived from OCRe into XSD, maintains semantic synchrony of the underlying representations while facilitating data acquisition using common XML technologies. Finally, the Query Integrator issues queries distributed over the data, OCRe, and other ontologies such as SNOMED in BioPortal. We report on a demonstration of this infrastructure on data acquired from institutional systems and from ClinicalTrials.gov. PMID:23304360

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

    PubMed

    Filler, Scott G

    2012-04-01

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

  16. Methodological issues in human studies of endocrine disrupting chemicals.

    PubMed

    Lee, Duk-Hee; Jacobs, David R

    2015-12-01

    Possible harm from endocrine disrupting chemicals (EDCs) in humans is speculated based on two types of evidence; 1) increasing trends of suspected diseases in ecological studies of populations and 2) findings from traditional epidemiological studies of individuals. However, ecological findings are not regarded as direct human evidence of the relation between EDCs and disease, while the evidence among epidemiological studies of individuals is often inconsistent. Thus, a criticism is that linking EDCs and health in human is naively presumed without solid evidence. However, human studies of EDCs are methodologically complex and understanding methodological issues will help to interpret findings from existing human studies and to properly design optimal human studies. The key issues are low reliability of exposure assessment of EDCs with short half-lives, EDC mixtures, possibility of non-monotonic dose-response relationships, non-existence of an unexposed group, difficulties in measuring exposure during critical periods, and interactions with established risk factors. Furthermore, EDC mixtures may affect human health through other mechanisms than traditional endocrine disruption, for example glutathione depletion or mitochondrial dysfunction. Given this complexity, the most plausible scenario in humans is that exposure to EDC mixtures leads to increasing risk of related diseases at the ecological level, but inconsistent associations would be expected in traditional epidemiological studies. Although epidemiologists have long relied on Bradford Hill's criteria to objectively evaluate whether associations observed in epidemiology can be interpreted as causal, there are challenges to use these criteria for EDCs, particularly concerning consistency across studies and the findings of linear dose-response relationships. At the individual level, compared to EDCs with short half-lives, epidemiological studies of EDCs with long half-lives among populations with a relatively low

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

    NASA Astrophysics Data System (ADS)

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

    2015-04-01

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

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

    NASA Astrophysics Data System (ADS)

    Mou, Qizheng; Mou, Kai

    2002-01-01

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

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

    PubMed

    Cassidy, V R

    1996-03-01

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

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

    PubMed Central

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

    1998-01-01

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

  1. Animal Models to Study Placental Development and Function throughout Normal and Dysfunctional Human Pregnancy.

    PubMed

    Grigsby, Peta L

    2016-01-01

    Abnormalities of placental development and function are known to underlie many pathologies of pregnancy, including spontaneous preterm birth, fetal growth restriction, and preeclampsia. A growing body of evidence also underscores the importance of placental dysfunction in the lifelong health of both mother and offspring. However, our knowledge regarding placental structure and function throughout pregnancy remains limited. Understanding the temporal growth and functionality of the human placenta throughout the entirety of gestation is important if we are to gain a better understanding of placental dysfunction. The utilization of new technologies and imaging techniques that could enable safe monitoring of placental growth and function in vivo has become a major focus area for the National Institutes of Child Health and Human Development, as evident by the establishment of the "Human Placenta Project." Many of the objectives of the Human Placenta Project will necessitate preclinical studies and testing in appropriately designed animal models that can be readily translated to the clinical setting. This review will describe the advantages and limitations of relevant animals such as the guinea pig, sheep, and nonhuman primate models that have been used to study the role of the placenta in fetal growth disorders, preeclampsia, or other maternal diseases during pregnancy.

  2. Fully validated LCMS bioanalysis of Bevacizumab in human plasma using nano-surface and molecular-orientation limited (nSMOL) proteolysis.

    PubMed

    Iwamoto, Noriko; Umino, Yukari; Aoki, Chikage; Yamane, Naoe; Hamada, Akinobu; Shimada, Takashi

    2016-02-01

    The chemistry of nano-surface and molecular-orientation limited (nSMOL) proteolysis is the Fab-selective limited proteolysis by making use the difference of protease nanoparticle diameter (200 nm) and antibody resin pore diameter (100 nm). In this report, we have demonstrated that the full validation for Bevacizumab bioanalysis in human plasma using nSMOL. The immunoglobulin fraction was collected by Protein A resin from plasma, then nSMOL reaction was performed using the FG nanoparticle-immobilized trypsin under the nondenaturing physiological condition at 50 °C for 6 h. After removal of resin and nanoparticles, the signature peptide of Bevacizumab complementarity-determining region (CDR) and internal standard P14R were simultaneously quantified by LCMS multiple reaction monitoring (MRM). This nSMOL method quantification of Bevacizumab showed sensitivity of 0.146 μg/ml and linearity of 0.146-300 μg/ml. The intra- and inter-assay precision of lower limit of quantification (LLOQ), low quality control (LQC), middle quality control (MQC), and high quality control (HQC) was 7.94-15.2% and 14.6%, 7.15-13.5% and 11.7%, 2.63-6.47% and 5.83%, and 3.09-4.35% and 4.45%, respectively. These results indicate that nSMOL is also significant method for Bevacizumab bioanalysis in human plasma.

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

    USGS Publications Warehouse

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

    1997-01-01

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

  4. In vivo localized proton spectroscopic studies of human gastrocnemius muscle

    SciTech Connect

    Narayana, P.A.; Jackson, E.F.; Hazle, J.D.; Fotedar, L.K.; Kulkarni, M.V.; Flamig, D.P.

    1988-10-01

    In vivo proton magnetic resonance spectroscopy studies of gastrocnemius muscle were performed in six normal volunteers. Both spatially resolved spectroscopy (SPARS) and stimulated echo acquisition mode (STEAM) sequences were used for volume localization. A number of water suppression sequences have been combined with these localization schemes. Among the various techniques investigated in these studies, STEAM with an inversion pulse (T1-discriminated spectrum) seems to have the best potential for in vivo localized high-resolution proton spectroscopy studies of human muscle.

  5. Limiting factor analysis and regulation for urban ecosystems—A case study of Ningbo, China

    NASA Astrophysics Data System (ADS)

    Yang, Z. F.; Su, M. R.; Zhang, B.; Zhang, Y.; Hu, T. L.

    2010-09-01

    Considering the importance of supporting system for the urban ecosystem development, the urban ecological carrying capacity (UECC) representing the supporting functions of biophysical environment for urban development is introduced into the analysis of urban ecosystem degradation. It is proposed in this paper that the urban ecosystem degradation can be attributed to the imbalance between supply and demand of UECC, i.e. the conflict between the infinite demand of urban development and finite supply of biophysical supporting system, which can be mainly described by the dominant limiting factors of UECC. Through the shortage indices of various factors that denoted by the ratio of the gap between the demand and supply to the demand, the limiting factors of UECC can be identified and graded with different levels. The urban ecosystem degradation can thus be regulated by adjusting the relationship of supply and demand in terms of limiting factors from both the layers of technical practice and goal-based government management. As for Ningbo City, the shortage of water resources quantity, the pressure of SO2 emission, insufficiency of sewage treatment and green area are the prominent limiting factors and corresponding regulation scheme is thereafter suggested to adjust the relationship between supply and demand of UECC.

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

    ERIC Educational Resources Information Center

    Giambo, Debra A.

    2010-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Luck, C. L.; Lee, S.

    1993-01-01

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

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

    ERIC Educational Resources Information Center

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

    2014-01-01

    In the first three sections of this paper we comment on some of the ideas developed in the forum papers, pointing out possible misunderstandings and constructing new explanations that clarify arguments we made in the original article. In the last section we expand the discussion raised in the original paper, elaborating on the limits of the use of…

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

    PubMed

    Attaianese, Erminia; Duca, Gabriella

    2012-01-01

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

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

    ERIC Educational Resources Information Center

    1971

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

  11. Two open states and rate-limiting gating steps revealed by intracellular Na+ block of human KCNQ1 and KCNQ1/KCNE1 K+ channels

    PubMed Central

    Pusch, Michael; Ferrera, Loretta; Friedrich, Thomas

    2001-01-01

    KCNQ1, the first member of a new K+ channel family, associates with the small KCNE1 subunit to form the slow cardiac delayed rectifier current, IKs. Mutations in both genes encoding these channels lead to cardiac arrhythmia. We studied the block by intracellular Na+ of human homomeric KCNQ1 (homomers) and heteromeric KCNQ1/KCNE1 (heteromers) expressed in CHO cells (Chinese hamster ovary cell line) using whole-cell patch recording. In the nominal absence of extracellular K+ and with 65 mm intracellular K+, the replacement of 65 mm intracellular N-methyl-d-glucamine (NMDG+) by 65 mm Na+ induced a decay of outward (K+) currents through homomers after maximal activation reminiscent of an inactivation process. The decay had a time constant in the hundreds of milliseconds range. The inactivation process of homomers was, however, not directly dependent on [Na+]i, as evidenced by unaltered biphasic deactivation at negative voltages. An instantaneous voltage-dependent Na+ block of homomers was revealed using tail current protocols with activating prepulses that saturated the gating processes of the channel. The instantaneous block was partially relieved at very large positive voltages (≥ 60 mV) and in 20 mm extracellular K+. The instantaneous block of homomers was much less pronounced if the tail currents were measured after short activating prepulses, demonstrating the presence of (at least) two open states: a first, relatively [Na+]i-insensitive and a subsequent [Na+]i-sensitive open state; the current decay reflects the transition between the two open states. Heteromers exhibited a very similar instantaneous block by Nai+ independently of the prepulse duration. Heteromers did not show a Nai+-induced current decay. Our results demonstrate the presence of two open states of KCNQ1 channels with different [Na+]i sensitivities. The rate-limiting step of homomeric KCNQ1 gating at positive voltages is the transition between these two open states. The rate-limiting step of the

  12. Two open states and rate-limiting gating steps revealed by intracellular Na+ block of human KCNQ1 and KCNQ1/KCNE1 K+ channels.

    PubMed

    Pusch, M; Ferrera, L; Friedrich, T

    2001-05-15

    KCNQ1, the first member of a new K+ channel family, associates with the small KCNE1 subunit to form the slow cardiac delayed rectifier current, IKs. Mutations in both genes encoding these channels lead to cardiac arrhythmia. We studied the block by intracellular Na+ of human homomeric KCNQ1 (homomers) and heteromeric KCNQ1/KCNE1 (heteromers) expressed in CHO cells (Chinese hamster ovary cell line) using whole-cell patch recording. In the nominal absence of extracellular K+ and with 65 mM intracellular K+, the replacement of 65 mM intracellular N-methyl-D-glucamine (NMDG+) by 65 mM Na+ induced a decay of outward (K+) currents through homomers after maximal activation reminiscent of an inactivation process. The decay had a time constant in the hundreds of milliseconds range. The inactivation process of homomers was, however, not directly dependent on [Na+]i, as evidenced by unaltered biphasic deactivation at negative voltages. An instantaneous voltage-dependent Na+ block of homomers was revealed using tail current protocols with activating prepulses that saturated the gating processes of the channel. The instantaneous block was partially relieved at very large positive voltages (> or = 60 mV) and in 20 mM extracellular K+. The instantaneous block of homomers was much less pronounced if the tail currents were measured after short activating prepulses, demonstrating the presence of (at least) two open states: a first, relatively [Na+]i-insensitive and a subsequent [Na+]i-sensitive open state; the current decay reflects the transition between the two open states. Heteromers exhibited a very similar instantaneous block by Na+i independently of the prepulse duration. Heteromers did not show a Na+i-induced current decay. Our results demonstrate the presence of two open states of KCNQ1 channels with different [Na+]i sensitivities. The rate-limiting step of homomeric KCNQ1 gating at positive voltages is the transition between these two open states. The rate-limiting step of

  13. Studying human immunodeficiencies in humans: advances in fundamental concepts and therapeutic interventions

    PubMed Central

    Su, Helen

    2017-01-01

    Immunodeficiencies reveal the crucial role of the immune system in defending the body against microbial pathogens. Given advances in genomics and other technologies, this is currently best studied in humans who have inherited monogenic diseases. Such investigations have provided insights into how gene products normally function in the natural environment and have opened the door to new, exciting treatments for these diseases.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed

    Auer, Michael; Griffiths, Mark D

    2013-12-01

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

  16. Studies of the disposition and metabolism of mefloquine HCl (WR 142,490), a quinolinemethanol antimalarial, in the rat. Limited studies with an analog, WR 30,090.

    PubMed

    Mu, J Y; Israili, Z H; Dayton, P G

    1975-01-01

    The overall fate of the quinolinemethanol antimalarial, mefloquine-HCl [WR 142,490, erythro-DL-alpha-(2-piperidyl)-2,9-bis(trifluoromethyl)-4-quinolinemethanol hydrochloride] was investigated in the rat with 14C-labeled drug. Despite its extensive binding to plasma proteins, high tissue/plasma concentration ratios were found. Fecal excretion accounted for most of the drug and metabolites. This fate was rationalized on the basis of physical properties of mefloquine (and its metabolites) and extensive biliary and gastric secretion, followed by reabsorption. Evidence was obtained for the formation of several metabolites. Limited studies were carried out in rats, dogs, and one human subject with another quinolinemethanol, WR 30,090-14C [DL-6,8-dichloro-2-(3',4'-dichlorophenyl)-alpha-(di-n-butylaminomethyl)-4-quinolinemethanol hydrochloride]. Its general fate and physical properties were similar to mefloquine. The disposition of the two quinoline compounds studied was compared to that of quinine and quinidine reported in the literature. This revealed that modification of the quinine molecule resulted in new drugs which were more highly bound and exhibited longer half-lives than quinine.

  17. Study of Laser Produced Plasma of Limiter of the Aditya Tokomak for Detection of Molecular Bands

    NASA Astrophysics Data System (ADS)

    Rai, Awadhesh Kumar

    2016-06-01

    The tokamak wall protection is one of the prime concerns, and for this purpose, limiters are used. Graphite is commonly used as a limiter material and first wall material for complete coverage of the internal vacuum vessel surfaces of the tokamak. From the past few years, we are working to identify and quantify the impurities deposited on the different part of Aditya Tokamak in collaboration with the Scientists at Institute of Plasma Research, Ahmedabad, India using Laser Induced Breakdown Spectroscopy (LIBS) [1-3]. Laser induced breakdown spectroscopy (LIBS) spectra of limiter of Aditya Tokamak have been recorded in the spectral range of 200-900 nm in open atmosphere. Along with atomic and ionic spectral lines of the constituent elements of the limiter (1-3), LIBS spectra also give the molecular bands. When a high power laser beam is focused on the sample, laser induced plasma is produced on its surface. In early stage of the plasma Back ground continuum is dominated due to free-free or free-bound emission. Just after few nanoseconds the light from the plasma is dominated by ionic emission. Atomic emission spectra is dominated from the laser induced plasma during the first few microsecond after an ablation pulse where as molecular spectra is generated later when the plasma further cools down. For this purpose the LIBS spectra has been recorded with varying gate delay and gate width. The spectra of the limiter show the presence of molecular bands of CN and C2. To get better signal to background ratios of the molecular bands, different experimental parameters like gate delay, gate width, collection angle and collection point (spatial analysis off the plasama) of the plasma have been optimized. Thus the present paper deals with the variation of spectral intensity of the molecular bands with different experimental parameters. Keywords: Limiter, Molecular bands, C2, CN. References: 1. Proof-of-concept experiment for On-line LIBS Analysis of Impurity Layer Deposited on

  18. Comparative outcome studies of clinical decision support software: limitations to the practice of evidence-based system acquisition.

    PubMed

    Dhiman, Gaurav Jay; Amber, Kyle T; Goodman, Kenneth W

    2015-04-01

    Clinical decision support systems (CDSSs) assist clinicians with patient diagnosis and treatment. However, inadequate attention has been paid to the process of selecting and buying systems. The diversity of CDSSs, coupled with research obstacles, marketplace limitations, and legal impediments, has thwarted comparative outcome studies and reduced the availability of reliable information and advice for purchasers. We review these limitations and recommend several comparative studies, which were conducted in phases; studies conducted in phases and focused on limited outcomes of safety, efficacy, and implementation in varied clinical settings. Additionally, we recommend the increased availability of guidance tools to assist purchasers with evidence-based purchases. Transparency is necessary in purchasers' reporting of system defects and vendors' disclosure of marketing conflicts of interest to support methodologically sound studies. Taken together, these measures can foster the evolution of evidence-based tools that, in turn, will enable and empower system purchasers to make wise choices and improve the care of patients.

  19. The Watershed as A Conceptual Framework for the Study of Environmental and Human Health

    PubMed Central

    Kolok, Alan S.; Beseler, Cheryl L.; Chen, Xun-Hong; Shea, Patrick J.

    2009-01-01

    The watershed provides a physical basis for establishing linkages between aquatic contaminants, environmental health and human health. Current attempts to establish such linkages are limited by environmental and epidemiological constraints. Environmental limitations include difficulties in characterizing the temporal and spatial dynamics of agricultural runoff, in fully understanding the degradation and metabolism of these compounds in the environment, and in understanding complex mixtures. Epidemiological limitations include difficulties associated with the organization of risk factor data and uncertainty about which measurable endpoints are most appropriate for an agricultural setting. Nevertheless, it is our contention that an adoption of the watershed concept can alleviate some of these difficulties. From an environmental perspective, the watershed concept helps identify differences in land use and application of agrichemicals at a level of resolution relevant to human health outcomes. From an epidemiological perspective, the watershed concept places data into a construct with environmental relevance. In this perspectives paper, we discuss how the watershed can provide a conceptual framework for studies in environmental and human health. PMID:20508751

  20. Preparing Global Citizens through the Study of Human Rights

    ERIC Educational Resources Information Center

    Kirkwood-Tucker, Toni Fuss

    2012-01-01

    The preparation of students for global citizenship represents a central challenge to social studies educators in the twenty-first century. Two-thirds of the world's poor are steeped in abject poverty and its grim consequences. The world refugee problem has reached staggering proportions. There is an international epidemic of human trafficking, and…

  1. Arts & Humanities in the Social Studies. NCSS Publications Bulletin 90.

    ERIC Educational Resources Information Center

    Selwyn, Douglas

    This bulletin is designed to help teachers integrate the arts and humanities into the social studies curriculum. The volume includes three chapters. Chapter 1, "Learning Through the Arts," features the following sections: (1) "Integration"; (2) "Assessment"; and (3) "References and For Further Reading." Chapter 2, "Using Theater in the Classroom,"…

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

    ERIC Educational Resources Information Center

    Cory, Suzanne N.; Hernandez, Abigail R.

    2014-01-01

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

  3. Squad Overmatch Study: Training Human Dimension to Enhance Performance

    DTIC Science & Technology

    2014-09-30

    Program. This provides an introduction to the common language associated with Enhance Performance Mental Skills Training and Sustainment. (50 students ... students can attend the one-week course at one time. d. Five-day Enhance Performance Training for Warrior Transition Battalion Soldiers. This course...Squad Overmatch Study Training Human Dimension to Enhance Performance FY14 Final Report 30 September 2014

  4. Human Exposures to PAHs: an Eastern United States Pilot Study

    EPA Science Inventory

    Personal exposure monitoring for select polycyclic aromatic hydrocarbons (PAHs) was performed as part of the National Human Exposure Assessment Survey (NHEXAS) Pilot Study in Baltimore, MD and in four surrounding counties (NHEXAS-Maryland). An objective of this effort was to esta...

  5. Communicator Style: A Study of Human Resource Managers.

    ERIC Educational Resources Information Center

    Evans, Jennifer Payne

    Researchers who have focused on issues of interpersonal communication in organizations have concluded that it is an essential component of organizational life. This paper presents findings of a study that examined the communicator image of human-resource managers. A survey instrument called the Norton Communicator Style Measure (CSM) was sent to…

  6. ORD BEST PRACTICES FOR OBSERVATIONAL HUMAN EXPOSURE MEASUREMENT STUDIES

    EPA Science Inventory

    This abstract describes a presentation for the 2007 Society of Toxicology Annual Meeting in Charlotte, NC on March 27, 2007. It will be included in a special Issues Session titled "Scientific and Ethical Considerations in Human Exposure Studies." The presentation desc...

  7. Forming limit prediction using a self-consistent crystal plasticity framework: a case study for body-centered cubic materials

    NASA Astrophysics Data System (ADS)

    Jeong, Youngung; Pham, Minh-Son; Iadicola, Mark; Creuziger, Adam; Foecke, Timothy

    2016-06-01

    A rate-dependent self-consistent crystal plasticity model was incorporated with the Marciniak-Kuczyński model in order to study the effects of anisotropy on the forming limits of BCC materials. The computational speed of the model was improved by a factor of 24 when running the simulations for several strain paths in parallel. This speed-up enabled a comprehensive investigation of the forming limits of various BCC textures, such as γ , σ , α , η and ɛ fibers and a uniform (random) texture. These simulations demonstrate that the crystallographic texture has significant (both positive and negative) effects on the resulting forming limit diagrams. For example, the γ fiber texture, which is often sought through thermo-mechanical processing due to a high r-value, had the highest forming limit in the balanced biaxial strain path but the lowest forming limit under the plane strain path among the textures under consideration. A systematic investigation based on the results produced by the current model, referred to as ‘VPSC-FLD’, suggests that the r-value does not serve as a good measure of forming limit strain. However, model predictions show a degree of correlation between the r-value and the forming limit stress.

  8. Breaking the diffraction limit by saturation in stimulated-Raman-scattering microscopy: A theoretical study

    NASA Astrophysics Data System (ADS)

    Gong, Li; Wang, Haifeng

    2014-07-01

    We present a theoretical investigation on the saturation of stimulated Raman scattering (SRS) and propose an application of it to break the diffraction limit in SRS microscopy. In our proposed scheme, a donut-shaped Stokes beam is used to saturate SRS at the rim of a focused Gaussian pump beam; thus the addition of another Gaussian Stokes beam can only induce additional stimulated Raman loss to the pump beam in a small area inside the donut-shaped beam. Resembling stimulated-emission-depletion microscopy, this method can significantly improve the lateral imaging resolution. Compared with the diffraction-limited resolution, theoretical simulations show that it may be possible to double the spatial resolution with a few TW/cm2 of laser intensity. Such super-resolution could greatly enhance the advantage of SRS microscopy for potential applications.

  9. A theoretical study of limit cycle oscillations of plenum air cushions

    NASA Astrophysics Data System (ADS)

    Hinchey, M. J.; Sullivan, P. A.

    1981-11-01

    Air cushion vehicles (ACV) are prone to the occurrence of dynamic instabilities which frequently appear as stable finite amplitude oscillations. The aim of this work is to ascertain if the non-linearities characteristics of ACV dynamics generate limit cycle oscillations for cushion systems operating at conditions for which a linear theory predicts instability. The types of non-linearity that can occur are discussed, and an analysis is presented for a single cell flexible skirted plenum chamber constrained to move in pure heave only. Two cushion feed cases are considered: a plenum box supply and a duct. The results obtained by a Galerkin/describing function analysis are compared with those generated by a full numerical simulation. For the plenum box supply system, it is shown that the limit cycles can be suppressed by using a piston to introduce high frequency small amplitude volume oscillations into the plenum chamber.

  10. Electric field induced in the human body by uniform 50 Hz electric or magnetic fields: bibliography analysis and method for conservatively deriving measurable limits.

    PubMed

    Magne, Isabelle; Deschamps, François

    2016-09-01

    Health guidelines for electric and magnetic fields in the low frequency range define exposure limits for electric and magnetic fields in terms of induced electric field in the human body, which is not directly measurable, requiring use of dosimetry. However many parameters, such as human models, calculation codes and post-processing methods influence the calculation results. Based upon many published papers and therefore covering a wide range of these influence parameters, this paper proposes a method for conservatively deriving measurable levels of electric and magnetic fields equivalent to the basic restrictions. Following this method, we found that, regarding exposure to uniform fields, the ICNIRP 2010 occupational basic restrictions are equivalent to a 2 mT and 7 mT magnetic field and to a 35 kV m(-1) and 35 kV m(-1) electric field at 50 Hz when applied respectively to the central and peripheral nervous system.

  11. Extravehicular activities limitations study. Volume 2: Establishment of physiological and performance criteria for EVA gloves

    NASA Technical Reports Server (NTRS)

    Ohara, John M.; Briganti, Michael; Cleland, John; Winfield, Dan

    1988-01-01

    One of the major probelms faced in Extravehicular Activity (EVA) glove development has been the absence of concise and reliable methods to measure the effects of EVA gloves on human hand capabilities. This report describes the development of a standardized set of tests designed to assess EVA-gloved hand capabilities in six measurement domains: Range of Motion, Strength, Tactile Perception, Dexterity, Fatigue, and Comfort. Based on an assessment of general human hand functioning and EVA task requirements several tests within each measurement domain were developed to provide a comprehensive evaluation. All tests were designed to be conducted in a glove box with the bare hand as a baseline and the EVA glove at operating pressure. A test program was conducted to evaluate the tests using a representative EVA glove. Eleven test subjects participated in a repeated-measures design. The report presents the results of the tests in each capability domain.

  12. INTEGRATING PARASITES AND PATHOGENS INTO THE STUDY OF GEOGRAPHIC RANGE LIMITS.

    PubMed

    Bozick, Brooke A; Real, Leslie A

    2015-12-01

    The geographic distributions of all species are limited, and the determining factors that set these limits are of fundamental importance to the fields of ecology and evolutionary biology. Plant and animal ranges have been of primary concern, while those of parasites, which represent much of the Earth's biodiversity, have been neglected. Here, we review the determinants of the geographic ranges of parasites and pathogens, and explore how parasites provide novel systems with which to investigate the ecological and evolutionary processes governing host/parasite spatial distributions. Although there is significant overlap in the causative factors that determine range borders of parasites and free-living species, parasite distributions are additionally constrained by the geographic range and ecology of the host species' population, as well as by evolutionary factors that promote host-parasite coevolution. Recently, parasites have been used to infer population demographic and ecological information about their host organisms and we conclude that this strategy can be further exploited to understand geographic range limitations of both host and parasite populations.

  13. 78 FR 69778 - Adjustments to Limitations on Designated School Official Assignment and Study by F-2 and M-2...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-21

    ... United States On September 16, 2011, Secretary of Homeland Security Janet Napolitano announced a ``Study...; ] DEPARTMENT OF HOMELAND SECURITY 8 CFR Part 214 RIN 1653-AA63 Adjustments to Limitations on Designated School Official Assignment and Study by F-2 and M-2 Nonimmigrants AGENCY: U.S. Immigration and Customs...

  14. Revised Medical Criteria for Evaluating Human Immunodeficiency Virus (HIV) Infection and for Evaluating Functional Limitations in Immune System Disorders. Final rule.

    PubMed

    2016-12-02

    We are revising the criteria in the Listing of Impairments (listings) that we use to evaluate claims involving human immunodeficiency virus (HIV) infection in adults and children under titles II and XVI of the Social Security Act (Act). We also are revising the introductory text of the listings that we use to evaluate functional limitations resulting from immune system disorders. The revisions reflect our program experience, advances in medical knowledge, our adjudicative experience, recommendations from a commissioned report, and comments from medical experts and the public.

  15. SAR changes in a human head model for plane wave exposure (500 - 2500 MHz) and a comparison with IEEE 2005 safety limits.

    PubMed

    Yelkenci, Tanju; Paker, Selcuk

    2008-01-01

    In this paper, external electric field values that are derived from the largest peak average 10 g SAR (Specific Absorption Rate) results in a realistic human head model are compared with current IEEE and ICNIRP reference levels. The head is illuminated by a plane wave source at seven different frequencies ranging from 500 MHz to 2500 MHz, with five different incident directions and three polarizations. Results reveal that the presence of metallic wire spectacles reduces the external electric field levels in the region above 900 MHz. Comparison of derived electric field values shows that the current IEEE and ICNIRP safety limits provide a conservative estimate.

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

    SciTech Connect

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

    1986-02-01

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

  17. Parametric studies of human thermal mechanisms and measurements.

    PubMed

    Thornton, S B; Nair, S S

    2000-04-01

    A systematic methodology is proposed for mathematically quantifying the effects of measurement inaccuracies due to instrument uncertainty in a human calorimetry project. Human thermal mechanisms are poorly understood at the systems level and this study investigates the importance of these mechanisms quantitatively. The proposed methodology uses sensitivity derivatives combined with sensor accuracies to quantify the effect of each heat transfer mechanism contributing to the errors in the system equations. The method is applicable to any differentiable model to be validated by experimentation. To illustrate the methodology, two example cases, a reclining nude resting subject and a reclining clothed working subject, are analyzed. The calculated expected errors clearly suggest specific modifications.

  18. Schistosoma mansoni Infection of Mice, Rats and Humans Elicits a Strong Antibody Response to a Limited Number of Reduction-Sensitive Epitopes on Five Major Tegumental Membrane Proteins

    PubMed Central

    Tremblay, Jacqueline M.; Oliveira, Sergio C.; Da’dara, Akram A.; Skelly, Patrick J.

    2017-01-01

    Schistosomiasis is a major disease of the developing world for which no vaccine has been successfully commercialized. While numerous Schistosoma mansoni worm antigens have been identified that elicit antibody responses during natural infections, little is known as to the identities of the schistosome antigens that are most prominently recognized by antibodies generated through natural infection. Non-reducing western blots probed with serum from schistosome-infected mice, rats and humans on total extracts of larval or adult schistosomes revealed that a small number of antigen bands predominate in all cases. Recognition of each of these major bands was lost when the blots were run under reducing condition. We expressed a rationally selected group of schistosome tegumental membrane antigens in insect host cells, and used the membrane extracts of these cells to unambiguously identify the major antigens recognized by S. mansoni infected mouse, rat and human serum. These results revealed that a limited number of dominant, reduction-sensitive conformational epitopes on five major tegumental surface membrane proteins: SmTsp2, Sm23, Sm29, SmLy6B and SmLy6F, are primary targets of mouse, rat and human S. mansoni infection sera antibodies. We conclude that, Schistosoma mansoni infection of both permissive (mouse) and non-permissive (rat) rodent models, as well as humans, elicit a dominant antibody response recognizing a limited number of conformational epitopes on the same five tegumental membrane proteins. Thus it appears that neither infecting schistosomula nor mature adult schistosomes are substantively impacted by the robust circulating anti-tegumental antibody response they elicit to these antigens. Importantly, our data suggest a need to re-evaluate host immune responses to many schistosome antigens and has important implications regarding schistosome immune evasion mechanisms and schistosomiasis vaccine development. PMID:28095417

  19. Studying synapses in human brain with array tomography and electron microscopy

    PubMed Central

    Kay, Kevin R.; Smith, Colin; Wright, Ann K.; Serrano-Pozo, Alberto; Pooler, Amy M.; Koffie, Robert; Bastin, Mark E.; Bak, Thomas H.; Abrahams, Sharon; Kopeikina, Katherine J.; McGuone, Declan; Frosch, Matthew P.; Gillingwater, Thomas H.; Hyman, Bradley T.; Spires-Jones, Tara L.

    2013-01-01

    Postmortem studies of synapses in human brain are problematic due to the axial resolution limit of light microscopy and the difficulty preserving and analyzing ultrastructure with electron microscopy. Array tomography overcomes these problems by embedding autopsy tissue in resin and cutting ribbons of ultrathin serial sections. Ribbons are imaged with immunofluorescence, allowing high-throughput imaging of tens of thousands of synapses to assess synapse density and protein composition. The protocol takes approximately 3 days per case, excluding image analysis, which is done at the end of the study. Parallel processing for transmission electron microscopy (TEM) using a protocol modified to preserve structure in human samples allows complimentary ultrastructural studies. Incorporation of array tomography and TEM into brain banking is a potent way of phenotyping synapses in well-characterized clinical cohorts to develop clinico-pathological correlations at the synapse level. This will be important for research in neurodegenerative disease, developmental diseases, and psychiatric illness. PMID:23787894

  20. Reconstructed epidermis versus human and animal skin in skin absorption studies.

    PubMed

    Schreiber, S; Mahmoud, A; Vuia, A; Rübbelke, M K; Schmidt, E; Schaller, M; Kandárová, H; Haberland, A; Schäfer, U F; Bock, U; Korting, H C; Liebsch, M; Schäfer-Korting, M

    2005-09-01

    European chemical policy in general and the REACH initiative in particular will increase the number of chemical substances submitted to toxicological evaluation by several orders of magnitude compared to the current status. To limit animal exposure the resulting enormous increase in testing, however, asks for validated in vitro test systems. While the OECD favours in vitro testing for cutaneous absorption using viable human and animal skin (Guideline 428) the availability of viable human skin is already limited today. We present a comparison of various in vitro techniques suitable for routine skin absorption studies including commercially available reconstructed human epidermis which may be a reliable alternative to excised human and animal skin. In order to develop a protocol for the subsequent transfer to partner laboratories the experimental set-up was analysed stepwise using the OECD reference compounds caffeine and testosterone. Franz cell type, the donor and receptor media for hydrophilic/lipophilic substances, albumin and tensid addition, and storage conditions of the excised skins were systematically varied. A protocol has been developed which now allows to proceed to the pre-validation process.

  1. Human Robotic Study at Houghton Crater - virtual reality study from NASA Ames (FFC) Future Fight

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Human Robotic Study at Houghton Crater - virtual reality study from NASA Ames (FFC) Future Fight Central simulator tower L-R: Dr Geoffrey Briggs; Jen Jasper (seated); Dr Jan Akins and Mr. Tony Gross, Ames

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

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

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

    Code of Federal Regulations, 2012 CFR

    2012-07-01

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

  4. 40 CFR 26.1605 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

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

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

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

  6. 40 CFR 26.1603 - Operation of the Human Studies Review Board.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

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

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

    NASA Astrophysics Data System (ADS)

    Horneck, G.

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

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

    NASA Technical Reports Server (NTRS)

    Polsgrove, Tara T.; Dwyer Cianciolo, Alicia

    2016-01-01

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

  9. Current progress of DNA vaccine studies in humans.

    PubMed

    Lu, Shan; Wang, Shixia; Grimes-Serrano, Jill M

    2008-03-01

    Despite remarkable progress in the field of DNA vaccine research since its discovery in the early 1990 s, the formal acceptance of this novel technology as a new modality of human vaccines depends on the successful demonstration of its safety and efficacy in advanced clinical trials. Although clinical trials conducted so far have provided overwhelming evidence that DNA vaccines are well tolerated and have an excellent safety profile, the early designs of DNA vaccines failed to demonstrate sufficient immunogenicity in humans. However, studies conducted over the last few years have led to promising results, particularly when DNA vaccines were used in combination with other forms of vaccines. Here, we provide a review of the data from reported DNA vaccine clinical studies with an emphasis on the ability of DNA vaccines to elicit antigen-specific, cell-mediated and antibody responses in humans. The majority of these trials are designed to test candidate vaccines against several major human pathogens and the remaining studies tested the immunogenicity of therapeutic vaccines against cancer.

  10. Helicobacter pylori virulence factors as tools to study human migrations.

    PubMed

    Queiroz, Dulciene Maria de Magalhães; Cunha, Roberto Penna de Almeida; Saraiva, Ivan Euclides Borges; Rocha, Andreia Maria Camargos

    2010-12-15

    Helicobacter pylori is one of the most common infections worldwide. In most individuals it consists in a lifelong host-pathogen relationship without consequences, but in some subjects it is associated with peptic ulcer disease and gastric cancer. Polymorphism in genes that code bacterial virulence factors, cagA and vacA, are independently associated with the infection severe outcomes and are geographically diverse. In the last decade, accumulated knowledge allowed to characterize typical H. pylori strain patterns for all the major human populations; patterns that can be used to study the origin of specific human groups. Thus, the presence or absence of cagA, cagA EPIYA genotypes, and vacA subtypes can be used as tools to study not only the geographic origin of specific human populations, but also to identify markers of historical contact between different ethnicities. We report here a study including a set of native Amazon Amerindians that had supposedly been some, but little, contact with European Brazilian colonizer and/or African slaves. They harbor H. pylori strains in a mixed pattern with Asian and Iberian Peninsula characteristics. It is possible that this finding represents H. pylori recombination upon short contact between human groups. Alternatively, it could be due to a founder effect from a small cluster of Asian origin native Americans.

  11. Ultracytochemical study on the permeability of the human amniotic epithelium.

    PubMed

    Matsubara, S; Tamada, T

    1991-06-01

    In order to elucidate and characterize the transport pathway of the substances in the amniotic fluid, the permeability of the term human amnion was studied ultracytochemically, with lanthanum or horse radish peroxidase (HRP) as a tracer. Pieces of the term human amnion were exposed to the solutions containing lanthanum or HRP, and processed for electronmicroscopy. Precipitates indicating lanthanum or HRP were observed in the lateral intercellular spaces of the amniotic epithelial cells through the entire depth of the spaces. Generally, pinocytosis of HPR was not observed. In rare cases, however, diffuse uptake of HRP was noticed in the cells of the electron-lucent cytoplasm. These facts indicated that the human amniotic epithelium is quite permeable and that this particular intercellular pathway is important in the mechanism of the transfer of substances between the mother and the fetus.

  12. Emerging studies of human HIV-specific antibody repertoires

    PubMed Central

    Hicar, Mark D.; Kalams, Spyros A.; Spearman, Paul W.; Crowe, James E.

    2010-01-01

    There has been an explosion of interest in the human B cell response to HIV infection of late. Recent advances in techniques for isolation of human antibodies and antibody secreting cell lines have facilitated a rapid expansion in the number of antibodies available for study. Early analysis of these repertoires reveals interesting features of the HIV-specific antibody response. HIV-specific repertoires exhibit a high level of clonality in circulating cells, and high levels of somatic mutations within the antibody variable gene segments. It appears that many if not most antibodies in circulation bind to virus envelope conformations that are found only in complex oligomeric structures on virion particles or virus-like particles. The rapid isolation of large panels of novel human neutralizing antibodies promises to reveal new insights into the fundamental principles underlying antibody-mediated neutralization of HIV. PMID:20510738

  13. Human Identification via Lateral Patella Radiographs: A Validation Study.

    PubMed

    Niespodziewanski, Emily; Stephan, Carl N; Guyomarc'h, Pierre; Fenton, Todd W

    2016-01-01

    This research examines the utility of patella outline shape for matching 3D scans of patellae to knee radiographs using elliptical Fourier analysis and subjective methods of human visual comparison of patellae across radiographs for identification purposes. Repeat radiographs were captured of cadaver's knees for visual comparison before patellae were extracted and skeletonized for quantitative comparisons. Quantitative methods provided significant narrowing down of the candidate pool to just a few potential matches (<5% of original sample), while the human analysts showed high capacity for correctly matching radiographs, irrespective of educational level (positive predictive value = 99.8%). The successful computerized matching based on a single quantified patella trait (outline shape) helps explain the potency achieved by subjective visual examination. This work adds to a growing body of studies demonstrating the value of single isolated infracranial bones for human identification via radiographic comparison.

  14. On the Psychometric Study of Human Life History Strategies.

    PubMed

    Richardson, George B; Sanning, Blair K; Lai, Mark H C; Copping, Lee T; Hardesty, Patrick H; Kruger, Daniel J

    2017-01-01

    This article attends to recent discussions of validity in psychometric research on human life history strategy (LHS), provides a constructive critique of the extant literature, and describes strategies for improving construct validity. To place the psychometric study of human LHS on more solid ground, our review indicates that researchers should (a) use approaches to psychometric modeling that are consistent with their philosophies of measurement, (b) confirm the dimensionality of life history indicators, and (c) establish measurement invariance for at least a subset of indicators. Because we see confirming the dimensionality of life history indicators as the next step toward placing the psychometrics of human LHS on more solid ground, we use nationally representative data and structural equation modeling to test the structure of middle adult life history indicators. We found statistically independent mating competition and Super-K dimensions and the effects of parental harshness and childhood unpredictability on Super-K were consistent with past research. However, childhood socioeconomic status had a moderate positive effect on mating competition and no effect on Super-K, while unpredictability did not predict mating competition. We conclude that human LHS is more complex than previously suggested-there does not seem to be a single dimension of human LHS among Western adults and the effects of environmental components seem to vary between mating competition and Super-K.

  15. Pilot studies of superfractionated radiotherapy and combination chemotherapy in limited oat cell carcinoma of the bronchus

    SciTech Connect

    Hodson, D.I.; Malaker, K.; Meikle, A.L.; Levitt, M.

    1984-10-01

    There are sound radiobiologic and suggestive clinical rationale for superfractionating the radiotherapeutic regimens employed for the therapy of rapidly growing malignancies. Oat cell carcinoma of the bronchus is such a tumor. The authors report their experience combining aggressive systemic combination chemotherapy with supperfractionated radiotherapy for the treatment of limited oat cell carcinoma of the bronchus. Overall, patient tolerance was satisfactory and a complete remission rate of 74% was achieved. It remains to be proven, in a prospective randomized fashion, whether this approach is superior to current conventional management.

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

    PubMed

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

    2011-09-01

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

  17. Advantages and limitations of commercially available electrocuting grids for studying mosquito behaviour

    PubMed Central

    2013-01-01

    Background Mosquito feeding behaviour plays a major role in determining malaria transmission intensity and the impact of specific prevention measures. Human Landing Catch (HLC) is currently the only method that can directly and consistently measure the biting rates of anthropophagic mosquitoes, both indoors and outdoors. However, this method exposes the participant to mosquito-borne pathogens, therefore new exposure-free methods are needed to replace it. Methods Commercially available electrocuting grids (EGs) were evaluated as an alternative to HLC using a Latin Square experimental design in Dar es Salaam, Tanzania. Both HLC and EGs were used to estimate the proportion of human exposure to mosquitoes occurring indoors (πi), as well as its two underlying parameters: the proportion of mosquitoes caught indoors (Pi) and the proportion of mosquitoes caught between the first and last hour when most people are indoors (Pfl). Results HLC and EGs methods accounted for 69% and 31% of the total number of female mosquitoes caught respectively and both methods caught more mosquitoes outdoors than indoors. Results from the gold standard HLC suggest that An. gambiae s.s. in Dar es Salaam is neither exophagic nor endophagic (Pi ≈ 0.5), whereas An. arabiensis is exophagic (Pi < < 0.5). Both species prefer to feed after 10pm when most people are indoors (Pfl > > 0.5). EGs yielded estimates of Pi for An. gambiae s.s., An. arabiensis and An. coustani, that were approximately equivalent to those with HLC but significantly underestimated Pfl for An. gambiae s.s. and An. coustani. The relative sampling sensitivity of EGs declined over the course of the night (p ≤ 0.001) for all mosquito taxa except An. arabiensis. Conclusions Commercial EGs sample human-seeking mosquitoes with high sensitivity both indoors and outdoors and accurately measure the propensity of Anopheles malaria vectors to bite indoors rather than outdoors. However, further modifications are needed

  18. Preservation of glial cytoarchitecture from ex vivo human tumor and non-tumor cerebral cortical explants: A human model to study neurological diseases.

    PubMed

    Chaichana, Kaisorn L; Capilla-Gonzalez, Vivian; Gonzalez-Perez, Oscar; Pradilla, Gustavo; Han, James; Olivi, Alessandro; Brem, Henry; Garcia-Verdugo, Jose Manuel; Quiñones-Hinojosa, Alfredo

    2007-08-30

    For the human brain, in vitro models that accurately represent what occurs in vivo are lacking. Organotypic models may be the closest parallel to human brain tissue outside of a live patient. However, this model has been limited primarily to rodent-derived tissue. We present an organotypic model to maintain intraoperatively collected human tumor and non-tumor explants ex vivo for a prolonged period of time ( approximately 11 days) without any significant changes to the tissue cytoarchitecture as evidenced through immunohistochemistry and electron microscopy analyses. The ability to establish and reliably predict the cytoarchitectural changes that occur with time in an organotypic model of tumor and non-tumor human brain tissue has several potential applications including the study of cell migration on actual tissue matrix, drug toxicity on neural tissue and pharmacological treatment for brain cancers, among others.

  19. Determination of actarit from human plasma for bioequivalence studies.

    PubMed

    Loya, P; Saraf, M N

    2010-11-01

    An analytical method based on high-performance liquid chromatography with ultraviolet detection (245 nm) was developed for the determination of actarit in human plasma. Coumarin was used as an internal standard. Chromatographic separation was achieved with a C8 column using a mobile phase of methanol: 1% acetic acid (50-50, v/v) with a flow rate of 1.0 ml/min. The calibration curve was linear over the range of 0.1-4.0 μg/ml (r(2) > 0.99) and the lower limit of quantification was 0.1 μg/ml. The method was validated for sensitivity, accuracy, precision, recovery and stability. The method was used to determine the concentration-time profiles of actarit in the plasma following oral administration of 100 mg actarit tablets.

  20. Human population studies and the World Health Organization.

    PubMed

    de Chadarevian, Soraya

    2015-01-01

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