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Sample records for humans preliminary analyses

  1. SARDA HITL Preliminary Human Factors Measures and Analyses

    NASA Technical Reports Server (NTRS)

    Hyashi, Miwa; Dulchinos, Victoria

    2012-01-01

    Human factors data collected during the SARDA HITL Simulation Experiment include a variety of subjective measures, including the NASA TLX, questionnaire questions regarding situational awareness, advisory usefulness, UI usability, and controller trust. Preliminary analysis of the TLX data indicate that workload may not be adversely affected by use of the advisories, additionally, the controller's subjective ratings of the advisories may suggest acceptance of the tool.

  2. Preliminary analyses of scenarios for potential human interference for repositories in three salt formations

    SciTech Connect

    Not Available

    1985-10-01

    Preliminary analyses of scenarios for human interference with the performance of a radioactive waste repository in a deep salt formation are presented. The following scenarios are analyzed: (1) the U-Tube Connection Scenario involving multiple connections between the repository and the overlying aquifer system; (2) the Single Borehole Intrusion Scenario involving penetration of the repository by an exploratory borehole that simultaneously connects the repository with overlying and underlying aquifers; and (3) the Pressure Release Scenario involving inflow of water to saturate any void space in the repository prior to creep closure with subsequent release under near lithostatic pressures following creep closure. The methodology to evaluate repository performance in these scenarios is described and this methodology is applied to reference systems in three candidate formations: bedded salt in the Palo Duro Basin, Texas; bedded salt in the Paradox Basin, Utah; and the Richton Salt Dome, Mississippi, of the Gulf Coast Salt Dome Basin.

  3. Preliminary analyses of the Heliothis virescens transcriptome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Generation and analysis of genomic resources for the tobacco budworm, Heliothis virescens, are necessary for detailed functional genomic studies of the physiology and biochemistry of this highly destructive pest. In this study we present preliminary analyses of the ~45,000 publicly available H. vir...

  4. Finite element analyses of CCAT preliminary design

    NASA Astrophysics Data System (ADS)

    Sarawit, Andrew T.; Kan, Frank W.

    2014-07-01

    This paper describes the development of the CCAT telescope finite element model (FEM) and the analyses performed to support the preliminary design work. CCAT will be a 25 m diameter telescope operating in the 0.2 to 2 mm wavelength range. It will be located at an elevation of 5600 m on Cerro Chajnantor in Northern Chile, near ALMA. The telescope will be equipped with wide-field cameras and spectrometers mounted at the two Nasmyth foci. The telescope will be inside an enclosure to protect it from wind buffeting, direct solar heating, and bad weather. The main structures of the telescope include a steel Mount and a carbon-fiber-reinforced-plastic (CFRP) primary truss. The finite element model developed in this study was used to perform modal, frequency response, seismic response spectrum, stress, and deflection analyses of telescope. Modal analyses of telescope were performed to compute the structure natural frequencies and mode shapes and to obtain reduced order modal output at selected locations in the telescope structure to support the design of the Mount control system. Modal frequency response analyses were also performed to compute transfer functions at these selected locations. Seismic response spectrum analyses of the telescope subject to the Maximum Likely Earthquake were performed to compute peak accelerations and seismic demand stresses. Stress analyses were performed for gravity load to obtain gravity demand stresses. Deflection analyses for gravity load, thermal load, and differential elevation drive torque were performed so that the CCAT Observatory can verify that the structures meet the stringent telescope surface and pointing error requirements.

  5. Preliminary Framework for Human-Automation Collaboration

    SciTech Connect

    Oxstrand, Johanna Helene; Le Blanc, Katya Lee; Spielman, Zachary Alexander

    2015-09-01

    The Department of Energy’s Advanced Reactor Technologies Program sponsors research, development and deployment activities through its Next Generation Nuclear Plant, Advanced Reactor Concepts, and Advanced Small Modular Reactor (aSMR) Programs to promote safety, technical, economical, and environmental advancements of innovative Generation IV nuclear energy technologies. The Human Automation Collaboration (HAC) Research Project is located under the aSMR Program, which identifies developing advanced instrumentation and controls and human-machine interfaces as one of four key research areas. It is expected that the new nuclear power plant designs will employ technology significantly more advanced than the analog systems in the existing reactor fleet as well as utilizing automation to a greater extent. Moving towards more advanced technology and more automation does not necessary imply more efficient and safer operation of the plant. Instead, a number of concerns about how these technologies will affect human performance and the overall safety of the plant need to be addressed. More specifically, it is important to investigate how the operator and the automation work as a team to ensure effective and safe plant operation, also known as the human-automation collaboration (HAC). The focus of the HAC research is to understand how various characteristics of automation (such as its reliability, processes, and modes) effect an operator’s use and awareness of plant conditions. In other words, the research team investigates how to best design the collaboration between the operators and the automated systems in a manner that has the greatest positive impact on overall plant performance and reliability. This report addresses the Department of Energy milestone M4AT-15IN2302054, Complete Preliminary Framework for Human-Automation Collaboration, by discussing the two phased development of a preliminary HAC framework. The framework developed in the first phase was used as the

  6. Preliminary neutron crystallographic study of human transthyretin

    PubMed Central

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

    2011-01-01

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

  7. 76 FR 39399 - Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Notice of Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-06

    ... AGENCY Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Notice of Availability... availability of EPA's preliminary human health risk assessment for the registration review of chlorpyrifos and... comprehensive preliminary human health risk assessment for all chlorpyrifos uses. After reviewing...

  8. 76 FR 52945 - Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Extension of Comment...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-24

    ... AGENCY Chlorpyrifos Registration Review; Preliminary Human Health Risk Assessment; Extension of Comment... availability of the chlorpyrifos registration review; preliminary human health risk assessment. This document... for the chlorpyrifos reregistration review, preliminary human health risk assessment, established...

  9. Preliminary characterization of human skin microbiome in healthy Egyptian individuals.

    PubMed

    Ramadan, M; Solyman, S; Taha, M; Hanora, A

    2016-01-01

    Human skin is a large, complex ecosystem that harbors diverse microbial communities. The rapid advances in molecular techniques facilitate the exploration of skin associated bacterial populations. The objective of this study was to perform a preliminary characterization of skin associated bacterial populations in Egyptian individuals. Samples were collected from five healthy subjects from two skin sites; Antecubital Fossa (AF) and Popliteal Fossa (PF). Genomic DNA was extracted and used to amplify bacterial 16S rRNA genes which were sequenced on Illumina MiSeq platform. The two sites showed distinct diversity where PF was more diverse than AF. Taxonomic analysis of sequences revealed four main phyla Proteobacteria, Firmicutes, Actinobacteria and Deinococcus-Thermus, with Proteobacteria presenting the highest diversity. Klebsiella, Bacillus, Pseudomonas and Escherichia were the most predominant genera. Our data suggest that environmental factors can shape the composition of the skin microbiome in certain geographical regions. This study presents a new insight for subsequent analyses of human microbiome in Egypt. PMID:27545210

  10. Chemical analyses of rocks, minerals, and detritus, Yucca Mountain--Preliminary report, special report No. 11

    SciTech Connect

    Hill, C.A.; Livingston, D.E.

    1993-09-01

    This chemical analysis study is part of the research program of the Yucca Mountain Project intended to provide the State of Nevada with a detailed assessment of the geology and geochemistry of Yucca Mountain and adjacent regions. This report is preliminary in the sense that more chemical analyses may be needed in the future and also in the sense that these chemical analyses should be considered as a small part of a much larger geological data base. The interpretations discussed herein may be modified as that larger data base is examined and established. All of the chemical analyses performed to date are shown in Table 1. There are three parts to this table: (1) trace element analyses on rocks (limestone and tuff) and minerals (calcite/opal), (2) rare earth analyses on rocks (tuff) and minerals (calcite/opal), and (3) major element analyses + CO{sub 2} on rocks (tuff) and detritus sand. In this report, for each of the three parts of the table, the data and its possible significance will be discussed first, then some overall conclusions will be made, and finally some recommendations for future work will be offered.

  11. Template for Performing Human Reliability Analyses, Lesson Plans

    SciTech Connect

    Hunnaman, W., I. B. Wall

    2002-06-30

    Probabilistic Safety Analyses incorporate Human Reliability Assessment (HRA) to account for possible errors by a nuclear power plant operating crew both prior to and during postulated accidents. Studies have shown that human errors are large contributors to the likelihood of such accidents. A cadre of experts has developed HRA technology by applying it in many risk studies. The report provides insights to non-experts for application of HRA concepts in to specific nuclear plant PSAs.

  12. Human excimer laser corneal surgery: preliminary report.

    PubMed Central

    L'Esperance, F A; Taylor, D M; Del Pero, R A; Roberts, A; Gigstad, J; Stokes, M T; Warner, J W; Telfair, W B; Martin, C A; Yoder, P R

    1988-01-01

    The first human trial utilizing the argon fluoride excimer laser at 193 nm to produce a superficial keratectomy in ten human eyes has been described with the histopathological evaluation of four eyes and the longer gross appearance of six eyes at intervals extending to 10 months post-excimer laser treatment. The process of laser superficial keratectomy has proved to be one of the promising areas of surgical intervention for reconstructive or refractive keratoplasty in the future. Intensive investigations need to be undertaken on the corneal wound healing process following laser ablation as well as the nature, and long-term stability of the corneal excisions or induced refractive corrections. It is essential that the optimal laser parameters be established for the various refractive corrections and other corneal surgical techniques, and that pathophysiologic and histopathologic changes that have been induced by the excimer laser-corneal tissue interaction in animals and humans be critically and extensively analyzed. Images FIGURE 1 FIGURE 19 A FIGURE 19 B FIGURE 20 A FIGURE 20 B FIGURE 21 A FIGURE 21 B FIGURE 22 A FIGURE 22 B FIGURE 23 FIGURE 24 FIGURE 25 FIGURE 26 FIGURE 27 FIGURE 28 FIGURE 29 A FIGURE 29 B FIGURE 29 C FIGURE 29 D FIGURE 30 A FIGURE 30 B FIGURE 31 A FIGURE 31 B FIGURE 32 FIGURE 33 FIGURE 34 FIGURE 35 FIGURE 36 FIGURE 37 A FIGURE 37 B FIGURE 37 C FIGURE 38 A FIGURE 38 B FIGURE 39 A FIGURE 39 B FIGURE 39 C FIGURE 40 A FIGURE 40 B PMID:2979049

  13. Kinematic and Moisture Environments of Convective Systems During TRMM-LBA: Preliminary Sounding Analyses

    NASA Technical Reports Server (NTRS)

    Halverson, J. B.; Rickenbach, T.; Pierce, H.; Roy, B.; Ferreira, R. N.; Fisch, G.; Einaudi, Franco (Technical Monitor)

    2000-01-01

    Preliminary radiosonde data are analyzed from a four station observation network that operated during TRMM-LBA. These data, which are undergoing quality control, are used to construct mean vertical profiles and time-height sections of u- and v- wind components, and also filtered time series analyses of layer mean relative humidity. Trends are identified in the humidity data which appear similar at all sites, and correlate well with multi-week changes in wind regime identified by Rickenbach et al. Higher-frequency modes of variation (3-5 day) also occur in the humidity and upper tropospheric winds and are spatially coherent among the four locations. The causes of these variations are explored, including interactions among upper tropospheric synoptic features. Finally, an attempt is made to relate the general morphology of convective systems to the vertical shear structure and thermodynamic changes that accompany contrasting wind regimes.

  14. T/H and transient analyses to confirm EFIT preliminary design

    NASA Astrophysics Data System (ADS)

    Meloni, P.; Bandini, G.; Polidori, M.

    2008-06-01

    One of the main objectives of the EUROTRANS Integral Project is the design of a several hundreds MWth transmutator based on the accelerator driven system (ADS) concept. The preliminary layout of European Facility for Industrial Transmutation (EFIT) has started with a set of basic options derived from the previous ADS demo design (PDS-XADS) with the adoption of U-free fuel instead of MOX and taking into account the economic requirements needed for an industrial power plant. To support the project, a thermal-hydraulic numerical model of the reactor has been developed for the RELAP5 system code with the support of multidimensional SIMMER code to improve the representation of the natural circulation paths in the reactor vessel. The presented analyses, addressed to verify the capability of EFIT to face up the high power densities and temperatures, have allowed a first positive evaluation of the inherent safety behavior of the plant mainly relying on the natural circulation.

  15. Preliminary Results of Ancillary Safety Analyses Supporting TREAT LEU Conversion Activities

    SciTech Connect

    Brunett, A. J.; Fei, T.; Strons, P. S.; Papadias, D. D.; Hoffman, E. A.; Kontogeorgakos, D. C.; Connaway, H. M.; Wright, A. E.

    2015-10-01

    Report (FSAR) [3]. Depending on the availability of historical data derived from HEU TREAT operation, results calculated for the LEU core are compared to measurements obtained from HEU TREAT operation. While all analyses in this report are largely considered complete and have been reviewed for technical content, it is important to note that all topics will be revisited once the LEU design approaches its final stages of maturity. For most safety significant issues, it is expected that the analyses presented here will be bounding, but additional calculations will be performed as necessary to support safety analyses and safety documentation. It should also be noted that these analyses were completed as the LEU design evolved, and therefore utilized different LEU reference designs. Preliminary shielding, neutronic, and thermal hydraulic analyses have been completed and have generally demonstrated that the various LEU core designs will satisfy existing safety limits and standards also satisfied by the existing HEU core. These analyses include the assessment of the dose rate in the hodoscope room, near a loaded fuel transfer cask, above the fuel storage area, and near the HEPA filters. The potential change in the concentration of tramp uranium and change in neutron flux reaching instrumentation has also been assessed. Safety-significant thermal hydraulic items addressed in this report include thermally-induced mechanical distortion of the grid plate, and heating in the radial reflector.

  16. Multitemporal satellite data analyses for archaeological mark detection: preliminary results in Italy and Argentina

    NASA Astrophysics Data System (ADS)

    Lasaponara, Rosa; Masini, Nicola

    2014-05-01

    within Basilicata and Puglia Region, southern Patagonia and Payunia-Campo Volcanicos Liancanelo e PayunMatru respectively, in Italy and Argentina. We focused our attention on diverse surfaces and soil types in different periods of the year in order to assess the capabilities of both optical and radar data to detect archaeological marks in different ecosystems and seasons. We investigated not only crop culture during the "favourable vegetative period" to enhance the presence of subsurface remains but also the "spectral response" of spontaneous, sparse herbaceous covers during periods considered and expected to be less favourable (as for example summer and winter) for this type of investigation. The main interesting results were the capability of radar (cosmoskymed) and multispectral optical data satellite data (Pleiades, Quickbird, Geoeye) to highlight the presence of structures below the surface even (i) in during period of years generally considered not "suitable for crop mark investigations" and even (ii) in areas only covered by sparse, spontaneous herbaceous plants in several test sites investigate din both Argentine and Italian areas of interest. Preliminary results conducted in both Italian and Argentina sites pointed out that Earth Observation (EO) technology can be successfully used for extracting useful information on traces the past human activities still fossilized in the modern landscape in different ecosystems and seasons. Moreover the multitemporal analyses of satellite data can fruitfully applied to: (i) improve knowledge, (ii) support monitoring of natural and cultural site, (iii) assess natural and man-made risks including emerging threats to the heritage sites. References Lasaponara R, N Masini 2009 Full-waveform Airborne Laser Scanning for the detection of medieval archaeological microtopographic relief Journal of Cultural Heritage 10, e78-e82 Ciminale M, D Gallo, R Lasaponara, N Masini 2009 A multiscale approach for reconstructing archae

  17. 9.4T Human MRI: Preliminary Results

    PubMed Central

    Vaughan, Thomas; DelaBarre, Lance; Snyder, Carl; Tian, Jinfeng; Akgun, Can; Shrivastava, Devashish; Liu, Wanzahn; Olson, Chris; Adriany, Gregor; Strupp, John; Andersen, Peter; Gopinath, Anand; van de Moortele, Pierre-Francois; Garwood, Michael; Ugurbil, Kamil

    2014-01-01

    This work reports the preliminary results of the first human images at the new high-field benchmark of 9.4T. A 65-cm-diameter bore magnet was used together with an asymmetric 40-cm-diameter head gradient and shim set. A multichannel transmission line (transverse electromagnetic (TEM)) head coil was driven by a programmable parallel transceiver to control the relative phase and magnitude of each channel independently. These new RF field control methods facilitated compensation for RF artifacts attributed to destructive interference patterns, in order to achieve homogeneous 9.4T head images or localize anatomic targets. Prior to FDA investigational device exemptions (IDEs) and internal review board (IRB)-approved human studies, preliminary RF safety studies were performed on porcine models. These data are reported together with exit interview results from the first 44 human volunteers. Although several points for improvement are discussed, the preliminary results demonstrate the feasibility of safe and successful human imaging at 9.4T. PMID:17075852

  18. Multitemporal satellite data analyses for archaeological mark detection: preliminary results in Italy and Argentina

    NASA Astrophysics Data System (ADS)

    Lasaponara, Rosa; Masini, Nicola

    2014-05-01

    within Basilicata and Puglia Region, southern Patagonia and Payunia-Campo Volcanicos Liancanelo e PayunMatru respectively, in Italy and Argentina. We focused our attention on diverse surfaces and soil types in different periods of the year in order to assess the capabilities of both optical and radar data to detect archaeological marks in different ecosystems and seasons. We investigated not only crop culture during the "favourable vegetative period" to enhance the presence of subsurface remains but also the "spectral response" of spontaneous, sparse herbaceous covers during periods considered and expected to be less favourable (as for example summer and winter) for this type of investigation. The main interesting results were the capability of radar (cosmoskymed) and multispectral optical data satellite data (Pleiades, Quickbird, Geoeye) to highlight the presence of structures below the surface even (i) in during period of years generally considered not "suitable for crop mark investigations" and even (ii) in areas only covered by sparse, spontaneous herbaceous plants in several test sites investigate din both Argentine and Italian areas of interest. Preliminary results conducted in both Italian and Argentina sites pointed out that Earth Observation (EO) technology can be successfully used for extracting useful information on traces the past human activities still fossilized in the modern landscape in different ecosystems and seasons. Moreover the multitemporal analyses of satellite data can fruitfully applied to: (i) improve knowledge, (ii) support monitoring of natural and cultural site, (iii) assess natural and man-made risks including emerging threats to the heritage sites. References Lasaponara R, N Masini 2009 Full-waveform Airborne Laser Scanning for the detection of medieval archaeological microtopographic relief Journal of Cultural Heritage 10, e78-e82 Ciminale M, D Gallo, R Lasaponara, N Masini 2009 A multiscale approach for reconstructing archaeological

  19. Global transcriptome analyses of human and murine terminal erythroid differentiation

    PubMed Central

    An, Xiuli; Schulz, Vincent P.; Li, Jie; Wu, Kunlu; Liu, Jing; Xue, Fumin; Hu, Jingping; Mohandas, Narla

    2014-01-01

    We recently developed fluorescence-activated cell sorting (FACS)-based methods to purify morphologically and functionally discrete populations of cells, each representing specific stages of terminal erythroid differentiation. We used these techniques to obtain pure populations of both human and murine erythroblasts at distinct developmental stages. RNA was prepared from these cells and subjected to RNA sequencing analyses, creating unbiased, stage-specific transcriptomes. Tight clustering of transcriptomes from differing stages, even between biologically different replicates, validated the utility of the FACS-based assays. Bioinformatic analyses revealed that there were marked differences between differentiation stages, with both shared and dissimilar gene expression profiles defining each stage within transcriptional space. There were vast temporal changes in gene expression across the differentiation stages, with each stage exhibiting unique transcriptomes. Clustering and network analyses revealed that varying stage-specific patterns of expression observed across differentiation were enriched for genes of differing function. Numerous differences were present between human and murine transcriptomes, with significant variation in the global patterns of gene expression. These data provide a significant resource for studies of normal and perturbed erythropoiesis, allowing a deeper understanding of mechanisms of erythroid development in various inherited and acquired erythroid disorders. PMID:24637361

  20. An Illumination Modeling System for Human Factors Analyses

    NASA Technical Reports Server (NTRS)

    Huynh, Thong; Maida, James C.; Bond, Robert L. (Technical Monitor)

    2002-01-01

    Seeing is critical to human performance. Lighting is critical for seeing. Therefore, lighting is critical to human performance. This is common sense, and here on earth, it is easily taken for granted. However, on orbit, because the sun will rise or set every 45 minutes on average, humans working in space must cope with extremely dynamic lighting conditions. Contrast conditions of harsh shadowing and glare is also severe. The prediction of lighting conditions for critical operations is essential. Crew training can factor lighting into the lesson plans when necessary. Mission planners can determine whether low-light video cameras are required or whether additional luminaires need to be flown. The optimization of the quantity and quality of light is needed because of the effects on crew safety, on electrical power and on equipment maintainability. To address all of these issues, an illumination modeling system has been developed by the Graphics Research and Analyses Facility (GRAF) and Lighting Environment Test Facility (LETF) in the Space Human Factors Laboratory at NASA Johnson Space Center. The system uses physically based ray tracing software (Radiance) developed at Lawrence Berkeley Laboratories, a human factors oriented geometric modeling system (PLAID) and an extensive database of humans and environments. Material reflectivity properties of major surfaces and critical surfaces are measured using a gonio-reflectometer. Luminaires (lights) are measured for beam spread distribution, color and intensity. Video camera performances are measured for color and light sensitivity. 3D geometric models of humans and the environment are combined with the material and light models to form a system capable of predicting lighting conditions and visibility conditions in space.

  1. Preliminary measurements of contrast in polarimetric signatures of humans

    NASA Astrophysics Data System (ADS)

    Hodgkin, Van A.; Deaver, Dawne M.; LeMaster, Daniel A.

    2014-05-01

    The reflective bands in modern imaging, i.e., the visible through the short wave infrared (SWIR), have become very attractive for use in both daytime and low light target acquisition and surveillance. In addition, the nature of the target in modern conflict again includes the human body as a principle target. The spectral natures of the reflectivities of humans, their clothing, what they may be carrying, and the environments in which they are immersed, along with the spectral nature and strength of the light sources that illuminate them, have been the essential components of the contrasts in the signatures that are used in models that predict probabilities of target acquisition and discrimination. What has been missing is the impact that polarization in these signatures can have on image contrast. This paper documents a preliminary investigation into the contrast in active and passive polarimetric signatures of humans holding two-handed objects in the SWIR.

  2. Uncertainty quantification for personalized analyses of human proximal femurs.

    PubMed

    Wille, Hagen; Ruess, Martin; Rank, Ernst; Yosibash, Zohar

    2016-02-29

    Computational models for the personalized analysis of human femurs contain uncertainties in bone material properties and loads, which affect the simulation results. To quantify the influence we developed a probabilistic framework based on polynomial chaos (PC) that propagates stochastic input variables through any computational model. We considered a stochastic E-ρ relationship and a stochastic hip contact force, representing realistic variability of experimental data. Their influence on the prediction of principal strains (ϵ1 and ϵ3) was quantified for one human proximal femur, including sensitivity and reliability analysis. Large variabilities in the principal strain predictions were found in the cortical shell of the femoral neck, with coefficients of variation of ≈40%. Between 60 and 80% of the variance in ϵ1 and ϵ3 are attributable to the uncertainty in the E-ρ relationship, while ≈10% are caused by the load magnitude and 5-30% by the load direction. Principal strain directions were unaffected by material and loading uncertainties. The antero-superior and medial inferior sides of the neck exhibited the largest probabilities for tensile and compression failure, however all were very small (pf<0.001). In summary, uncertainty quantification with PC has been demonstrated to efficiently and accurately describe the influence of very different stochastic inputs, which increases the credibility and explanatory power of personalized analyses of human proximal femurs. PMID:26873282

  3. Competing endogenous RNA and interactome bioinformatic analyses on human telomerase.

    PubMed

    Arancio, Walter; Pizzolanti, Giuseppe; Genovese, Swonild Ilenia; Baiamonte, Concetta; Giordano, Carla

    2014-04-01

    We present a classic interactome bioinformatic analysis and a study on competing endogenous (ce) RNAs for hTERT. The hTERT gene codes for the catalytic subunit and limiting component of the human telomerase complex. Human telomerase reverse transcriptase (hTERT) is essential for the integrity of telomeres. Telomere dysfunctions have been widely reported to be involved in aging, cancer, and cellular senescence. The hTERT gene network has been analyzed using the BioGRID interaction database (http://thebiogrid.org/) and related analysis tools such as Osprey (http://biodata.mshri.on.ca/osprey/servlet/Index) and GeneMANIA (http://genemania.org/). The network of interaction of hTERT transcripts has been further analyzed following the competing endogenous (ce) RNA hypotheses (messenger [m] RNAs cross-talk via micro [mi] RNAs) using the miRWalk database and tools (www.ma.uni-heidelberg.de/apps/zmf/mirwalk/). These analyses suggest a role for Akt, nuclear factor-κB (NF-κB), heat shock protein 90 (HSP90), p70/p80 autoantigen, 14-3-3 proteins, and dynein in telomere functions. Roles for histone acetylation/deacetylation and proteoglycan metabolism are also proposed. PMID:24713059

  4. Analyses of volatile organic compounds from human skin

    PubMed Central

    Gallagher, M.; Wysocki, C.J.; Leyden, J.J.; Spielman, A.I.; Sun, X.; Preti, G.

    2008-01-01

    Summary Background Human skin emits a variety of volatile metabolites, many of them odorous. Much previous work has focused upon chemical structure and biogenesis of metabolites produced in the axillae (underarms), which are a primary source of human body odour. Nonaxillary skin also harbours volatile metabolites, possibly with different biological origins than axillary odorants. Objectives To take inventory of the volatile organic compounds (VOCs) from the upper back and forearm skin, and assess their relative quantitative variation across 25 healthy subjects. Methods Two complementary sampling techniques were used to obtain comprehensive VOC profiles, viz., solid-phase micro extraction and solvent extraction. Analyses were performed using both gas chromatography/mass spectrometry and gas chromatography with flame photometric detection. Results Nearly 100 compounds were identified, some of which varied with age. The VOC profiles of the upper back and forearm within a subject were, for the most part, similar, although there were notable differences. Conclusions The natural variation in nonaxillary skin odorants described in this study provides a baseline of compounds we have identified from both endogenous and exogenous sources. Although complex, the profiles of volatile constituents suggest that the two body locations share a considerable number of compounds, but both quantitative and qualitative differences are present. In addition, quantitative changes due to ageing are also present. These data may provide future investigators of skin VOCs with a baseline against which any abnormalities can be viewed in searching for biomarkers of skin diseases. PMID:18637798

  5. Preliminary organic analyses of the DSDP /JOIDES/ cores - Legs V-IX.

    NASA Technical Reports Server (NTRS)

    Simoneit, B. R.; Burlingame, A. L.

    1972-01-01

    Descriptions of the methods used and results obtained in analyses of deep sea drilling cores. The analyses were performed in two phases (differing in degree of particularization) depending on the amount of core sample available. The results are presented in relation to the ages and to the fossil fauna and flora of the sediments.

  6. Human temporal lobe epilepsy analyses by tissue proteomics.

    PubMed

    Mériaux, Céline; Franck, Julien; Park, Dan Bi; Quanico, Jusal; Kim, Young Hye; Chung, Chun Kee; Park, Young Mok; Steinbusch, Harry; Salzet, Michel; Fournier, Isabelle

    2014-06-01

    Although there are many types of epilepsy, temporal lobe epilepsy (TLE) is probably in humans the most common and most often studied. TLE represents 40% of the total epilepsy form of the disease and is difficult to treat. Despite a wealth of descriptive data obtained from the disease history of patients, the EEG recording, imaging techniques, and histological studies, the epileptogenic process remains poorly understood. However, it is unlikely that a single factor or a single mechanism can cause many changes associated with this neuropathological phenomenon. MALDI mass spectrometry imaging (MSI) coupled to protein identification, because of its ability to study a wide range of molecules, appears to be suitable for the preparation of molecular profiles in TLE. Seven neuropeptides have been have been identified in Dental gyrus regions of the hippocampus in relation with TLE pathology. Shot-gun studies taking into account gender influence have been performed. Tissue microextraction from control (10) toward 10 TLE patients have been analyzed after trypsin digestion followed by separation on nanoLC coupled to LTQ orbitrap. From the shot-gun analyses, results confirmed the presence of specific neuropeptides precursors and receptors in TLE patients as well as proteins involved in axons regeneration including neurotrophins, ECM proteins, cell surface proteins, membrane proteins, G-proteins, cytoskeleton proteins and tumor suppressors. Among the tumor suppressors identified, the Leucine-rich glioma inactivated 1 (LGI1) protein was found. LGI1 gene recently been demonstrated being implicated in heritability of TLE. We have also demonstrate the presence a complete profile of tumor suppressors in TLE patients, 7 have been identified. Refining this analysis taken into account the gender influence in both control and in TLE reflected the presence of specific proteins between male and female and thus mechanisms in pathology development could be completely different. PMID:24449190

  7. Preliminary analyses of the excavation investigation experiments proposed for the exploratory shaft at Yucca Mountain, Nevada Test Site

    SciTech Connect

    Costin, L.S.; Bauer, S.J.

    1988-12-01

    The Yucca Mountain Project (YMP), is examining the feasibility of siting a repository for high-level nuclear waste at Yucca Mountain on and adjacent to the Nevada Test Site. Three excavation experiments, Shaft Convergence, Demonstration Breakout Rooms, and Sequential Drift Mining, will provide some of the data required to (1) assess the mechanical behavior of repository-size openings and (2) validate numerical models that may be used in the repository design process. In this report, the results of preliminary analyses of the three excavation experiments are presented. The major objective of these analyses was to provide some guidance to the experiment planners regarding the expected displacements and stresses near the experimental drifts so that selection and placement of instrumentation could be optimized. Further, successful completion of these analyses demonstrates the ability to model the experiments, given the simplifying assumptions presented. Limitations of the analyses performed and the experiments as currently designed are also discussed. Finally, the results of these analyses provided some indication of how the variation of some key geometric and material parameters would affect the predicted results. Once the experiment design is finalized and site-specific material data are collected, pretest predictive analyses will be conducted using the mechanical and material models that require validation. 15 refs., 123 figs., 13 tabs.

  8. Preliminary analyses of SIB-B radar data for recent Hawaii lava flows

    NASA Technical Reports Server (NTRS)

    Kaupp, V. H.; Derryberry, B. A.; Macdonald, H. C.; Gaddis, L. R.; Mouginis-Mark, P. J.

    1986-01-01

    The Shuttle Imaging Radar (SIR-B) experiment acquired two L-band (23 cm wavelength) radar images (at about 28 and 48 deg incidence angles) over the Kilauea Volcano area of southeastern Hawaii. Geologic analysis of these data indicates that, although aa lava flows and pyroclastic deposits can be discriminated, pahoehoe lava flows are not readily distinguished from surrounding low return materials. Preliminary analysis of data extracted from isolated flows indicates that flow type (i.e., aa or pahoehoe) and relative age can be determined from their basic statistics and illumination angle.

  9. Low Order Modeling Tools for Preliminary Pressure Gain Combustion Benefits Analyses

    NASA Technical Reports Server (NTRS)

    Paxson, Daniel E.

    2012-01-01

    Pressure gain combustion (PGC) offers the promise of higher thermodynamic cycle efficiency and greater specific power in propulsion and power systems. This presentation describes a model, developed under a cooperative agreement between NASA and AFRL, for preliminarily assessing the performance enhancement and preliminary size requirements of PGC components either as stand-alone thrust producers or coupled with surrounding turbomachinery. The model is implemented in the Numerical Propulsion Simulation System (NPSS) environment allowing various configurations to be examined at numerous operating points. The validated model is simple, yet physics-based. It executes quickly in NPSS, yet produces realistic results.

  10. On protection of Freedom's solar dynamic radiator from the orbital debris environment. Part 1: Preliminary analyses and testing

    NASA Technical Reports Server (NTRS)

    Rhatigan, Jennifer L.; Christiansen, Eric L.; Fleming, Michael L.

    1990-01-01

    A great deal of experimentation and analysis was performed to quantify penetration thresholds of components which will experience orbital debris impacts. Penetration was found to depend upon mission specific parameters such as orbital altitude, inclination, and orientation of the component; and upon component specific parameters such as material, density and the geometry particular to its shielding. Experimental results are highly dependent upon shield configuration and cannot be extrapolated with confidence to alternate shield configurations. Also, current experimental capabilities are limited to velocities which only approach the lower limit of predicted orbital debris velocities. Therefore, prediction of the penetrating particle size for a particular component having a complex geometry remains highly uncertain. An approach is described which was developed to assess on-orbit survivability of the solar dynamic radiator due to micrometeoroid and space debris impacts. Preliminary analyses are presented to quantify the solar dynamic radiator survivability, and include the type of particle and particle population expected to defeat the radiator bumpering (i.e., penetrate a fluid flow tube). Results of preliminary hypervelocity impact testing performed on radiator panel samples (in the 6 to 7 km/sec velocity range) are also presented. Plans for further analyses and testing are discussed. These efforts are expected to lead to a radiator design which will perform to requirements over the expected lifetime.

  11. On protection of Freedom's solar dynamic radiator from the orbital debris environment. Part 1. Preliminary analyses and testing

    SciTech Connect

    Rhatigan, J.L.; Christiansen, E.L.; Fleming, M.L.

    1990-01-01

    A great deal of experimentation and analysis was performed to quantify penetration thresholds of components which will experience orbital debris impacts. Penetration was found to depend upon mission specific parameters such as orbital altitude, inclination, and orientation of the component; and upon component specific parameters such as material, density and the geometry particular to its shielding. Experimental results are highly dependent upon shield configuration and cannot be extrapolated with confidence to alternate shield configurations. Also, current experimental capabilities are limited to velocities which only approach the lower limit of predicted orbital debris velocities. Therefore, prediction of the penetrating particle size for a particular component having a complex geometry remains highly uncertain. An approach is described which was developed to assess on-orbit survivability of the solar dynamic radiator due to micrometeoroid and space debris impacts. Preliminary analyses are presented to quantify the solar dynamic radiator survivability, and include the type of particle and particle population expected to defeat the radiator bumpering (i.e., penetrate a fluid flow tube). Results of preliminary hypervelocity impact testing performed on radiator panel samples (in the 6 to 7 km/sec velocity range) are also presented. Plans for further analyses and testing are discussed. These efforts are expected to lead to a radiator design which will perform to requirements over the expected lifetime.

  12. Preliminary analyses for perchlorate in selected natural materials and their derivative products

    USGS Publications Warehouse

    Orris, G.J.; Harvey, G.J.; Tsui, D.T.; Eldrige, J.E.

    2003-01-01

    Increasing concern about sources of perchlorate contamination in ground and surface waters has led to interest in identifying potential sources of natural perchlorate and products derived from these natural sources. To date, most perchlorate found in ground and surface waters has been attributed to its major uses as an oxidizer in solid propellants for rockets, in fireworks and other explosives, and a variety of other uses of man-made perchlorate salts. However, perchlorate found in the soils, surface water, and ground water of some locations cannot be linked to an anthropogenic source. This paper contains preliminary data on the detection and non-detection of perchlorate in a variety of natural materials and their products, including some fertilizer materials. These data were previously presented at two conferences; once in poster session and once orally (Harvey and others, 1999; Orris and others, 2000). Although the results presented here are included in a journal article awaiting publication, the lack of public information on this topic has led to repeated requests for the data used as the basis for our presentations in 1999 and 2000.

  13. NAA For Human Serum Analysis: Comparison With Conventional Analyses

    SciTech Connect

    Oliveira, Laura C.; Zamboni, Cibele B.; Medeiros, Jose A. G.; Azevedo, Maria R.

    2010-08-04

    Instrumental and Comparator methods of Neutron Activation Analysis (NAA) were applied to determine elements of clinical relevancy in serum samples of adult population (Sao Paulo city, Brazil). A comparison with the conventional analyses, Colorimetric for calcium, Titrymetric for chlorine and Ion Specific Electrode for sodium and potassium determination were also performed permitting a discussion about the performance of NAA methods for clinical chemistry research.

  14. COMPUTER MODEL OF HUMAN LUNG MORPHOLOGY TO COMPLEMENT SPECT ANALYSES

    EPA Science Inventory

    Aerosol therapy protocols could be improved if inhaled pharmacologic drugs were selectively deposited within the human lung. he targeted delivery to specific sites, such as receptors and sensitive airway cells, would enhance the efficacies of airborne pharmaceuticals. he high res...

  15. Genome-wide analyses of human perisylvian cerebral cortical patterning

    PubMed Central

    Abrahams, B. S.; Tentler, D.; Perederiy, J. V.; Oldham, M. C.; Coppola, G.; Geschwind, D. H.

    2007-01-01

    Despite the well established role of the frontal and posterior perisylvian cortices in many facets of human-cognitive specializations, including language, little is known about the developmental patterning of these regions in the human brain. We performed a genome-wide analysis of human cerebral patterning during midgestation, a critical epoch in cortical regionalization. A total of 345 genes were identified as differentially expressed between superior temporal gyrus (STG) and the remaining cerebral cortex. Gene ontology categories representing transcription factors were enriched in STG, whereas cell-adhesion and extracellular matrix molecules were enriched in the other cortical regions. Quantitative RT-PCR or in situ hybridization was performed to validate differential expression in a subset of 32 genes, most of which were confirmed. LIM domain-binding 1 (LDB1), which we show to be enriched in the STG, is a recently identified interactor of LIM domain only 4 (LMO4), a gene known to be involved in the asymmetric pattering of the perisylvian region in the developing human brain. Protocadherin 17 (PCDH17), a neuronal cell adhesion molecule, was highly enriched in focal regions of the human prefrontal cortex. Contactin associated protein-like 2 (CNTNAP2), in which mutations are known to cause autism, epilepsy, and language delay, showed a remarkable pattern of anterior-enriched cortical expression in human that was not observed in mouse or rat. These data highlight the importance of expression analysis of human brain and the utility of cross-species comparisons of gene expression. Genes identified here provide a foundation for understanding molecular aspects of human-cognitive specializations and the disorders that disrupt them. PMID:17978184

  16. Preliminary Performance Analyses of the Constellation Program ARES 1 Crew Launch Vehicle

    NASA Technical Reports Server (NTRS)

    Phillips, Mark; Hanson, John; Shmitt, Terri; Dukemand, Greg; Hays, Jim; Hill, Ashley; Garcia, Jessica

    2007-01-01

    By the time NASA's Exploration Systems Architecture Study (ESAS) report had been released to the public in December 2005, engineers at NASA's Marshall Space Flight Center had already initiated the first of a series of detailed design analysis cycles (DACs) for the Constellation Program Crew Launch Vehicle (CLV), which has been given the name Ares I. As a major component of the Constellation Architecture, the CLV's initial role will be to deliver crew and cargo aboard the newly conceived Crew Exploration Vehicle (CEV) to a staging orbit for eventual rendezvous with the International Space Station (ISS). However, the long-term goal and design focus of the CLV will be to provide launch services for a crewed CEV in support of lunar exploration missions. Key to the success of the CLV design effort and an integral part of each DAC is a detailed performance analysis tailored to assess nominal and dispersed performance of the vehicle, to determine performance sensitivities, and to generate design-driving dispersed trajectories. Results of these analyses provide valuable design information to the program for the current design as well as provide feedback to engineers on how to adjust the current design in order to maintain program goals. This paper presents a condensed subset of the CLV performance analyses performed during the CLV DAC-1 cycle. Deterministic studies include development of the CLV DAC-1 reference trajectories, identification of vehicle stage impact footprints, an assessment of launch window impacts to payload performance, and the computation of select CLV payload partials. Dispersion studies include definition of input uncertainties, Monte Carlo analysis of trajectory performance parameters based on input dispersions, assessment of CLV flight performance reserve (FPR), assessment of orbital insertion accuracy, and an assessment of bending load indicators due to dispersions in vehicle angle of attack and side slip angle. A short discussion of the various

  17. Stardust Interstellar Preliminary Examination V: XRF analyses of interstellar dust candidates at ESRF ID13

    NASA Astrophysics Data System (ADS)

    Brenker, Frank E.; Westphal, Andrew J.; Vincze, Laszlo; Burghammer, Manfred; Schmitz, Sylvia; Schoonjans, Tom; Silversmit, Geert; Vekemans, Bart; Allen, Carlton; Anderson, David; Ansari, Asna; Bajt, SašA.; Bastien, Ron K.; Bassim, Nabil; Bechtel, Hans A.; Borg, Janet; Bridges, John; Brownlee, Donald E.; Burchell, Mark; Butterworth, Anna L.; Changela, Hitesh; Cloetens, Peter; Davis, Andrew M.; Doll, Ryan; Floss, Christine; Flynn, George; Fougeray, Patrick; Frank, David R.; Gainsforth, Zack; Grün, Eberhard; Heck, Philipp R.; Hillier, Jon K.; Hoppe, Peter; Hudson, Bruce; Huth, Joachim; Hvide, Brit; Kearsley, Anton; King, Ashley J.; Lai, Barry; Leitner, Jan; Lemelle, Laurence; Leroux, Hugues; Leonard, Ariel; Lettieri, Robert; Marchant, William; Nittler, Larry R.; Ogliore, Ryan; Ong, Wei Ja; Postberg, Frank; Price, Mark C.; Sandford, Scott A.; Tresseras, Juan-Angel Sans; Simionovici, Alexandre S.; Solé, Vicente A.; Srama, Ralf; Stadermann, Frank; Stephan, Thomas; Sterken, Veerle J.; Stodolna, Julien; Stroud, Rhonda M.; Sutton, Steven; Trieloff, Mario; Tsou, Peter; Tsuchiyama, Akira; Tyliszczak, Tolek; Korff, Joshua; Wordsworth, Naomi; Zevin, Daniel; Zolensky, Michael E.

    2014-09-01

    Here, we report analyses by synchrotron X-ray fluorescence microscopy of the elemental composition of eight candidate impact features extracted from the Stardust Interstellar Dust Collector (SIDC). Six of the features were unambiguous tracks, and two were crater-like features. Five of the tracks are so-called "midnight" tracks—that is, they had trajectories consistent with an origin either in the interstellar dust stream or as secondaries from impacts on the Sample Return Capsule (SRC). In a companion paper reporting synchrotron X-ray diffraction analyses of ISPE candidates, we show that two of these particles contain natural crystalline materials: the terminal particle of track 30 contains olivine and spinel, and the terminal particle of track 34 contains olivine. Here, we show that the terminal particle of track 30, Orion, shows elemental abundances, normalized to Fe, that are close to CI values, and a complex, fine-grained structure. The terminal particle of track 34, Hylabrook, shows abundances that deviate strongly from CI, but shows little fine structure and is nearly homogenous. The terminal particles of other midnight tracks, 29 and 37, had heavy element abundances below detection threshold. A third, track 28, showed a composition inconsistent with an extraterrestrial origin, but also inconsistent with known spacecraft materials. A sixth track, with a trajectory consistent with secondary ejecta from an impact on one of the spacecraft solar panels, contains abundant Ce and Zn. This is consistent with the known composition of the glass covering the solar panel. Neither crater-like feature is likely to be associated with extraterrestrial materials. We also analyzed blank aerogel samples to characterize background and variability between aerogel tiles. We found significant differences in contamination levels and compositions, emphasizing the need for local background subtraction for accurate quantification.

  18. Genomewide Association Analyses of Electrophysiological Endophenotypes for Schizophrenia and Psychotic Bipolar Disorders: A Preliminary Report

    PubMed Central

    Hall, Mei-Hua; Chen, Chia-Yen; Cohen, Bruce M.; Spencer, Kevin M.; Levy, Deborah L.; Öngür, Dost; Smoller, Jordan W.

    2015-01-01

    Several event-related potentials (ERP), including P3, sensory gating (P50), and gamma oscillation, are robustly impaired in patients with schizophrenia (SCZ) and bipolar disorder (BIP). Although these ERPs are known to be heritable, little is known about the specific genetic loci involved and the degree to which they overlap with loci influencing mood and psychotic disorders. In the present study, we conducted GWAS to a) identify common variants associated with ERP endophenotypes, and b) construct polygenic risk scores (PRS) to examine overlap between genetic components of ERPs and mood and psychotic disorders. The sample consisted of 271 patients with SCZ or psychotic BIP diagnosis and 128 controls for whom ERP and genomewide data were available. GWAS were conducted using the full sample. PRS, derived from the Psychiatric Genomics Consortium (PGC) analyses of SCZ, BIP, and major depressive disorder were applied to each ERP phenotype. We identified a region on chromosome 14 that was significantly associated with sensory gating (peak SNP rs10132223, P = 1.27 × 10−9). This locus has not been previously associated with psychotic illness in PGC-GWAS. In the PRS analyses, patients with a higher load of SCZ risk alleles had reduced gamma response whereas patients with a higher load of BIP risk alleles had smaller P3 amplitude. We observed a genomewide significant locus on chromosome 14 for P50. This locus may influence P50 but not psychotic illness. Among patients with psychotic illness, PRS results indicated genetic overlap between SCZ loci and gamma oscillation and between BIP loci and P3 amplitude. PMID:25740047

  19. Preliminary analyses of space radiation protection for lunar base surface systems

    NASA Technical Reports Server (NTRS)

    Nealy, John E.; Wilson, John W.; Townsend, Lawrence W.

    1989-01-01

    Radiation shielding analyses are performed for candidate lunar base habitation modules. The study primarily addresses potential hazards due to contributions from the galactic cosmic rays. The NASA Langley Research Center's high energy nucleon and heavy ion transport codes are used to compute propagation of radiation through conventional and regolith shield materials. Computed values of linear energy transfer are converted to biological dose-equivalent using quality factors established by the International Commision of Radiological Protection. Special fluxes of heavy charged particles and corresponding dosimetric quantities are computed for a series of thicknesses in various shield media and are used as an input data base for algorithms pertaining to specific shielded geometries. Dosimetric results are presented as isodose contour maps of shielded configuration interiors. The dose predictions indicate that shielding requirements are substantial, and an abbreviated uncertainty analysis shows that better definition of the space radiation environment as well as improvement in nuclear interaction cross-section data can greatly increase the accuracy of shield requirement predictions.

  20. Biochemical analyses of the cement float of the goose barnacle Dosima fascicularis--a preliminary study.

    PubMed

    Zheden, Vanessa; Klepal, Waltraud; von Byern, Janek; Bogner, Fabian Robert; Thiel, Karsten; Kowalik, Thomas; Grunwald, Ingo

    2014-09-01

    The goose barnacle Dosima fascicularis produces an excessive amount of adhesive (cement), which has a double function, being used for attachment to various substrata and also as a float (buoy). This paper focuses on the chemical composition of the cement, which has a water content of 92%. Scanning electron microscopy with EDX was used to measure the organic elements C, O and N in the foam-like cement. Vibrational spectroscopy (FTIR, Raman) provided further information about the overall secondary structure, which tended towards a β-sheet. Disulphide bonds could not be detected by Raman spectroscopy. The cystine, methionine, histidine and tryptophan contents were each below 1% in the cement. Analyses of the cement revealed a protein content of 84% and a total carbohydrate content of 1.5% in the dry cement. The amino acid composition, 1D/2D-PAGE and MS/MS sequence analysis revealed a de novo set of peptides/proteins with low homologies with other proteins such as the barnacle cement proteins, largely with an acidic pI between 3.5 and 6.0. The biochemical composition of the cement of D. fascicularis is similar to that of other barnacles, but it shows interesting variations. PMID:25237772

  1. Preliminary analyses of WL experiment No. 701, space environment effects on operating fiber optic systems

    NASA Technical Reports Server (NTRS)

    Taylor, E. W.; Berry, J. N.; Sanchez, A. D.; Padden, R. J.; Chapman, S. P.

    1992-01-01

    A brief overview of the analyses performed to date on WL Experiment-701 is presented. Four active digital fiber optic links were directly exposed to the space environment for a period of 2114 days. The links were situated aboard the Long Duration Exposure Facility (LDEF) with the cabled, single fiber windings atop an experimental tray containing instrumentation for exercising the experiment in orbit. Despite the unplanned and prolonged exposure to trapped and galactic radiation, wide temperature extremes, atomic oxygen interactions, and micro-meteorite and debris impacts, in most instances the optical data links performed well within the experimental limits. Analysis of the recorded orbital data clearly indicates that fiber optic applications in space will meet with success. Ongoing tests and analysis of the experiment at the Phillips Laboratory's Optoelectronics Laboratory will expand this premise, and establish the first known and extensive database of active fiber optic link performance during prolonged space exposure. WL Exp-701 was designed as a feasibility demonstration for fiber optic technology in space applications, and to study the performance of operating fiber systems exposed to space environmental factors such as galactic radiation, and wide temperature cycling. WL Exp-701 is widely acknowledged as a benchmark accomplishment that clearly demonstrates, for the first time, that fiber optic technology can be successfully used in a variety of space applications.

  2. Compositional diversity of the lunar North Pole: Preliminary analyses of Galileo SSI data

    NASA Technical Reports Server (NTRS)

    Pieters, C. M.; Belton, M.; Head, James W.; Greeley, R.; Mcewen, A.; Fischer, E. M.; Sunshine, J. M.; Klaasen, K.; Plutchak, J.; Neukum, G.

    1993-01-01

    In December 1992, the Galileo spacecraft passed through the Earth-Moon system for its final gravity assist to Jupiter. The SSI camera obtained several 6-color mosaics of the lunar north polar region and the sunlit nearside and eastern limb at approximately 1.3 km/pixel. Initial analyses have concentrated on the north polar areas to assess the composition of the crust in that region. Representative 6-color calibration SSI spectra (typically 5 x 5 pixels) are shown. Photometric corrections have not yet been applied, and all spectra are scaled to unity at 0.56 microns. The data were first calibrated relative to MS2, a standard are in Mare Serenitatis (18.7 deg N, 21.5 deg E), and the top four plots of highlands, highland craters, maria, and mare craters are displayed relative to MS2. SSI spectra of areas measured with telescopic data (mare MT1/MS2 and mare crater MSA/MS2) agree well with previous data, confirming that the calibration procedures and SSI data are spectrally accurate. The bottom three plots of craters/sun have been calibrated to reflectance using previously obtained telescopic spectra of Apollo 16/MS2 (shown with Highlands/MS2) and laboratory spectra of mature Apollo 16 soil (shown for reference with the Highland Craters/Sun). Although some variations in these spectra mimic previously observed spectra of lunar terrains, several characteristics are unusual. Familiar and unfamiliar properties are observed in these northern latitudes and both types merit further investigation in their geologic context.

  3. Crucial role of detailed function, task, timeline, link and human vulnerability analyses in HRA

    SciTech Connect

    Ryan, T.G.; Haney, L.N.; Ostrom, L.T.

    1992-10-01

    This paper addresses one major cause for large uncertainties in human reliability analysis (HRA) results, that is, an absence of detailed function, task, timeline, link and human vulnerability analyses. All too often this crucial step in the HRA process is done in a cursory fashion using word of mouth or written procedures which themselves may incompletely or inaccurately represent the human action sequences and human error vulnerabilities being analyzed. The paper examines the potential contributions these detailed analyses can make in achieving quantitative and qualitative HRA results which are: (1) creditable, that is, minimize uncertainty, (2) auditable, that is, systematically linking quantitative results and qualitative information from which the results are derived, (3) capable of supporting root cause analyses on human reliability factors determined to be major contributors to risk, and (4) capable of repeated measures and being combined with similar results from other analyses to examine HRA issues transcending individual systems and facilities. Based on experience analyzing test and commercial nuclear reactors, and medical applications of nuclear technology, an iterative process is suggested for doing detailed function, task, timeline, link and human vulnerability analyses using documentation reviews, open-ended and structured interviews, direct observations, and group techniques. Finally, the paper concludes that detailed analyses done in this manner by knowledgeable human factors practitioners, can contribute significantly to the credibility, auditability, causal factor analysis, and combining goals of the HRA.

  4. Crucial role of detailed function, task, timeline, link and human vulnerability analyses in HRA. [Human Reliability Analysis (HRA)

    SciTech Connect

    Ryan, T.G.; Haney, L.N.; Ostrom, L.T.

    1992-01-01

    This paper addresses one major cause for large uncertainties in human reliability analysis (HRA) results, that is, an absence of detailed function, task, timeline, link and human vulnerability analyses. All too often this crucial step in the HRA process is done in a cursory fashion using word of mouth or written procedures which themselves may incompletely or inaccurately represent the human action sequences and human error vulnerabilities being analyzed. The paper examines the potential contributions these detailed analyses can make in achieving quantitative and qualitative HRA results which are: (1) creditable, that is, minimize uncertainty, (2) auditable, that is, systematically linking quantitative results and qualitative information from which the results are derived, (3) capable of supporting root cause analyses on human reliability factors determined to be major contributors to risk, and (4) capable of repeated measures and being combined with similar results from other analyses to examine HRA issues transcending individual systems and facilities. Based on experience analyzing test and commercial nuclear reactors, and medical applications of nuclear technology, an iterative process is suggested for doing detailed function, task, timeline, link and human vulnerability analyses using documentation reviews, open-ended and structured interviews, direct observations, and group techniques. Finally, the paper concludes that detailed analyses done in this manner by knowledgeable human factors practitioners, can contribute significantly to the credibility, auditability, causal factor analysis, and combining goals of the HRA.

  5. Overview of a Preliminary Destination Mission Concept for a Human Orbital Mission to the Martial Moons

    NASA Technical Reports Server (NTRS)

    Mazanek, D. D.; Abell, P. A.; Antol, J.; Barbee, B. W.; Beaty, D. W.; Bass, D. S.; Castillo-Rogez, J. C.; Coan, D. A.; Colaprete, A.; Daugherty, K. J.; Drake, B. G.; Earle, K. D.; Graham, L. D.; Hembree, R. M.; Hoffman, S. J.; Jefferies, S. A.; Lupisella, M. L.; Reeves, David M.

    2012-01-01

    The National Aeronautics and Space Administration s Human Spaceflight Architecture Team (HAT) has been developing a preliminary Destination Mission Concept (DMC) to assess how a human orbital mission to one or both of the Martian moons, Phobos and Deimos, might be conducted as a follow-on to a human mission to a near-Earth asteroid (NEA) and as a possible preliminary step prior to a human landing on Mars. The HAT Mars-Phobos-Deimos (MPD) mission also permits the teleoperation of robotic systems by the crew while in the Mars system. The DMC development activity provides an initial effort to identify the science and exploration objectives and investigate the capabilities and operations concepts required for a human orbital mission to the Mars system. In addition, the MPD Team identified potential synergistic opportunities via prior exploration of other destinations currently under consideration.

  6. Analyses of the Effects of Global Change on Human Health and Welfare and Human Systems (Sap 4.6)

    EPA Science Inventory

    EPA has released the draft document, Analyses of the Effects of Global Change on Human Health and Welfare and Human Systems for public review and comment. The notice has been posted by NOAA/ Department of Commerce on behalf of the U.S. Climate Change Science Program (CCS...

  7. Analyses of the Effects of Global Change on Human Health and Welfare and Human Systems (SAP 4.6)

    EPA Science Inventory

    EPA has announced the final report entitled, Synthesis and Assessment Product 4.6: Analyses of the Effects of Global Change on Human Health and Welfare and Human Systems . This Synthesis and Assessment Product 4.6 (SAP 4.6) focuses on impacts of global climate change, es...

  8. Statistical analyses in trials for the comprehensive understanding of organogenesis and histogenesis in humans and mice.

    PubMed

    Otani, Hiroki; Udagawa, Jun; Naito, Kanta

    2016-06-01

    Statistical analyses based on the quantitative data from real multicellular organisms are useful as inductive-type studies to analyse complex morphogenetic events in addition to deductive-type analyses using mathematical models. Here, we introduce several of our trials for the statistical analysis of organogenesis and histogenesis of human and mouse embryos and foetuses. Multidimensional scaling has been applied to prove the existence and examine the mode of interkinetic nuclear migration, a regulatory mechanism of stem cell proliferation/differentiation in epithelial tubular tissues. Several statistical methods were used on morphometric data from human foetuses to establish the multidimensional standard growth curve and to describe the relation among the developing organs and body parts. Although the results are still limited, we show that these analyses are not only useful to understand the normal and abnormal morphogenesis in humans and mice but also to provide clues that could correlate aspects of prenatal developmental events with postnatal diseases. PMID:26935132

  9. Crystallization and Preliminary Diffraction Analysis of Truncated Human Pleckstrin

    SciTech Connect

    S Jackson; S Sugiman-Marangos; K Cheung; M Junop

    2011-12-31

    Pleckstrin is a major substrate of protein kinase C in platelets and leukocytes and appears to play an important role in exocytosis through a currently unknown mechanism. Pleckstrin function is regulated by phosphorylation, which is thought to cause dissociation of pleckstrin dimers, thereby facilitating phosphoinositide interactions and membrane localization. Evidence also exists suggesting that phosphorylation causes a subtle conformational change in pleckstrin. Structural studies of pleckstrin have been initiated in order to characterize these structural changes and ultimately advance understanding of pleckstrin function. Here, the crystallization and preliminary X-ray diffraction analysis of a truncated version of pleckstrin consisting of the N-terminal PH domain, the protein kinase C phosphorylation sites and the DEP domain (NPHDEP) are reported. In addition, the oligomeric state and phospholipid-binding properties of NPHDEP were analyzed. This work demonstrates that NPHDEP behaves as a monomer in solution and suggests that all three pleckstrin domains contribute to the dimerization interface. Furthermore, based on the binding properties of NPHDEP, the C-terminal PH domain appears to increase the specificity of pleckstrin for phosphoinositides. This work represents a significant step towards determining the structure of pleckstrin.

  10. Preliminary Work Domain Analysis for Human Extravehicular Activity

    NASA Technical Reports Server (NTRS)

    McGuire, Kerry; Miller, Matthew; Feigh, Karen

    2015-01-01

    A work domain analysis (WDA) of human extravehicular activity (EVA) is presented in this study. A formative methodology such as Cognitive Work Analysis (CWA) offers a new perspective to the knowledge gained from the past 50 years of living and working in space for the development of future EVA support systems. EVA is a vital component of human spaceflight and provides a case study example of applying a work domain analysis (WDA) to a complex sociotechnical system. The WDA presented here illustrates how the physical characteristics of the environment, hardware, and life support systems of the domain guide the potential avenues and functional needs of future EVA decision support system development.

  11. Preliminary Exploration of Adaptive State Predictor Based Human Operator Modeling

    NASA Technical Reports Server (NTRS)

    Trujillo, Anna C.; Gregory, Irene M.

    2012-01-01

    Control-theoretic modeling of the human operator dynamic behavior in manual control tasks has a long and rich history. In the last two decades, there has been a renewed interest in modeling the human operator. There has also been significant work on techniques used to identify the pilot model of a given structure. The purpose of this research is to attempt to go beyond pilot identification based on collected experimental data and to develop a predictor of pilot behavior. An experiment was conducted to quantify the effects of changing aircraft dynamics on an operator s ability to track a signal in order to eventually model a pilot adapting to changing aircraft dynamics. A gradient descent estimator and a least squares estimator with exponential forgetting used these data to predict pilot stick input. The results indicate that individual pilot characteristics and vehicle dynamics did not affect the accuracy of either estimator method to estimate pilot stick input. These methods also were able to predict pilot stick input during changing aircraft dynamics and they may have the capability to detect a change in a subject due to workload, engagement, etc., or the effects of changes in vehicle dynamics on the pilot.

  12. Characterizing human retinotopic mapping with conformal geometry: a preliminary study

    NASA Astrophysics Data System (ADS)

    Ta, Duyan; Shi, Jie; Barton, Brian; Brewer, Alyssa; Lu, Zhong-Lin; Wang, Yalin

    2014-03-01

    Functional magnetic resonance imaging (fMRI) has been widely used to measure the retinotopic organization of early visual cortex in the human brain. Previous studies have identified multiple visual field maps (VFMs) based on statistical analysis of fMRI signals, but the resulting geometry has not been fully characterized with mathematical models. Here we test whether VFMs V1 and V2 obey the least restrictive of all geometric mappings; that is, whether they are anglepreserving and therefore maintain conformal mapping. We measured retinotopic organization in individual subjects using standard traveling-wave fMRI methods. Visual stimuli consisted of black and white, drifting checkerboards comprising rotating wedges and expanding rings to measure the cortical representations of polar angle and eccentricity, respectively. These representations were then projected onto a 3D cortical mesh of each hemisphere. By generating a mapped unit disk that is conformal of the VFMs using spherical stereographic projection and computing the parameterized coordinates of the eccentricity and polar angle gradients, we computed Beltrami coefficients to check whether the mapping from the visual field to the V1 and V2 cortical representations is conformal. We find that V1 and V2 exhibit local conformality. Our analysis of the Beltrami coefficient shows that selected regions of V1 and V2 that contain reasonably smooth eccentricity and polar angle gradients do show significant local conformality, warranting further investigation of this approach for analysis of early and higher visual cortex. These results suggest that such a mathematical model can be used to characterize the early VFMs in human visual cortex.

  13. GENE EXPRESSION IN THE TESTES OF NORMOSPERMIC VERSUS TERATOSPERMIC DOMESTIC CATS USING HUMAN CDNA MICROARRAY ANALYSES

    EPA Science Inventory

    GENE EXPRESSION IN THE TESTES OF NORMOSPERMIC VERSUS TERATOSPERMIC DOMESTIC CATS USING HUMAN cDNA MICROARRAY ANALYSES

    B.S. Pukazhenthi1, J. C. Rockett2, M. Ouyang3, D.J. Dix2, J.G. Howard1, P. Georgopoulos4, W.J. J. Welsh3 and D. E. Wildt1

    1Department of Reproductiv...

  14. Computer-based thermal imaging of human gingiva: preliminary investigation.

    PubMed

    Barnett, M L; Gilman, R M; Charles, C H; Bartels, L L

    1989-11-01

    Computer-based thermal imaging techniques were used to compare the rewarming rates of normal and inflamed human gingiva following cooling. A Modified Gingival Index (MGI) score, gingival crevicular fluid (GCF) measurement, and clinical photograph were obtained from a maxillary or mandibular anterior facial region in 20 subjects, aged 25 to 44. Baseline thermograms of the marginal/papillary (M/P) and adjacent attached gingiva (AG) were recorded following an acclimatization period with the patient seated and chin resting on a positioning apparatus. The tissue was then cooled with a gentle stream of air and thermograms were recorded at 10 second intervals for 3 minutes as the tissue rewarmed. Rewarming slopes were calculated based on these thermograms. Correlation coefficients were calculated for MGI with GCF, as well as for both MGI and GCF with AG and M/P rewarming slopes. Mean baseline (SE) temperatures (degrees F) for AG were 75.9 (0.9), 78.0 (0.6), and 80.3 (1.3) for normal, mildly inflamed, and moderately-severely inflamed gingivae, respectively; corresponding mean (SE) temperature differences (degrees F) between AG and M/P were 0.5 (0.2), 0.9 (0.2), and 1.4 (0.3). Intragroup mean M/P temperatures were less than mean AG temperatures, with the mean regional differences increasing with greater severity of inflammation. Rewarming rates also increased as inflammation became more severe, with the rewarming slopes of both the AG and M/P having statistically significant correlations with the MGI and the GCF. The correlation between MGI and GCF was also statistically significant. This study suggests that computer-based thermal imaging techniques can detect both static and dynamic temperature differences between normal gingiva and gingivae with increasing severities of inflammation.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2600750

  15. IMPROVING CONTROL ROOM DESIGN AND OPERATIONS BASED ON HUMAN FACTORS ANALYSES OR HOW MUCH HUMAN FACTORS UPGRADE IS ENOUGH ?

    SciTech Connect

    HIGGINS,J.C.; OHARA,J.M.; ALMEIDA,P.

    2002-09-19

    THE JOSE CABRERA NUCLEAR POWER PLANT IS A ONE LOOP WESTINGHOUSE PRESSURIZED WATER REACTOR. IN THE CONTROL ROOM, THE DISPLAYS AND CONTROLS USED BY OPERATORS FOR THE EMERGENCY OPERATING PROCEDURES ARE DISTRIBUTED ON FRONT AND BACK PANELS. THIS CONFIGURATION CONTRIBUTED TO RISK IN THE PROBABILISTIC SAFETY ASSESSMENT WHERE IMPORTANT OPERATOR ACTIONS ARE REQUIRED. THIS STUDY WAS UNDERTAKEN TO EVALUATE THE IMPACT OF THE DESIGN ON CREW PERFORMANCE AND PLANT SAFETY AND TO DEVELOP DESIGN IMPROVEMENTS.FIVE POTENTIAL EFFECTS WERE IDENTIFIED. THEN NUREG-0711 [1], PROGRAMMATIC, HUMAN FACTORS, ANALYSES WERE CONDUCTED TO SYSTEMATICALLY EVALUATE THE CR-LA YOUT TO DETERMINE IF THERE WAS EVIDENCE OF THE POTENTIAL EFFECTS. THESE ANALYSES INCLUDED OPERATING EXPERIENCE REVIEW, PSA REVIEW, TASK ANALYSES, AND WALKTHROUGH SIMULATIONS. BASED ON THE RESULTS OF THESE ANALYSES, A VARIETY OF CONTROL ROOM MODIFICATIONS WERE IDENTIFIED. FROM THE ALTERNATIVES, A SELECTION WAS MADE THAT PROVIDED A REASONABLEBALANCE BE TWEEN PERFORMANCE, RISK AND ECONOMICS, AND MODIFICATIONS WERE MADE TO THE PLANT.

  16. Integrative analyses of human reprogramming reveal dynamic nature of induced pluripotency

    PubMed Central

    Cacchiarelli, Davide; Trapnell, Cole; Ziller, Michael J.; Soumillon, Magali; Cesana, Marcella; Karnik, Rahul; Donaghey, Julie; Smith, Zachary D.; Ratanasirintrawoot, Sutheera; Zhang, Xiaolan; Ho Sui, Shannan J.; Wu, Zhaoting; Akopian, Veronika; Gifford, Casey A.; Doench, John; Rinn, John L.; Daley, George Q.; Meissner, Alexander; Lander, Eric S.; Mikkelsen, Tarjei S.

    2015-01-01

    Summary Induced pluripotency is a promising avenue for disease modeling and therapy, but the molecular principles underlying this process, particularly in human cells, remain poorly understood due to donor-to-donor variability and intercellular heterogeneity. Here we constructed and characterized a clonal, inducible human reprogramming system that provides a reliable source of cells at any stage of the process. This system enabled integrative transcriptional and epigenomic analysis across the human reprogramming timeline at high resolution. We observed distinct waves of gene network activation, including the ordered reactivation of broad developmental regulators followed by early embryonic patterning genes and culminating in the emergence of a signature reminiscent of pre-implantation stages. Moreover, complementary functional analyses allowed us to identify and validate novel regulators of the reprogramming process. Altogether, this study sheds light on the molecular underpinnings of induced pluripotency in human cells and provides a robust cell platform for further studies. PMID:26186193

  17. 1,3-Butadiene, styrene and lymphohematopoietic cancer among male synthetic rubber industry workers--Preliminary exposure-response analyses.

    PubMed

    Sathiakumar, Nalini; Brill, Ilene; Leader, Mark; Delzell, Elizabeth

    2015-11-01

    We updated the mortality experience of North American synthetic rubber industry workers to include follow-up from 1944 through 2009, adding 11 years of mortality data to previous investigations. The present analysis used Cox regression to examine the exposure-response relationship between 1,3-butadiene (BD) and styrene (STY) parts per million (ppm)-years and leukemia (N = 114 deaths), non-Hodgkin lymphoma (NHL) (N = 89) and multiple myeloma (MM) (N = 48). A pattern of largely monotonically increasing rate ratios across deciles of BD ppm-years and a positive, statistically significant exposure-response trend were observed for BD ppm-years and leukemia. Using continuous, untransformed BD ppm-years the regression coefficient (β) adjusted only for age was 2.6 × 10(-4) (p < 0.01); the regression coefficient adjusted for age, year of birth, race and plant was 2.9 × 10(-4) (p < 0.01). STY ppm-years also displayed a positive exposure-response association with leukemia. STY and BD were strongly correlated, and the separate effects of these two agents could not be estimated. For NHL, a pattern of approximately monotonically increasing rate ratios across deciles of exposure was seen for STY but not for BD; the test of trend was statistically significant in one of five models that used different STY exposure metrics and adjusted for age and other covariates. BD ppm-years and STY ppm-years were not associated with MM. The present analyses indicated a positive exposure-response relationship between BD cumulative exposure and leukemia. This result along with other research and biological information support an interpretation that BD causes leukemia in humans. STY exposure also was positively associated with leukemia, but its independent effect could not be delineated because of its strong correlation with BD, and there is no external support for a STY-leukemia association. STY, but not BD, was associated positively with NHL. The interpretation of this result is

  18. Phylogenomic analyses reveal convergent patterns of adaptive evolution in elephant and human ancestries.

    PubMed

    Goodman, Morris; Sterner, Kirstin N; Islam, Munirul; Uddin, Monica; Sherwood, Chet C; Hof, Patrick R; Hou, Zhuo-Cheng; Lipovich, Leonard; Jia, Hui; Grossman, Lawrence I; Wildman, Derek E

    2009-12-01

    Specific sets of brain-expressed genes, such as aerobic energy metabolism genes, evolved adaptively in the ancestry of humans and may have evolved adaptively in the ancestry of other large-brained mammals. The recent addition of genomes from two afrotherians (elephant and tenrec) to the expanding set of publically available sequenced mammalian genomes provided an opportunity to test this hypothesis. Elephants resemble humans by having large brains and long life spans; tenrecs, in contrast, have small brains and short life spans. Thus, we investigated whether the phylogenomic patterns of adaptive evolution are more similar between elephant and human than between either elephant and tenrec lineages or human and mouse lineages, and whether aerobic energy metabolism genes are especially well represented in the elephant and human patterns. Our analyses encompassed approximately 6,000 genes in each of these lineages with each gene yielding extensive coding sequence matches in interordinal comparisons. Each gene's nonsynonymous and synonymous nucleotide substitution rates and dN/dS ratios were determined. Then, from gene ontology information on genes with the higher dN/dS ratios, we identified the more prevalent sets of genes that belong to specific functional categories and that evolved adaptively. Elephant and human lineages showed much slower nucleotide substitution rates than tenrec and mouse lineages but more adaptively evolved genes. In correlation with absolute brain size and brain oxygen consumption being largest in elephants and next largest in humans, adaptively evolved aerobic energy metabolism genes were most evident in the elephant lineage and next most evident in the human lineage. PMID:19926857

  19. Comparative Analyses of QTLs Influencing Obesity and Metabolic Phenotypes in Pigs and Humans

    PubMed Central

    Jacobsen, Mette J.; Cirera, Susanna; Kogelman, Lisette J. A.; Bruun, Camilla S.; Mark, Thomas; Jørgensen, Claus B.; Grarup, Niels; Appel, Emil V. R.; Galjatovic, Ehm A. A.; Hansen, Torben; Pedersen, Oluf; Guerin, Maryse; Huby, Thierry; Lesnik, Philipppe; Meuwissen, Theo H. E.; Kadarmideen, Haja N.; Fredholm, Merete

    2015-01-01

    The pig is a well-known animal model used to investigate genetic and mechanistic aspects of human disease biology. They are particularly useful in the context of obesity and metabolic diseases because other widely used models (e.g. mice) do not completely recapitulate key pathophysiological features associated with these diseases in humans. Therefore, we established a F2 pig resource population (n = 564) designed to elucidate the genetics underlying obesity and metabolic phenotypes. Segregation of obesity traits was ensured by using breeds highly divergent with respect to obesity traits in the parental generation. Several obesity and metabolic phenotypes were recorded (n = 35) from birth to slaughter (242 ± 48 days), including body composition determined at about two months of age (63 ± 10 days) via dual-energy x-ray absorptiometry (DXA) scanning. All pigs were genotyped using Illumina Porcine 60k SNP Beadchip and a combined linkage disequilibrium-linkage analysis was used to identify genome-wide significant associations for collected phenotypes. We identified 229 QTLs which associated with adiposity- and metabolic phenotypes at genome-wide significant levels. Subsequently comparative analyses were performed to identify the extent of overlap between previously identified QTLs in both humans and pigs. The combined analysis of a large number of obesity phenotypes has provided insight in the genetic architecture of the molecular mechanisms underlying these traits indicating that QTLs underlying similar phenotypes are clustered in the genome. Our analyses have further confirmed that genetic heterogeneity is an inherent characteristic of obesity traits most likely caused by segregation or fixation of different variants of the individual components belonging to cellular pathways in different populations. Several important genes previously associated to obesity in human studies, along with novel genes were identified. Altogether, this study provides novel insight that

  20. p53 Response to Ultrasound: Preliminary Observations in MCF7 Human Breast Cancer Cells

    NASA Astrophysics Data System (ADS)

    Burns, Janis M.; Campbell, Paul A.

    2011-09-01

    Mutated p53 can be found in approximately half of all human cancers. Strategies which seek to restore, or at least exercise a level of external control over, p53 functionality are thus potentially useful as adjuncts to therapy. Here, we report our preliminary measurements in this area, and demonstrate that short-burst pulsed ultrasound can indeed affect p53 activity. Specifically, we have observed that expression of the p53 protein can be regulated in the period immediately following low intensity short pulse (millisecond) ultrasound exposure, and that altered activity levels return to basal levels over a 24 hour period post-insonation.

  1. A model of the human lumbar vertebral column: a preliminary study.

    PubMed

    Vanneuville, G; Cluzel, P; Massaux, M; Bressolette, P; Kyndt, T; Garcier, J M; Guillot, M; Gabrillargues, J; Chandezon, R; Poumarat, G

    1995-01-01

    Finite element modelling of the human lumbar vertebral column employs data-processing procedures for study of the linear and nonlinear elasticity of materials such as are currently used in mechanics or in civil engineering. Thanks to developments in computer science, requiring a close collaboration between doctors and engineers, we put forward in this preliminary study a linear computerised model of the lumbar column comprising 4824 meshes and 6813 nodes. By reducing the simplificatory hypotheses and integrating new parameters, this model as developed is capable of important clinical applications in surgery and ergonomics. PMID:7597566

  2. New Genetic and Linguistic Analyses Show Ancient Human Influence on Baobab Evolution and Distribution in Australia

    PubMed Central

    Rangan, Haripriya; Bell, Karen L.; Baum, David A.; Fowler, Rachael; McConvell, Patrick; Saunders, Thomas; Spronck, Stef; Kull, Christian A.; Murphy, Daniel J.

    2015-01-01

    This study investigates the role of human agency in the gene flow and geographical distribution of the Australian baobab, Adansonia gregorii. The genus Adansonia is a charismatic tree endemic to Africa, Madagascar, and northwest Australia that has long been valued by humans for its multiple uses. The distribution of genetic variation in baobabs in Africa has been partially attributed to human-mediated dispersal over millennia, but this relationship has never been investigated for the Australian species. We combined genetic and linguistic data to analyse geographic patterns of gene flow and movement of word-forms for A. gregorii in the Aboriginal languages of northwest Australia. Comprehensive assessment of genetic diversity showed weak geographic structure and high gene flow. Of potential dispersal vectors, humans were identified as most likely to have enabled gene flow across biogeographic barriers in northwest Australia. Genetic-linguistic analysis demonstrated congruence of gene flow patterns and directional movement of Aboriginal loanwords for A. gregorii. These findings, along with previous archaeobotanical evidence from the Late Pleistocene and Holocene, suggest that ancient humans significantly influenced the geographic distribution of Adansonia in northwest Australia. PMID:25830225

  3. New genetic and linguistic analyses show ancient human influence on baobab evolution and distribution in Australia.

    PubMed

    Rangan, Haripriya; Bell, Karen L; Baum, David A; Fowler, Rachael; McConvell, Patrick; Saunders, Thomas; Spronck, Stef; Kull, Christian A; Murphy, Daniel J

    2015-01-01

    This study investigates the role of human agency in the gene flow and geographical distribution of the Australian baobab, Adansonia gregorii. The genus Adansonia is a charismatic tree endemic to Africa, Madagascar, and northwest Australia that has long been valued by humans for its multiple uses. The distribution of genetic variation in baobabs in Africa has been partially attributed to human-mediated dispersal over millennia, but this relationship has never been investigated for the Australian species. We combined genetic and linguistic data to analyse geographic patterns of gene flow and movement of word-forms for A. gregorii in the Aboriginal languages of northwest Australia. Comprehensive assessment of genetic diversity showed weak geographic structure and high gene flow. Of potential dispersal vectors, humans were identified as most likely to have enabled gene flow across biogeographic barriers in northwest Australia. Genetic-linguistic analysis demonstrated congruence of gene flow patterns and directional movement of Aboriginal loanwords for A. gregorii. These findings, along with previous archaeobotanical evidence from the Late Pleistocene and Holocene, suggest that ancient humans significantly influenced the geographic distribution of Adansonia in northwest Australia. PMID:25830225

  4. Evidence for Balancing Selection from Nucleotide Sequence Analyses of Human G6PD

    PubMed Central

    Verrelli, Brian C.; McDonald, John H.; Argyropoulos, George; Destro-Bisol, Giovanni; Froment, Alain; Drousiotou, Anthi; Lefranc, Gerard; Helal, Ahmed N.; Loiselet, Jacques; Tishkoff, Sarah A.

    2002-01-01

    Glucose-6-phosphate dehydrogenase (G6PD) mutations that result in reduced enzyme activity have been implicated in malarial resistance and constitute one of the best examples of selection in the human genome. In the present study, we characterize the nucleotide diversity across a 5.2-kb region of G6PD in a sample of 160 Africans and 56 non-Africans, to determine how selection has shaped patterns of DNA variation at this gene. Our global sample of enzymatically normal B alleles and A, A−, and Med alleles with reduced enzyme activities reveals many previously uncharacterized silent-site polymorphisms. In comparison with the absence of amino acid divergence between human and chimpanzee G6PD sequences, we find that the number of G6PD amino acid polymorphisms in human populations is significantly high. Unlike many other G6PD-activity alleles with reduced activity, we find that the age of the A variant, which is common in Africa, may not be consistent with the recent emergence of severe malaria and therefore may have originally had a historically different adaptive function. Overall, our observations strongly support previous genotype-phenotype association studies that proposed that balancing selection maintains G6PD deficiencies within human populations. The present study demonstrates that nucleotide sequence analyses can reveal signatures of both historical and recent selection in the genome and may elucidate the impact that infectious disease has had during human evolution. PMID:12378426

  5. Preliminary scoping safety analyses of the limiting design basis protected accidents for the Fast Flux Test Facility tritium production core

    SciTech Connect

    Heard, F.J.

    1997-11-19

    The SAS4A/SASSYS-l computer code is used to perform a series of analyses for the limiting protected design basis transient events given a representative tritium and medical isotope production core design proposed for the Fast Flux Test Facility. The FFTF tritium and isotope production mission will require a different core loading which features higher enrichment fuel, tritium targets, and medical isotope production assemblies. Changes in several key core parameters, such as the Doppler coefficient and delayed neutron fraction will affect the transient response of the reactor. Both reactivity insertion and reduction of heat removal events were analyzed. The analysis methods and modeling assumptions are described. Results of the analyses and comparison against fuel pin performance criteria are presented to provide quantification that the plant protection system is adequate to maintain the necessary safety margins and assure cladding integrity.

  6. Analyses of human milk samples collected in Hawaii for residues of organochlorine pesticides and polychlorobiphenyls

    SciTech Connect

    Takei, G.H.; Kauahikaua, S.M.; Leong, G.H.

    1983-01-01

    This work has revealed that the chlorinated hydrocarbon residues found in human milk samples collected from residents in the State of Hawaii were statistically the same residues found in mainland human milk samples. Moreover, the levels at which these residues were detected in Hawaiian samples were comparable to those detected in mainland samples, and differences between the two groups of samples were not apparent. The close correlation between residue analyses was unexpected considering Hawaii's geographic isolation and the distinct ethnic diets of its populations. They do indicate, however, that the uptake of chlorinated hdyrocarbon contaminants by the population of this state is not specific and is most likely due to some physiological means of entry which is common to the populations of the mainland states.

  7. Preliminary structural characterization of human SOUL, a haem-binding protein

    PubMed Central

    Freire, Filipe; Romão, Maria João; Macedo, Anjos L.; Aveiro, Susana S.; Goodfellow, Brian J.; Carvalho, Ana Luísa

    2009-01-01

    Human SOUL (hSOUL) is a 23 kDa haem-binding protein that was first identified as the PP23 protein isolated from human full-term placentas. Here, the overexpression, purification and crystallization of hSOUL are reported. The crystals belonged to space group P6422, with unit-cell parameters a = b = 145, c = 60 Å and one protein molecule in the asymmetric unit. X-ray diffraction data were collected to 3.5 Å resolution at the ESRF. A preliminary model of the three-dimensional structure of hSOUL was obtained by molecular replacement using the structures of murine p22HBP (PDB codes 2gov and 2hva), obtained by solution NMR, as search models. PMID:19574650

  8. Detection and preliminary screening of the human gene expression profile for Hirschsprung's disease

    PubMed Central

    WANG, XIN; WANG, SHIQI; JIN, XIANQING; WANG, NING; LUO, YUANYUAN; TENG, YINPING

    2016-01-01

    The present study investigated a genome microarray of colorectal lesions (spasm segments) in children with Hirschsprung's disease (HSCR), and analyzed the results. In addition, the present study screened for differentially expressed genes in children with HSCR. Microarray technology was used to examine the human gene expression profiles of the colorectal lesions (spasm segments) of six children with HSCR, and three normal colon tissue samples. The data were analyzed be determining P-values of significance and absolute fold changes. Preliminary screening was performed to identify genes exhibiting significant differential expression in children with HSCR, and these target genes were analyzed in subsequent verification and analytical investigations. Of >20,000 detected human genes, the preliminary screenings demonstrated that 3,850 genes were differentially expressed and upregulated, with P<0.05 and >2-fold absolute changes in expression. In addition, 645 differentially expressed genes with P<0.05 and >2-fold absolute changes were downregulated. Of the upregulated genes, 118 were involved in classic signaling pathways, compared with 11 of the downregulated genes (P<0.001; absolute fold change >2-fold). HSCR etiology is complex and often involves multiple gene changes. Microarray technology can produce large quantities of gene expression data simultaneously, and analyzing this data using various techniques may provide a fast and efficient method for identifying novel gene targets and for investigating the mechanisms underlying HSCR pathogenesis. PMID:26648025

  9. Immunophenotypic analysis of cerebrospinal fluid cell populations with the Cell-Dyn Sapphire haematology analyser: method feasibility and preliminary observations.

    PubMed

    Adam, P; Sobek, O; Scott, C S; Dolezil, D; Kasik, J; Hajdukova, L; Adam, D

    2010-02-01

    Cerebrospinal fluid (CSF) samples (n=50) from patients with neurological disease (bacterial infection, viral infection, neuroborreliosis and multiple sclerosis) were analysed to characterize cell populations by fluorescent immunocytometry with the CD-Sapphire haematology analyser. Reagent combinations applied to all CSF samples comprised CD3/CD19/HLA-DR and CD4/CD8, with some being further analysed using CD3/CD4, CD3/CD16 and CD3/CD25 protocols. Of the 50 samples, 11 were excluded because of high proportions of nonviable cells (n=2) or insufficient cell numbers (n=9). Apart from bacterial infection with granulocytosis, all diagnostic groups showed high proportions (51.4-77.0%) of CD3+ T cells. There was a modest association between T-cell and B-cell counts, but absolute B-cell numbers exceeded 5 cells/microl in only 7/39 cases (neuroborreliosis, n=6; bacterial meningitis, n=1). CD3/Ia antigen (activation) co-expression was low and only exceeded 5% in 7/39 samples with no diagnostic correlation. Primary CD4+ and CD8+ T-cell subsets showed similar quantitative trends and CD4/CD8 co-analysis revealed the presence in all diagnostic groups (neuroborreliosis and multiple sclerosis in particular) of a CD4+CD8int fraction that was predominantly CD3+ and CD16- and had a morphological profile consistent with small lymphoid cells. Supplementary CD-Sapphire cellular immunological analysis of most CSF samples is feasible using the procedure detailed in this communication. PMID:19500178

  10. Microgravity and Materials Processing Facility study (MMPF): Requirements and Analyses of Commercial Operations (RACO) preliminary data release

    NASA Technical Reports Server (NTRS)

    1988-01-01

    This requirements and analyses of commercial operations (RACO) study data release reflects the current status of research activities of the Microgravity and Materials Processing Facility under Modification No. 21 to NASA/MSFC Contract NAS8-36122. Section 1 includes 65 commercial space processing projects suitable for deployment aboard the Space Station. Section 2 contains reports of the R:BASE (TM) electronic data base being used in the study, synopses of the experiments, and a summary of data on the experimental facilities. Section 3 is a discussion of video and data compression techniques used as well as a mission timeline analysis.

  11. Joint analyses model for total cholesterol and triglyceride in human serum with near-infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Yao, Lijun; Lyu, Ning; Chen, Jiemei; Pan, Tao; Yu, Jing

    2016-04-01

    The development of a small, dedicated near-infrared (NIR) spectrometer has promising potential applications, such as for joint analyses of total cholesterol (TC) and triglyceride (TG) in human serum for preventing and treating hyperlipidemia of a large population. The appropriate wavelength selection is a key technology for developing such a spectrometer. For this reason, a novel wavelength selection method, named the equidistant combination partial least squares (EC-PLS), was applied to the wavelength selection for the NIR analyses of TC and TG in human serum. A rigorous process based on the various divisions of calibration and prediction sets was performed to achieve modeling optimization with stability. By applying EC-PLS, a model set was developed, which consists of various models that were equivalent to the optimal model. The joint analyses model of the two indicators was further selected with only 50 wavelengths. The random validation samples excluded from the modeling process were used to validate the selected model. The root-mean-square errors, correlation coefficients and ratio of performance to deviation for the prediction were 0.197 mmol L- 1, 0.985 and 5.6 for TC, and 0.101 mmol L- 1, 0.992 and 8.0 for TG, respectively. The sensitivity and specificity for hyperlipidemia were 96.2% and 98.0%. These findings indicate high prediction accuracy and low model complexity. The proposed wavelength selection provided valuable references for the designing of a small, dedicated spectrometer for hyperlipidemia. The methodological framework and optimization algorithm are universal, such that they can be applied to other fields.

  12. Joint analyses model for total cholesterol and triglyceride in human serum with near-infrared spectroscopy.

    PubMed

    Yao, Lijun; Lyu, Ning; Chen, Jiemei; Pan, Tao; Yu, Jing

    2016-04-15

    The development of a small, dedicated near-infrared (NIR) spectrometer has promising potential applications, such as for joint analyses of total cholesterol (TC) and triglyceride (TG) in human serum for preventing and treating hyperlipidemia of a large population. The appropriate wavelength selection is a key technology for developing such a spectrometer. For this reason, a novel wavelength selection method, named the equidistant combination partial least squares (EC-PLS), was applied to the wavelength selection for the NIR analyses of TC and TG in human serum. A rigorous process based on the various divisions of calibration and prediction sets was performed to achieve modeling optimization with stability. By applying EC-PLS, a model set was developed, which consists of various models that were equivalent to the optimal model. The joint analyses model of the two indicators was further selected with only 50 wavelengths. The random validation samples excluded from the modeling process were used to validate the selected model. The root-mean-square errors, correlation coefficients and ratio of performance to deviation for the prediction were 0.197mmolL(-1), 0.985 and 5.6 for TC, and 0.101mmolL(-1), 0.992 and 8.0 for TG, respectively. The sensitivity and specificity for hyperlipidemia were 96.2% and 98.0%. These findings indicate high prediction accuracy and low model complexity. The proposed wavelength selection provided valuable references for the designing of a small, dedicated spectrometer for hyperlipidemia. The methodological framework and optimization algorithm are universal, such that they can be applied to other fields. PMID:26827178

  13. Origin of carbonate deposits in the vicinity of Yucca Mountain, Nevada. Preliminary results of strontium-isotope analyses

    USGS Publications Warehouse

    Marshall, B.D.; Futa, K.; Mahan, S.A.; Peterman, Z.E.; Stuckless, J.S.; Downey, J.S.; Gutentag, E.D.

    1990-01-01

    As part of the paleohydrology study of the Yucca Mountain Project, strontium-isotope analyses of carbonate deposits, ground water, and major rock reservoirs of strontium are in progress. This paper presents a summary of the strontium-isotope data obtained through 1989. Calcium carbonate is ubiquitous in the vicinity of Yucca Mountain, where it occurs as pedogenic horizons and rhizoliths, small veins and fracture fillings in Tertiary volcanic rocks, large veins and masses along faults, and freshwater and marine limestones. With the exception of marine limestones, which are Paleozoic, the calcium carbonate has been precipitated directly from water during the past 107 years. This paper reports strontium-isotope compositions of the following carbonate groups: 1) limestones of the Paleozoic basement, 2) calcite-silica veins, 3) small calcite veins, 4) pedogenic carbonate deposits, and 5) spring deposits (i.e., tufa). The authors have also analyzed the strontium from samples of Tertiary volcanic rocks and from ground water.

  14. Precision measurement of lead isotopes ratios: preliminary analyses from the U.S. mine, Bingham Canyon, Utah

    USGS Publications Warehouse

    Stacey, J.S.; Moore, W.J.; Rubright, R.D.

    1967-01-01

    A gas-source mass spectrometer has been constructed for the precise measurement of lead isotope ratios. Sixteen analyses on 4 different preparations of the same galena made over a period of 2 months gave 95% confidence limits (per analysis) of 206Pb/204Pb = 0.080%, 207Pb/206Pb = 0.042% and208Pb/206Pb = 0.046%. Eight samples from the U.S. mine in the Bingham district have a linear relationship over the 1% range of their 206Pb/204Pb ratios. The simplest model fitting these data suggests that the lead was separated from a primary system (??=8.98) 1630??150 m.y. ago and subsequently mixed with a radiogenic lead of similar age; biotite K-Ar dates for altered intrusive rocks associated with the ores provide an apparent age of mineralization and suggest that isotopic evolution of the lead was terminated about 36 m.y. ago. ?? 1967.

  15. Full genomic analyses of human rotavirus strains possessing the rare P[8]b VP4 subtype.

    PubMed

    Ghosh, Souvik; Paul, Shyamal Kumar; Yamamoto, Dai; Nagashima, Shigeo; Kobayashi, Nobumichi

    2011-08-01

    Rotaviruses with the P[8] VP4 genotype are a major cause of acute infantile diarrhea. The P[8] genotype is classified into two genetically distinct subtypes, P[8]a and P[8]b. Most of the P[8] strains belong to subtype P[8]a, whilst P[8]b strains are rare. To date, the whole genomes of a few P[8]a strains have been analyzed, whilst there are no reports on full genomic analysis of the P[8]b strains. To determine the genetic makeup of the rare P[8]b strains and their overall genetic relatedness to the P[8]a strains, the present study analyzed the full genomes of a human G9P[8]b strain, MMC38, and a G1P[8]b strain, MMC71, detected in Bangladesh in 2005. By nucleotide sequence identities and phylogenetic analyses, strains MMC38 and MMC71 exhibited a human rotavirus Wa-like genotype constellation. Except for the VP4 gene, all the genes of strains MMC38 and MMC71 were closely related to cognate genes of the contemporary and more recent human Wa-like G1P[8]a, G9P[8]a, G11P[8]a, G11P[25], G12P[6] and G12P[8]a strains, including those from Bangladesh. Therefore, strains MMC38 and MMC71 possessed the genetically distinct P[8]b VP4 gene on a common human Wa-like genetic backbone, pointing towards their possible origin from reassortment events between common human Wa-like strains and unidentified rotavirus strains possessing the rare P[8]b-like VP4 gene. Since strains with this stable Wa-like genetic backbone can spread rapidly, and it is not certain as to whether the current rotavirus vaccines will be equally efficacious against the P[8]b strains as the P[8]a strains, proper detection of P[8]b strains and their whole genomic analyses might be of public health significance. To our knowledge, the present study is the first report on full genomic analysis of the rare P[8]b rotavirus strains. PMID:21640848

  16. Preliminary perspectives on DNA collection in anti-human trafficking efforts.

    PubMed

    Katsanis, Sara H; Kim, Joyce; Minear, Mollie A; Chandrasekharan, Subhashini; Wagner, Jennifer K

    2014-01-01

    Forensic DNA methodologies have potential applications in the investigation of human trafficking cases. DNA and relationship testing may be useful for confirmation of biological relationship claims in immigration, identification of trafficked individuals who are missing persons, and family reunification of displaced individuals after mass disasters and conflicts. As these applications rely on the collection of DNA from non-criminals and potentially vulnerable individuals, questions arise as to how to address the ethical challenges of collection, security, and privacy of collected samples and DNA profiles. We administered a survey targeted to victims' advocates to gain preliminary understanding of perspectives regarding human trafficking definitions, DNA and sex workers, and perceived trust of authorities potentially involved in DNA collection. We asked respondents to consider the use of DNA for investigating adoption fraud, sex trafficking, and post-conflict child soldier cases. We found some key differences in perspectives on defining what qualifies as "trafficking." When we varied terminology between "sex worker" and "sex trafficking victim" we detected differences in perception on which authorities can be trusted. Respondents were supportive of the hypothetical models proposed to collect DNA. Most were favorable of DNA specimens being controlled by an authority outside of law enforcement. Participants voiced concerns focused on privacy, misuse of DNA samples and data, unintentional harms, data security, and infrastructure. These preliminary data indicate that while there is perceived value in programs to use DNA for investigating cases of human trafficking, these programs may need to consider levels of trust in authorities as their logistics are developed and implemented. PMID:25687341

  17. Expression, crystallization and preliminary X-ray crystallographic analyses of two N-terminal acetyltransferase-related proteins from Thermoplasma acidophilum

    SciTech Connect

    Han, Sang Hee; Ha, Jun Yong; Kim, Kyoung Hoon; Oh, Sung Jin; Kim, Do Jin; Kang, Ji Yong; Yoon, Hye Jin; Kim, Se-Hee; Seo, Ji Hae; Kim, Kyu-Won; Suh, Se Won

    2006-11-01

    An N-terminal acetyltransferase ARD1 subunit-related protein (Ta0058) and an N-terminal acetyltransferase-related protein (Ta1140) from T. acidophilum were crystallized. X-ray diffraction data were collected to 2.17 and 2.40 Å, respectively. N-terminal acetylation is one of the most common protein modifications in eukaryotes, occurring in approximately 80–90% of cytosolic mammalian proteins and about 50% of yeast proteins. ARD1 (arrest-defective protein 1), together with NAT1 (N-acetyltransferase protein 1) and possibly NAT5, is responsible for the NatA activity in Saccharomyces cerevisiae. In mammals, ARD1 is involved in cell proliferation, neuronal development and cancer. Interestingly, it has been reported that mouse ARD1 (mARD1{sup 225}) mediates ∊-acetylation of hypoxia-inducible factor 1α (HIF-1α) and thereby enhances HIF-1α ubiquitination and degradation. Here, the preliminary X-ray crystallographic analyses of two N-terminal acetyltransferase-related proteins encoded by the Ta0058 and Ta1140 genes of Thermoplasma acidophilum are reported. The Ta0058 protein is related to an N-terminal acetyltransferase complex ARD1 subunit, while Ta1140 is a putative N-terminal acetyltransferase-related protein. Ta0058 shows 26% amino-acid sequence identity to both mARD1{sup 225} and human ARD1{sup 235}.The sequence identity between Ta0058 and Ta1140 is 28%. Ta0058 and Ta1140 were overexpressed in Escherichia coli fused with an N-terminal purification tag. Ta0058 was crystallized at 297 K using a reservoir solution consisting of 0.1 M sodium acetate pH 4.6, 8%(w/v) polyethylene glycol 4000 and 35%(v/v) glycerol. X-ray diffraction data were collected to 2.17 Å. The Ta0058 crystals belong to space group P4{sub 1} (or P4{sub 3}), with unit-cell parameters a = b = 49.334, c = 70.384 Å, α = β = γ = 90°. The asymmetric unit contains a monomer, giving a calculated crystal volume per protein weight (V{sub M}) of 2.13 Å{sup 3} Da{sup −1} and a solvent content of 42

  18. Naturally induced secondary radiation in interplanetary space: Preliminary analyses for gamma radiation and radioisotope production from thermal neutron activation

    NASA Astrophysics Data System (ADS)

    Plaza-Rosado, Heriberto

    1991-09-01

    Thermal neutron activation analyses were carried out for various space systems components to determine gamma radiation dose rates and food radiation contamination levels. The space systems components selected were those for which previous radiation studies existed. These include manned space vehicle radiation shielding, liquid hydrogen propellant tanks for a Mars mission, and a food supply used as space vehicle radiation shielding. The computational method used is based on the fast neutron distribution generated by the BRYNTRN and HZETRN transport codes for Galactic Cosmic Rays (GCR) at solar minimum conditions and intense solar flares in space systems components. The gamma dose rates for soft tissue are calculated for water and aluminum space vehicle slab shields considering volumetric source self-attenuation and exponential buildup factors. In the case of the lunar habitat with regolith shielding, a completely exposed spherical habitat was assumed for mathematical convenience and conservative calculations. Activation analysis of the food supply used as radiation shielding is presented for four selected nutrients: potassium, calcium, sodium, and phosphorus. Radioactive isotopes that could represent a health hazard if ingested are identified and their concentrations are identified. For nutrients soluble in water, it was found that all induced radioactivity was below the accepted maximum permissible concentrations.

  19. Naturally induced secondary radiation in interplanetary space: Preliminary analyses for gamma radiation and radioisotope production from thermal neutron activation

    NASA Technical Reports Server (NTRS)

    Plaza-Rosado, Heriberto

    1991-01-01

    Thermal neutron activation analyses were carried out for various space systems components to determine gamma radiation dose rates and food radiation contamination levels. The space systems components selected were those for which previous radiation studies existed. These include manned space vehicle radiation shielding, liquid hydrogen propellant tanks for a Mars mission, and a food supply used as space vehicle radiation shielding. The computational method used is based on the fast neutron distribution generated by the BRYNTRN and HZETRN transport codes for Galactic Cosmic Rays (GCR) at solar minimum conditions and intense solar flares in space systems components. The gamma dose rates for soft tissue are calculated for water and aluminum space vehicle slab shields considering volumetric source self-attenuation and exponential buildup factors. In the case of the lunar habitat with regolith shielding, a completely exposed spherical habitat was assumed for mathematical convenience and conservative calculations. Activation analysis of the food supply used as radiation shielding is presented for four selected nutrients: potassium, calcium, sodium, and phosphorus. Radioactive isotopes that could represent a health hazard if ingested are identified and their concentrations are identified. For nutrients soluble in water, it was found that all induced radioactivity was below the accepted maximum permissible concentrations.

  20. Preliminary performance assessment for the Waste Isolation Pilot Plant, December 1992. Volume 5, Uncertainty and sensitivity analyses of gas and brine migration for undisturbed performance

    SciTech Connect

    Not Available

    1993-08-01

    Before disposing of transuranic radioactive waste in the Waste Isolation Pilot Plant (WIPP), the United States Department of Energy (DOE) must evaluate compliance with applicable long-term regulations of the United States Environmental Protection Agency (EPA). Sandia National Laboratories is conducting iterative performance assessments (PAs) of the WIPP for the DOE to provide interim guidance while preparing for a final compliance evaluation. This volume of the 1992 PA contains results of uncertainty and sensitivity analyses with respect to migration of gas and brine from the undisturbed repository. Additional information about the 1992 PA is provided in other volumes. Volume 1 contains an overview of WIPP PA and results of a preliminary comparison with 40 CFR 191, Subpart B. Volume 2 describes the technical basis for the performance assessment, including descriptions of the linked computational models used in the Monte Carlo analyses. Volume 3 contains the reference data base and values for input parameters used in consequence and probability modeling. Volume 4 contains uncertainty and sensitivity analyses with respect to the EPA`s Environmental Standards for the Management and Disposal of Spent Nuclear Fuel, High-Level and Transuranic Radioactive Wastes (40 CFR 191, Subpart B). Finally, guidance derived from the entire 1992 PA is presented in Volume 6. Results of the 1992 uncertainty and sensitivity analyses indicate that, conditional on the modeling assumptions and the assigned parameter-value distributions, the most important parameters for which uncertainty has the potential to affect gas and brine migration from the undisturbed repository are: initial liquid saturation in the waste, anhydrite permeability, biodegradation-reaction stoichiometry, gas-generation rates for both corrosion and biodegradation under inundated conditions, and the permeability of the long-term shaft seal.

  1. Emergence and Evolutionary Analysis of the Human DDR Network: Implications in Comparative Genomics and Downstream Analyses

    PubMed Central

    Arcas, Aida; Fernández-Capetillo, Oscar; Cases, Ildefonso; Rojas, Ana M.

    2014-01-01

    The DNA damage response (DDR) is a crucial signaling network that preserves the integrity of the genome. This network is an ensemble of distinct but often overlapping subnetworks, where different components fulfill distinct functions in precise spatial and temporal scenarios. To understand how these elements have been assembled together in humans, we performed comparative genomic analyses in 47 selected species to trace back their emergence using systematic phylogenetic analyses and estimated gene ages. The emergence of the contribution of posttranslational modifications to the complex regulation of DDR was also investigated. This is the first time a systematic analysis has focused on the evolution of DDR subnetworks as a whole. Our results indicate that a DDR core, mostly constructed around metabolic activities, appeared soon after the emergence of eukaryotes, and that additional regulatory capacities appeared later through complex evolutionary process. Potential key posttranslational modifications were also in place then, with interacting pairs preferentially appearing at the same evolutionary time, although modifications often led to the subsequent acquisition of new targets afterwards. We also found extensive gene loss in essential modules of the regulatory network in fungi, plants, and arthropods, important for their validation as model organisms for DDR studies. PMID:24441036

  2. XeCl excimer laser-induced autofluorescence spectroscopy for human cerebral tumor diagnosis: preliminary study

    NASA Astrophysics Data System (ADS)

    Avrillier, Sigrid; Hor, Frederic; Desgeorges, Michel; Ettori, Dominique; Sitbon, Jean R.

    1993-09-01

    Three-hundred-eight nm laser-induced autofluorescence spectra of the normal human brain, astrocytoma grade IV and glioblastoma grade IV specimens, have been recorded in vitro two hours after surgical resection. Typical fluorescence spectra for normal (N) and malignant (M) tissue show 4 maxima at about 352, 362, 383, and 460 nm. These spectra are analyzed in detail. Subtle differences in normalized spectra of N and M tissues appear to be large enough for diagnosis. Several criteria such as maxima and minima absolute intensity and intensity ratios at typical wavelengths are computed and used to classify the tissue. This preliminary study shows that fluorescence spectroscopy with 308 nm UV excitation could be a valid technique for discriminating tumor types. However, it should be noted that these measurements are made in vitro. Living tissues may have different spectral characteristics, therefore future in vivo investigations must be performed.

  3. A preliminary report on noble gas isotope analyses using the Helix-MC multi-collector mass spectrometer

    NASA Astrophysics Data System (ADS)

    Honda, M.; Zhang, X.; Phillips, D.; Szczepanski, S.; Deerberg, M.; Hamilton, D.; Krummen, M.; Schwieters, J.

    2013-12-01

    Analyses of noble gas isotopes by multi-collector mass spectrometry substantially improve measurement precision and accuracy, with the potential to revolutionise applications to cosmo-geo-sciences. The Helix-MC noble gas mass spectrometer manufactured by Thermo-Fisher is a 350mm, 120 degree extended geometry, high resolution, multi-collector mass spectrometer for the simultaneous analysis of noble gas isotopes. The detector array includes a fixed axial (Ax) detector, 2 adjustable high mass (H1 and H2) detectors and 2 adjustable low mass (L1 and L2) detectors. Each detector is equipped with a Faraday/ion counting multiplier CFM (Combined Faraday and CDD Multiplier) detector. Mass resolution and mass resolving power on the H2, Ax and L2 detectors of the Helix-MC installed at the Australian National University (ANU) are approximately 1,800 and 8,000, respectively. The noble gas handling system on-line to the Helix-MC consists of: (1) a resistively-heated, double-vacuum, tantalum furnace system, (2) air actuated vacuum crusher, (3) Photon-Machines diode laser heating system, (4) Janis He cryogenic trap assembly, (5) gas purification system and (6) standard gas pipette tanks, which are totally automated and controlled by the Qtegra software platform developed by Thermo-Fisher. Eleven repeat measurements of atmospheric Ar using the H2 Faraday (1E11 ohm resistor) and L2 CDD collectors on the Helix-MC, yield a mean 40Ar/36Ar ratio of 322.09 +- 0.28 (0.089%) with a 4,700 fA 40Ar beam current. This result compares favourably with the precision achieved by the Argus VI at the University of Melbourne (318.12 +- 0.17; 0.052%; n = 10) with a similar beam size of 4,200 fA. The high mass resolution of the L2 collector permits complete separation of the 36Ar and interfering 3 x 12C (required mass resolution (MR) of 1,100) and partial separation of H35Cl (MR = 3,900). This capability enables evaluation of the significance of Ar isotopic interferences related to the correction of

  4. Effects of Idazoxan on Alcohol Pharmacokinetics and Intoxication: A Preliminary Human Laboratory Study

    PubMed Central

    Haass-Koffler, Carolina L.; Leggio, Lorenzo; Davidson, Dena; Swift, Robert M.

    2015-01-01

    Background Preliminary basic and human studies suggest that the α2-adrenergic antagonist idazoxan may represent a novel medication for alcohol dependence (AD). The goal of this study was to evaluate the safety and tolerability of the co-administration of idazoxan with alcohol and explore whether pharmacokinetics (PK) and biobehavioral (Pharmacodynamics, PD) mechanisms of idazoxan may alter alcohol's effects. Methods This was a preliminary double-blind, single-dose, placebo-controlled, cross-over, randomized human laboratory study. Ten social drinkers were dosed, in two different alcohol challenge sessions (ACS), with a single oral dose of idazoxan (40-mg) or placebo, followed by a fixed alcohol dose 60 minutes later. Participants returned after a one-week wash-out and they were crossed over to the opposite medication condition. Results There were no significant differences in adverse events (AEs) between idazoxan and placebo. Moreover, during the ACS paradigm, 40-mg idazoxan was well tolerated with no significant autonomic effects compared to placebo; idazoxan reduced the peak blood alcohol level (Cmax) (p<.01) and time to peak (tmax) (p<.05) compared to placebo. A PK/PD model aligned the biobehavioral effects, demonstrating that the co-administration of 40-mg idazoxan with alcohol, decreased alcohol-related stimulation (p<.05) and increased alcohol-related sedation (p<.05). Conclusions This study supports the safety and tolerability of 40-mg idazoxan when co-administered with alcohol. Additionally, this study suggests that idazoxan may alter the biphasic effects of alcohol by decreasing stimulation and increasing sedation. These findings have implications for further investigation of using idazoxan as a probe to develop potential novel medications to treat alcoholic patients. PMID:25833022

  5. Investigation of human exposure to triclocarban after showering and preliminary evaluation of its biological effects.

    PubMed

    Schebb, Nils Helge; Inceoglu, Bora; Ahn, Ki Chang; Morisseau, Christophe; Gee, Shirley J; Hammock, Bruce D

    2011-04-01

    The antibacterial soap additive triclocarban (TCC) is widely used in personal care products. TCC has a high environmental persistence. We developed and validated a sensitive online solid-phase extraction-LC-MS/MS method to rapidly analyze TCC and its major metabolites in urine and other biological samples to assess human exposure. We measured human urine concentrations 0-72 h after showering with a commercial bar soap containing 0.6% TCC. The major route of renal elimination was excretion as N-glucuronides. The absorption was estimated at 0.6% of the 70±15 mg of TCC in the soap used. The TCC-N-glucuronide urine concentration varied widely among the subjects, and continuous daily use of the soap led to steady state levels of excretion. In order to assess potential biological effects arising from this exposure, we screened TCC for the inhibition of human enzymes in vitro. We demonstrate that TCC is a potent inhibitor of the enzyme soluble epoxide hydrolase (sEH), whereas TCC's major metabolites lack strong inhibitory activity. Topical administration of TCC at similar levels to rats in a preliminary in vivo study, however, failed to alter plasma biomarkers of sEH activity. Overall the analytical strategy described here revealed that use of TCC soap causes exposure levels that warrant further evaluation. PMID:21381656

  6. Investigation of human exposure to triclocarban after showering, and preliminary evaluation of its biological effects

    PubMed Central

    Schebb, Nils Helge; Inceoglu, Bora; Ahn, Ki Chang; Morisseau, Christophe; Gee, Shirley; Hammock, Bruce D.

    2012-01-01

    The antibacterial soap additive triclocarban (TCC) is widely used in personal care products. TCC has a high environmental persistence. We developed and validated a sensitive online solid phase extraction-LC-MS/MS method to rapidly analyze TCC and its major metabolites in urine and other biological samples to assess human exposure. We measured human urine concentrations 0–72 h after showering with a commercial bar soap containing 0.6% TCC. The major route of renal elimination was excretion as N-glucuronides. The absorption was estimated at 0.6% of the 70±15 mg TCC in the soap used. The TCC N-glucuronide urine concentration varied widely among the subjects and continuous daily use of the soap led to steady state levels of excretion. In order to assess potential biological effects arising from this exposure we screened TCC for the inhibition of human enzymes in vitro. We demonstrate that TCC is a potent inhibitor of the enzyme soluble epoxide hydrolase (sEH), whereas TCC′s major metabolites lack strong inhibitory activity. Topical administration of TCC at similar levels to rats in a preliminary in vivo study however failed to alter plasma biomarkers of sEH activity. Overall the analytical strategy described here revealed that use of TCC soap causes exposure levels that warrant further evaluation. PMID:21381656

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

    PubMed Central

    Lover, Andrew A.

    2015-01-01

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

  8. Molecular cytogenetic analysis of human blastocysts andcytotrophoblasts by multi-color FISH and Spectra Imaging analyses

    SciTech Connect

    Weier, Jingly F.; Ferlatte, Christy; Baumgartner, Adolf; Jung,Christine J.; Nguyen, Ha-Nam; Chu, Lisa W.; Pedersen, Roger A.; Fisher,Susan J.; Weier, Heinz-Ulrich G.

    2006-02-08

    Numerical chromosome aberrations in gametes typically lead to failed fertilization, spontaneous abortion or a chromosomally abnormal fetus. By means of preimplantation genetic diagnosis (PGD), we now can screen human embryos in vitro for aneuploidy before transferring the embryos to the uterus. PGD allows us to select unaffected embryos for transfer and increases the implantation rate in in vitro fertilization programs. Molecular cytogenetic analyses using multi-color fluorescence in situ hybridization (FISH) of blastomeres have become the major tool for preimplantation genetic screening of aneuploidy. However, current FISH technology can test for only a small number of chromosome abnormalities and hitherto failed to increase the pregnancy rates as expected. We are in the process of developing technologies to score all 24 chromosomes in single cells within a 3 day time limit, which we believe is vital to the clinical setting. Also, human placental cytotrophoblasts (CTBs) at the fetal-maternal interface acquire aneuploidies as they differentiate to an invasive phenotype. About 20-50% of invasive CTB cells from uncomplicated pregnancies were found aneuploidy, suggesting that the acquisition of aneuploidy is an important component of normal placentation, perhaps limiting the proliferative and invasive potential of CTBs. Since most invasive CTBs are interphase cells and possess extreme heterogeneity, we applied multi-color FISH and repeated hybridizations to investigate individual CTBs. In summary, this study demonstrates the strength of Spectral Imaging analysis and repeated hybridizations, which provides a basis for full karyotype analysis of single interphase cells.

  9. Integrative analyses shed new light on human ribosomal protein gene regulation.

    PubMed

    Li, Xin; Zheng, Yiyu; Hu, Haiyan; Li, Xiaoman

    2016-01-01

    Ribosomal protein genes (RPGs) are important house-keeping genes that are well-known for their coordinated expression. Previous studies on RPGs are largely limited to their promoter regions. Recent high-throughput studies provide an unprecedented opportunity to study how human RPGs are transcriptionally modulated and how such transcriptional regulation may contribute to the coordinate gene expression in various tissues and cell types. By analyzing the DNase I hypersensitive sites under 349 experimental conditions, we predicted 217 RPG regulatory regions in the human genome. More than 86.6% of these computationally predicted regulatory regions were partially corroborated by independent experimental measurements. Motif analyses on these predicted regulatory regions identified 31 DNA motifs, including 57.1% of experimentally validated motifs in literature that regulate RPGs. Interestingly, we observed that the majority of the predicted motifs were shared by the predicted distal and proximal regulatory regions of the same RPGs, a likely general mechanism for enhancer-promoter interactions. We also found that RPGs may be differently regulated in different cells, indicating that condition-specific RPG regulatory regions still need to be discovered and investigated. Our study advances the understanding of how RPGs are coordinately modulated, which sheds light to the general principles of gene transcriptional regulation in mammals. PMID:27346035

  10. Construction and analyses of human large-scale tissue specific networks.

    PubMed

    Liu, Wei; Wang, Jianying; Wang, Tengjiao; Xie, Hongwei

    2014-01-01

    Construction and analyses of tissue specific networks is crucial to unveil the function and organizational structure of biological systems. As a direct method to detect protein dynamics, human proteome-wide expression data provide an valuable resource to investigate the tissue specificity of proteins and interactions. By integrating protein expression data with large-scale interaction network, we constructed 30 tissue/cell specific networks in human and analyzed their properties and functions. Rather than the tissue specificity of proteins, we mainly focused on the tissue specificity of interactions to distill tissue specific networks. Through comparing our tissue specific networks with those inferred from gene expression data, we found our networks have larger scales and higher reliability. Furthermore, we investigated the similar extent of multiple tissue specific networks, which proved that tissues with similar functions tend to contain more common interactions. Finally, we found that the tissue specific networks differed from the static network in multiple topological properties. The proteins in tissue specific networks are interacting looser and the hubs play more important roles than those in the static network. PMID:25513809

  11. Integrative analyses shed new light on human ribosomal protein gene regulation

    PubMed Central

    Li, Xin; Zheng, Yiyu; Hu, Haiyan; Li, Xiaoman

    2016-01-01

    Ribosomal protein genes (RPGs) are important house-keeping genes that are well-known for their coordinated expression. Previous studies on RPGs are largely limited to their promoter regions. Recent high-throughput studies provide an unprecedented opportunity to study how human RPGs are transcriptionally modulated and how such transcriptional regulation may contribute to the coordinate gene expression in various tissues and cell types. By analyzing the DNase I hypersensitive sites under 349 experimental conditions, we predicted 217 RPG regulatory regions in the human genome. More than 86.6% of these computationally predicted regulatory regions were partially corroborated by independent experimental measurements. Motif analyses on these predicted regulatory regions identified 31 DNA motifs, including 57.1% of experimentally validated motifs in literature that regulate RPGs. Interestingly, we observed that the majority of the predicted motifs were shared by the predicted distal and proximal regulatory regions of the same RPGs, a likely general mechanism for enhancer-promoter interactions. We also found that RPGs may be differently regulated in different cells, indicating that condition-specific RPG regulatory regions still need to be discovered and investigated. Our study advances the understanding of how RPGs are coordinately modulated, which sheds light to the general principles of gene transcriptional regulation in mammals. PMID:27346035

  12. Do Lambs Perceive Regular Human Stroking as Pleasant? Behavior and Heart Rate Variability Analyses

    PubMed Central

    Coulon, Marjorie; Nowak, Raymond; Peyrat, Julie; Chandèze, Hervé; Boissy, Alain; Boivin, Xavier

    2015-01-01

    Stroking by humans is beneficial to the human-animal relationship and improves welfare in many species that express intraspecific allogrooming, but very few studies have looked at species like sheep that do not express such contact except around parturition. This study investigated the way lambs perceive regular human tactile contact using behavioral and physiological responses. Twenty-four lambs were reared and bucket-fed in groups of four. All were stroked daily by their familiar caregiver. At 8 weeks of age, the lambs were individually tested in their home pen but in a 1×1m open-barred pen after a 15h period of habituation to physical separation from peers while remaining in visual and auditory contact. Half of the lambs received stroking by their caregiver for 8min and half were exposed to their caregiver’s immobile presence. Heart rate and heart rate variability were recorded and analyzed by 2-min slots over the same interval based on three measures: mean heart rate value (HR), root mean square of successive differences (RMSSD) and standard deviation of all intervals measured between consecutive sinus beats (SDNN). Behavioral responses (ear postures of the lamb and time spent in contact with the familiar caregiver, on the knees of the familiar caregiver, and moving) were recorded throughout the test. Lamb HR decreased continuously while in the presence of their caregiver. Lambs being stroked showed slower HR and higher RMSSD which reflected positive emotional states compared to lambs left unstroked. All behavioral variables were highly correlated with the main component axis of the PCA analyses: the more the animals stayed in contact with their caregiver, the less they moved and the more their ears were hanging. This first component clearly differentiates lambs being stroked or not. Behavioral and physiological observations support the hypothesis that gentle physical contact with the caregiver is perceived positively by lambs. PMID:25714604

  13. In vitro and in vivo analyses of human embryonic stem cell-derived dopamine neurons.

    PubMed

    Park, Chang-Hwan; Minn, Yang-Ki; Lee, Ji-Yeon; Choi, Dong Ho; Chang, Mi-Yoon; Shim, Jae-Won; Ko, Ji-Yun; Koh, Hyun-Chul; Kang, Min Jeong; Kang, Jin Sun; Rhie, Duck-Joo; Lee, Yong-Sung; Son, Hyeon; Moon, Shin Yong; Kim, Kwang-Soo; Lee, Sang-Hun

    2005-03-01

    Human embryonic stem (hES) cells, due to their capacity of multipotency and self-renewal, may serve as a valuable experimental tool for human developmental biology and may provide an unlimited cell source for cell replacement therapy. The purpose of this study was to assess the developmental potential of hES cells to replace the selectively lost midbrain dopamine (DA) neurons in Parkinson's disease. Here, we report the development of an in vitro differentiation protocol to derive an enriched population of midbrain DA neurons from hES cells. Neural induction of hES cells co-cultured with stromal cells, followed by expansion of the resulting neural precursor cells, efficiently generated DA neurons with concomitant expression of transcriptional factors related to midbrain DA development, such as Pax2, En1 (Engrailed-1), Nurr1, and Lmx1b. Using our procedure, the majority of differentiated hES cells (> 95%) contained neuronal or neural precursor markers and a high percentage (> 40%) of TuJ1+ neurons was tyrosine hydroxylase (TH)+, while none of them expressed the undifferentiated ES cell marker, Oct 3/4. Furthermore, hES cell-derived DA neurons demonstrated functionality in vitro, releasing DA in response to KCl-induced depolarization and reuptake of DA. Finally, transplantation of hES-derived DA neurons into the striatum of hemi-parkinsonian rats failed to result in improvement of their behavioral deficits as determined by amphetamine-induced rotation and step-adjustment. Immunohistochemical analyses of grafted brains revealed that abundant hES-derived cells (human nuclei+ cells) survived in the grafts, but none of them were TH+. Therefore, unlike those from mouse ES cells, hES cell-derived DA neurons either do not survive or their DA phenotype is unstable when grafted into rodent brains. PMID:15715675

  14. Do lambs perceive regular human stroking as pleasant? Behavior and heart rate variability analyses.

    PubMed

    Coulon, Marjorie; Nowak, Raymond; Peyrat, Julie; Chandèze, Hervé; Boissy, Alain; Boivin, Xavier

    2015-01-01

    Stroking by humans is beneficial to the human-animal relationship and improves welfare in many species that express intraspecific allogrooming, but very few studies have looked at species like sheep that do not express such contact except around parturition. This study investigated the way lambs perceive regular human tactile contact using behavioral and physiological responses. Twenty-four lambs were reared and bucket-fed in groups of four. All were stroked daily by their familiar caregiver. At 8 weeks of age, the lambs were individually tested in their home pen but in a 1×1m open-barred pen after a 15 h period of habituation to physical separation from peers while remaining in visual and auditory contact. Half of the lambs received stroking by their caregiver for 8 min and half were exposed to their caregiver's immobile presence. Heart rate and heart rate variability were recorded and analyzed by 2-min slots over the same interval based on three measures: mean heart rate value (HR), root mean square of successive differences (RMSSD) and standard deviation of all intervals measured between consecutive sinus beats (SDNN). Behavioral responses (ear postures of the lamb and time spent in contact with the familiar caregiver, on the knees of the familiar caregiver, and moving) were recorded throughout the test. Lamb HR decreased continuously while in the presence of their caregiver. Lambs being stroked showed slower HR and higher RMSSD which reflected positive emotional states compared to lambs left unstroked. All behavioral variables were highly correlated with the main component axis of the PCA analyses: the more the animals stayed in contact with their caregiver, the less they moved and the more their ears were hanging. This first component clearly differentiates lambs being stroked or not. Behavioral and physiological observations support the hypothesis that gentle physical contact with the caregiver is perceived positively by lambs. PMID:25714604

  15. Purification, crystallization and preliminary crystallographic analysis of human cystathionine β-synthase

    PubMed Central

    Oyenarte, Iker; Majtan, Tomas; Ereño, June; Corral-Rodríguez, María Angeles; Kraus, Jan P.; Martínez-Cruz, Luis Alfonso

    2012-01-01

    Human cystathionine β-synthase (CBS) is a pyridoxal-5′-phosphate-dependent hemeprotein, whose catalytic activity is regulated by S-adenosylmethionine. CBS catalyzes the β-replacement reaction of homocysteine (Hcy) with serine to yield cystathionine. CBS is a key regulator of plasma levels of the thrombogenic Hcy and deficiency in CBS is the single most common cause of homocystinuria, an inherited metabolic disorder of sulfur amino acids. The properties of CBS enzymes, such as domain organization, oligomerization degree or regulatory mechanisms, are not conserved across the eukaryotes. The current body of knowledge is insufficient to understand these differences and their impact on CBS function and physiology. To overcome this deficiency, we have addressed the crystallization and preliminary crystallographic analysis of a protein construct (hCBS516–525) that contains the full-length CBS from Homo sapiens (hCBS) and just lacks amino-acid residues 516–525, which are located in a disordered loop. The human enzyme yielded crystals belonging to space group I222, with unit-cell parameters a = 124.98, b = 136.33, c = 169.83 Å and diffracting X-rays to a resolution of 3.0 Å. The crystal structure appears to contain two molecules in the asymmetric unit which presumably correspond to a dimeric form of the enzyme. PMID:23143240

  16. Preliminary study of cytotoxic effects of photodynamic therapy and immunotherapy on human pancreatic cancer cells

    NASA Astrophysics Data System (ADS)

    Wang, Luowei; Liu, Bolin; Chen, Yang K.; Li, Zhaoshen; Hetzel, Fred W.; Huang, Zheng

    2009-02-01

    Pancreatic cancer is the fourth most common cause of cancer death in the western world. The disease is very resistant to radiotherapy and chemotherapy. One reason for that is the resistance of pancreatic cancer cells to apoptosis. Among the current investigational approaches, targeting human epidermal growth factor receptor (HER-1/EGFR) and interstitial photodynamic therapy (PDT) show promises. When used alone or together, these new approaches might provide an alternative modality to treat pancreatic cancer. This study examined and compared cytotoxic effects of antibody C225 (an anti-HER-1/EGFR monoclonal antibody) and Photofrin-mediated PDT on two human pancreatic cancer cell lines (BxPc-3, HPAF-II). Preliminary in vitro data indicated that these treatments could block various proliferation pathways of pancreatic cancer cells through different mechanisms. For instance, PDT could induce early apoptosis. C225 could induce G1 arrest. These findings might help to design new strategies such as the combination of PDT and immunotherapy for the treatment of pancreatic cancer.

  17. Proteome profiling of cadmium-induced apoptosis by antibody array analyses in human bronchial epithelial cells

    PubMed Central

    Xu, Yan-Ming; Yu, Fei-Yuan; Yang, Feng; Yao, Yue; Zhou, Yuan; Ching, Yick-Pang; Lau, Andy T. Y.

    2016-01-01

    Protein array technology is a powerful platform for the simultaneous determination of the expression levels of a number of proteins as well as post-translational modifications such as phosphorylation. Here, we screen and report for the first time, the dominant signaling cascades and apoptotic mediators during the course of cadmium (Cd)-induced cytotoxicity in human bronchial epithelial cells (BEAS-2B) by antibody array analyses. Proteins from control and Cd-treated cells were captured on Proteome Profiler™ Arrays for the parallel determination of the relative levels of protein phosphorylation and proteins associated with apoptosis. Our results indicated that the p38 MAPK- and JNK-related signal transduction pathways were dramatically activated by Cd treatment. Cd potently stimulates the phosphorylations of p38α (MAPK14), JNK1/2 (MAPK8/9), and JUN; while the phosphorylations of Akt1, ERK1/2 (MAPK3/1), GSK3β, and mTOR were suppressed. Moreover, there was an induction of proapoptotic protein BAX, release of cytochrome c (CYCS) from mitochondria, activation of caspase-3/9 (CASP3/9); as well as decreased expression of cell cycle checkpoint proteins (TP53, p21, and p27) and several inhibitors of apoptosis proteins (IAPs) [including cIAP-1/2 (BIRC2/3), XIAP (BIRC4), and survivin (BIRC5)]. Pretreatment of cells with the thiol antioxidant glutathione or p38 MAPK/JNK inhibitors before Cd treatment effectively abrogated ROS activation of p38 MAPK/JNK pathways and apoptosis-related proteins. Taken together, our results demonstrate that Cd causes oxidative stress-induced apoptosis; and the p38 MAPK/JNK and mitochondrial pathways are more importantly participated for signal transduction and the induction of apoptosis in Cd-exposed human lung cells. PMID:26716417

  18. Next Generation Munitions Handler: Human-Machine Interface and Preliminary Performance Evaluation

    SciTech Connect

    Draper, J.V.; Jansen, J.F.; Pin, F.G.; Rowe, J.C.

    1999-04-25

    The Next Generation Munitions Handler/Advanced Technology Demonstrator (NGMI-VATTD) is a technology demonstrator for the application of an advanced robotic device for re-arming U.S. Air Force (USAF) and U.S. Navy (USN) tactical fighters. It comprises two key hardware components: a heavy-lift dexterous manipulator (HDM) and a nonholonomic mobility platform. The NGMWATTD is capable of lifting weapons up to 4400 kg (2000 lb) and placing them on any weapons rack on existing fighters (including the F-22 Raptor). This report describes the NGMH mission with particular reference to human-machine interfaces. It also describes preliminary testing to garner feedback about the heavy-lift manipulator arm from experienced fighter load crewmen. The purpose of the testing was to provide preliminary information about control system parameters and to gather feed- back from users about manipulator arm functionality. To that end, the Air Force load crewmen interacted with the NGMWATTD in an informal testing session and provided feedback about the performance of the system. Certain con- trol system parameters were changed during the course of the testing and feedback from the participants was used to make a rough estimate of "good" initial operating parameters. Later, formal testing will concentrate within this range to identify optimal operating parameters. User reactions to the HDM were generally positive, All of the USAF personnel were favorably impressed with the capabilities of the system. Fine-tuning operating parameters created a system even more favorably regarded by the load crews. Further adjustment to control system parameters will result in a system that is operationally efficient, easy to use, and well accepted by users.

  19. A preliminary report on stem cell therapy for neuropathic pain in humans

    PubMed Central

    Vickers, E Russell; Karsten, Elisabeth; Flood, John; Lilischkis, Richard

    2014-01-01

    Objective Mesenchymal stem cells (MSCs) have been shown in animal models to attenuate chronic neuropathic pain. This preliminary study investigated if: i) injections of autologous MSCs can reduce human neuropathic pain and ii) evaluate the safety of the procedure. Methods Ten subjects with symptoms of neuropathic trigeminal pain underwent liposuction. The lipoaspirate was digested with collagenase and washed with saline three times. Following centrifugation, the stromal vascular fraction was resuspended in saline, and then transferred to syringes for local injections into the pain fields. Outcome measures at 6 months assessed reduction in: i) pain intensity measured by standard numerical rating scale from 0–10 and ii) daily dosage requirements of antineuropathic pain medication. Results Subjects were all female (mean age 55.3 years ± standard deviation [SD] 14.67; range 27–80 years) with pain symptoms lasting from 4 months to 6 years and 5 months. Lipoaspirate collection ranged from 102–214 g with total cell numbers injected from 33 million to 162 million cells. Cell viability was 62%–91%. There were no systemic or local tissue side effects from the stem cell therapy (n=41 oral and facial injection sites). Clinical pain outcomes showed that at 6 months, 5/9 subjects had reduced both pain intensity scores and use of antineuropathic medication. The mean pain score pre-treatment was 7.5 (SD 1.58) and at 6 months had decreased to 4.3 (SD 3.28), P=0.018, Wilcoxon signed-rank test. Antineuropathic pain medication use showed 5/9 subjects reduced their need for medication (gabapentin, P=0.053, Student’s t-test). Conclusion This preliminary open-labeled study showed autologous administration of stem cells for neuropathic trigeminal pain significantly reduced pain intensity at 6 months and is a safe and well tolerated intervention. PMID:24855388

  20. Building-related symptoms among U.S. office workers and risks factors for moisture and contamination: Preliminary analyses of U.S. EPA BASE Data

    SciTech Connect

    Mendell, Mark J.; Cozen, Myrna

    2002-09-01

    dirty cooling coils were associated with a nonsignificant increase in lower respiratory symptoms. These preliminary findings suggest that some factors that indicate risks for moisture or contamination in office buildings may have adverse effects on respiratory or neurologic health of office workers. More refined analyses are underway that will include these risk factors in simultaneous multivariate models along with additional risk factors that may be confounders, such as ventilation rate and indoor temperature. Future analyses will also use more refined metrics for both health outcomes and environmental risks, as well as assess risk in susceptible sub-groups.

  1. Activity determination, kinetic analyses and isoenzyme identification of gamma glutamyltransferase in human neutrophils.

    PubMed

    Sener, Azize; Yardimci, Turay

    2005-05-31

    Gamma-glutamyltransferase (GGT, EC 2.3.2.2) which hydrolyzes glutathione (GSH), is required for the maintenance of normal intracellular GSH concentration. GGT is a membrane enzyme present in leukocytes and platelets. Its activity has also been observed in human neutrophils. In this study, GGT was purified from Triton X-100 solubilized neutrophils and its kinetic parameters were determined. For kinetic analyses of transpeptidation reaction, gamma-glutamyl p-nitroanilide was used as the substrate and glycylglycine as the acceptor. Apparent K(m) values were determined as 1.8 mM for gamma-glutamyl p-nitroanilide and 16.9 mM for glycylglycine. The optimum pH of GGT activity was 8.2 and the optimum temperature was 37 degrees C. It had thermal stability with 58 % relative activity at 56 degrees C for 30 min incubation. L-serine, in the presence of borate, was detected as the competitive inhibitor. Bromcresol green inhibited neutrophil GGT activity as a noncompetitive inhibitor. The neutrophils seem to contain only the isoenzyme that is present in platelets. We characterized the kinetic properties and compared the type of the isoenzyme of neutrophil GGT with platelet GGT via polyacrylamide gel electrophoresis (PAGE) under a standard set of conditions. PMID:15943911

  2. Development of phantom for quantitative analyses of human dentin mineral density.

    PubMed

    Hayashi-Sakai, Sachiko; Kondo, Tatsuya; Kasuga, Yuto; Sakamoto, Makoto; Endo, Hideaki; Sakai, Jun

    2015-01-01

    The purpose of the present study was to develop a novel-designed phantom that could be scanned with a sample in the same image, that specialize for quantitative analyses of human dentin mineral density using the X-ray attenuation method. A further attempt was made to demonstrate the intracoronal dentin mineral density using this phantom in mandibular incisors. The phantom prepared with a 15 mm hole in the center of an acrylic resin bar having an outside diameter of 25 mm and 8 small holes (diameter, 3 mm) were made at equal intervals around the center. Liquid dipotassium hydrogen phosphate (K2HPO4) solutions were established at 0.4, 0.6, 0.8 and 1.0 g/cm3, and were arranged to these holes. The mean value of the intracoronal dentin mineral density was 1.486 ± 0.016 g/cm3 in the present study. As the results of the present study corresponded to previous reports, this new phantom was considered to be useful. This phantom enables the analysis of samples that are not readily available by conventional mechanical tests and may facilitate biomechanical investigations using X-ray images. It was suggested that this system is a simple, accurate and novel mineralization measuring system. PMID:26484556

  3. Tissue gas and blood analyses of human subjects breathing 80% argon and 20% oxygen

    NASA Technical Reports Server (NTRS)

    Horrigan, D. J.; Wells, C. H.; Guest, M. M.; Hart, G. B.; Goodpasture, J. E.

    1979-01-01

    Eight human volunteers, individually studied in a hyperbaric chamber, breathed: (1) air at 1 ATA; (2) 80% argon and 20% oxygen at 1 ATA for 30 min; (3) air at 1 ATA for 30 min; (4) 100% O2 at 1 ATA for 30 min; (5) air at 1 ATA for 30 min; (6) 100% O2 at 2 ATA for 60 min; and (7) 80% argon and 20% oxygen at 1 ATA for 30 min. Oxygen, carbon dioxide, nitrogen, and argon tensions were measured in muscle and subcutaneous tissue by mass spectroscopic analyses. Venous blood obtained at regular intervals was analyzed for coagulation and fibrinolytic factors. Inert gas narcosis was not observed. After breathing argon for 30 min, muscle argon tensions were almost three times the subcutaneous tensions. Argon wash-in mirrored nitrogen wash-out. Argon wash-in and wash-out had no effect on tissue PO2 or PCO2. Coagulation and fibrinolytic changes usually associated with vascular bubbles were absent.

  4. Expression, purification, crystallization and preliminary crystallographic analysis of human myotubularin-related protein 3

    PubMed Central

    Son, Ji Young; Lee, Jee Un; Yoo, Ki-Young; Shin, Woori; Im, Dong-Won; Kim, Seung Jun; Ryu, Seong Eon; Heo, Yong-Seok

    2014-01-01

    Myotubularin-related proteins are a large family of phosphatases that have the catalytic activity of dephosphorylating the phospholipid molecules phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate. Each of the 14 family members contains a phosphatase catalytic domain, which is inactive in six family members owing to amino-acid changes in a key motif for the activity. All of the members also bear PH-GRAM domains, which have low homologies between them and have roles that are not yet clear. Here, the cloning, expression, purification and crystallization of human myotubularin-related protein 3 encompassing the PH-GRAM and the phosphatase catalytic domain are reported. Preliminary X-ray crystallographic analysis shows that the crystals diffracted to 3.30 Å resolution at a synchrotron X-ray source. The crystals belonged to space group C2, with unit-cell parameters a = 323.3, b = 263.3, c = 149.4 Å, β = 109.7°. PMID:25195900

  5. Preliminary report on the correlations among pineal concretions, prostatic calculi and age in human adult males.

    PubMed

    Mori, Ryoichi; Kodaka, Tetsuo; Sano, Tsuneyoshi

    2003-09-01

    By using quantitative image analysis of soft X-ray photographs on the bulk of extracted pineal glands and prostates, we made a preliminary investigation into the correlations among pineal concretions (% by mass), prostatic calculi (% by mass) and age (years) in 40 human adult males, ranging in age from 31 to 95 years (mean (+/-SD) 69.9 +/- 15.2 years), who died and underwent the routine dissection course. The mass concentrations of pineal concretions and prostatic calculi were 17.68 +/- 13.56% (range 0-51.34%) and 0.93 +/- 1.31% (range 0-5.82%), respectively. There was no correlation between the mass concentration of pineal concretions and aging (r = 0.03; P < 1.0). There was no correlation between mass concentration of prostatic calculi and aging (r = 0.28; P < 0.5). No pineal concretions and no prostatic calculi were observed in seven and 10 cases, respectively; in addition, in one case, neither-concretions nor calculi were seen. From such data and from the previously reported suggestion on the counteracting functions between the pineal gland and prostate, a negative correlation between the mass concentrations of pineal concretions and prostatic calculi was expected. This was certainly obtained, but the correlation was low (r = -0.39; P < 0.05). Such a low correlation and no correlations between the concentrations of pineal concretions and aging or between prostatic calculi and aging may have been caused by the examination of relatively older humans. Therefore, further investigations using a number of pair samples collected from males including younger age generations will be necessary. PMID:14527133

  6. Volume analysis of heat-induced cracks in human molars: A preliminary study

    PubMed Central

    Sandholzer, Michael A.; Baron, Katharina; Heimel, Patrick; Metscher, Brian D.

    2014-01-01

    Context: Only a few methods have been published dealing with the visualization of heat-induced cracks inside bones and teeth. Aims: As a novel approach this study used nondestructive X-ray microtomography (micro-CT) for volume analysis of heat-induced cracks to observe the reaction of human molars to various levels of thermal stress. Materials and Methods: Eighteen clinically extracted third molars were rehydrated and burned under controlled temperatures (400, 650, and 800°C) using an electric furnace adjusted with a 25°C increase/min. The subsequent high-resolution scans (voxel-size 17.7 μm) were made with a compact micro-CT scanner (SkyScan 1174). In total, 14 scans were automatically segmented with Definiens XD Developer 1.2 and three-dimensional (3D) models were computed with Visage Imaging Amira 5.2.2. The results of the automated segmentation were analyzed with an analysis of variance (ANOVA) and uncorrected post hoc least significant difference (LSD) tests using Statistical Package for Social Sciences (SPSS) 17. A probability level of P < 0.05 was used as an index of statistical significance. Results: A temperature-dependent increase of heat-induced cracks was observed between the three temperature groups (P < 0.05, ANOVA post hoc LSD). In addition, the distributions and shape of the heat-induced changes could be classified using the computed 3D models. Conclusion: The macroscopic heat-induced changes observed in this preliminary study correspond with previous observations of unrestored human teeth, yet the current observations also take into account the entire microscopic 3D expansions of heat-induced cracks within the dental hard tissues. Using the same experimental conditions proposed in the literature, this study confirms previous results, adds new observations, and offers new perspectives in the investigation of forensic evidence. PMID:25125923

  7. Human factors evaluation of remote afterloading brachytherapy. Supporting analyses of human-system interfaces, procedures and practices, training and organizational practices and policies. Volume 3

    SciTech Connect

    Callan, J.R.; Kelly, R.T.; Quinn, M.L.

    1995-07-01

    A human factors project on the use of nuclear by-product material to treat cancer using remotely operated afterloaders was undertaken by the Nuclear Regulatory Commission. The purpose of the project was to identify factors that contribute to human error in the system for remote afterloading brachytherapy (RAB). This report documents the findings from the second, third, fourth, and fifth phases of the project, which involved detailed analyses of four major aspects of the RAB system linked to human error: human-system interfaces; procedures and practices; training practices and policies; and organizational practices and policies, respectively. Findings based on these analyses provided factual and conceptual support for the final phase of this project, which identified factors leading to human error in RAB. The impact of those factors on RAB performance was then evaluated and prioritized in terms of safety significance, and alternative approaches for resolving safety significant problems were identified and evaluated.

  8. Preliminary 3-D finite element analyses of the triggering mechanism of an occasional reactivation of a large landslide in stiff clays

    NASA Astrophysics Data System (ADS)

    Lollino, Piernicola; Fazio, Nunzio Luciano; Vennari, Carmela; Parise, Mario

    2015-04-01

    In December 2013 a large landslide occurred along a clay slope located at the south-western outskirts of the Montescaglioso village (Basilicata, Southern Italy) as a consequence of intense and prolonged rainfalls that presumably caused a significant increment of the pore water pressures in the slope. The slope is formed of stiff clays belonging to the formation of the Subappennine Blue Clays, which are over-consolidated and characterized by medium plasticity. According to aerial photos dating back to 1950s, the slope was already affected by previous landslide processes, so that the examined landslide process can be classified as an occasional reactivation according to the well-known classification of Cruden & Varnes (1996). Also, during the last decades several man-made actions in the area resulted in strong changes in the original water surface network that could have played some role in the slope reactivation. Based on displacement data, obtained from a monitoring system installed few days after the phenomenon, and still in function, at present the landslide does not show relevant signs of activity. Preliminary 2-D and 3-D finite element analyses have been carried out to investigate the factors that controlled the mechanism of reactivation of the landslide. The numerical model has been setup based on the available topographical, geological and geomorphological information, the geotechnical properties of the involved soils and the information concerning the piezometric regime in the slope. The results indicate that the mobilized shear strength of the clays ranges between the typical post-peak and residual values for this type of material and confirmed that the strong increment of the pore water pressures in the slope induced by the exceptional rainfalls occurred in the previous days can be identified as the main triggering factor of the reactivation.

  9. Comparative proteome analyses of human plasma following in vivo lipopolysaccharide administration using multidimensional separations coupled with tandem mass spectrometry

    SciTech Connect

    Qian, Weijun; Jacobs, Jon M.; Camp, David G.; Monroe, Matthew E.; Moore, Ronald J.; Gritsenko, Marina A.; Calvano, Steven E.; Lowry, Stephen F.; Xiao, Wenzhong; Moldawer, Lyle L.; Davis, Ronald W.; Tompkins, Ronald G.; Smith, Richard D.

    2005-02-05

    There is significant interest in characterization of the human plasma proteome due to its potential for providing biomarkers applicable to clinical diagnosis and treatment and for gaining a better understanding of human diseases. We describe here a strategy for comparative proteome analyses of human plasma, which is applicable to biomarker identifications for various disease states. Multidimensional liquid chromatography-mass spectrometry has been applied to make comparative proteome analyses of plasma samples from an individual prior to and 9 h after lipopolysaccharide (LPS) administration. Peptide peak areas and the number of peptide identifications for each protein were used to evaluate the reproducibility of LC-MS/MS and to compare relative changes in protein concentration between the samples following LPS treatment. A total of 1563 distinct plasma proteins were confidently identified with 26 proteins observed to be significantly increased in concentration following LPS administration, including several known inflammatory response or acute-phase mediators, and thus constitute potential biomarkers for inflammatory response.

  10. Association of Different Human Rhinovirus Species with Asthma in Children: A Preliminary Study

    PubMed Central

    Zhao, Min; Zhu, Wen-Jing; Qian, Yuan; Sun, Yu; Zhu, Ru-Nan; Deng, Jie; Wang, Fang; Ding, Ya-Xin; Tian, Run; Liu, Chuan-He; Meng, Ling-Hui; Zhao, Lin-Qing

    2016-01-01

    Background: Human rhinoviruses (HRVs) are divided into three genetic species: HRV-A, HRV-B, and HRV-C. The association of different HRV species with asthma in children in China has not yet been evaluated. This preliminary study aimed to assess the associations between different HRV species, particularly HRV-C, and asthma in young children in China. Methods: A total of 702 nasopharyngeal aspirates were obtained from 155 children with asthma (asthma group), 461 children with acute respiratory infection (ARI) without asthma (nonasthma ARI group), and 86 children from the control group. Semi-nested polymerase chain reaction (PCR) was used to detect HRVs, and PCR products were sequenced for species identification. Epidemiological characteristics of HRV-positive cases were analyzed. Results: HRVs were the most common pathogen (15.4%; 108/702) in the patients in this study. The prevalence of HRV was significantly different (F = 20.633, P = 0.000) between the asthma (25.8%) and nonasthma ARI groups (11.1%). Phylogenetic analysis indicated that in the 108 cases positive for HRVs, 41 were identified as HRV-A, 8 as HRV-B, and 56 as HRV-C. Comparing the asthma with the nonasthma ARI group, Spearman's rank correlation analysis revealed an association between HRV-A (P < 0.05) and C (P < 0.01) and asthma, confirmed by regression analysis, with odds ratios of 2.2 (HRV-A) and 4.2 (HRV-C). Conclusions: Our data revealed a high prevalence of HRVs in children in China, regardless of clinical status. HRV-C was the dominant species and may be one of the key factors in the association of HRVs with asthma. PMID:27364785

  11. A model system to analyse the ability of human keratinocytes to form hair follicles.

    PubMed

    Thangapazham, Rajesh L; Klover, Peter; Li, Shaowei; Wang, Ji-An; Sperling, Leonard; Darling, Thomas N

    2014-06-01

    Earlier studies showed that dermal cells lose trichogenic capacity with passage, but studies on the effect of keratinocyte passage on human hair follicle neogenesis and graft quality have been hampered by the lack of a suitable model system. We recently documented human hair follicle neogenesis in grafted dermal-epidermal composites, and in the present study, we determined the effects of keratinocyte passage on hair follicle neogenesis. Dermal equivalents were made with cultured human dermal papilla cells and were overlaid with either primary or passaged human keratinocytes to form dermal-epidermal composites; these were then grafted onto immunodeficient mice. Superior hair follicle neogenesis was observed using early keratinocyte cultures. Characteristics such as formation of hair shafts and sebaceous glands, presence of hair follicles with features of anagen or telogen follicles, and reproducible hair and skin function parameters make this model a tool to study human hair follicle neogenesis and development. PMID:24758480

  12. Beech Fructification and Bank Vole Population Dynamics - Combined Analyses of Promoters of Human Puumala Virus Infections in Germany

    PubMed Central

    Reil, Daniela; Imholt, Christian; Eccard, Jana Anja; Jacob, Jens

    2015-01-01

    The transmission of wildlife zoonoses to humans depends, amongst others, on complex interactions of host population ecology and pathogen dynamics within host populations. In Europe, the Puumala virus (PUUV) causes nephropathia epidemica in humans. In this study we investigated complex interrelations within the epidemic system of PUUV and its rodent host, the bank vole (Myodes glareolus). We suggest that beech fructification and bank vole abundance are both decisive factors affecting human PUUV infections. While rodent host dynamics are expected to be directly linked to human PUUV infections, beech fructification is a rather indirect predictor by serving as food source for PUUV rodent hosts. Furthermore, we examined the dependence of bank vole abundance on beech fructification. We analysed a 12-year (2001-2012) time series of the parameters: beech fructification (as food resource for the PUUV host), bank vole abundance and human incidences from 7 Federal States of Germany. For the first time, we could show the direct interrelation between these three parameters involved in human PUUV epidemics and we were able to demonstrate on a large scale that human PUUV infections are highly correlated with bank vole abundance in the present year, as well as beech fructification in the previous year. By using beech fructification and bank vole abundance as predictors in one model we significantly improved the degree of explanation of human PUUV incidence. Federal State was included as random factor because human PUUV incidence varies considerably among states. Surprisingly, the effect of rodent abundance on human PUUV infections is less strong compared to the indirect effect of beech fructification. Our findings are useful to facilitate the development of predictive models for host population dynamics and the related PUUV infection risk for humans and can be used for plant protection and human health protection purposes. PMID:26214509

  13. Preliminary Assessment of Education and Human Resources in Thailand. Volume I, Report of the Joint Task Force; Volume II, Working Papers.

    ERIC Educational Resources Information Center

    Palakawongsa, Nai Nob; And Others

    This report was prepared by the Joint Thai-US Task Force on Human Resource Development in Thailand. Volume I of the Report includes: Human Resources Development in Thailand--A Preliminary Assessment; The Educational System and Human Resource Development in Thailand; Manpower Demand; Adjusting Educational Supply to Manpower Demand; Education…

  14. Functional Analyses of Transcription Factor Binding Sites that Differ between Present-Day and Archaic Humans.

    PubMed

    Weyer, Sven; Pääbo, Svante

    2016-02-01

    We analyze 25 previously identified transcription factor binding sites that carry DNA sequence changes that are present in all or nearly all present-day humans, yet occur in the ancestral state in Neandertals and Denisovans, the closest evolutionary relatives of humans. When the ancestral and derived forms of the transcription factor binding sites are tested using reporter constructs in 3 neuronal cell lines, the activity of 12 of the derived versions of transcription factor binding sites differ from the respective ancestral variants. This suggests that the majority of this class of evolutionary differences between modern humans and Neandertals may affect gene expression in at least some tissue or cell type. PMID:26454764

  15. Functional Analyses of Transcription Factor Binding Sites that Differ between Present-Day and Archaic Humans

    PubMed Central

    Weyer, Sven; Pääbo, Svante

    2016-01-01

    We analyze 25 previously identified transcription factor binding sites that carry DNA sequence changes that are present in all or nearly all present-day humans, yet occur in the ancestral state in Neandertals and Denisovans, the closest evolutionary relatives of humans. When the ancestral and derived forms of the transcription factor binding sites are tested using reporter constructs in 3 neuronal cell lines, the activity of 12 of the derived versions of transcription factor binding sites differ from the respective ancestral variants. This suggests that the majority of this class of evolutionary differences between modern humans and Neandertals may affect gene expression in at least some tissue or cell type. PMID:26454764

  16. U-series and radiocarbon analyses of human and faunal remains from Wajak, Indonesia.

    PubMed

    Storm, Paul; Wood, Rachel; Stringer, Chris; Bartsiokas, Antonis; de Vos, John; Aubert, Maxime; Kinsley, Les; Grün, Rainer

    2013-05-01

    Laser ablation U-series dating results on human and faunal bone fragments from Wajak, Indonesia, indicate a minimum age of between 37.4 and 28.5 ka (thousands of years ago) for the whole assemblage. These are significantly older than previously published radiocarbon estimates on bone carbonate, which suggested a Holocene age for a human bone fragment and a late Pleistocene age for a faunal bone. The analysis of the organic components in the faunal material show severe degradation and a positive δ(13)C ratio indicate a high degree of secondary carbonatisation. This may explain why the thermal release method used for the original age assessments yielded such young ages. While the older U-series ages are not in contradiction with the morphology of the Wajak human fossils or Javanese biostratigraphy, they will require a reassessment of the evolutionary relationships of modern human remains in Southeast Asia and Oceania. It can be expected that systematic direct dating of human fossils from this area will lead to further revisions of our understanding of modern human evolution. PMID:23465338

  17. Cell-specific expression and pathway analyses reveal alterations in trauma-related human T cell and monocyte pathways

    PubMed Central

    Laudanski, Krzysztof; Miller-Graziano, Carol; Xiao, Wenzhong; Mindrinos, Michael N.; Richards, Daniel R.; De, Asit; Moldawer, Lyle L.; Maier, Ronald V.; Bankey, Paul; Baker, Henry V.; Brownstein, Bernard H.; Cobb, J. Perren; Calvano, Steve E.; Davis, Ronald W.; Tompkins, Ronald G.

    2006-01-01

    Monitoring genome-wide, cell-specific responses to human disease, although challenging, holds great promise for the future of medicine. Patients with injuries severe enough to develop multiple organ dysfunction syndrome have multiple immune derangements, including T cell apoptosis and anergy combined with depressed monocyte antigen presentation. Genome-wide expression analysis of highly enriched circulating leukocyte subpopulations, combined with cell-specific pathway analyses, offers an opportunity to discover leukocyte regulatory networks in critically injured patients. Severe injury induced significant changes in T cell (5,693 genes), monocyte (2,801 genes), and total leukocyte (3,437 genes) transcriptomes, with only 911 of these genes common to all three cell populations (12%). T cell-specific pathway analyses identified increased gene expression of several inhibitory receptors (PD-1, CD152, NRP-1, and Lag3) and concomitant decreases in stimulatory receptors (CD28, CD4, and IL-2Rα). Functional analysis of T cells and monocytes confirmed reduced T cell proliferation and increased cell surface expression of negative signaling receptors paired with decreased monocyte costimulation ligands. Thus, genome-wide expression from highly enriched cell populations combined with knowledge-based pathway analyses leads to the identification of regulatory networks differentially expressed in injured patients. Importantly, application of cell separation, genome-wide expression, and cell-specific pathway analyses can be used to discover pathway alterations in human disease. PMID:17032758

  18. Stereoselective pharmacokinetics and metabolism of the enantiomers of cyclophosphamide. Preliminary results in humans and rabbits.

    PubMed

    Holm, K A; Kindberg, C G; Stobaugh, J F; Slavik, M; Riley, C M

    1990-04-15

    [R(+),S(-)]-Cyclophosphamide [(R,S)-CP] is an anticancer drug, containing a chiral phosphorous atom, which is prepared and used clinically as the racemic mixture. A new high-performance liquid chromatographic assay suitable for pharmacokinetic studies of CP enantiomers in plasma has been reported recently by this laboratory (Reid et al., Anal Chem 61: 441-446, 1989). Briefly, the assay involves ethyl acetate extraction of CP enantiomers from plasma followed by derivatization to diastereomers in a two-step process utilizing chloral and (+)-naproxen acid chloride. Chromatographic analysis was performed on a reversed phase (ODS) column with detection at 232 nm. In the present study, preliminary results on the applicability of this assay to pharmacokinetic studies are presented. Several rabbits were used to compare the influence of i.p., i.v., and oral routes of administration on the stereoselective disposition of (R,S)-CP. Following i.p. administration, S-CP was cleared faster than R-CP. Following oral administration, only R-CP was detectable in plasma, while i.v. administration resulted in minor or no stereoselective disposition. These results indicated that there was a marked stereoselective metabolism of the S-CP enantiomer, with the i.p. and oral routes producing the greatest differences due to first-pass metabolism. Incubation of rabbit-liver microsomes with (R,S)-CP demonstrated that the monooxygenase system can exhibit marked stereoselectivity in its metabolism of CP. The ratio of R-CP to S-CP in the incubation medium increased during the incubation period from 1:1 initially to 4.5:1 after 60 min. The results from the experiments with rabbits indicate that the first-pass metabolism of this drug is highly stereoselective; in contrast, cancer patients who had received (R,S)-CP as an i.v. infusion showed no stereoselectivity in the elimination of the enantiomers. Pharmacokinetic studies with cancer patients, receiving (R,S)-CP as an oral dose, are in progress in

  19. CELLPEDIA: a repository for human cell information for cell studies and differentiation analyses.

    PubMed

    Hatano, Akiko; Chiba, Hirokazu; Moesa, Harry Amri; Taniguchi, Takeaki; Nagaie, Satoshi; Yamanegi, Koji; Takai-Igarashi, Takako; Tanaka, Hiroshi; Fujibuchi, Wataru

    2011-01-01

    CELLPEDIA is a repository database for current knowledge about human cells. It contains various types of information, such as cell morphologies, gene expression and literature references. The major role of CELLPEDIA is to provide a digital dictionary of human cells for the biomedical field, including support for the characterization of artificially generated cells in regenerative medicine. CELLPEDIA features (i) its own cell classification scheme, in which whole human cells are classified by their physical locations in addition to conventional taxonomy; and (ii) cell differentiation pathways compiled from biomedical textbooks and journal papers. Currently, human differentiated cells and stem cells are classified into 2260 and 66 cell taxonomy keys, respectively, from which 934 parent-child relationships reported in cell differentiation or transdifferentiation pathways are retrievable. As far as we know, this is the first attempt to develop a digital cell bank to function as a public resource for the accumulation of current knowledge about human cells. The CELLPEDIA homepage is freely accessible except for the data submission pages that require authentication (please send a password request to cell-info@cbrc.jp). Database URL: http://cellpedia.cbrc.jp/ PMID:22039163

  20. Clonal analyses and gene profiling identify genetic biomarkers of human brown and white preadipocyte thermogenic potential

    PubMed Central

    Xue, Ruidan; Lynes, Matthew D.; Dreyfuss, Jonathan M.; Shamsi, Farnaz; Schulz, Tim J.; Zhang, Hongbin; Huang, Tian Lian; Townsend, Kristy L.; Li, Yiming; Takahashi, Hirokazu; Weiner, Lauren S.; White, Andrew P.; Lynes, Maureen S.; Rubin, Lee L.; Goodyear, Laurie J.; Cypess, Aaron M.; Tseng, Yu-Hua

    2015-01-01

    Targeting brown adipose tissue (BAT) content or activity has therapeutic potential for treating obesity and the metabolic syndrome by increasing energy expenditure. Both inter- and intra-individual differences contribute to heterogeneity in human BAT and potentially to differential thermogenic capacity in human populations. Here, we demonstrated the generated clones of brown and white preadipocytes from human neck fat of four individuals and characterized their adipogenic differentiation and thermogenic function. Combining an uncoupling protein 1(UCP1) reporter system and expression profiling, we defined novel sets of gene signatures in human preadipocytes that could predict the thermogenic potential of the cells once they were maturated in culture. Knocking out the positive UCP1 regulators identified by this approach, PREX1 and EDNRB in brown preadipocytes using CRISPR/Cas9 markedly abolished the high level of UCP1 in brown adipocytes differentiated from the preadipocytes. Finally, we were able to prospectively isolate adipose progenitors with great thermogenic potential using cell surface marker CD29. These data provide new insights into the cellular heterogeneity in human fat and offer the identification of possible biomarkers of thermogenically competent preadipocytes. PMID:26076036

  1. Molecular analyses of in vivo hprt mutations in human T-lymphocytes: IV. Studies in newborns

    SciTech Connect

    McGinniss, M.J.; Nicklas, J.A.; Albertini, R.J. )

    1989-01-01

    In order to characterize in vivo gene mutations that occur during fetal development, molecular analyses were undertaken of mutant 6-thioguanine resistant T-lymphocytes isolated from placental cord blood samples of 13 normal male newborns. These mutant T-cells were studied to define hypoxanthine-guanine phosphoribosyltransferase (hprt) gene structural alterations and to determine T-cell receptor (TCR) gene rearrangement patterns. Structural hprt alterations, as shown by Southern blot analyses, occurred in 85% of these mutant clones. These alterations consisted mostly of deletion of exons 2 and 3. These findings contrast with the 10-20% of gross structural alterations occurring randomly across the entire gene previously reported for T-cell mutants isolated from normal young adults. Iterative analyses of hprt structural alterations and TCR gene rearrangement patterns show that approximately one-third of the newborn derived mutants may have originated as pre- or intrathymic hprt mutations. This too contrasts with previous findings in adults where the background in vivo hprt mutations appeared to originate in postthymic T-lymphocytes.

  2. Human Infections with Spirometra decipiens Plerocercoids Identified by Morphologic and Genetic Analyses in Korea.

    PubMed

    Jeon, Hyeong-Kyu; Park, Hansol; Lee, Dongmin; Choe, Seongjun; Kim, Kyu-Heon; Huh, Sun; Sohn, Woon-Mok; Chai, Jong-Yil; Eom, Keeseon S

    2015-06-01

    Tapeworms of the genus Spirometra are pseudophyllidean cestodes endemic in Korea. At present, it is unclear which Spirometra species are responsible for causing human infections, and little information is available on the epidemiological profiles of Spirometra species infecting humans in Korea. Between 1979 and 2009, a total of 50 spargana from human patients and 2 adult specimens obtained from experimentally infected carnivorous animals were analyzed according to genetic and taxonomic criteria and classified as Spirometra erinaceieuropaei or Spirometra decipiens depending on the morphology. Morphologically, S. erinaceieuropaei and S. decipiens are different in that the spirally coiled uterus in S. erinaceieuropaei has 5-7 complete coils, while in S. decipiens it has only 4.5 coils. In addition, there is a 9.3% (146/1,566) sequence different between S. erinaceieuropaei and S. decipiens in the cox1 gene. Partial cox1 sequences (390 bp) from 35 Korean isolates showed 99.4% (388/390) similarity with the reference sequence of S. erinaceieuropaei from Korea (G1724; GenBank KJ599680) and an additional 15 Korean isolates revealed 99.2% (387/390) similarity with the reference sequences of S. decipiens from Korea (G1657; GenBank KJ599679). Based on morphologic and molecular databases, the estimated population ratio of S. erinaceieuropaei to S. decipiens was 35: 15. Our results indicate that both S. erinaceieuropaei and S. decipiens found in Korea infect humans, with S. erinaceieuropaei being 2 times more prevalent than S. decipiens. This study is the first to report human sparganosis caused by S. decipiens in humans in Korea. PMID:26174823

  3. Evolution of the human hand: approaches to acquiring, analysing and interpreting the anatomical evidence

    PubMed Central

    MARZKE, MARY W.; MARZKE, R. F.

    2000-01-01

    The discovery of fossil hand bones from an early human ancestor at Olduvai Gorge in 1960, at the same level as primitive stone tools, generated a debate about the role of tools in the evolution of the human hand that has raged to the present day. Could the Olduvai hand have made the tools? Did the human hand evolve as an adaptation to tool making and tool use? The debate has been fueled by anatomical studies comparing living and fossil human and nonhuman primate hands, and by experimental observations. These have assessed the relative abilities of apes and humans to manufacture the Oldowan tools, but consensus has been hampered by disagreements about how to translate experimental data from living species into quantitative models for predicting the performance of fossil hands. Such models are now beginning to take shape as new techniques are applied to the capture, management and analysis of data on kinetic and kinematic variables ranging from hand joint structure, muscle mechanics, and the distribution and density of bone to joint movements and muscle recruitment during manipulative behaviour. The systematic comparative studies are highlighting a functional complex of features in the human hand facilitating a distinctive repertoire of grips that are apparently more effective for stone tool making than grips characterising various nonhuman primate species. The new techniques are identifying skeletal variables whose form may provide clues to the potential of fossil hominid hands for one-handed firm precision grips and fine precision manoeuvering movements, both of which are essential for habitual and effective tool making and tool use. PMID:10999274

  4. Preliminary genetic imaging study of the association between estrogen receptor-α gene polymorphisms and harsh human maternal parenting.

    PubMed

    Lahey, Benjamin B; Michalska, Kalina J; Liu, Chunyu; Chen, Qi; Hipwell, Alison E; Chronis-Tuscano, Andrea; Waldman, Irwin D; Decety, Jean

    2012-09-01

    A failure of neural changes initiated by the estrogen surge in late pregnancy to reverse the valence of infant stimuli from aversive to rewarding is associated with dysfunctional maternal behavior in nonhuman mammals. Estrogen receptor-α plays the crucial role in mediating these neural effects of estrogen priming. This preliminary study examines associations between estrogen receptor-α gene polymorphisms and human maternal behavior. Two polymorphisms were associated with human negative maternal parenting. Furthermore, hemodynamic responses in functional magnetic resonance imaging to child stimuli in neural regions associated with social cognition fully mediated the association between genetic variation and negative parenting. This suggests testable hypotheses regarding a biological pathway between genetic variants and dysfunctional human maternal parenting. PMID:22819972

  5. Clear genetic distinctiveness between human- and pig-derived Trichuris based on analyses of mitochondrial datasets.

    PubMed

    Liu, Guo-Hua; Gasser, Robin B; Su, Ang; Nejsum, Peter; Peng, Lifei; Lin, Rui-Qing; Li, Ming-Wei; Xu, Min-Jun; Zhu, Xing-Quan

    2012-01-01

    The whipworm, Trichuris trichiura, causes trichuriasis in ∼600 million people worldwide, mainly in developing countries. Whipworms also infect other animal hosts, including pigs (T. suis), dogs (T. vulpis) and non-human primates, and cause disease in these hosts, which is similar to trichuriasis of humans. Although Trichuris species are considered to be host specific, there has been considerable controversy, over the years, as to whether T. trichiura and T. suis are the same or distinct species. Here, we characterised the entire mitochondrial genomes of human-derived Trichuris and pig-derived Trichuris, compared them and then tested the hypothesis that the parasites from these two host species are genetically distinct in a phylogenetic analysis of the sequence data. Taken together, the findings support the proposal that T. trichiura and T. suis are separate species, consistent with previous data for nuclear ribosomal DNA. Using molecular analytical tools, employing genetic markers defined herein, future work should conduct large-scale studies to establish whether T. trichiura is found in pigs and T. suis in humans in endemic regions. PMID:22363831

  6. Clear Genetic Distinctiveness between Human- and Pig-Derived Trichuris Based on Analyses of Mitochondrial Datasets

    PubMed Central

    Liu, Guo-Hua; Gasser, Robin B.; Su, Ang; Nejsum, Peter; Peng, Lifei; Lin, Rui-Qing; Li, Ming-Wei; Xu, Min-Jun; Zhu, Xing-Quan

    2012-01-01

    The whipworm, Trichuris trichiura, causes trichuriasis in ∼600 million people worldwide, mainly in developing countries. Whipworms also infect other animal hosts, including pigs (T. suis), dogs (T. vulpis) and non-human primates, and cause disease in these hosts, which is similar to trichuriasis of humans. Although Trichuris species are considered to be host specific, there has been considerable controversy, over the years, as to whether T. trichiura and T. suis are the same or distinct species. Here, we characterised the entire mitochondrial genomes of human-derived Trichuris and pig-derived Trichuris, compared them and then tested the hypothesis that the parasites from these two host species are genetically distinct in a phylogenetic analysis of the sequence data. Taken together, the findings support the proposal that T. trichiura and T. suis are separate species, consistent with previous data for nuclear ribosomal DNA. Using molecular analytical tools, employing genetic markers defined herein, future work should conduct large-scale studies to establish whether T. trichiura is found in pigs and T. suis in humans in endemic regions. PMID:22363831

  7. Health and Human Services. Occupational Analyses. Worker Task Lists and Supplementary Information for Selected Occupations.

    ERIC Educational Resources Information Center

    Henrico County Public Schools, Glen Allen, VA. Virginia Vocational Curriculum and Resource Center.

    This publication contains worker task lists and supplementary information for eight occupations in the health and human services cluster: (1) criminal justice; (2) protective services; (3) dental assistant; (4) dental hygienist; (5) diagnostic medical sonographer; (6) medical office assistant; (7) fire medic; and (8) parks and recreation manager.…

  8. Integrated Genomic and Network-Based Analyses of Complex Diseases and Human Disease Network.

    PubMed

    Al-Harazi, Olfat; Al Insaif, Sadiq; Al-Ajlan, Monirah A; Kaya, Namik; Dzimiri, Nduna; Colak, Dilek

    2016-06-20

    A disease phenotype generally reflects various pathobiological processes that interact in a complex network. The highly interconnected nature of the human protein interaction network (interactome) indicates that, at the molecular level, it is difficult to consider diseases as being independent of one another. Recently, genome-wide molecular measurements, data mining and bioinformatics approaches have provided the means to explore human diseases from a molecular basis. The exploration of diseases and a system of disease relationships based on the integration of genome-wide molecular data with the human interactome could offer a powerful perspective for understanding the molecular architecture of diseases. Recently, subnetwork markers have proven to be more robust and reliable than individual biomarker genes selected based on gene expression profiles alone, and achieve higher accuracy in disease classification. We have applied one of these methodologies to idiopathic dilated cardiomyopathy (IDCM) data that we have generated using a microarray and identified significant subnetworks associated with the disease. In this paper, we review the recent endeavours in this direction, and summarize the existing methodologies and computational tools for network-based analysis of complex diseases and molecular relationships among apparently different disorders and human disease network. We also discuss the future research trends and topics of this promising field. PMID:27318646

  9. Human Rights in Social Science Textbooks: Cross-National Analyses, 1970-2008

    ERIC Educational Resources Information Center

    Meyer, John W.; Bromley, Patricia; Ramirez, Francisco O.

    2010-01-01

    In reaction to the disasters of the first half the 20th century and World War II, a dramatic world movement arose emphasizing the human rights of persons in global society. The contrast--celebrated in international treaties, intergovernmental and nongovernmental organizations, and much cultural discourse--was with narrower world emphases on the…

  10. UNCERTAINTY AND SENSITIVITY ANALYSES FOR INTEGRATED HUMAN HEALTH AND ECOLOGICAL RISK ASSESSMENT OF HAZARDOUS WASTE DISPOSAL

    EPA Science Inventory

    While there is a high potential for exposure of humans and ecosystems to chemicals released from hazardous waste sites, the degree to which this potential is realized is often uncertain. Conceptually divided among parameter, model, and modeler uncertainties imparted during simula...

  11. Preliminary studies of fluorescence image-guided photothermal therapy of human oesophageal adenocarcinoma in vivo using multifunctional gold nanorods

    NASA Astrophysics Data System (ADS)

    Nabavi, Elham; Singh, Mohan; Zhou, Yu; Gallina, Maria Elena; Zhao, Hailin; Ma, Daqing; Cass, Anthony; Hanna, George; Elson, Daniel S.

    2016-03-01

    We present a preliminary in vivo study of fluorescence imaging and photothermal therapy (PTT) of human oesophageal adenocarcinoma using multi-functionalised gold nanorods (GNRs). After establishing tumour xenograft in mouse functionalised GNRs were administrated intravenously (IV). Fluorescence imaging was performed to detect the tumour area. The intensity of the fluorescence signal varied significantly across the tumour site and surrounding tissues. PTT was then performed using a 808 nm continuous wave diode laser to irradiate the tumour for 3 minutes, inducing a temperature rise of ~44°C, which photothermally ablated the tumour.

  12. Analysing the influence of human activity on runoff in the Weihe River basin

    NASA Astrophysics Data System (ADS)

    Shen, C.; Qiang, H.

    2015-05-01

    Changing runoff patterns can have profound effects on the economic development of river basins. To assess the impact of human activity on runoff in the Weihe River basin, principal component analysis (PCA) was applied to a set of 17 widely used indicators of economic development to construct general combined indicators reflecting different types of human activity. Grey relational analysis suggested that the combined indicator associated with agricultural activity was most likely to have influenced the changes in runoff observed within the river basin during 1994-2011. Curve fitting was then performed to characterize the relationship between the general agricultural indicator and the measured runoff, revealing a reasonably high correlation (R2 = 0.393) and an exponential relationship. Finally, a sensitivity analysis was performed to assess the influence of the 17 individual indicators on the measured runoff, confirming that indicators associated with agricultural activity had profound effects whereas those associated with urbanization had relatively little impact.

  13. Transplantation of human amniotic epithelial cells repairs brachial plexus injury: pathological and biomechanical analyses

    PubMed Central

    Yang, Qi; Luo, Min; Li, Peng; Jin, Hai

    2014-01-01

    A brachial plexus injury model was established in rabbits by stretching the C6 nerve root. Immediately after the stretching, a suspension of human amniotic epithelial cells was injected into the injured brachial plexus. The results of tensile mechanical testing of the brachial plexus showed that the tensile elastic limit strain, elastic limit stress, maximum stress, and maximum strain of the injured brachial plexuses were significantly increased at 24 weeks after the injection. The treatment clearly improved the pathological morphology of the injured brachial plexus nerve, as seen by hematoxylin eosin staining, and the functions of the rabbit forepaw were restored. These data indicate that the injection of human amniotic epithelial cells contributed to the repair of brachial plexus injury, and that this technique may transform into current clinical treatment strategies. PMID:25657737

  14. Proteomics analyses for the global proteins in the brain tissues of different human prion diseases.

    PubMed

    Shi, Qi; Chen, Li-Na; Zhang, Bao-Yun; Xiao, Kang; Zhou, Wei; Chen, Cao; Zhang, Xiao-Mei; Tian, Chan; Gao, Chen; Wang, Jing; Han, Jun; Dong, Xiao-Ping

    2015-04-01

    Proteomics changes of brain tissues have been described in different neurodegenerative diseases including Alzheimer's disease and Parkinson's disease. However, the brain proteomics of human prion disease remains less understood. In the study, the proteomics patterns of cortex and cerebellum of brain tissues of sporadic Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD were analyzed with isobaric tags for relative and absolute quantitation combined with multidimensional liquid chromatography and MS analysis, with the brains from three normal individuals as controls. Global protein profiling, significant pathway, and functional categories were analyzed. In total, 2287 proteins were identified with quantitative information both in cortex and cerebellum regions. Cerebellum tissues appeared to contain more up- and down-regulated proteins (727 proteins) than cortex regions (312 proteins) of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD. Viral myocarditis, Parkinson's disease, Alzheimer's disease, lysosome, oxidative phosphorylation, protein export, and drug metabolism-cytochrome P450 were the most commonly affected pathways of the three kinds of diseases. Almost coincident biological functions were identified in the brain tissues of the three diseases. In all, data here demonstrate that the brain tissues of Creutzfeldt-Jakob disease, fatal familial insomnia, and G114V genetic CJD have obvious proteomics changes at their terminal stages, which show the similarities not only among human prion diseases but also with other neurodegeneration diseases. This is the first study to provide a reference proteome map for human prion diseases and will be helpful for future studies focused on potential biomarkers for the diagnosis and therapy of human prion diseases. PMID:25616867

  15. Multidimensional Genome-wide Analyses Show Accurate FVIII Integration by ZFN in Primary Human Cells

    PubMed Central

    Sivalingam, Jaichandran; Kenanov, Dimitar; Han, Hao; Nirmal, Ajit Johnson; Ng, Wai Har; Lee, Sze Sing; Masilamani, Jeyakumar; Phan, Toan Thang; Maurer-Stroh, Sebastian; Kon, Oi Lian

    2016-01-01

    Costly coagulation factor VIII (FVIII) replacement therapy is a barrier to optimal clinical management of hemophilia A. Therapy using FVIII-secreting autologous primary cells is potentially efficacious and more affordable. Zinc finger nucleases (ZFN) mediate transgene integration into the AAVS1 locus but comprehensive evaluation of off-target genome effects is currently lacking. In light of serious adverse effects in clinical trials which employed genome-integrating viral vectors, this study evaluated potential genotoxicity of ZFN-mediated transgenesis using different techniques. We employed deep sequencing of predicted off-target sites, copy number analysis, whole-genome sequencing, and RNA-seq in primary human umbilical cord-lining epithelial cells (CLECs) with AAVS1 ZFN-mediated FVIII transgene integration. We combined molecular features to enhance the accuracy and activity of ZFN-mediated transgenesis. Our data showed a low frequency of ZFN-associated indels, no detectable off-target transgene integrations or chromosomal rearrangements. ZFN-modified CLECs had very few dysregulated transcripts and no evidence of activated oncogenic pathways. We also showed AAVS1 ZFN activity and durable FVIII transgene secretion in primary human dermal fibroblasts, bone marrow- and adipose tissue-derived stromal cells. Our study suggests that, with close attention to the molecular design of genome-modifying constructs, AAVS1 ZFN-mediated FVIII integration in several primary human cell types may be safe and efficacious. PMID:26689265

  16. Assessing human diet and movement in the Tongan maritime chiefdom using isotopic analyses.

    PubMed

    Stantis, Christina; Kinaston, Rebecca L; Richards, Michael P; Davidson, Janet M; Buckley, Hallie R

    2015-01-01

    The rise of stratified societies fundamentally influences the interactions between status, movement, and food. Using isotopic analyses, we assess differences in diet and mobility of individuals excavated from two burial mounds located at the `Atele burial site on Tongatapu, the main island of the Kingdom of Tonga (c. 500 - 150 BP). The first burial mound (To-At-1) was classified by some archaeologists as a commoner's mound while the second burial mound (To-At-2) was possibly used for interment of the chiefly class. In this study, stable isotope analyses of diet (δ13C, δ15N, and δ34S; n = 41) are used to asses paleodiet and 87Sr/86Sr ratios (n = 30) are analyzed to investigate individual mobility to test whether sex and social status affected these aspects of life. Our results show significant differences in diet between burial mounds and sexes. Those interred in To-At-2 displayed lower δ13C values, indicating they ate relatively more terrestrial plants (likely starchy vegetable staples) compared with To-At-1 individuals. Females displayed significantly lower δ15N values compared with males within the entire assemblage. No differences in δ34S values were observed between sexes or burial mound but it is possible that sea spray or volcanism may have affected these values. One individual displayed the strontium isotopic composition representative of a nonlocal immigrant (outside 2SD of the mean). This suggests the hegemonic control over interisland travel, may have prevented long-term access to the island by non-Tongans exemplifying the political and spiritual importance of the island of Tongatapu in the maritime chiefdom. PMID:25822619

  17. Assessing Human Diet and Movement in the Tongan Maritime Chiefdom Using Isotopic Analyses

    PubMed Central

    Stantis, Christina; Kinaston, Rebecca L.; Richards, Michael P.; Davidson, Janet M.; Buckley, Hallie R.

    2015-01-01

    The rise of stratified societies fundamentally influences the interactions between status, movement, and food. Using isotopic analyses, we assess differences in diet and mobility of individuals excavated from two burial mounds located at the `Atele burial site on Tongatapu, the main island of the Kingdom of Tonga (c. 500 - 150 BP). The first burial mound (To-At-1) was classified by some archaeologists as a commoner’s mound while the second burial mound (To-At-2) was possibly used for interment of the chiefly class. In this study, stable isotope analyses of diet (δ13C, δ15N, and δ34S; n = 41) are used to asses paleodiet and 87Sr/86Sr ratios (n = 30) are analyzed to investigate individual mobility to test whether sex and social status affected these aspects of life. Our results show significant differences in diet between burial mounds and sexes. Those interred in To-At-2 displayed lower δ13C values, indicating they ate relatively more terrestrial plants (likely starchy vegetable staples) compared with To-At-1 individuals. Females displayed significantly lower δ15N values compared with males within the entire assemblage. No differences in δ34S values were observed between sexes or burial mound but it is possible that sea spray or volcanism may have affected these values. One individual displayed the strontium isotopic composition representative of a nonlocal immigrant (outside 2SD of the mean). This suggests the hegemonic control over interisland travel, may have prevented long-term access to the island by non-Tongans exemplifying the political and spiritual importance of the island of Tongatapu in the maritime chiefdom. PMID:25822619

  18. Global Geometric Morphometric Analyses of the Human Pelvis Reveal Substantial Neutral Population History Effects, Even across Sexes

    PubMed Central

    Betti, Lia; von Cramon-Taubadel, Noreen; Manica, Andrea; Lycett, Stephen J.

    2013-01-01

    Recent applications of population genetic models to human craniodental traits have revealed a strong neutral component to patterns of global variation. However, little work has been undertaken to determine whether neutral processes might also be influencing the postcranium, perhaps due to substantial evidence for selection and plastic environmental responses in these regions. Recent work has provided evidence for neutral effects in the pelvis, but has been limited in regard to shape data (small numbers of linear measurements) and restricted only to males. Here, we use geometric morphometric methods to examine population variation in the human os coxae (pelvic bone) in both males and females. Neutrality is examined via apportionment of variance patterns and fit to an Out-of-Africa serial founder effect model, which is known to structure neutral genetic patterns. Moreover, we compare males and females directly, and the true versus false pelvis, in order to examine potential obstetrical effects. Our results indicate evidence for substantial neutral population history effects on pelvic shape variation. They also reveal evidence for the effect of obstetrical constraints, but these affect males and females to equivalent extents. Our results do not deny an important role for selection in regard to specific aspects of human pelvic variation, especially in terms of features associated with body size and proportions. However, our analyses demonstrate that at a global level, the shape of the os coxae reveals substantial evidence for neutral variation. Our analyses thus indicate that population variation in the human pelvis might be used to address important questions concerning population history, just as the human cranium has done. PMID:23409086

  19. Comparative Genomic Analyses of the Human NPHP1 Locus Reveal Complex Genomic Architecture and Its Regional Evolution in Primates

    PubMed Central

    Yuan, Bo; Liu, Pengfei; Gupta, Aditya; Beck, Christine R.; Tejomurtula, Anusha; Campbell, Ian M.; Gambin, Tomasz; Simmons, Alexandra D.; Withers, Marjorie A.; Harris, R. Alan; Rogers, Jeffrey; Schwartz, David C.; Lupski, James R.

    2015-01-01

    Many loci in the human genome harbor complex genomic structures that can result in susceptibility to genomic rearrangements leading to various genomic disorders. Nephronophthisis 1 (NPHP1, MIM# 256100) is an autosomal recessive disorder that can be caused by defects of NPHP1; the gene maps within the human 2q13 region where low copy repeats (LCRs) are abundant. Loss of function of NPHP1 is responsible for approximately 85% of the NPHP1 cases—about 80% of such individuals carry a large recurrent homozygous NPHP1 deletion that occurs via nonallelic homologous recombination (NAHR) between two flanking directly oriented ~45 kb LCRs. Published data revealed a non-pathogenic inversion polymorphism involving the NPHP1 gene flanked by two inverted ~358 kb LCRs. Using optical mapping and array-comparative genomic hybridization, we identified three potential novel structural variant (SV) haplotypes at the NPHP1 locus that may protect a haploid genome from the NPHP1 deletion. Inter-species comparative genomic analyses among primate genomes revealed massive genomic changes during evolution. The aggregated data suggest that dynamic genomic rearrangements occurred historically within the NPHP1 locus and generated SV haplotypes observed in the human population today, which may confer differential susceptibility to genomic instability and the NPHP1 deletion within a personal genome. Our study documents diverse SV haplotypes at a complex LCR-laden human genomic region. Comparative analyses provide a model for how this complex region arose during primate evolution, and studies among humans suggest that intra-species polymorphism may potentially modulate an individual’s susceptibility to acquiring disease-associated alleles. PMID:26641089

  20. Comparative Proteome Analyses of Human Plasma Following in vivo Lipopolysaccharide Administration Using Multidimensional Separations Coupled with Tandem Mass Spectrometry

    SciTech Connect

    Qian, Weijun; Jacobs, Jon M.; Camp, David G.; Monroe, Matthew E.; Moore, Ronald J.; Gritsenko, Marina A.; Calvano, Steven E.; Lowry, Stephen F.; Xiao, Wenzhong; Moldawer, Lyle L.; Davis, Ronald W.; Tompkins, Ronald G.; Smith, Richard D.

    2005-01-03

    There is significant interest in characterization of the human plasma proteome due to its potential for providing biomarkers applicable to clinical diagnosis and treatment and for gaining a better understanding of human diseases. We describe here a strategy for comparative proteome analyses of human plasma, which is applicable to biomarker identifications for various disease states. Multidimensional liquid chromatography-mass spectrometry has been applied to make comparative proteome analyses of plasma samples from an individual prior to and 9 h after lipopolysaccharide (LPS) administration. Peptide peak areas and the number of peptide identifications for each protein were used to evaluate the reproducibility of LC-MS/MS and to compare relative changes in protein concentration between the samples following LPS treatment. A total of 804 distinct plasma proteins (not including immunoglobulins) were confidently identified with 32 proteins observed to be significantly increased in concentration following LPS administration, including several known inflammatory response or acute-phase mediators such as C-reactive protein, serum amyloid A and A2, LPS-binding protein, LPS-responsive and beige-like anchor protein, hepatocyte growth factor activator and von Willebrand factor, and thus constituting potential biomarkers for inflammatory response.

  1. Substrate specificity and inhibitor analyses of human steroid 5β-reductase (AKR1D1)

    PubMed Central

    Chen, Mo; Drury, Jason E.; Penning, Trevor M.

    2011-01-01

    Human steroid 5β-reductase (Aldo-keto Reductase 1D1) catalyzes the stereospecific NADPH-dependent reduction of the C4-C5 double bond of Δ4-ketosteroids to yield an A/B cis-ring junction. This cis-configuration is crucial for bile acid biosynthesis and plays important roles in steroid metabolism. The biochemical properties of the enzyme have not been thoroughly studied and conflicting data have been reported, partially due to the lack of highly homogeneous protein. In the present study, we systematically determined the substrate specificity of homogeneous human recombinant AKR1D1 using C18, C19, C21, and C27 Δ4-ketosteroids and assessed the pH-rate dependence of the enzyme. Our results show that AKR1D1 proficiently reduced all the steroids tested at physiological pH, indicating AKR1D1 is the only enzyme necessary for all the 5β-steroid metabolite present in humans. Substrate inhibition was observed with C18 to C21 steroids provided that the side-chain at C17 was unsubstituted. This structure activity relationship can be explained by the existence of a small alternative substrate binding pocket revealed by the AKR1D1 crystal structure. Non-steroidal anti-inflammatory drugs which are potent inhibitors of the related AKR1C enzymes do not inhibit AKR1D1 by contrast chenodeoxycholate and ursodeoxycholate were found to be potent non-competitive inhibitors suggesting that bile-acids may regulate their own synthesis at the level of AKR1D1 inhibition. PMID:21255593

  2. Experiments on Analysing Voice Production: Excised (Human, Animal) and In Vivo (Animal) Approaches

    PubMed Central

    Döllinger, Michael; Kobler, James; Berry, David A.; Mehta, Daryush D.; Luegmair, Georg; Bohr, Christopher

    2015-01-01

    Experiments on human and on animal excised specimens as well as in vivo animal preparations are so far the most realistic approaches to simulate the in vivo process of human phonation. These experiments do not have the disadvantage of limited space within the neck and enable studies of the actual organ necessary for phonation, i.e., the larynx. The studies additionally allow the analysis of flow, vocal fold dynamics, and resulting acoustics in relation to well-defined laryngeal alterations. Purpose of Review This paper provides an overview of the applications and usefulness of excised (human/animal) specimen and in vivo animal experiments in voice research. These experiments have enabled visualization and analysis of dehydration effects, vocal fold scarring, bifurcation and chaotic vibrations, three-dimensional vibrations, aerodynamic effects, and mucosal wave propagation along the medial surface. Quantitative data will be shown to give an overview of measured laryngeal parameter values. As yet, a full understanding of all existing interactions in voice production has not been achieved, and thus, where possible, we try to indicate areas needing further study. Recent Findings A further motivation behind this review is to highlight recent findings and technologies related to the study of vocal fold dynamics and its applications. For example, studies of interactions between vocal tract airflow and generation of acoustics have recently shown that airflow superior to the glottis is governed by not only vocal fold dynamics but also by subglottal and supraglottal structures. In addition, promising new methods to investigate kinematics and dynamics have been reported recently, including dynamic optical coherence tomography, X-ray stroboscopy and three-dimensional reconstruction with laser projection systems. Finally, we touch on the relevance of vocal fold dynamics to clinical laryngology and to clinically-oriented research. PMID:26581597

  3. Heritability and Genome-Wide Association Analyses of Human Gait Suggest Contribution of Common Variants.

    PubMed

    Adams, Hieab H H; Verlinden, Vincentius J A; Callisaya, Michele L; van Duijn, Cornelia M; Hofman, Albert; Thomson, Russell; Uitterlinden, André G; Vernooij, Meike W; van der Geest, Jos N; Srikanth, Velandai; Ikram, M Arfan

    2016-06-01

    Human gait is a complex neurological and musculoskeletal function, of which the genetic basis remains largely unknown. To determine the influence of common genetic variants on gait parameters, we studied 2,946 participants of the Rotterdam Study, a population-based cohort of unrelated elderly individuals. We assessed 30 gait parameters using an electronic walkway, which yielded seven independent gait domains after principal component analysis. Genotypes of participants were imputed to the 1,000 Genomes reference panel for generating genetic relationship matrices to estimate heritability of gait parameters, and for subsequent genome-wide association scans (GWASs) to identify specific variants. Gait domains with the highest age- and sex-adjusted heritability were Variability (h (2) = 61%), Rhythm (37%), and Tandem (32%). For other gait domains, heritability estimates attenuated after adjustment for height and weight. Genome-wide association scans identified a variant on 1p22.3 that was significantly associated with single support time, a variable from the Rhythm domain (rs72953990; N = 2,946; β [SE] = 0.0069 (0.0012), p = 2.30×10(-8)). This variant did not replicate in an independent sample (N = 362; p = .78). In conclusion, human gait has highly heritable components that are explained by common genetic variation, which are partly attributed to height and weight. Collaborative efforts are needed to identify robust single variant associations for the heritable parameters. PMID:26219847

  4. Structural and functional analyses of human cerebral cortex using a surface-based atlas

    NASA Technical Reports Server (NTRS)

    Van Essen, D. C.; Drury, H. A.

    1997-01-01

    We have analyzed the geometry, geography, and functional organization of human cerebral cortex using surface reconstructions and cortical flat maps of the left and right hemispheres generated from a digital atlas (the Visible Man). The total surface area of the reconstructed Visible Man neocortex is 1570 cm2 (both hemispheres), approximately 70% of which is buried in sulci. By linking the Visible Man cerebrum to the Talairach stereotaxic coordinate space, the locations of activation foci reported in neuroimaging studies can be readily visualized in relation to the cortical surface. The associated spatial uncertainty was empirically shown to have a radius in three dimensions of approximately 10 mm. Application of this approach to studies of visual cortex reveals the overall patterns of activation associated with different aspects of visual function and the relationship of these patterns to topographically organized visual areas. Our analysis supports a distinction between an anterior region in ventral occipito-temporal cortex that is selectively involved in form processing and a more posterior region (in or near areas VP and V4v) involved in both form and color processing. Foci associated with motion processing are mainly concentrated in a region along the occipito-temporal junction, the ventral portion of which overlaps with foci also implicated in form processing. Comparisons between flat maps of human and macaque monkey cerebral cortex indicate significant differences as well as many similarities in the relative sizes and positions of cortical regions known or suspected to be homologous in the two species.

  5. Cynical beliefs about human nature and income: Longitudinal and cross-cultural analyses.

    PubMed

    Stavrova, Olga; Ehlebracht, Daniel

    2016-01-01

    Based on the existing literature on worldview beliefs, cynical hostility, and Machiavellian cynicism, we suggest that holding cynical beliefs about human nature can be detrimental for individuals' income. Cynical individuals are more likely to avoid cooperation and trust or to overinvest in monitoring, control, and other means of protection from potential exploitation. As a result, they are more likely to forgo valuable opportunities for cooperation and consequently less likely to reap the benefits of joint efforts and mutual help compared with their less cynical counterparts. Studies 1 and 2, using nationally representative longitudinal surveys of the American population, show that individuals who endorsed cynical beliefs about human nature at baseline earned comparatively lower incomes 9 (Study 1) and 2 (Study 2) years later. In Study 3, applying a multilevel model of change to a nationally representative panel study of the German population, we show that cynical beliefs at baseline undermined an income increase in the course of the following 9 years. In Study 4, the negative effect of cynical beliefs on income proved to be independent of individual differences in the Big Five personality dimensions. Study 5 provided the first tentative evidence of the hypothesized mechanism underlying this effect. Using survey data from 41 countries, it revealed that the negative effect of cynical beliefs on income is alleviated in sociocultural contexts with low levels of prosocial behavior, high homicide rates and high overall societal cynicism levels. Holding cynical beliefs about others has negative economic outcomes unless such beliefs hold true. PMID:26011659

  6. The purification, crystallization and preliminary structural characterization of human MAWDBP, a member of the phenazine biosynthesis-like protein family

    SciTech Connect

    Herde, Petra; Blankenfeldt, Wulf

    2006-06-01

    The purification, crystallization and preliminary structural characterization of human MAWD-binding protein (MAWDBP) are described. MAWDBP is the only representative of the phenazine biosynthesis-like protein family in the human genome. Its expression is elevated in several disease processes, including insulin resistance, folate deficiency and hypotension, and it may also be involved in carcinogenesis. The exact molecular function of MAWDBP is unknown. Native and seleno-l-methionine-labelled MAWDBP were expressed in Escherichia coli and crystallized at room temperature from precipitants containing 10 mM KF, 14%(w/v) PEG 3350 and 0.1 M sodium citrate pH 5.4. Crystals belong to space group H32, with unit-cell parameters a = b = 187, c = 241 Å, indicative of three to five monomers per asymmetric unit. Crystals were cryoprotected with 15%(v/v) glycerol and data have been collected to 2.7 Å resolution.

  7. Nitrogen recovery from source-separated human urine using clinoptilolite and preliminary results of its use as fertilizer.

    PubMed

    Beler-Baykal, B; Allar, A D; Bayram, S

    2011-01-01

    The use of source separated human urine as fertilizer is one of the major suggestions of the new sanitation concept ECOSAN. Urine is rich in nitrogen, phosphorus and potassium which act as plant nutrients, however its salinity is high for agricultural and landscape purposes. Moreover, characteristics change significantly throughout storage where salinity increases to higher values as the predominant form of nitrogen shifts from urea to ammonium. Transferring nitrogen in human urine onto the natural zeolite clinoptilolite and using the subsequently recovered ammonium from the exhausted clinoptilolite for agricultural/landscape purposes is suggested as an indirect route of using urine in this work. Results reporting the outcome of the proposed process together with characterization of fresh and stored urine, and preliminary work on the application of the product on the landscape plant Ficus elastica are presented. Up to 97% of the ammonium in stored urine could be transferred onto clinoptilolite through ion exchange and about 88% could be recovered subsequently from exhausted clinoptilolite, giving an overall recovery of 86%. Another important merit of the suggested process was the successful elimination of salinity. Preliminary experiments with Ficus elastica had shown that the product, i.e. clinoptilolite exhausted with ammonium, was compatible with the synthetic fertilizer tested. PMID:21330732

  8. A critical review of cost-effectiveness analyses of vaccinating males against human papillomavirus

    PubMed Central

    Jiang, Yiling; Gauthier, Aline; Postma, Maarten J; Ribassin-Majed, Laureen; Largeron, Nathalie; Bresse, Xavier

    2013-01-01

    A critical review of cost-effectiveness analyses of HPV vaccination in males was conducted and nine studies were identified in different countries. Due to the heterogeneity among these studies in terms of modeling approach, vaccination strategies, health outcomes considered, assumptions and parameters, limited conclusions can be drawn with regard to the absolute cost-effectiveness. Nevertheless, key drivers were identified. More favorable cost-effectiveness appeared when all HPV-related diseases outcomes were considered, a suboptimal vaccine coverage among girls and/or lower vaccine prices were assumed. There was a general lack of transparency to fully describe the details of the methodological approach of modeling and calibration. Further research should be conducted to generate robust evidence-based data sets (HPV-related diseases epidemiology, costs and quality of life). The best modeling practice for HPV vaccination and how to better capture the true economic value of vaccination beyond cost-effectiveness in a broader policy context need to be investigated. PMID:23880955

  9. A critical review of cost-effectiveness analyses of vaccinating males against human papillomavirus.

    PubMed

    Jiang, Yiling; Gauthier, Aline; Postma, Maarten J; Ribassin-Majed, Laureen; Largeron, Nathalie; Bresse, Xavier

    2013-11-01

    A critical review of cost-effectiveness analyses of HPV vaccination in males was conducted and nine studies were identified in different countries. Due to the heterogeneity among these studies in terms of modeling approach, vaccination strategies, health outcomes considered, assumptions and parameters, limited conclusions can be drawn with regard to the absolute cost-effectiveness. Nevertheless, key drivers were identified. More favorable cost-effectiveness appeared when all HPV-related diseases outcomes were considered, a suboptimal vaccine coverage among girls and/or lower vaccine prices were assumed. There was a general lack of transparency to fully describe the details of the methodological approach of modeling and calibration. Further research should be conducted to generate robust evidence-based data sets (HPV-related diseases epidemiology, costs and quality of life). The best modeling practice for HPV vaccination and how to better capture the true economic value of vaccination beyond cost-effectiveness in a broader policy context need to be investigated. PMID:23880955

  10. Kinetic Analyses of Data from a Human Serum Albumin Assay Using the liSPR System

    PubMed Central

    Henseleit, Anja; Pohl, Carolin; Kaltenbach, Hans-Michael; Hettwer, Karina; Simon, Kirsten; Uhlig, Steffen; Haustein, Natalie; Bley, Thomas; Boschke, Elke

    2015-01-01

    We used the interaction between human serum albumin (HSA) and a high-affinity antibody to evaluate binding affinity measurements by the bench-top liSPR system (capitalis technology GmbH). HSA was immobilized directly onto a carboxylated sensor layer, and the mechanism of interaction between the antibody and HSA was investigated. The bivalence and heterogeneity of the antibody caused a complex binding mechanism. Three different interaction models (1:1 binding, heterogeneous analyte, bivalent analyte) were compared, and the bivalent analyte model best fit the curves obtained from the assay. This model describes the interaction of a bivalent analyte with one or two ligands (A + L ↔ LA + L ↔ LLA). The apparent binding affinity for this model measured 37 pM for the first reaction step, and 20 pM for the second step. PMID:25607476

  11. Further analyses of human kidney cell populations separated on the space shuttle

    NASA Astrophysics Data System (ADS)

    Stewart, Robin M.; Todd, Paul; Cole, Kenneth D.; Morrison, Dennis R.

    Cultured human embryonic kidney cells were separated into electrophoretic subpopulations in laboratory experiments and in two separation experiments on the STS-8 (Challenger) Space Shuttle flight using the mid-deck Continuous Flow Electrophoretic Separator (CFES). Populations of cells from each fraction were cultured for the lifetime of the cells, and supernatant medium was withdrawn and replaced at 4-day intervals. Withdrawn medium was frozen at -120°C for subsequent analysis. Enzyme assays, antibodies and gel electrophoresis were used as analytical tools for the detection and quantitation of plasminogen activators in these samples. These assays of frozen culture supernatant fluids confirmed the electrophoretic separation of plasminogen-activator producing cells from non-producing cells, the isolation of cells capable of sustained production, and the separation of cells that produce different plasminogen activators from one another.

  12. [Animal models of human retinal and optic nerve diseases analysed using electroretinography].

    PubMed

    Kondo, Mineo

    2010-03-01

    Investigations of animal models with diseases found in humans are important to the understanding of their pathophysiology and for developing new treatments. Both naturally occurring and genetically-manipulated animal models of human retinal and optic nerve diseases have been studied in this manner. Electroretinography (ERG) is valuable for the evaluation of the visual function of animal models, because a layer-by-layer assessment of the retina can be done objectively. We used ERGs to analyze the visual functions of animal models of human retinal and and optic nerve diseases. To investigate the contribution of the cone ON- and OFF-pathways to the mouse photopic ERGs, we studied the properties of the photopic ERGs of metabotropic glutamate receptor subtype 6-deficient mice. The results of the ERG and the effect of an intravitreous injection of cis-2,3 piperidine dicarboxylic acid (PDA) in these mice suggest that the contribution of the post-synaptic ON-pathway to the photopic ERG of mice is larger than that of the OFF-pathway. The ERGs of pikachurin-deficient mice had normal a-waves with severely delayed b-waves, indicating that the signal transmission from the photoreceptors to the bipolar cells was impaired in these mutant mice. We also generated a rabbit model of retinitis pigmentosa (RP), the rhodopsin P347L transgenic (Tg) rabbit, by using bacterial artificial chromosome (BAC) transgenesis. These rabbits showed a rod-dominant, progressive retinal degeneration with marked regional variations in the loss of photoreceptors. All ERG components of the Tg rabbits decreased progressively with the a-waves more affected than the b-waves, and with the oscillatory potentials (OPs) the best preserved. Interestingly, the OP amplitudes of young Tg rabbits were significantly larger than those of wild-type rabbits. Pharmacological experiments showed that the significantly larger OPs in young Tg rabbits resulted from secondary alterations in the inner retinal function. This type

  13. Further analyses of human kidney cell populations separated on the Space Shuttle

    NASA Technical Reports Server (NTRS)

    Stewart, Robin M.; Todd, Paul; Cole, Kenneth D.; Morrison, Dennis R.

    1992-01-01

    Cultured human embryonic kidney cells were separated into electrophoretic subpopulations in laboratory experiments and in two separation experiments on the STS-8 (Challenger) Space Shuttle flight using the mid-deck Continuous Flow Electrophoretic Separator (CFES). Populations of cells from each fraction were cultured for the lifetime of the cells, and supernatant medium was withdrawn and replaced at 4-day intervals. Withdrawn medium was frozen at -120 C for subsequent analysis. Enzyme assays, antibodies and gel electrophoresis were used as analytical tools for the detection and quantization of plasminogen activators in these samples. These assays of frozen-culture supernatant fluids confirmed the electrophoretic separation of plasminogen-activator-producing cells from nonproducing cells, the isolation of cells capable of sustained production, and the separation of cells that produce different plasminogen activators from one other.

  14. Further analyses of human kidney cell populations separated on the Space Shuttle.

    PubMed

    Stewart, R M; Todd, P; Cole, K D; Morrison, D R

    1992-01-01

    Cultured human embryonic kidney cells were separated into electrophoretic subpopulations in laboratory experiments and in two separation experiments on the STS-8 (Challenger) Space Shuttle flight using the mid-deck Continuous Flow Electrophoretic Separator (CFES). Populations of cells from each fraction were cultured for the lifetime of the cells, and supernatant medium was withdrawn and replaced at 4-day intervals. Withdrawn medium was frozen at -120 degrees C for subsequent analysis. Enzyme assays, antibodies and gel electrophoresis were used as analytical tools for the detection and quantitation of plasminogen activators in these samples. These assays of frozen culture supernatant fluids confirmed the electrophoretic separation of plasminogen-activator producing cells from non-producing cells, the isolation of cells capable of sustained production, and the separation of cells that produce different plasminogen activators from one another. PMID:11537068

  15. Melanin fate in the human epidermis: a reassessment of how best to detect and analyse histologically.

    PubMed

    Joly-Tonetti, Nicolas; Wibawa, Judata I D; Bell, Mike; Tobin, Desmond

    2016-07-01

    Melanin is the predominant pigment responsible for skin colour and is synthesized by the melanocyte in the basal layer of the epidermis and then transferred to surrounding keratinocytes. Despite its optical properties, melanin is barely detectable in unstained sections of human epidermis. However, identification and localization of melanin is of importance for the study of skin pigmentation in health and disease. Current methods for the histologic quantification of melanin are suboptimal and are associated with significant risk of misinterpretation. The aim of this study was to reassess the existing literature and to develop a more effective histological method of melanin quantification in human skin. Moreover, we confirm that Warthin-Starry (WS) stain provides a much more sensitive and more specific melanin detection method than the commonplace Fontana-Masson (FM) stain. For example, WS staining sensitivity allowed the visualization of melanin even in very pale Caucasian skin that was missed by FM or Von Kossa (VK) stains. From our reassessment of the histology-related literature, we conclude that so-called melanin dust is most likely an artifact of discoloration due to non-specific silver deposition in the stratum corneum. Unlike FM and VK, WS was not associated with this non-specific stratum corneum darkening, misinterpreted previously as 'degraded' melanin. Finally, WS melanin particle counts were largely similar to previously reported manual counts by transmission electron microscopy, in contrast to both FM and VK. Together these findings allow us to propose a new histology/Image J-informed method for the accurate and precise quantification of epidermal melanin in skin. PMID:26998907

  16. Fluorescent in situ hybridization analyses of human oocytes in trisomy 18 and 21

    SciTech Connect

    Cheng, E.Y.; Chen, Y.J.; Gartler, S.M.

    1994-09-01

    The commonly accepted view of synapsis is that only 2 homologues can synapse at any one site and that this restriction applies to polyploids as well. However, triple synapsis has been observed is some triploid plants and in triploid chicken. In humans, triple synapsis of the long arm of chromosome 21 was detected in sperm of a trisomic 21 individual. More recently, studies of oocytes from trisomic 21 and 18 fetuses also indicated extensive triple synapsis along the entire length of the chromosomes. To further investigate this question, we undertook an evaluation of trivalent synapsis in fetal oocytes from 2 trisomic 21 and 2 trisomic 18 fetuses using fluorescent in situ hybridization (FISH) with whole chromosome probes. Oocytes were hybridized with whole chromosome probes obtained from ONCOR, Inc. after fixation with methanol and acetic acid. Slides were scored for the distribution of prophase stages, hybridization efficiency, and hybridization characteristics of chromosomes 18 and 21 in the trisomic 18 and 21 fetuses respectively. Fifty-eight per cent (379/650) of pachytenes analyzed for chromosome 18 contained a conspicous trivalent and 319 (48%) of these nuclei contained a single, thick, continuous fluorescent signal consistent with complete triple synapsis along the entire length of all 3 chromosomes. Sixteen per cent (104/650) of pachytene contained 2 signals consistent with a bivalent and a univalent, and 9 cells contained 3 thin signals consistent with asynapsis of all 3 chromosomes. The remaining 158 pachytenes had unusual pairing configurations that we could not classify, but they most likely represent trivalents with partial pairing between different homologues. In the 2 trisomic 21 fetuses, the majority (143/232) of pachytenes also contained one signal while only 52 cells contained a bivalent and univalent. Five cells contained 3 separate signals. These results confirm the existence of triple synapsis in human meiosis.

  17. Microarray analyses and molecular profiling of steatosis induction in immortalized human hepatocytes.

    PubMed

    De Gottardi, Andrea; Vinciguerra, Manlio; Sgroi, Antonino; Moukil, Moulay; Ravier-Dall'Antonia, Florence; Pazienza, Valerio; Pugnale, Paolo; Foti, Michelangelo; Hadengue, Antoine

    2007-08-01

    Hepatic steatosis is an important risk factor for the development of inflammation, fibrosis and impaired liver regeneration. The factors regulating lipid accumulation and driving hepatic steatosis toward inflammation, fibrosis and impaired regeneration are largely unknown. The aim of this study was to identify major alterations in gene expression occurring in steatotic hepatocytes, and to analyze how these changes impact cellular processes associated with steatosis. Microarray gene chips and RT-PCR were performed to analyze changes in gene expression induced in fatty human immortalized hepatocytes after treatment with 50 muM oleic acid for 7 days. Lipid metabolism and triglyceride accumulation in these cells was examined by Oil-Red-O staining, thin-layer chromatography (TLC) and immunofluorescence. Caspase 3 activity, BrdU incorporation and trypan blue exclusion were used to study apoptosis, proliferation and cell viability. Finally, quantitative analysis of signalling induced by insulin was performed by Western blot. Characterization of steatosis in three hepatocyte-derived cell lines indicated that the immortalized human hepatocytes (IHH) line was the most appropriate cell line for this study. Gene expression analysis showed significant alterations in the transcription of two major classes of genes involved either in cholesterol and fatty acid biosynthesis, as well as lipid export, or in apoptosis and cell proliferation. Such changes were functionally relevant, since TLC indicated that synthesis and accumulation of triglycerides were increased in steatotic cells, while synthesis of cholesterol and fatty acids were decreased. Lipid accumulation in IHH was associated with an increased apoptosis and an inhibition of cell proliferation and viability. No detectable changes in genes associated with insulin resistance were observed in steatotic cells, but signalling induced by insulin was more efficient in steatotic IHH as compared to control cells. We conclude that IHH

  18. Meta-Analyses of Human Cell-Based Cardiac Regeneration Therapies: Controversies in Meta-Analyses Results on Cardiac Cell-Based Regenerative Studies.

    PubMed

    Gyöngyösi, Mariann; Wojakowski, Wojciech; Navarese, Eliano P; Moye, Lemuel À

    2016-04-15

    In contrast to multiple publication-based meta-analyses involving clinical cardiac regeneration therapy in patients with recent myocardial infarction, a recently published meta-analysis based on individual patient data reported no effect of cell therapy on left ventricular function or clinical outcome. A comprehensive review of the data collection, statistics, and the overall principles of meta-analyses provides further clarification and explanation for this controversy. The advantages and pitfalls of different types of meta-analyses are reviewed here. Each meta-analysis approach has a place when pivotal clinical trials are lacking and sheds light on the magnitude of the treatment in a complex healthcare field. PMID:27081108

  19. A Preliminary Exploration of Occupations in the Arts and the Humanities.

    ERIC Educational Resources Information Center

    Hansen, Mary Lewis; And Others

    Summary information on arts and humanities occupational clusters, obtaining occupational information, career ladder and lattice possibilities, job projections, and job competencies for arts and humanities careers is presented in this report of research, which resulted in a series of 11 arts and humanities career exploration resource guides for…

  20. Analysing inter-relationships among water, governance, human development variables in developing countries

    NASA Astrophysics Data System (ADS)

    Dondeynaz, C.; Carmona Moreno, C.; Céspedes Lorente, J. J.

    2012-10-01

    The "Integrated Water Resources Management" principle was formally laid down at the International Conference on Water and Sustainable development in Dublin 1992. One of the main results of this conference is that improving Water and Sanitation Services (WSS), being a complex and interdisciplinary issue, passes through collaboration and coordination of different sectors (environment, health, economic activities, governance, and international cooperation). These sectors influence or are influenced by the access to WSS. The understanding of these interrelations appears as crucial for decision makers in the water sector. In this framework, the Joint Research Centre (JRC) of the European Commission (EC) has developed a new database (WatSan4Dev database) containing 42 indicators (called variables in this paper) from environmental, socio-economic, governance and financial aid flows data in developing countries. This paper describes the development of the WatSan4Dev dataset, the statistical processes needed to improve the data quality, and finally, the analysis to verify the database coherence is presented. Based on 25 relevant variables, the relationships between variables are described and organised into five factors (HDP - Human Development against Poverty, AP - Human Activity Pressure on water resources, WR - Water Resources, ODA - Official Development Aid, CEC - Country Environmental Concern). Linear regression methods are used to identify key variables having influence on water supply and sanitation. First analysis indicates that the informal urbanisation development is an important factor negatively influencing the percentage of the population having access to WSS. Health, and in particular children's health, benefits from the improvement of WSS. Irrigation is also enhancing Water Supply service thanks to multi-purpose infrastructure. Five country profiles are also created to deeper understand and synthetize the amount of information gathered. This new

  1. Structural and biochemical analyses of monoubiquitinated human histones H2B and H4

    PubMed Central

    Machida, Shinichi; Sekine, Satoshi; Nishiyama, Yuuki; Horikoshi, Naoki; Kurumizaka, Hitoshi

    2016-01-01

    Monoubiquitination is a major histone post-translational modification. In humans, the histone H2B K120 and histone H4 K31 residues are monoubiquitinated and may form transcriptionally active chromatin. In this study, we reconstituted nucleosomes containing H2B monoubiquitinated at position 120 (H2Bub120) and/or H4 monoubiquitinated at position 31 (H4ub31). We found that the H2Bub120 and H4ub31 monoubiquitinations differently affect nucleosome stability: the H2Bub120 monoubiquitination enhances the H2A–H2B association with the nucleosome, while the H4ub31 monoubiquitination decreases the H3–H4 stability in the nucleosome, when compared with the unmodified nucleosome. The H2Bub120 and H4ub31 monoubiquitinations both antagonize the Mg2+-dependent compaction of a poly-nucleosome, suggesting that these monoubiquitinations maintain more relaxed conformations of chromatin. In the crystal structure, the H2Bub120 and H4ub31 monoubiquitinations do not change the structure of the nucleosome core particle and the ubiquitin molecules were flexibly disordered in the H2Bub120/H4ub31 nucleosome structure. These results revealed the differences and similarities of the H2Bub120 and H4ub31 monoubiquitinations at the mono- and poly-nucleosome levels and provide novel information to clarify the roles of monoubiquitination in chromatin. PMID:27335322

  2. Feasible muscle activation ranges based on inverse dynamics analyses of human walking.

    PubMed

    Simpson, Cole S; Sohn, M Hongchul; Allen, Jessica L; Ting, Lena H

    2015-09-18

    Although it is possible to produce the same movement using an infinite number of different muscle activation patterns owing to musculoskeletal redundancy, the degree to which observed variations in muscle activity can deviate from optimal solutions computed from biomechanical models is not known. Here, we examined the range of biomechanically permitted activation levels in individual muscles during human walking using a detailed musculoskeletal model and experimentally-measured kinetics and kinematics. Feasible muscle activation ranges define the minimum and maximum possible level of each muscle's activation that satisfy inverse dynamics joint torques assuming that all other muscles can vary their activation as needed. During walking, 73% of the muscles had feasible muscle activation ranges that were greater than 95% of the total muscle activation range over more than 95% of the gait cycle, indicating that, individually, most muscles could be fully active or fully inactive while still satisfying inverse dynamics joint torques. Moreover, the shapes of the feasible muscle activation ranges did not resemble previously-reported muscle activation patterns nor optimal solutions, i.e. static optimization and computed muscle control, that are based on the same biomechanical constraints. Our results demonstrate that joint torque requirements from standard inverse dynamics calculations are insufficient to define the activation of individual muscles during walking in healthy individuals. Identifying feasible muscle activation ranges may be an effective way to evaluate the impact of additional biomechanical and/or neural constraints on possible versus actual muscle activity in both normal and impaired movements. PMID:26300401

  3. Analyses of the Secondary Particle Radiation and the DNA Damage it Causes to Human Keratinocytes

    SciTech Connect

    Lebel E. A.; Tafrov S.; Rusek, A.; Sivertz, M. B.; Yip, K.; Thompson, K. H.

    2011-11-01

    High-energy protons, and high mass and energy ions, along with the secondary particles they produce, are the main contributors to the radiation hazard during space explorations. Skin, particularly the epidermis, consisting mainly of keratinocytes with potential for proliferation and malignant transformation, absorbs the majority of the radiation dose. Therefore, we used normal human keratinocytes to investigate and quantify the DNA damage caused by secondary radiation. Its manifestation depends on the presence of retinol in the serum-free media, and is regulated by phosphatidylinositol 3-kinases. We simulated the generation of secondary radiation after the impact of protons and iron ions on an aluminum shield. We also measured the intensity and the type of the resulting secondary particles at two sample locations; our findings agreed well with our predictions. We showed that secondary particles inflict DNA damage to different extents, depending on the type of primary radiation. Low-energy protons produce fewer secondary particles and cause less DNA damage than do high-energy protons. However, both generate fewer secondary particles and inflict less DNA damage than do high mass and energy ions. The majority of cells repaired the initial damage, as denoted by the presence of 53BPI foci, within the first 24 hours after exposure, but some cells maintained the 53BP1 foci longer.

  4. Analyses of the secondary particle radiation and the DNA damage it causes to human keratinocytes

    SciTech Connect

    Lebel E.; Rusek A.; Sivertz, M.; Yip, K.; Thompson, K.; Tafrov, S.

    2011-11-22

    High-energy protons, and high mass and energy ions, along with the secondary particles they produce, are the main contributors to the radiation hazard during space explorations. Skin, particularly the epidermis, consisting mainly of keratinocytes with potential for proliferation and malignant transformation, absorbs the majority of the radiation dose. Therefore, we used normal human keratinocytes to investigate and quantify the DNA damage caused by secondary radiation. Its manifestation depends on the presence of retinol in the serum-free media, and is regulated by phosphatidylinositol 3-kinases. We simulated the generation of secondary radiation after the impact of protons and iron ions on an aluminum shield. We also measured the intensity and the type of the resulting secondary particles at two sample locations; our findings agreed well with our predictions. We showed that secondary particles inflict DNA damage to different extents, depending on the type of primary radiation. Low-energy protons produce fewer secondary particles and cause less DNA damage than do high-energy protons. However, both generate fewer secondary particles and inflict less DNA damage than do high mass and energy ions. The majority of cells repaired the initial damage, as denoted by the presence of 53BPI foci, within the first 24 hours after exposure, but some cells maintained the 53BP1 foci longer.

  5. Functional Mapping of Human Dynamin-1-Like GTPase Domain Based on X-ray Structure Analyses

    PubMed Central

    Fröhlich, Chris; Eibl, Clarissa; Gimeno, Ana; Hessenberger, Manuel; Puehringer, Sandra; Daumke, Oliver; Goettig, Peter

    2013-01-01

    Human dynamin-1-like protein (DNM1L) is a GTP-driven molecular machine that segregates mitochondria and peroxisomes. To obtain insights into its catalytic mechanism, we determined crystal structures of a construct comprising the GTPase domain and the bundle signaling element (BSE) in the nucleotide-free and GTP-analogue-bound states. The GTPase domain of DNM1L is structurally related to that of dynamin and binds the nucleotide 5′-Guanylyl-imidodiphosphate (GMP-PNP) via five highly conserved motifs, whereas the BSE folds into a pocket at the opposite side. Based on these structures, the GTPase center was systematically mapped by alanine mutagenesis and kinetic measurements. Thus, residues essential for the GTPase reaction were characterized, among them Lys38, Ser39 and Ser40 in the phosphate binding loop, Thr59 from switch I, Asp146 and Gly149 from switch II, Lys216 and Asp218 in the G4 element, as well as Asn246 in the G5 element. Also, mutated Glu81 and Glu82 in the unique 16-residue insertion of DNM1L influence the activity significantly. Mutations of Gln34, Ser35, and Asp190 in the predicted assembly interface interfered with dimerization of the GTPase domain induced by a transition state analogue and led to a loss of the lipid-stimulated GTPase activity. Our data point to related catalytic mechanisms of DNM1L and dynamin involving dimerization of their GTPase domains. PMID:23977156

  6. Quantitative proteomics analyses of activation states of human THP-1 macrophages.

    PubMed

    Meijer, Kees; Weening, Desiree; de Vries, Marcel P; Priebe, Marion G; Vonk, Roel J; Roelofsen, Han

    2015-10-14

    Macrophages display large functional and phenotypical plasticity. They can adopt a broad range of activation states depending on their microenvironment. Various surface markers are used to characterize these differentially polarized macrophages. However, this is not informative for the functions of the macrophage. In order to have a better understanding of the functional changes of macrophages upon differential polarization, we studied differences in LPS- and IL4-stimulated macrophages. The THP-1 human monocytic cell line, was used as a model system. Cells were labeled, differentiated and stimulated with either LPS or IL-4 in a quantitative SILAC proteomics set-up. The resulting sets of proteins were functionally clustered. LPS-stimulated macrophages show increased secretion of proinflammatory peptides, leading to increased pressure on protein biosynthesis and processing. IL4-stimulated macrophages show upregulation of cell adhesion and extracellular matrix remodeling. Our approach provides an integrated view of polarization-induced functional changes and proves useful for studying functional differences between subsets of macrophages. Moreover, the identified polarization specific proteins may contribute to a better characterization of different activation states in situ and their role in various inflammatory processes. PMID:26200757

  7. Preliminary results on the tectonic activity of the Ovacık Fault (Malatya-Ovacık Fault Zone, Turkey): Implications of the morphometric analyses

    NASA Astrophysics Data System (ADS)

    Yazıcı, Müge; Zabci, Cengiz; Sançar, Taylan; Sunal, Gürsel; Natalin, Boris A.

    2016-04-01

    The Anatolian 'plate' is being extruded westward relative to the Eurasia along two major tectonic structures, the North Anatolian and the East Anatolian shear zones, respectively making its northern and eastern boundaries. Although the main deformation is localized along these two structures, there is remarkable intra-plate deformation within Anatolia, especially which are characterized by NE-striking sinistral and NW-striking dextral strike-slip faults (Şengör et al. 1985). The Malatya-Ovacık Fault Zone (MOFZ) and its northeastern member, the Ovacık Fault (OF), is a one of the NE-striking sinistral strike slip faults in the central 'ova' neotectonic province of Anatolia, located close to its eastern boundary. Although this fault zone is claimed to be an inactive structure in some studies, the recent GPS measurements (Aktuǧ et al., 2013) and microseismic activity (AFAD, 2013) strongly suggest the opposite. In order to understand rates and patterns of vertical ground motions along the OF, we studied the certain morphometric analyses such as hypsometric curves and integrals, longitudinal channel profiles, and asymmetry of drainage basins. The Karasu (Euphrates) and Munzur rivers form the main drainage systems of the study area. We extracted all drainage network from SRTM-based Digital Elevation Model with 30 m ground pixel resolution and totally identified 40 sub-drainage basins, which are inhomogeneously distributed to the north and to the south of the OF. Most of these basins show strong asymmetry, which are mainly tilted to SW. The asymmetry relatively decreases from NE to SW in general. The only exception is at the margins of the Ovacık Basin (OB), where almost the highest asymmetry values were calculated. On the other hand, the characteristics of hypsometric curves and the calculated hypsometric integrals do not show the similar systematic spatial pattern. The hypsometric curves with convex-shaped geometry, naturally indicating relatively young morphology

  8. Preliminary results on the tectonic activity of the Ovacık Fault (Malatya-Ovacık Fault Zone, Turkey): Implications of the morphometric analyses

    NASA Astrophysics Data System (ADS)

    Yazıcı, Müge; Zabci, Cengiz; Sançar, Taylan; Sunal, Gürsel; Natalin, Boris A.

    2016-04-01

    The Anatolian 'plate' is being extruded westward relative to the Eurasia along two major tectonic structures, the North Anatolian and the East Anatolian shear zones, respectively making its northern and eastern boundaries. Although the main deformation is localized along these two structures, there is remarkable intra-plate deformation within Anatolia, especially which are characterized by NE-striking sinistral and NW-striking dextral strike-slip faults (Şengör et al. 1985). The Malatya-Ovacık Fault Zone (MOFZ) and its northeastern member, the Ovacık Fault (OF), is a one of the NE-striking sinistral strike slip faults in the central 'ova' neotectonic province of Anatolia, located close to its eastern boundary. Although this fault zone is claimed to be an inactive structure in some studies, the recent GPS measurements (Aktuǧ et al., 2013) and microseismic activity (AFAD, 2013) strongly suggest the opposite. In order to understand rates and patterns of vertical ground motions along the OF, we studied the certain morphometric analyses such as hypsometric curves and integrals, longitudinal channel profiles, and asymmetry of drainage basins. The Karasu (Euphrates) and Munzur rivers form the main drainage systems of the study area. We extracted all drainage network from SRTM-based Digital Elevation Model with 30 m ground pixel resolution and totally identified 40 sub-drainage basins, which are inhomogeneously distributed to the north and to the south of the OF. Most of these basins show strong asymmetry, which are mainly tilted to SW. The asymmetry relatively decreases from NE to SW in general. The only exception is at the margins of the Ovacık Basin (OB), where almost the highest asymmetry values were calculated. On the other hand, the characteristics of hypsometric curves and the calculated hypsometric integrals do not show the similar systematic spatial pattern. The hypsometric curves with convex-shaped geometry, naturally indicating relatively young morphology

  9. In silico analyses of substrate interactions with human serum paraoxonase 1.

    PubMed

    Hu, Xin; Jiang, Xiaohui; Lenz, David E; Cerasoli, Douglas M; Wallqvist, Anders

    2009-05-01

    Human paraoxonase (HuPON1) is a serum enzyme that exhibits a broad spectrum of hydrolytic activities, including the hydrolysis of various organophosphates, esters, and recently identified lactone substrates. Despite intensive site-directed mutagenesis and other biological studies, the structural basis for the specificity of substrate interactions of HuPON1 remains elusive. In this study, we apply homology modeling, docking, and molecular dynamic (MD) simulations to probe the binding interactions of HuPON1 with representative substrates. The results suggest that the active site of HuPON1 is characterized by two distinct binding regions: the hydrophobic binding site for arylesters/lactones, and the paraoxon binding site for phosphotriesters. The unique binding modes proposed for each type of substrate reveal a number of key residues governing substrate specificity. The polymorphic residue R/Q192 interacts with the leaving group of paraoxon, suggesting it plays an important role in the proper positioning of this substrate in the active site. MD simulations of the optimal binding complexes show that residue Y71 undergoes an "open-closed" conformational change upon ligand binding, and forms strong interactions with substrates. Further binding free energy calculations and residual decomposition give a more refined molecular view of the energetics and origin of HuPON1/substrate interactions. These studies provide a theoretical model of substrate binding and specificity associated with wild type and mutant forms of HuPON1, which can be applied in the rational design of HuPON1 variants as bioscavengers with enhanced catalytic activity. PMID:18951406

  10. Biochemical, Biophysical, and Mutational Analyses of Subunit Interactions of the Human Cytomegalovirus Nuclear Egress Complex▿

    PubMed Central

    Sam, My D.; Evans, Brady T.; Coen, Donald M.; Hogle, James M.

    2009-01-01

    Nuclear egress, the trafficking of herpesvirus nucleocapsids from the nucleus to the cytoplasm, involves two conserved viral proteins that form a complex at the nuclear envelope, referred to as the nuclear egress complex. In human cytomegalovirus, these two proteins are called UL50 and UL53. To study UL50 and UL53 in molecular detail, these proteins were expressed in bacteria and purified. To obtain highly expressed, pure proteins, it was necessary to truncate both constructs based on sequence conservation and predicted secondary structural elements. Size exclusion chromatography and analytical ultracentrifugation studies indicated that the truncated form of UL50 is a monomer in solution, that the truncated form of UL53 is a homodimer, and that, when mixed, the two proteins form a heterodimer. To identify residues of UL53 crucial for homodimerization and for heterodimerization with UL50, we constructed and expressed mutant forms of UL53 containing alanine substitutions in a predicted helix. Isothermal titration calorimetry was used to measure the binding affinities of the UL53 mutants to UL50. UL53 residues, the replacement of which reduced binding to UL50, form a surface on one face of the predicted helix. Moreover, most of the substitutions that reduce UL53-UL50 interactions also reduced homodimerization. Substitutions that reduced the interaction between UL50 and UL53 in vitro also reduced colocalization of full-length UL50 and UL53 at the nuclear rim in transfected cells. These results demonstrate direct protein-protein interactions between these proteins that are likely to be mediated by a helix, and they have implications for understanding nuclear egress and for drug discovery. PMID:19153235

  11. Comparative Genetic Analyses of Human Rhinovirus C (HRV-C) Complete Genome from Malaysia

    PubMed Central

    Khaw, Yam Sim; Chan, Yoke Fun; Jafar, Faizatul Lela; Othman, Norlijah; Chee, Hui Yee

    2016-01-01

    Human rhinovirus-C (HRV-C) has been implicated in more severe illnesses than HRV-A and HRV-B, however, the limited number of HRV-C complete genomes (complete 5′ and 3′ non-coding region and open reading frame sequences) has hindered the in-depth genetic study of this virus. This study aimed to sequence seven complete HRV-C genomes from Malaysia and compare their genetic characteristics with the 18 published HRV-Cs. Seven Malaysian HRV-C complete genomes were obtained with newly redesigned primers. The seven genomes were classified as HRV-C6, C12, C22, C23, C26, C42, and pat16 based on the VP4/VP2 and VP1 pairwise distance threshold classification. Five of the seven Malaysian isolates, namely, 3430-MY-10/C22, 8713-MY-10/C23, 8097-MY-11/C26, 1570-MY-10/C42, and 7383-MY-10/pat16 are the first newly sequenced complete HRV-C genomes. All seven Malaysian isolates genomes displayed nucleotide similarity of 63–81% among themselves and 63–96% with other HRV-Cs. Malaysian HRV-Cs had similar putative immunogenic sites, putative receptor utilization and potential antiviral sites as other HRV-Cs. The genomic features of Malaysian isolates were similar to those of other HRV-Cs. Negative selections were frequently detected in HRV-Cs complete coding sequences indicating that these sequences were under functional constraint. The present study showed that HRV-Cs from Malaysia have diverse genetic sequences but share conserved genomic features with other HRV-Cs. This genetic information could provide further aid in the understanding of HRV-C infection. PMID:27199901

  12. Comparative Genetic Analyses of Human Rhinovirus C (HRV-C) Complete Genome from Malaysia.

    PubMed

    Khaw, Yam Sim; Chan, Yoke Fun; Jafar, Faizatul Lela; Othman, Norlijah; Chee, Hui Yee

    2016-01-01

    Human rhinovirus-C (HRV-C) has been implicated in more severe illnesses than HRV-A and HRV-B, however, the limited number of HRV-C complete genomes (complete 5' and 3' non-coding region and open reading frame sequences) has hindered the in-depth genetic study of this virus. This study aimed to sequence seven complete HRV-C genomes from Malaysia and compare their genetic characteristics with the 18 published HRV-Cs. Seven Malaysian HRV-C complete genomes were obtained with newly redesigned primers. The seven genomes were classified as HRV-C6, C12, C22, C23, C26, C42, and pat16 based on the VP4/VP2 and VP1 pairwise distance threshold classification. Five of the seven Malaysian isolates, namely, 3430-MY-10/C22, 8713-MY-10/C23, 8097-MY-11/C26, 1570-MY-10/C42, and 7383-MY-10/pat16 are the first newly sequenced complete HRV-C genomes. All seven Malaysian isolates genomes displayed nucleotide similarity of 63-81% among themselves and 63-96% with other HRV-Cs. Malaysian HRV-Cs had similar putative immunogenic sites, putative receptor utilization and potential antiviral sites as other HRV-Cs. The genomic features of Malaysian isolates were similar to those of other HRV-Cs. Negative selections were frequently detected in HRV-Cs complete coding sequences indicating that these sequences were under functional constraint. The present study showed that HRV-Cs from Malaysia have diverse genetic sequences but share conserved genomic features with other HRV-Cs. This genetic information could provide further aid in the understanding of HRV-C infection. PMID:27199901

  13. Epitope-mapped monoclonal antibodies as tools for functional and morphological analyses of the human urokinase receptor in tumor tissue.

    PubMed Central

    Luther, T.; Magdolen, V.; Albrecht, S.; Kasper, M.; Riemer, C.; Kessler, H.; Graeff, H.; Müller, M.; Schmitt, M.

    1997-01-01

    uPAR (CD87), the receptor for the urokinase-type plasminogen activator (uPA) facilitates tumor cell invasion and metastasis by focusing uPA proteolytic activity to the cell surface. As uPAR exists in various molecular forms, it is desirable to use well defined antibodies for analyses of uPAR antigen expression in human malignant tumors by immunological methods. Therefore, twelve monoclonal antibodies (MAbs) directed against uPAR were generated by using nonglycosylated, recombinant human uPAR (spanning amino acids 1 to 284), expressed in Escherichia coli, as the immunogen. The reaction pattern of these MAbs with the immunogen and a series of carboxyl-terminally truncated versions of uPAR demonstrated that at least six different epitopes of uPAR are recognized. All MAbs reacted under reducing conditions in immunoblot analyses with E. coli-expressed uPA and also with highly glycosylated, functionally intact, recombinant human uPAR expressed in Chinese hamster ovary (CHO) cells. Seven of the MAbs recognized CHO uPAR under nonreducing conditions as well. By flow cytofluorometric analyses, three of these MAbs were shown to bind to native human uPAR present on the cell surface of monocytoid U937 cells with MAb IIIF10 being the best. Saturation of uPAR with uPA on U937 cells completely blocked interaction of MAb IIIF10 with uPAR (mapped epitope, amino acids 52 to 60 of domain I of uPAR). In turn, preincubation of U937 cells with MAb IIIF10 efficiently reduced binding of uPA to uPAR, indicating that the epitope detected by MAb IIIF10 is located within or closely to the uPA-binding site of uPAR, and thus, this site may be a target to influence uPA/uPAR-mediated proteolysis in tumors. Binding of MAbs IID7 or IIIB11 (mapped epitope, amino acids 125 to 132 of domain II of uPAR) to uPAR is not affected when uPAR is occupied by uPA. As these MAbs reacted strongly with cellular uPAR antigen in formalin-fixed paraffin-embedded tumor sections, the domain-II-specific antibodies IID7

  14. Genetic analyses of the human eye colours using a novel objective method for eye colour classification.

    PubMed

    Andersen, Jeppe D; Johansen, Peter; Harder, Stine; Christoffersen, Susanne R; Delgado, Mikaela C; Henriksen, Sarah T; Nielsen, Mette M; Sørensen, Erik; Ullum, Henrik; Hansen, Thomas; Dahl, Anders L; Paulsen, Rasmus R; Børsting, Claus; Morling, Niels

    2013-09-01

    In this study, we present a new objective method for measuring the eye colour on a continuous scale that allows researchers to associate genetic markers with different shades of eye colour. With the use of the custom designed software Digital Iris Analysis Tool (DIAT), the iris was automatically identified and extracted from high resolution digital images. DIAT was made user friendly with a graphical user interface. The software counted the number of blue and brown pixels in the iris image and calculated a Pixel Index of the Eye (PIE-score) that described the eye colour quantitatively. The PIE-score ranged from -1 to 1 (brown to blue). The software eliminated the need for user based interpretation and qualitative eye colour categories. In 94% (570) of 605 analyzed eye images, the iris region was successfully extracted and a PIE-score was calculated. A very high correlation between the PIE-score and the human perception of eye colour was observed. The correlations between the PIE-scores and the six IrisPlex SNPs (HERC2 rs12913832, OCA2 rs1800407, SLC24A4 rs12896399, TYR rs1393350, SLC45A2 rs16891982 and IRF4 rs12203592) were analyzed in 570 individuals. Significant differences (p<10(-6)) in the PIE-scores of the individuals typed as HERC2 rs12913832 G (PIE=0.99) and rs12913832 GA (PIE=-0.71) or A (PIE=-0.87) were observed. We adjusted for the effect of HERC2 rs12913832 and showed that the quantitative PIE-scores were significantly associated with SNPs with minor effects (OCA2 rs1800407, SLC24A4 rs12896399 and TYR rs1393350) on the eye colour. We evaluated the two published prediction models for eye colour (IrisPlex [1] and Snipper[2]) and compared the predictions with the PIE-scores. We found good concordance with the prediction from individuals typed as HERC2 rs12913832 G. However, both methods had difficulties in categorizing individuals typed as HERC2 rs12913832 GA because of the large variation in eye colour in HERC2 rs12913832 GA individuals. With the use of

  15. Anti-apoptotic Effects of Bone Marrow on Human Islets: A Preliminary Report

    PubMed Central

    Luo, Lu-Guang; Luo, John ZQ

    2015-01-01

    Apoptosis is one of the major factors contributing to the failure of human islet transplantation. Contributors to islet apoptosis exist in both the pre-transplantation and post transplantation stages. Factors include the islet isolation process, deterioration in vitro prior to transplantation, and immune rejection post transplantation. Previous studies have demonstrated that co-cultured bone marrow cells with human islets not only significantly enhanced the longevity of human islets but also maintained function. We hypothesized that the protective effects of bone marrow cells on human islets are through mechanisms related to preventing apoptosis. This study observed the levels of inflammatory factors such as interleukin-1β (IL-1β), the release of extracellular ATP in vitro, and expression levels of P2X7 ATP receptor (P2X7R), all of which lead to the occurrence of apoptosis in human islets. When human islets were co-cultured with human bone marrow, there was a reduction in the rate of apoptosis correlated with the reduction in inflammatory factors, extra cellular ATP accumulation, and ATP receptor P2X7R expression versus human islets cultured alone. These results suggest that co-culturing bone marrow cells with human islets inhibits inflammation and reduces apoptosis, thus protecting islets from self-deterioration. PMID:26229735

  16. Preliminary Study of Open Quotient in an Ex-Vivo Perfused Human Larynx Model

    PubMed Central

    Mendelsohn, Abie H.; Zhang, Zhaoyan; Luegmair, Georg; Orestes, Michael; Berke, Gerald S.

    2016-01-01

    Importance Scientific understanding human voice production to date is a product of indirect investigations including animal models, cadaveric tissue study, or computational modeling. Due to its invasive nature, direct experimentation of human voice production has previously not been possible. The feasibility of an ex-vivo perfused human phonatory model has recently allowed systematic investigation in virtually living human larynges with parametric laryngeal muscle stimulation. Objective In this study, the relationship between adductor muscle group stimulation and the open quotient (OQ) of vocal fold vibration was investigated using an ex-vivo perfused human larynx. Design Human perfused tissue study. Setting Physiology Laboratory. Participants Human larynx is recovered from research-consented organ donors within two hours of cardiac death. Interventions, Main Outcomes and Measures Perfusion with donated human blood is re-established shortly after cardiac death. Human perfused phonation is achieved by providing subglottal airflow under graded neuromuscular electrical stimulation bilaterally to the intrinsic adductor groups and cricothyroid muscles. The phonation resulting from the graded states of neuromuscular stimulations are evaluated through high-speed vibratory imaging. OQ is derived through digital kymography and glottal area waveform analysis. Results Under constant glottal flow, step-wise increase in adductor muscle group stimulation decreased OQ. Quantitatively, OQ values reached a lower limit of 0.42. Increased stimulation above maximal muscle deformation was unable to affect OQ beyond this lower limit. Conclusions and Relevance For the first time in a neuromuscularly activated human larynx, a negative relationship between adductor muscle group stimulation and phonatory OQ was demonstrated. Further experience with the ex-vivo perfused human phonatory model will work to systematically define this causal relationship. PMID:26181642

  17. Direct Dating and Physico-Chemical Analyses Cast Doubts on the Coexistence of Humans and Dwarf Hippos in Cyprus

    PubMed Central

    Zazzo, Antoine; Lebon, Matthieu; Quiles, Anita; Reiche, Ina; Vigne, Jean-Denis

    2015-01-01

    In the Mediterranean, the island dwarf megafaunas became extinct around the end of the Pleistocene, during a period of rapid and global climate change. In Cyprus, this coincided with the first human presence on the island, as attested by the rock shelter of Akrotiri-Aetokremnos where an Epipaleolithic anthropogenic layer (stratum 2) was found overlying a massive accumulation of pygmy hippopotamus (Phanourios minor (Desmarest, 1822)) [Boekschoten and Sondaar, 1972] bones (stratum 4). The relationship between the two layers is highly controversial and the role played by humans in hippo extinction remains fiercely debated. Here, we provide new, direct radiocarbon and physico-chemical analyses on calcined bones which elucidates the complex depositional history of the assemblage. Bone turquoise was identified using micro-PIXE analysis and depth-profiling together with Vis spectroscopy, demonstrating that these bones were not freshly burned. Bayesian modeling of the radiocarbon dates indicates that stratum 4 accumulated during the first half of the 13th mill cal BP and that calcination occurred several hundred years later. We conclude that accumulation occurred naturally during the beginning of the Younger Dryas and that Epipalaeolithic visitors subsequently used the bones as fuel, starting from the mid-13th mill cal BP. At that time, dwarf hippos were probably already extinct or at least highly endangered. Our results shed new light on the possible causes of hippo extinction, on the subsequent introduction of the wild boar and on the earliest occupation of the island by humans. PMID:26284623

  18. Comparative analyses of the proteins from Mycobacterium tuberculosis and human genomes: Identification of potential tuberculosis drug targets.

    PubMed

    Sridhar, Settu; Dash, Pallabini; Guruprasad, Kunchur

    2016-03-15

    Tuberculosis, one of the major infectious diseases affecting human beings is caused by the bacillus Mycobacterium tuberculosis. Increased resistance to known drugs commonly used for the treatment of tuberculosis has created an urgent need to identify new targets for validation and to develop drugs. In this study, we have used various bioinformatics tools, to compare the protein sequences from twenty-three M. tuberculosis genome strains along with the known human protein sequences, in order to identify the 'conserved' M. tuberculosis proteins absent in human. Further, based on the analysis of protein interaction networks, we selected one-hundred and forty proteins that were predicted as potential M. tuberculosis drug targets and prioritized according to the ranking of 'clusters' of interacting proteins. Comparison of the predicted 140 TB targets with literature indicated that 46 of them were previously reported, thereby increasing the confidence in our predictions of the remaining 94 targets too. The analyses of the structures and functions corresponding to the predicted potential TB drug targets indicated a diverse range of proteins that included ten 'druggable' targets with some of the known drugs. PMID:26762852

  19. Direct Dating and Physico-Chemical Analyses Cast Doubts on the Coexistence of Humans and Dwarf Hippos in Cyprus.

    PubMed

    Zazzo, Antoine; Lebon, Matthieu; Quiles, Anita; Reiche, Ina; Vigne, Jean-Denis

    2015-01-01

    In the Mediterranean, the island dwarf megafaunas became extinct around the end of the Pleistocene, during a period of rapid and global climate change. In Cyprus, this coincided with the first human presence on the island, as attested by the rock shelter of Akrotiri-Aetokremnos where an Epipaleolithic anthropogenic layer (stratum 2) was found overlying a massive accumulation of pygmy hippopotamus (Phanourios minor (Desmarest, 1822)) [Boekschoten and Sondaar, 1972] bones (stratum 4). The relationship between the two layers is highly controversial and the role played by humans in hippo extinction remains fiercely debated. Here, we provide new, direct radiocarbon and physico-chemical analyses on calcined bones which elucidates the complex depositional history of the assemblage. Bone turquoise was identified using micro-PIXE analysis and depth-profiling together with Vis spectroscopy, demonstrating that these bones were not freshly burned. Bayesian modeling of the radiocarbon dates indicates that stratum 4 accumulated during the first half of the 13th mill cal BP and that calcination occurred several hundred years later. We conclude that accumulation occurred naturally during the beginning of the Younger Dryas and that Epipalaeolithic visitors subsequently used the bones as fuel, starting from the mid-13th mill cal BP. At that time, dwarf hippos were probably already extinct or at least highly endangered. Our results shed new light on the possible causes of hippo extinction, on the subsequent introduction of the wild boar and on the earliest occupation of the island by humans. PMID:26284623

  20. Comparative Study of Human Liver Ferritin and Chicken Liver by Mössbauer Spectroscopy. Preliminary Results

    NASA Astrophysics Data System (ADS)

    Oshtrakh, M. I.; Milder, O. B.; Semionkin, V. A.; Prokopenko, P. G.; Malakheeva, L. I.

    2004-12-01

    A comparative study of normal human liver ferritin and livers from normal chicken and chicken with Marek disease was made by Mössbauer spectroscopy. Small differences of quadrupole splitting and isomer shift were found for human liver ferritin and chicken liver. Mössbauer parameters for liver from normal chicken and chicken with Marek disease were the same.

  1. A Preliminary Study of Peer-to-Peer Human-Robot Interaction

    NASA Technical Reports Server (NTRS)

    Fong, Terrence; Flueckiger, Lorenzo; Kunz, Clayton; Lees, David; Schreiner, John; Siegel, Michael; Hiatt, Laura M.; Nourbakhsh, Illah; Simmons, Reid; Ambrose, Robert

    2006-01-01

    The Peer-to-Peer Human-Robot Interaction (P2P-HRI) project is developing techniques to improve task coordination and collaboration between human and robot partners. Our work is motivated by the need to develop effective human-robot teams for space mission operations. A central element of our approach is creating dialogue and interaction tools that enable humans and robots to flexibly support one another. In order to understand how this approach can influence task performance, we recently conducted a series of tests simulating a lunar construction task with a human-robot team. In this paper, we describe the tests performed, discuss our initial results, and analyze the effect of intervention on task performance.

  2. Purification, crystallization and preliminary crystallographic characterization of the caspase-recruitment domain of human Nod1

    SciTech Connect

    Srimathi, Thiagarajan; Robbins, Sheila L.; Dubas, Rachel L.; Seo, Jang-Hoon; Park, Young Chul

    2007-01-01

    The caspase-recruitment domain of the cytosolic pathogen receptor Nod1 was crystallized. X-ray diffraction data were collected to 1.9 Å resolution. The caspase-recruitment domain (CARD) is known to play an important role in apoptosis and inflammation as an essential protein–protein interaction domain. The CARD of the cytosolic pathogen receptor Nod1 was overexpressed in Escherichia coli and purified by affinity chromatography and gel filtration. The purified CARD was crystallized at 277 K using the microseeding method. X-ray diffraction data were collected to 1.9 Å resolution. The crystals belong to space group P3{sub 1} or P3{sub 2}, with unit-cell parameters a = b = 79.1, c = 80.9 Å. Preliminary analysis indicates that there is one dimeric CARD molecule in the asymmetric unit.

  3. Is a Swine Model of Arteriovenous Malformation Suitable for Human Extracranial Arteriovenous Malformation? A Preliminary Study

    SciTech Connect

    Lv, Ming-ming; Fan, Xin-dong; Su, Li-xin

    2013-10-15

    Objective: A chronic arteriovenous malformation (AVM) model using the swine retia mirabilia (RMB) was developed and compared with the human extracranial AVM (EAVM) both in hemodynamics and pathology, to see if this brain AVM model can be used as an EAVM model. Methods: We created an arteriovenous fistula between the common carotid artery and the external jugular vein in eight animals by using end-to-end anastomosis. All animals were sacrificed 1 month after surgery, and the bilateral retia were obtained at autopsy and performed hematoxylin and eosin staining and immunohistochemistry. Pre- and postsurgical hemodynamic evaluations also were conducted. Then, the blood flow and histological changes of the animal model were compared with human EAVM. Results: The angiography after operation showed that the blood flow, like human EAVM, flowed from the feeding artery, via the nidus, drained to the draining vein. Microscopic examination showed dilated lumina and disrupted internal elastic lamina in both RMB of model and nidus of human EAVM, but the thickness of vessel wall had significant difference. Immunohistochemical reactivity for smooth muscle actin, angiopoietin 1, and angiopoietin 2 were similar in chronic model nidus microvessels and human EAVM, whereas vascular endothelial growth factor was significant difference between human EAVM and RMB of model. Conclusions: The AVM model described here is similar to human EAVM in hemodynamics and immunohistochemical features, but there are still some differences in anatomy and pathogenetic mechanism. Further study is needed to evaluate the applicability and efficacy of this model.

  4. Regulation of human immune gene expression as influenced by a commercial blended Echinacea product: preliminary studies.

    PubMed

    Randolph, R K; Gellenbeck, K; Stonebrook, K; Brovelli, E; Qian, Y; Bankaitis-Davis, D; Cheronis, J

    2003-10-01

    Consumption of Echinacea at the first sign of symptoms has been clinically shown to reduce both the severity and duration of cold and flu. Quantitative polymerase chain reaction optimized for precision and reproducibility was utilized to explore in vitro and in vivo changes in the expression of immunomodulatory genes in response to Echinacea. In vitro exposure of THP-1 cells to 250 microg/ml of Echinacea species extracts induced expression (up to 10-fold) of the interleukin-1alpha, interleukin-1beta, tumor necrosis factor-alpha, intracellular adhesion molecule, interleukin-8, and interleukin-10 genes. This preliminary result is consistent with a general immune response and activation of the nonspecific immune response cytokines. In vivo gene expression within peripheral leukocytes was evaluated in six healthy nonsmoking subjects (18-65 years of age). Blood samples were obtained at baseline and on Days 2, 3, 5, and 12 after consuming a commercial blended Echinacea product, three tablets three times daily (1518 mg/day) for two days plus one additional dose (506 mg) on day three. Serum chemistry and hematological values were not different from baseline, suggesting that liver or bone marrow responses were not involved in acute responses to Echinacea. The overall gene expression pattern at 48 hr to 12 days after taking Echinacea was consistent with an antiinflammatory response. The expression of interleukin-1beta, tumor necrosis factor-alpha, intracellular adhesion molecule, and interleukin-8 was modestly decreased up through Day 5, returning to baseline by day 12. The expression of interferon-alpha steadily rose through Day 12, consistent with an antiviral response. These preliminary data present a gene expression response pattern that is consistent with Echinacea's reported ability to reduce both the duration and intensity of cold and flu symptoms. PMID:14530514

  5. Searching for the vomeronasal organ of adult humans: preliminary findings on location, structure, and size.

    PubMed

    Smith, T D; Siegel, M I; Burrows, A M; Mooney, M P; Burdi, A R; Fabrizio, P A; Clemente, F R

    1998-06-15

    The adult human vomeronasal organ (VNO) has been the focus of numerous recent investigations, yet its developmental continuity from the human fetal VNO is poorly understood. The present study compared new data on the adult human "VNO" with previous findings on the fetal human VNO. Nasal septa were removed from twelve adult human cadavers and each specimen was histologically sectioned. Coronal sections were stained with hematoxylin-eosin and periodic acid-Schiff-hematoxylin. The sections were examined by light microscopy for the presence of VNOs and the anterior paraseptal cartilages (PC). VNOs were quantified using a computer reconstruction technique to obtain VNO length, volume, and vomeronasal epithelium (VNE) volume. Histologically, VNOs and PCs were identified in eleven specimens. VNOs had ciliated, pseudostratified columnar epithelium with goblet cells. Variations (e.g., multiple communications to the nasal cavity) were observed in several specimens. Quantification was possible for 16 right or left VNOs. Right or left VNOs ranged from 3.5 to 11.8 mm in length, from 1.8 to 33.8 x 10(-4)cc in volume, and from 2.7 to 18.1 x 10(-4)cc in VNE volume. Results indicated that the adult human VNO was similar in VNE morphology, lumen shape, and spatial relationships when compared to human fetal VNOs. By comparison with previous fetal VNO measures, mean VNO length, volume, and VNE volume were larger in adult humans. These results support previous suggestions that postnatal VNO growth occurs. Findings on location and spatial relationships of the adult VNO were similar to those seen in human fetuses, but critical questions remain regarding the ontogeny of the vomeronasal nerves and VNE. PMID:9712196

  6. Crystallization and preliminary X-ray diffraction analysis of human phosphate-binding protein

    SciTech Connect

    Contreras-Martel, Carlos; Carpentier, Philippe; Morales, Renaud; Renault, Frédérique; Chesne-Seck, Marie-Laure; Rochu, Daniel; Masson, Patrick; Fontecilla-Camps, Juan Carlos; Chabrière, Eric

    2006-01-01

    The purification, detergent-exchange protocol and crystallization conditions that led to the discovery of HPBP are reported. HPBP is a new human apoprotein that is absent from the genomic database and is the first phosphate transporter characterized in human plasma. Human phosphate-binding protein (HPBP) was serendipitously discovered by crystallization and X-ray crystallography. HPBP belongs to a eukaryotic protein family named DING that is systematically absent from the genomic database. This apoprotein of 38 kDa copurifies with the HDL-associated apoprotein paraoxonase (PON1) and binds inorganic phosphate. HPBP is the first identified transporter capable of binding phosphate ions in human plasma. Thus, it may be regarded as a predictor of phosphate-related diseases such as atherosclerosis. In addition, HPBP may be a potential therapeutic protein for the treatment of such diseases. Here, the purification, detergent-exchange protocol and crystallization conditions that led to the discovery of HPBP are reported.

  7. Human events reference for ATHEANA (HERA) database description and preliminary user`s manual

    SciTech Connect

    Auflick, J.L.; Hahn, H.A.; Pond, D.J.

    1998-05-27

    The Technique for Human Error Analysis (ATHEANA) is a newly developed human reliability analysis (HRA) methodology that aims to facilitate better representation and integration of human performance into probabilistic risk assessment (PRA) modeling and quantification by analyzing risk-significant operating experience in the context of existing behavioral science models. The fundamental premise of ATHEANA is that error-forcing contexts (EFCs), which refer to combinations of equipment/material conditions and performance shaping factors (PSFs), set up or create the conditions under which unsafe actions (UAs) can occur. Because ATHEANA relies heavily on the analysis of operational events that have already occurred as a mechanism for generating creative thinking about possible EFCs, a database, called the Human Events Reference for ATHEANA (HERA), has been developed to support the methodology. This report documents the initial development efforts for HERA.

  8. Human Events Reference for ATHEANA (HERA) Database Description and Preliminary User's Manual

    SciTech Connect

    Auflick, J.L.

    1999-08-12

    The Technique for Human Error Analysis (ATHEANA) is a newly developed human reliability analysis (HRA) methodology that aims to facilitate better representation and integration of human performance into probabilistic risk assessment (PRA) modeling and quantification by analyzing risk-significant operating experience in the context of existing behavioral science models. The fundamental premise of ATHEANA is that error forcing contexts (EFCs), which refer to combinations of equipment/material conditions and performance shaping factors (PSFs), set up or create the conditions under which unsafe actions (UAs) can occur. Because ATHEANA relies heavily on the analysis of operational events that have already occurred as a mechanism for generating creative thinking about possible EFCs, a database (db) of analytical operational events, called the Human Events Reference for ATHEANA (HERA), has been developed to support the methodology. This report documents the initial development efforts for HERA.

  9. Exploratory Metabolomic Analyses Reveal Compounds Correlated with Lutein Concentration in Frontal Cortex, Hippocampus, and Occipital Cortex of Human Infant Brain

    PubMed Central

    Lieblein-Boff, Jacqueline C.; Johnson, Elizabeth J.; Kennedy, Adam D.; Lai, Chron-Si; Kuchan, Matthew J.

    2015-01-01

    Lutein is a dietary carotenoid well known for its role as an antioxidant in the macula, and recent reports implicate a role for lutein in cognitive function. Lutein is the dominant carotenoid in both pediatric and geriatric brain tissue. In addition, cognitive function in older adults correlated with macular and postmortem brain lutein concentrations. Furthermore, lutein was found to preferentially accumulate in the infant brain in comparison to other carotenoids that are predominant in diet. While lutein is consistently related to cognitive function, the mechanisms by which lutein may influence cognition are not clear. In an effort to identify potential mechanisms through which lutein might influence neurodevelopment, an exploratory study relating metabolite signatures and lutein was completed. Post-mortem metabolomic analyses were performed on human infant brain tissues in three regions important for learning and memory: the frontal cortex, hippocampus, and occipital cortex. Metabolomic profiles were compared to lutein concentration, and correlations were identified and reported here. A total of 1276 correlations were carried out across all brain regions. Of 427 metabolites analyzed, 257 were metabolites of known identity. Unidentified metabolite correlations (510) were excluded. In addition, moderate correlations with xenobiotic relationships (2) or those driven by single outliers (3) were excluded from further study. Lutein concentrations correlated with lipid pathway metabolites, energy pathway metabolites, brain osmolytes, amino acid neurotransmitters, and the antioxidant homocarnosine. These correlations were often brain region—specific. Revealing relationships between lutein and metabolic pathways may help identify potential candidates on which to complete further analyses and may shed light on important roles of lutein in the human brain during development. PMID:26317757

  10. Crystallization and preliminary X-ray analysis of the open form of human ecto-5′-nucleotidase (CD73)

    PubMed Central

    Knapp, Karen Maree; Zebisch, Matthias; Sträter, Norbert

    2012-01-01

    Eukaryotic ecto-5′-nucleotidase (e5NT) catalyses the hydrolysis of extracellular AMP to adenosine and plays a pivotal role in switching on adenosine signalling via the P1 receptors of the purinergic signalling pathway. With such an important regulatory role, e5NT has become an appealing new drug target, with potential applications in the treatment of inflammation, chronic pain, hypoxia and cancer. In order to gain insight into the structure and function of the eukaryotic e5NT enzymes and to assist in structure-based drug design, the crystal structure of human e5NT has been solved. Recombinant human e5NT comprising four asparagine-to-aspartate surface mutations targeting potential glycosylation sites was refolded from bacterial inclusion bodies. Refolded and purified human e5NT crystallized in space group P4332 and a data set to 1.85 Å resolution was obtained. The structure could be solved by molecular replacement using a polyalanine model generated from Thermus thermophilus 5′-nucleotidase (5NT). An anomalous data set revealed the presence of a metal-ion binding site, as well as calcium and chloride ion-binding sites. Structural comparisons with bacterial 5NT homologues showed that the human e5NT crystal structure has an open conformation in which the metal- and substrate-binding sites are distant from each other. Here, the crystallization and preliminary X-ray crystallo­graphic analysis of an open structural conformation of human e5NT are described. PMID:23192044

  11. Human-Centered Technologies and Procedures for Future Air Traffic Management: A Preliminary Overview of 1996 Studies and Results

    NASA Technical Reports Server (NTRS)

    Smith, Philip; McCoy, Elaine; Denning, Rebecca; Woods, David; Sarter, Nadine; Dekker, Sidney; Billings, Charles

    1996-01-01

    In this project, we have been exploring the use of a general methodology to predict the impact of future Air Traffic Management (ATM) concepts and technologies. In applying this methodology, our emphasis has been on the importance of modeling coordination and cooperation among the multiple agents within this system, and on understanding how the interactions among these agents will be influenced as new roles, responsibilities, procedures and technologies are introduced. To accomplish this, we have been collecting data on performance under the current air traffic management system, trying to identify critical problem areas and looking for exemplars suggestive of general approaches for solving such problems. Based on the results of these field studies, we have developed a set of scenarios centered around potential future system designs, and have conducted studies using these scenarios involving a total 40 controllers, dispatchers, pilots and traffic managers. The purpose of this report is to provide NASA with an early summary of the major recommendations that have resulted from our research under the AATT Program thus far. Recommendations 1-3 deal with general approaches that our findings suggest should be incorporated in future AATT Program activities, while Recommendations 4-11 identify some specific topics and technologies that merit research and development activities. Detailed technical reports containing supporting data, as well as the results of our still ongoing analyses, will be provided at a later date. The remainder of this report is organized as follows. Section 1 briefly describes the general design philosophy supported by our empirical studies. Section 2 presents the research methods we have used for identifying requirements for future system designs and for evaluating alternative design solutions. Section 3 discusses preliminary results from an initial set of investigations that we have conducted using these research methods. Section 4 then provides an

  12. The Neogene Ogallala Formation in Southwestern Kansas and Northeastern New Mexico: Preliminary Magnetostratigraphic Analyses for the High Plains-Ogallala Drilling Program

    NASA Astrophysics Data System (ADS)

    Zeigler, K. E.; Petronis, M. S.; Smith, J. J.; Ludvigson, G. A.; Doveton, J.

    2012-12-01

    A better understanding of the Ogallala Formation is critical in terms of refining groundwater flow models and management policies for communities relying on aquifers in heterolithic sequences around the globe. The High Plains aquifer remains under increasing stress with the growth of both urban and agricultural areas and therefore, developing the best groundwater management policies will depend on the most accurate characterization of the aquifer, the aquifer materials and their stratigraphic and geochronologic framework. Although mammalian faunal assemblages and volcanic ash bed tephrochronology provide a basic geochronologic framework for the Ogallala Formation, better precision in terms of correlation is needed in order to understand formative processes and depositional histories for the primary water-bearing units in the High Plains aquifer and confining strata. The High Plains-Ogallala Drilling Program (HPODP) was developed to advance understanding of sedimentary facies, stratigraphic framework, and chronostratigraphy of the Ogallala Formation and overlying units that comprise the central High Plains aquifer. The drilling program began in the early summer of 2011 in Haskell Co., western Kansas. By early fall 2011; the drill crew was at 92 m with about 32 m to go until they expect to hit bedrock. The final 32 meters of core was extracted during the summer 2012. Here we report the preliminary magnetostratigraphic and rock magnetic data from the first section of core. We scanned the entire 92 meters of core using an ASC Core Analysis System with a Bartington Instruments MS2C magnetic susceptibility coil allowing for bulk susceptibility measurements to be obtained along the length of the core. In addition, we collected 40 sub samples for paleomagnetic and rock magnetic. Bulk susceptibility data reveal depth dependent changes in rock magnetic properties that we interpret to reflect either climatic driven variations impacting the depositional system or a change in

  13. Crystallization and preliminary X-ray analysis of the PIN domain of human EST1A

    SciTech Connect

    Takeshita, Daijiro; Zenno, Shuhei; Lee, Woo Cheol; Saigo, Kaoru; Tanokura, Masaru

    2006-07-01

    The PIN domain of human EST1A was expressed, purified and crystallized by the sitting-drop vapour-diffusion method. Human EST1A (ever shorter telomeres 1A) is associated with most or all active telomerase in cell extracts and is involved either directly or indirectly in telomere elongation and telomere capping. The C-terminal region of EST1A contains the PIN (PilT N-terminus) domain, a putative nuclease domain. The PIN domain of human EST1A was expressed, purified and crystallized by the sitting-drop vapour-diffusion method. The crystals belonged to space group C2, with unit-cell parameters a = 107.3, b = 51.6, c = 100.5 Å, β = 119.3°, and diffracted X-rays to 1.8 Å resolution. The asymmetric unit contained two molecules of the PIN domain and the solvent content was 57%.

  14. Expression, purification, crystallization and preliminary crystallographic analysis of human Rad GTPase

    SciTech Connect

    Yanuar, Arry; Sakurai, Shigeru; Kitano, Ken; Hakoshima, Toshio

    2005-11-01

    Human Rad has been crystallized. A diffraction data set was collected to a resolution of 1.8 Å. Human Rad is a new member of the Ras GTPase superfamily and is overexpressed in human skeletal muscle of individuals with type II diabetes. The GTPase core domain was overexpressed in Escherichia coli and purified for crystallization. Crystals were obtained at 293 K by vapour diffusion using a crystallization robot. The crystals were found to belong to space group P2{sub 1}, with unit-cell parameters a = 52.2, b = 58.6, c = 53.4 Å, β = 97.9°, and contained two Rad molecules in the crystallographic asymmetric unit. A diffraction data set was collected to a resolution of 1.8 Å using synchrotron radiation at SPring-8.

  15. Preclinical TSPO Ligand PET to Visualize Human Glioma Xenotransplants: A Preliminary Study

    PubMed Central

    Buck, Jason R.; McKinley, Eliot T.; Fu, Allie; Abel, Ty W.; Thompson, Reid C.; Chambless, Lola; Watchmaker, Jennifer M.; Harty, James P.; Cooper, Michael K.; Manning, H. Charles

    2015-01-01

    Current positron emission tomography (PET) imaging biomarkers for detection of infiltrating gliomas are limited. Translocator protein (TSPO) is a novel and promising biomarker for glioma PET imaging. To validate TSPO as a potential target for molecular imaging of glioma, TSPO expression was assayed in a tumor microarray containing 37 high-grade (III, IV) gliomas. TSPO staining was detected in all tumor specimens. Subsequently, PET imaging was performed with an aryloxyanilide-based TSPO ligand, [18F]PBR06, in primary orthotopic xenograft models of WHO grade III and IV gliomas. Selective uptake of [18F]PBR06 in engrafted tumor was measured. Furthermore, PET imaging with [18F]PBR06 demonstrated infiltrative glioma growth that was undetectable by traditional magnetic resonance imaging (MRI). Preliminary PET with [18F]PBR06 demonstrated a preferential tumor-to-normal background ratio in comparison to 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). These results suggest that TSPO PET imaging with such high-affinity radiotracers may represent a novel strategy to characterize distinct molecular features of glioma growth, as well as better define the extent of glioma infiltration for therapeutic purposes. PMID:26517124

  16. Preliminary assessment of nutritional value of plant-based diets in relation to human nutrients.

    PubMed

    Aberoumand, Ali

    2009-01-01

    In this research, we present preliminary nutritional data for traditional vegetables and fruits including their content of mineral elements (calcium, potassium, sodium, zinc, and iron) and antioxidant phenolic compounds levels. Eight vegetables and vegetables were studied. Plant foods Asparagus officinalis DC, Chlorophytum comosum Linn., Cordia myxa Roxb., Portulaca oleracia Linn. and Solanum indicum Linn. were collected in Behbehan, south Iran, and also Alocacia indica Sch., Eulophia ocherata Lindl. and Momordica dioica Roxb. were collected from the south of India. Nutrients were measured with food analytical standard methods. The results of this study provide evidence that these local traditional vegetables, which do not require formal cultivation, could be important contributors to improving the nutritional content of Pune and Behbehan people. Results indicate that 50% of the vegetables have significant energy values ranging from 281.4 to 303.9 kcal/100 g. From this study, it was determined that five vegetables, namely A. officinalis, C. comosum, E. ocherata, P. oleracia and S. indicum, provide mineral concentrations exceeding 2% of the plant dry weight and are much higher than typical mineral concentrations in conventional edible vegetables; they are thus recommended for future commercial cultivation. High levels of antioxidant compounds were noticed in P. oleracia and S. indicum. The three plants S. indicum, A. officinalis and P. oleracia are suitable for high-temperature food processes. PMID:19274594

  17. Preclinical TSPO Ligand PET to Visualize Human Glioma Xenotransplants: A Preliminary Study.

    PubMed

    Buck, Jason R; McKinley, Eliot T; Fu, Allie; Abel, Ty W; Thompson, Reid C; Chambless, Lola; Watchmaker, Jennifer M; Harty, James P; Cooper, Michael K; Manning, H Charles

    2015-01-01

    Current positron emission tomography (PET) imaging biomarkers for detection of infiltrating gliomas are limited. Translocator protein (TSPO) is a novel and promising biomarker for glioma PET imaging. To validate TSPO as a potential target for molecular imaging of glioma, TSPO expression was assayed in a tumor microarray containing 37 high-grade (III, IV) gliomas. TSPO staining was detected in all tumor specimens. Subsequently, PET imaging was performed with an aryloxyanilide-based TSPO ligand, [18F]PBR06, in primary orthotopic xenograft models of WHO grade III and IV gliomas. Selective uptake of [18F]PBR06 in engrafted tumor was measured. Furthermore, PET imaging with [18F]PBR06 demonstrated infiltrative glioma growth that was undetectable by traditional magnetic resonance imaging (MRI). Preliminary PET with [18F]PBR06 demonstrated a preferential tumor-to-normal background ratio in comparison to 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). These results suggest that TSPO PET imaging with such high-affinity radiotracers may represent a novel strategy to characterize distinct molecular features of glioma growth, as well as better define the extent of glioma infiltration for therapeutic purposes. PMID:26517124

  18. Genetic Structure and Preliminary Findings of Cryptic Diversity of the Malaysian Mahseer (Tor tambroides Valenciennes: Cyprinidae) Inferred from Mitochondrial DNA and Microsatellite Analyses

    PubMed Central

    Abdul Rahim, Khairul Adha

    2013-01-01

    This study examines the population genetic structure of Tor tambroides, an important freshwater fish species in Malaysia, using fifteen polymorphic microsatellite loci and sequencing of 464 base pairs of the mitochondrial cytochrome c oxidase I (COI) gene. A total of 152 mahseer samples were collected from eight populations throughout the Malaysia river system. Microsatellites results found high levels of intrapopulation variations, but mitochondrial COI results found high levels of interpopulations differentiation. The possible reasons for their discrepancies might be the varying influence of genetic drift on each marker or the small sample sizes used in most of the populations. The Kelantan population showed very low levels of genetic variations using both mitochondrial and microsatellite analyses. Phylogenetic analysis of the COI gene found a unique haplotype (ER8∗), possibly representing a cryptic lineage of T. douronensis, from the Endau-Rompin population. Nevertheless, the inclusion of nuclear microsatellite analyses could not fully resolve the genetic identity of haplotype ER8∗ in the present study. Overall, the findings showed a serious need for more comprehensive and larger scale samplings, especially in remote river systems, in combination with molecular analyses using multiple markers, in order to discover more cryptic lineages or undescribed “genetic species” of mahseer. PMID:24455674

  19. What Happened, and Why: Toward an Understanding of Human Error Based on Automated Analyses of Incident Reports. Volume 1

    NASA Technical Reports Server (NTRS)

    Maille, Nicolas P.; Statler, Irving C.; Ferryman, Thomas A.; Rosenthal, Loren; Shafto, Michael G.; Statler, Irving C.

    2006-01-01

    The objective of the Aviation System Monitoring and Modeling (ASMM) project of NASA s Aviation Safety and Security Program was to develop technologies that will enable proactive management of safety risk, which entails identifying the precursor events and conditions that foreshadow most accidents. This presents a particular challenge in the aviation system where people are key components and human error is frequently cited as a major contributing factor or cause of incidents and accidents. In the aviation "world", information about what happened can be extracted from quantitative data sources, but the experiential account of the incident reporter is the best available source of information about why an incident happened. This report describes a conceptual model and an approach to automated analyses of textual data sources for the subjective perspective of the reporter of the incident to aid in understanding why an incident occurred. It explores a first-generation process for routinely searching large databases of textual reports of aviation incident or accidents, and reliably analyzing them for causal factors of human behavior (the why of an incident). We have defined a generic structure of information that is postulated to be a sound basis for defining similarities between aviation incidents. Based on this structure, we have introduced the simplifying structure, which we call the Scenario as a pragmatic guide for identifying similarities of what happened based on the objective parameters that define the Context and the Outcome of a Scenario. We believe that it will be possible to design an automated analysis process guided by the structure of the Scenario that will aid aviation-safety experts to understand the systemic issues that are conducive to human error.

  20. Gene Microarray Analyses of Daboia russelli russelli Daboiatoxin Treatment of THP-1 Human Macrophages Infected with Burkholderia pseudomallei.

    PubMed

    Perumal Samy, R; Manikandan, J; Pachiappan, A; Ooi, E E; Aw, L T; Stiles, B G; Franco, O L; Kandasamy, M; Mathi, K M; Rane, G; Siveen, K S; Arunachalam, C; Zayed, M E; Alharbi, S A; Kumar, A P; Sethi, G; Lim, L H K; Chow, V T

    2015-01-01

    Burkholderia pseudomallei is the causative agent of melioidosis and represents a potential bioterrorism threat. In this study, the transcriptomic responses of B. pseudomallei infection of a human macrophage cell model were investigated using whole-genome microarrays. Gene expression profiles were compared between infected THP-1 human monocytic leukemia cells with or without treatment with Daboia russelli russelli daboiatoxin (DRRDbTx) or ceftazidime (antibiotic control). Microarray analyses of infected and treated cells revealed differential upregulation of various inflammatory genes such as interleukin-1 (IL-1), IL-6, tumor necrosis factor-alpha (TNF-α), cyclooxygenase (COX-2), vascular endothelial growth factor (VEGF), chemokine C-X-C motif ligand 4 (CXCL4), transcription factor p65 (NF-kB); and several genes involved in immune and stress responses, cell cycle, and lipid metabolism. Moreover, following DRR-DbTx treatment of infected cells, there was enhanced expression of the tolllike receptor 2 (TLR-2) mediated signaling pathway involved in recognition and initiation of acute inflammatory responses. Importantly, we observed that highly inflammatory cytokine gene responses were similar in infected cells exposed to DRR-DbTx or ceftazidime after 24 h. Additionally, there were increased transcripts associated with cell death by caspase activation that can promote host tissue injury. In summary, the transcriptional responses during B. pseudomallei infection of macrophages highlight a broad range of innate immune mechanisms that are activated within 24 h post-infection. These data provide insights into the transcriptomic kinetics following DRR-DbTx treatment of human macrophages infected with B. pseudomallei. PMID:26592245

  1. Preliminary characterization of voltage-activated whole-cell currents in developing human vestibular hair cells and calyx afferent terminals.

    PubMed

    Lim, Rebecca; Drury, Hannah R; Camp, Aaron J; Tadros, Melissa A; Callister, Robert J; Brichta, Alan M

    2014-10-01

    We present preliminary functional data from human vestibular hair cells and primary afferent calyx terminals during fetal development. Whole-cell recordings were obtained from hair cells or calyx terminals in semi-intact cristae prepared from human fetuses aged between 11 and 18 weeks gestation (WG). During early fetal development (11-14 WG), hair cells expressed whole-cell conductances that were qualitatively similar but quantitatively smaller than those observed previously in mature rodent type II hair cells. As development progressed (15-18 WG), peak outward conductances increased in putative type II hair cells but did not reach amplitudes observed in adult human hair cells. Type I hair cells express a specific low-voltage activating conductance, G K,L. A similar current was first observed at 15 WG but remained relatively small, even at 18 WG. The presence of a "collapsing" tail current indicates a maturing type I hair cell phenotype and suggests the presence of a surrounding calyx afferent terminal. We were also able to record from calyx afferent terminals in 15-18 WG cristae. In voltage clamp, these terminals exhibited fast inactivating inward as well as slower outward conductances, and in current clamp, discharged a single action potential during depolarizing steps. Together, these data suggest the major functional characteristics of type I and type II hair cells and calyx terminals are present by 18 WG. Our study also describes a new preparation for the functional investigation of key events that occur during maturation of human vestibular organs. PMID:24942706

  2. Preliminary evidence for an association between LRP-1 genotype and body mass index in humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The LDL receptor-related protein-1 gene (LRP-1) has been associated with obesity in animal models, but no such association has yet been reported in humans. As data suggest this increase in fat mass may be mediated through a mechanism involving the clearance of plasma triglyceride-rich lipoproteins (...

  3. Guide to Paperback Translations in the Humanities: A Teacher's Handbook. Preliminary Edition.

    ERIC Educational Resources Information Center

    Raffel, Burton, Comp.

    This teacher's handbook is a guide to available paperback translations of primary material in the humanities field. The selections chosen to be included are recommended by the compiler as the best English translations available. The book is divided into sections chronologically: (1) ancient, to 450 A.D.; (2) medieval, 450-1500 A.D.; (3) early…

  4. Human Relations and Community Life in Rural New York State: A Preliminary Report.

    ERIC Educational Resources Information Center

    New York State Legislative Commission on Rural Resources, Albany.

    Trends, strengths and assets, weaknesses and problem areas, goals, and public policy questions in the area of human relations and community life in rural New York state are presented with supporting statistics. Trends considered include rural and elderly rural population increases; suicide, homicide, and domestic violence rate increases; demands…

  5. Preliminary evidence for human globus pallidus pars interna neurons signaling reward and sensory stimuli.

    PubMed

    Howell, Nicholas A; Prescott, Ian A; Lozano, Andres M; Hodaie, Mojgan; Voon, Valerie; Hutchison, William D

    2016-07-22

    The globus pallidus pars interna (GPi) is a component of the basal ganglia, a network of subcortical nuclei that process motor, associative, and limbic information. While non-human primate studies have suggested a role for the GPi in non-motor functions, there have been no single-unit studies of non-motor electrophysiological behavior of human GPi neurons. We therefore sought to extend these findings by collecting single-unit recordings from awake patients during functional stereotactic neurosurgery targeting the GPi for deep brain stimulation. To assess cellular responses to non-motor information, patients performed a reward task where virtual money could be won, lost, or neither, depending on their performance while cellular activity was monitored. Changes in the firing rates of isolated GPi neurons after the presentation of reward-related stimuli were compared between different reward contingencies (win, loss, null). We observed neurons that modulated their firing rate significantly to the presentation of reward-related stimuli. We furthermore found neurons that responded to visual-stimuli more broadly. This is the first single-unit evidence of human GPi neurons carrying non-motor information. These results are broadly consistent with previous findings in the animal literature and suggest non-motor information may be represented in the single-unit activity of human GPi neurons. PMID:27109924

  6. The Preliminary Study Of Giant Magnetoresistance Sensor For Detection Of Oxygen In Human Blood

    NASA Astrophysics Data System (ADS)

    Ramli, Ramli; Muhtadi, Almas Hilman; Sahdan, Muhammad Fauzi; Haryanto, Freddy; Khairurrijal; Djamal, Mitra

    2010-12-01

    In recent years, there has been great progress for applications of nanomaterials in medicine field. Human body consists of many atoms and they can be treated like as nanomaterials. One of them is oxygen. Oxygen is always found in the human blood. Its concentration in human blood gives information about the metabolism in the body. The purpose of this study was to look for a possibility for developing tool to detect the concentration of oxygen in blood. In this study, the giant-magneto-resistance (GMR) sensor is implemented. The GMR sensor has many attractive features, for example: reduced size, low-power consumption, low price, as compared to other magnetic sensors and its electric and magnetic properties can be varied in very wide range. In this experiment, we developed the structure of GMR materials NiCoFe/Cu/NiCoFe sandwich as a GMR sensor. The NiCoFe/Cu/NiCoFe sandwiches were grown onto Si (111) substrates by the dc-opposed target magnetron sputtering (dc-OTMS) technique. The sputtering targets were NiCoFe and Cu. To achieve the aims of this study, the blood transports in human will be simulated using a simple experimental model. This model has some parameters representing those in blood transport. Furthermore, the nanomagnetic material will be made as a contaminant particle in blood. Using this material some properties of the transport will be investigated.

  7. Chinese herbs as modulators of human mesangial cell proliferation: preliminary studies.

    PubMed

    Kuo, Y C; Sun, C M; Tsai, W J; Ou, J C; Chen, W P; Lin, C Y

    1998-07-01

    In the hope of identifying agents of therapeutic value in immunoglobulin A nephropathy (IgA-N), we tested crude methanol extracts of 15 Chinese herbs for their effect on human mesangial cel proliferation in vitro. The results indicated that 7 out of the 15 crude extracts inhibited human mesangial cell proliferation activated by interleukin-1beta and interleukin-6. The extracts and their median inhibitory concentrations were as follows (in microg/ml): Selaginella tamariscina (MLS-032), 56.0 +/- 2.0; Ixeris chinensis (MLS-033), 62.7 +/- 1.7; Polygonum hypoleucum Ohwi (MLS-034), 25.0 +/- 1.5; Scutellaris rivularis (MLS-036), 39.6 +/- 1.1; Condonacanthus paucifiorus (MLS-042),63.6 +/- 2.6; Xanthium strumarium (MLS-043), 42.8 +/- 1.3; Daemonoropus margaritae (MLS-044), 56.1 +/- 1.9. These findings indicate that human mesangial cells were most sensitive to MLS-034 treatment. These herbs also decreased interleukin-1beta and tumor necrosis factor-alpha production. Moreover, TNF-alpha mRNA expression was inhibited by MLS-034. It is unlikely that cytotoxicity was involved, because no cell deaths were observable. We hypothesize that the inhibitory mechanisms of these Chinese herbs may be related to the impairments of gene expression and production of cytokines in human mesangial cells. Plans are underway for the isolation of pure compounds from these Chinese herbs and the elucidation of their mechanisms of action. PMID:9665376

  8. The use of cadaver dogs in locating scattered, scavenged human remains: preliminary field test results.

    PubMed

    Komar, D

    1999-03-01

    Specially trained air scent detection canines (Canis familiaris) are commonly used by law enforcement to detect narcotics, explosives or contraband, and by fire investigators to detect the presence of accelerants. Dogs are also used by police, military, and civilian groups to locate lost or missing persons, as well as victims of natural or mass disasters. A further subspecialty is "cadaver" searching, or the use of canines to locate buried or concealed human remains. Recent forensic investigations in central Alberta demonstrated that the use of cadaver dogs could be expanded to include locating partial, scattered human remains dispersed by repeated animal scavenging. Eight dog-and-handler teams participated in a two-month training program using human and animal remains in various stages of decay as scent sources. Ten blind field tests were then conducted which simulated actual search conditions. Recovery rates ranged between 57% and 100%, indicating that properly trained cadaver dogs can make significant contributions in the location and recovery of scattered human remains. PMID:10097372

  9. Evaluation of the interaction between calcifying nanoparticles and human dental pulp cells: a preliminary investigation.

    PubMed

    Yang, Fang; Zeng, Jinfeng; Zhang, Wei; Sun, Xi; Ling, Junqi

    2011-01-01

    Calcifying nanoparticles (CNPs, previously called nanobacteria) are self-propagating, cultivable macromolecular complexes. Their extraordinary characteristic is that they can aggregate carbonate apatite on their envelope from soluble calcium and phosphorus at physiologic concentrations and display cytotoxic effects on murine and human fibroblast cell lines. The question arises whether CNPs contribute to the degeneration of pulp tissue and thus result in clinically significant human dental pulp stones as nidies. This study evaluates CNPs' effects upon human dental pulp cells (HDPCs, the host cells in pulp tissue). We observed the ultrastructural variation of HDPCs attacked by CNPs. The spatial relationship of HDPCs and CNPs after coculture was also identified by immunofluorescence staining. Furthermore, it was verified by MTT viability assay that CNPs isolated from dental pulp stones exerted cytotoxic effect on HDPCs. Therefore, it could be concluded that the existence of CNPs might interfere with the normal physiologic function of the cells, and that might lead to dental pulp calcification. Elucidation of the cytotoxic characteristics of CNPs may offer a new perspective for understanding the etiology of human dental pulp stones. PMID:21289977

  10. Purification, crystallization and preliminary crystallographic analysis of the CBS pair of the human metal transporter CNNM4

    PubMed Central

    Gómez García, Inmaculada; Oyenarte, Iker; Martínez-Cruz, Luis Alfonso

    2011-01-01

    This work describes the purification and preliminary crystallographic analysis of the CBS-pair regulatory domain of the human ancient domain protein 4 (ACDP4), also known as CNNM4. ACDP proteins represent the least-studied members of the eight different types of magnesium transporters that have been identified in mammals to date. In humans the ACDP family includes four members: CNNM1–4. CNNM1 acts as a cytosolic copper chaperone and has been associated with urofacial syndrome, whereas CNNM2 and CNNM4 have been identified as magnesium transporters. Interestingly, mutations in the CNNM4 gene have clinical consequences that are limited to retinal function and biomineralization and are considered to be the cause of Jalili syndrome, which consists of autosomal recessive cone-rod dystrophy and amelogenesis imperfecta. The truncated protein was overexpressed, purified and crystallized in the orthorhombic space group C222. The crystals diffracted X-rays to 3.6 Å resolution using synchrotron radiation. Matthews volume calculations suggested the presence of two molecules in the asymmetric unit, which were likely to correspond to a CBS module of the CBS pair of CNNM4. PMID:21393841

  11. Enhanced Contaminated Human Remains Pouch: initial development and preliminary performance assessments

    SciTech Connect

    Iseli, A.M.; Kwen, H.D.; Ul-Alam, M.; Balasubramanian, M.; Rajagopalan, S.

    2011-11-07

    The objective is to produce a proof of concept prototype Enhanced Contaminated Human Remains Pouch (ECHRP) with self-decontamination capability to provide increased protection to emergency response personnel. The key objective was to decrease the concentration of toxic chemicals through the use of an absorbent and reactive nanocellulose liner. Additionally, nanomaterials with biocidal properties were developed and tested as a 'stand-alone' treatment. The setting was a private company research laboratory. The main outcome measures were production of a functional prototype. A functional prototype capable of mitigating the threats due to sulfur mustard, Soman, and a large variety of liquid and vapor toxic industrial chemicals was produced. Stand-alone biocidal treatment efficacy was validated. The ECHRP provides superior protection from both chemical and biological hazards to various emergency response personnel and human remains handlers.

  12. Crystallization and preliminary crystallographic studies of human indoleamine 2,3-dioxygenase

    SciTech Connect

    Oda, Shun-ichiro; Sugimoto, Hiroshi; Yoshida, Tadashi; Shiro, Yoshitsugu

    2006-03-01

    Human indoleamine 2,3-dioxygenase, a haem-containing dioxygenase, was crystallized. The crystal diffracted to 2.3 Å resolution. Indoleamine 2,3-dioxygenase (IDO) is a haem-containing dioxygenase that catalyzes the oxidative cleavage of the pyrrole ring of indoleamines by the insertion of molecular oxygen. This reaction is the first and the rate-limiting step in the kynurenine pathway, the major Trp catabolic pathway in mammals. Recombinant human IDO was crystallized by the vapour-diffusion technique. The addition of 4-phenylimidazole as a haem ligand was essential for crystallization. The crystals belong to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 86.1, b = 98.0, c = 131.0 Å. Diffraction data were collected to 2.3 Å resolution.

  13. Expression, crystallization and preliminary X-ray crystallographic analysis of human agmatinase

    SciTech Connect

    Kim, Kyoung Hoon; Ahn, Hyung Jun; Kim, Do Jin; Lee, Hyung Ho; Ha, Jun-Yong; Kim, Hye-Kyung; Yoon, Hye-Jin; Suh, Se Won

    2005-10-01

    Human agmatinase (Ala36–Val352) was overexpressed and crystallized, and X-ray diffraction data were collected to 2.49 Å. Agmatine, which results from the decarboxylation of l-arginine by arginine decarboxylase, is a metabolic intermediate in the biosynthesis of putresine and higher polyamines (spermidine and spermine). Recent studies indicate that agmatine can have several important biochemical effects in humans, ranging from effects on the central nervous system to cell proliferation in cancer and viral replication. Agmatinase catalyses the hydrolysis of agmatine to putresine and urea and is a major target for drug action and development. The human agmatinase gene encodes a 352-residue protein with a putative mitochondrial targeting sequence at the N-terminus. Human agmatinase (residues Ala36–Val352) has been overexpressed as a fusion with both N- and C-terminal purification tags in Escherichia coli and crystallized in the presence of Mn{sup 2+} and 1,6-diaminohexane at 297 K using polyethylene glycol 4000 as a precipitant. X-ray diffraction data were collected at 100 K to 2.49 Å from a flash-frozen crystal. The crystals are tetragonal, belonging to space group P4{sub 2}, with unit-cell parameters a = b = 114.54, c = 125.65 Å, α = β = γ = 90°. Three monomers are likely to be present in the asymmetric unit, giving a crystal volume per protein weight (V{sub M}) of 3.66 Å{sup 3} Da{sup −1} and a solvent content of 66.4%.

  14. Expression, purification and preliminary crystallographic studies of human glutamate oxaloacetate transaminase 1 (GOT1).

    PubMed

    Jiang, Xiuping; Chang, Haiyang; Zhou, Yong

    2015-09-01

    Glutamate oxaloacetate transaminase (GOT) catalyzes the reversible reaction of l-aspartate and α-ketoglutarate into oxaloacetate and L-glutamate and plays a key role in carbon and nitrogen metabolism in all organisms. In human tissues, GOTs are pyridoxal 5'-phosphate-dependent (PLP) enzymes which exist in cytoplasm and mitochondrial forms, GOT1 and GOT2, respectively. GOT1 expression correlates with the growth of several tumors because cancer cells can utilize the amino acid glutamine to fuel anabolic processes, and therefore, GOT1 represents a new therapeutic target in cancer. In this work, human GOT1 was expressed in Escherichia coli periplasmic space, and purified by a combination of His-tag immobilized metal-ion affinity chromatography and anion exchange chromatography. Optimal activity of the enzyme occurred at a temperature of 37 °C and a pH of 7.5. Cations such as Na(+), K(+) and Mg(2+) slightly inhibited the activity of recombinant human GOT1, while Zn(2+), Mn(2+), Cu(2+), Ni(2+), Co(2+) and Ca(2+) had stronger inhibitory effects. Crystals of human GOT1 were grown using the hanging-drop vapor diffusion method at 4°C with 0.1M Bis-Tris pH 6.0% and 21% (w/v) PEG 3350. The crystals diffracted to 2.99Å resolution and belonged to space group P43212 with the unit cell parameters a = b = 93.4, c = 107.4Å, α = β = γ = 90°. PMID:26003525

  15. The impact of body worlds on adult visitors' knowledge on human anatomy: A preliminary study.

    PubMed

    Fonseca, Guilherme R B C; Finn, Gabrielle M

    2016-05-01

    Body Worlds is an anatomical exhibition that shows human remains to the public. It has been considered controversial since it raises ethical tensions and issues. However, organizers and supporters of Body Worlds have claimed the exhibition is intended to promote visitors' understanding over the human body. Despite these claims, no studies were found that support or refute the hypothesis that a visit to Body Worlds increases the public's objective knowledge on human anatomy. Consequently, the objective of this study was to determine the impact of Body Worlds on anatomical knowledge. We constructed and delivered a questionnaire to both a previsit random sample and a postvisit random sample of visitors of Body Worlds' event Facets of Life, in Berlin. The questionnaire was available in both English and German languages and contained (a) basic sociodemographic questions and (b) a valid and reliable anatomy quiz. The quiz consisted of 16 multiple-choice questions that assessed the ability to identify the location of major anatomical structures on the human body. Average scores achieved on the quiz by the postvisit sample (X¯= 9.08, s = 2.48, n = 164) were significantly higher (unpaired t = 3.3957, P = 0.0008) than those achieved by the previsit sample (X¯= 8.11, s = 2.69, n = 167). Our results suggest that a visit to Body Worlds' event Facets of Life may have a beneficial effect in anatomical knowledge. However, further studies with better empirical designs and fewer limitations are needed to confirm our results. Clin. Anat. 29:439-445, 2016. © 2016 Wiley Periodicals, Inc. PMID:26789643

  16. Preliminary evidence for human fecal contamination in corals of the Florida Keys, USA.

    PubMed

    Lipp, Erin K; Jarrell, Jennifer L; Griffin, Dale W; Lukasik, Jerzy; Jacukiewicz, Jennifer; Rose, Joan B

    2002-07-01

    Corals and reef environments are under increased stress from anthropogenic activities, particularly those in the vicinity of heavily populated areas such as the Florida Keys. The potential adverse impacts of wastewater can affect both the environment and human health; however, because of the high decay rate of bacterial indicators in coral reef waters it has been difficult to document the presence of microbial contaminants and to assign risks in these environments. Here we show initial evidence that microorganisms associated with human feces are concentrated along the surface of coral heads relative to the overlying water column in the Florida Keys. Bacterial indicators (fecal coliform bacteria, enterococci or Clostridium perfringens) were detected in 66.7% of the coral surface microlayer (CSM) samples at levels between five and 1000 CFU/100 ml, but were found infrequently and at low numbers in the overlying water column ( < or = 2.5 CFU/100 ml). Similarly, enterovirus nucleic acid sequences, an indicator of human-specific waste, were detected in 93.3% of the CSM samples and only once in the water column by cell culture. Results show that coral mucus may accumulate enteric microorganisms in reef environments, and may indicate a risk to public and environmental health despite low indicator levels in the surrounding water. PMID:12222890

  17. Preliminary performance assessment for the Waste Isolation Pilot Plant, December 1992. Volume 4: Uncertainty and sensitivity analyses for 40 CFR 191, Subpart B

    SciTech Connect

    Not Available

    1993-08-01

    Before disposing of transuranic radioactive waste in the Waste Isolation Pilot Plant (WIPP), the United States Department of Energy (DOE) must evaluate compliance with applicable long-term regulations of the United States Environmental Protection Agency (EPA). Sandia National Laboratories is conducting iterative performance assessments (PAs) of the WIPP for the DOE to provide interim guidance while preparing for a final compliance evaluation. This volume of the 1992 PA contains results of uncertainty and sensitivity analyses with respect to the EPA`s Environmental Protection Standards for Management and Disposal of Spent Nuclear Fuel, High-Level and Transuranic Radioactive Wastes (40 CFR 191, Subpart B). Additional information about the 1992 PA is provided in other volumes. Results of the 1992 uncertainty and sensitivity analyses indicate that, conditional on the modeling assumptions, the choice of parameters selected for sampling, and the assigned parameter-value distributions, the most important parameters for which uncertainty has the potential to affect compliance with 40 CFR 191B are: drilling intensity, intrusion borehole permeability, halite and anhydrite permeabilities, radionuclide solubilities and distribution coefficients, fracture spacing in the Culebra Dolomite Member of the Rustler Formation, porosity of the Culebra, and spatial variability of Culebra transmissivity. Performance with respect to 40 CFR 191B is insensitive to uncertainty in other parameters; however, additional data are needed to confirm that reality lies within the assigned distributions.

  18. Facilitating myoelectric-control with transcranial direct current stimulation: a preliminary study in healthy humans

    PubMed Central

    2014-01-01

    during 'proportional EMG control’ when compared to M1 anodal and sham tDCS. Conclusions The preliminary results from healthy subjects showed specific, and at least partially antagonistic effects, of M1 and cerebellar anodal tDCS on motor performance during myoelectric control. These results are encouraging, but further studies are necessary to better define how tDCS over particular regions of the cerebellum may facilitate learning of myoelectric control for brain machine interfaces. PMID:24507410

  19. Depositional sequences of offshore Canterbury, New Zealand, and preliminary results of stable isotope analyses of the samples from IODP Expedition 317

    NASA Astrophysics Data System (ADS)

    Hoyanagi, K.; Koto, S.; Kawagata, S.; Fulthorpe, C.; Blum, P.; Shipboard Scientific Party, E.

    2010-12-01

    INTRODUCTION Integrated Ocean Drilling Program Expedition 317 was devoted to understanding the relative importance of global sea level (eustasy) versus local tectonic and sedimentary processes in controlling continental-margin sedimentary cycles. In order to achieve these objectives, upper Miocene to Recent sedimentary sequences were cored in a transect of three sites on the continental shelf (landward to basinward, Sites U1353, U1354, U1351). Highest recovery was achieved in cores of upper Pliocene (3.5 Ma) to Recent sediments. We also drilled one site (Site U1352) on the continental slope, reaching a depth of 1927.5 m below sea floor and obtaining Eocene samples. CORRELATION OF SEISMIC SEQUENCE BOUNDARIES AND DISCONTINUITIES IN THE CORES Nineteen regional seismic sequence boundaries (U1-U19, in ascending order) were idendified in the middle Miocene to recent shelf-slope sediment prism of the offshore Canterbury Basin (Lu and Fulthope, 2004). Discontinuities identified in cores may correlate to U19-U8 at Site U1353, and to U19-U10 at Sites U1354 and U1351. We estimate the ages of the discontinuities, based on shipboard analyses, to correspond to both Marine Isotope Stages (Lisiecki and Raymo, 2005) and global sequence boundaries (Haq et al., 1987). STABLE ISOTOPE MEASUREMENTS OF THE ORGANIC MATTER AND FORAMINIFERA TESTS We are analyzing carbon isotopic ratios of organic matter in the sediments and oxygen isotopic ratios of foraminifer tests. Carbon isotopic ratio indicates whether the origin of the organic matter is terrestrial or marine. Samples for stable isotope analysis of organic carbon are treated with HCl to dissolve calcium carbonate. Analyses are carried out at the Faculty of Science, Shinshu University, using an elemental analyzer (FlashEA1122, ThermoQuest Ltd.) and a mass spectrometer (Delta V, ThermoQuest Ltd.). We are picking foraminifera tests from core samples from slope Site U1352 and measure oxygen isotope ratios of the calcium carbonate to

  20. Preliminary experiments on dynamic biology of micro-organisms to avoid any specific full-blown syndrome on humans

    NASA Astrophysics Data System (ADS)

    Meer, Sneer

    2002-06-01

    The aim of this paper is to apply an efficient system to detect, identify and quicken suppression of any dangerous micro-organism which threatens the health of the human body in any form. It is well known that some specimens of this kind of possess a specific energy related to their speed of division, toxin emissions and high-powered interaction with human and animal cells which have the capacity to provide certain deadly full-blown syndromes. Many problems relating to the above-mentioned properties have not been clarified to date, and it is vital to find a rapid and valid reply as soon as possible. Inter-disciplinary sciences directed us to start some experiments to solve such problems, considering that the human body is dotted with a multiple interactive system of energy release, a fact which can explain the source of the micro-organism's energy also, for their necessity to manifest their deadly pathology. From practical preliminary experiments with some micro-mechanical systems using light-microscopy, connected to video TV Recorder System, one obtains optical enlarged TV images of certain processes which indicated the right way towards our crucial target; ie: the preparation of safe vaccines and safe medicines. This will constitute a basic system to a void deadly manifestations of dangerous micro-organisms and/or even regular infections on earth and in space, a system which will probably be applied at the ISS Space Station and other future actions in space in long and very long flights. We look forward to applying this system of dynamic biology towards preparation of a real and valid vaccine(s) against HIV virus on AIDS diseases.

  1. Mouse and Human Genetic Analyses Associate Kalirin with Ventral Striatal Activation during Impulsivity and with Alcohol Misuse

    PubMed Central

    Peña-Oliver, Yolanda; Carvalho, Fabiana M.; Sanchez-Roige, Sandra; Quinlan, Erin B.; Jia, Tianye; Walker-Tilley, Tom; Rulten, Stuart L.; Pearl, Frances M. G.; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun L. W.; Büchel, Christian; Conrod, Patricia J.; Flor, Herta; Gallinat, Jürgen; Garavan, Hugh; Heinz, Andreas; Gowland, Penny; Paillere Martinot, Marie-Laure; Paus, Tomáš; Rietschel, Marcella; Robbins, Trevor W.; Smolka, Michael N.; Schumann, Gunter; Stephens, David N.

    2016-01-01

    Impulsivity is associated with a spectrum of psychiatric disorders including drug addiction. To investigate genetic associations with impulsivity and initiation of drug taking, we took a two-step approach. First, we identified genes whose expression level in prefrontal cortex, striatum and accumbens were associated with impulsive behavior in the 5-choice serial reaction time task across 10 BXD recombinant inbred (BXD RI) mouse strains and their progenitor C57BL/6J and DBA2/J strains. Behavioral data were correlated with regional gene expression using GeneNetwork (www.genenetwork.org), to identify 44 genes whose probability of association with impulsivity exceeded a false discovery rate of < 0.05. We then interrogated the IMAGEN database of 1423 adolescents for potential associations of SNPs in human homologs of those genes identified in the mouse study, with brain activation during impulsive performance in the Monetary Incentive Delay task, and with novelty seeking scores from the Temperament and Character Inventory, as well as alcohol experience. There was a significant overall association between the human homologs of impulsivity-related genes and percentage of premature responses in the MID task and with fMRI BOLD-response in ventral striatum (VS) during reward anticipation. In contrast, no significant association was found between the polygenic scores and anterior cingulate cortex activation. Univariate association analyses revealed that the G allele (major) of the intronic SNP rs6438839 in the KALRN gene was significantly associated with increased VS activation. Additionally, the A-allele (minor) of KALRN intronic SNP rs4634050, belonging to the same haplotype block, was associated with increased frequency of binge drinking. PMID:27092175

  2. Mouse and Human Genetic Analyses Associate Kalirin with Ventral Striatal Activation during Impulsivity and with Alcohol Misuse.

    PubMed

    Peña-Oliver, Yolanda; Carvalho, Fabiana M; Sanchez-Roige, Sandra; Quinlan, Erin B; Jia, Tianye; Walker-Tilley, Tom; Rulten, Stuart L; Pearl, Frances M G; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Büchel, Christian; Conrod, Patricia J; Flor, Herta; Gallinat, Jürgen; Garavan, Hugh; Heinz, Andreas; Gowland, Penny; Paillere Martinot, Marie-Laure; Paus, Tomáš; Rietschel, Marcella; Robbins, Trevor W; Smolka, Michael N; Schumann, Gunter; Stephens, David N

    2016-01-01

    Impulsivity is associated with a spectrum of psychiatric disorders including drug addiction. To investigate genetic associations with impulsivity and initiation of drug taking, we took a two-step approach. First, we identified genes whose expression level in prefrontal cortex, striatum and accumbens were associated with impulsive behavior in the 5-choice serial reaction time task across 10 BXD recombinant inbred (BXD RI) mouse strains and their progenitor C57BL/6J and DBA2/J strains. Behavioral data were correlated with regional gene expression using GeneNetwork (www.genenetwork.org), to identify 44 genes whose probability of association with impulsivity exceeded a false discovery rate of < 0.05. We then interrogated the IMAGEN database of 1423 adolescents for potential associations of SNPs in human homologs of those genes identified in the mouse study, with brain activation during impulsive performance in the Monetary Incentive Delay task, and with novelty seeking scores from the Temperament and Character Inventory, as well as alcohol experience. There was a significant overall association between the human homologs of impulsivity-related genes and percentage of premature responses in the MID task and with fMRI BOLD-response in ventral striatum (VS) during reward anticipation. In contrast, no significant association was found between the polygenic scores and anterior cingulate cortex activation. Univariate association analyses revealed that the G allele (major) of the intronic SNP rs6438839 in the KALRN gene was significantly associated with increased VS activation. Additionally, the A-allele (minor) of KALRN intronic SNP rs4634050, belonging to the same haplotype block, was associated with increased frequency of binge drinking. PMID:27092175

  3. Hindlimb muscle architecture in non-human great apes and a comparison of methods for analysing inter-species variation.

    PubMed

    Myatt, Julia P; Crompton, Robin H; Thorpe, Susannah K S

    2011-08-01

    By relating an animal's morphology to its functional role and the behaviours performed, we can further develop our understanding of the selective factors and constraints acting on the adaptations of great apes. Comparison of muscle architecture between different ape species, however, is difficult because only small sample sizes are ever available. Further, such samples are often comprised of different age-sex classes, so studies have to rely on scaling techniques to remove body mass differences. However, the reliability of such scaling techniques has been questioned. As datasets increase in size, more reliable statistical analysis may eventually become possible. Here we employ geometric and allometric scaling techniques, and ancovas (a form of general linear model, GLM) to highlight and explore the different methods available for comparing functional morphology in the non-human great apes. Our results underline the importance of regressing data against a suitable body size variable to ascertain the relationship (geometric or allometric) and of choosing appropriate exponents by which to scale data. ancova models, while likely to be more robust than scaling for species comparisons when sample sizes are high, suffer from reduced power when sample sizes are low. Therefore, until sample sizes are radically increased it is preferable to include scaling analyses along with ancovas in data exploration. Overall, the results obtained from the different methods show little significant variation, whether in muscle belly mass, fascicle length or physiological cross-sectional area between the different species. This may reflect relatively close evolutionary relationships of the non-human great apes; a universal influence on morphology of generalised orthograde locomotor behaviours or, quite likely, both. PMID:21507000

  4. Fukushima nuclear accident: preliminary assessment of the risks to non-human biota.

    PubMed

    Aliyu, Abubakar Sadiq; Ramli, Ahmad Termizi; Garba, Nuraddeen Nasiru; Saleh, Muneer Aziz; Gabdo, Hamman Tukur; Liman, Muhammad Sanusi

    2015-02-01

    This study assesses the 'radio-ecological' impacts of Fukushima nuclear accident on non-human biota using the ERICA Tool, which adopts an internationally verified methodology. The paper estimates the impacts of the accident on terrestrial and marine biota based on the environmental data reported in literature for Japan, China, South Korea and the USA. Discernible impacts have been detected in the marine biota around Fukushima Daiichi nuclear power plant. This study confirms that the Fukushima accident had caused heavier damage to marine bionts compared with terrestrial flora and fauna, in Japan. PMID:24827576

  5. Trace metal content in distinct genotypes of human neuroblastoma cells: Preliminary results

    NASA Astrophysics Data System (ADS)

    Ortega, R.; Gouget, B.; Moretto, Ph.; Michelet, C.; Bénard, J.; Sergeant, C.; Llabador, Y.; Simonoff, M.

    1997-07-01

    Some transition metals play important regulatory roles in gene expression. The disturbance of their cellular levels could be involved in oncogene expression and tumorigenesis. Nuclear Microprobe Analysis (NMPA) was used to measure cellular trace metal levels (Mn, Fe, Cu, Zn) in two human neuroblastoma cell lines characterized by distinct genotypes. In this paper, a specific protocol established for sample preparation of neuronal cultured cells is described. Trace metal concentrations in SK-N-SH and IGR-N-91 cells exhibiting respectively a single copy, and 60 copies, of the N- myc oncogene are reported. A brief discussion on experiment design for NMPA of trace metal functions in gene expression is also presented.

  6. Crystallization and preliminary X-ray crystallographic analysis of human peptidylarginine deiminase type I

    PubMed Central

    Unno, Masaki; Kinjo, Saya; Kizawa, Kenji; Takahara, Hidenari

    2013-01-01

    Peptidylarginine deiminase (PAD) catalyzes the post-translational conversion of peptidylarginine to peptidylcitrulline in the presence of calcium ions. Among the five known human PAD isozymes (PAD1–4 and PAD6), PAD1 exhibits the broadest substrate specificity. Crystals of PAD1 obtained using polyethylene glycol 3350 as a precipitant diffracted to 3.70 Å resolution using synchrotron radiation. Two PAD1 molecules were contained in the asymmetric unit and the crystals belonged to space group P61, with unit-cell parameters a = b = 90.3, c = 372.3 Å. The solvent content was 58.2%. PMID:24316829

  7. Crystallization and preliminary X-ray crystallographic analysis of human peptidylarginine deiminase type I.

    PubMed

    Unno, Masaki; Kinjo, Saya; Kizawa, Kenji; Takahara, Hidenari

    2013-12-01

    Peptidylarginine deiminase (PAD) catalyzes the post-translational conversion of peptidylarginine to peptidylcitrulline in the presence of calcium ions. Among the five known human PAD isozymes (PAD1-4 and PAD6), PAD1 exhibits the broadest substrate specificity. Crystals of PAD1 obtained using polyethylene glycol 3350 as a precipitant diffracted to 3.70 Å resolution using synchrotron radiation. Two PAD1 molecules were contained in the asymmetric unit and the crystals belonged to space group P6(1), with unit-cell parameters a = b = 90.3, c = 372.3 Å. The solvent content was 58.2%. PMID:24316829

  8. [Generation and preliminary immunological efficacy of a recombinant human adenovirus-rabies virus glycoprotein].

    PubMed

    Wang, Ying; Zhang, Shou-Feng; Liu, Ye; Zhang, Fei; Zhang, Jin-Xia; Hu, Rong-Liang

    2011-09-01

    To construct a recombinant human adenovirus type 5 expressing glycoprotein (GP) of attenuated rabies virus SRV9 and testing immunological efficacy on the immunized mice. Open reading frame of rabies virus GP gene of SRV9 strain was cloned into the shuttle vector of adenovirus expression system in multiple cloning sites to construct the recombinant shuttle plasmid pacAd5 CMV-Gs9, cotransfection was performed into 293AD cells mediated by FuGENE Transfection Reagent with linearized backbone plasmid and recombinant shuttle plasmid, cell cultures were collected after CPE appearance and were identified by PCR and electronmicroscopy, virus titer was measured in 293AD cells. Kunming mice were intraperitoneally injected with 10(6) TCID50 adenovirus, blood for serum preparation was collected through caudal vein pre-immune and post-immune and tested for VNA appearance by fluorescent antibody virus neutralization test (FAVN) detection. Recombinant shuttle plasmid pacAd5 CMV-Gs9 was constructed correctly. A recombinant human adenovirus type 5 was obtained expressing GP protein of rabies virus SRV9. The virus titer reached 10(6) CFU/mL at the least. All mice developed a certain amount of the anti-rabies neutralizing antibody 14 days after intraperitoneal inoculation, while the effective protection rates were 90%. In conclusion, Recombinant adenovirus expressing the rabies virus GP was constructed successfully and a certain amount of neutralizing antibodies were induced in mice, which laid the material foundation for further development of new rabies vaccine. PMID:21998956

  9. Purification, crystallization and preliminary X-ray diffraction analysis of human enolase-phosphatase E1

    SciTech Connect

    Wang, Hui; Pang, Hai; Ding, Yi; Li, Yi; Wu, Xiao’ai; Rao, Zihe

    2005-05-01

    Recombinant human E1 enzyme has been crystallized using the hanging-drop vapour-diffusion method and diffraction-quality crystals were grown at 291 K using PEG 4000 as precipitant. Enolase-phosphatase E1 (MASA) is a bifunctional enzyme in the ubiquitous methionine-salvage pathway and catalyzes the continuous reaction of 2,3-diketo-5-methylthio-1-phosphopentane to yield the acireductone metabolite. Recombinant human E1 enzyme has been crystallized using the hanging-drop vapour-diffusion method and diffraction-quality crystals were grown at 291 K using PEG 4000 as precipitant. Diffraction data were collected to 1.7 Å resolution from SeMet-derivative crystals at 100 K using synchrotron radiation. The crystals belong to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 54.02, b = 57.55, c = 87.32 Å. The structure was subsequently solved by the multi-wavelength anomalous diffraction (MAD) phasing method.

  10. A preliminary neuropathological study of Japanese encephalitis in humans and a mouse model.

    PubMed

    German, Allison C; Myint, Khin Saw Aye; Mai, Nguyen Thi Hoang; Pomeroy, Ian; Phu, Nguyen Hoan; Tzartos, John; Winter, Peter; Collett, Jennifer; Farrar, Jeremy; Barrett, Alan; Kipar, Anja; Esiri, Margaret M; Solomon, Tom

    2006-12-01

    Japanese encephalitis virus is a mosquito-borne flavivirus that causes approximately 10000 deaths annually in Asia. After a brief viraemia, the virus enters the central nervous system, but the means of crossing the blood-brain barrier is uncertain. We used routine histological staining, immunohistology and electron microscopy to examine brain material from four fatal human cases, and made comparisons with material from a mouse model. In human material there was oedema, perivascular inflammation, haemorrhage, microglial nodules and acellular necrotic foci, as has been described previously. In addition, there was new evidence suggestive of viral replication in the vascular endothelium, with endothelial cell damage; this included occasional viral antigen staining, uneven binding of the vascular endothelial cells to Ulex europaeus agglutinin I and ultrastructural changes. Viral antigen was also found in neurons. There was an active astrocytic response, as shown by glial fibrillary acidic protein staining, and activation of microglial cells was demonstrated by an increase in major histocompatibility complex class II expression. Similar inflammatory infiltrates and a microglial reaction were observed in mouse brain tissue. In addition, beta-amyloid precursor protein staining indicated impaired axonal transport. Whether these findings are caused by viral replication in the vascular endothelium or the immune response merits further investigation. PMID:16814333

  11. Single cell confocal Raman spectroscopy of human osteoarthritic chondrocytes: a preliminary study.

    PubMed

    Kumar, Rajesh; Singh, Gajendra P; Grønhaug, Kirsten M; Afseth, Nils K; de Lange Davies, Catharina; Drogset, Jon O; Lilledahl, Magnus B

    2015-01-01

    A great deal of effort has been focused on exploring the underlying molecular mechanism of osteoarthritis (OA) especially at the cellular level. We report a confocal Raman spectroscopic investigation on human osteoarthritic chondrocytes. The objective of this investigation is to identify molecular features and the stage of OA based on the spectral signatures corresponding to bio-molecular changes at the cellular level in chondrocytes. In this study, we isolated chondrocytes from human osteoarthritic cartilage and acquired Raman spectra from single cells. Major spectral differences between the cells obtained from different International Cartilage Repair Society (ICRS) grades of osteoarthritic cartilage were identified. During progression of OA, a decrease in protein content and an increase in cell death were observed from the vibrational spectra. Principal component analysis and subsequent cross-validation was able to associate osteoarthritic chondrocytes to ICRS Grade I, II and III with specificity 100.0%, 98.1%, and 90.7% respectively, while, sensitivity was 98.6%, 82.8%, and 97.5% respectively. The overall predictive efficiency was 92.2%. Our pilot study encourages further use of Raman spectroscopy as a noninvasive and label free technique for revealing molecular features associated with osteoarthritic chondrocytes. PMID:25918938

  12. Overexpression, purification and preliminary crystallographic analysis of human M-ficolin fibrinogen-like domain

    SciTech Connect

    Tanio, Michikazu; Kondo, Shin; Sugio, Shigetoshi; Kohno, Toshiyuki

    2006-07-01

    Human M-ficolin fibrinogen-like domain has been overexpressed in P. pastoris, purified and crystallized. Diffraction data have been collected to 1.9 Å. Ficolins, which are comprised of a collagen-like domain and a fibrinogen-like domain, are a kind of pattern-recognition molecule for pathogens in the innate immunity system. To investigate the molecular mechanism of the discrimination between self and non-self by ficolins, human M-ficolin fibrinogen-like domain (FD1), which contains the ligand-binding site, was overexpressed in Pichia pastoris, purified and crystallized using the vapour-diffusion method at 293 K. The crystals belong to the monoclinic space group P2{sub 1}, with unit-cell parameters a = 55.16, b = 117.45, c = 55.19 Å, β = 99.88°, and contain three molecules per asymmetric unit. An X-ray data set was collected to 1.9 Å resolution using synchrotron radiation at beamline BL24XU at the SPring-8 facility in Japan.

  13. Crystallization and preliminary crystallographic analysis of human Atg4B–LC3 complex

    SciTech Connect

    Satoo, Kenji; Suzuki, Nobuo N.; Fujioka, Yuko; Mizushima, Noboru; Ohsumi, Yoshinori; Inagaki, Fuyuhiko

    2007-02-01

    Human Atg4B and LC3 were expressed, purified and crystallized as a complex. Diffraction data were collected to a resolution of 1.9 Å. The reversible modification of Atg8 with phosphatidylethanolamine (PE) is crucial for autophagy, the bulk degradation process of cytoplasmic components by the vacuolar/lysosomal system. Atg4 is a cysteine protease that is responsible for the processing and deconjugation of Atg8. Human Atg4B (HsAtg4B; a mammalian orthologue of yeast Atg4) and LC3 (a mammalian orthologue of yeast Atg8) were expressed and purified and two complexes, one consisting of HsAtg4B(1–354) and LC3(1–120) (complex I; the product complex) and the other consisting of HsAtg4B(1–354) and LC3(1–124) (complex II; the substrate complex), were crystallized using polyethylene glycol 3350 as a precipitant. In both complexes His280 of HsAtg4B was mutated to alanine. The crystals belong to the same space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 47.5, b = 91.8, c = 102.6 Å for complex I and a = 46.9, b = 90.9, c = 102.5 Å for complex II. Diffraction data were collected to a resolution of 1.9 Å from both crystals.

  14. Purification, crystallization and preliminary X-ray characterization of the human GTP fucose pyrophosphorylase

    SciTech Connect

    Quirk, Stephen; Seley-Radtke, Katherine L.

    2006-04-01

    The human GTP fucose pyrophosphohydrolase protein has been crystallized via the hanging-drop technique over a reservoir of polyethylene glycol (MW 8000) and ethylene glycol. The orthorhombic crystals diffract to 2.8 Å resolution. The human nucleotide-sugar metabolizing enzyme GTP fucose pyrophosphorylase (GFPP) has been purified to homogeneity by an affinity chromatographic procedure that utilizes a novel nucleoside analog. This new purification regime results in a protein preparation that produces significantly better crystals than traditional purification methods. The purified 66.6 kDa monomeric protein has been crystallized via hanging-drop vapor diffusion at 293 K. Crystals of the native enzyme diffract to 2.8 Å and belong to the orthorhombic space group P2{sub 1}2{sub 1}2{sub 1}. There is a single GFPP monomer in the asymmetric unit, giving a Matthews coefficient of 2.38 Å{sup 3} Da{sup −1} and a solvent content of 48.2%. A complete native data set has been collected as a first step in determining the three-dimensional structure of this enzyme.

  15. Caffeine as an indicator of human fecal contamination in the Sinos River: a preliminary study.

    PubMed

    Linden, R; Antunes, M V; Heinzelmann, L S; Fleck, J D; Staggemeier, R; Fabres, R B; Vecchia, A D; Nascimento, C A; Spilki, F R

    2015-05-01

    The preservation of hydric resources is directly related to fecal contamination monitoring, in order to allow the development of strategies for the management of polluting sources. In the present study, twenty-five water samples from six water public supply collection sites were used for the evaluation of the presence of caffeine, total and fecal coliforms. Caffeine was detected in all samples, with concentrations ranging from 0.15 ng mL-1 to 16.72 ng mL-1. Total coliforms were detected in all samples, with concentrations in the range of 52 NMP/100 mL to higher than 24196 NMP/100 mL, whether the concentration range for fecal coliforms was in the range of below 1 NMP/100 mL to 7800 NMP/100 mL. No significant correlation was found between total coliforms and caffeine concentrations (rs = 0.35, p = 0.09). However, a moderate correlation between fecal coliforms and caffeine concentrations was found (rs = 0.412, p <0.05), probably indicating a human source for these bacteria. Caffeine determination in water may be a useful strategy to evaluate water contamination by human fecal waste. PMID:26270218

  16. Expression, purification, crystallization and preliminary crystallographic analysis of human Pim-1 kinase

    SciTech Connect

    Qian, Kevin C.; Studts, Joey; Wang, Lian; Barringer, Kevin; Kronkaitis, Anthony; Peng, Charline; Baptiste, Alistair; LaFrance, Roger; Mische, Sheenah; Farmer, Bennett

    2005-01-01

    Pim kinases, belong to a distinctive serine/threonine protein-kinase family and are involved in cytokine-induced signal transduction and the development of lymphoid malignancies. Human Pim-1 kinase has been cloned, expressed and crystallized Pim kinases, including Pim-1, Pim-2 and Pim-3, belong to a distinctive serine/threonine protein-kinase family. They are involved in cytokine-induced signal transduction and the development of lymphoid malignancies. Their kinase domains are highly homologous to one another, but share low sequence identity to other kinases. Specifically, there are two proline residues in the conserved hinge-region sequence ERPXPX separated by a residue that is non-conserved among Pim kinases. Full-length human Pim-1 kinase (1–313) was cloned and expressed in Escherichia coli as a GST-fusion protein and truncated to Pim-1 (14–313) by thrombin digestion during purification. The Pim-1 (14–313) protein was purified to high homogeneity and monodispersity. This protein preparation yielded small crystals in the initial screening and large crystals after optimization. The large crystals of apo Pim-1 enzyme diffracted to 2.1 Å resolution and belong to space group P6{sub 5}, with unit-cell parameters a = b = 95.9, c = 80.0 Å, β = 120° and one molecule per asymmetric unit.

  17. Dissecting the Calcium-Induced Differentiation of Human Primary Keratinocytes Stem Cells by Integrative and Structural Network Analyses

    PubMed Central

    Toufighi, Kiana; Yang, Jae-Seong; Luis, Nuno Miguel; Aznar Benitah, Salvador; Lehner, Ben; Serrano, Luis; Kiel, Christina

    2015-01-01

    The molecular details underlying the time-dependent assembly of protein complexes in cellular networks, such as those that occur during differentiation, are largely unexplored. Focusing on the calcium-induced differentiation of primary human keratinocytes as a model system for a major cellular reorganization process, we look at the expression of genes whose products are involved in manually-annotated protein complexes. Clustering analyses revealed only moderate co-expression of functionally related proteins during differentiation. However, when we looked at protein complexes, we found that the majority (55%) are composed of non-dynamic and dynamic gene products (‘di-chromatic’), 19% are non-dynamic, and 26% only dynamic. Considering three-dimensional protein structures to predict steric interactions, we found that proteins encoded by dynamic genes frequently interact with a common non-dynamic protein in a mutually exclusive fashion. This suggests that during differentiation, complex assemblies may also change through variation in the abundance of proteins that compete for binding to common proteins as found in some cases for paralogous proteins. Considering the example of the TNF-α/NFκB signaling complex, we suggest that the same core complex can guide signals into diverse context-specific outputs by addition of time specific expressed subunits, while keeping other cellular functions constant. Thus, our analysis provides evidence that complex assembly with stable core components and competition could contribute to cell differentiation. PMID:25946651

  18. Insights into human phosphoglycerate kinase 1 deficiency as a conformational disease from biochemical, biophysical, and in vitro expression analyses.

    PubMed

    Pey, Angel L; Maggi, Maristella; Valentini, Giovanna

    2014-11-01

    Mutations in genes encoding metabolic enzymes are often the cause of inherited diseases. Mutations usually affect the ability of proteins to fold properly, thus leading to enzyme loss of function. In this work, we explored the relationships between protein stability, aggregation, and degradation in vitro and inside cells in a large set of mutants associated with human phosphoglycerate kinase 1 (hPGK1) deficiency. To this end, we studied a third of the pathogenic alleles reported in the literature using expression analyses and biochemical, biophysical, and computational procedures. Our results show that most pathogenic variants studied had an increased tendency to aggregate when expressed in Escherichia coli, well correlating with the denaturation half-lives measured by thermal denaturation in vitro. Further, the most deleterious mutants show reduced stability toward chemical denaturation and proteolysis, supporting a pivotal role of thermodynamic stability in the propensity toward aggregation and proteolysis of pathogenic hPGK1 mutants in vitro and inside cells. Our strategy allowed us to unravel the complex relationships between protein stability, aggregation, and degradation in hPGK1 deficiency, which might be used to understand disease mechanisms in many inborn errors of metabolism. Our results suggest that pharmacological chaperones and protein homeostasis modulators could be considered as good candidates for therapeutic approaches for hPGK1 deficiency. PMID:24838780

  19. What Happened, and Why: Toward an Understanding of Human Error Based on Automated Analyses of Incident Reports. Volume 2

    NASA Technical Reports Server (NTRS)

    Ferryman, Thomas A.; Posse, Christian; Rosenthal, Loren J.; Srivastava, Ashok N.; Statler, Irving C.

    2006-01-01

    The objective of the Aviation System Monitoring and Modeling project of NASA's Aviation Safety and Security Program was to develop technologies to enable proactive management of safety risk, which entails identifying the precursor events and conditions that foreshadow most accidents. Information about what happened can be extracted from quantitative data sources, but the experiential account of the incident reporter is the best available source of information about why an incident happened. In Volume I, the concept of the Scenario was introduced as a pragmatic guide for identifying similarities of what happened based on the objective parameters that define the Context and the Outcome of a Scenario. In this Volume II, that study continues into the analyses of the free narratives to gain understanding as to why the incident occurred from the reporter s perspective. While this is just the first experiment, the results of our approach are encouraging and indicate that it will be possible to design an automated analysis process guided by the structure of the Scenario that can achieve the level of consistency and reliability of human analysis of narrative reports.

  20. Microarray Analyses Reveal Marked Differences in Growth Factor and Receptor Expression Between 8-Cell Human Embryos and Pluripotent Stem Cells

    PubMed Central

    Vlismas, Antonis; Bletsa, Ritsa; Mavrogianni, Despina; Mamali, Georgina; Pergamali, Maria; Dinopoulou, Vasiliki; Partsinevelos, George; Drakakis, Peter; Loutradis, Dimitris

    2016-01-01

    Previous microarray analyses of RNAs from 8-cell (8C) human embryos revealed a lack of cell cycle checkpoints and overexpression of core circadian oscillators and cell cycle drivers relative to pluripotent human stem cells [human embryonic stem cells/induced pluripotent stem (hES/iPS)] and fibroblasts, suggesting growth factor independence during early cleavage stages. To explore this possibility, we queried our combined microarray database for expression of 487 growth factors and receptors. Fifty-one gene elements were overdetected on the 8C arrays relative to hES/iPS cells, including 14 detected at least 80-fold higher, which annotated to multiple pathways: six cytokine family (CSF1R, IL2RG, IL3RA, IL4, IL17B, IL23R), four transforming growth factor beta (TGFB) family (BMP6, BMP15, GDF9, ENG), one fibroblast growth factor (FGF) family [FGF14(FH4)], one epidermal growth factor member (GAB1), plus CD36, and CLEC10A. 8C-specific gene elements were enriched (73%) for reported circadian-controlled genes in mouse tissues. High-level detection of CSF1R, ENG, IL23R, and IL3RA specifically on the 8C arrays suggests the embryo plays an active role in blocking immune rejection and is poised for trophectoderm development; robust detection of NRG1, GAB1, -2, GRB7, and FGF14(FHF4) indicates novel roles in early development in addition to their known roles in later development. Forty-four gene elements were underdetected on the 8C arrays, including 11 at least 80-fold under the pluripotent cells: two cytokines (IFITM1, TNFRSF8), five TGFBs (BMP7, LEFTY1, LEFTY2, TDGF1, TDGF3), two FGFs (FGF2, FGF receptor 1), plus ING5, and WNT6. The microarray detection patterns suggest that hES/iPS cells exhibit suppressed circadian competence, underexpression of early differentiation markers, and more robust expression of generic pluripotency genes, in keeping with an artificial state of continual uncommitted cell division. In contrast, gene expression patterns of the 8C embryo suggest that

  1. Microarray Analyses Reveal Marked Differences in Growth Factor and Receptor Expression Between 8-Cell Human Embryos and Pluripotent Stem Cells.

    PubMed

    Vlismas, Antonis; Bletsa, Ritsa; Mavrogianni, Despina; Mamali, Georgina; Pergamali, Maria; Dinopoulou, Vasiliki; Partsinevelos, George; Drakakis, Peter; Loutradis, Dimitris; Kiessling, Ann A

    2016-01-15

    Previous microarray analyses of RNAs from 8-cell (8C) human embryos revealed a lack of cell cycle checkpoints and overexpression of core circadian oscillators and cell cycle drivers relative to pluripotent human stem cells [human embryonic stem cells/induced pluripotent stem (hES/iPS)] and fibroblasts, suggesting growth factor independence during early cleavage stages. To explore this possibility, we queried our combined microarray database for expression of 487 growth factors and receptors. Fifty-one gene elements were overdetected on the 8C arrays relative to hES/iPS cells, including 14 detected at least 80-fold higher, which annotated to multiple pathways: six cytokine family (CSF1R, IL2RG, IL3RA, IL4, IL17B, IL23R), four transforming growth factor beta (TGFB) family (BMP6, BMP15, GDF9, ENG), one fibroblast growth factor (FGF) family [FGF14(FH4)], one epidermal growth factor member (GAB1), plus CD36, and CLEC10A. 8C-specific gene elements were enriched (73%) for reported circadian-controlled genes in mouse tissues. High-level detection of CSF1R, ENG, IL23R, and IL3RA specifically on the 8C arrays suggests the embryo plays an active role in blocking immune rejection and is poised for trophectoderm development; robust detection of NRG1, GAB1, -2, GRB7, and FGF14(FHF4) indicates novel roles in early development in addition to their known roles in later development. Forty-four gene elements were underdetected on the 8C arrays, including 11 at least 80-fold under the pluripotent cells: two cytokines (IFITM1, TNFRSF8), five TGFBs (BMP7, LEFTY1, LEFTY2, TDGF1, TDGF3), two FGFs (FGF2, FGF receptor 1), plus ING5, and WNT6. The microarray detection patterns suggest that hES/iPS cells exhibit suppressed circadian competence, underexpression of early differentiation markers, and more robust expression of generic pluripotency genes, in keeping with an artificial state of continual uncommitted cell division. In contrast, gene expression patterns of the 8C embryo suggest that

  2. Purification, crystallization and preliminary X-ray diffraction of human S100A15

    SciTech Connect

    Boeshans, Karen M.; Wolf, Ronald; Voscopoulos, Christopher; Gillette, William; Esposito, Dominic; Mueser, Timothy C.; Yuspa, Stuart H.; Ahvazi, Bijan

    2006-05-01

    S100 proteins are differentially expressed during epithelial cell maturation, tumorigenesis and inflammation. The novel human S100A15 protein has been cloned, expressed, purified and crystallized in two crystal forms, a triclinic and a monoclinic form, which diffract to 1.7 and 2.0 Å, respectively. Human S100A15 is a novel member of the S100 family of EF-hand calcium-binding proteins and was recently identified in psoriasis, where it is significantly upregulated in lesional skin. The protein is implicated as an effector in calcium-mediated signal transduction pathways. Although its biological function is unclear, the association of the 11.2 kDa S100A15 with psoriasis suggests that it contributes to the pathogenesis of the disease and could provide a molecular target for therapy. To provide insight into the function of S100A15, the protein was crystallized to visualize its structure and to further the understanding of how the many similar calcium-binding mediator proteins in the cell distinguish their cognate target molecules. The S100A15 protein has been cloned, expressed and purified to homogeneity and produced two crystal forms. Crystals of form I are triclinic, with unit-cell parameters a = 33.5, b = 44.3, c = 44.8 Å, α = 71.2, β = 68.1, γ = 67.8° and an estimated two molecules in the asymmetric unit, and diffract to 1.7 Å resolution. Crystals of form II are monoclinic, with unit-cell parameters a = 82.1, b = 33.6, c = 52.2 Å, β = 128.2° and an estimated one molecule in the asymmetric unit, and diffract to 2.0 Å resolution. This structural analysis of the human S100A15 will further aid in the phylogenic comparison between the other members of the S100 protein family, especially the highly homologous paralog S100A7.

  3. Human adaptation to isolated and confined environments: Preliminary findings of a seven month Antarctic winter-over human factors study

    NASA Technical Reports Server (NTRS)

    Evans, Gary W.; Stokols, Daniel; Carrere, Sybil

    1988-01-01

    This field study was conducted during the last decade of an austral winter-over at Palmer Station in the Antarctic. The purpose of the study was to understand temporal patterns in physiological arousal and psychological mood over the course of the mission. The investigators were principally interested in how people adapted over time to chronic and acute stressors, and how people use and modify their built environment. Physiological and psychological data were collected several times a week, and information on behavior and the use of physical facilities was collected monthly. Physiological and psychological data were compared with social changes in the setting toward the development of a sequential model of human-environment transactional relationships. Based on the study results, guidelines for design of future isolated and confined environments (ICEs) included: plan space for items which make people feel at home, provide materials to allow people to personalize their environment, allow for flexible environments, provide areas for visual and auditory privacy, equip areas for socializing and remove them from private areas, and provide facilities for exercise and for projects involving physical activity. The study offers guidelines about patterns of adaption that could be expected in an ICE, discusses how these settings can be programmed to facilitate successful adjustment, and provides information about how to design future ICE habitats to maximize a healthy living environment.

  4. Crystallization and preliminary neutron diffraction experiment of human farnesyl pyrophosphate synthase complexed with risedronate

    PubMed Central

    Yokoyama, Takeshi; Ostermann, Andreas; Mizuguchi, Mineyuki; Niimura, Nobuo; Schrader, Tobias E.; Tanaka, Ichiro

    2014-01-01

    Nitrogen-containing bisphosphonates (N-BPs), such as risedronate and zoledronate, are currently used as a clinical drug for bone-resorption diseases and are potent inhibitors of farnesyl pyrophosphate synthase (FPPS). X-ray crystallographic analyses of FPPS with N-BPs have revealed that N-BPs bind to FPPS with three magnesium ions and several water molecules. To understand the structural characteristics of N-BPs bound to FPPS, including H atoms and hydration by water, neutron diffraction studies were initiated using BIODIFF at the Heinz Maier-Leibnitz Zentrum (MLZ). FPPS–risedronate complex crystals of approximate dimensions 2.8 × 2.5 × 1.5 mm (∼3.5 mm3) were obtained by repeated macro-seeding. Monochromatic neutron diffraction data were collected to 2.4 Å resolution with 98.4% overall completeness. Here, the first successful neutron data collection from FPPS in complex with N-BPs is reported. PMID:24699741

  5. Crystallization and preliminary crystallographic studies of human septin 1 with site-directed mutations

    PubMed Central

    Hu, Hao; Yu, Wen-bo; Li, Shu-xing; Ding, Xiang-ming; Yu, Long; Bi, Ru-Chang

    2006-01-01

    Septin 1 is a member of an evolutionarily conserved family of GTP-binding and filament-forming proteins named septins, which function in diverse processes including cytokinasis, vesicle trafficking, apoptosis, remodelling of the cytoskeleton, infection, neurodegeneration and neoplasia. Human septin 1 has been expressed and purified, but suffers from severe aggregation. Studies have shown that septin 1 with site-directed mutations of five serine residues (Ser19, Ser206, Ser307, Ser312 and Ser315) has a much lower degree of aggregation and better structural homogeneity and that the mutations cause only slight perturbations in the secondary structure of septin 1. This septin 1 mutant was crystallized and diffraction data were collected to 2.5 Å resolution. The space group is P422, with unit-cell parameters a = b = 106.028, c = 137.852 Å. PMID:16511282

  6. A preliminary screening study on human cystic echinococcosis in Cairo slaughter house personnel.

    PubMed

    Ramadan, N I; el Damaty, S I

    2000-04-01

    A descriptive serological screening study was done on human cystic echinococcosis (CE) in high risk groups selected from Cairo slaughter house employees and the household nearby using indirect haemagglutination (IHA) and enzyme-linked immunoelectrotransfer blot (EITB) tests. Characterized camel hydatid cyst fluid (HCF) antigen by 12.5% sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) was used. Three asymptomatic clinical cases (1.3%) were seropositive using EITB assay (reacting with six HCF protein bands of molecular weights approximately 7, 21, 28, 35, 127 and 210 kilodaltons 'kDa') but one case was seronegative by the IHA test. All three cases had typical lesions of CE in liver and lung revealed by abdominal ultrasonography (US), computerized tomography (CT) scan and chest X-ray. The prevalence of CE in Cairo slaughter house workers was 1.6% versus 1.1% in the household nearby. PMID:10786044

  7. Crystallization and Preliminary X-Ray Crystallographic Analysis of Human Plasma Platelet Activating Factor Acetylhydrolase

    SciTech Connect

    Samanta, U.; Wilder, C; Bahnson, B

    2009-01-01

    The plasma form of the human enzyme platelet activating factor acetylhydrolase (PAF-AH) has been crystallized, and X-ray diffraction data were collected at a synchrotron source to a resolution of 1.47 {angstrom}. The crystals belong to space group C2, with unit cell parameters of a = 116.18, b = 83.06, c = 96.71 {angstrom}, and {beta} = 115.09 and two molecules in the asymmetric unit. PAF-AH functions as a general anti-inflammatory scavenger by reducing the levels of the signaling molecule PAF. Additionally, the LDL bound enzyme has been linked to atherosclerosis due to its hydrolytic activities of pro-inflammatory agents, such as sn-2 oxidatively fragmented phospholipids.

  8. Preliminary Toxicological Analysis of the Effect of Coal Slurry Impoundment Water on Human Liver Cells

    USGS Publications Warehouse

    Bunnell, Joseph E.

    2008-01-01

    Coal is usually 'washed' with water and a variety of chemicals to reduce its content of sulfur and mineral matter. The 'washings' or 'coal slurry' derived from this process is a viscous black liquid containing fine particles of coal, mineral matter, and other dissolved and particulate substances. Coal slurry may be stored in impoundments or in abandoned underground mines. Human health and environmental effects potentially resulting from leakage of chemical substances from coal slurry into drinking water supplies or aquatic ecosystems have not been systematically examined. Impoundments are semipermeable, presenting the possibility that inorganic and organic substances, some of which may be toxic, may contaminate ground or surface water. The Agency for Toxic Substances and Disease Registry, part of the Centers for Disease Control and Prevention, has concluded that well water in Mingo County, West Virginia, constitutes a public health hazard.

  9. Single-photon emission computed tomography in human immunodeficiency virus encephalopathy: A preliminary report

    SciTech Connect

    Masdeu, J.C.; Yudd, A.; Van Heertum, R.L.; Grundman, M.; Hriso, E.; O'Connell, R.A.; Luck, D.; Camli, U.; King, L.N. )

    1991-08-01

    Depression or psychosis in a previously asymptomatic individual infected with the human immunodeficiency virus (HIV) may be psychogenic, related to brain involvement by the HIV or both. Although prognosis and treatment differ depending on etiology, computed tomography (CT) and magnetic resonance imaging (MRI) are usually unrevealing in early HIV encephalopathy and therefore cannot differentiate it from psychogenic conditions. Thirty of 32 patients (94%) with HIV encephalopathy had single-photon emission computed tomography (SPECT) findings that differed from the findings in 15 patients with non-HIV psychoses and 6 controls. SPECT showed multifocal cortical and subcortical areas of hypoperfusion. In 4 cases, cognitive improvement after 6-8 weeks of zidovudine (AZT) therapy was reflected in amelioration of SPECT findings. CT remained unchanged. SPECT may be a useful technique for the evaluation of HIV encephalopathy.

  10. Crystallization and preliminary crystallographic analysis of human muscle phosphofructokinase, the main regulator of glycolysis

    PubMed Central

    Kloos, Marco; Brüser, Antje; Kirchberger, Jürgen; Schöneberg, Torsten; Sträter, Norbert

    2014-01-01

    Whereas the three-dimensional structure and the structural basis of the allosteric regulation of prokaryotic 6-phosphofructokinases (Pfks) have been studied in great detail, knowledge of the molecular basis of the allosteric behaviour of the far more complex mammalian Pfks is still very limited. The human muscle isozyme was expressed heterologously in yeast cells and purified using a five-step purification protocol. Protein crystals suitable for diffraction experiments were obtained by the vapour-diffusion method. The crystals belonged to space group P6222 and diffracted to 6.0 Å resolution. The 3.2 Å resolution structure of rabbit muscle Pfk (rmPfk) was placed into the asymmetric unit and optimized by rigid-body and group B-factor refinement. Interestingly, the tetrameric enzyme dissociated into a dimer, similar to the situation observed in the structure of rmPfk. PMID:24817713