Note: This page contains sample records for the topic limited human studies from Science.gov.
While these samples are representative of the content of Science.gov,
they are not comprehensive nor are they the most current set.
We encourage you to perform a real-time search of Science.gov
to obtain the most current and comprehensive results.
Last update: August 15, 2014.
1

Limiter study  

SciTech Connect

Studies of energy deposition on a mushroom-shaped limiter have been performed on ZT-40M. Total energy deposition, estimated power deposition per unit area, the effects of gas puffing and vertical and error field application, and approximate time histories of the extent of the impact area are presented for two different current levels (120 and 190 kA), protrusions into the body of the plasma (+2 - +12 mm from the wall) and limiter materials. Photographs of a bare graphite and TiC-coated graphite limiter before and after exposure to the plasma are shown. Massive spallation of the TiC-coated limiter is observed at the higher current level. Spallation occurs during the discharge and after termination. The degree of spallation is dependent on the current level. The average power deposition on the limiter over the discharge is estimated to be less than or equal to 1 MW.

Downing, J.N.; Gordon, R.A.; Thomas, K.S.; Watt, R.G.

1983-08-01

2

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

Microsoft Academic Search

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

W. Slob; M. N. Pieters

1998-01-01

3

The Limits of Human Vision  

Microsoft Academic Search

A model of the perception limits of the human visual system is presented, resulting in an esti- mate of approximately 15 million variable resolution pixels per eye. Assuming a 60 Hz stereo display with a depth complexity of 6, we make the prediction that a rendering rate of approxi- mately ten billion triangles per second is sufficient to saturate the

Michael F. Deering

4

Overcoming current limitations in humanized mouse research.  

PubMed

Immunodeficient mice engrafted with human cells and tissues have provided an exciting alternative to in vitro studies with human tissues and nonhuman primates for the study of human immunobiology. A major breakthrough in the early 2000s was the introduction of a targeted mutation in the interleukin 2 (IL-2) receptor common gamma chain (IL2rg(null)) into mice that were already deficient in T and B cells. Among other immune defects, natural killer (NK) cells are disrupted in these mice, permitting efficient engraftment with human hematopoietic cells that generate a functional human immune system. These humanized mouse models are becoming increasingly important for preclinical studies of human immunity, hematopoiesis, tissue regeneration, cancer, and infectious diseases. In particular, humanized mice have enabled studies of the pathogenesis of human-specific pathogens, including human immunodeficiency virus type 1, Epstein Barr virus, and Salmonella typhi. However, there are a number of limitations in the currently available humanized mouse models. Investigators are continuing to identify molecular mechanisms underlying the remaining defects in the engrafted human immune system and are generating "next generation" models to overcome these final deficiencies. This article provides an overview of some of the emerging models of humanized mice, their use in the study of infectious diseases, and some of the remaining limitations that are currently being addressed. PMID:24151318

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

2013-11-01

5

Limits of Pattern Discrimination in Human Vision.  

National Technical Information Service (NTIS)

The studies reported in Annual Technical Report 1 were designed to probe various aspects of spatial pattern discrimination. Several important findings have emerged allowing limits of pattern discrimination to be related to structural properties of the pho...

J. Hirsch

1984-01-01

6

The limits of agency in walking humans.  

PubMed

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. PMID:20144893

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

2010-05-01

7

Limited proteolysis of human histone deacetylase 1  

PubMed Central

Background Histone deacetylase (HDAC) proteins are associated with cell proliferation, differentiation, apoptosis, and cancer. Specifically, HDAC1 is linked with cell growth, a hallmark of cancer formation. HDAC1 is a phosphoprotein and phosphorylation at S421 and S423 promotes HDAC1 enzymatic activity and protein association. While single and double point mutants of HDAC1 at S421 and S423 appear functionally similar, the evidence suggests that HDAC1 is phosphorylated simultaneously at both S421 and S423 in vivo. Additional experiments are necessary to probe the role of double phosphorylation of HDAC1 at S421 and S423. Results To characterize HDAC1 phosphorylation at S421 and S423, limited proteolysis of HDAC1 was performed for the first time. HDAC1 degraded without production of discrete fragments. By performing concentration-dependent proteolysis, HDAC1 double point mutants with disrupted phosphorylation at S421 and S423 displayed different trypsin sensitivities compared to wild type HDAC1. Unexpectedly, HDAC1 single point mutants with disrupted phosphorylation at either S421 or S423 demonstrated protease sensitivity similar to the wild type HDAC1. Conclusion Concentration-dependent proteolysis experiments provide evidence that phosphorylation of S421 and S423 individually contribute to HDAC1 function. In addition, the limited proteolysis experiments support a model where associated proteins promote HDAC1 enzymatic activity, reinforcing the importance of protein interactions in HDAC1 structure and function. Finally, because HDAC1 does not display distinct regions of protease sensitivity, the proteolysis studies suggest that HDAC1 comprises inter-related structural regions.

Kamath, Nayana; Karwowska-Desaulniers, Paulina; Pflum, Mary Kay H

2006-01-01

8

Experimental studies on pump limiters  

SciTech Connect

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

Mioduszewski, P.

1982-01-01

9

Teleoperator human factors study  

NASA Technical Reports Server (NTRS)

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.

1986-01-01

10

Approaching the Limit of Predictability in Human Mobility  

PubMed Central

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.

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

2013-01-01

11

Human exposure limits to hypergolic fuels  

NASA Technical Reports Server (NTRS)

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.

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

1992-01-01

12

Hierarchical implicit surface joint limits for human body tracking  

Microsoft Academic Search

To increase the reliability of existing human motion tracking algorithms, we propose a method for imposing limits on the underlying hierarchical joint structures in a way that is true to life. Unlike most existing approaches, we explicitly represent dependencies between the various degrees of freedom and derive these limits from actual experimental data. To this end, we use quaternions to

L. Herda; Raquel Urtasun; P. Fua

2005-01-01

13

[The pharmacological correction of factors limiting human work capacity].  

PubMed

The problem of pharmacological correction of working capacity and rehabilitation after exhausting physical exertion is discussed from the standpoint of current advances and detection of factors limiting man's working capacity. The removal of factors interfering with the development of optimal possibilities of man through the effect of medicinal drugs is considered. The article discusses the energy sources providing for the performance of physical work differing in power and duration in accordance with the specificity of a type of sports as a most convenient model for studying adaptation to physical exertion. Factors limiting the working capacity of athletes are classified on the basis of current advances in biochemistry and physiology. All pharmacological agents influencing human working capacity are classified according to the potency zones determining the supply of energy. Pharmacological monitoring of man's capacity for work is in fact disclosure of factors limiting it and their pharmacological correction. This allows planning of the means for excluding the use of dope drugs in sports medicine and scientifically substantiated use of drugs in heavy branches of industry, for promoting climato-zone adaptation, and in extreme conditions. It is shown that the use of strongly active drugs is not necessary because a large reserve is available of drugs of plant and animal origin possessing much lesser side effects. PMID:9575403

Se?fulla, R D

1998-01-01

14

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

ERIC Educational Resources Information Center

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

Ryan, James

1994-01-01

15

Closed Ecological Systems (CES) Functional Stability Limits and Human Control  

NASA Astrophysics Data System (ADS)

newline Global planet The Earth Closed System stability of functioning is based on principle of statistical regulations and provided by enormous planetary buffer capacities atmosphere water soil time and sources of energy natural and fossilized All current deviations caused by human activity in Earth Biosphere are being easily eliminated and absorbed by these planetary buffers Man-made Closed Ecosystems function at the limits of their natural stability due to insufficient buffer capacities we have to minimize system size and physical mass to get it into the space principle of statistical regulations becomes insufficient for stability maintenance and needs to be replaced by other control approaches It had been indicated qualitatively earlier Gitelson et al 1975 that Human Factor HF purposeful control can increase these systems stability levels if applies algorithms compatible to man-made CES natural functioning mechanisms Theoretical analysis is being done on the basis of the results obtained in different experiments for closed ecosystems of different scale Biosphere of the Earth Biosphere -- 2 BIOS -- 3 etc It is shown that certain limits of functional stability exist for each specific system in terms of average cycle rate and fluctuations range These limits are determined primarily by newline - system s natural buffer capacities newline - rate of slowest material cycle in the system - natural structure of the chemical elements cycles - HF human consumption conversion material load on to the cycles

Rygalov, V.; Nelson, M.; de Silva, S.

16

Density limit studies on DIII-D  

SciTech Connect

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

Maingi, R. [Oak Ridge National Lab., TN (United States); Mahdavi, M.A.; Petrie, T.W. [General Atomics, San Diego, CA (United States)] [and others

1998-08-01

17

Artificial Closed Ecosystems Stability and Human Control Limitations  

NASA Astrophysics Data System (ADS)

The stability of the complex ecological system of the Earth accommodates statistical variation through the existence of extensive planetary buffers in atmosphere, water, soil, time, and energy sources. Variation in the Earth biosphere caused by either natural mechanisms or human activity is readily absorbed by these systemic, planetary buffers. Artificial Closed Ecological Systems (CES) for long-term life support in space are marginally stable to unstable due to insufficient buffer capacities stemming from significantly smaller system size and mass in space adaptations. Manual control can improve stability of such systems if CES system-specific control algorithms are applied. This paper introduces a conceptual model for CES stability and suggests system characteristics to maintain this stability for extended durations. Numerical estimates for CES of various scales and configurations, e.g., Biosphere of the Earth, Biosphere 2 (USA), BIOS 3 (Russia), Closed Ecological Experimental Facility (CEEF, Japan), etc., show that stability limits exist and differ for each specific system. These limits are determined primarily by: 1. The slowest circulating (so called limiting) material cycle in the system; 2. The buffer capacities for this cycle (cycle reservoirs); 3. The natural structure and intensity (rate) of the material turnover. Humans as an element of the system can exert control in a variety of manners. Human control can improve stability significantly but the controller must have a comprehensive understanding of closed material cycles structural (network related) and dynamical (turnover time related) characteristics. This understanding requires better models of the Earth biosphere mechanisms, as well as greater extensive experimentation with these models.

Rygalov, Vadim; Casler, James G.; Holubnyak, Yevhen

18

The Limits of Human Stereopsis in Space and Time  

PubMed Central

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.

Kane, David; Guan, Phillip

2014-01-01

19

Limitations in simulator time-based human reliability analysis methods  

SciTech Connect

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

Wreathall, J.

1989-01-01

20

Parvocellular Neurons Limit Motion Acuity in Human Peripheral Vision  

Microsoft Academic Search

It is generally believed that the perception of moving targets is mediated by the magnocellular (M) pathway in primate vision, but evidence is emerging that the parvocellular (P) pathway may also play a role in motion perception. Human peripheral vision is susceptible to anomalous motion perception because of spatial aliasing, and in this study we used this fact to determine

Stephen J. Anderson; Neville Drasdo; Caroline M. Thompson

1995-01-01

21

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

PubMed

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

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

2011-06-01

22

The limit to exercise tolerance in humans: mind over muscle?  

PubMed

In exercise physiology, it has been traditionally assumed that high-intensity aerobic exercise stops at the point commonly called exhaustion because fatigued subjects are no longer able to generate the power output required by the task despite their maximal voluntary effort. We tested the validity of this assumption by measuring maximal voluntary cycling power before (mean +/- SD, 1,075 +/- 214 W) and immediately after (731 +/- 206 W) (P < 0.001) exhaustive cycling exercise at 242 +/- 24 W (80% of peak aerobic power measured during a preliminary incremental exercise test) in ten fit male human subjects. Perceived exertion during exhaustive cycling exercise was strongly correlated (r = -0.82, P = 0.003) with time to exhaustion (10.5 +/- 2.1 min). These results challenge the long-standing assumption that muscle fatigue causes exhaustion during high-intensity aerobic exercise, and suggest that exercise tolerance in highly motivated subjects is ultimately limited by perception of effort. PMID:20221773

Marcora, Samuele Maria; Staiano, Walter

2010-07-01

23

Limiter  

DOEpatents

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.

Cohen, S.A.; Hosea, J.C.; Timberlake, J.R.

1984-10-19

24

Human exploration mission studies  

NASA Technical Reports Server (NTRS)

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.

Cataldo, Robert L.

1990-01-01

25

Limiter  

DOEpatents

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.

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

1986-01-01

26

Physiology for High School - Human Physiological Limits to Exploring Mars  

NSDL National Science Digital Library

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

PhD James A Pawelczyk (Pennsylvania State University)

2008-04-05

27

Human factor and computational intelligence limitations in resilient control systems  

Microsoft Academic Search

Humans are very capable of solving many scientific and engineering problems, but during the solution process they have a tendency to make mistakes. For example, humans without computer aided tools, would not be able to design VLSI chips larger than 100 transistors. This imperfection of humans make them very unreliable elements in resilient control systems. There is a tendency of

Bogdan M. Wilamowski

2010-01-01

28

Humanized Mouse Models to Study Human Diseases  

PubMed Central

Purpose of review Update on humanized mouse models and their use in biomedical research. Recent findings The recent description of immunodeficient mice bearing a mutated IL-2 receptor gamma chain (IL2ry) facilitated greatly the engraftment and function of human hematolymphoid cells and other cells and tissues. These mice permit the development of human immune systems, including functional T and B cells, following engraftment of hematopoietic stem cells (HSC). The engrafted functional human immune systems are capable of T and B cell-dependent immune responses, antibody production, anti-viral responses, and allograft rejection. Immunodeficient IL2rynull mice also support heightened engraftment of primary human cancers and malignant progenitor cells, permitting in vivo investigation of pathogenesis and function. In addition, human-specific infectious agents for which animal models were previously unavailable can now be studied in vivo using these new generation humanized mice. Summary Immunodeficient mice bearing an IL2rynull mutated gene can be engrafted with functional human cells and tissues, including human immune systems, following engraftment with human hematolymphoid cells. These mice are now used as in vivo models to study human hematopoiesis, immunity, regeneration, stem cell function, cancer, and human-specific infectious agents without putting patients at risk.

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

2010-01-01

29

Inhibition of telomerase limits the growth of human cancer cells  

Microsoft Academic Search

Telomerase is a ribonucleoprotein enzyme that maintains the protective structures at the ends of eukaryotic chromosomes, called telomeres. In most human somatic cells, telomerase expression is repressed, and telomeres shorten progressively with each cell division. In contrast, most human tumors express telomerase, resulting in stabilized telomere length. These observations indicate that telomere maintenance is essential to the proliferation of tumor

William C. Hahn; Sheila A. Stewart; Mary W. Brooks; Shoshana G. York; Elinor Eaton; Akiko Kurachi; Roderick L. Beijersbergen; Joan H. M. Knoll; Matthew Meyerson; Robert A. Weinberg

1999-01-01

30

Limited interaction between translation and visual motion aftereffects in humans  

PubMed Central

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

2012-01-01

31

Health care, human worth and the limits of the particular.  

PubMed Central

An ethics concerned with health care developments and systems must be historically continuous, especially as it concerns the application to managed structures of key moral-epistemic concepts such as care, love and empathy. These concepts are traditionally most at home in the personal, individual domain. Human beings have non-instrumental worth just because they are human beings and not by virtue of their capacities. Managed health care systems tend to abstract from this worth in respect of both individuals' distinctness and individual identity. The first, a common feature of quantitative approaches to health care assessment and delivery, is avoidable. The second, by contrast, is necessarily sacrificed in impersonally managed structures. Failure to distinguish the two encourages confusion and distress, and the demand for impossible medico-moral relationships.

Cherry, C

1997-01-01

32

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

PubMed

The species-specific determinants of repolarization are poorly understood. This study compared the contribution of various currents to cardiac repolarization in canine and human ventricle. Conventional microelectrode, whole-cell patch-clamp, molecular biological and mathematical modelling techniques were used. Selective IKr block (50-100 nmol l(-1) dofetilide) lengthened AP duration at 90% of repolarization (APD90) >3-fold more in human than dog, suggesting smaller repolarization reserve in humans. Selective IK1 block (10 ?mol l(-1) BaCl2) and IKs block (1 ?mol l(-1) HMR-1556) increased APD90 more in canine than human right ventricular papillary muscle. Ion current measurements in isolated cardiomyocytes showed that IK1 and IKs densities were 3- and 4.5-fold larger in dogs than humans, respectively. IKr density and kinetics were similar in human versus dog. ICa and Ito were respectively ~30% larger and ~29% smaller in human, and Na(+)-Ca(2+) exchange current was comparable. Cardiac mRNA levels for the main IK1 ion channel subunit Kir2.1 and the IKs accessory subunit minK were significantly lower, but mRNA expression of ERG and KvLQT1 (IKr and IKs ?-subunits) were not significantly different, in human versus dog. Immunostaining suggested lower Kir2.1 and minK, and higher KvLQT1 protein expression in human versus canine cardiomyocytes. IK1 and IKs inhibition increased the APD-prolonging effect of IKr block more in dog (by 56% and 49%, respectively) than human (34 and 16%), indicating that both currents contribute to increased repolarization reserve in the dog. A mathematical model incorporating observed human-canine ion current differences confirmed the role of IK1 and IKs in repolarization reserve differences. Thus, humans show greater repolarization-delaying effects of IKr block than dogs, because of lower repolarization reserve contributions from IK1 and IKs, emphasizing species-specific determinants of repolarization and the limitations of animal models for human disease. PMID:23878377

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

2013-09-01

33

Problems and Limitations in Studies on Screening for Language Delay  

ERIC Educational Resources Information Center

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…

Eriksson, Marten; Westerlund, Monica; Miniscalco, Carmela

2010-01-01

34

Basic principles governing limitations on individual rights and freedoms in human rights instruments  

Microsoft Academic Search

Individual freedom has to be balanced with the freedom of other individuals and with the reasonable demands of the community. A significant element in the development of international instruments protecting human rights was the movement away from the use of single limitation clauses to the elaboration of specific limitation clauses in each article. The limitation provisions are found in several

Mohamed Elewa Badar

2003-01-01

35

Primary structure of the human laminin A chain. Limited expression in human tissues.  

PubMed Central

cDNA clones for the human laminin A chain were isolated from libraries prepared from human gestational choriocarcinoma cell line (JAR) RNA. They cover approx. 8 kb from the 5'-end of the 9.5 kb mRNA coding for this protein. Our clones contain 94 nucleotide residues for the 5'-end untranslated region and 7885 nucleotide residues of coding sequence. The complete human laminin A chain contains a 17-amino acid-residue signal peptide and a 3058-residue A chain proper. The human laminin A chain has a distinct domain structure with numerous internal cysteine-rich repeats. The large globular domain G has five repeats, which have several conserved glycine and cysteine residues. Furthermore the A chain contains 20 internal cysteine-rich repeats present in tandem arrays in three separate clusters (domains IIIa, IIIb and V). Domain I + II has a predicted continuous alpha-helical structure characterized by heptad repeats and three domains (IVa, IVb and VI) are predicted to contain a number of beta-sheets and coiled-coil structures. Northern-blot analysis was used to study the laminin A chain expression in the JAR cell line, full-term placenta and newborn-human tissues (kidney, spleen, lung, heart muscle, psoas muscle and diaphragm muscle). The expression was detectable in newborn-human kidney and JAR cell line only. The overall amino acid sequence identity between human and mouse is 76%. The human chain has only one Arg-Gly-Asp (RGD) sequence, which is located in the long arm within domain G, whereas the single RGD sequence in the mouse chain is located in the short arm in domain IIIb. The degree of identity between the human laminin A chain sequence and the sequence available for merosin [Ehrig, Leivo, Argraves, Ruoslahti & Engvall (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 3264-3268] is about 41% and when conservative substitutions are included the degree of similarity is 54%. Images Fig. 3.

Nissinen, M; Vuolteenaho, R; Boot-Handford, R; Kallunki, P; Tryggvason, K

1991-01-01

36

Limited impact of homeostatic plasticity on motor learning in humans.  

PubMed

Neuroplasticity is the adaptive modification of network connectivity in response to environmental demands and has been identified as a major physiological correlate of learning. Since unrestricted neuroplastic modifications of network connectivity will result in a de-stabilization of the system, metaplastic modification rules have been proposed for keeping plastic connectivity changes within a useful dynamic range. In this connection, the modification threshold to achieve synaptic strengthening is thought to correlate negatively with the history of activity of the respective neurons, i.e. high previous activity enhances the threshold for synaptic strengthening and vice versa. However, the relevance of metaplasticity for actual learning processes has not been tested so far. We reduced or enhanced motor cortex excitability before performance of the serial reaction time task (SRTT), a sequential motor learning paradigm, and a reaction time task (RTT) by transcranial direct current stimulation (tDCS). If homeostatic rules apply, excitability-diminishing cathodal tDCS should improve subsequent motor learning, especially if combined with the partial NMDA receptor-agonist d-cycloserine, which selectively enhances efficacy of active receptors, while excitability-enhancing anodal tDCS should reduce it. Only the results for anodal tDCS, when combined with d-cycloserine, were in accordance with the rules of homeostatic plasticity. We conclude that homeostatic plasticity, as tested here, has a limited influence on implicit sequential motor learning. PMID:18394661

Kuo, Min-Fang; Unger, Mandy; Liebetanz, David; Lang, Nicolas; Tergau, Frithjof; Paulus, Walter; Nitsche, Michael A

2008-01-01

37

STUDIES ON HUMAN ANTIBODIES  

PubMed Central

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

Moreno, Carlos; Kabat, Elvin A.

1969-01-01

38

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

NASA Technical Reports Server (NTRS)

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.

Bishop, Phillip A.; Greenisen, Mike

1993-01-01

39

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

NASA Technical Reports Server (NTRS)

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.

Bishop, Phillip A.; Greenisen, Mike

1992-01-01

40

Pump limiter studies on the Heliotron-E device  

SciTech Connect

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

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

1986-05-01

41

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

PubMed

The International Agency for Research on Cancer (IARC) classifies electromagnetic fields (EMFs) as 'possibly carcinogenic' to humans that might transform normal cells into cancer cells. Owing to high utilisation of electricity in day-to-day life, exposure to power-frequency (50 or 60 Hz) EMFs is unavoidable. Melatonin is a natural hormone produced by pineal gland activity in the brain that regulates the body's sleep-wake cycle. How man-made EMFs may influence the pineal gland is still unsolved. The pineal gland is likely to sense EMFs as light but, as a consequence, may decrease the melatonin production. In this study, more than one hundred experimental data of human and animal studies of changes in melatonin levels due to power-frequency electric and magnetic fields exposure were analysed. Then, the results of this study were compared with the International Committee of Non-Ionizing Radiation Protection (ICNIRP) limit and also with the existing experimental results in the literature for the biological effect of magnetic fields, in order to quantify the effects. The results show that this comparison does not seem to be consistent despite the fact that it offers an advantage of drawing attention to the importance of the exposure limits to weak EMFs. In addition to those inconsistent results, the following were also observedfrom this work: (i) the ICNIRP recommendations are meant for the well-known acute effects, because effects of the exposure duration cannot be considered and (ii) the significance of not replicating the existing experimental studies is another limitation in the power-frequency EMFs. Regardless of these issues, the above observation agrees with our earlier study in which it was confirmed that it is not a reliable method to characterise biological effects by observing only the ratio of AC magnetic field strength to frequency. This is because exposure duration does not include the ICNIRP limit. Furthermore, the results show the significance of disruption of melatonin due to exposure to weak EMFs, which may possibly lead to long-term health effects in humans. PMID:23051584

Halgamuge, Malka N

2013-05-01

42

A Dual Reporter Mouse Model of the Human ?-Globin Locus: Applications and Limitations  

PubMed Central

The human ?-globin locus contains the ?-like globin genes (i.e. fetal ?-globin and adult ?-globin), which heterotetramerize with ?-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 ?-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 ?- and ?-globin genes with GFP and DsRed fluorescent proteins respectively in the endogenous human ?-globin locus. Erythroid cell lines derived from this mouse model were tested for their capacity to reactivate the ?-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.

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

2012-01-01

43

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

PubMed Central

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

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

2006-01-01

44

A dual reporter mouse model of the human ?-globin locus: applications and limitations.  

PubMed

The human ?-globin locus contains the ?-like globin genes (i.e. fetal ?-globin and adult ?-globin), which heterotetramerize with ?-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 ?-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 ?- and ?-globin genes with GFP and DsRed fluorescent proteins respectively in the endogenous human ?-globin locus. Erythroid cell lines derived from this mouse model were tested for their capacity to reactivate the ?-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

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

45

The limiting distribution of the effective population size of the ancestor of humans and chimpanzees.  

PubMed

The effective population size is a fundamental parameter for the understanding of microevolutionary process. Indeed, the consideration of population-level phenomena within phylogenies provides insight into the influence of the past evolutionary demography on the genetic diversity of living species. Although the effective population size of the last common ancestor of humans and chimpanzees has been extensively investigated by molecular evolutionists, variance in the estimates of this parameter among studies is large. However, with the availability of genome sequences, the estimation of evolutionary parameters may be conducted with minimum stochastic error, and the limiting distribution of the estimates may be obtained. This statistical property was utilized in the present study and coupled with analytical derivations from the coalescent theory to examine the limiting distribution of the ancestral effective population size of Homo-Pan. The mean ancestral effective population size of Homo-Pan was inferred at approximately 47,500, and the results showed that the uncertainty of the estimates was large, even under the limiting distribution. Further reductions of the estimates are feasible only if additional calibration information from the fossil record is provided and if a probabilistic model of ancestral generation time is envisioned. PMID:24834834

Schrago, Carlos G

2014-09-21

46

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

Microsoft Academic Search

BACKGROUND: Dogs are the most common pet animals worldwide. They may harbour a wide range of parasites with zoonotic potential, thus causing a health risk to humans. In Nigeria, epidemiological knowledge on these parasites is limited. METHODS: In a community-based study, we examined 396 dogs in urban and rural areas of Ilorin (Kwara State, Central Nigeria) for ectoparasites and intestinal

Uade Samuel Ugbomoiko; Liana Ariza; Jorg Heukelbach

2008-01-01

47

Limited Transfer of Newly Acquired Movement Patterns across Walking and Running in Humans  

PubMed Central

The two major modes of locomotion in humans, walking and running, may be regarded as a function of different speed (walking as slower and running as faster). Recent results using motor learning tasks in humans, as well as more direct evidence from animal models, advocate for independence in the neural control mechanisms underlying different locomotion tasks. In the current study, we investigated the possible independence of the neural mechanisms underlying human walking and running. Subjects were tested on a split-belt treadmill and adapted to walking or running on an asymmetrically driven treadmill surface. Despite the acquisition of asymmetrical movement patterns in the respective modes, the emergence of asymmetrical movement patterns in the subsequent trials was evident only within the same modes (walking after learning to walk and running after learning to run) and only partial in the opposite modes (walking after learning to run and running after learning to walk) (thus transferred only limitedly across the modes). Further, the storage of the acquired movement pattern in each mode was maintained independently of the opposite mode. Combined, these results provide indirect evidence for independence in the neural control mechanisms underlying the two locomotive modes.

Ogawa, Tetsuya; Kawashima, Noritaka; Ogata, Toru; Nakazawa, Kimitaka

2012-01-01

48

Challenge studies of human volunteers: ethical issues  

PubMed Central

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.

Hope, T; McMillan, J

2004-01-01

49

Nonlinear transmission, scattering and optical limiting studies of graphene dispersions  

Microsoft Academic Search

Employing high-yield production of graphene by liquid-phase exfoliation, a series of dispersions with large populations of graphene single and few layers was prepared. Nonlinear optical properties of these graphene dispersions were studied using the open aperture Z-scan technique at 532 nm and 1064 nm. The graphene dispersions exhibit broadband nonlinear scattering induced optical limiting.

Jun Wang; Mustafa Lotya; Yenny Hernandez; Jonathan N. Coleman; Werner J. Blau

2010-01-01

50

On the design of experiments to study extreme field limits  

NASA Astrophysics Data System (ADS)

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.

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

2012-12-01

51

SANTA CREEK, BENEWAH COUNTY, IDAH - EFFLUENT LIMITATION STUDY. 1986  

EPA Science Inventory

A water quality study was initiated on Santa Creek, Idaho (17010304) to determine if new effluent limitations are necessary for the discharge from the City of Emida wastewater lagoon. The City of Emida provides secondary treatment of domestic sewage in an unaerated facultative l...

52

Cardiovascular Deconditioning in Humans: Human Studies Core  

NASA Technical Reports Server (NTRS)

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.

Williams, Gordon

1999-01-01

53

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

SciTech Connect

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.

Gore, B.R.; Dukelow, J.S. Jr.; Mitts, T.M.; Nicholson, W.L. [Pacific Northwest Lab., Richland, WA (United States)

1995-10-01

54

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

PubMed Central

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.

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

1997-01-01

55

Humanizing Home Study.  

ERIC Educational Resources Information Center

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…

Hass, Glen; Fleury, Donna

56

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

PubMed

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. PMID:21930965

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

2011-10-15

57

Human responses to unfairness with primary rewards and their biological limits  

PubMed Central

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

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

2012-01-01

58

Defining Limits of Treatment with Humanized Neutralizing Monoclonal Antibody for West Nile Virus Neurological Infection in a Hamster Model  

Microsoft Academic Search

Received 1 February 2007\\/Returned for modification 21 March 2007\\/Accepted 13 April 2007 A potent anti-West Nile virus (anti-WNV)-neutralizing humanized monoclonal antibody, hE16, was previously shown to improve the survival of WNV-infected hamsters when it was administered intraperi- toneally (i.p.), even after the virus had infected neurons in the brain. In this study, we evaluated the therapeutic limit of hE16 for

John D. Morrey; Venkatraman Siddharthan; Aaron L. Olsen; Hong Wang; Justin G. Julander; Jeffery O. Hall; Hua Li; Jeffrey L. Nordstrom; Scott Koenig; Syd Johnson; Michael S. Diamond

2007-01-01

59

Gated viewing in the atmosphere: a study of performance limits  

NASA Astrophysics Data System (ADS)

The main purpose of the work presented here is to study the potential for an active imaging system for target recognition at long distances. This work is motivated by the fact that there are a number of outdoor imaging needs where conventional passive electro optical (EO) and infrared (IR) imaging systems are limited due to lack of photons, disturbing background, obscurants or bad weather. With a pulsed illuminating source, several of these problems are overcome. Using a laser for target illumination, target recognition at 10's of km can be achieved. Powerful diode pumped lasers and camera tubes with high spatial and time resolution will make this technique an interesting complement to passive EO imaging. Beside military applications, civilian applications of gated viewing for search and rescue, vehicle enhanced vision and other applications are in progress. To study the performance limitations of gated viewing systems due to camera, optics and the atmosphere an experimental system was developed. Measurements up to 10 km were made. The measurements were taken at the wavelength 532 nm. To extrapolate the results to future system performance at an eye safe wavelength, 1.5 micrometers nm, a theoretical performance model was developed. This model takes into account the camera and atmospheric influence on resolution and image quality, measured as a signal-to-noise-ratio, SNR. The result indicates turbulence influence, in agreement with the modeling. Different techniques were tested for image quality improvement and the best results were obtained by applying several processing techniques to the images. Moreover, the tests showed that turbulence seriously limits the resolution for horizontal paths close to the ground. A tactical system at 1.5 micrometers should have better performance than the used 532 nm in atmospheric-limited applications close to ground level. The potential to use existing laser range finders and the eye safety issue motivates the future use of 1.5 micrometers for gated viewing.

Klasen, Lena M.; Steinvall, Ove K.; Bolander, Goeran; Elmqvist, Magnus

2002-07-01

60

Study of human chromosome V  

Microsoft Academic Search

The induction of fragile sites on human chromosomes has been demonstrated under various conditions that cause thymidylate stress, including exposure to uridine. In this study, we examined common fragile site expression by initially exposing peripheral lymphocytes to uridine, followed by repair of the fragile sites with media containing various concentrations of thymidine. Lymphocytes were cultured in medium 199 with 2

Shio Jean Lin; Christine Figueiredo; Leonard J. Sciorra; Ming-liang Lee

1987-01-01

61

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

PubMed

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 ?m/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. PMID:22717091

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

2012-10-01

62

Study of MHD Instabilities in ET near the Troyon Limit  

NASA Astrophysics Data System (ADS)

Spontaneous particle accumulation in Ohmic discharges in the Electric Tokamak leads to ramps in core density terminated by internal disruptions. These disruptions are preceded by increased MHD activity and occur at values of plasma beta which are consistent with the Troyon limit in ET. An array of 36 Mirnov coils, 14 toroidal and 24 poloidal, has been fabricated and installed to study the nature of MHD instabilities associated with the observed internal disruptions. The coils are mounted externally, either behind large-area plastic vacuum windows or in re-entrant thin-wall stainless steel tubes. The coils and associated electronics are capable of measuring fluctuations from < 1kHz to 100 kHz, the upper limit set by skin currents in the thin-wall stainless tubes. Toroidal and poloidal mode numbers and poloidal structure of the modes will be studied. Initial measurements showed growing m/n = 2/1 modes prior to the disruption and 3/2 modes have also been observed. The effects of plasma rotation on MHD stability will be studied.

Yates, T. F.; Taylor, R. J.; Carter, T. C.; Gauvreau, J.-L.; Gourdain, P.-A.; Grossman, A.; Lafonteese, D. J.; Pace, D. C.; Schmitz, L. W.; White, A. E.

2004-11-01

63

Feasibility study on superconducting fault current limiting transformer (SFCLT)  

Microsoft Academic Search

This paper proposes a “superconducting fault current limiting transformer (SFCLT)” with functions of both superconducting fault current limiters and superconducting transformers. Concepts of the SFCLT are as follows: (1) When a fault occurs in a power system, the SFCLT acts as a fault current limiter with limiting impedance due to quench of the SFCLT windings, which improves the transient stability

N. Hayakawa; S. Chigusa; N. Kashima; S. Nagaya; H. Okubo

2000-01-01

64

Why study human limb malformations?  

PubMed Central

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

Wilkie, Andrew OM

2003-01-01

65

Vagus nerve stimulation suppresses pain but has limited effects on neurogenic inflammation in humans  

Microsoft Academic Search

Left vagus nerve stimulation reduces pain perception in humans. In animal studies it has been shown that beyond the inhibitory effect, which the vagus nerve exerts via its widespread central connections, there might be also a peripheral effect on nociceptors. In humans, the exact mechanisms of VNS-mediated analgesia are still unclear.To test whether VNS also affects activation of primary nociceptive

Annette Kirchner; Hermann Stefan; Katrin Bastian; Frank Birklein

2006-01-01

66

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

PubMed

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

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

2014-06-01

67

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

Microsoft Academic Search

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

Tiziano GomieroMaurizio; Maurizio G. Paoletti; David Pimentel

2010-01-01

68

Finite element method-based calculation of the theoretical limit of sensitivity for detecting weak magnetic fields in the human brain using magnetic-resonance imaging  

Microsoft Academic Search

Detection of weak magnetic fields induced by neuronal electrical activities using magnetic-resonance imaging is a potentially effective method for functional imaging of the brain. In this study, we performed a numerical analysis of the theoretical limit of sensitivity for detecting weak magnetic fields induced in the human brain. The limit of sensitivity was estimated from the intensities of signal and

Tomohisa Hatada; Masaki Sekino; Shoogo Ueno

2005-01-01

69

Interpreting Disasters From Limited Data Availability: A Guatemalan Study Case  

NASA Astrophysics Data System (ADS)

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

Soto Gomez, A.

2012-12-01

70

Microvascular studies on the origins of perfusion-limited hypoxia.  

PubMed Central

Two forms of hypoxia are thought to exist in tumours: (1) hypoxia caused by limitations of its diffusion (chronic hypoxia); and (2) hypoxia caused by changes in perfusion (acute hypoxia). Indirect information suggests the existence of perfusion-limited hypoxia, but there is no direct proof that fluctuations in blood flow can lead to hypoxia, nor is there any information regarding potential causes of fluctuant flow. In this study, we have begun to explore these questions using R3230AC tumours transplanted into rat dorsal-flap window chambers. Two types of fluctuant flow have been observed. The first type, usually confined to single vessels, is typified by instability of flow magnitude and direction, and total vascular stasis occurs, but only for a few seconds at a time (4% incidence). The second type of fluctuation occurs in groups of vessels and is cyclic, with cycle times ranging from 20-60 min. Total vascular stasis does not necessarily occur, but the fluctuations in red cell flux are accompanied by changes in vascular oxygen content, as measured by microelectrodes. Another source of chronic hypoxia has also been identified in these experiments. Nine per cent (9%) of vessels examined had plasma flow, but very low or absent red cell flux over periods of many minutes. Images Figure 1

Dewhirst, M. W.; Kimura, H.; Rehmus, S. W.; Braun, R. D.; Papahadjopoulos, D.; Hong, K.; Secomb, T. W.

1996-01-01

71

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

PubMed Central

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

Williams, Alun G; Folland, Jonathan P

2008-01-01

72

Studies on human urinary arylamidases  

NASA Technical Reports Server (NTRS)

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.

Raina, P. N.; Ellis, S.

1975-01-01

73

Finite element method-based calculation of the theoretical limit of sensitivity for detecting weak magnetic fields in the human brain using magnetic-resonance imaging  

NASA Astrophysics Data System (ADS)

Detection of weak magnetic fields induced by neuronal electrical activities using magnetic-resonance imaging is a potentially effective method for functional imaging of the brain. In this study, we performed a numerical analysis of the theoretical limit of sensitivity for detecting weak magnetic fields induced in the human brain. The limit of sensitivity was estimated from the intensities of signal and noise in the magnetic-resonance images. The signal intensity was calculated with parameters which are commonly used in measurements of the human brain. The noise due to the head was calculated using the finite element method. The theoretical limit of sensitivity was approximately 10-8 T.

Hatada, Tomohisa; Sekino, Masaki; Ueno, Shoogo

2005-05-01

74

Study of capabilities and limitations of 3D printing technology  

NASA Astrophysics Data System (ADS)

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.

Lemu, H. G.

2012-04-01

75

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

PubMed

Unbiased and frank discussion of study limitations by authors represents a crucial part of the scientific discourse and progress. In today's culture of publishing many authors or scientific teams probably balance 'utter honesty' when discussing limitations of their research with the risk of being unable to publish their work. Currently, too few papers in the medical literature frankly discuss how limitations could have affected the study findings and interpretations. The goals of this commentary are to review how limitations are currently acknowledged in the medical literature, to discuss the implications of limitations in biomedical studies, and to make suggestions as to how to openly discuss limitations for scientists submitting their papers to journals. This commentary was developed through discussion and logical arguments by the authors who are doing research in the area of hedging (use of language to express uncertainty) and who have extensive experience as authors and editors of biomedical papers. We strongly encourage authors to report on all potentially important limitations that may have affected the quality and interpretation of the evidence being presented. This will not only benefit science but also offers incentives for authors: If not all important limitations are acknowledged readers and reviewers of scientific articles may perceive that the authors were unaware of them. Authors should take advantage of their content knowledge and familiarity with the study to prevent misinterpretations of the limitations by reviewers and readers. Articles discussing limitations help shape the future research agenda and are likely to be cited because they have informed the design and conduct of future studies. Instead of perceiving acknowledgment of limitations negatively, authors, reviewers and editors should recognize the potential of a frank and unbiased discussion of study limitations that should not jeopardize acceptance of manuscripts. PMID:22360847

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

2012-01-01

76

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

PubMed Central

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

2012-01-01

77

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

NASA Astrophysics Data System (ADS)

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

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

2004-11-01

78

Exploring the Limits of RF Shimming for High-Field MRI of the Human Head  

PubMed Central

Several methods have been proposed for overcoming the effects of radiofrequency (RF) magnetic field inhomogeneity in high-field MRI. Some of these methods rely at least in part on the ability to independently control magnitude and phase of different drives in either one multielement RF coil or in different RF coils in a transmit array. The adjustment of these drive magnitudes and phases alone to create uniform RF magnetic (B1) fields has been called RF shimming, and has certain limits at every frequency as dictated by possible solutions to Maxwell’s equations. Here we use numerical calculations to explore the limits of RF shimming in the human head. We found that a 16-element array can effectively shim a single slice at frequencies up to 600 MHz and the whole brain at up to 300 MHz, while an 80-element array can shim the whole brain at up to 600 MHz.

Mao, Weihua; Smith, Michael B.; Collins, Christopher M.

2014-01-01

79

Midland/Penetang Limiting Set-Point Thermostat Study.  

National Technical Information Service (NTIS)

This report was initiated to evaluate the validity of limiting set point thermostats as an economical means of conserving energy in low density public housing. The investigation was based on the following assumption: a certain proportion of public housing...

1982-01-01

80

Technical and ethical limitations in making human monoclonal antibodies (an overview).  

PubMed

In the broadest sense there are no longer any technical limitations to making human mAbs. Biological issues involving the type and nature of either a synthetic or a natural antibody, advantages of various B cell immunological compartments, and various assays needed to qualitate and quantitate mAbs have essentially been solved. If the target antigen is known then procedures to optimize antibody development can be readily planned out and implemented. When the antigen or target is unknown and specificity is the driving force in generating a human mAb then considerations about the nature and location of the B cell making the sought after antibody become important. And, therefore, the person the B cell is obtained from can be an ethical challenge and a limitation. For the sources of B cells special considerations must be taken to insure the anonymity and privacy of the patient. In many cases informed consent is adequate for antibody development as well as using discarded tissues. After the antibody has been generated then manufacturing technical issues become important that greatly depend upon the amounts of mAb required. For kilogram quantities then special considerations for manufacturing that include FDA guidelines will be necessary. PMID:24037834

Glassy, Mark C; Gupta, Rishab

2014-01-01

81

Humanized mouse model to study bacterial infections targeting the microvasculature.  

PubMed

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

Melican, Keira; Aubey, Flore; Duménil, Guillaume

2014-01-01

82

Initial ALT-I pump limiter studies on TEXOR  

SciTech Connect

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

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

1984-05-01

83

Physical Limitations on Salmonella typhi Entry into Cultured Human Intestinal Epithelial Cells  

Microsoft Academic Search

Kinetic studies of Salmonella typhi invasion of INT407 cells at different multiplicities of infection (MOIs) have revealed a strict physical limitation on S. typhi entry at MOIs of >40. Staining of infected monolayers to distinguish intracellular from extracellular bacteria revealed that all monolayer cells are susceptible to infection and that internalized bacteria are typically contained in one to three separate

XIAO-ZHE HUANG; BEN TALL; WILLIAM R. SCHWAN; DENNIS J. KOPECKO

1998-01-01

84

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

PubMed Central

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.

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

2013-01-01

85

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

PubMed Central

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

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

2011-01-01

86

Energy Aware Computing through Probabilistic Switching: A Study of Limits  

Microsoft Academic Search

The mathematical technique of randomization yielding probabilistic algorithms is shown, for the first time, through a physical interpretation based on statistical thermodynamics, to be a basis for energy savings in computing. Concretely, at the fundamental limit, it is shown that the energy needed to compute a single probabilistic bit or PBIT is proportional to the probability p of computing a

Krishna V. Palem

2005-01-01

87

Creation of "Humanized" Mice to Study Human Immunity  

PubMed Central

Humanized” mice are a promising translational model for studying human hematopoiesis and immunity. Their utility has been enhanced by the development of new stocks of immunodeficient hosts, most notably mouse strains such as NOD-scid IL2r? null mice that lack the IL-2 receptor common gamma chain. These stocks of mice lack adaptive immune function, display multiple defects in innate immunity, and support heightened levels of human hematolymphoid engraftment. Humanized mice can support studies in many areas of immunology, including autoimmunity, transplantation, infectious diseases, and cancer. These models are particularly valuable in experimentation where there is no appropriate small animal model of the human disease, as in the case of certain viral infections. This unit details the creation of humanized mice by engraftment of immunodeficient mice with hematopoietic stem cells or peripheral blood mononuclear cells, provides methods for evaluating engraftment, and discusses considerations for choosing the appropriate model system to meet specific goals.

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

2010-01-01

88

Nutrient limitation governs Staphylococcus aureus metabolism and niche adaptation in the human nose.  

PubMed

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

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

2014-01-01

89

Animal carcinogenicity studies: 1. Poor human predictivity.  

PubMed

The regulation of human exposure to potentially carcinogenic chemicals constitutes society's most important use of animal carcinogenicity data. Environmental contaminants of greatest concern within the USA are listed in the Environmental Protection Agency's (EPA's) Integrated Risk Information System (IRIS) chemicals database. However, of the 160 IRIS chemicals lacking even limited human exposure data but possessing animal data that had received a human carcinogenicity assessment by 1 January 2004, we found that in most cases (58.1%; 93/160), the EPA considered animal carcinogenicity data inadequate to support a classification of probable human carcinogen or non-carcinogen. For the 128 chemicals with human or animal data also assessed by the World Health Organisation's International Agency for Research on Cancer (IARC), human carcinogenicity classifications were compatible with EPA classifications only for those 17 having at least limited human data (p = 0.5896). For those 111 primarily reliant on animal data, the EPA was much more likely than the IARC to assign carcinogenicity classifications indicative of greater human risk (p < 0.0001). The IARC is a leading international authority on carcinogenicity assessments, and its significantly different human carcinogenicity classifications of identical chemicals indicate that: 1) in the absence of significant human data, the EPA is over-reliant on animal carcinogenicity data; 2) as a result, the EPA tends to over-predict carcinogenic risk; and 3) the true predictivity for human carcinogenicity of animal data is even poorer than is indicated by EPA figures alone. The EPA policy of erroneously assuming that tumours in animals are indicative of human carcinogenicity is implicated as a primary cause of these errors. PMID:16522147

Knight, Andrew; Bailey, Jarrod; Balcombe, Jonathan

2006-02-01

90

A Negative Feedback Loop Mediated by STAT3 Limits Human Th17 Responses.  

PubMed

The transcription factor STAT3 is critically required for the differentiation of Th17 cells, a T cell subset involved in various chronic inflammatory diseases. In this article, we report that STAT3 also drives a negative-feedback loop that limits the formation of IL-17-producing T cells within a memory population. By activating human memory CD4(+)CD45RO(+) T cells at a high density (HiD) or a low density (LoD) in the presence of the pro-Th17 cytokines IL-1?, IL-23, and TGF-?, we observed that the numbers of Th17 cells were significantly higher under LoD conditions. Assessment of STAT3 phosphorylation revealed a more rapid and stronger STAT3 activation in HiD cells than in LoD cells. Transient inhibition of active STAT3 in HiD cultures significantly enhanced Th17 cell numbers. Expression of the STAT3-regulated ectonucleotidase CD39, which catalyzes ATP hydrolysis, was higher in HiD, than in LoD, cell cultures. Interestingly, inhibition of CD39 ectonucleotidase activity enhanced Th17 responses under HiD conditions. Conversely, blocking the ATP receptor P2X7 reduced Th17 responses in LoD cultures. These data suggest that STAT3 negatively regulates Th17 cells by limiting the availability of ATP. This negative-feedback loop may provide a safety mechanism to limit tissue damage by Th17 cells during chronic inflammation. Furthermore, our results have relevance for the design of novel immunotherapeutics that target the STAT3-signaling pathway, because inhibition of this pathway may enhance, rather than suppress, memory Th17 responses. PMID:24973454

Purvis, Harriet A; Anderson, Amy E; Young, David A; Isaacs, John D; Hilkens, Catharien M U

2014-08-01

91

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

PubMed Central

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

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

2008-01-01

92

Protein secondary structure. Studies on the limits of prediction accuracy.  

PubMed

A secondary structure prediction technique is proposed which includes nucleation site determination through multiplication of conformational preference parameters as well as weighting factors to represent structurally stabilizing short range interactions. The prediction accuracy of the method is calculated using data bases categorized according to the four protein structural classes and with differing assignments of secondary structural regions. The results indicate that nearest neighbor prediction techniques (a) are insensitive to various assignment criteria for the secondary structural spans, (b) have nearly achieved their upper limit of prediction accuracy, and (c) can be somewhat improved through the use of stereochemical weighting factors and conformational parameters derived from the four structural groups. PMID:7118409

Palau, J; Argos, P; Puigdomenech, P

1982-04-01

93

Use of human tissue explants to study human infectious agents.  

PubMed

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

Grivel, Jean-Charles; Margolis, Leonid

2009-01-01

94

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

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…

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

95

Hanford study: a review of its limitations and controversial conclusions  

SciTech Connect

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

Gilbert, E.S.

1984-10-01

96

Mockups and human productivity studies  

NASA Technical Reports Server (NTRS)

Idea outlines are presented concerning mockup candidates, mockup utilization and schedules/sequence in mockup development. Mockup candidates which aid in human productivity investigations and assessment are given. Areas which are considered in the mockups are the safe haven zone, general purpose workstations, maintenance and servicing area, sleep quaters, multiple docking adapter, airlock, hygiene station, food station, habitation zones, group gathering area and lab areas. Some aesthetic concerns in human productivity are also given.

Fisher, T.

1985-01-01

97

Limited terminal transferase in human DNA polymerase mu defines the required balance between accuracy and efficiency in NHEJ.  

PubMed

DNA polymerase mu (Polmu) is a family X member implicated in DNA repair, with template-directed and terminal transferase (template-independent) activities. It has been proposed that the terminal transferase activity of Polmu can be specifically required during non-homologous end joining (NHEJ) to create or increase complementarity of DNA ends. By site-directed mutagenesis in human Polmu, we have identified a specific DNA ligand residue (Arg(387)) that is responsible for its limited terminal transferase activity compared to that of human TdT, its closest homologue (42% amino acid identity). Polmu mutant R387K (mimicking TdT) displayed a large increase in terminal transferase activity, but a weakened interaction with ssDNA. That paradox can be explained by the regulatory role of Arg(387) in the translocation of the primer from a non-productive E:DNA complex to a productive E:DNA:dNTP complex in the absence of a templating base, which is probably the rate limiting step during template-independent synthesis. Further, we show that the Polmu switch from terminal transferase to templated insertions in NHEJ reactions is triggered by recognition of a 5'-P at a second DNA end, whose 3'-protrusion could provide a templating base to facilitate such a special "pre-catalytic translocation step." These studies shed light on the mechanism by which a rate-limited terminal transferase activity in Polmu could regulate the balance between accuracy and necessary efficiency, providing some variability during NHEJ. PMID:19805281

Andrade, Paula; Martín, María José; Juárez, Raquel; López de Saro, Francisco; Blanco, Luis

2009-09-22

98

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

Microsoft Academic Search

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

G. Horneck

2004-01-01

99

Potential and limitations of diffusion MRI tractography for the study of language.  

PubMed

Diffusion magnetic resonance imaging (MRI) is a tremendously promising tool for imaging tissue microstructure, and for inferring large scale structural connectivity in vivo. However, the sensitivity of the technique is highly dependent on methodological details. Acquisition parameters, pre-processing steps, reconstruction models, and statistical analysis all affect the final sensitivity, specificity, and accuracy of a study. In the case of fiber pathway reconstruction in the central nervous system, termed tractography, false positive and false negative results abound, and interpretation of results must take into account the potential shortcomings of the techniques used. This article will review the strengths and limitations of different types of diffusion MRI tractography analysis, and highlight what one can realistically hope to learn from such imaging studies of the human brain. PMID:23910928

Campbell, Jennifer S W; Pike, G Bruce

2014-04-01

100

Study on Optical Filter Heating in Background Limited Detector Experiments  

NASA Astrophysics Data System (ADS)

Cryogenic test setups with controlled stray light environments capable of reaching ultra-low radiative background levels are required to test far infrared (FIR) and submillimeter (sub-mm) wave radiation detectors for future space based observatories. In recent experiments (Nature Commun 5:3130, 2014), in which 1.54 THz radiation was coupled onto an antenna-coupled kinetic inductance detector (KID), we found a higher than expected optical loading. We show that this can be explained by assuming heating of the metal mesh IR filters and re-radiation onto the KID. Note that the total power from the cryogenic black body source used in the experiments (at T = 3 -25 K) is much larger than the power inside the 1.5 -1.6 THz band we use to calibrate our detector. The out-of-band radiation can have up to 5 orders of magnitude more power than inside the 1.5 -1.6 THz band of interest. A strategy to mitigate the filter heating problem is presented, and when it is implemented, the validated upper limit for stray light at the detector level is down to few aW.

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

2014-04-01

101

Defining the critical limit of oxygen extraction in the human small intestine.  

PubMed

Although animal models have been used to characterize the relation between oxygen consumption and blood flow, reliable data have not been generated in the human small intestine. We perfused segments of human small intestine by using an ex vivo perfusion circuit that allowed precise manipulation of blood flow and perfusion pressure. Our goal was to define the critical level of intestinal blood flow necessary to maintain the metabolic needs of the tissue. Human small intestine (n = 5) tissue obtained at transplantation harvest was transported on ice to the laboratory. A 40-cm mid-jejunal segment was selected for perfusion, and appropriate inflow and outflow vessels were identified and cannulated. Perfusion with an autologous blood solution was initiated through an extracorporeal membrane oxygenation circuit. After a 30-minute equilibration period, arterial and venous blood gases were measured at varying flow rates while maintaining a constant hematocrit level. Arterial and venous oxygen content, arteriovenous oxygen difference (A-VO2 diff), and oxygen consumption (VO2) were then calculated. Our results demonstrated that at blood flows > 30 ml/min/100 g, VO2 is independent of blood flow (1.6 +/- 0.06 ml/min/100 g), and oxygen extraction is inversely related to flow. Below this blood flow rate of 30 ml/min/100 g, oxygen extraction does not increase further (6.3 +/- 0.3 vol%), and VO2 becomes flow dependent. This ex vivo preparation defines for the first time a threshold value of blood flow for small intestine below which oxygen consumption decreases (30 ml/min/100 g). Previous animal studies have correlated such a decrease in oxygen consumption with functional and histologic evidence of tissue injury. This "critical" flow rate in human intestine is similar to that found previously in canine and feline intestine, but lower than that of rodent species. PMID:8667504

Desai, T R; Sisley, A C; Brown, S; Gewertz, B L

1996-05-01

102

Studies on the human choroid plexus in vitro  

PubMed Central

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

2013-01-01

103

Studies on the human choroid plexus in vitro.  

PubMed

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

Redzic, Zoran B

2013-01-01

104

Investigation of the human pathogen Acinetobacter baumannii under iron limiting conditions  

PubMed Central

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

2011-01-01

105

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

SciTech Connect

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

Samei, E.; Kearfott, K.J. [Univ. of Michigan, Ann Arbor, MI (United States)

1995-12-01

106

Evidence of a molecular barrier limiting susceptibility of humans, cattle and sheep to chronic wasting disease  

PubMed Central

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of deer and elk, and little is known about its transmissibility to other species. An important factor controlling interspecies TSE susceptibility is prion protein (PrP) homology between the source and recipient species/genotypes. Furthermore, the efficiency with which the protease-resistant PrP (PrP-res) of one species induces the in vitro conversion of the normal PrP (PrP-sen) of another species to the protease-resistant state correlates with the cross-species transmissibility of TSE agents. Here we show that the CWD-associated PrP-res (PrPCWD) of cervids readily induces the conversion of recombinant cervid PrP-sen molecules to the protease-resistant state in accordance with the known transmissibility of CWD between cervids. In contrast, PrPCWD-induced conversions of human and bovine PrP-sen were much less efficient, and conversion of ovine PrP-sen was intermediate. These results demonstrate a barrier at the molecular level that should limit the susceptibility of these non-cervid species to CWD.

Raymond, G.J.; Bossers, A.; Raymond, L.D.; O'Rourke, K.I.; McHolland, L.E.; Bryant III, P.K.; Miller, M.W.; Williams, E.S.; Smits, M.; Caughey, B.

2000-01-01

107

Solution convergence study during launch phase using limited tracking data  

NASA Technical Reports Server (NTRS)

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.

Premkumar, R. I.

1988-01-01

108

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

PubMed

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

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

2013-12-01

109

Evidence for Viral Virulence as a Predominant Factor Limiting Human Immunodeficiency Virus Vaccine Efficacy  

PubMed Central

Current strategies in human immunodeficiency virus type 1 (HIV-1) vaccine development are often based on the production of different vaccine antigens according to particular genetic clades of HIV-1 variants. To determine if virus virulence or genetic distance had a greater impact on HIV-1 vaccine efficacy, we designed a series of heterologous chimeric simian/human immunodeficiency virus (SHIV) challenge experiments in HIV-1 subunit-vaccinated rhesus macaques. Of a total of 22 animals, 10 nonimmunized animals served as controls; the remainder were vaccinated with the CCR5 binding envelope of HIV-1W6.1D. In the first study, heterologous challenge included two nonpathogenic SHIV chimeras encoding the envelopes of the divergent clade B HIV-1han2 and HIV-1sf13 strains. In the second study, all immunized animals were rechallenged with SHIV89.6p, a virus closely related to the vaccine strain but highly virulent. Protection from either of the divergent SHIVsf13 or SHIVhan2 challenges was demonstrated in the majority of the vaccinated animals. In contrast, upon challenge with the more related but virulent SHIV89.6p, protection was achieved in only one of the previously protected vaccinees. A secondary but beneficial effect of immunization on virus load and CD4+ T-cell counts was observed despite failure to protect from infection. In addition to revealing different levels of protective immunity, these results suggest the importance of developing vaccine strategies capable of protecting from particularly virulent variants of HIV-1.

Mooij, Petra; Bogers, Willy M. J. M.; Oostermeijer, Herman; Koornstra, Wim; Ten Haaft, Peter J. F.; Verstrepen, Babs E.; Van Der Auwera, Gert; Heeney, Jonathan L.

2000-01-01

110

Association studies including genotype by environment interactions: prospects and limits  

PubMed Central

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

2014-01-01

111

Pharmacogenetics Studies in STAR*D: Strengths, Limitations, and Results  

PubMed Central

Several lines of evidence support an important genetic contribution to the wide individual variation in therapeutic response to antidepressant medications. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study provided the largest cohort assembled to date of DNA from patients with nonpsychotic major depressive disorder, uniformly treated with citalopram and followed prospectively for up to 12 weeks. This pivotal study changed the face of pharmacogenetics research by increasing the sample size by an order of magnitude as well as by providing detailed prospective information about antidepressant response and tolerability. Several groups have identified markers in genes and tested the replication of previous findings of genes associated with outcome and side effects of antidepressant treatment. Variants in HTR2A, GRIK4, and KCNK2 were associated with citalopram treatment outcome. Replication was achieved in markers in the FKBP5 gene. Other findings in PDE11A and BDNF were not successfully replicated, and reports of potential confounders in previous associations with serotonin transporter variation (SLC6A4) were identified. Polymorphisms in pharmacokinetic genes involved in metabolism and transmembrane transport were also not associated with antidepressant response. Adverse events were also tested. Treatment-emergent suicidal ideation was associated with GRIK2, GRIA3, PAPLN, IL28RA, and CREB1. Sexual dysfunction was linked with variation in GRIN3A, GRIA1 GRIA3, and GRIK2. Reported and future findings of pharmacogenetics studies in STAR*D could help elucidate pathways involved in major depression and those pertinent to antidepressant outcome and side effects. Replication of these findings in independent samples could lead to the development of new treatments and to optimization of available treatments.

Laje, Gonzalo; Perlis, Roy H.; Rush, A. John; McMahon, Francis J.

2013-01-01

112

Selection of Opa+ Neisseria gonorrhoeae by limited availability of normal human serum.  

PubMed Central

Experimental infections of human male volunteers with Neisseria gonorrhoeae have provided valuable insights into the early stages of gonorrheal disease. Bacterial variants expressing outer membrane opacity (Opa) proteins appear to be selected from the inoculum during a period in which total recoverable numbers of bacteria decrease rapidly. This apparent survival advantage occurs simultaneously with the onset of an inflammatory response, characterized by local production of interleukin 6 (IL-6) and IL-8 and the appearance of leukocytes in urine. Since the inflammatory response may also result in the presence of serum factors on the mucosal surface, we investigated the possibility that killing in normal human serum (NHS) leads to the selection of Opa+ variants. We therefore studied killing of separate populations and mixtures of Opa- and Opa+ N. gonorrhoeae MS11mk in NHS. Expression of an Opa protein conferred a survival advantage upon the organism; i.e., the Opa+ variants were more serum resistant than their isogenic Opa- counterparts, resulting in a selection for Opa+ phenotypes when a mixture of Opa+ and Opa- gonococci (GC) was exposed to submaximal doses of NHS. This selection was observed in three different lipooligosaccharide (LOS) backgrounds, indicating that it was not due to a difference in LOS expression between Opa- and Opa+ phenotypes. Incubation in NHS of sialylated GC resulted in a similar selection for Opa+ variants. The presence of normal human urine during the serum killing assay had no effect on the selection phenomenon but drastically depleted NHS of bactericidal activity, which was found to be at least partly due to complement inhibition. The results suggest that serum killing may contribute to the transition from Opa- to Opa+ phenotypes during the early stages of infection of the male urethra.

Bos, M P; Hogan, D; Belland, R J

1997-01-01

113

Advantages and limitations of brain imaging methods in the research of absence epilepsy in humans and animal models.  

PubMed

The purpose of this review is to analyze research possibilities and limitations of several methods, technical tools and their combinations for elucidation of absence epilepsy mechanisms, particularly the childhood absences. Despite the notable collection of simultaneous recording of clinical electroencephalography (EEG) and behavioral changes in relation to absence seizures, shortcomings of scalp EEG in both spatial resolution and precise detection of subcortical centers have limited the understanding of the fundamental mechanisms of altered brain function during and after recurrent epileptic paroxysms. Therefore, in the past decade, EEG recordings have often been combined with simultaneous imaging methods in epilepsy studies. Among imaging methods, the following ones are used regularly: functional magnetic resonance imaging (fMRI), positron-emission tomography (PET), low-resolution electromagnetic tomography (LORETA), single photon emission spectroscopy (SPECT), near-infrared spectroscopy (NIRS), and optical imaging of intrinsic signals (IOS). In addition, voltage-sensitive dye optical imaging method and even photoacoustic microscopy can be applied to animal models of epilepsy. Samplings of some of the most relevant data obtained by the above methods are presented. It appears that the elaboration of more adequate animal models of the patterns of absence seizures during the early postnatal period is necessary for better correspondence of human and animal absence phenomena. PMID:23137652

Lenkov, Dmitry N; Volnova, Anna B; Pope, Anna R D; Tsytsarev, Vassiliy

2013-01-30

114

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

PubMed

American Studies is an academic discipline whose object of study is the United States of America and everything associated with it, and American sociologists largely ignore it. American Studies largely ignores American sociology. What causes this mutual exclusion? An outline of the disciplinary history of American Studies and journal article citation data show that the relationship between sociology and American Studies is weak and asymmetrical; American Studies cites sociology more often, but very little and not by much. I argue that mutual exclusion is due to mutual distrust in methods: sociology sees itself as a science, while American Studies, with roots in history and literature, does not. This article serves as a case study in the limits of interdisciplinarity. PMID:22131556

Dubrow, Joshua Kjerulf

2011-12-01

115

Study of hepatitis C virus entry in genetically humanized mice.  

PubMed

Approximately 2% of the world's population is chronically infected with hepatitis C virus (HCV). Chronic hepatitis C can culminate in end stage liver disease and liver cancer if the infection is untreated. Current therapy is only partially effective and a vaccine for HCV does not exist. Since the discovery of HCV as the etiologic agent causing hepatitis C several experimental tools have been developed which have improved our understanding of the viral life cycle and the interaction of HCV with human cells. However, it remains challenging to study HCV infection in its native liver environment given its narrow species tropism, limited to humans and chimpanzees. Mice can be rendered susceptible to HCV infection by transplanting human hepatocytes into immunocompromized liver injury strains. Such human liver chimeric mice are useful as a challenge model for human hepatotropic pathogens but their utility is hampered by their inability to mount functional immune responses and practical aspects including high costs, low throughput, and donor-to-donor variability. The barriers that restrict HCV species tropism are incompletely understood. We have previously shown that expression of human CD81 and human OCLN is required for HCV uptake into mouse cells. This led to the construction of a genetically humanized mouse model for HCV infection. Here, we provide a detailed protocol for the generation of these animals and highlight some of its applications for studying HCV biology and preclinical testing of drug and vaccine candidates. PMID:22687621

Dorner, Marcus; Rice, Charles M; Ploss, Alexander

2013-02-01

116

Study of hepatitis C virus entry in genetically humanized mice  

PubMed Central

Approximately 2% of the world’s population is chronically infected with hepatitis C virus (HCV). Chronic hepatitis C can culminate in end stage liver disease and liver cancer if the infection is untreated. Current therapy is only partially effective and a vaccine for HCV does not exist. Since the discovery of HCV as the etiologic agent causing hepatitis C several experimental tools have been developed which have improved our understanding of the viral life cycle and the interaction of HCV with human cells. However, it remains challenging to study HCV infection in its native liver environment given its narrow species tropism, limited to humans and chimpanzees. Mice can be rendered susceptible to HCV infection by transplanting human hepatocytes into immunocompromized liver injury strains. Such human liver chimeric mice are useful as a challenge model for human hepatotropic pathogens but their utility is hampered by their inability to mount functional immune responses and practical aspects including high costs, low throughput, and donor-to-donor variability. The barriers that restrict HCV species tropism are incompletely understood. We have previously shown that expression of human CD81 and human OCLN is required for HCV uptake into mouse cells. This led to the construction of a genetically humanized mouse model for HCV infection. Here, we provide a detailed protocol for the generation of these animals and highlight some of its applications for studying HCV biology and preclinical testing of drug and vaccine candidates.

Dorner, Marcus; Rice, Charles M.; Ploss, Alexander

2013-01-01

117

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

PubMed

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. PMID:14984129

O'Connor, Thomas G

2003-01-01

118

Technological advances for studying human behavior  

NASA Technical Reports Server (NTRS)

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.

Roske-Hofstrand, Renate J.

1990-01-01

119

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

NASA Astrophysics Data System (ADS)

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.

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

2013-04-01

120

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

PubMed

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. PMID:23679480

Rocha, Luis E C; Blondel, Vincent D

2013-04-01

121

Study of the Human Mitochondrial DNA Polymorphism  

Microsoft Academic Search

Traces of Paleolithic exodus routes of modern humans from Africa to Europe have been studied genetically using female specific ancestral lineages via mitochondrial DNA (mtDNA). We suggest modern humans entered Europe near the Carpathian Mountains and Hungarian Valley. If so, isolated populations of highlanders in Carpathian Europe may carry a genetic fingerprint of the ancient European predecessors and illustrate the

Catherine Willis

2006-01-01

122

Study of sound localization by owls and its relevance to humans  

Microsoft Academic Search

Human psychoacoustical studies have been the main sources of information from which the brain mechanisms of sound localization are inferred. The value of animal models would be limited, if humans and the animals did not share the same perceptual experience and the neural mechanisms for it. Barn owls and humans use the same method of computing interaural time differences for

Masakazu Konishi

2000-01-01

123

Date seed oil limit oxidative injuries induced by hydrogen peroxide in human skin organ culture.  

PubMed

The skin is chronically exposed to pro-oxidant agents, leading to the generation of reactive oxygen species (ROS). To protect the skin against an over-load of oxidant species, we studied the chemoprotective effect of one new natural product: "date seed oil: DSO". This oil may serve as a potential source of natural antioxidants such as phenols and tocopherols. Here, the antioxidative potential of DSO was compared that of to extra virgin olive oil. Adult human skin was maintained in organ culture in the presence of the DSO and extra virgin olive oil before the addition of hydrogen peroxide (H2O2), in order to prevent the tissue from its oxidizing effects. Skin specimens were collected for histology and for melanin studies. In the investigated model system, DSO protects skin against oxidative injuries. It has a significant chemoprotective effect, by inhibition of damage caused by H_{2}O_{2} compared with specimens without such addition endowing with a radical scavenging ability. The various components from DSO were much more potent antioxidant and more free radical scavengers of the H2O2 than those of olive oil. Our study shows that topical DSO treatment of the skin stimulates events in the epidermis leading to repair skin damage possibly due to antioxidant synergisms. PMID:17673830

Dammak, Ines; Abdallah, Fatma Ben; Boudaya, Sonia; Besbes, Souhail; Keskes, Leila; El Gaied, Amel; Turki, Hamida; Attia, Hammadi; Hentati, Basma

2007-01-01

124

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

PubMed Central

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

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

2009-01-01

125

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...

126

Study of human bone tumor slice by SRXRF microprobe  

NASA Astrophysics Data System (ADS)

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

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

2001-07-01

127

Predicting Nursing Human Resources: An Exploratory Study  

PubMed Central

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.

Squires, Allison; Beltran-Sanchez, Hiram

2010-01-01

128

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

PubMed

Both the human factors engineering (HFE) and formal methods communities are concerned with improving the design of safety-critical systems. This work discusses a modeling effort that leveraged methods from both fields to perform formal verification of human-automation interaction with a programmable device. This effort utilizes a system architecture composed of independent models of the human mission, human task behavior, human-device interface, device automation, and operational environment. The goals of this architecture were to allow HFE practitioners to perform formal verifications of realistic systems that depend on human-automation interaction in a reasonable amount of time using representative models, intuitive modeling constructs, and decoupled models of system components that could be easily changed to support multiple analyses. This framework was instantiated using a patient controlled analgesia pump in a two phased process where models in each phase were verified using a common set of specifications. The first phase focused on the mission, human-device interface, and device automation; and included a simple, unconstrained human task behavior model. The second phase replaced the unconstrained task model with one representing normative pump programming behavior. Because models produced in the first phase were too large for the model checker to verify, a number of model revisions were undertaken that affected the goals of the effort. While the use of human task behavior models in the second phase helped mitigate model complexity, verification time increased. Additional modeling tools and technological developments are necessary for model checking to become a more usable technique for HFE. PMID:21572930

Bolton, Matthew L; Bass, Ellen J

2010-03-25

129

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

PubMed

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

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

2014-01-01

130

Evidence for Viral Virulence as a Predominant Factor Limiting Human Immunodeficiency Virus Vaccine Efficacy  

Microsoft Academic Search

Current strategies in human immunodeficiency virus type 1 (HIV-1) vaccine development are often based on the production of different vaccine antigens according to particular genetic clades of HIV-1 variants. To determine if virus virulence or genetic distance had a greater impact on HIV-1 vaccine efficacy, we designed a series of heterologous chimeric simian\\/human immunodeficiency virus (SHIV) challenge experiments in HIV-1

PETRA MOOIJ; WILLY M. J. M. BOGERS; HERMAN OOSTERMEIJER; WIM KOORNSTRA; PETER J. F. TEN HAAFT; BABS E. VERSTREPEN; GERT VAN DER AUWERA; JONATHAN L. HEENEY

2000-01-01

131

Virtues of being faithful: can we limit the genetic variation in human immunodeficiency virus?  

Microsoft Academic Search

Human immunodeficiency virus (HIV) infections are characterized by a high degree of viral variation. The genetic variation\\u000a is thought to be a combined effect of a high error rate of reverse transcriptase (RT), viral genomic recombination, the selection\\u000a forces of the human immune system, the requirement for growth in multiple cell types during pathogenesis, and persistent immune\\u000a activation associated with

William C. Drosopoulos; Lisa F. Rezende; Mark A. Wainberg; Vinayaka R. Prasad

1998-01-01

132

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

PubMed Central

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.

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.; Muhlhauser, Ingrid; Richter, Bernd; Singh, Sonal; Goodman, Steven; Puhan, Milo A.

2013-01-01

133

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

PubMed

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. PMID:18175202

Robert, L; Robert, A M; Fülöp, T

2008-04-01

134

Studies of human mutation rates  

SciTech Connect

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.

Neel, J.V.

1991-07-15

135

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

PubMed

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

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

136

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

PubMed Central

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.

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

2013-01-01

137

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

PubMed

A literature review was conducted to determine the state of the science related to medication errors and light. The limited literature is discussed in relationship to human vision and light needs. Little systematic action has been taken to increase nurses' awareness of the connection between lighting and potential medication errors. Implications for nursing practice and research about light conditions are provided. Interventions from other industries may aid nursing in making decisions about light conditions. PMID:24335492

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

2014-01-01

138

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

PubMed

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

Grimm, Herwig; Hartnack, Sonja

2013-01-01

139

A pair of roseate terns fledges three young with limited human assistance  

USGS Publications Warehouse

In 1994 when the availability of small fish appeared to be relatively good, the smallest chick from an inadvertantly artificially-created 3-egg clutch received occasional supplemental feedings by humans for two weeks. These supplemental feedings probably prevented this chick from starving. During its period of most rapid growth (after the linear growth phase of its two siblings had ended), however, it did not receive supplemental feedings from humans, but was instead was fed only by the two adult birds attending the nest. All the chicks in this brood eventually fledged, indicating that the pair was capable of meeting the feeding demands of three large chicks.

Spendelow, J.A.; Zingo, J.M.; Foss, S.

1997-01-01

140

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

USGS Publications Warehouse

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)

Cobb, Ernest D.

1986-01-01

141

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

ERIC Educational Resources Information Center

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…

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

2012-01-01

142

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

Microsoft Academic Search

Human space flight represents a heady mix of bravery and drama which can be inspirational to nations and to humankind but at huge economic cost. Due to the current high launch costs only a handful of people have ventured beyond low Earth orbit and walked on the Moon, propelled by aspirations related more to the Cold War than to science.

Andrew J. Coates

2001-01-01

143

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

Microsoft Academic Search

ABSTRACTSome opponents of reproductive human cloning have argued that, because of its experimental nature, any attempt to create a child by way of cloning would risk serious birth defects or genetic abnormalities and would therefore be immoral. Some versions of this argument appeal to the consent of the person to be conceived in this way. In particular, they assume that

2006-01-01

144

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

ERIC Educational Resources Information Center

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

Anderson, James A.; Meyer, Timothy P.

145

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

ERIC Educational Resources Information Center

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

Halquist, Don

146

On the generality and limits of abstraction in rats and humans  

Microsoft Academic Search

In this review, we address the question, central to cognition, of whether nonhuman animals such as rats are capable of extracting\\u000a and extending information from a given learning situation to a new learning situation without generalizing through a physical\\u000a dimension of the stimuli. This capacity underlies abstraction, which is a hallmark of human cognition and necessary for complex\\u000a information processing

Gonzalo P. UrcelayRalph; Ralph R. Miller

2010-01-01

147

Brain temperature and limits on transcranial cooling in humans: quantitative modeling results  

Microsoft Academic Search

Selective brain cooling (SBC) of varying strengths has been demonstrated in a number of mammals and appears to play a role\\u000a in systemic thermoregulation. Although primates lack obvious specialization for SBC, the possibility of brain cooling in humans\\u000a has been debated for many years. This paper reports on the use of mathematical modeling to explore whether surface cooling\\u000a can control

D. A. Nelson; S. A. Nunneley

1998-01-01

148

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

Microsoft Academic Search

Human space flight represents a heady mix of bravery and drama which can be inspirational to nations and to humankind but\\u000a at huge economic cost. Due to the current high launch costs only a handful of people have ventured beyond low Earth orbit\\u000a and walked on the Moon, propelled by aspirations related more to the Cold War than to science.

Andrew J. Coates

1999-01-01

149

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

PubMed Central

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

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

2013-01-01

150

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

PubMed Central

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 IFN? 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.

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

2013-01-01

151

Human Challenge Pilot Study with Cyclospora cayetanensis  

PubMed Central

We describe a pilot study that attempted to infect human volunteers with Cyclospora cayetanensis. Seven healthy volunteers ingested an inoculum of Cyclospora oocysts (approximately 200–49,000 oocysts). The volunteers did not experience symptoms of gastroenteritis, and no oocysts were detected in any stool samples during the 16 weeks volunteers were monitored.

Eberhard, Mark L.; Seed, John R.; Weber, David J.; Won, Kimberly Y.; Nace, Eva K.; Moe, Christine L.

2004-01-01

152

MONOAMINE OXIDASE: RADIOTRACER DEVELOPMENT AND HUMAN STUDIES  

Microsoft Academic Search

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.).

J. S. FOWLER; J. LOGAN; N. D. VOLKOW; G. J. WANG; R. R. MACGREGOR; Y. S. DING

2000-01-01

153

Monoamine oxidase: radiotracer development and human studies.  

National Technical Information Service (NTIS)

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...

Fowler Logan Volkow Wang MacGregor Ding

2000-01-01

154

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

SciTech Connect

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

Higgins, J.C.

1990-01-01

155

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

SciTech Connect

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.

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

1988-04-01

156

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

PubMed

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

Frost, Ginger

2011-01-01

157

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

PubMed

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

Flueck, Martin

2010-03-01

158

Human Transportation System (HTS) study, volume 1  

NASA Technical Reports Server (NTRS)

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.

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

1993-01-01

159

Reporting Participants in Research Studies to Child Protective Services: Limited Risk to Attrition  

Microsoft Academic Search

This study examines the impact of Child Protective Services (CPS) reports made by research study staff on participant retention and discusses human subjects protocols that may minimize either the need to make such reports or the negative impact of reporting on participants and on participant retention. Among 1, 354 primary caregiver-child pairs in the Longitudinal Studies of Child Abuse and

Elizabeth Dawes Knight; Jamie B. Smith; Howard Dubowitz; Alan J. Litrownik; Jonathan B. Kotch; Diana English; Mark D. Everson; Desmond K. Runyan

2006-01-01

160

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

SciTech Connect

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.

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

2011-03-04

161

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...

162

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

PubMed

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. PMID:17039631

Lane, Robert

2006-06-01

163

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

NASA Astrophysics Data System (ADS)

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.

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

2013-06-01

164

Tea and Health: Studies in Humans  

PubMed Central

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

Khan, Naghma; Mukhtar, Hasan

2014-01-01

165

Experimental and Numerical Study on Temperature Evolution for Rapid Evaluation of Fatigue Limit  

NASA Astrophysics Data System (ADS)

This study is intended to verify the technique of rapid evaluation of fatigue limit through numerical simulation. Temperature evolution of a notched stainless steel specimen subjected to cyclic loading is simulated by elasto-plastic finite element analysis. Amplitude of second harmonic is obtained from the temperature evolution. It has been shown that the fatigue limit evaluated from the second harmonic amplitude agree fairly well with those obtained by thermography experiment and Wöhler method.

Ly, H. A.; Inoue, H.; Irie, Y.

2010-06-01

166

The Rational Choice Approach to Human Studies: A Reexamination  

Microsoft Academic Search

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

Milan Zafirovski

2003-01-01

167

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

PubMed Central

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

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

2012-01-01

168

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)

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.

Kleidon, Axel

2014-05-01

169

A dynamic morphometric model of the normal lung for studying expiratory flow limitation in mechanical ventilation.  

PubMed

A nonlinear dynamic morphometric model of breathing mechanics during artificial ventilation is described. On the basis of the Weibel symmetrical representation of the tracheo-bronchial tree, the model accurately accounts for the geometrical and mechanical characteristics of the conductive zone and packs the respiratory zone into a viscoelastic Voigt body. The model also accounts for the main mechanisms limiting expiratory flow (wave speed limitation and viscous flow limitation), in order to reproduce satisfactorily, under dynamic conditions, the expiratory flow limitation phenomenon occurring in normal subjects when the difference between alveolar pressure and tracheal pressure (driving pressure) is high. Several expirations characterized by different levels of driving pressure are simulated and expiratory flow limitation is detected by plotting the isovolume pressure-flow curves. The model is used to study the time course of resistance and total cross-sectional area as well as the ratio of fluid velocity to wave speed (speed index), in conductive airway generations. The results highlight that the coupling between dissipative pressure losses and airway compliance leads to onset of expiratory flow limitation in normal lungs when driving pressure is increased significantly by applying a subatmospheric pressure to the outlet of the ventilator expiratory channel; wave speed limitation becomes predominant at still higher driving pressures. PMID:15909658

Barbini, Paolo; Brighenti, Chiara; Cevenini, Gabriele; Gnudi, Gianni

2005-04-01

170

Numerical Study of Limit Cycle Oscillation Using Conventional and Supercritical Airfoils  

Microsoft Academic Search

Limit Cycle Oscillation is a type of aircraft wing structural vibration caused by the non-linearity of the system. The objective of this thesis is to provide a numerical study of this aeroelastic behavior. A CFD solver is used to simulate airfoils displaying such an aeroelastic behavior under certain airflow conditions. Two types of airfoils are used for this numerical study,

Felipe Manuel Loo

2008-01-01

171

A non-Newtonian model based on limiting shear stress and slip planes—parametric studies  

Microsoft Academic Search

Parametric studies and corresponding results are presented using a rheological model based on the limiting shear stress and possible occurrence of slip planes. The model is applied to elastohydrodynamically lubricated line contacts with smooth surfaces and isothermal conditions. A few investigations are carried out where different parameters are varied. The first study investigates the influence on the film thickness distribution

Jonas Stĺhl; Bo O. Jacobson

2003-01-01

172

A Study of Computer-Assisted Instruction: Its Uses, Effects, Advantages, and Limitations.  

ERIC Educational Resources Information Center

The purpose of this study is to present information that will help educators to gain a better understanding of microcomputer capabilities and limitations and to inform them as to the role of microcomputers in the classroom. Through examination of studies and articles six topics related to computer-assisted instruction (CAI) are addressed: (1) age…

Rupe, Vickie S.

173

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

NASA Astrophysics Data System (ADS)

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

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

174

Limiting the location of a putative human prostate cancer tumor suppressor gene at chromosome 13q14.3  

Microsoft Academic Search

We studied loss of heterozygosity (LOH) on human chromosome 13q in prostate cancer specimens to determine the location of a putative tumor suppressor gene (TSG) and to correlate these losses with the clinicopathological stage of the disease. Overall 13 (21%) of 61 specimens analysed had an allele loss on the long arm of chromosome 13. The most frequent (37%) LOH

Zhengnan Yin; Margaret R Spitz; Richard J Babaian; Sara S Strom; Patricia Troncoso; Jacob Kagan

1999-01-01

175

Mars Rotorcraft: Possibilities, Limitations, and Implications For Human/Robotic Exploration  

NASA Technical Reports Server (NTRS)

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.

Young, Larry A.; Aiken, Edwin; Lee, Pascal; Briggs, Geoffrey

2005-01-01

176

Quantifying the performance limits of human saccadic targeting during visual search  

NASA Technical Reports Server (NTRS)

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

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

2001-01-01

177

Fundamental Limitation on Applicability of Statistical Methods to Study of Living Organisms and Other Complex Systems  

NASA Astrophysics Data System (ADS)

A living organism is a complex system whose state is characterized by extremely large number of variables that far exceeds the number of individual organisms that can be experimentally studied. Since the relations between these variables and even their identities are largely unknown, the applicability of statistical methods of inference to the outcome of experiments in biomedical sciences is severely limited. Far from being a purely theoretical issue, this explains the recently proposed "Truth Wears Off" effect and sets a fundamental limitation on the applicability of machine-like approaches to the study of living organisms.

Rabin, Yitzhak

2011-07-01

178

Human Transportation System (HTS) study, volume 2  

NASA Technical Reports Server (NTRS)

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.

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

1993-01-01

179

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

ERIC Educational Resources Information Center

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…

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

180

Dual rover human habitation field study  

NASA Astrophysics Data System (ADS)

For the last 3 years, the National Aeronautics and Space Administration (NASA) has been testing a pressurized rover prototype in the deserts of Arizona to obtain human-in-the-loop performance data. This year's field trial consisted of operating two rovers simultaneously while embarking on two 7-day flight-like exploration missions. During the 2010 Desert Research and Technology Studies (DRATS) at Black Point Lava Flow and SP Mountain in Arizona, NASA human factors investigators, in cooperation with other engineers and scientists, collected data on both the daily living and working within and around the Space Exploration Vehicle (SEV). Both objective and subjective data were collected using standard human factors metrics. Over 305 h of crew habitability data were recorded during the field trial with 65 elements of habitation examined. Acceptability of the vehicles over the course of the missions was considered satisfactory by the majority of the crews. As with previous testing, habitation was considered acceptable by the crews, but some issues concerning stowage, Waste Containment System (WCS) volume, and sleep curtains need to be considered for redesign for the next generation vehicle.

Litaker, Harry L.; Thompson, Shelby G.; Szabo, Richard; Twyford, Evan S.; Conlee, Carl S.; Howard, Robert L.

2013-10-01

181

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

EPA Science Inventory

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

182

Study on the effects of the energy crisis and 55 mph speed limit in Michigan  

Microsoft Academic Search

The report is a presentation of the findings and conclusions derived from an analysis of Michigan traffic accident data and related data for the periods before, during, and after the peak energy crisis months of 1974. A major objective of this study was to identify the effect of the speed limits imposed as a result of the energy shortage. Some

J. Oday; D. J. Minahan; D. Golomb

1975-01-01

183

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

EPA Science Inventory

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

184

A Study of the Operating Limits of the Stannate Immersion Bath.  

National Technical Information Service (NTIS)

A study was conducted to determine the operating limits of the stannate immersion process for minimizing galvanic corrosion of magnesium-steel couples. Salt spray tests on specimens treated and then painted indicated that 100 sq. feet of work containing u...

W. H. Deaver

1967-01-01

185

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

ERIC Educational Resources Information Center

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…

Picasso de Oyague, Alfredo

186

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

NASA Technical Reports Server (NTRS)

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.

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

1998-01-01

187

METABOLIC PHENOTYPING GUIDELINES: Studying eating behaviour in humans.  

PubMed

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. PMID:25052364

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

2014-08-01

188

Expression of human CEACAM1 in transgenic mice limits the Opa-specific immune response against meningococcal outer membrane vesicles.  

PubMed

Outer membrane vesicles (OMVs) have been extensively investigated as meningococcal vaccine candidates. Among their major components are the opacity (Opa) proteins, a family of surface-exposed outer membrane proteins important for bacterial adherence and entry into host cells. Many Opa-dependent interactions are mediated through the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family of receptors. Importantly, binding of Opa to CEACAM1 has been reported to suppress human CD4 T cell proliferation in vitro in response to OMV preparations. This raises the question whether OMV vaccines should contain Opa proteins at all. Until now it has been difficult to answer this question, as the proposed immunosuppressive effect was only demonstrated with human cells in vitro, while immunization experiments in mice are not informative because the Opa interaction is specific for human CEACAM1. In the present study we have used Opa+ and Opa- OMVs for immunization experiments in a human CEACAM1 transgenic mouse model. OMVs were prepared from a meningococcal strain H44/76 variant expressing the CEACAM1-binding OpaJ protein, and from an isogenic variant in which all opa genes have been inactivated. Both the CEACAM1 expressing transgenic mice and their congenic littermates lacking it were immunized twice with the OMV preparations, and the sera were analyzed for bactericidal activity and ELISA antibody titres. Total IgG antibodies against the OMVs were similar in both mouse strains. Yet the titres for IgG antibodies specific for purified OpaJ protein were significantly lower in the mice expressing human CEACAM1 than in the nontransgenic mice. No significant differences were found in bactericidal titres among the four groups. Overall, these data indicate that expression of human CEACAM1 confers a reduced Opa-specific antibody response in vivo without affecting the overall immune response against other OMV antigens. PMID:23933369

Zariri, Afshin; van Dijken, Harry; Hamstra, Hendrik-Jan; van der Flier, Michiel; Vidarsson, Gestur; van Putten, Jos P M; Boog, Claire J P; van den Dobbelsteen, Germie; van der Ley, Peter

2013-11-12

189

Estimation by limiting dilution analysis of human IL 2-secreting T cells: detection of IL 2 produced by single lymphokine-secreting T cells  

Microsoft Academic Search

We present here a culture method for the estimation, in human blood, of the number of lymphocytes that can respond to mitogen by producing interleukin 2 (IL 2). T cells are cultured at limiting dilutions with PHA or Con A in the presence of Epstein Barr virus-transformed human lymphoblastoid cells (EB-LCL), and supernatants are tested 3 days later for IL

H. Vie; R. A. Miller

1986-01-01

190

STUDIES ON THE HUMAN CORPUS LUTEUM  

PubMed Central

The ultrastructure of human corpora lutea obtained during the 6th, 10th, 16th, and 35th week of pregnancy is reported. Differences between the established luteal cell of pregnancy and the transitory luteal cell of the menstrual cycle are noted. In pregnancy the luteal cell is more compartmentalized into a peripheral mass of ER (endoplasmic reticulum) and a central area where mitochondria and Golgi complexes are concentrated. The latter area extends to a cell surface where microvilli face on a perivascular space. Long bundles of filaments are prominent within the luteal cell cytoplasm and, in contiguous cells, appear to arise from adjacent desmosomal regions. Bilateral subsurface cisternae of granular ER at lateral cell borders appear to be areas of specialized junctional surfaces. Certain luteal cells with irregular nuclear membranes are also characterized by vesicular aggregates enclosed within a single membrane. These aggregates are found within the peripheral nucleoplasm or the perinuclear cytoplasm. Their single limiting membrane often appears continuous with either the inner or outer leaflet of the nuclear membrane.

Adams, Eleanor C.; Hertig, Arthur T.

1969-01-01

191

Clinical studies of human islet transplantation.  

PubMed Central

Recent advantages in techniques for the isolation of human pancreatic islets of Langerhans have led to the introduction of clinical trials of islet transplantation in diabetic patients who are already immunosuppressed because they have received a kidney transplant for end-stage renal failure. This paper describes the techniques used and the outcome in three diabetic patients who have received intraportal islet transplants. The first two patients received islets pooled from multiple cadaveric organ donors, the third patient received islets from a single well major histocompatibility complex (MHC) matched donor. The islet grafts in the first two patients failed rapidly, almost certainly due to rejection. The islet graft in the third patient continues to function after 18 months. Taken together with the worldwide experience, the results of this small series suggest that islet transplantation from a single well MHC matched donor may be optimal. For this approach to be a realistic option, techniques for islet isolation need to be further improved so that large numbers of islets can be regularly isolated from a single pancreas. The collagenase digestion phase of the islet isolation process is the major limiting factor and this area requires further detailed research.

London, N. J.

1995-01-01

192

Preliminary neutron crystallographic study of human transthyretin  

PubMed Central

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

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

2011-01-01

193

Wideband limit study of a GaN power amplifier using two-tone measurements  

Microsoft Academic Search

This paper studies the wideband limit (WBL) of a GaN RF power amplifier (PA). The WBL study is achieved by a PA characterization using two-tone measurements. The characterization method allows to identify the dependency of PA memory effects on the two-tone frequency spacing. PA memory effects (MEs) are measured using the opening in the AM\\/AM and AM\\/PM curves and they

Felice Francesco Tafuri; Daniel Sira; Troels Studsgaard Nielsen; Ole Kiel Jensen; Torben Larsen

2011-01-01

194

Implications of Limits of Detection of Various Methods for Bacillus anthracis in Computing Risks to Human Health? †  

PubMed Central

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/cm2 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.

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

2009-01-01

195

MONOAMINE OXIDASE: RADIOTRACER DEVELOPMENT AND HUMAN STUDIES.  

SciTech Connect

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.

FOWLER,J.S.; LOGAN,J.; VOLKOW,N.D.; WANG,G.J.; MACGREGOR,R.R.; DING,Y.S.

2000-09-28

196

Pars intermedia peptides: studies in adult humans.  

PubMed

A combination of radioimmunoassays and chromatography under acid-dissociating conditions has been used to obtain profiles of ACTH and LPH-related peptides in human plasma and cerebrospinal fluid. The spectra of peptides observed in these two fluids differ markedly. ACTH, beta-LPH, gamma-LPH and beta-endorphin are observed in the plasma of normal subjects and patients with increased pituitary ACTH secretion, whereas cerebrospinal fluid contains ACTH, beta-LPH, gamma-LPH and beta-endorphin, a 31 000-molecular-weight putative precursor having ACTH, LPH and gamma-MSH immunoreactivities, as well as pro-gamma-MSH(1-77) and smaller immunoreactive gamma-MSH fragments, alpha-MSH was not observed in blood or cerebrospinal fluid but this pars intermedia peptide and corticotropin-like intermediate lobe peptide (CLIP) were both found in tumour tissues obtained from patients with the ectopic ACTH syndrome. In vitro studies of human pituitary tumour tissues confirmed concomitant secretion of ACTH, beta-LPH, gamma-LPH, beta-endorphin and pro-gamma-MSH, which could be stimulated by a preparation of crude stalk median eminence and synthetic arginine vasopressin, from the rat, and could be suppressed by hydrocortisone. Clinical studies in which electroacupuncture was used to alleviate the symptoms of heroin withdrawal or recurrent pain revealed that concentrations of met-enkephalin and beta-endorphin, respectively, may rise in cerebrospinal fluid in association with relief of symptoms. PMID:6268379

Ratter, S J; McLoughlin, L; Gillies, G; Clement-Jones, V; Hope, J; Rees, L H

1981-01-01

197

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

PubMed

In this study, the maximum received power obtainable through wireless power transfer (WPT) by a small receiver (Rx) coil from a relatively large transmitter (Tx) coil is numerically estimated in the frequency range from 100 kHz to 10 MHz based on human body exposure limits. Analytical calculations were first conducted to determine the worst-case coupling between a homogeneous cylindrical phantom with a radius of 0.65 m and a Tx coil positioned 0.1 m away with the radius ranging from 0.25 to 2.5 m. Subsequently, three high-resolution anatomical models were employed to compute the peak induced field intensities with respect to various Tx coil locations and dimensions. Based on the computational results, scaling factors which correlate the cylindrical phantom and anatomical model results were derived. Next, the optimal operating frequency, at which the highest transmitter source power can be utilized without exceeding the exposure limits, is found to be around 2 MHz. Finally, a formulation is proposed to estimate the maximum obtainable power of WPT in a typical room scenario while adhering to the human body exposure compliance mandates. PMID:24889372

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

2014-07-01

198

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

NASA Astrophysics Data System (ADS)

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.

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

2014-07-01

199

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

PubMed Central

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

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

2013-01-01

200

Fronto-striatal connections in the human brain: A probabilistic diffusion tractography study  

Microsoft Academic Search

Anatomical studies in animals have described multiple striatal circuits and suggested that sub-components of the striatum, although functionally related, project to distinct cortical areas. To date, anatomical investigations in humans have been limited by methodological constraints such that most of our knowledge of fronto-striatal networks relies on nonhuman primate studies. To better identify the fronto-striatal pathways in the human brain,

Sandra E. Leh; Alain Ptito; M. Mallar Chakravarty; Antonio P. Strafella

2007-01-01

201

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

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Human Studies Review Board review of proposed...Research § 26.1606 Human Studies Review Board review of proposed...submitted to it by EPA, the Human Studies Review Board must consider the scientific merits and ethical...

2013-07-01

202

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

Code of Federal Regulations, 2013 CFR

...2013-07-01 false Human Studies Review Board review of completed...Research § 26.1607 Human Studies Review Board review of completed...submitted to it by EPA, the Human Studies Review Board must consider the scientific merits and ethical...

2013-07-01

203

Paediatric palliative care: development and pilot study of a 'Directory' of life-limiting conditions  

PubMed Central

Background Children’s palliative care services are developing. Rational service development requires sound epidemiological data that are difficult to obtain owing to ambiguity in the definitions both of the population who needs palliative care and of palliative care itself. Existing definitions are of trajectory archetypes. The aim of this study was to develop and pilot a directory of the commonest specific diagnoses that map on to those archetypes. Methods The diagnoses of patients under the care of five children hospices and a tertiary specialist palliative medicine service in the UK were recorded. Duplicates and diagnoses that were not life-limiting conditions according to the ACT/RCPCH criteria or were not primary were removed. The resulting Directory of life-limiting conditions was piloted by analysing Death Certificate data of children in Wales between 2002 and 2007. Results 1590 diagnoses from children’s hospices and 105 from specialist palliative medicine were combined. After removals there were 376 diagnostic label. All ICD10 chapter headings were represented by at least one condition. The pilot study showed that 569 (54%) deaths in Wales were caused by LLC. Only four LLC resulted in ten or more deaths. Among deaths from LLC, the ten commonest diagnoses accounted for 32%, while the 136 diagnoses that caused one or two deaths accounted for 25%. The majority occurred from a small number of life-limiting conditions. Conclusion The Directory is a practical tool for identifying most life-limiting conditions using ICD10 codes that facilitates extraction and analysis of data from existing sources in respect of life-limiting conditions in children such as death certificate data, offering the potential for rapid and precise studies in paediatric palliative care.

2013-01-01

204

A strategy to study genotoxicity: application to aquatic toxins, limits and solutions.  

PubMed

Humans can be exposed to aquatic toxins mainly through contamination of food and water (drinking and recreational). Among these toxins, contamination by both phycotoxins occurring in shellfish and cyanotoxins mostly involved in freshwater bodies are of concern for public health. Whereas regulations exist to evaluate the genotoxicity of most compounds to which humans are exposed, including drugs and chemicals, no regulations have been established for these compounds. In this paper, we show that the same strategy including both in vitro and in vivo tests can be followed to evaluate the genotoxicity of aquatic toxins (phycotoxins and cyanotoxins). However, this strategy encountered different limits which arise when completing an overview of the genotoxic potential of toxins. The most restrictive one is undoubtedly the low amount (even the lack sometimes) of purified toxins available. Solutions and recommendations for testing the genotoxicity of aquatic toxins are suggested to overcome the specific problems encountered with these compounds. It must be kept in mind that recent developments in drug toxicology should be considered and that experiments must be conducted in respect of the 3Rs principle of refinement, reduction and replacement for animal experimentation. PMID:20446082

Fessard, Valérie; Le Hégarat, Ludovic

2010-07-01

205

An in vitro model for the study of human implantation  

PubMed Central

Problem Implantation remains the rate-limiting step for the success of in vitro fertilization (IVF). Appropriate models to study the molecular aspects of human implantation are necessary in order to improve fertility. Methods First trimester trophoblast cells are differentiated into blastocyst-like spheroids (BLS) by culturing them in low attachment plates. Immortalized human endometrial stromal cells (hESC) and epithelial cells (ECC-1) were stably transfected with GFP or tdTomato. Co-culture experiments were monitored using Volocity imaging analysis system. Results This method demonstrates attachment and invasion of BLS, formed by trophoblast cells, into stromal cells but not to uterine epithelial cells. Conclusion We have developed an in vitro model of uterine implantation. The manipulation of this system allows for dual color monitoring of the cells over time. Additionally, specific compounds can be added to the culture media to test how this may affect implantation and invasion. This model is a helpful tool in understanding the complexity of human implantation.

Holmberg, Jennie C.; Haddad, Severina; Wunsche, Vera; Yang, Yang; Aldo, Paulomi B.; Gnainsky, Yulia; Granot, Irit; Dekel, Nava; Mor, Gil

2013-01-01

206

Insulin Stimulates Liver Glucose Uptake in Humans: An 18F-FDG PET Study  

Microsoft Academic Search

The liver is vital for the regulation of glucose metabolism, but inaccessibility of the organ for direct assessments has limited the study of its metabolic role in vivo. Methods: The effect of insulin and insulin sensitivity (IS) on hepatic glucose uptake was investigated using PET, 18F-FDG, and graphical analysis and 3-compartment modeling in humans. We studied 16 healthy sedentary men

Patricia Iozzo; Fabian Geisler; Vesa Oikonen; Maija Maki; Teemu Takala; Olof Solin; Ele Ferrannini; Juhani Knuuti; Pirjo Nuutila

207

Study of the W +W ? ? process and limits on anomalous quartic gauge boson couplings at LEP  

Microsoft Academic Search

The process e+e??W+W?? is studied using the data collected by the L3 detector at LEP. New results, corresponding to an integrated luminosity of 427.4 pb?1 at centre-of-mass energies from 192 to 207 GeV, are presented.The W+W?? cross sections are measured to be in agreement with Standard Model expectations. No hints of anomalous quartic gauge boson couplings are observed. Limits at 95% confidence

P. Achard; O. Adriani; M. Aguilar-Benitez; J. Alcaraz; G. Alemanni; J. Allaby; A. Aloisio; M. G. Alviggi; H. Anderhub; V. P. Andreev; F. Anselmo; A. Arefiev; T. Azemoon; T. Aziz; P. Bagnaia; A. Bajo; G. Baksay; L. Baksay; S. V. Baldew; S. Banerjee; A. Barczyk; R. Barillčre; P. Bartalini; M. Basile; N. Batalova; R. Battiston; A. Bay; F. Becattini; U. Becker; F. Behner; L. Bellucci; R. Berbeco; J. Berdugo; P. Berges; B. Bertucci; B. L. Betev; M. Biasini; M. Biglietti; A. Biland; J. J. Blaising; S. C. Blyth; G. J. Bobbink; A. Böhm; L. Boldizsar; B. Borgia; S. Bottai; D. Bourilkov; M. Bourquin; S. Braccini; J. G. Branson; F. Brochu; A. Buijs; J. D. Burger; W. J. Burger; X. D. Cai; M. Capell; G. Carlino; A. Cartacci; J. Casaus; F. Cavallari; N. Cavallo; C. Cecchi; M. Cerrada; M. Chamizo; Y. H. Chang; M. Chemarin; A. Chen; G. Chen; H. F. Chen; H. S. Chen; G. Chiefari; L. Cifarelli; F. Cindolo; I. Clare; R. Clare; G. Coignet; N. Colino; S. Costantini; S. Cucciarelli; P. Déglon; J. Debreczeni; A. Degré; K. Deiters; E. Delmeire; P. Denes; F. DeNotaristefani; M. Diemoz; M. Dierckxsens; C. Dionisi; M. Dittmar; A. Doria; M. T. Dova; D. Duchesneau; P. Duinker; B. Echenard; A. Eline; A. Engler; F. J. Eppling; A. Ewers; P. Extermann; M. A. Falagan; S. Falciano; A. Favara; J. Fay; O. Fedin; M. Felcini; T. Ferguson; H. Fesefeldt; E. Fiandrini; J. H. Field; F. Filthaut; P. H. Fisher; W. Fisher; I. Fisk; G. Forconi; K. Freudenreich; C. Furetta; Yu. Galaktionov; S. N. Ganguli; P. Garcia-Abia; M. Gataullin; S. Gentile; S. Giagu; Z. F. Gong; G. Grenier; O. Grimm; M. W. Gruenewald; M. Guida; V. K. Gupta; A. Gurtu; L. J. Gutay; D. Haas; D. Hatzifotiadou; T. Hebbeker; A. Hervé; J. Hirschfelder; H. Hofer; M. Hohlmann; G. Holzner; S. R. Hou; Y. Hu; B. N. Jin; L. W. Jones; I. Josa-Mutuberr??a; D. Käfer; M. Kaur; M. N. Kienzle-Focacci; J. K. Kim; J. Kirkby; W. Kittel; A. Klimentov; A. C. König; M. Kopal; V. Koutsenko; M. Kräber; R. W. Kraemer; W. Krenz; A. Krüger; A. Kunin; I. Laktineh; G. Landi; M. Lebeau; A. Lebedev; P. Lebrun; P. Lecomte; P. Lecoq; R. Leiste; P. Levtchenko; C. Li; S. Likhoded; C. H. Lin; W. T. Lin; F. L. Linde; L. Lista; Z. A. Liu; W. Lohmann; E. Longo; Y. S. Lu; K. Lübelsmeyer; C. Luci; L. Luminari; W. Lustermann; W. G. Ma; L. Malgeri; A. Malinin; C. Mańa; D. Mangeol; J. Mans; J. P. Martin; F. Marzano; K. Mazumdar; R. R. McNeil; S. Mele; L. Merola; M. Meschini; W. J. Metzger; A. Mihul; H. Milcent; G. Mirabelli; J. Mnich; G. B. Mohanty; G. S. Muanza; A. J. M. Muijs; B. Musicar; M. Musy; S. Nagy; S. Natale; M. Napolitano; F. Nessi-Tedaldi; H. Newman; T. Niessen; A. Nisati; H. Nowak; R. Ofierzynski; G. Organtini; C. Palomares; D. Pandoulas; P. Paolucci; R. Paramatti; G. Passaleva; S. Patricelli; T. Paul; M. Pauluzzi; C. Paus; F. Pauss; M. Pedace; S. Pensotti; D. Perret-Gallix; B. Petersen; D. Piccolo; F. Pierella; M. Pioppi; P. A. Piroué; E. Pistolesi; V. Plyaskin; M. Pohl; V. Pojidaev; J. Pothier; D. O. Prokofiev; J. Quartieri; G. Rahal-Callot; M. A. Rahaman; P. Raics; N. Raja; R. Ramelli; P. G. Rancoita; R. Ranieri; A. Raspereza; P. Razis; D. Ren; M. Rescigno; S. Reucroft; S. Riemann; K. Riles; B. P. Roe; L. Romero; A. Rosca; S. Rosier-Lees; S. Roth; C. Rosenbleck; B. Roux; J. A. Rubio; G. Ruggiero; H. Rykaczewski; A. Sakharov; S. Saremi; S. Sarkar; J. Salicio; E. Sanchez; M. P. Sanders; C. Schäfer; V. Schegelsky; S. Schmidt-Kaerst; D. Schmitz; H. Schopper; D. J. Schotanus; G. Schwering; C. Sciacca; L. Servoli; S. Shevchenko; N. Shivarov; V. Shoutko; E. Shumilov; A. Shvorob; T. Siedenburg; D. Son; P. Spillantini; M. Steuer; D. P. Stickland; B. Stoyanov; A. Straessner; K. Sudhakar; G. Sultanov; L. Z. Sun; S. Sushkov; H. Suter; J. D. Swain; Z. Szillasi; X. W. Tang; P. Tarjan; L. Tauscher; L. Taylor; B. Tellili; D. Teyssier; C. Timmermans; S. M. Ting; S. C. Tonwar; J. Tóth; C. Tully; K. L. Tung; J. Ulbricht; E. Valente; V. Veszpremi; G. Vesztergombi; I. Vetlitsky; D. Vicinanza; P. Violini; G. Viertel; S. Villa; M. Vivargent; S. Vlachos; I. Vodopianov; H. Vogel; H. Vogt; I. Vorobiev; A. A. Vorobyov; M. Wadhwa; W. Wallraff; X. L. Wang; Z. M. Wang; M. Weber; P. Wienemann; H. Wilkens; S. Wynhoff; L. Xia; Z. Z. Xu; J. Yamamoto; B. Z. Yang; C. G. Yang; H. J. Yang; M. Yang; S. C. Yeh; An. Zalite; Yu. Zalite; Z. P. Zhang; J. Zhao; G. Y. Zhu; R. Y. Zhu; H. L. Zhuang; A. Zichichi; G. Zilizi; B. Zimmermann; M. Z. Zöller

2002-01-01

208

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

PubMed Central

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

Feng, Yi; Li, Xin; Shao, Ruijin

2013-01-01

209

Metabolomic studies of human gastric cancer: Review  

PubMed Central

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

Jayavelu, Naresh Doni; Bar, Nadav S

2014-01-01

210

A multiple imputation approach to disclosure limitation for high-age individuals in longitudinal studies  

PubMed Central

Disclosure limitation is an important consideration in the release of public use data sets. It is particularly challenging for longitudinal data sets, since information about an individual accumulates with repeated measures over time. Research on disclosure limitation methods for longitudinal data has been very limited. We consider here problems created by high ages in cohort studies. Because of the risk of disclosure, ages of very old respondents can often not be released; in particular this is a specific stipulation of the Health Insurance Portability and Accountability Act (HIPAA) for the release of health data for individuals. Top-coding of individuals beyond a certain age is a standard way of dealing with this issue, and it may be adequate for cross-sectional data, when a modest number of cases are affected. However, this approach leads to serious loss of information in longitudinal studies when individuals have been followed for many years. We propose and evaluate an alternative to top-coding for this situation based on multiple imputation (MI). This MI method is applied to a survival analysis of simulated data, and data from the Charleston Heart Study (CHS), and is shown to work well in preserving the relationship between hazard and covariates.

An, Di; Little, Roderick J.A.; McNally, James W.

2010-01-01

211

78 FR 35031 - Human Studies Review Board Advisory Committee  

Federal Register 2010, 2011, 2012, 2013

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

2013-06-11

212

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

NASA Astrophysics Data System (ADS)

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.

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

213

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

PubMed

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

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

2013-12-01

214

Studies on the tolerance limit of fluoride in food in China  

SciTech Connect

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.

Chen, S.L.; Gong, Y.J.; Fu, Y.G. (Zhejiang Academy of Medicine (China))

1988-10-01

215

Studies of WW and WZ production and limits on anomalous WW? and WWZ couplings  

NASA Astrophysics Data System (ADS)

Evidence of anomalous WW and WZ production was sought in ppŻ collisions at a center-of-mass energy of s=1.8 TeV. The final states WW(WZ)-->?? jet jet+X, WZ-->??ee+X and WZ-->e?ee+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 WW? and WWZ couplings and were combined with our previous results. The combined 95% confidence level anomalous coupling limits for ?=2 TeV are -0.25<=??<=0.39 (?=0) and -0.18<=?<=0.19 (??=0), assuming the WW? couplings are equal to the WWZ couplings.

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.; Magańa-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

216

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

Microsoft Academic Search

The limited source of human nail plate for studying drug permeation inspired us to develop a nail plate model made of human hair keratin. The manufacturing process consisted of keratin extraction, dialysis, molding, solvent evaporation, and curing, producing a water-resistant film. The permeability of the film was examined using three markers: sodium fluorescein, rhodamine B, and fluorescein isothiocyanate–dextran as water-soluble,

Lusiana; Stephan Reichl; Christel C. Müller-Goymann

2011-01-01

217

An HPLC method for the measurement of 5-fluorouracil in human plasma with a low detection limit and a high extraction yield.  

PubMed

High performance liquid chromatographic (HPLC) techniques for the quantification of 5-fluorouracil (5-FU) in human plasma have been reported in the literature, however, a low limit of detection was generally found to result in a comparatively low extraction yield. We have developed a simple, rapid and sensitive HPLC method for the measurement of 5-FU in plasma which provides both a low limit of quantification and a high extraction yield. This method involves the solid phase extraction of 5-FU from a 500 microl plasma sample. The extract is then injected into an HPLC system equipped with a C18 (mu)Bondapak column, and a UV detector set at 260 nm. Ethyl acetate and potassium dihydrogen phosphate are used for the solid phase extraction and the HPLC mobile phase, respectively. This method provides in a good baseline, a sharp and symmetrical peak for 5-FU, and a high resolution between 5-FU and the internal standard. The retention time of 5-FU using this method is 4.7 min with a limit of detection of 5 ng/ml, and an extraction yield of 96.2+/-0.5% (SE). The next injection is possible in 11 min, and the coefficients of variation are 4.2-8.9% for interday precision, and 5.2-10.6% for day-to-day reproducibility. An HPLC method has been developed that has a low limit of detection and a high extraction yield. This technique was successfully applied in a clinical pharmacokinetic study of 5-FU. PMID:12239603

Nassim, Mark Adel; Shirazi, Farshad H; Cripps, Christine M; Veerasinghan, Shereeni; Molepo, Matshela J; Obrocea, Mihail; Redmond, Diedre; Bates, Susan; Fry, Diane; Stewart, David J; Goel, Rakesh

2002-10-01

218

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

PubMed Central

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.

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

2013-01-01

219

A Brief History of Soils and Human Health Studies  

NASA Astrophysics Data System (ADS)

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

Brevik, Eric C.; Sauer, Thomas J.

2013-04-01

220

Implementing surgical services in a rural, resource-limited setting: a study protocol  

PubMed Central

Introduction There are well-established protocols and procedures for the majority of common surgical diseases, yet surgical services remain largely inaccessible for much of the world's rural poor. Data on the process and outcome of surgical care expansion, however, are very limited, and the roll-out process of rural surgical implementation in particular has never been studied. Here, we propose the first implementation research study to assess the surgical scale-up process in the rural district of Achham, Nepal. Methods and analysis Based primarily on the protocols of the WHO's Integrated Management for Emergency and Essential Surgical Care (IMEESC), this study's threefold implementation strategy will include: (1) the core IMEESC surgical care program, (2) community-based follow-up via health workers, and (3) hospital-based quality improvement programs. The implementation program will employ additional emergency and surgical care protocols developed collaboratively by physicians, nurses and the authors. This strategy will be referred to as IMEESC-Plus. This study will employ both qualitative and quantitative research methodologies to collect clinical data and information on the reception and utilisation of services. The first 18?months of the implementation process will be studied and divided into an initial phase (first 6?months) and a consolidation phase (subsequent 12?months). Discussion This study aims to describe the logistics of the implementation process of IMEESC-Plus, and assess the quality of the resulting IMEESC-Plus services during the course of the implementation process. Using data generated from this study, larger, multi-site implementation studies can be planned that assess the scale-up of surgical services worldwide in resource-limited areas.

Maru, Duncan Smith-Rohrberg; Schwarz, Ryan; Schwarz, Dan; Andrews, Jason; Panizales, Maria Theresa; Karelas, Gregory; Rogers, Selwyn

2011-01-01

221

Subjective Quantitative Studies of Human Agency  

ERIC Educational Resources Information Center

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

Alkire, Sabina

2005-01-01

222

The multidomain structure of ceruloplasmin from calorimetric and limited proteolysis studies.  

PubMed

Differential scanning calorimetry has been used to investigate the thermal stability of three different ceruloplasmins (from sheep, chicken, and turtle) in their native state and after limited proteolysis. The three undegraded proteins showed a similar structural organization in three calorimetric domains, although their temperature of unfolding varied from 57.8 degrees C (turtle) to 71.2 degrees C (sheep) to 82.1 degrees C (chicken). The spectroscopic and the catalytic properties were totally lost at temperatures corresponding to the unfolding of the less thermostable domain in the case of sheep and chicken ceruloplasmins and to the unfolding of the most thermostable domain in the turtle protein. Trypsin, but not plasmin, digestion caused a significant decrease of the thermal stability of sheep and chicken ceruloplasmins. Turtle ceruloplasmin was insensitive to both proteases. Comparing the thermodynamic parameters of the sheep protein in its undegraded and cleaved states revealed a mismatch between the three calorimetric domains and the 3-fold internal replication of the primary structure, which is evident in the highly homologous, fully sequenced human protein. Copper removal caused the rearrangement of the molecule in only two calorimetric domains, suggesting a role of the metal atoms in organizing a new calorimetric domain, which was tentatively assigned to the less thermostable cooperative unit of the native protein. PMID:2250007

Bonaccorsi di Patti, M C; Musci, G; Giartosio, A; D'Alessio, S; Calabrese, L

1990-12-01

223

Studying the immune response to human viral infections using zebrafish.  

PubMed

Humans and viruses have a long co-evolutionary history. Viral illnesses have and will continue to shape human history: from smallpox, to influenza, to HIV, and beyond. Animal models of human viral illnesses are needed in order to generate safe and effective antiviral medicines, adjuvant therapies, and vaccines. These animal models must support the replication of human viruses, recapitulate aspects of human viral illnesses, and respond with conserved immune signaling cascades. The zebrafish is perhaps the simplest, most commonly used laboratory model organism in which innate and/or adaptive immunity can be studied. Herein, we will discuss the current zebrafish models of human viral illnesses and the insights they have provided. We will highlight advantages of early life stage zebrafish and the importance of innate immunity in human viral illnesses. We will also discuss viral characteristics to consider before infecting zebrafish with human viruses as well as predict other human viruses that may be able to infect zebrafish. PMID:24718256

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

2014-09-01

224

Human tetranectin: methodological and clinical studies.  

PubMed

From its discovery in 1986 tetranectin (TN) has been suggested to participate in proteolytic processes through its binding to plasminogen, which enhances the activation of plasminogen to plasmin. Because extracellular proteolysis is an important factor in the ability of malignant cells to infiltrate normal tissues and metastasize, TN was considered to be a potential marker for this proteolysis. We have studied the variations in blood and tissue levels of TN in clinical conditions such as cancer and infection, where increased proteolysis can be expected. Five monoclonal antibodies (MAbs) were produced against human TN, and our study is the first report of stable hybridomas producing MAbs against human TN. All the MAbs reacted with epitopes located within aa-residues 50-181 of the primary sequence. In relative epitope mapping with enzyme immuno assay and isotachophoresis the five MAbs defined two independent epitope groups. Different combinations of MAbs were suitable for enzyme immuno assays and two MAbs could be used for immunohistochemical detection of TN in both fresh frozen and paraffin embedded tissues. The MAbs will facilitate future studies on structure, function, clinical significance and immunolocalization of TN. In primary ovarian cancer neither s/p-TN nor CA 125 were found valuable for diagnosis of localized cancer versus benign tumors. However, s/p-TN combined with CA 125, increased both sensitivity and specificity. S/p-TN should therefore be considered one of the screening markers in conjunction with CA 125, or other comparable markers, in future ovarian cancer screening research studies. Preoperative s-TN was significantly correlated to residual tumor and survival in ovarian cancer patients undergoing second or third look surgery. In conjunction with CA 125 and CASA the predictive value of TN for residual tumor was greatly improved, as the markers were found to supplement each other. If the second look operation had been restricted to patients who had a marker negative test, up to 37% would have avoided surgery. We therefore recommend that these tests are included as potential selection parameters in other studies evaluating second-look surgery. Low p-TN concentration and heavy extracellular staining of TN in the tumors was significantly correlated with a poor prognosis for patients with localized stage I or II or advanced primary ovarian cancer. The prognostic information can be especially valuable for patients with a localized ovarian cancer stage I or II, because about 20% of these patients, believed to be radically operated later present with relapse. We found the p-TN level to be especially useful for patients with localized cancer, indicating that adjuvant chemotherapy may be considered if the p-TN level is low. For patients with advanced primary ovarian cancer and low p-TN the survival was significantly reduced compared to patients with a higher p-TN. The p-TN level was significantly negatively correlated to the extracellular (stromal) staining of TN in the tumors. A heavy stromal TN staining was correlated with a shortened survival and was an independent prognostic factor in the Cox analyses. Patients with advanced primary cancer and a low p-TN, possibly in combination with a heavy stromal staining of TN in the tumors, should tentatively be offered palliative treatment or experimental chemotherapy. Furthermore, patients receiving chemotherapy may be monitored by s/p-TN measurements, as a decrease in TN concentration indicated recurrence 3.6 months prior to clinical diagnosis. A decrease in TN concentration during chemotherapy may therefore indicate change of treatment. Serum TN was a very strong independent prognostic factor of poor treatment response and a shortened survival in patients with metastatic breast cancer. A low pre-chemotherapy s-TN value together with clinical signs of poor treatment response may be an ominous combination, which may suggest change of treatment. For patients with Dukes' stage PMID:9868384

Hřgdall, C K

1998-01-01

225

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...

226

A study of human serum sickness.  

PubMed

Twelve patients with bone marrow failure, who were undergoing therapy with daily intravenous infusions of horse antithymocyte globulin, were studied for the development of serum sickness. Eleven of 12 patients developed typical signs and symptoms of serum sickness 8-13 days after the initiation of treatment. These included fever, malaise, cutaneous eruptions, arthralgias, gastrointestinal disturbances, and lymphadenopathy. Eleven of 12 patients developed high levels of circulating immune complexes during serum sickness. All 12 patients also had concomitant decreases of serum C3 and C4 levels. In addition to urticarial and/or morbilliform eruptions, 8 of 11 patients also developed a serpiginous band of erythema along the sides of the fingers, hands, toes, or feet as an early cutaneous sign of serum sickness. Direct immunofluorescence of lesional skin biopsies during serum sickness revealed deposits of immunoglobulin or complement in the walls of small cutaneous blood vessels in 3 of 5 patients. These findings indicate that circulating immune complexes play a central role in the pathophysiology of human sickness. PMID:3891879

Lawley, T J; Bielory, L; Gascon, P; Yancey, K B; Young, N S; Frank, M M

1985-07-01

227

Studies of human breast cancer metastasis using nude mice  

Microsoft Academic Search

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

Janet E. Price; Ruo Dan Zhang

1990-01-01

228

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

ERIC Educational Resources Information Center

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)

O'Brien, Ed

1999-01-01

229

Restless legs syndrome and functional limitations among American elders in the Health and Retirement Study  

PubMed Central

Background Restless legs syndrome (RLS) is a common condition associated with decreased quality of life in older adults. This study estimates the prevalence, risk factors, and functional correlates of among U.S. elders. Methods Subjects (n?=?1,008) were sub-sampled from the 2002 cross-sectional interview survey of the Health and Retirement Study (HRS), a nationally representative study of U.S. elders. Symptoms and sleep disturbances consistent with RLS were identified. Activities of daily living (ADL), instrumental activities of daily living (IADL), and limitations for mobility, large muscle groups, gross and fine motor function were measured using standardized questions. Incident functional limitations were detected over six years of observation. Results The prevalence of RLS among U.S. elders born before 1947 was 10.6%. Factors associated with increased prevalence RLS at baseline included: overweight body mass index (multivariate adjusted prevalence ratio?=?1.77; 95% confidence interval (CI) 1.05-2.99); mild-to-moderate pain (2.67, 1.47-4.84) or pain inferring with activity (3.44, 2.00-5.93); three or more chronic medications (2.54, 1.26-5.12), highest quartile of out-of-pocket medical expenses (2.12, 1.17-3.86), frequent falls (2.63, 1.49-4.66), health limiting ability to work (2.91, 1.75-4.85), or problems with early waking or frequent wakening (1.69, 1.09-2.62 and 1.55, 1.00-2.41, respectively). Current alcohol consumption (0.59, 0.37-0.92) and frequent healthcare provider visits (0.49, 0.27-0.90) were associated with decreased RLS prevalence. RLS did not predict incident disability for aggregate measures but was associated with increased risk for specific limitations, including: difficulty climbing several stair flights (multivariate-adjusted hazard ratio?=?2.38, 95% CI 1.39-4.06), prolonged sitting (2.17, 1.25-3.75), rising from a chair (2.54, 1.62-3.99), stooping (2.66, 1.71-4.15), moving heavy objects (1.79, 1.08-2.99), carrying ten pounds (1.61, 1.05-2.97), raising arms (1.76, 1.05-2.97), or picking up a dime (1.97, 1.12-3.46). Conclusions RLS sufferers are more likely to have functional disability, even after adjusting for health status and pain syndrome correlates.

2012-01-01

230

Semen Quality and Human Fertility: A Prospective Study With Healthy Couples  

Microsoft Academic Search

Measures of semen quality are used as surrogate measures of male fertility in clinical andrology, reproductive toxicol- ogy, epidemiology, and risk assessment. However, only limited data are available to relate those measures to fertility. This prospective study with 210 reproductive-age couples was conducted to provide information on the value of semen quality measures for predicting human male fertility potential and

MICHAEL J. ZINAMAN; CHARLES C. BROWN; SHERRY G. SELEVAN; ERIC D. CLEGG

2000-01-01

231

Global Proficiency Study of Human Papillomavirus Genotyping ?  

PubMed Central

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

Eklund, Carina; Zhou, Tiequn; Dillner, Joakim

2010-01-01

232

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

PubMed Central

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.

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

2009-01-01

233

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

SciTech Connect

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.

Lee, E.W.; Terzo, T.S.; D'Arcy, J.B.; Gross, K.B.; Schreck, R.M. (Biomedical Science Department, General Motors Research Laboratories, Warren, MI (United States))

1992-02-01

234

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

PubMed Central

Two live attenuated single-deletion mutant simian immunodeficiency virus (SIV) constructs, SIV239?nef and SIVPBj6.6?nef, were tested for their abilities to stimulate protective immunity in macaques. During the immunization period the animals were examined for specific immune responses and virus growth. Each construct generated high levels of specific immunity in all of the immunized animals. The SIV239?nef construct was found to grow to high levels in all immunized animals, with some animals remaining positive for virus isolation and plasma RNA throughout the immunization period. The SIVPBj6.6?nef was effectively controlled by all of the immunized animals, with virus mostly isolated only during the first few months following immunization and plasma RNA never detected. Following an extended period of immunization of over 80 weeks, the animals were challenged with a pathogenic simian-human immunodeficiency virus (SHIV) isolate, SIV89.6PD, by intravenous injection. All of the SIV239?nef-immunized animals became infected with the SHIV isolate; two of five animals eventually controlled the challenge and three of five animals, which failed to check the immunizing virus, progressed to disease state before the unvaccinated controls. One of five animals immunized with SIVPBj6.6?nef totally resisted infection by the challenge virus, while three others limited its growth and the remaining animal became persistently infected and eventually died of a pulmonary thrombus. These data indicate that vaccination with attenuated SIV can protect macaques from disease and in some cases from infection by a divergent SHIV. However, if animals are unable to control the immunizing virus, potential damage that can accelerate the disease course of a pathogenic challenge virus may occur.

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

1999-01-01

235

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

PubMed Central

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.

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

236

Permeability of human red cells to a homologous series of aliphatic alcohols. Limitations of the continuous flow-tube method  

PubMed Central

Human red cell permeability to the homologous series of methanol, ethanol, n-propanol, n-butanol, and n-hexanol was determined in tracer efflux experiments by the continuous flow tube method, whose time resolution is 2-3 ms. Control experiments showed that unstirred layers in the cell suspension were less than 2 X 10(-4) cm, and that permeabilities less than or equal to 10(-2) cm s-1 can be determined with the method. Alcohol permeability varied with the chain length (25 degrees C): Pmeth 3.7 X 10(-3) cm s-1, Peth 2.1 X 10(-3) cm s-1, Pprop 6.5 X 10(-3) cm s-1, Pbut less than or equal to 61 X 10(-3) cm s-1, Phex 8.7 X 10(-3) cm s-1. The permeability for methanol, ethanol, and n- propanol was concentration independent (1-500 mM). The permeability to n-butanol and n-hexanol, however, increased above the upper limit of determination at alcohol concentrations of 100 and 25 mM, respectively. The activation energies for the permeability to methanol, n-propanol, and n-hexanol were similar, 50-63 kJ mol-1. Methanol permeability was not reduced by p-chloromercuribenzene sulfonate (PCMBS), thiourea, or phloretin, which inhibit transport of water or hydrophilic nonelectrolytes. It is concluded (a) that all the alcohols predominantly permeate the membrane lipid bilayer structure; (b) that both the distribution coefficient and the diffusion coefficient of the alcohols within the membrane determine the permeability, and (c) that the relative importance of the two factors varies with changes in the chain length.

1983-01-01

237

Pharmacokinetic and chemoprevention studies on tea in humans.  

PubMed

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

Chow, H-H Sherry; Hakim, Iman A

2011-08-01

238

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

USGS Publications Warehouse

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.

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

2009-01-01

239

Study of all-optical switching and optical limiting properties in phenoxy-phthalocyanines liquid  

NASA Astrophysics Data System (ADS)

The pump-probe technique and transmission measurement technique were used to study the all-optical switching (A-OS) and optical limiting (OL) behavior of 2, 9, 16, 23-phenoxy-phthalocyanine (Pc1) and 2, 9, 16, 23-phenoxy-phthalocyanine-zinc (Pc2) in predominantly the monomeric solution form. The results show that the A-OS response time of Pc2 is longer than that of Pc1, and switch-off and -on times of A-OS for Pc2 are 1.2 and 11.6 ?s and for Pc1 are 2.3 and 7.8 ?s at the same intensity. Moreover, the results of OL experiments reveal that Pc1 and Pc2 exhibit strong OL effect at nanosecond laser pulses. These studies make the samples a promising possibility for device realization.

Yao, Cheng-Bao; Zhang, Yun-dong; Chen, Deng-Tai; Yin, Hai-Tao; Yu, Chang-Qiu; Li, Jin; Yuan, Ping

2013-04-01

240

An investigation of genome-wide studies reported susceptibility loci for ulcerative colitis shows limited replication in north Indians.  

PubMed

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

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

2011-01-01

241

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

PubMed Central

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

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

2011-01-01

242

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

PubMed

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 4 pi 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 26 Mg(n,gamma)27 Mg reaction produces gamma -rays of 0.843 MeV from the decay of 27 Mg, which interfere with the 0.847 MeV gamma -rays from the decay of 56 Mn,produced by the 55 Mn(n,gamma)56 Mn 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 microg/g Ca. It also provides a revised estimate of expected referent levels of manganese in bone, now estimated to be 0.63 microg/g Ca and highlights the extent to which technical improvements will be required to further extend the application of the technique for in vivo measurements in non-exposed human subjects. PMID:18782941

Aslam; Pejovi?-Mili?, A; Chettle, D R; McNeill, F E

2008-08-01

243

Teacher Leader Human Relations Skills: A Comparative Study  

ERIC Educational Resources Information Center

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…

Roby, Douglas E.

2012-01-01

244

Study on the limiting ability of shaping aspheric surfaces by FEM  

NASA Astrophysics Data System (ADS)

To shape aspheric surfaces on ultra-thin spherical mirrors can avoid problems of manufacture and measurement for large-aperture aspherical mirrors. In order to study the ability of shaping aspheric surfaces and find out some aspherical parameters that can describe the ability, the limit ability of shaping aspheric surfaces is investigated. Firstly, the relation between asphericity gradient and stress of shaping aspheric surfaces on ultra-thin mirrors is analyzed, and the asphericity gradient of spheres is determined to represent the limit ability. Secondly, based on an example of off-axis large-aperture ultra-thin mirrors, the spheres with the different asphericity gradient are worked out, and the figure errors and the maximal stresses for shaping aspheric surfaces are gotten by Finite Element Method (FEM). Thirdly, according to analysis results, the relation between maximal asphericity gradient of sphere and maximal stresses is created, and the relation between initial figure errors of spheres and maximal asphericity gradient is presented on ZERODUR material. Finally, the maximal stresses of other materials after deformation are solved by using Hook law and FEM. Above analysis results show that the material ZERODUR applied shaping aspherical surfaces is not broken under conditions of the asphericity gradient threshold 1.62e-5, the corresponding initial figure errors RMS threshold 0.49mm, and the P-V threshold 1.74mm, when the aspherical accuracy is 21.09nm. In addition, according to the maximal stresses of ZERODUR, the maximal stresses of other materials are estimated, and their limit ability of shaping aspheric surfaces also can be defined.

Zeng, Chunmei; Yu, Jingchi

2009-05-01

245

Breaking the theoretical limit of SiC unipolar power device A simulation study  

NASA Astrophysics Data System (ADS)

SiC is known as the next generation material for power semiconductor devices. One important issue in the design of high voltage power devices is the trade-off between breakdown voltage and specific on-resistance. In this paper, possibility of developing 4H-SiC devices beyond its own unipolar theoretical limit R?VBR2.43 by using the super-junction concept has been investigated for the first time. Effects of structural parameters on the voltage blocking capability and specific on-resistance are studied. Device structures achieving optimum FOMs (Figure of Merit) at various voltage ranges have been designed and their advantages over the conventional structures are quantified. In addition, simple models have also been developed and verified by 2D numerical simulations for 4H-SiC super-junction structures to predict their voltage blocking and forward conduction capability. The results show that, with currently available technology, device FOM (for the same VBR) exceeding the 4H-SiC theoretical unipolar limit by 300% is possible.

Yu, L. C.; Sheng, K.

2006-06-01

246

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

PubMed Central

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

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

2011-01-01

247

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

NASA Astrophysics Data System (ADS)

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

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

2010-01-01

248

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

ERIC Educational Resources Information Center

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…

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

2009-01-01

249

Potential and limitations of multidecadal satellite soil moisture observations for selected climate model evaluation studies  

NASA Astrophysics Data System (ADS)

Soil moisture is an essential climate variable (ECV) of major importance for land-atmosphere interactions and global hydrology. An appropriate representation of soil moisture dynamics in global climate models is therefore important. Recently, a first multidecadal, observation-based soil moisture dataset has become available that provides information on soil moisture dynamics from satellite observations (ECVSM, essential climate variable soil moisture). The present study investigates the potential and limitations of this new dataset for several applications in climate model evaluation. We compare soil moisture data from satellite observations, reanalysis and simulations from a state-of-the-art land surface model and analyze relationships between soil moisture and precipitation anomalies in the different dataset. Other potential applications like model parameter optimization or model initialization are not investigated in the present study. In a detailed regional study, we show that ECVSM is capable to capture well the interannual and intraannual soil moisture and precipitation dynamics in the Sahelian region. Current deficits of the new dataset are critically discussed and summarized at the end of the paper to provide guidance for an appropriate usage of the ECVSM dataset for climate studies.

Loew, A.; Stacke, T.; Dorigo, W.; de Jeu, R.; Hagemann, S.

2013-09-01

250

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

NASA Astrophysics Data System (ADS)

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.

Lima, Paulo; Ostermann, Fernanda; Rezende, Flavia

2014-05-01

251

Study of the acceptable dc current limit in core-form power transformers  

SciTech Connect

The temperature rise in power transformers subjected to a dc source of excitation was measured on core-form single-phase 735-kV autotransformers rated 370-MVA and 550-MVA. The measurements were compared to the temperature rise values obtained on the same transformers operating in overexcitation at 1.95 T. The results show that the tie plates of this particular type of transformer are the components most susceptible to rapid temperature rise. Smaller-scale tests on 100-kVA transformers were performed to take a specific look at these tie plates under the effect of a temperature increase. Finite-element simulations combined with analytical studies of temperature rise were performed in an attempt to determine a tolerable dc current limit based on permissible temperature standards.

Picher, P.; Bolduc, L. [Institut de Recherche d`Hydro-Quebec (IREQ), Varennes, Quebec (Canada)] [Institut de Recherche d`Hydro-Quebec (IREQ), Varennes, Quebec (Canada); Dutil, A. [Hydro-Quebec, Montreal, Quebec (Canada). System Planning Dept.] [Hydro-Quebec, Montreal, Quebec (Canada). System Planning Dept.; Pham, V.Q. [ABB Canada, Varennes, Quebec (Canada). Power Transformer Div.] [ABB Canada, Varennes, Quebec (Canada). Power Transformer Div.

1997-01-01

252

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

NASA Astrophysics Data System (ADS)

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.

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

2014-02-01

253

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

NASA Technical Reports Server (NTRS)

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.

Rastogi, P. K.

1983-01-01

254

Electrophysiological Studies of Face Perception in Humans  

Microsoft Academic Search

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

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

1996-01-01

255

Human Services Study. Report on Counseling.  

National Technical Information Service (NTIS)

Counseling is discussed as one aspect of the countywide human service planning program of the Johnson County Regional Planning Commission in Iowa. The report on counseling is one in a series of eight reports describing the program. The overall goal of the...

1977-01-01

256

Human Services Study. Report on Adult Corrections.  

National Technical Information Service (NTIS)

Adult corrections is discussed as one component of the countywide human services planning program of the Johnson County Regional Planning Commission in Iowa. The report on adult corrections is one in a series of eight reports describing the program. The o...

1977-01-01

257

Human Services Study. Report on Juvenile Justice.  

National Technical Information Service (NTIS)

Juvenile justice is considered as one component of the countywide human services planning program of the Johnson County Regional Planning Commission in Iowa. The report on juvenile justice is one in a series of eight reports describing the program. The ov...

1977-01-01

258

Human Reliability Analysis: A Case Study.  

National Technical Information Service (NTIS)

This paper describes method using the Technique for Human Error Rate Prediction (THERP) as presented in NUREG/CR-2254. The entire analysis is documented, including the assumptions made based on a task analysis of the plant and of the accident being evalua...

B. J. Bell

1982-01-01

259

Human Services Study. Report on Mental Health.  

National Technical Information Service (NTIS)

The mental health component of the countywide human services planning program of the Johnson County Regional Planning Commission in Iowa is described. The report on mental health is one in a series of eight reports outlining the program. The overall goal ...

1977-01-01

260

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

PubMed Central

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.

2011-01-01

261

Radiocarbon blank correction: Methodologies and limitations in a major urban study of carbonaceous aerosols  

NASA Astrophysics Data System (ADS)

The Northern Front Range Air Quality Study (NFRAQS) was the latest and most ambitious of a series of efforts to apportion sources of carbonaceous aerosol "soot" in the Denver, Colorado metropolitan area. The study was mandated by the Colorado State Legislature as a result of the continuing impact of aerosol carbon on visibility in the region. Apportionment of fossil and biomass carbon was based on blank-corrected values of carbon mass concentrations (?g/m 3) and 14C data ( fM, fraction of modern carbon) of a selected subset of the samples collected in conjunction with this program. Over 100 14C measurements were made on size segregated (?2.5 ?m diameter) atmospheric aerosol samples collected during the summer of 1996 and the winter of 1996-1997. The reported fM values required correction for both the mass and fM of the overall carbon blank. Lack of direct fM data for the field blanks had a substantial effect on the estimated uncertainty of the final results, and in a few of the most extreme cases blank-corrected fM data had to be designated as "indeterminate". Blank correction procedures and limitations will be illustrated with quantitative data from the NFRAQS study.

Klinedinst, Donna B.; Currie, Lloyd A.

2000-10-01

262

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

PubMed

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

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

2013-01-01

263

Antisense tools for functional studies of human Argonaute proteins  

PubMed Central

The Argonaute proteins play essential roles in development and cellular metabolism in many organisms, including plants, flies, worms, and mammals. Whereas in organisms such as Caenorhabditis elegans and Arabidopsis thaliana, creation of Argonaute mutant strains allowed the study of their biological functions, in mammals the application of this approach is limited by its difficulty and in the specific case of Ago2 gene, by the lethality of such mutation. Hence, in human cells, functional studies of Ago proteins relied on phenotypic suppression using small interfering RNA (siRNA) which involves Ago proteins and the RNA interference mechanism. This bears the danger of undesired or unknown interference effects which may lead to misleading results. Thus, alternative methods acting by different regulatory mechanisms would be advantageous in order to exclude unspecific effects. The knockdown may be achieved by using specific antisense oligonucleotides (asONs) which act via an RNase H-dependent mechanism, not thought to interfere with processes in which Agos are involved. Different functional observations in the use of siRNA versus asONs indicate the relevance of this assumption. We developed asONs specific for the four human Agos (hAgos) and compared their activities with those obtained by siRNA. We confirm that hAgo2 is involved in microRNA (miRNA)- and in siRNA-mediated silencing pathways, while the other hAgos play a role only in miRNA-based gene regulation. Using combinations of asONs we found that the simultaneous down-regulation of hAgo1, hAgo2, and hAgo4 led to the strongest decrease in miRNA activity, indicating a main role of these proteins.

Mescalchin, Alessandra; Detzer, Anke; Weirauch, Ulrike; Hahnel, Maximilian J.; Engel, Christina; Sczakiel, Georg

2010-01-01

264

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

PubMed

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. PMID:23404214

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

2013-07-01

265

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

SciTech Connect

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.

Monteiro-Riviere, N.A. [Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606 (United States); Inman, A.O.; Zhang, L.W. [Center for Chemical Toxicology Research and Pharmacokinetics, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606 (United States)

2009-01-15

266

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

PubMed Central

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 estimate. For the estimate of association, all methods produced similar estimates to the complete data. Conclusions For data with a limited range, multiple imputation using techniques that restrict the range of imputed values can result in biased estimates for the marginal mean when data are highly skewed.

2014-01-01

267

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

PubMed

Human-specific or disproportionately abundant human metabolites of drug candidates that are not adequately formed and qualified in preclinical safety assessment species pose an important drug development challenge. Furthermore, the overall metabolic profile of drug candidates in humans is an important determinant of their drug-drug interaction susceptibility. These risks can be effectively assessed and/or mitigated if human metabolic profile of the drug candidate could reliably be determined in early development. However, currently available in vitro human models (e.g., liver microsomes, hepatocytes) are often inadequate in this regard. Furthermore, the conduct of definitive radiolabeled human ADME studies is an expensive and time-consuming endeavor that is more suited for later in development when the risk of failure has been reduced. We evaluated a recently developed chimeric mouse model with humanized liver on uPA/SCID background for its ability to predict human disposition of four model drugs (lamotrigine, diclofenac, MRK-A, and propafenone) that are known to exhibit human-specific metabolism. The results from these studies demonstrate that chimeric mice were able to reproduce the human-specific metabolite profile for lamotrigine, diclofenac, and MRK-A. In the case of propafenone, however, the human-specific metabolism was not detected as a predominant pathway, and the metabolite profiles in native and humanized mice were similar; this was attributed to the presence of residual highly active propafenone-metabolizing mouse enzymes in chimeric mice. Overall, the data indicate that the chimeric mice with humanized liver have the potential to be a useful tool for the prediction of human-specific metabolism of xenobiotics and warrant further investigation. PMID:24700822

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

2014-06-01

268

MEG studies of human vision: Retinotopic organization of V1  

SciTech Connect

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.

Aine, C.; George, J.; Ranken, D.; Best, E.; Tiee, W.; Vigil, V.; Flynn, E.; Wood, C. [Los Alamos National Lab., NM (United States); Supek, S. [Zagreb Univ. (Croatia). Dept. of Physics

1993-12-31

269

Designing studies of drug conditioning in humans  

Microsoft Academic Search

There has been much recent interest in the possibility that signals for drug use in humans acquire the ability to evoke classically\\u000a conditioned (learned) states which motivate drug taking. Much data now suggest that cues paired with drug use come to elicit\\u000a physiological responses and subjective reports of drug-related feelings like craving and withdrawal. However, the designs\\u000a employed do not

Steven J. Robbins; Ronald N. Ehrman

1992-01-01

270

Forming limit studies on different thickness aluminium 6xxx series alloys used in automotive applications  

Microsoft Academic Search

During sheet metal forming, one of the major measures of success for the material is to show forming strains below the safe\\u000a limit of a forming limit curve (FLC) and to show minimum thinning in critical areas in the forming die. To understand this\\u000a behaviour, tensile tests and 7 point FLC tests were conducted to evaluate the forming limit of

R. Bhattacharya; M. Stanton; I. Dargue; G. Williams; R. Aylmore

2010-01-01

271

Cumulative impact mapping: Advances, relevance and limitations to marine management and conservation, using Canada's Pacific waters as a case study  

Microsoft Academic Search

Analysis of cumulative human impacts in the marine environment is still in its infancy but developing rapidly. In this study, existing approaches were expanded upon, aiming for a realistic consideration of cumulative impacts at a regional scale. Thirty-eight human activities were considered, with each broken down according to stressor types and a range of spatial influences. To add to the

Natalie C. Ban; Hussein M. Alidina; Jeff A. Ardron

2010-01-01

272

Controls on Hyporheic Nitrate Removal: Assessing Transport and Substrate Limitations with 15N Tracer Studies (Invited)  

NASA Astrophysics Data System (ADS)

We examined transport time and substrate controls on hyporheic (HZ) nitrification and denitrification in an upland agricultural stream with a series of 15N tracer studies - whole-stream and in situ well-to-well steady-state 15NO3- and conservative tracer (Cl-) addition experiments. For the whole-stream experiment, we measured relevant solute, 15N isotope, and hydraulic transport conditions of the reach and along HZ flowpaths of an instrumented gravel bar. HZ exchange was observed across the entire gravel bar with flowpath lengths up to 4.2m and corresponding median residence times greater than 28.5h. The HZ transitioned from a net nitrification environment at its head (small residence times, <6.9h) to a net denitrification environment at its tail (large residence times, 6.9-28.5h). HZ denitrification was confirmed as 15N2 was produced across the entire gravel bar. Production of 15N2 across all observed flowpaths and residence times indicated that denitrification microsites are present even where net nitrification occurred. At large residence times, the rate of denitrification decreased despite persistent anoxic conditions, indicating substrate (NO3- and carbon) limitations. Consequently, we conducted in situ 15NO3-, conservative tracers (Cl- and Br), and acetate injection experiments to determine how the availability of labile dissolved organic carbon (DOC) as acetate influences microbial denitrification in the HZ, especially along anoxic flowpaths with large residence times. The acetate addition to the HZ stimulated significant increases in 15N2 production by factors of 2.7 to 26.1 in all receiving wells, and significant decreases of NO3- and DOC aromaticity in the wells most hydrologically connected to the injection. Further, 100% of acetate was retained in the HZ, a portion of which is due to biological consumption. These studies demonstrate that: 1. the HZ is an active nitrogen sink in this study system, 2. the distinction between net nitrification and denitrification in the HZ is a function of residence time and exhibits threshold behavior, and 3. microbial denitrification in anaerobic portions of the HZ can be limited by labile DOC supply.

Zarnetske, J. P.; Haggerty, R.; Wondzell, S. M.; Baker, M. A.

2010-12-01

273

Limited suppression of the interferon-beta production by hepatitis C virus serine protease in cultured human hepatocytes.  

PubMed

Toll-like receptors and RNA helicase family members [retinoic acid-inducible gene I (RIG-I) and melanoma differentiation associated gene-5 (MDA5)] play important roles in the induction of interferon-beta as a major event in innate immune responses after virus infection. TRIF (adaptor protein of Toll-like receptor 3)-mediated and Cardif (adaptor protein of RIG-I or MDA5)-mediated signaling pathways contribute rapid induction of interferon-beta through the activation of interferon regulatory factor-3 (IRF-3). Previously, it has been reported that the hepatitis C virus NS3-4A serine protease blocks virus-induced activation of IRF-3 in the human hepatoma cell line HuH-7, and that NS3-4A cleaves TRIF and Cardif molecules, resulting in the interruption of antiviral signaling pathways. On the other hand, it has recently been reported that non-neoplastic human hepatocyte PH5CH8 cells retain robust TRIF- and Cardif-mediated pathways, unlike HuH-7 cells, which lack a TRIF-mediated pathway. In the present study, we further investigated the effect of NS3-4A on antiviral signaling pathways. Although we confirmed that PH5CH8 cells were much more effective than HuH-7 cells for the induction of interferon-beta, we obtained the unexpected result that NS3-4A could not suppress the interferon-beta production induced by the TRIF-mediated pathway, although it suppressed the Cardif-mediated pathway by cleaving Cardif at the Cys508 residue. Using PH5CH8, HeLa, and HuH-7-derived cells, we further showed that NS3-4A could not cleave TRIF, in disagreement with a previous report describing the cleavage of TRIF by NS3-4A. Taken together, our findings suggest that the blocking of the interferon production by NS3-4A is not sufficient in HCV-infected hepatocyte cells. PMID:17651439

Dansako, Hiromichi; Ikeda, Masanori; Kato, Nobuyuki

2007-08-01

274

A comparative investigation of methods for longitudinal data with limits of detection through a case study.  

PubMed

The statistical analysis of continuous longitudinal data may be complicated since quantitative levels of bioassay cannot always be determined. Values beyond the limits of detection (LOD) in the assays may not be observed and thus censored, rendering complexity to the analysis of such data. This article examines how both left-censoring and right censoring of HIV-1 plasma RNA measurements, collected for the study on AIDS-related Non-Hodgkin's lymphoma (AR-NHL) in East Africa, affects the quantification of viral load and explores the natural history of viral load measurements over time in AR-NHL patients receiving anticancer chemotherapy. Data analyses using Monte Carlo EM algorithm (MCEM) are compared to analyses where the LOD or LOD/2 (left censoring) value is substituted for the censored observations, and also to other methods such as multiple imputation, and maximum likelihood estimation for censored data (generalized Tobit regression). Simulations are used to explore the sensitivity of the results to changes in the model parameters. In conclusion, the antiretroviral treatment was associated with a significant decrease in viral load after controlling the effects of other covariates. A simulation study with finite sample size shows MCEM is the least biased method and the estimates are least sensitive to the censoring mechanism. PMID:22504231

Fu, P; Hughes, J; Zeng, G; Hanook, S; Orem, J; Mwanda, O W; Remick, S C

2012-04-13

275

Experimental Evaluation of Accelerated T1rho Relaxation Quantification in Human Liver Using Limited Spin-Lock Times  

PubMed Central

Objective It was reported lately that to obtain consistent liver T1rho measurement, at 3T MRI using six spin-lock times (SLTs), is feasible. In this study, the feasibility of using three or two SLT points to measure liver T1rho relaxation time was explored. Materials and Methods Seventeen healthy volunteers underwent 36 examinations. Three representative axial slices were selected to cut through the upper, middle, and lower liver. A rotary echo spin-lock pulse was implemented in a 2D fast field echo sequence. Spin-lock frequency was 500 Hz and the spin-lock times of 1, 10, 20, 30, 40, and 50 milliseconds (ms) were used for T1rho mapping. T1rho maps were constructed by using all 6 SLT points, three SLT points of 1, 20, and 50 ms, or two SLTs of 1 and 50 ms, respectively. Intra-class correlation coefficient (ICC) and Bland and Altman plot were used to assess the measurement agreement. Results Two examinations were excluded, due to motion artifact at the SLT of 50 ms. With the remaining 34 examinations, the ICC for 6-SLT vs. 3-SLT T1rho measurements was 0.922, while the ICC for 6-SLT vs. 2-SLT T1rho measurement was 0.756. The Bland and Altman analysis showed a mean difference of 0.19 (95% limits of agreement: -1.34, 1.73) for 6-SLT vs. 3-SLT T1rho measurement, and the mean difference of 0.89 (95% limits of agreement: -1.67, 3.45) for 6-SLT vs. 2-SLT T1rho measurement. The scan re-scan reproducibility ICC (n = 11 subjects) was 0.755, 0.727, and 0.528 for 6-SLT measurement, 3-SLT measurement, and 2-SLT measurement, respectively. Conclusion Adopting 3 SLTs of 1, 20, and 50 ms can be an acceptable alternative for the liver T1rho measurement, while 2 SLTs of 1 and 50 ms do not provide reliable measurement.

Zhao, Feng; Deng, Min; Yuan, Jing; Teng, Gao-Jun; Ahuja, Anil T

2012-01-01

276

Estimation of the Upper Limit of Human Butyrylcholinesterase Dose Required for Protection against Organophosphates Toxicity: a Mathematically Based Toxicokinetic Model  

Microsoft Academic Search

Human butyrylcholinesterase (HuBChE) is a drug candidate for protection against organophosphates (OP) intoxication. A mathe- matically based model was validated and employed to better understand the role of the endogenous HuBChE in detoxification of OPs and to estimate the dose of exogenous HuBChE required for enhancing protection of humans from lethal exposure to OPs. The model addresses the relationship between

Yacov Ashani; Shlomi Pistinner

2004-01-01

277

Applicability limits of the stationary combustion model in the study of explosive initiation  

Microsoft Academic Search

Imperfections in the physical models of detonation ignition in heterogeneous systems has led to unsatisfactory analysis and use of the experimental data. A significant improvement in the models used may be obtained through the establishment of limits for the rate of change of pressure and temperature gradient at the hearth. The present paper proposes limiting values for the parameters of

S. G. Andreev; A. I. Chernov; A. N. Isaev; V. S. Solovev

1983-01-01

278

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

SciTech Connect

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.

Bodek, A.

1996-10-01

279

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

Microsoft Academic Search

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.

Arie Bodek

1996-01-01

280

Application studies of superconducting fault current limiters in electric power systems  

Microsoft Academic Search

In power systems, superconducting fault current limiters (SFCLs) can limit the prospective short-circuit currents to lower levels, so that the underrated switchgear can be operated safely. This paper presents a detailed theoretical analysis of improving power system stability by using SFCLs. Electromagnetic Transient Program (EMTP) simulation results based on a model system also show that SFCLs are effective for enhancing

Lin Ye; LiangZhen Lin; Klaus-Peter Juengst

2002-01-01

281

An experimental study of droplet ignition characteristics near the ignitable limit  

Microsoft Academic Search

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

T. Saitoh; S. Ishiguro; T. Niioka

1982-01-01

282

Study of Anticipated Impact on DOE Programs from Proposed Reductions to the External Occupational Radiation Exposure Limit.  

National Technical Information Service (NTIS)

A study of the impact of reducing the occupational radiation exposure limit from 5 rem/yr to 2.5, 1.0 and 0.5 rem/yr, respectively produced the following conclusions: reduction of the occupational exposure limit would result in significant increase in tot...

1981-01-01

283

Musculoskeletal comorbidities in cardiovascular disease, diabetes and respiratory disease: the impact on activity limitations; a representative population-based study  

Microsoft Academic Search

BACKGROUND: The purpose of this study was to quantify the contribution of comorbidity to activity limitations in populations with chronic cardiovascular disease, diabetes or respiratory disease (index conditions), with emphasis on musculoskeletal comorbidity (arthritis or back problems). METHODS: Analysis of the 2005 Canadian Community Health Survey 3.1 (age 20+ years, n = 115,915). Prevalence ratios for activity limitations in people

Morgan Slater; Anthony V Perruccio; Elizabeth M Badley

2011-01-01

284

A study on DC hybrid three-phase fault current limiting interrupter for a power distribution system  

NASA Astrophysics Data System (ADS)

For the purpose of protecting electric power system, many researches and developments of fault current limiters are being performed. The authors studied a dc hybrid three-phase fault current limiting interrupter (FCLI) composed of a superconducting reactor and an S/N transition element, connected in series each other. The dc hybrid type fault current limiting interrupter can limit a fault current by means of the inductance of high temperature superconducting (HTS) coil together with the normal transition of HTS bulk material (HTSB). In the case of an accident, the normal transition of the bulk material can be accelerated by the magnetic field of the HTS coil. In this paper, the dc hybrid type fault current limiting interrupter for 5.5 km long 6.6 kV-600 A power distribution system is analyzed, and performances of fault current limitation and interruption are confirmed. Moreover, a reclosing operation is discussed for this power distribution system.

Shao, Hongtian; Satoh, Tomoyuki; Yamaguchi, Mitsugi; Fukui, Satoshi; Ogawa, Jun; Satoh, Takao; Ishikawa, Hiroyuki

2005-10-01

285

Polarization and charge limit studies of strained GaAs photocathodes  

SciTech Connect

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.

Saez, P.J.

1997-03-01

286

An Interdisciplinary Deer and Human Population Study  

NSDL National Science Digital Library

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

Webb, William J.

2009-01-01

287

STUDIES IN HUMAN IMMUNIZATION AGAINST INFLUENZA  

PubMed Central

The administration to human beings of formalin-killed influenza virus, concentrated from allantoic fluid, resulted in a high order of antibody response within 2 weeks after injection. Even after 1 year the great majority of individuals vaccinated had antibody levels considerably above their prevaccination titer for the PR8, Lee, and a current 1943 strain. An investigation of the occurrence of epidemic influenza A in seven widely separated populations, 1 year after vaccination of part of these groups, showed that the attack rate among vaccinated persons was consistently lower than that of control individuals. The average reduction in attack rate was of the order of 35 per cent.

Hirst, G. K.; Rickard, E. R.; Friedewald, W. F.

1944-01-01

288

Trait Mindfulness as a Limiting Factor for Residual Depressive Symptoms: An Explorative Study Using Quantile Regression  

PubMed Central

Mindfulness has been suggested to be an important protective factor for emotional health. However, this effect might vary with regard to context. This study applied a novel statistical approach, quantile regression, in order to investigate the relation between trait mindfulness and residual depressive symptoms in individuals with a history of recurrent depression, while taking into account symptom severity and number of episodes as contextual factors. Rather than fitting to a single indicator of central tendency, quantile regression allows exploration of relations across the entire range of the response variable. Analysis of self-report data from 274 participants with a history of three or more previous episodes of depression showed that relatively higher levels of mindfulness were associated with relatively lower levels of residual depressive symptoms. This relationship was most pronounced near the upper end of the response distribution and moderated by the number of previous episodes of depression at the higher quantiles. The findings suggest that with lower levels of mindfulness, residual symptoms are less constrained and more likely to be influenced by other factors. Further, the limiting effect of mindfulness on residual symptoms is most salient in those with higher numbers of episodes.

Radford, Sholto; Eames, Catrin; Brennan, Kate; Lambert, Gwladys; Crane, Catherine; Williams, J. Mark G.; Duggan, Danielle S.; Barnhofer, Thorsten

2014-01-01

289

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

NASA Astrophysics Data System (ADS)

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.

Bender, Peter L.

2012-03-01

290

Trait mindfulness as a limiting factor for residual depressive symptoms: an explorative study using quantile regression.  

PubMed

Mindfulness has been suggested to be an important protective factor for emotional health. However, this effect might vary with regard to context. This study applied a novel statistical approach, quantile regression, in order to investigate the relation between trait mindfulness and residual depressive symptoms in individuals with a history of recurrent depression, while taking into account symptom severity and number of episodes as contextual factors. Rather than fitting to a single indicator of central tendency, quantile regression allows exploration of relations across the entire range of the response variable. Analysis of self-report data from 274 participants with a history of three or more previous episodes of depression showed that relatively higher levels of mindfulness were associated with relatively lower levels of residual depressive symptoms. This relationship was most pronounced near the upper end of the response distribution and moderated by the number of previous episodes of depression at the higher quantiles. The findings suggest that with lower levels of mindfulness, residual symptoms are less constrained and more likely to be influenced by other factors. Further, the limiting effect of mindfulness on residual symptoms is most salient in those with higher numbers of episodes. PMID:24988072

Radford, Sholto; Eames, Catrin; Brennan, Kate; Lambert, Gwladys; Crane, Catherine; Williams, J Mark G; Duggan, Danielle S; Barnhofer, Thorsten

2014-01-01

291

Studying the inspection limits in detecting buried objects by using infrared thermography  

NASA Astrophysics Data System (ADS)

In Japan it happens that building parts made of concrete suddenly collapse to create obstacles to the traffic in tunnels, on highways and bridges. Thus, the safety issue has become a serious social problem. Therefore, the detection of hidden defects in concrete building constructions in order to prevent an accidental damage is the important application area for nondestructive testing (NDT) techniques. Until now, the inspection is typically performed by using a hammer that is subjective and takes too much time. Infrared thermography is a promising NDT technique that might help in the fast detection of invisible (hidden) defects. Transient, or active, thermal NDT requires external thermal stimulation of the defects under test by warming up or cooling down the defect surface. However, low-power and long heating is significantly affected by environmental conditions. Recent Japanese research in this area has been rather qualitative, i.e. without putting the accent on evaluating parameters of hidden defects. In this study, the experimental results are modeled and processed by using the thermal NDT package developed at the Tomsk Institute of Introscopy. This has allowed not only optimizing test parameters but also obtaining reasonable estimates of defect parameters for air-filled voids and inclusions in concrete. It is shown that MRTD values experimented by us are of a little help while evaluating detection limits.

Kamoi, Arao; Okamoto, Yoshizo; Vavilov, Vladimir P.

2003-04-01

292

Limits of movement in the human knee. Effect of sectioning the posterior cruciate ligament and posterolateral structures.  

PubMed

We applied specific forces and moments to the knees of fifteen whole lower limbs of cadavera and measured, with a six degrees-of-freedom electrogoniometer, the position of the tibia at which the ligaments and the geometry of the joint limited motion. The limits were determined for anterior and posterior tibial translation, internal and external rotation, and varus and valgus angulation from zero to 90 degrees of flexion. The limits were measured in the intact knee and then the changes that occurred with removal of the posterior cruciate ligament, the lateral collateral ligament, the popliteus tendon at its femoral attachment, and the arcuate complex were measured. The cutting order was varied, allowing us to determine the changes in the limits that occurred when each structure was cut alone and the amount of motion of the joint that was required for each structure to become taut and to limit additional motion when the other supporting structures had been removed. Removal of only the posterior cruciate ligament increased the limit for posterior tibial translation, with no change in the limits for tibial rotation or varus and valgus angulation. The additional posterior translation was least at full extension and increased progressively, reaching 11.4 millimeters at 90 degrees of flexion. The progressive increase in posterior translation with flexion was apparently due to slackening of the posterior portion of the capsule, as the translation nearly doubled when the posterolateral structures subsequently were removed. Removal of only the posterolateral extra-articular restraints increased the amount of external rotation and varus angulation. The average increase in external rotation depended on the angle of flexion; it was greatest at 30 degrees of flexion and decreased with additional flexion. At 90 degrees of flexion, the intact posterior cruciate ligament limited the increase in external rotation to only 5.3 degrees, less than one-half of the 13.0-degree increase that occurred at 30 degrees of flexion. Subsequent removal of the posterior cruciate ligament markedly increased external rotation at 90 degrees of flexion, resulting in a total increase of 20.9 degrees. The limit for varus angulation was normal as long as the lateral collateral ligament was intact. When the lateral collateral ligament was cut, the limit increased 4.5 degrees (approximately 4.5 millimeters of additional joint opening) when the knee was partially flexed (to 15 degrees).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3335577

Grood, E S; Stowers, S F; Noyes, F R

1988-01-01

293

Hypoxia limits differentiation and up-regulates expression and activity of prostaglandin H synthase 2 in cultured trophoblast from term human placenta  

Microsoft Academic Search

Objective: We determined the effect of hypoxic conditions on cellular differentiation and prostaglandin H synthase expression in cultured human term trophoblast. Study Design: Cytotrophoblasts isolated from term placentas were cultured for 24-72 hours in a standard (20% oxygen) or hypoxic (1% to 2% oxygen) atmosphere. Trophoblast biochemical differentiation was determined by release of human chorionic gonadotropin. Morphologic differentiation was evaluated

D. Michael Nelson; Roger D. Johnson; Steven D. Smith; Eyal Y. Anteby; Yoel Sadovsky

1999-01-01

294

Identifying the genomic determinants of aging and longevity in human population studies: progress and challenges.  

PubMed

Human lifespan variation is mainly determined by environmental factors, whereas the genetic contribution is 25-30% and expected to be polygenic. Two complementary fields go hand in hand in order to unravel the mechanisms of biological aging: genomic and biomarker research. Explorative and candidate gene studies of the human genome by genetic, transcriptomic, and epigenomic approaches have resulted in the identification of a limited number of interesting positive linkage regions, genes, and pathways that contribute to lifespan variation. The possibilities to further exploit these findings are rapidly increasing through the use of novel technologies, such as next-generation sequencing. Genomic research is progressively being integrated with biomarker studies on aging, including the application of (noninvasive) deep phenotyping and omics data - generated using novel technologies - in a wealth of studies in human populations. Hence, these studies may assist in obtaining a more holistic perspective on the role of the genome in aging and lifespan regulation. PMID:23423909

Deelen, Joris; Beekman, Marian; Capri, Miriam; Franceschi, Claudio; Slagboom, P Eline

2013-04-01

295

42 CFR 93.105 - Time limitations.  

Code of Federal Regulations, 2013 CFR

...Time limitations. 93.105 Section 93.105 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES HEALTH ASSESSMENTS AND HEALTH EFFECTS STUDIES OF HAZARDOUS SUBSTANCES RELEASES AND FACILITIES PUBLIC...

2013-10-01

296

Comparative Analysis, Global Policy Studies and the Human Condition.  

ERIC Educational Resources Information Center

This paper examines the role that comparative analysis and global policy studies can play in explaining the human condition in the contemporary world. It investigates economic well-being, one dimension of the human condition, and examines some of the attributes that represent it and some of the forces that affect it in villages, social groupings,…

Bertsch, Gary K.

297

EVALUATING ``HUMAN + ADVISORY COMPUTER'' SYSTEMS: A CASE STUDY  

Microsoft Academic Search

We studied the impact of a Computer Aided Detection (CAD) tool on human's decisions in mammography. We used data from an independent clinical trial, which compared the average performance of breast screening professionals with and without CAD. Standard analyses of these data showed no statistically significant effect of CAD's output on humans' cancer detection rate. We conducted statistical modelling and

Andrey A. Povyakalo; Eugenio Alberdi; Peter Ayton; Lorenzo Strigini

2004-01-01

298

Study of Human Factors in Public Transportation Safety.  

National Technical Information Service (NTIS)

The study examined the human factors in transit safety, namely the safety problems of fixed-route bus operations. Human factors related to bus driver and passenger safety were examined, and special emphasis was given to problems encountered by the elderly...

K. Hunter R. Layton R. Safford

1989-01-01

299

Improved Neuropsychological and Neurological Functioning Across Three Antiretroviral Regimens in Diverse Resource-Limited Settings: AIDS Clinical Trials Group Study A5199, the International Neurological Study  

PubMed Central

Background.?AIDS Clinical Trials Group (ACTG) A5199 compared the neurological and neuropsychological (NP) effects of 3 antiretroviral regimens in participants infected with human immunodeficiency virus type 1 (HIV-1) in resource-limited settings. Methods.?Participants from Brazil, India, Malawi, Peru, South Africa, Thailand, and Zimbabwe were randomized to 3 antiretroviral treatment arms: A (lamivudine-zidovudine plus efavirenz, n = 289), B (atazanavir, emtricitabine, and didanosine-EC, n = 293), and C (emtricitabine-tenofovir-disoproxil fumarate plus efavirenz, n = 278) as part of the ACTG PEARLS study (A5175). Standardized neurological and neuropsychological (NP) screening examinations (grooved pegboard, timed gait, semantic verbal fluency, and finger tapping) were administered every 24 weeks from February 2006 to May 2010. Associations with neurological and neuropsychological function were estimated from linear and logistic regression models using generalized estimating equations. Results.?The median weeks on study was 168 (Q1 = 96, Q3 = 192) for the 860 participants. NP test scores improved (P < .05) with the exception of semantic verbal fluency. No differences in neurological and neuropsychological functioning between treatment regimens were detected (P > .10). Significant country effects were noted on all NP tests and neurological outcomes (P < .01). Conclusions.?The study detected no significant differences in neuropsychological and neurological outcomes between randomized ART regimens. Significant improvement occurred in neurocognitive and neurological functioning over time after initiation of ARTs. The etiology of these improvements is likely multifactorial, reflecting reduced central nervous system HIV infection, better general health, and practice effects. This study suggests that treatment with either of the World Health Organization –recommended first-line antiretroviral regimens in resource-limited settings will improve neuropsychological functioning and reduce neurological dysfunction. Clinical trials registration. ?NCT00096824.

Robertson, K.; Jiang, H.; Kumwenda, J.; Supparatpinyo, K.; Evans, S.; Campbell, T. B.; Price, R.; Tripathy, S.; Kumarasamy, N.; La Rosa, A.; Santos, B.; Silva, M. T.; Montano, S.; Kanyama, C.; Faesen, S.; Murphy, R.; Hall, C.; Marra, C. M.; Marcus, C.; Berzins, B.; Allen, R.; Housseinipour, M.; Amod, F.; Sanne, I.; Hakim, J.; Walawander, A.; Nair, A.

2012-01-01

300

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

...Adjustments to Limitations on Designated School Official Assignment and Study by F-2...students. The proposed rule would grant school officials more flexibility in determining the number of designated school officials to nominate for the...

2013-11-21

301

Validated assay for studying activity profiles of human liver UGTs after drug exposure: inhibition and induction studies  

Microsoft Academic Search

UDP-glucuronsyltransferases (UGTs) are a family of conjugating enzymes that participate in the metabolism of many drugs. The\\u000a study of potential drug–drug interactions involving UGTs has been largely hindered by the limited availability of selective\\u000a functional assays for individual UGT enzymes. We propose a sensitive and reproducible procedure for the activity measurements\\u000a of four major human hepatic UGT forms. The assays

M. Teresa Donato; Sandra Montero; José V. Castell; M. José Gómez-Lechón; Agustín Lahoz

2010-01-01

302

Development of humanized mouse models to study human malaria parasite infection  

PubMed Central

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.

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

2013-01-01

303

Comparative study of rabbit pyrogen test and human whole blood assay on human serum albumin.  

PubMed

A comparative study of rabbit pyrogen test and human whole blood assay was performed on released preparations of human serum albumin. In addition, the samples were spiked with 5 IU/ml (in whole blood 0.5 IU/ml too) and 10 IU endotoxin/ml. The unspiked samples were negative in both assays. The human whole blood test resulted in the same level of security for the products as the rabbit pyrogen test did. Both, the borderline 5 IU/kg and the 10 IU/kg-Spike partially lead to results of the rabbit test which would cause further testing with additional animals. In contrast, the human whole blood assay resulted in a 100% detection for the 5 IU/ml and 10 IU/ml-Spike. We designed a study protocol for a minimised number of test animals and were able to show the general usefulness of the human whole blood assay. PMID:12096333

Spreitzer, Ingo; Fischer, Matthias; Hartzsch, Katja; Lüderitz-Püchel, Ursel; Montag, Thomas

2002-01-01

304

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

PubMed

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

McFarland, Sam; Webb, Matthew; Brown, Derek

2012-11-01

305

A review on thiazolidinediones and bladder cancer in human studies.  

PubMed

There is a concern of an increased risk of bladder cancer associated with the use of thiazolidinediones, a class of oral glucose-lowering drugs commonly used in patients with type 2 diabetes with a mechanism of improving insulin resistance. Human studies on related issues are reviewed, followed by a discussion on potential concerns on the causal inference in current studies. Pioglitazone and rosiglitazone are discussed separately, and findings from different geographical regions are presented. Randomized controlled trials designed for primarily answering such a cancer link are lacking, and evidence from clinical trials with available data for evaluating the association may not be informative. Observational studies have been reported with the use of population-based administrative databases, single-hospital records, drug adverse event reporting system, and case series collection. Meta-analysis has also been performed by six different groups of investigators. These studies showed a signal of higher risk of bladder cancer associated with pioglitazone, especially at a higher cumulative dose or after prolonged exposure; however, a weaker signal or null association is observed with rosiglitazone. In addition, there are some concerns on the causal inference, which may be related to the use of secondary databases, biases in sampling, differential detection, and confounding by indications. Lack of full control of smoking and potential biases related to study designs and statistical approaches such as prevalent user bias and immortal time bias may be major limitations in some studies. Overlapping populations and opposing conclusions in studies using the same databases may be of concern and weaken the reported conclusions of the studies. Because randomized controlled trials are expensive and unethical in providing an answer to this cancer issue, observational studies are expected to be the main source in providing an answer in the future. Furthermore, international comparison studies using well-designed and uniform methodology to clarify the risk in specific sexes, ethnicities, and other subgroups and to evaluate the interaction with other environmental risk factors or medications will be helpful to identify patients at risk. PMID:24598039

Tseng, Chin-Hsiao

2014-01-01

306

Role of the medial structures in the intact and anterior cruciate ligament-deficient knee. Limits of motion in the human knee.  

PubMed

We measured motion limits in human cadaveric knees before and after sectioning the anterior cruciate ligament and the medial structures. Sectioning the medial collateral ligament in an anterior cruciate ligament-deficient knee increased the anterior translation limit at 90 degrees of flexion but not at 30 degrees of flexion. The tibia displaced straight anteriorly without exhibiting the coupled internal rotation that occurred in intact and anterior cruciate ligament-deficient knees. A lateral 15 N-m abduction moment produced a coupled external rotation in the medial collateral ligament-deficient knee. This was in marked contrast to intact, anterior cruciate ligament-deficient, or combined medial collateral ligament and anterior cruciate ligament-deficient knees, in which an abduction moment produced a coupled internal rotation. Sectioning only the medial collateral ligament caused a small but significant increase in the abduction rotation limit, whereas larger increases in the abduction rotation limit occurred when the posterior oblique ligament and posterior medial capsule were cut in addition to the medial collateral ligament. Cutting the medial collateral ligament increased the external rotation limit. The increase was independent of whether the anterior cruciate ligament was intact or sectioned. Subsequent cutting of the posterior oblique ligament and posterior medial capsule further increased the external rotation limit. PMID:8037282

Haimes, J L; Wroble, R R; Grood, E S; Noyes, F R

1994-01-01

307

Foot pain and functional limitation in healthy adults with hallux valgus: a cross-sectional study  

PubMed Central

Background Hallux valgus (HV) is a very common deformity of the first metatarsophalangeal joint that often requires surgical correction. However, the association between structural HV deformity and related foot pain and disability is unclear. Furthermore, no previous studies have investigated concerns about appearance and difficulty with footwear in a population with HV not seeking surgical correction. The aim of this cross-sectional study was to investigate foot pain, functional limitation, concern about appearance and difficulty with footwear in otherwise healthy adults with HV compared to controls. Methods Thirty volunteers with HV (radiographic HV angle >15 degrees) and 30 matched controls were recruited for this study (50 women, 10 men; mean age 44.4 years, range 20 to 76 years). Differences between groups were examined for self-reported foot pain and disability, satisfaction with appearance, footwear difficulty, and pressure-pain threshold at the first metatarsophalangeal joint. Functional measures included balance tests, walking performance, and hallux muscle strength (abduction and plantarflexion). Mean differences (MD) and 95% confidence intervals (CI) were calculated. Results All self-report measures showed that HV was associated with higher levels of foot pain and disability and significant concerns about appearance and footwear (p < 0.001). Lower pressure-pain threshold was measured at the medial first metatarsophalangeal joint in participants with HV (MD = ?133.3 kPa, CI: -251.5 to ?15.1). Participants with HV also showed reduced hallux plantarflexion strength (MD = ?37.1 N, CI: -55.4 to ?18.8) and abduction strength (MD = ?9.8 N, CI: -15.6 to ?4.0), and increased mediolateral sway when standing with both feet with eyes closed (MD = 0.34 cm, CI: 0.04 to 0.63). Conclusions These findings show that HV negatively impacts on self-reported foot pain and function, and concerns about foot appearance and footwear in otherwise healthy adults. There was also evidence of impaired hallux muscle strength and increased postural sway in HV subjects compared to controls, although general physical functioning and participation in physical activity were not adversely affected.

2012-01-01

308

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

Microsoft Academic Search

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

Luis Garicano

2007-01-01

309

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

PubMed Central

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

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

2013-01-01

310

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...

311

Human tracking studies involving an actively powered, augmented exoskeleton  

Microsoft Academic Search

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

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

1996-01-01

312

Experimental Spinal Trauma Studies in the Human and Monkey Cadaver.  

National Technical Information Service (NTIS)

Compression studies were conducted on the ligamentous thoracolumbar spines of fresh human male cadavers. For comparison, forces were applied to the posterior upper thoracic region of intact seated cadavers. Since this type of injury routinely involves lig...

A. Sances D. Maiman F. Pintar J. Myklebust M. Chilbert

1982-01-01

313

Coordination Mechanisms in Fast Human Movement. Experimental and Modelling Studies.  

National Technical Information Service (NTIS)

Result summaries are provided for the modeling and experimental studies of coordination mechanisms in fast human movement. Both isotonic and isometric exercise regimens were used to produce two different levels of fatigue in the agonist or antagonist musc...

W. P. Kroll W. L. Kilmer

1984-01-01

314

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...

315

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

NASA Astrophysics Data System (ADS)

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.

Harris, Robert A.

2003-11-01

316

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

NASA Astrophysics Data System (ADS)

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.

Tsui, Lap-Chee

2003-04-01

317

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

SciTech Connect

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.

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

1995-06-01

318

Tea and Cancer Prevention: Studies in Animals and Humans  

Microsoft Academic Search

ABSTRACT 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

Fung-lung Chung; Joel Schwartz; Christopher R. Herzog; Yang-ming Yang

319

Emotion and Cognition: Insights from Studies of the Human Amygdala  

Microsoft Academic Search

? Abstract Traditional approaches,to the study of cognition emphasize,an inform- ation-processing view that has generally excluded emotion. In contrast, the recent emergence,of cognitive neuroscience,as an inspiration for understanding,human,cog- nition has highlighted its interaction with emotion. This review explores insights into the relations between,emotion,and cognition that have resulted from,studies of the human amygdala. Five topics are explored: emotional learning, emotion and

Elizabeth A. Phelps

2006-01-01

320

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

PubMed

The aim of this study was to generate a local confidence limit (CL) for intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) techniques used at Waikato Regional Cancer Centre. This work was carried out based on the American Association of Physicists in Medicine (AAPM) Task Group (TG) 119 report. The AAPM TG 119 report recommends CLs as a bench mark for IMRT commissioning and delivery based on its multiple institutions planning and dosimetry comparisons. In this study the locally obtained CLs were compared to TG119 benchmarks. Furthermore, the same bench mark was used to test the capabilities and quality of the VMAT technique in our clinic. The TG 119 test suite consists of two primary and four clinical tests for evaluating the accuracy of IMRT planning and dose delivery systems. Pre defined structure sets contoured on computed tomography images were downloaded from AAPM website and were transferred to a locally designed phantom. For each test case two plans were generated using IMRT and VMAT optimisation. Dose prescriptions and planning objectives recommended by TG119 report were followed to generate the test plans in Eclipse Treatment Planning System. For each plan the point dose measurements were done using an ion chamber at high dose and low dose regions. The planar dose distribution was analysed for percentage of points passing the gamma criteria of 3%/3 mm, for both the composite plan and individual fields of each plan. The CLs were generated based on the results from the gamma analysis and point dose measurements. For IMRT plans, the CLs obtained were (1) from point dose measurements: 2.49% at high dose region and 2.95% for the low dose region (2) from gamma analysis: 2.12% for individual fields and 5.9% for the composite plan. For VMAT plans, the CLs obtained were (1) from point dose measurements: 2.56% at high dose region and 2.6% for the low dose region (2) from gamma analysis: 1.46% for individual fields and 0.8% for the composite plan. All these CLs were well within the TG119 recommended bench marks. Based on these analysis which were performed in line with the TG119 recommendations, it is evident that the local clinic has commissioned IMRT and VMAT techniques with adequate accuracy. These results compliment our clinical confidence of using IMRT and VMAT routinely and expanding to different clinical sites. PMID:24414337

Thomas, M; Chandroth, M

2014-03-01

321

Study on Required Performance of Fault Current Limiter for Dispersed Generator  

NASA Astrophysics Data System (ADS)

It is expected that a number of dispersed generators interconnecting with power distribution systems will be increased with progress of deregulation in electric power industry. In order to allow large capacity of the interconnection, a certain current limitation measure is required in present distribution systems because of allowable short circuit capacity as a restriction. One of effective measures is fault current limiter (FCL) which suppress short circuit current within a time of half cycle. However, a required performance of FCL applied to dispersed generators is not made clear. The authors look for necessary conditions on the FCL performance for above-mentioned purpose using EMTP simulation. This paper presents necessary performance of FCL, which includes a commutation type FCL with resistance and reactance as a limitation element.

Genji, Takamu; Miyazato, Kenji; Tsutsushio, Hidefumi; Nishiwaki, Tadao

322

Study and Analysis of Heat Transfer Limitation of Separated Heat Pipe  

NASA Astrophysics Data System (ADS)

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

Mou, Qizheng; Mou, Kai

2002-01-01

323

In-vitro model systems for the study of human embryo-endometrium interactions.  

PubMed

Implantation requires highly orchestrated interactions between the developing embryo and maternal endometrium. The association between abnormal implantation and reproductive failure is evident, both in normal pregnancy and in assisted reproduction patients. Failure of implantation is the pregnancy rate-limiting step in assisted reproduction, but, as yet, empirical interventions have largely failed to address this problem. Better understanding of the mechanisms underlying human embryo-endometrium signalling is a prerequisite for the further improvement of assisted reproduction outcomes and the development of effective interventions to prevent early pregnancy loss. Studying human embryo implantation is challenging since in-vivo experiments are impractical and unethical, and studies in animal models do not always translate well to humans. However, in recent years in-vitro models have been shown to provide a promising way forward. This review discusses the principal models used to study early human embryo development and initial stages of implantation in vitro. While each model has limitations, exploiting these models will improve understanding of the molecular mechanisms and embryo-endometrium cross-talk at the early implantation site. They provide valuable tools to study early embryo development and pathophysiology of reproductive disorders and have revealed novel disease mechanisms such as the role of epigenetic modifications in recurrent miscarriage. PMID:24055530

Weimar, Charlotte H E; Post Uiterweer, Emiel D; Teklenburg, Gijs; Heijnen, Cobi J; Macklon, Nick S

2013-11-01

324

Reprint of: In-vitro model systems for the study of human embryo-endometrium interactions.  

PubMed

Implantation requires highly orchestrated interactions between the developing embryo and maternal endometrium. The association between abnormal implantation and reproductive failure is evident, both in normal pregnancy and in assisted reproduction patients. Failure of implantation is the pregnancy rate-limiting step in assisted reproduction, but, as yet, empirical interventions have largely failed to address this problem. Better understanding of the mechanisms underlying human embryo-endometrium signalling is a prerequisite for the further improvement of assisted reproduction outcomes and the development of effective interventions to prevent early pregnancy loss. Studying human embryo implantation is challenging since in-vivo experiments are impractical and unethical, and studies in animal models do not always translate well to humans. However, in recent years in-vitro models have been shown to provide a promising way forward. This review discusses the principal models used to study early human embryo development and initial stages of implantation in vitro. While each model has limitations, exploiting these models will improve understanding of the molecular mechanisms and embryo-endometrium cross-talk at the early implantation site. They provide valuable tools to study early embryo development and pathophysiology of reproductive disorders and have revealed novel disease mechanisms such as the role of epigenetic modifications in recurrent miscarriage. PMID:24161843

Weimar, Charlotte H E; Post Uiterweer, Emiel D; Teklenburg, Gijs; Heijnen, Cobi J; Macklon, Nick S

2013-12-01

325

Hairless Mouse Skin is Limited as a Model for Assessing the Effects of Penetration Enhancers in Human Skin  

Microsoft Academic Search

The permeability coefficient of 5-fluorouracil through human abdominal and hairless mouse skins was used as an indicator of the relative effects of 12-h pretreatment of the skins with either penetration-enhancer mixtures [including laurocapram (Azone), decylmethylsulfoxide, oleic acid, and propylene glycol] or saline (control). After treatment with saline, fluxes of 5-fluorouracil through the two skin types were similar, but the mouse

John Russell Bond; Brian William Barry

1988-01-01

326

BLT humanized mice as model to study HIV vaginal transmission.  

PubMed

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

Deruaz, Maud; Luster, Andrew D

2013-11-01

327

Improved detection limit in rapid detection of human enterovirus 71 and coxsackievirus A16 by a novel reverse transcription-isothermal multiple-self-matching-initiated amplification assay.  

PubMed

Rapid detection of human enterovirus 71 (EV71) and coxsackievirus A16 (CVA16) is important in the early phase of hand-foot-and-mouth disease (HFMD). In this study, we developed and evaluated a novel reverse transcription-isothermal multiple-self-matching-initiated amplification (RT-IMSA) assay for the rapid detection of EV71 and CVA16 by use of reverse transcriptase, together with a strand displacement DNA polymerase. Real-time RT-IMSA assays using a turbidimeter and visual RT-IMSA assays to detect EV71 and CVA16 were established and completed in 1 h, and the reported corresponding real-time reverse transcription-loop-mediated isothermal amplification (RT-LAMP) assays targeting the same regions of the VP1 gene were adopted as parallel tests. Through testing VP1 RNAs transcribed in vitro, the real-time RT-IMSA assays exhibited better linearity of quantification, with R(2) values of 0.952 (for EV71) and 0.967 (for CVA16), than the real-time RT-LAMP assays, which had R(2) values of 0.803 (for EV71) and 0.904 (for CVA16). Additionally, the detection limits of the real-time RT-IMSA assays (approximately 937 for EV71 and 67 for CVA16 copies/reaction) were higher than those of real-time RT-LAMP assays (approximately 3,266 for EV71 and 430 for CVA16 copies/reaction), and similar results were observed in the visual RT-IMSA assays. The new approaches also possess high specificities for the corresponding targets, with no cross-reactivity observed. In clinical assessment, compared to commercial reverse transcription-quantitative PCR (qRT-PCR) kits, the diagnostic sensitivities of the real-time RT-IMSA assays (96.4% for EV71 and 94.6% for CVA16) were higher than those of the real-time RT-LAMP assays (91.1% for EV71 and 90.8% for CVA16). The visual RT-IMSA assays also exhibited the same results. In conclusion, this proof-of-concept study suggests that the novel RT-IMSA assay is superior to the RT-LAMP assay in terms of detection limit and has the potential to rapidly detect EV71 and CVA16 viruses. PMID:24648558

Ding, Xiong; Nie, Kai; Shi, Lei; Zhang, Yong; Guan, Li; Zhang, Dan; Qi, Shunxiang; Ma, Xuejun

2014-06-01

328

Human factors in resuscitation: Lessons learned from simulator studies  

PubMed Central

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.

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

2010-01-01

329

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

USGS Publications Warehouse

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

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

1997-01-01

330

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

NASA Technical Reports Server (NTRS)

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.

Luck, C. L.; Lee, S.

1993-01-01

331

Applicability limits of the stationary combustion model in the study of explosive initiation  

Microsoft Academic Search

Imperfections in the physical models have led to unsatisfactory results in accumulating data on detonation initiation in heterogenous systems. This is largely due to the fact that the termination or severe retardation of the process upon a drop in pressure is not considered in the models. In the present paper, using the theory of stationary combustion, the limiting values for

S. G. Andreev; A. I. Chernov; A. N. Isaev; V. S. Solovev

1983-01-01

332

Environmental characteristics in oligotrophic waters: Data evaluation and statistical limitations in water quality studies  

Microsoft Academic Search

Standard statistical tests of nutrient variability in the euphotic layer of an oligotrophic system in the S.E. Aegean Sea were performed. Practical problems resulting from data handling, such as high errors associated with low concentrations, nonlinearity and interaction among variables were examined. The practical problems in the analysis of environmental data, arising from statistical limitations were considered: linear correlations between

Penelope Vounatsou; Michael Karydis

1991-01-01

333

Measures of Effect Size for Comparative Studies: Applications, Interpretations, and Limitations  

Microsoft Academic Search

Although dissatisfaction with the limitations associated with tests for statistical significance has been growing for several decades, applied researchers have continued to rely almost exclusively on these indicators of effect when reporting their findings. To encourage an increased use of alternative measures of effect, the present paper discusses several measures of effect size that might be used in group comparison

Stephen Olejnik; James Algina

2000-01-01

334

Benefits assessment of fault current limiters in a refinery power plant: a case study  

Microsoft Academic Search

Growth of industrial power plants and load increasing typically result in increased available short circuit currents that can easily exceed the interrupting capacity of the installed circuit breakers, whose capacity is also limited by aging. Complete replacement of the existing breakers, whose characteristics are no longer suitable to that application, may not be economical and can require customized breakers, as

A. Cali; S. Conti; F. Santonoceto; G. Tina

2000-01-01

335

Experimental study and simulation of a micro-discharge with limited cathode area  

NASA Astrophysics Data System (ADS)

We report in this paper simulation results and experimental measurements to characterize a micro-discharge generated in a single micro cavity device operating in helium. By spatially limiting the cathode surface area using a dielectric layer, we demonstrate the ability of the micro-discharge to work in a steady-state abnormal glow regime. The physical properties of this regime are discussed.

Dufour, T.; Overzet, L. J.; Dussart, R.; Pitchford, L. C.; Sadeghi, N.; Lefaucheux, P.; Kulsreshath, M.; Ranson, P.

2010-12-01

336

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

Microsoft Academic Search

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

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

1995-01-01

337

Study on the Effect of Fault Current Limiter in Power System With Dispersed Generators  

Microsoft Academic Search

Dispersed generators are being introduced to power systems to secure the electric power supply. However, a short-circuit capacity of the power system increases with the introduction of dispersed generators. As a result, there is concern that a fault current will increase further, and instantaneous voltage sag might be caused. It is proposed to apply a superconducting fault current limiter in

Takao Sato; Mitsugi Yamaguchi; Tohru Terashima; Satoshi Fukui; Jun Ogawa; Hirotaka Shimizu; Tomoyuki Sato

2007-01-01

338

Analytical and experimental studies of the stability limits of nonpremixed flames in a co-flowing stream  

Microsoft Academic Search

Stability limits of non-premixed jet flames into a co-flowing oxidizing stream have been studied both experimentally and analytically in this work. The combined effect of jet velocity and co-flowing stream velocity on flame stability were investigated experimentally for methane, propane, ethylene and hydrogen as jet fuels. Four different types of flame stability limits were observed: liftoff, reattachment, blowout of lifted

Massoumeh Karbassi

1997-01-01

339

Democratizing Qualitative Research: Photovoice and the Study of Human Communication  

Microsoft Academic Search

This essay discusses the possibilities of photovoice as a method to advance the study of human communication. Via a democratizing of the research process, photovoice can significantly affect the study of communication. Originally proposed by Wang and Burris (1994), photovoice traditionally has been used to study the social worlds of marginalized persons (e.g., rural, learning disabled, people without homes). Photovoice

David R. Novak

2010-01-01

340

Impact of Design Trade Studies on System Human Resources.  

ERIC Educational Resources Information Center

This study focused on two objectives. The first objective was to identify and classify the characteristics of conceptual design trade studies that have high potential impact on human resource requirements of Air Force weapon systems. The approach used was a case history review and analysis of 129 F-15 aircraft design trade studies. The analysis…

Whalen, Gary V.; Askren, William B.

341

Lesson Study as a Human Science  

ERIC Educational Resources Information Center

Neither experimental nor design research in education is as well developed in Japan as in the United States. Yet Japanese educational practice employs a type of educational research called "lesson study" that is credited for instructional improvements, including the shift from "teaching as telling" to "teaching for understanding" in science and…

Lewis, Catherine C.; Akita, Kiyomi; Sato, Manabu

2010-01-01

342

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

SciTech Connect

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.

Fabrikant, J.I.

1982-08-01

343

Baboons as a Model to Study Genetics and Epigenetics of Human Disease  

PubMed Central

A major challenge for understanding susceptibility to common human diseases is determining genetic and environmental factors that influence mechanisms underlying variation in disease-related traits. The most common diseases afflicting the US population are complex diseases that develop as a result of defects in multiple genetically controlled systems in response to environmental challenges. Unraveling the etiology of these diseases is exceedingly difficult because of the many genetic and environmental factors involved. Studies of complex disease genetics in humans are challenging because it is not possible to control pedigree structure and often not practical to control environmental conditions over an extended period of time. Furthermore, access to tissues relevant to many diseases from healthy individuals is quite limited. The baboon is a well-established research model for the study of a wide array of common complex diseases, including dyslipidemia, hypertension, obesity, and osteoporosis. It is possible to acquire tissues from healthy, genetically characterized baboons that have been exposed to defined environmental stimuli. In this review, we describe the genetic and physiologic similarity of baboons with humans, the ability and usefulness of controlling environment and breeding, and current genetic and genomic resources. We discuss studies on genetics of heart disease, obesity, diabetes, metabolic syndrome, hypertension, osteoporosis, osteoarthritis, and intrauterine growth restriction using the baboon as a model for human disease. We also summarize new studies and resources under development, providing examples of potential translational studies for targeted interventions and therapies for human disease.

Cox, Laura A.; Comuzzie, Anthony G.; Havill, Lorena M.; Karere, Genesio M.; Spradling, Kimberly D.; Mahaney, Michael C.; Nathanielsz, Peter W.; Nicolella, Daniel P.; Shade, Robert E.; Voruganti, Saroja; VandeBerg, John L.

2013-01-01

344

A CYCLOSCOPIC STUDY OF THE HUMAN ELECTROENCEPHALOGRAM  

PubMed Central

Cycloscopic analyses of a series of electroencephalograms obtained from a mixed group of individuals, clinically classified as normal, schizophrenic, and "frank" epileptic, show the following characteristics: 1. A rather closely regulated potential oscillation which remains predominant throughout the sample of record under study. 2. Associated with this dominant cycle other definite anharmonic cycles are clearly evident. These associated cycles may operate in intermittent sequences or simultaneously with the dominant cycle. Subjects with "atypical" epilepsy show an apparently characteristic spread of low intensity cycles.

Cohn, Robert

1942-01-01

345

Using Humanoid Robots to Study Human Behavior  

Microsoft Academic Search

cept the eye DOFs, which have noload sensing. The robot is currently mountedat the pelvis, so that we do not have to worryabout balance and can focus our studies onupper-body movement. We plan to explorefull-body motion in the future, probably witha new robot design.Inverse kinematics andtrajectory formationOne problem that robots with eyes face isvisually guided manipulation---for example,choosing appropriate joint angles

Christopher G. Atkeson; Joshua G. Hale; Frank E. Pollick; Marcia Riley; Shinya Kotosaka; Stefan Schaal; Tomohiro Shibata; Gaurav Tevatia; Ales Ude; Sethu Vijayakumar; Mitsuo Kawato

2000-01-01

346

Extravehicular activities limitations study. Volume 2: Establishment of physiological and performance criteria for EVA gloves  

NASA Technical Reports Server (NTRS)

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.

Ohara, John M.; Briganti, Michael; Cleland, John; Winfield, Dan

1988-01-01

347

Computational Study of the Ultimate Scaling Limits of CNT Tunneling Devices  

Microsoft Academic Search

The ultimate scaling limits of p-i-n carbon-nanotube field-effect transistors (CNT-FETs) are investigated through numerical simulations based on a quantum-mechanical transport within the nonequilibrium Green's function formalism, based on an energy-dependent effective mass, including inelastic phonon scattering. Starting from the projected specifications of the International Technology Roadmap for Semiconductors for the low-operating-power double-gate MOSFETs, the effect of variations of oxide thickness,

Stefano Poli; Susanna Reggiani; Antonio Gnudi; Elena Gnani; Giorgio Baccarani

2008-01-01

348

Experimental study on superconducting fault current limiting transformer for fault current suppression and system stability improvement  

Microsoft Academic Search

We have been developing a superconducting fault current limiting transformer (SFCLT) with 3-phase, 500\\/275 kV, 625 MVA and optimized the main parameters by EMTP simulation. In this paper, we designed and fabricated an experimental scale-down model of SFCLT with 3-phase, 275\\/105 V, 6.25 kVA, using NbTi superconducting wire. We introduced the experimental model SFCLT into a transient network analyzer consisted

H. Kagawa; N. Hayakawa; N. Kashima; S. Nagaya; H. Okubo

2002-01-01

349

Limits of interacting stellar winds model of planetary nebulae - A numerical study  

NASA Astrophysics Data System (ADS)

The dynamical evolution of planetary nebulae (PNe) was calculated numerically in the scenario of the interacting stellar wind model (ISWM). Radiative losses and heat conduction were included in the calculations together with the SLIC method to follow the surface separating the winds. The general trend of PN evolution is discussed and comparison with some observations are made. Limitations to the validity of ISWM are presented, both based on dynamical and observational grounds. Details of the numerical code are given in the Appendix.

Bedogni, R.; Dercole, A.

1986-03-01

350

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

Microsoft Academic Search

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

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

2005-01-01

351

Ischemic preconditioning induces autophagy and limits necrosis in human recipients of fatty liver grafts, decreasing the incidence of rejection episodes  

PubMed Central

Whether ischemic preconditioning (IP) reduces ischemia/reperfusion (I/R) injury in human normal and fatty livers remains controversial. We compared two independent groups of liver donor transplants with versus without steatosis to evaluate IP consequences. Liver donors with (n=22) or without (n=28) steatosis either did or did not undergo IP before graft retrieval. Clinical data from the recipients, as well as histological and immunohistological characteristics of post-reperfusion biopsies were analyzed. Incidence of post-reperfusion necrosis was increased (10/10 versus 9/14, respectively; P<0.05) and the clinical outcome of recipients was worse for non-IP steatotic liver grafts compared with non-IP non-steatotic grafts. IP significantly lowered the transaminase values only in patients receiving a non-steatotic liver. An increased expression of beclin-1 and LC3, two pro-autophagic proteins, tended to decrease the incidence of necrosis (P=0.067) in IP steatotic livers compared with non-IP steatotic group. IP decreased the incidence of acute and chronic rejection episodes in steatotic livers (2/12 versus 6/10; P=0.07 and 2/12 versus 7/10; P<0.05, respectively), but not in non-steatotic livers. Thus, IP may induce autophagy in human steatotic liver grafts and reduce rejection in their recipients.

Degli Esposti, D; Sebagh, M; Pham, P; Reffas, M; Pous, C; Brenner, C; Azoulay, D; Lemoine, A

2011-01-01

352

Limited Applicability of GW9662 to Elucidate PPAR?-Mediated Fatty Acid Effects in Primary Human T-Helper Cells  

PubMed Central

Synthetic antagonists of the nuclear receptor PPAR? such as GW9662 are widely used to elucidate receptor-mediated ligand effects. In addition and complementary to recent work, we examined whether GW9662 is suitable to serve for mechanistic investigation in T-helper cells. Human peripheral blood mononuclear cells (PBMC) were preincubated with increasing concentrations of GW9662 (0, 0.4, 2, and 10??mol/L) 30?min before adding the c9,t11-isomer of conjugated linoleic acid (c9,t11-CLA) as representative of PPAR?-activating fatty acids with immunomodulatory properties. Corresponding cultures were incubated with GW9662 in the absence of the fatty acid. After 19?h, cells were mitogen stimulated for further 5?h. Subsequently, intracellular IL-2 was measured in CD3+CD4+ lymphocytes by means of flow cytometry. 100??mol/L c9,t11-CLA reduced the number of T-helper cells expressing IL-2 by 68%. GW9662 failed to abrogate this fatty acid effect, likely due to the fact that the compound exerted an own inhibitory effect on IL-2 production. Moreover, GW9662 dose-dependently induced cell death in human leukocytes. These results suggest that application of GW9662 is not conducive in this experimental setting.

Jaudszus, Anke; Gruen, Michael; Roth, Alexander; Jahreis, Gerhard

2014-01-01

353

The study of human mutation rates  

SciTech Connect

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.

Neel, J.V.

1992-01-01

354

Studies on the nucleic acid of human bladder carcinoma  

SciTech Connect

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

Nabih, I.; Mantawy, M.M.; Abdel-Hamid, A.Z. (National Research Centre, Dokki, Cairo (Egypt))

1990-01-01

355

Post-study caffeine administration enhances memory consolidation in humans.  

PubMed

It is currently not known whether caffeine has an enhancing effect on long-term memory in humans. We used post-study caffeine administration to test its effect on memory consolidation using a behavioral discrimination task. Caffeine enhanced performance 24 h after administration according to an inverted U-shaped dose-response curve; this effect was specific to consolidation and not retrieval. We conclude that caffeine enhanced consolidation of long-term memories in humans. PMID:24413697

Borota, Daniel; Murray, Elizabeth; Keceli, Gizem; Chang, Allen; Watabe, Joseph M; Ly, Maria; Toscano, John P; Yassa, Michael A

2014-02-01

356

Human factors and cardiac surgery: A multicenter study  

Microsoft Academic Search

Objective: To study the role of human factors on surgical outcomes, with a series of 243 arterial switch operations performed by 21 surgeons taken as a model. Methods: The following data were collected: patient-specific and procedural variables, self-assessment questionnaires, and a written report from a human factors researcher who observed the operation. The relationship of patient-specific variables to outcomes (death

Marc R. de Leval; Jane Carthey; David J. Wright; Vernon T. Farewell; James T. Reason

2000-01-01

357

Duty-hour limits and patient care and resident outcomes: can high-quality studies offer insight into complex relationships?  

PubMed

Long hours are an accepted component of resident education, yet data suggest they contribute to fatigue that may compromise patient safety. A systematic review confirms that limiting duty hours increases residents' hours of sleep and improves objective measures of alertness. Most studies of operative experience for surgical residents found no effect, and there is evidence of a limited positive effect on residents' mood. We find a mixed effect on patient safety, although problems with supervision, rather than the limits, may be responsible or contibute; evidence of reduced continuity of care and reduced continuity in residents' clinical education; and evidence that increased workload under the limits has a negative effect on patient and resident outcomes. We highlight specific areas for research and offer recommendations for national policy. PMID:23121182

Philibert, Ingrid; Nasca, Thomas; Brigham, Timothy; Shapiro, Jane

2013-01-01

358

Personality and Reduced Incidence of Walking Limitation in Late Life: Findings From the Health, Aging, and Body Composition Study  

PubMed Central

Objectives. To examine the association between openness to experience and conscientiousness and incident reported walking limitation. Method. The study population consisted of 786 men and women aged 71–81 years (M = 75 years, SD = 2.7) participating in the Health, Aging, and Body Composition—Cognitive Vitality Substudy. Results. Nearly 20% of participants (155/786) developed walking limitation during 6 years of follow-up. High openness was associated with a reduced risk of walking limitation (hazard ratio [HR] = 0.83, 95% confidence interval [CI] = 0.69–0.98), independent of sociodemographic factors, health conditions, and conscientiousness. This association was not mediated by lifestyle factors and was not substantially modified by other risk factors for functional disability. Conscientiousness was not associated with risk of walking limitation (HR = 0.91, 95% CI = 0.77–1.07). Discussion. Findings suggest that personality dimensions, specifically higher openness to experience, may contribute to functional resilience in late life.

Ferrucci, Luigi; Costa, Paul T.; Faulkner, Kimberly; Rosano, Caterina; Satterfield, Suzanne; Ayonayon, Hilsa N.; Simonsick, Eleanor M.

2012-01-01

359

A comparative study on the optical limiting properties of different nano spinel ferrites with Z-scan technique  

SciTech Connect

Highlights: ? First report in which the optical limiting properties of five different nano spinel ferrites are compared. ? The obtained nonlinearity fits to a two-photon like absorption process. ? Except for NiFe{sub 2}O{sub 4}, the observed nonlinearity has contributions from excited state absorption. ? A size dependent optical limiting response is obtained. ? Among the investigated ferrites, ZnFe{sub 2}O{sub 4} is found to be a better candidate for the optical limiting applications. -- Abstract: We report the optical limiting properties of five different spinel ferrites, NiFe{sub 2}O{sub 4}, Ni{sub 0.5}Zn{sub 0.5}Fe{sub 2}O{sub 4}, ZnFe{sub 2}O{sub 4}, Ni{sub 0.5}Co{sub 0.5}Fe{sub 2}O{sub 4}, and CoFe{sub 2}O{sub 4} with an average particle grain size of 8 nm. The optical limiting properties are investigated using the open aperture Z-scan technique. The obtained nonlinearity fits to a two-photon like absorption process. Except for NiFe{sub 2}O{sub 4}, the observed nonlinearity has contributions from excited state absorption. The optical limiting response is also studied against particle size and the nonlinearity is found to increase with increasing particle size within the range of our investigations. On comparing the optical limiting properties, ZnFe{sub 2}O{sub 4} is found to be a better candidate for the optical limiting applications. To the best of our knowledge, this is the first report where the optical limiting properties of spinel ferrites are compared.

Thomas, Jeevan Job; Krishnan, Shiji [School of Pure and Applied Physics, Mahatma Gandhi University, Kottayam, Kerala 686560 (India)] [School of Pure and Applied Physics, Mahatma Gandhi University, Kottayam, Kerala 686560 (India); Sridharan, K.; Philip, Reji [Light and Matter Physics Group, Raman Research Institute, C.V. Raman Avenue, Sadashivanagar, Bangalore 560080 (India)] [Light and Matter Physics Group, Raman Research Institute, C.V. Raman Avenue, Sadashivanagar, Bangalore 560080 (India); Kalarikkal, Nandakumar, E-mail: nkkalarikkal@mgu.ac.in [School of Pure and Applied Physics, Mahatma Gandhi University, Kottayam, Kerala 686560 (India) [School of Pure and Applied Physics, Mahatma Gandhi University, Kottayam, Kerala 686560 (India); Centre for Nanoscience and Nanotechnology, Mahatma Gandhi University, Kottayam, Kerala 686560 (India)

2012-08-15

360

A clinicopathological study of human yellow fever.  

PubMed

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

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

1972-01-01

361

A clinicopathological study of human yellow fever*  

PubMed Central

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

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

1972-01-01

362

Advantages and limitations of commercially available electrocuting grids for studying mosquito behaviour  

PubMed Central

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 (?i), 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). 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 to stabilize sampling sensitivity over a full nocturnal cycle so that they can be used to survey patterns of human exposure to mosquitoes.

2013-01-01

363

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

Federal Register 2010, 2011, 2012, 2013

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

2011-12-27

364

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

Federal Register 2010, 2011, 2012, 2013

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

2013-09-18

365

Density limit study focusing on the edge plasma parameters in LHD  

NASA Astrophysics Data System (ADS)

In the Large Helical Device (LHD) experiment, complete detachment takes place when the plasma column shrinks inside the last-closed-flux-surface (LCFS). The density at the LCFS that results in this shrinking corresponds to the maximum LCFS density achievable under the attached condition. The critical LCFS density increases with the square root of the heating power, as is predicted by the conventional density limit scaling for helical plasmas, called the Sudo scaling. High line-averaged electron densities reaching 3 × 1020 m-3, which correspond to ~3 times as high as the Sudo scaling, have been achieved in the plasmas with strongly peaked density profiles generated by hydrogen ice pellet injection. Even in the pellet-fuelled plasmas, however, the LCFS densities are similar to those in gas-fuelled plasmas with flat density profiles and well reproduced by Sudo scaling with a factor 0.8. According to these observations, Sudo scaling has been reinterpreted as the 'edge' density limit scaling. The square root type power dependence in the Sudo scaling has been reconsidered. Instead of a simple power balance between the heating power and the radiation loss, it is deduced by combining the critical LCFS temperature for complete detachment and the electron temperature dependence on the heating power and the electron density. Higher edge density than in the attached plasmas can be sustained in the completely detached plasmas, where the plasma edge shrinks inside the LCFS. The edge density limit scaling is extended for completely detached plasmas by taking into account the shrinking plasma edge.

Miyazawa, J.; Sakamoto, R.; Masuzaki, S.; Peterson, B. J.; Tamura, N.; Goto, M.; Yamada, I.; Narihara, K.; Tanaka, K.; Tokuzawa, T.; Shoji, M.; Kobayashi, M.; Arimoto, H.; Kondo, K.; Murakami, S.; Funaba, H.; Sakakibara, S.; Osakabe, M.; Morita, S.; Nagayama, Y.; Ohyabu, N.; Yamada, H.; Komori, A.; Motojima, O.; LHD Experimental Group

2008-01-01

366

An Experimental Study of the Emergence of Human Communication Systems  

ERIC Educational Resources Information Center

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…

Galantucci, Bruno

2005-01-01

367

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

ERIC Educational Resources Information Center

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

Wisconsin State Dept. of Public Instruction, Madison.

368

Reliability of Experimental Studies for Predicting Hazards to Human Development.  

National Technical Information Service (NTIS)

Contains a detailed review of human and animal data taking into account the endpoints evaluated, the relative power of the studies, the dose-response patterns, and overall toxicity to the maternal and fetal systems to assess the usefulness of animal studi...

C. A. Kimmel J. F. Holson C. J. Hogue G. Carlo

1984-01-01

369

Prenatal Human Lateral Geniculate Nucleus: A Quantitative Light Microscopic Study  

Microsoft Academic Search

Using morphometric methods, a quantitative study has been carried out on the lateral geniculate nucleus (LGN) of human fetuses ranging in gestational age from 13 to 38 weeks. The volume of the nucleus as well as the neuronal, glial and dead cell populations have been studied in Nissl preparations. While the volume of the LGN shows a progressive increase throughout

Aijaz A. Khan; Shashi Wadhwa; R. M. Pandey; Veena Bijlani

1993-01-01

370

Age and decisions to limit life support for patients with acute lung injury: a prospective cohort study  

PubMed Central

Introduction The proportion of elderly Americans admitted to the intensive care unit (ICU) in the last month of life is rising. Hence, challenging decisions regarding the appropriate use of life support are increasingly common. The objective of this study was to estimate the association between patient age and the rate of new limitations in the use of life support, independent of daily organ dysfunction status, following acute lung injury (ALI) onset. Methods This was a prospective cohort study of 490 consecutive patients without any limitations in life support at the onset of ALI. Patients were recruited from 11 ICUs at three teaching hospitals in Baltimore, Maryland, USA, and monitored for the incidence of six pre-defined limitations in life support, with adjustment for baseline comorbidity and functional status, duration of hospitalization before ALI onset, ICU severity of illness, and daily ICU organ dysfunction score. Results The median patient age was 52 (range: 18 to 96), with 192 (39%) having a new limitation in life support in the ICU. Of patients with a new limitation, 113 (59%) had life support withdrawn and died, 53 (28%) died without resuscitation, and 26 (14%) survived to ICU discharge. Each ten-year increase in patient age was independently associated with a 24% increase in the rate of limitations in life support (Relative Hazard 1.24; 95% CI 1.11 to 1.40) after adjusting for daily ICU organ dysfunction score and all other covariates. Conclusions Older critically ill patients are more likely to have new limitations in life support independent of their baseline status, ICU-related severity of illness, and daily organ dysfunction status. Future studies are required to determine whether this association is a result of differences in patient preferences by age, or differences in the treatment options discussed with the families of older versus younger patients.

2014-01-01

371

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

Microsoft Academic Search

Although they have several important limitations primary human hepatocytes still represent the in vitro gold standard model for xenobiotic metabolism and toxicity studies. The large use of human liver cell lines either from tumoral origin or obtained by oncogenic immortalisation is prevented by the loss of various liver-specific functions, especially many cytochrome P450 (CYP)-related enzyme activities. We review here recent

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

2007-01-01

372

Fraud Detection by Human Agents: A Pilot Study  

NASA Astrophysics Data System (ADS)

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.

Almendra, Vinicius; Schwabe, Daniel

373

The Benefits of Humanized Yeast Models to Study Parkinson's Disease  

PubMed Central

Over the past decade, the baker's yeast Saccharomyces cerevisiae has proven to be a useful model system to investigate fundamental questions concerning the pathogenic role of human proteins in neurodegenerative diseases such as Parkinson's disease (PD). These so-called humanized yeast models for PD initially focused on ?-synuclein, which plays a key role in the etiology of PD. Upon expression of this human protein in the baker's yeast Saccharomyces cerevisiae, the events leading to aggregation and the molecular mechanisms that result in cellular toxicity are faithfully reproduced. More recently, a similar model to study the presumed pathobiology of the ?-synuclein interaction partner synphilin-1 has been established. In this review we will discuss recent advances using these humanized yeast models, pointing to new roles for cell wall integrity signaling, Ca2+ homeostasis, mitophagy, and the cytoskeleton.

Franssens, V.; Bynens, T.; Van den Brande, J.; Vandermeeren, K.; Verduyckt, M.; Winderickx, J.

2013-01-01

374

Prospective study on stereotactic radiotherapy of limited-stage non-small-cell lung cancer  

SciTech Connect

Purpose: To test the effect of stereotactic body radiotherapy (SBRT) in the treatment of medically inoperable patients with limited-stage non-small-cell lung cancer (NSCLC) in a Phase II trial. Methods and Materials: Forty patients with Stage I NSCLC were treated with SBRT with a central dose of 15 Gy x 3 within 5-8 days. Results: Eight patients (20%) obtained a complete response, 15 (38%) had a partial response, and 12 (30%) had no change or could not be evaluated. Only 3 patients had a local recurrence, and the local control rate 2 years after SBRT was 85%. At 2 years, 54% were without local or distant progression, and overall survival was 47%. Within 6 months after treatment, one or more Grade {>=}2 reactions were observed in 48% of the patients. Conclusions: Stereotactic body radiotherapy in patients with limited-stage NSCLC resulted in a high probability of local control and a promising survival rate. The toxicity after SBRT of lung tumors was moderate. However, deterioration in performance status, respiratory insufficiency, and other side effects were observed.

Hoyer, Morten [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark)]. E-mail: hoyer@as.aaa.dk; Roed, Henrik D. [Department of Radiation Oncology, Copenhagen University Hospital, Copenhagen (Denmark); Hansen, Anders Traberg [Department of Medical Physics, Aarhus University Hospital, Aarhus (Denmark); Ohlhuis, Lars [Department of Radiation Oncology, Copenhagen University Hospital, Copenhagen (Denmark); Petersen, Jorgen [Department of Medical Physics, Aarhus University Hospital, Aarhus (Denmark); Nellemann, Hanne [Department of Radiology, Aarhus University Hospital, Aarhus (Denmark); Berthelsen, Anne Kiil [Department of Radiation Oncology, Copenhagen University Hospital, Copenhagen (Denmark); Grau, Cai D. [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark); Engelholm, Svend Aage D. [Department of Radiation Oncology, Copenhagen University Hospital, Copenhagen (Denmark); Maase, Hans D. von der [Department of Oncology, Aarhus University Hospital, Aarhus (Denmark)

2006-11-15

375

Application Study of a High Temperature Superconducting Fault Current Limiter for Electric Power System  

NASA Astrophysics Data System (ADS)

Using high temperature superconductor, a Superconducting Fault Current Limiter (SFCL) was made and tested. Superconductor and vacuum interrupter as commutation switch are connected in parallel with bypass coil. When a fault occurs and the excessive current flows, superconductor is first quenched and the current is transferred to bypass coil because on voltage drop of superconductor. At the same time, since magnetic field is generated by current which flows in bypass coil, commutation switch is immediately driven by electromagnetic repulsion plate connected to driving rod of vacuum interrupter, and superconductor is separated from this circuit. Using the testing model, we could separate the superconductor from a circuit due to movement of vacuum interrupter within half-cycle current and transfer all current to bypass coil. Since operation of a commutation switch is included in current limiting operation of this testing model, it is one of helpful circuit of development of SFCL in the future. Moreover, since it can make the consumed energy of superconductor small during fault state due to realization of high-speed switch with simple composition, the burden of superconductor is reduced compared with conventional resistive type SFCL and it is considered that the flexibility of a SFCL design increases. Cooperation with a circuit breaker was also considered, the trial calculation of a parameter and energy of operation is conducted and discussion in the case of installing the SFCL to electric power system is made.

Naito, Yuji; Shimizu, Iwao; Yamaguchi, Iwao; Kaiho, Katsuyuki; Yanabu, Satoru

376

Thyroid hormone transport by the human monocarboxylate transporter 8 and its rate-limiting role in intracellular metabolism.  

PubMed

Cellular entry of thyroid hormone is mediated by plasma membrane transporters. We have identified rat monocarboxylate transporter 8 (MCT8) as an active and specific thyroid hormone transporter. The MCT8 gene is located on the X-chromosome. The physiological relevance of MCT8 has been demonstrated by the identification of hemizygous mutations in this gene in males with severe psychomotor retardation and elevated serum T(3) levels. We have characterized human (h) MCT8 by analysis of iodothyronine uptake and metabolism in cell lines transiently transfected with hMCT8 cDNA alone or together with cDNA coding for iodothyronine deiodinase D1, D2, or D3. MCT8 mRNA was detected by RT-PCR in a number of human cell lines as well as in COS1 cells but was low to undetectable in other cell lines, including JEG3 cells. MCT8 protein was not detected in nontransfected cell lines tested by immunoblotting using a polyclonal C-terminal hMCT8 antibody but was detectable in transfected cells at the expected size (61 kDa). Transfection of COS1 and JEG3 cells with hMCT8 cDNA resulted in 2- to 3-fold increases in uptake of T(3) and T(4) but little or no increase in rT(3) or 3,3'-diiodothyronine (3,3'-T(2)) uptake. MCT8 expression produced large increases in T(4) metabolism by cotransfected D2 or D3, T(3) metabolism by D3, rT(3) metabolism by D1 or D2, and 3,3'-T(2) metabolism by D3. Affinity labeling of hMCT8 protein was observed after incubation of intact transfected cells with N-bromoacetyl-[(125)I]T(3). hMCT8 also facilitated affinity labeling of cotransfected D1 by bromoacetyl-T(3). Our findings indicate that hMCT8 mediates plasma membrane transport of iodothyronines, thus increasing their intracellular availability. PMID:16887882

Friesema, Edith C H; Kuiper, George G J M; Jansen, Jurgen; Visser, Theo J; Kester, Monique H A

2006-11-01

377

Ontology-Based Federated Data Access to Human Studies Information  

PubMed Central

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.

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

378

Limiting human exposures through the ``as low as reasonably achievable`` process at a Department of Energy mixed waste site  

SciTech Connect

Applying a process to reduce human exposures to levels as low as reasonably achievable (ALARA) is a cornerstone of the US Department of Energy`s radiation protection program, and this process is being used to develop cleanup levels for contaminated sites across the country. Under the ALARA process, exposures and risks are reduced as far below protective criteria as can reasonably be achieved--considering technical, economic, and social factors. Risk-based cleanup levels have been developed for radionuclides and chemicals in surface water and soil at the Weldon Spring site in Missouri, following explicit applications of the ALARA process. Among the lessons learned during these applications were the importance of three factors: (1) soliciting early input from the parties involved--because the ALARA process involves a range of technical and nontechnical issues; (2) maintaining site specificity for the ALARA analyses--because contaminant types and distributions will vary, as will local conditions and constraints; and (3) identifying cleanup levels in the planning phase that are distinct from those developed for the field phase--because remedies can be over-designed if the decision levels are the same as the ALARA goals for field work, such that little increased risk reduction is achieved for substantially higher costs.

MacDonell, M.; Peterson, J.; Haroun, L.; Blunt, D.; Dunning, D.

1994-09-01

379

The intracellular sensor NOD2 induces microRNA-29 expression in human dendritic cells to limit IL-23 release.  

PubMed

NOD2 is an intracellular sensor that contributes to immune defense and inflammation. Here we investigated whether NOD2 mediates its effects through control of microRNAs (miRNAs). miR-29 expression was upregulated in human dendritic cells (DCs) in response to NOD2 signals, and miR-29 regulated the expression of multiple immune mediators. In particular, miR-29 downregulated interleukin-23 (IL-23) by targeting IL-12p40 directly and IL-23p19 indirectly, likely via reduction of ATF2. DSS-induced colitis was worse in miR-29-deficient mice and was associated with elevated IL-23 and T helper 17 signature cytokines in the intestinal mucosa. Crohn's disease (CD) patient DCs expressing NOD2 polymorphisms failed to induce miR-29 upon pattern recognition receptor stimulation and showed enhanced release of IL-12p40 on exposure to adherent invasive E. coli. Therefore, we suggest that loss of miR-29-mediated immunoregulation in CD DCs might contribute to elevated IL-23 in this disease. PMID:24054330

Brain, Oliver; Owens, Benjamin M J; Pichulik, Tica; Allan, Philip; Khatamzas, Elham; Leslie, Alasdair; Steevels, Tessa; Sharma, Sameer; Mayer, Alice; Catuneanu, Ana Maria; Morton, Victoria; Sun, Mei-Yi; Jewell, Derek; Coccia, Margherita; Harrison, Oliver; Maloy, Kevin; Schönefeldt, Susann; Bornschein, Simon; Liston, Adrian; Simmons, Alison

2013-09-19

380

An Experimental Study of n-Heptane and JP-7 Extinction Limits in an Opposed Jet Burner  

NASA Technical Reports Server (NTRS)

Propulsion engine combustor design and analysis requires experimentally verified data on the chemical kinetics of fuel. Among the important data is the combustion extinction limit as measured by observed maximum flame strain rate. The extinction limit relates to the ability to maintain a flame in a combustor during operation. Extinction limit data can be obtained for a given fuel by means of a laminar flame experiment using an opposed jet burner (OJB). Laminar extinction limit data can be applied to the turbulent application of a combustor via laminar flamelet modeling. The OJB consists of two axi-symmetric tubes (one for fuel and one for oxidizer), which produce a flat, disk-like counter-flow diffusion flame. This paper presents results of experiments to measure extinction limits for n-heptane and the military specification fuel JP-7, obtained from an OJB. JP-7 is an Air Force-developed fuel that continues to be important in the area of hypersonics. Because of its distinct properties it is currently the hydrocarbon fuel of choice for use in Scramjet engines. This study provides much-desired data for JP-7, for which very little information previously existed. The interest in n-heptane is twofold. First, there has been a significant amount of previous extinction limit study and resulting data with this fuel. Second, n-heptane (C7H16) is a pure substance, and therefore does not vary in composition as does JP-7, which is a mixture of several different hydrocarbons. These two facts allow for a baseline to be established by comparing the new OJB results to those previously taken. Additionally, the data set for n-heptane, which previously existed for mixtures up to 26 mole percent in nitrogen, is completed up to 100% n-heptane. The extinction limit data for the two fuels are compared, and complete experimental results are included.

Convery, Janet L.; Pellett, Gerald L.; O'Brien, Walter F., Jr.; Wilson, Lloyd G.; Williams, John

2005-01-01

381

Experimental study of lean flammability limits of methane/hydrogen/air mixtures in tubes of different diameters  

SciTech Connect

Lean limit flames in methane/hydrogen/air mixtures propagating in tubes of internal diameters (ID) of 6.0, 8.9, 12.3, 18.4, 25.2, 35.0, and 50.2 mm have been experimentally studied. The flames propagated upward from the open bottom end of the tube to the closed upper end. The content of hydrogen in the fuel gas has been varied in the range 0-40 mol%. Lean flammability limits have been determined; flame shapes recorded and the visible speed of flame propagation measured. Most of the observed limit flames in tubes with diameters in the range of 8.9-18.4 mm had enclosed shape, and could be characterized as distorted or spherical flame balls. The tendency was observed for mixtures with higher hydrogen content to form smaller size, more uniform flame balls in a wider range of tube diameters. At hydrogen content of 20% or more in the fuel gas, limit flames in largest diameters (35.0 mm and 50.2 mm ID) tubes had small, compared to the tube diameter, size and were ''lens''-shaped. ''Regular'' open-front lean limit flames were observed only for the smallest diameters (6.0 mm and 8.9 mm) and largest diameters (35.0 and 50.2 mm ID), and only for methane/air and (90% CH{sub 4} + 10% H{sub 2})/air mixtures, except for 6 mm ID tube in which all limit flames had open front. In all experiments, except for the lean limit flames in methane/air and (90% CH{sub 4} + 10% H{sub 2})/air mixtures in the 8.9 mm ID tube, and all limit flames in 6.0 mm ID tube, visible flame speeds very weakly depended on the hydrogen content in the fuel gas and were close to- or below the theoretical estimate of the speed of a rising hot bubble. This observation suggests that the buoyancy is the major factor which determines the visible flame speed for studied limit flames, except that last mentioned. A decrease of the lean flammability limit value with decreasing the tube diameter was observed for methane/air and (90% CH{sub 4} + 10% H{sub 2})/air mixtures for tubes having internal diameters in the range of 18.4-50.2 mm. This effect has been attributed to the stronger combined effect of the preferential diffusion and flame stretch in narrower tubes for flames which resemble rising bubble. (author)

Shoshin, Y.L.; Goey, L.P.H. de [Eindhoven University of Technology, Mechanical Engineering, Eindhoven (Netherlands)

2010-04-15

382

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

PubMed Central

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.

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

1998-01-01

383

THE KECK + MAGELLAN SURVEY FOR LYMAN LIMIT ABSORPTION. II. A CASE STUDY ON METALLICITY VARIATIONS  

SciTech Connect

We present an absorption line analysis of the Lyman limit system (LLS) at z approx 3.55 in our Magellan/MIKE spectrum of PKS2000 - 330. Our analysis of the Lyman limit and full H I Lyman series constrains the total H I column density of the LLS (N{sub H{sub I}} = 10{sup 18.0+}-{sup 0.25} cm{sup -2} for b{sub H{sub I}} >= 20 km s{sup -1}) and also the N{sub H{sub I}} values of the velocity subsystems comprising the absorber. We measure ionic column densities for metal-line transitions associated with the subsystems and use these values to constrain the ionization state (>90% ionized) and relative abundances of the gas. We find an order of magnitude dispersion in the metallicities of the subsystems, marking the first detailed analysis of metallicity variations in an optically thick absorber. The results indicate that metals are not well mixed within the gas surrounding high z galaxies. Assuming a single-phase photoionization model, we also derive an N{sub H}-weighted metallicity, ([Si/H]) = -1.66 +- 0.25, which matches the mean metallicity in the neutral interstellar medium in high z damped Lyalpha systems (DLAs). Because the line density of LLSs is over 10x higher than the DLAs, we propose that the former dominate the metal mass-density at z approx 3 and that these metals reside in the galaxy/intergalactic medium interface. Considerations of a multi-phase model do not qualitatively change these conclusions. Finally, we comment on an anomalously large O{sup 0}/Si{sup +} ratio in the LLS that suggests an ionizing radiation field dominated by soft UV sources (e.g., a starburst galaxy). Additional abundance analysis is performed on the super-LLS systems at z approx 3.19.

Prochter, Gabriel E.; Prochaska, J. Xavier; Bernstein, Rebecca A. [Department of Astronomy and Astrophysics, UCO/Lick Observatory, University of California, 1156 High Street, Santa Cruz, CA 95064 (United States); O'Meara, John M. [Department of Chemistry and Physics, Saint Michael's College, One Winooski Park, Colchester, VT 05439 (United States); Burles, Scott [Visiting Astronomer, Las Campanas Observatory (Chile)

2010-01-10

384

The Institute for the Interdisciplinary Study of Human & Machine Cognition  

NSDL National Science Digital Library

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

385

The Watershed as A Conceptual Framework for the Study of Environmental and Human Health  

PubMed Central

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.

Kolok, Alan S.; Beseler, Cheryl L.; Chen, Xun-Hong; Shea, Patrick J.

2009-01-01

386

Detection limits and cost comparisons of human- and gull-associated conventional and quantitative PCR assays in artificial and environmental waters.  

PubMed

Some molecular methods for tracking fecal pollution in environmental waters have both PCR and quantitative PCR (qPCR) assays available for use. To assist managers in deciding whether to implement newer qPCR techniques in routine monitoring programs, we compared detection limits (LODs) and costs of PCR and qPCR assays with identical targets that are relevant to beach water quality assessment. For human-associated assays targeting Bacteroidales HF183 genetic marker, qPCR LODs were 70 times lower and there was no effect of target matrix (artificial freshwater, environmental creek water, and environmental marine water) on PCR or qPCR LODs. The PCR startup and annual costs were the lowest, while the per reaction cost was 62% lower than the Taqman based qPCR and 180% higher than the SYBR based qPCR. For gull-associated assays, there was no significant difference between PCR and qPCR LODs, target matrix did not effect PCR or qPCR LODs, and PCR startup, annual, and per reaction costs were lower. Upgrading to qPCR involves greater startup and annual costs, but this increase may be justified in the case of the human-associated assays with lower detection limits and reduced cost per sample. PMID:24583609

Riedel, Timothy E; Zimmer-Faust, Amity G; Thulsiraj, Vanessa; Madi, Tania; Hanley, Kaitlyn T; Ebentier, Darcy L; Byappanahalli, Muruleedhara; Layton, Blythe; Raith, Meredith; Boehm, Alexandria B; Griffith, John F; Holden, Patricia A; Shanks, Orin C; Weisberg, Stephen B; Jay, Jennifer A

2014-04-01

387

Mysid Population Responses to Resource Limitation Differ from those Predicted by Cohort Studies  

EPA Science Inventory

Effects of anthropogenic stressors on animal populations are often evaluated by assembling vital rate responses from isolated cohort studies into a single demographic model. However, models constructed from cohort studies are difficult to translate into ecological predictions be...

388

The intake of dietary indigestible fraction in the Spanish diet shows the limitations of dietary fibre data for nutritional studies  

Microsoft Academic Search

Objective: To compare the intakes of dietary fibre (DF) and dietary indigestible fraction (DIF) in the Spanish diet and also to show the limitations of DF values for nutritional and epidemiological studies.Design: This includes the following: (i) estimation of plant foods consumption in Spanish diet from national food consumption data obtained from annual surveys (6000 households, 700 hotels and restaurants

F D Saura-Calixto; I Gońi

2004-01-01

389

A Study of Suburban Secondary Education Mathematics Programs: The Programmatic Impact of Limited Early Access to Algebra on Student Performance  

ERIC Educational Resources Information Center

The purpose of this researcher was to investigate the programmatic impact of school districts' practice of limited early access to algebra on student performance. School districts selected for the study are located in the counties of Nassau and Suffolk, Long Island, New York. School districts that reported Mathematics A and Integrated Algebra…

Watkins, Donna Moguel

2010-01-01

390

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

PubMed Central

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

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

2009-01-01

391

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

PubMed Central

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

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

2012-01-01

392

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

PubMed

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. PMID:22317033

Attaianese, Erminia; Duca, Gabriella

2012-01-01

393

Studying synapses in human brain with array tomography and electron microscopy  

PubMed Central

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.

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

394

Bound states in two-dimensional spin systems near the Ising limit: A quantum finite-lattice study  

SciTech Connect

We analyze the properties of low-energy bound states in the transverse-field Ising model and in the XXZ model on the square lattice. To this end, we develop an optimized implementation of perturbative continuous unitary transformations. The Ising model is studied in the small-field limit which is found to be a special case of the toric code model in a magnetic field. To analyze the XXZ model, we perform a perturbative expansion about the Ising limit in order to discuss the fate of the elementary magnon excitations when approaching the Heisenberg point.

Dusuel, Sebastien [Lycee Saint-Louis, 44 Boulevard Saint-Michel, 75006 Paris (France); Kamfor, Michael; Schmidt, Kai Phillip [Lehrstuhl fuer Theoretische Physik I, Otto-Hahn-Strasse 4, TU Dortmund, 44221 Dortmund (Germany); Thomale, Ronny [Lehrstuhl fuer Theoretische Physik I, Otto-Hahn-Strasse 4, TU Dortmund, 44221 Dortmund (Germany); Institut fuer Theorie der Kondensierten Materie, Universitaet Karlsruhe, D-76128 Karlsruhe (Germany); Department of Physics, Princeton University, Princeton, New Jersey 08544 (United States); Vidal, Julien [Laboratoire de Physique Theorique de la Matiere Condensee, CNRS UMR 7600, Universite Pierre et Marie Curie, 4 Place Jussieu, 75252 Paris Cedex 05 (France)

2010-02-01

395

A Hubble Space Telescope Study of Lyman Limit Systems: Census and Evolution  

NASA Astrophysics Data System (ADS)

We present a survey for optically thick Lyman limit absorbers at z < 2.6 using archival Hubble Space Telescope observations with the Faint Object Spectrograph and Space Telescope Imaging Spectrograph. We identify 206 Lyman limit systems (LLSs), increasing the number of cataloged LLSs at z < 2.6 by a factor of ~10. We compile a statistical sample of 50 ?LLS >= 2 LLSs drawn from 249 QSO sight lines that avoid known targeting biases. The incidence of such LLSs per unit redshift, l(z) = dn/dz, at these redshifts is well described by a single power law, l(z)vprop(1 + z)?, with ? = 1.33 ± 0.61 at z < 2.6, or with ? = 1.83 ± 0.21 over the redshift range 0.2 <= z <= 4.9. The incidence of LLSs per absorption distance, l(X), decreases by a factor of ~1.5 over the ~0.6 Gyr from z = 4.9 to 3.5; l(X) evolves much more slowly at low redshifts, decreasing by a similar factor over the ~8 Gyr from z = 2.6 to 0.25. We show that the column density distribution function, f(N H I ), at low redshift is not well fitted by a single power-law index (f(N H I ) vprop N -? H I ) over the column density range 13 <= log N H I <= 22 or log N H I >= 17.2. While low- and high-redshift f(N H I ) distributions are consistent for log N H I >19.0, there is some evidence that f(N H I ) evolves with z for log N H I <~ 17.7, possibly due to the evolution of the UV background and galactic feedback. Assuming LLSs are associated with individual galaxies, we show that the physical cross section of the optically thick envelopes of galaxies decreased by a factor of ~9 from z ~ 5 to 2 and has remained relatively constant since that time. We argue that a significant fraction of the observed population of LLSs arises in the circumgalactic gas of sub-L * galaxies. Based on observations made with the NASA/ESA Hubble Space Telescope, obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract No. NAS5-26555.

Ribaudo, Joseph; Lehner, Nicolas; Howk, J. Christopher

2011-07-01

396

A HUBBLE SPACE TELESCOPE STUDY OF LYMAN LIMIT SYSTEMS: CENSUS AND EVOLUTION  

SciTech Connect

We present a survey for optically thick Lyman limit absorbers at z < 2.6 using archival Hubble Space Telescope observations with the Faint Object Spectrograph and Space Telescope Imaging Spectrograph. We identify 206 Lyman limit systems (LLSs), increasing the number of cataloged LLSs at z < 2.6 by a factor of {approx}10. We compile a statistical sample of 50 {tau}{sub LLS} {>=} 2 LLSs drawn from 249 QSO sight lines that avoid known targeting biases. The incidence of such LLSs per unit redshift, l(z) = dn/dz, at these redshifts is well described by a single power law, l(z){proportional_to}(1 + z){sup {gamma}}, with {gamma} = 1.33 {+-} 0.61 at z < 2.6, or with {gamma} = 1.83 {+-} 0.21 over the redshift range 0.2 {<=} z {<=} 4.9. The incidence of LLSs per absorption distance, l(X), decreases by a factor of {approx}1.5 over the {approx}0.6 Gyr from z = 4.9 to 3.5; l(X) evolves much more slowly at low redshifts, decreasing by a similar factor over the {approx}8 Gyr from z = 2.6 to 0.25. We show that the column density distribution function, f(N{sub HI}), at low redshift is not well fitted by a single power-law index (f(N{sub HI}) {proportional_to} N{sup -}{beta}{sub HI}) over the column density range 13 {<=} log N{sub HI} {<=} 22 or log N{sub HI} {>=} 17.2. While low- and high-redshift f(N{sub HI}) distributions are consistent for log N{sub HI}>19.0, there is some evidence that f(N{sub HI}) evolves with z for log N{sub HI} {approx}< 17.7, possibly due to the evolution of the UV background and galactic feedback. Assuming LLSs are associated with individual galaxies, we show that the physical cross section of the optically thick envelopes of galaxies decreased by a factor of {approx}9 from z {approx} 5 to 2 and has remained relatively constant since that time. We argue that a significant fraction of the observed population of LLSs arises in the circumgalactic gas of sub-L{sub *} galaxies.

Ribaudo, Joseph; Lehner, Nicolas; Howk, J. Christopher [Department of Physics, University of Notre Dame, Notre Dame, IN 46556 (United States)

2011-07-20

397

Limited-angle x-ray luminescence tomography: methodology and feasibility study  

NASA Astrophysics Data System (ADS)

X-ray luminescence tomography (XLT) has recently been proposed as a new imaging modality for biological imaging applications. This modality utilizes phosphor nanoparticles which luminesce near-infrared light when excited by x-ray photons. The advantages of this modality are that it uniquely combines the high sensitivity of radioluminescent nanoparticles and the high spatial localization of collimated x-ray beams. Currently, XLT has been demonstrated using x-ray spatial encoding to resolve the imaging volume. However, there are applications where the x-ray excitation may be limited by geometry, where increased temporal resolution is desired, or where a lower dose is mandatory. This paper extends the utility of XLT to meet these requirements by incorporating a photon propagation model into the reconstruction algorithm in an x-ray limited-angle (LA) geometry. This enables such applications as image-guided surgery, where the ability to resolve lesions at depths of several centimeters can be the key to successful resection. The hybrid x-ray/diffuse optical model is first formulated and then demonstrated in a breast-sized phantom, simulating a breast lumpectomy geometry. Both numerical and experimental phantoms are tested, with lesion-simulating objects of various sizes and depths. Results show localization accuracy with median error of 2.2 mm, or 4% of object depth, for small 2-14 mm diameter lesions positioned from 1 to 4.5 cm in depth. This compares favorably with fluorescence optical imaging, which is not able to resolve such small objects at this depth. The recovered lesion size has lower size bias in the x-ray excitation direction than the optical direction, which is expected due to the increased optical scatter. However, the technique is shown to be quite invariant in recovered size with respect to depth, as the standard deviation is less than 2.5 mm. Sensitivity is a function of dose; radiological doses are found to provide sufficient recovery for µg ml-1 concentrations, while therapy dosages provide recovery for ng ml-1 concentrations. Experimental phantom results agree closely with the numerical results, with positional errors recovered within 8.6% of the effective depth for a 5 mm object, and within 5.2% of the depth for a 10 mm object. Object-size median error is within 2.3% and 2% for the 5 and 10 mm objects, respectively. For shallow-to-medium depth applications where optical and radio-emission imaging modalities are not ideal, such as in intra-operative procedures, LAXLT may be a useful tool to detect molecular signatures of disease.

Carpenter, C. M.; Pratx, G.; Sun, C.; Xing, L.

2011-06-01

398

Reynolds number limits for jet propulsion: a numerical study of simplified jellyfish.  

PubMed

The Scallop theorem states that reciprocal methods of locomotion, such as jet propulsion or paddling, will not work in Stokes flow (Reynolds number=0). In nature the effective limit of jet propulsion is still in the range where inertial forces are significant. It appears that almost all animals that use jet propulsion swim at Reynolds numbers (Re) of about 5 or more. Juvenile squid and octopods hatch from the egg already swimming in this inertial regime. Juvenile jellyfish, or ephyrae, break off from polyps swimming at Re greater than 5. Many other organisms, such as scallops, rarely swim at Re less than 100. The limitations of jet propulsion at intermediate Re is explored here using the immersed boundary method to solve the 2D Navier-Stokes equations coupled to the motion of a simplified jellyfish. The contraction and expansion kinematics are prescribed, but the forward and backward swimming motions of the idealized jellyfish are emergent properties determined by the resulting fluid dynamics. Simulations are performed for both an oblate bell shape using a paddling mode of swimming and a prolate bell shape using jet propulsion. Average forward velocities and work put into the system are calculated for Re between 1 and 320. The results show that forward velocities rapidly decay with decreasing Re for all bell shapes when Re<10. Similarly, the work required to generate the pulsing motion increases significantly for Re<10. When compared to actual organisms, the swimming velocities and vortex separation patterns for the model prolate agree with those observed in Nemopsis bachei. The forward swimming velocities of the model oblate jellyfish after two pulse cycles are comparable to those reported for Aurelia aurita, but discrepancies are observed in the vortex dynamics between when the 2D model oblate jellyfish and the organism. This discrepancy is likely due to a combination of the differences between the 3D reality of the jellyfish and the 2D simplification, as well as the rigidity of the time varying geometry imposed by the idealized model. PMID:21669208

Herschlag, Gregory; Miller, Laura

2011-09-21

399

Human hephaestin expression is not limited to enterocytes of the gastrointestinal tract but is also found in the antrum, the enteric nervous system, and pancreatic {beta}-cells.  

PubMed

Hephaestin (Hp) is a membrane protein with ferroxidase activity that converts Fe(II) to Fe(III) during the absorption of nutritional iron in the gut. Using anti-peptide antibodies to predicted immunogenic regions of rodent Hp, previous immunocytochemical studies in rat, mouse, and human gut tissues localized Hp to the basolateral membranes of the duodenal enterocytes where the Hp was predicted to aid in the transfer of Fe(III) to transferrin in the blood. We used a recombinant soluble form of human Hp to obtain a high-titer polyclonal antibody to Hp. This antibody was used to identify the intracellular location of Hp in human gut tissue. Our immunocytochemical studies confirmed the previous localization of Hp in human enterocytes. However, we also localized Hp to the entire length of the gastrointestinal tract, the antral portion of the stomach, and to the enteric nervous system (both the myenteric and submucous plexi). Hp was also localized to human pancreatic beta-cells. In addition to its expression in the same cells as Hp, ferroportin was also localized to the ductal cells of the exocrine pancreas. The localization of the ferroxidase Hp to the neuronal plexi and the pancreatic beta cells suggests a role for the enzymatic function of Hp in the protection of these specialized cell types from oxidative damage. PMID:20019163

Hudson, David M; Curtis, Susan B; Smith, Valerie C; Griffiths, Tanya A M; Wong, Ann Y K; Scudamore, Charles H; Buchan, Alison M J; MacGillivray, Ross T A

2010-03-01

400

CASE STUDY OF STABILITY AS SESSMENT OF ROCK SLOPE BY LIMIT EQUILIBRIUM ANALYSIS  

NASA Astrophysics Data System (ADS)

Simple stability assessment was carried out for the rock slope which collapsed in 2007 and consists of Neogene massive pyroclastic rock. The assessment met hod is the 2-D and 3-D limit equilibrium analysis using tensile strength and tensile stress, which was developed by the authors using the centrifuge model test. As a result, safety factor obtained by 2-D analysis is about 1.0 (1.1). Safety factor by 3-D analysis becomes under 1.0 when the part of intact rock of the block is less than 5.2m and 6.9m by the Crackplane Estimation Method and the Least Crack Angl e Method, respectively. As the both figures are slightly above the figure of the real intact part (5.0m) of the collapsed block, the both methods estimate the block stability precisely and sately. In conclusion, 2-D analysis is suitable for the screening of rock slopes, while 3-D analysis is suitable for more detailed estimation of target slopes.

Kusakabe, Yuki; Miura, Kin-Ya; Ito, Yoshihiko; Omote, Shin-Ya

401

Discrete-Ordinates and Flux-Limited-Diffusion Methods for Radiation Transport: A Comparison Study  

NASA Astrophysics Data System (ADS)

The Center for Radiative Shock Hydrodynamics (CRASH) seeks to improve the predictive capability for models of Omega laser experiments of radiative shock waves. The laser is used to shock, ionize, and accelerate a beryllium plate into a xenon-filled shock tube. These shocks, when driven above a threshold velocity of about 60 km/s, become strongly radiative and convert most of the incoming energy flux into radiation. Radiative shocks have properties that are significantly different from purely hydrodynamic shocks and, in modeling this phenomenon numerically, it is important to compute radiative effects accurately. In this presentation, we examine approaches to modeling radiation transport by comparing two methods: (i) a computationally efficient approximation (multigroup flux-limited diffusion), currently in use in the CRASH code, with (ii) a more accurate discrete-ordinates treatment that is offered by the code PDT. We present a selection of updated results from a suite of comparison tests, showing both idealized problems and those that are representative of conditions found in the CRASH experiment. This research was supported by the DOE NNSA/ASC under the Predictive Science Academic Alliance Program by grant number DEFC52-08NA28616.

Myra, Eric S.; Hawkins, W. D.

2012-05-01