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Sample records for factor complex human

  1. Clearance of human factor XIa-inhibitor complexes in rats.

    PubMed

    Wuillemin, W A; Bleeker, W K; Agterberg, J; Rigter, G; ten Cate, H; Hack, C E

    1996-06-01

    The serpins C1 esterase inhibitor (C1Inh), antithrombin (AT), alpha 1-antitrypsin (alpha 1AT) and alpha 2-antiplasmin (alpha 2AP) are known inhibitors of coagulation factor XIa (FXIa). Although initial studies suggested alpha 1AT to be the main inhibitor of FXIa, we recently demonstrated C1Inh to be a predominant inhibitor of FXIa in vitro in human plasma. The present study was performed to investigate the plasma elimination kinetics of preformed human FXIa-FXIa inhibitor complexes injected in rats. The amounts of complexes remaining in circulation were measured using enzyme-linked immunosorbent assays. The plasma half-life time of clearance (t1/2) was 98 min for FXIa-alpha 1AT complexes, whereas it was considerably shorter, i.e. 19, 18 and 15 min for FXIa-C1Inh, FXIa-alpha 2AP and FXIa-AT complexes, respectively. Thus, due to this different plasma t1/2, preferentially FXIa-alpha 1AT complexes may be detected in clinical samples. Furthermore, measuring FXIa-FXIa inhibitor complexes in patient samples may not help to clarify the relative contribution of the individual serpins to inactivation of FXIa in vivo.

  2. Human factoring the procedures element in a complex manufacturing system

    SciTech Connect

    Caccamise, D.J.; Mecherikoff, M.

    1993-06-01

    As a result of Human Factors evaluations of procedures associated with incidents at Rocky Flats Plant (RFP) it was determined that the existing procedure format created significant opportunities for confusion in their attempt to convey information about a work process. For instance, there was no mechanism to clearly identify the participants and their roles during the instructions portion of the procedure. In addition, procedure authors frequently used complex logic to convey a series of contingent actions within steps. It was also difficult to discern the actual procedure steps from other types of information in the procedure. These and other inadequacies prompted the Human Factors Engineering (HFE) department to propose solutions to these problems that followed well-researched principles of cognitive psychology, dealing with how humans process information. Format and style contribute to procedure usability, and therefore to safety and efficiency in operations governed by the procedures. Since it was difficult to tie specific performance failures to specific format and style characteristics and thereby dearly define costs and benefits, it was difficult on that basis to sell the idea that changes in procedure format and style were really necessary to improve safety and efficiency. In addition, we found that the socio-political systems governing this process, particularly at the subprocess interface level, were not functioning efficiently. Both the technological aspects of the process and the socio-political aspects were contributing to waste and considerable re-work. Fixing the customer feedback loop to the process owners not only minimized re-work and waste, but also provided the data to persuade subprocess owners to make the necessary changes that heretofore were being met with great resistance.

  3. Assembly factors for the membrane arm of human complex I.

    PubMed

    Andrews, Byron; Carroll, Joe; Ding, Shujing; Fearnley, Ian M; Walker, John E

    2013-11-19

    Mitochondrial respiratory complex I is a product of both the nuclear and mitochondrial genomes. The integration of seven subunits encoded in mitochondrial DNA into the inner membrane, their association with 14 nuclear-encoded membrane subunits, the construction of the extrinsic arm from 23 additional nuclear-encoded proteins, iron-sulfur clusters, and flavin mononucleotide cofactor require the participation of assembly factors. Some are intrinsic to the complex, whereas others participate transiently. The suppression of the expression of the NDUFA11 subunit of complex I disrupted the assembly of the complex, and subcomplexes with masses of 550 and 815 kDa accumulated. Eight of the known extrinsic assembly factors plus a hydrophobic protein, C3orf1, were associated with the subcomplexes. The characteristics of C3orf1, of another assembly factor, TMEM126B, and of NDUFA11 suggest that they all participate in constructing the membrane arm of complex I.

  4. Towards a framework of human factors certification of complex human-machine systems

    NASA Technical Reports Server (NTRS)

    Bukasa, Birgit

    1994-01-01

    As far as total automation is not realized, the combination of technical and social components in man-machine systems demands not only contributions from engineers but at least to an equal extent from behavioral scientists. This has been neglected far too long. The psychological, social and cultural aspects of technological innovations were almost totally overlooked. Yet, along with expected safety improvements the institutionalization of human factors is on the way. The introduction of human factors certification of complex man-machine systems will be a milestone in this process.

  5. EpiFactors: a comprehensive database of human epigenetic factors and complexes

    PubMed Central

    Medvedeva, Yulia A.; Lennartsson, Andreas; Ehsani, Rezvan; Kulakovskiy, Ivan V.; Vorontsov, Ilya E.; Panahandeh, Pouda; Khimulya, Grigory; Kasukawa, Takeya; Drabløs, Finn

    2015-01-01

    Epigenetics refers to stable and long-term alterations of cellular traits that are not caused by changes in the DNA sequence per se. Rather, covalent modifications of DNA and histones affect gene expression and genome stability via proteins that recognize and act upon such modifications. Many enzymes that catalyse epigenetic modifications or are critical for enzymatic complexes have been discovered, and this is encouraging investigators to study the role of these proteins in diverse normal and pathological processes. Rapidly growing knowledge in the area has resulted in the need for a resource that compiles, organizes and presents curated information to the researchers in an easily accessible and user-friendly form. Here we present EpiFactors, a manually curated database providing information about epigenetic regulators, their complexes, targets and products. EpiFactors contains information on 815 proteins, including 95 histones and protamines. For 789 of these genes, we include expressions values across several samples, in particular a collection of 458 human primary cell samples (for approximately 200 cell types, in many cases from three individual donors), covering most mammalian cell steady states, 255 different cancer cell lines (representing approximately 150 cancer subtypes) and 134 human postmortem tissues. Expression values were obtained by the FANTOM5 consortium using Cap Analysis of Gene Expression technique. EpiFactors also contains information on 69 protein complexes that are involved in epigenetic regulation. The resource is practical for a wide range of users, including biologists, pharmacologists and clinicians. Database URL: http://epifactors.autosome.ru PMID:26153137

  6. Crystal structure of human factor VIIa/tissue factor in complex with peptide mimetic inhibitor.

    PubMed

    Kadono, Shojiro; Sakamoto, Akihisa; Kikuchi, Yasufumi; Oh-eda, Masayoshi; Yabuta, Naohiro; Koga, Takaki; Hattori, Kunihiro; Shiraishi, Takuya; Haramura, Masayuki; Kodama, Hirofumi; Esaki, Toru; Sato, Haruhiko; Watanabe, Yoshiaki; Itoh, Susumu; Ohta, Masateru; Kozono, Toshiro

    2004-11-26

    The 3D structure of human factor VIIa/soluble tissue factor in complex with a peptide mimetic inhibitor, propylsulfonamide-D-Thr-Met-p-aminobenzamidine, is determined by X-ray crystallography. As compared with the interactions between thrombin and thrombin inhibitors, the interactions at S2 and S3 sites characteristic of factor VIIa and factor VIIa inhibitors are revealed. The S2 site has a small pocket, which is filled by the hydrophobic methionine side chain in P2. The small S3 site fits the small size residue, D-threonine in P3. The structural data and SAR data of the peptide mimetic inhibitor show that these interactions in the S2 and S3 sites play an important role for the improvement of selectivity versus thrombin. The results will provide valuable information for the structure-based drug design of specific inhibitors for FVIIa/TF. PMID:15504346

  7. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    SciTech Connect

    Chi Ki Ngo,J.; Huang, M.; Roth, D.; Furie, B.; Furie, B.

    2008-01-01

    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca(2+) and two Cu(2+) ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  8. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex

    SciTech Connect

    Ngo, J.C.; Huang, M.; Roth, D.A.; Furie, B.C.; Furie, B.

    2008-06-03

    Factor VIII is a procofactor that plays a critical role in blood coagulation, and is missing or defective in hemophilia A. We determined the X-ray crystal structure of B domain-deleted human factor VIII. This protein is composed of five globular domains and contains one Ca{sup 2+} and two Cu{sup 2+} ions. The three homologous A domains form a triangular heterotrimer where the A1 and A3 domains serve as the base and interact with the C2 and C1 domains, respectively. The structurally homologous C1 and C2 domains reveal membrane binding features. Based on biochemical studies, a model of the factor IXa-factor VIIIa complex was constructed by in silico docking. Factor IXa wraps across the side of factor VIII, and an extended interface spans the factor VIII heavy and light chains. This model provides insight into the activation of factor VIII and the interaction of factor VIIIa with factor IXa on the membrane surface.

  9. Linkage map of the human major histocompatibility complex including the tumor necrosis factor genes

    SciTech Connect

    Carroll, M.C.; Katzman, P.; Alicot, E.M.; Koller, B.H.; Geraghty, D.E.; Orr, H.T.; Strominger, J.L.; Spies, T.

    1987-12-01

    The tumor necrosis factor (TNF) ..cap alpha.. and ..beta.. gene pair has been linked in the human major histocompatibility complex to HLA-B, HLA-C, and, tentatively, HLA-E and HLA-A on one side and to the class III complement/steroid 21-hydroxylase gene cluster on the other by pulsed-field gel electrophoresis. The TNF genes are located 200 kilobases (kb) centromeric of HLA-B and about 350 kb telomeric of the class III cluster. Together with previous data on the linkage and structures of the class II and class III regions, a restriction map of the entire human major histocompatibility complex of about 3500 kb has been prepared.

  10. Human factors issues for resolving adverse effects of human work underload and workload transitions in complex human-machine systems

    SciTech Connect

    Ryan, T.G.

    1995-10-01

    A workshop was conducted whose specific purpose was to build on earlier work of the United States National Research Council, United States Federal government agencies, and the larger human factors community to: (1) clarify human factors issues pertaining to degraded performance in advanced human-machine systems (e.g., nuclear production, transportation, aerospace) due to human work underload and workload transition, and (2) develop strategies for resolving these issues. Recent history demonstrates that: (1) humans often react adversely to their diminishing roles in advanced human-machine systems, and therefore (2) new allocation models and strategies are required if humans are to be willing and able to assume diminishing and shifting roles assigned to them in these systems, and are to accept new technologies making up these systems. Problems associated with theses diminishing and shifting human roles are characterized as work underload and workload transitions. The workshop affirmed that: (1) work underload and workload transition are issues that will have to be addressed by designers of advanced human-machine systems, especially those relying on automation, if cost, performance, safety, and operator acceptability are to be optimized, (2) human machine allocation models, standards, and guidelines which go beyond simple capability approaches will be needed to preclude or seriously diminish the work underload and workload transition problems, and (3) the 16 workload definition, measurement, situational awareness, and trust issues identified during the workshop, need resolution if these models, standards, and guidelines are to be achieved.

  11. Binding of transcription factors and creation of a large nucleoprotein complex on the human cytomegalovirus enhancer

    SciTech Connect

    Ghazal, P.; Lubon, H.; Fleckenstein, B.; Hennighausen, L.

    1987-06-01

    The effect of the human cytomegalovirus immediate early region 1 enhancer on transcription was studied in vitro with HeLa cell nuclear extract. Stimulation of in vitro transcription mediated by the enhancer element involves its recognition by specific trans-acting factors present in the nuclear extract. DNase I protection analysis was used to determine at the nucleotide level those enhancer sequences that interact with nuclear factors. At least nine sites of protein-DNA interaction were detected over approx. = 400 base pairs of enhancer sequence. The regions of nuclease protection are associated with 21-, 19-, 18-, and 17-base-pair repeat elements as well as with a unique sequence, creating a large nucleoprotein complex. The relationship between the protein binding and the activity of the immediate early region 1 enhancer is discussed.

  12. Crystal structure of human intrinsic factor: Cobalamin complex at 2.6-Å resolution

    PubMed Central

    Mathews, F. S.; Gordon, M. M.; Chen, Z.; Rajashankar, K. R.; Ealick, S. E.; Alpers, D. H.; Sukumar, N.

    2007-01-01

    The structure of intrinsic factor (IF) in complex with cobalamin (Cbl) was determined at 2.6-Å resolution. The overall fold of the molecule is that of an α6/α6 barrel. It is a two-domain protein, and the Cbl is bound at the interface of the domains in a base-on conformation. Surprisingly, two full-length molecules, each comprising an α- and a β-domain and one Cbl, and two truncated molecules with only an α- domain are present in the same asymmetric unit. The environment around Cbl is dominated by uncharged residues, and the sixth coordinate position of Co2+ is empty. A detailed comparison between the IF-B12 complex and another Cbl transport protein complex, trans-Cbl-B12, has been made. The pH effect on the binding of Cbl analogues in transport proteins is analyzed. A possible basis for the lack of interchangeability of human and rat IF receptors is presented. PMID:17954916

  13. Performance improvement through best practice team management: human factors in complex trauma.

    PubMed

    Mercer, Simon; Arul, G S; Pugh, H E J

    2014-06-01

    Human factors or non-technical skills are now commonplace in the medical literature, having taken the lead from the airline and nuclear industries and more recently Formula One motor racing. They have been suggested as playing a vital role in the success of the trauma teams in recent conflicts. This article outlines the background to human factors, referring to early papers and reports and also outlines high profile cases that highlight their importance. We then describe the importance of human factors in the deployed setting and some of the lessons that have been learnt from current conflicts.

  14. Cdk-activating kinase complex is a component of human transcription factor TFIIH.

    PubMed

    Shiekhattar, R; Mermelstein, F; Fisher, R P; Drapkin, R; Dynlacht, B; Wessling, H C; Morgan, D O; Reinberg, D

    1995-03-16

    Transcription factor IIH (TFIIH) contains a kinase capable of phosphorylating the carboxy-terminal domain (CTD) of the largest subunit of RNA polymerase II (RNAPII). Here we report the identification of the Cdk-activating kinase (Cak) complex (Cdk7 and cyclin H) as a component of TFIIH after extensive purification of TFIIH by chromatography. We find that affinity-purified antibodies directed against cyclin H inhibit TFIIH-dependent transcription and that both cyclin H and Cdk7 antibodies inhibit phosphorylation of the CTD of the largest subunit of the RNAPII in the preinitiation complex. Cak is present in at least two distinct complexes, TFIIH and a smaller complex that is unable to phosphorylate RNAPII in the preinitiation complex. Both Cak complexes, as well as recombinant Cak, phosphorylate a CTD peptide. Finally, TFIIH was shown to phosphorylate both Cdc2 and Cdk2, suggesting that there could be a link between transcription and the cell cycle machinery.

  15. Modulation of Innate Host Factors by Mycobacterium avium Complex in Human Macrophages Includes Interleukin 17

    PubMed Central

    Vázquez, Nancy; Rekka, Sofia; Gliozzi, Maria; Feng, Carl G.; Amarnath, Shoba; Orenstein, Jan M.; Wahl, Sharon M.

    2012-01-01

    Background. Although opportunistic infections due to Mycobacterium avium complex (MAC) have been less common since the introduction of highly active antiretroviral therapy, globally, human immunodeficiency virus-1 (HIV-1)–positive patients remain predisposed to these infections. Absence of a properly functioning acquired immune response allows MAC persistence within macrophages localized in lymph nodes coinfected with HIV and MAC. Although a deficiency in interferon γ appears to play a part in the ability of MAC to deflect the macrophage-associated antimicrobial attack, questions about this process remain. Our study examines the ability of MAC to regulate interleukin 17 (IL-17), a proinflammatory cytokine involved in host cell recruitment. Methods. Coinfected lymph nodes were examined for IL-17 by immunohistochemical analysis. In vitro, macrophages exposed to mycobacteria were evaluated for transcription activities, proteins, and signaling pathways responsible for IL-17 expression. Infected macrophages were also analyzed for expression of interleukin 21 (IL-21) and negative regulators of immune responses. Results. Infection of macrophages triggered synthesis of IL-17, correlating with IL-17 expression by macrophages in coinfected lymph nodes. Infected macrophages exposed to exogenous IL-17 expressed CXCL10, which favors recruitment of new macrophages as targets for infection. Blockade of nuclear factor κ-light-chain-enhancer of activated B cells and mitogen-activated protein kinase pathways suppressed mycobacteria-induced IL-17 expression. MAC triggered expression of IL-21, IRF4, and STAT3 genes related to IL-17 regulation, as well as expression of the negative immunoregulators CD274(PD-L1) and suppressors of cytokine signaling. Conclusions. MAC-infected macrophages can provide an alternative source for IL-17 that favors accumulation of new targets for perpetuating bacterial and viral infection while suppressing host antimicrobial immune responses. PMID

  16. Independent Verification and Validation of Complex User Interfaces: A Human Factors Approach

    NASA Technical Reports Server (NTRS)

    Whitmore, Mihriban; Berman, Andrea; Chmielewski, Cynthia

    1996-01-01

    The Usability Testing and Analysis Facility (UTAF) at the NASA Johnson Space Center has identified and evaluated a potential automated software interface inspection tool capable of assessing the degree to which space-related critical and high-risk software system user interfaces meet objective human factors standards across each NASA program and project. Testing consisted of two distinct phases. Phase 1 compared analysis times and similarity of results for the automated tool and for human-computer interface (HCI) experts. In Phase 2, HCI experts critiqued the prototype tool's user interface. Based on this evaluation, it appears that a more fully developed version of the tool will be a promising complement to a human factors-oriented independent verification and validation (IV&V) process.

  17. Functional properties of an isolated. cap alpha beta. heterodimeric human placenta insulin-like growth factor 1 receptor complex

    SciTech Connect

    Feltz, S.M.; Swanson, M.L.; Wemmie, J.A.; Pessin, J.E.

    1988-05-03

    Treatment of human placenta membranes at pH 8.5 in the presence of 2.0 mM dithiothreitol (DTT) for 5 min, followed by the simultaneous removal of the DTT and pH adjustment of pH 7.6, resulted in the formation of a functional ..cap alpha beta.. heterodimeric insulin-like growth factor 1 (IGF-1) receptor complex from the native ..cap alpha../sub 2/..beta../sub 2/ heterotetrameric disulfide-linked state. The membrane-bound ..cap alpha beta.. heterodimeric complex displayed similar curvilinear /sup 125/I-IGF-1 equilibrium binding compared to the ..cap alpha../sub 2/..beta../sub 2/ heterotetrameric complex. /sup 125/I-IGF-1 binding to both the isolated ..cap alpha../sub 2/..beta../sub 2/ heterotetrameric and ..cap alpha beta.. heterodimeric complexes demonstrated a marked straightening of the Scatchard plots, compared to the placenta membrane-bound IGF-1 receptors, with a 2-fold increase in the high-affinity binding component. IGF-1 stimulation of IGF-1 receptor autophosphorylation indicated that the ligand-dependent activation of ..cap alpha beta.. heterodimeric protein kinase activity occurred concomitant with the reassociation into a covalent ..cap alpha../sub 2/..beta../sub 2/ heterotetrameric state. These data demonstrate that (i) a combination of alkaline pH and DTT treatment of human placenta membranes results in the formation of an ..cap alpha beta.. heterodimeric IGF-1 receptor complex, (ii) unlike the insulin receptor, high-affinity homogeneous IGF-1 binding occurs in both the ..cap alpha../sub 2/..beta../sub 2/ heterotetrameric and ..cap alpha beta.. heterodimeric complexes, and (iii) IGF-1-dependent autophosphorylation of the ..cap alpha beta.. heterodimeric IGF-1 receptor complex correlates wit an IGF-1 dependent covalent reassociation into an ..cap alpha../sub 2/..beta../sub 2/ heterotetrameric disulfide-linked state.

  18. Assessment of Human Factors

    NASA Technical Reports Server (NTRS)

    Mount, Frances; Foley, Tico

    1999-01-01

    Human Factors Engineering, often referred to as Ergonomics, is a science that applies a detailed understanding of human characteristics, capabilities, and limitations to the design, evaluation, and operation of environments, tools, and systems for work and daily living. Human Factors is the investigation, design, and evaluation of equipment, techniques, procedures, facilities, and human interfaces, and encompasses all aspects of human activity from manual labor to mental processing and leisure time enjoyments. In spaceflight applications, human factors engineering seeks to: (1) ensure that a task can be accomplished, (2) maintain productivity during spaceflight, and (3) ensure the habitability of the pressurized living areas. DSO 904 served as a vehicle for the verification and elucidation of human factors principles and tools in the microgravity environment. Over six flights, twelve topics were investigated. This study documented the strengths and limitations of human operators in a complex, multifaceted, and unique environment. By focusing on the man-machine interface in space flight activities, it was determined which designs allow astronauts to be optimally productive during valuable and costly space flights. Among the most promising areas of inquiry were procedures, tools, habitat, environmental conditions, tasking, work load, flexibility, and individual control over work.

  19. The human translation initiation multi-factor complex promotes methionyl-tRNAi binding to the 40S ribosomal subunit

    PubMed Central

    Sokabe, Masaaki; Fraser, Christopher S.; Hershey, John W. B.

    2012-01-01

    The delivery of Met-tRNAi to the 40S ribosomal subunit is thought to occur by way of a ternary complex (TC) comprising eIF2, GTP and Met-tRNAi. We have generated from purified human proteins a stable multifactor complex (MFC) comprising eIF1, eIF2, eIF3 and eIF5, similar to the MFC reported in yeast and plants. A human MFC free of the ribosome also is detected in HeLa cells and rabbit reticulocytes, indicating that it exists in vivo. In vitro, the MFC-GTP binds Met-tRNAi and delivers the tRNA to the ribosome at the same rate as the TC. However, MFC-GDP shows a greatly reduced affinity to Met-tRNAi compared to that for eIF2-GDP, suggesting that MFC components may play a role in the release of eIF2-GDP from the ribosome following AUG recognition. Since an MFC–Met-tRNAi complex is detected in cell lysates, it may be responsible for Met-tRNAi–40S ribosome binding in vivo, possibly together with the TC. However, the MFC protein components also bind individually to 40S ribosomes, creating the possibility that Met-tRNAi might bind directly to such 40S-factor complexes. Thus, three distinct pathways for Met-tRNAi delivery to the 40S ribosomal subunit are identified, but which one predominates in vivo remains to be elucidated. PMID:21940399

  20. The complexity of human ribosome biogenesis revealed by systematic nucleolar screening of Pre-rRNA processing factors.

    PubMed

    Tafforeau, Lionel; Zorbas, Christiane; Langhendries, Jean-Louis; Mullineux, Sahra-Taylor; Stamatopoulou, Vassiliki; Mullier, Romain; Wacheul, Ludivine; Lafontaine, Denis L J

    2013-08-22

    Mature ribosomal RNAs (rRNAs) are produced from polycistronic precursors following complex processing. Precursor (pre)-rRNA processing has been extensively characterized in yeast and was assumed to be conserved in humans. We functionally characterized 625 nucleolar proteins in HeLa cells and identified 286 required for processing, including 74 without a yeast homolog. For selected candidates, we demonstrated that pre-rRNA processing defects are conserved in different cell types (including primary cells), defects are not due to activation of a p53-dependent nucleolar tumor surveillance pathway, and they precede cell-cycle arrest and apoptosis. We also investigated the exosome's role in processing internal transcribed spacers (ITSs) and report that 3' end maturation of 18S rRNA involves EXOSC10/Rrp6, a yeast ITS2 processing factor. We conclude that human cells adopt unique strategies and recruit distinct trans-acting factors to carry out essential processing steps, posing fundamental implications for understanding ribosomopathies at the molecular level and developing effective therapeutic agents. PMID:23973377

  1. ISS Payload Human Factors

    NASA Technical Reports Server (NTRS)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

    The ISS Payload Human Factors Implementation Team (HFIT) is the Payload Developer's resource for Human Factors. HFIT is the interface between Payload Developers and ISS Payload Human Factors requirements in SSP 57000. ? HFIT provides recommendations on how to meet the Human Factors requirements and guidelines early in the design process. HFIT coordinates with the Payload Developer and Astronaut Office to find low cost solutions to Human Factors challenges for hardware operability issues.

  2. Inactivation of factor XIa in human plasma assessed by measuring factor XIa-protease inhibitor complexes: major role for C1-inhibitor.

    PubMed

    Wuillemin, W A; Minnema, M; Meijers, J C; Roem, D; Eerenberg, A J; Nuijens, J H; ten Cate, H; Hack, C E

    1995-03-15

    From experiments with purified proteins, it has been concluded that factor XIa (FXIa) is inhibited in plasma mainly by alpha 1-antitrypsin (a1AT), followed by antithrombin III (ATIII), C1-inhibitor (C1Inh), and alpha 2-antiplasmin (a2AP). However, the validity of this concept has never been studied in plasma. We established the relative contribution of different inhibitors to the inactivation of FXIa in human plasma, using enzyme-linked immunosorbent assays (ELISAs) for the quantification of complexes of FXIa with a1AT, C1Inh, a2AP, and ATIII. We found that 47% of FXIa added to plasma formed complexes with C1Inh, 24.5% with a2AP, 23.5% with a1AT, and 5% with ATIII. The distribution of FXIa between these inhibitors in plasma was independent of whether FXIa was added to plasma, or was activated endogenously by kaolin, celite, or glass. However, in the presence of heparin (1 or 50 U/mL), C1Inh appeared to be the major inhibitor of FXIa, followed by ATIII. Furthermore, at lower temperatures, less FXIa-C1Inh and FXIa-a1AT complexes but more FXIa-a2AP complexes were formed. These data demonstrate that the contribution of the different inhibitors to inactivation of FXIa in plasma may vary, but C1Inh is the principal inhibitor under most conditions.

  3. Statistical Factors in Complexation Reactions.

    ERIC Educational Resources Information Center

    Chung, Chung-Sun

    1985-01-01

    Four cases which illustrate statistical factors in complexation reactions (where two of the reactants are monodentate ligands) are presented. Included are tables showing statistical factors for the reactions of: (1) square-planar complexes; (2) tetrahedral complexes; and (3) octahedral complexes. (JN)

  4. Crystal structure of a TAF1-TAF7 complex in human transcription factor IID reveals a promoter binding module

    PubMed Central

    Wang, Hui; Curran, Elizabeth C; Hinds, Thomas R; Wang, Edith H; Zheng, Ning

    2014-01-01

    The general transcription factor IID (TFIID) initiates RNA polymerase II-mediated eukaryotic transcription by nucleating pre-initiation complex formation at the core promoter of protein-encoding genes. TAF1, the largest integral subunit of TFIID, contains an evolutionarily conserved yet poorly characterized central core domain, whose specific mutation disrupts cell proliferation in the temperature-sensitive mutant hamster cell line ts13. Although the impaired TAF1 function in the ts13 mutant has been associated with defective transcriptional regulation of cell cycle genes, the mechanism by which TAF1 mediates transcription as part of TFIID remains unclear. Here, we present the crystal structure of the human TAF1 central core domain in complex with another conserved TFIID subunit, TAF7, which biochemically solubilizes TAF1. The TAF1-TAF7 complex displays an inter-digitated compact architecture, featuring an unexpected TAF1 winged helix (WH) domain mounted on top of a heterodimeric triple barrel. The single TAF1 residue altered in the ts13 mutant is buried at the junction of these two structural domains. We show that the TAF1 WH domain has intrinsic DNA-binding activity, which depends on characteristic residues that are commonly used by WH fold proteins for interacting with DNA. Importantly, mutations of these residues not only compromise DNA binding by TAF1, but also abrogate its ability to rescue the ts13 mutant phenotype. Together, our results resolve the structural organization of the TAF1-TAF7 module in TFIID and unveil a critical promoter-binding function of TAF1 in transcription regulation. PMID:25412659

  5. Structure of the human factor VIII C2 domain in complex with the 3E6 inhibitory antibody

    DOE PAGESBeta

    Wuerth, Michelle E.; Cragerud, Rebecca K.; Spiegel, P. Clint

    2015-11-24

    Blood coagulation factor VIII is a glycoprotein cofactor that is essential for the intrinsic pathway of the blood coagulation cascade. Inhibitory antibodies arise either spontaneously or in response to therapeutic infusion of functional factor VIII into hemophilia A patients, many of which are specific to the factor VIII C2 domain. The immune response is largely parsed into “classical” and “non-classical” inhibitory antibodies, which bind to opposing faces cooperatively. In this study, the 2.61 Å resolution structure of the C2 domain in complex with the antigen-binding fragment of the 3E6 classical inhibitory antibody is reported. The binding interface is largely conservedmore » when aligned with the previously determined structure of the C2 domain in complex with two antibodies simultaneously. Further inspection of the B factors for the C2 domain in various X-ray crystal structures indicates that 3E6 antibody binding decreases the thermal motion behavior of surface loops in the C2 domain on the opposing face, thereby suggesting that cooperative antibody binding is a dynamic effect. Furthermore, understanding the structural nature of the immune response to factor VIII following hemophilia A treatment will help lead to the development of better therapeutic reagents.« less

  6. Structure of the human factor VIII C2 domain in complex with the 3E6 inhibitory antibody

    SciTech Connect

    Wuerth, Michelle E.; Cragerud, Rebecca K.; Spiegel, P. Clint

    2015-11-24

    Blood coagulation factor VIII is a glycoprotein cofactor that is essential for the intrinsic pathway of the blood coagulation cascade. Inhibitory antibodies arise either spontaneously or in response to therapeutic infusion of functional factor VIII into hemophilia A patients, many of which are specific to the factor VIII C2 domain. The immune response is largely parsed into “classical” and “non-classical” inhibitory antibodies, which bind to opposing faces cooperatively. In this study, the 2.61 Å resolution structure of the C2 domain in complex with the antigen-binding fragment of the 3E6 classical inhibitory antibody is reported. The binding interface is largely conserved when aligned with the previously determined structure of the C2 domain in complex with two antibodies simultaneously. Further inspection of the B factors for the C2 domain in various X-ray crystal structures indicates that 3E6 antibody binding decreases the thermal motion behavior of surface loops in the C2 domain on the opposing face, thereby suggesting that cooperative antibody binding is a dynamic effect. Furthermore, understanding the structural nature of the immune response to factor VIII following hemophilia A treatment will help lead to the development of better therapeutic reagents.

  7. Human eukaryotic initiation factor 2 (eIF2)-GTP-Met-tRNAi ternary complex and eIF3 stabilize the 43 S preinitiation complex.

    PubMed

    Sokabe, Masaaki; Fraser, Christopher S

    2014-11-14

    The formation of a stable 43 S preinitiation complex (PIC) must occur to enable successful mRNA recruitment. However, the contributions of eIF1, eIF1A, eIF3, and the eIF2-GTP-Met-tRNAi ternary complex (TC) in stabilizing the 43 S PIC are poorly defined. We have reconstituted the human 43 S PIC and used fluorescence anisotropy to systematically measure the affinity of eIF1, eIF1A, and eIF3j in the presence of different combinations of 43 S PIC components. Our data reveal a complicated network of interactions that result in high affinity binding of all 43 S PIC components with the 40 S subunit. Human eIF1 and eIF1A bind cooperatively to the 40 S subunit, revealing an evolutionarily conserved interaction. Negative cooperativity is observed between the binding of eIF3j and the binding of eIF1, eIF1A, and TC with the 40 S subunit. To overcome this, eIF3 dramatically increases the affinity of eIF1 and eIF3j for the 40 S subunit. Recruitment of TC also increases the affinity of eIF1 for the 40 S subunit, but this interaction has an important indirect role in increasing the affinity of eIF1A for the 40 S subunit. Together, our data provide a more complete thermodynamic framework of the human 43 S PIC and reveal important interactions between its components to maintain its stability.

  8. Aerospace Human Factors

    NASA Technical Reports Server (NTRS)

    Jordan, Kevin

    1999-01-01

    The following contains the final report on the activities related to the Cooperative Agreement between the human factors research group at NASA Ames Research Center and the Psychology Department at San Jose State University. The participating NASA Ames division has been, as the organization has changed, the Aerospace Human Factors Research Division (ASHFRD and Code FL), the Flight Management and Human Factors Research Division (Code AF), and the Human Factors Research and Technology Division (Code IH). The inclusive dates for the report are November 1, 1984 to January 31, 1999. Throughout the years, approximately 170 persons worked on the cooperative agreements in one capacity or another. The Cooperative Agreement provided for research personnel to collaborate with senior scientists in ongoing NASA ARC research. Finally, many post-MA/MS and post-doctoral personnel contributed to the projects. It is worth noting that 10 former cooperative agreement personnel were hired into civil service positions directly from the agreements.

  9. Introduction to human factors

    SciTech Connect

    Winters, J.M.

    1988-03-01

    Some background is given on the field of human factors. The nature of problems with current human/computer interfaces is discussed, some costs are identified, ideal attributes of graceful system interfaces are outlined, and some reasons are indicated why it's not easy to fix the problems. (LEW)

  10. Human Factors in Training

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Byme, Vicky; Arsintescu, Lucia

    2008-01-01

    Future space missions will be significantly longer than current Shuttle missions and new systems will be more complex than current systems. Increasing communication delays between crews and Earth-based support means that astronauts need to be prepared to handle the unexpected on their own. As crews become more autonomous, their potential span of control and required expertise must grow to match their autonomy. It is not possible to train for every eventuality ahead of time on the ground, or to maintain trained skills across long intervals of disuse. To adequately prepare NASA personnel for these challenges, new training approaches, methodologies, and tools are required. This research project aims at developing these training capabilities. Training efforts in FY07 strongly focused on crew medical training, but also began exploring how Space Flight Resource Management training for Mission Operations Directorate (MOD) Flight Controllers could be integrated with systems training for optimal Mission Control Center operations. Beginning in January 2008, the training research effort will include team training prototypes and tools. The Training Task addresses Program risks that lie at the intersection of the following three risks identified by the Project: 1) Risk associated with poor task design; 2) Risk of error due to inadequate information; 3) Risk associated with reduced safety and efficiency due to poor human factors design.

  11. Human Factors in Training

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Byrne, Vicky; Arsintescu, Lucia; Connell, Erin; Sandor, Aniko

    2009-01-01

    Future space missions will be significantly longer than current shuttle missions and new systems will be more complex than current systems. Increasing communication delays between crews and Earth-based support means that astronauts need to be prepared to handle the unexpected on their own. As crews become more autonomous, their potential span of control and required expertise must grow to match their autonomy. It is not possible to train for every eventuality ahead of time on the ground, or to maintain trained skills across long intervals of disuse. To adequately prepare NASA personnel for these challenges, new training approaches, methodologies, and tools are required. This research project aims at developing these training capabilities. By researching established training principles, examining future needs, and by using current practices in space flight training as test beds, both in Flight Controller and Crew Medical domains, this research project is mitigating program risks and generating templates and requirements to meet future training needs. Training efforts in Fiscal Year 08 (FY08) strongly focused on crew medical training, but also began exploring how Space Flight Resource Management training for Mission Operations Directorate (MOD) Flight Controllers could be integrated with systems training for optimal Mission Control Center (MCC) operations. The Training Task addresses Program risks that lie at the intersection of the following three risks identified by the Project: (1) Risk associated with poor task design (2) Risk of error due to inadequate information (3) Risk associated with reduced safety and efficiency due to poor human factors design

  12. Human Factors in Training

    NASA Technical Reports Server (NTRS)

    Barshi, Immanuel; Byrne, Vicky; Arsintescu, Lucia; Connell, Erin

    2010-01-01

    Future space missions will be significantly longer than current shuttle missions and new systems will be more complex than current systems. Increasing communication delays between crews and Earth-based support means that astronauts need to be prepared to handle the unexpected on their own. As crews become more autonomous, their potential span of control and required expertise must grow to match their autonomy. It is not possible to train for every eventuality ahead of time on the ground, or to maintain trained skills across long intervals of disuse. To adequately prepare NASA personnel for these challenges, new training approaches, methodologies, and tools are required. This research project aims at developing these training capabilities. By researching established training principles, examining future needs, and by using current practices in space flight training as test beds, both in Flight Controller and Crew Medical domains, this research project is mitigating program risks and generating templates and requirements to meet future training needs. Training efforts in Fiscal Year 09 (FY09) strongly focused on crew medical training, but also began exploring how Space Flight Resource Management training for Mission Operations Directorate (MOD) Flight Controllers could be integrated with systems training for optimal Mission Control Center (MCC) operations. The Training Task addresses Program risks that lie at the intersection of the following three risks identified by the Project: 1) Risk associated with poor task design; 2) Risk of error due to inadequate information; and 3) Risk associated with reduced safety and efficiency due to poor human factors design.

  13. Human STAGA complex is a chromatin-acetylating transcription coactivator that interacts with pre-mRNA splicing and DNA damage-binding factors in vivo.

    PubMed

    Martinez, E; Palhan, V B; Tjernberg, A; Lymar, E S; Gamper, A M; Kundu, T K; Chait, B T; Roeder, R G

    2001-10-01

    GCN5 is a histone acetyltransferase (HAT) originally identified in Saccharomyces cerevisiae and required for transcription of specific genes within chromatin as part of the SAGA (SPT-ADA-GCN5 acetylase) coactivator complex. Mammalian cells have two distinct GCN5 homologs (PCAF and GCN5L) that have been found in three different SAGA-like complexes (PCAF complex, TFTC [TATA-binding-protein-free TAF(II)-containing complex], and STAGA [SPT3-TAF(II)31-GCN5L acetylase]). The composition and roles of these mammalian HAT complexes are still poorly characterized. Here, we present the purification and characterization of the human STAGA complex. We show that STAGA contains homologs of most yeast SAGA components, including two novel human proteins with histone-like folds and sequence relationships to yeast SPT7 and ADA1. Furthermore, we demonstrate that STAGA has acetyl coenzyme A-dependent transcriptional coactivator functions from a chromatin-assembled template in vitro and associates in HeLa cells with spliceosome-associated protein 130 (SAP130) and DDB1, two structurally related proteins. SAP130 is a component of the splicing factor SF3b that associates with U2 snRNP and is recruited to prespliceosomal complexes. DDB1 (p127) is a UV-damaged-DNA-binding protein that is involved, as part of a complex with DDB2 (p48), in nucleotide excision repair and the hereditary disease xeroderma pigmentosum. Our results thus suggest cellular roles of STAGA in chromatin modification, transcription, and transcription-coupled processes through direct physical interactions with sequence-specific transcription activators and with components of the splicing and DNA repair machineries. PMID:11564863

  14. Activation of human factor IX (Christmas factor).

    PubMed

    Di Scipio, R G; Kurachi, K; Davie, E W

    1978-06-01

    Human Factor IX (Christmas factor) is a single-chain plasma glycoprotein (mol wt 57,000) that participates in the middle phase of the intrinsic pathway of blood coagulation. It is present in plasma as a zymogen and is converted to a serine protease, Factor IXabeta, by Factor XIa (activated plasma thromboplastin antecedent) in the presence of calcium ions. In the activation reaction, two internal peptide bonds are hydrolyzed in Factor IX. These cleavages occur at a specific arginyl-alanine peptide bond and a specific arginyl-valine peptide bond. This results in the release of an activation peptide (mol wt approximately equal to 11,000) from the internal region of the precursor molecule and the generation of Factor IXabeta (mol wt approximately equal to 46,000). Factor IXabeta is composed of a light chain (mol wt approximately equal to 18,000) and a heavy chain (mol wt approximately equal to 28,000), and these chains are held together by a disulfide bond(s). The light chain originates from the amino terminal portion of the precursor molecule and has an amino terminal sequence of Tyr-Asn-Ser-Gly-Lys. The heavy chain originates from the carboxyl terminal region of the precursor molecule and contains an amino terminal sequence of Val-Val-Gly-Gly-Glu. The heavy chain of Factor IXabeta also contains the active site sequence of Phe-Cys-Ala-Gly-Phe-His-Glu-Gly-Arg-Asp-Ser-Cys-Gln-Gly-Asp-SER-Gly-Gly-Pro. The active site serine residue is shown in capital letters. Factor IX is also converted to Factor IXaalpha by a protease from Russell's viper venom. This activation reaction, however, occurs in a single step and involves only the cleavage of the internal arginyl-valine peptide bond. Human Factor IXabeta was inhibited by human antithrombin III by the formation of a one-to-one complex of enzyme and inhibitor. In this reaction, the inhibitor was tightly bound to the heavy chain of the enzyme. These data indicate that the mechanism of activation of human Factor IX and its

  15. Human Factors Review Plan

    SciTech Connect

    Paramore, B.; Peterson, L.R.

    1985-12-01

    ''Human Factors'' is concerned with the incorporation of human user considerations into a system in order to maximize human reliability and reduce errors. This Review Plan is intended to assist in the assessment of human factors conditions in existing DOE facilities. In addition to specifying assessment methodologies, the plan describes techniques for improving conditions which are found to not adequately support reliable human performance. The following topics are addressed: (1) selection of areas for review describes techniques for needs assessment to assist in selecting and prioritizing areas for review; (2) human factors engineering review is concerned with optimizing the interfaces between people and equipment and people and their work environment; (3) procedures review evaluates completeness and accuracy of procedures, as well as their usability and management; (4) organizational interface review is concerned with communication and coordination between all levels of an organization; and (5) training review evaluates training program criteria such as those involving: trainee selection, qualification of training staff, content and conduct of training, requalification training, and program management.

  16. Abnormal immune complex processing and spontaneous glomerulonephritis in complement factor H-deficient mice with human complement receptor 1 on erythrocytes.

    PubMed

    Alexander, Jessy J; Hack, Bradley K; Jacob, Alexander; Chang, Anthony; Haas, Mark; Finberg, Robert W; Quigg, Richard J

    2010-09-15

    Complement receptor 1 (CR1) on human erythrocytes (Es) and complement factor H (CFH) on rodent platelets perform immune adherence, which is a function that allows the processing of immune complexes (ICs) bearing C3 by the mononuclear phagocyte system. Similar immune adherence occurs in the glomerular podocyte by CR1 in humans and CFH in rodents. As a model for human IC processing, we studied transgenic mice lacking CFH systemically but with human CR1 on Es. These CR1(hu)Tg/CFH(-/-) mice spontaneously developed proliferative glomerulonephritis, which was accelerated in a chronic serum sickness model by active immunization with heterologous apoferritin. ICs containing Ag, IgG and C3 bound to Es in CR1(hu)Tg/CFH(-/-) mice. In this setting, there was increased IC deposition in glomeruli, attributable to the presence of CR1 on Es, together with the absence of CFH on platelets and podocytes. In the absence of plasma CFH, the accumulated ICs activated complement, which led to spontaneous and chronic serum sickness-induced proliferative glomerulonephritis. These findings illustrate the complexities of complement-dependent IC processing by blood cells and in the glomerulus, and the importance of CFH as a plasma complement regulator.

  17. Human nonsense-mediated mRNA decay factor UPF2 interacts directly with eRF3 and the SURF complex

    PubMed Central

    López-Perrote, Andrés; Castaño, Raquel; Melero, Roberto; Zamarro, Teresa; Kurosawa, Hitomi; Ohnishi, Tetsuo; Uchiyama, Akiko; Aoyagi, Kyoko; Buchwald, Gretel; Kataoka, Naoyuki; Yamashita, Akio; Llorca, Oscar

    2016-01-01

    Nonsense-mediated mRNA decay (NMD) is an mRNA degradation pathway that regulates gene expression and mRNA quality. A complex network of macromolecular interactions regulates NMD initiation, which is only partially understood. According to prevailing models, NMD begins by the assembly of the SURF (SMG1–UPF1–eRF1–eRF3) complex at the ribosome, followed by UPF1 activation by additional factors such as UPF2 and UPF3. Elucidating the interactions between NMD factors is essential to comprehend NMD, and here we demonstrate biochemically and structurally the interaction between human UPF2 and eukaryotic release factor 3 (eRF3). In addition, we find that UPF2 associates with SURF and ribosomes in cells, in an UPF3-independent manner. Binding assays using a collection of UPF2 truncated variants reveal that eRF3 binds to the C-terminal part of UPF2. This region of UPF2 is partially coincident with the UPF3-binding site as revealed by electron microscopy of the UPF2–eRF3 complex. Accordingly, we find that the interaction of UPF2 with UPF3b interferes with the assembly of the UPF2–eRF3 complex, and that UPF2 binds UPF3b more strongly than eRF3. Together, our results highlight the role of UPF2 as a platform for the transient interactions of several NMD factors, including several components of SURF. PMID:26740584

  18. Helicopter human factors

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.

    1988-01-01

    The state-of-the-art helicopter and its pilot are examined using the tools of human-factors analysis. The significant role of human error in helicopter accidents is discussed; the history of human-factors research on helicopters is briefly traced; the typical flight tasks are described; and the noise, vibration, and temperature conditions typical of modern military helicopters are characterized. Also considered are helicopter controls, cockpit instruments and displays, and the impact of cockpit design on pilot workload. Particular attention is given to possible advanced-technology improvements, such as control stabilization and augmentation, FBW and fly-by-light systems, multifunction displays, night-vision goggles, pilot night-vision systems, night-vision displays with superimposed symbols, target acquisition and designation systems, and aural displays. Diagrams, drawings, and photographs are provided.

  19. Human Factors in Space Exploration

    NASA Technical Reports Server (NTRS)

    Jones, Patricia M.; Fiedler, Edna

    2010-01-01

    The exploration of space is one of the most fascinating domains to study from a human factors perspective. Like other complex work domains such as aviation (Pritchett and Kim, 2008), air traffic management (Durso and Manning, 2008), health care (Morrow, North, and Wickens, 2006), homeland security (Cooke and Winner, 2008), and vehicle control (Lee, 2006), space exploration is a large-scale sociotechnical work domain characterized by complexity, dynamism, uncertainty, and risk in real-time operational contexts (Perrow, 1999; Woods et ai, 1994). Nearly the entire gamut of human factors issues - for example, human-automation interaction (Sheridan and Parasuraman, 2006), telerobotics, display and control design (Smith, Bennett, and Stone, 2006), usability, anthropometry (Chaffin, 2008), biomechanics (Marras and Radwin, 2006), safety engineering, emergency operations, maintenance human factors, situation awareness (Tenney and Pew, 2006), crew resource management (Salas et aI., 2006), methods for cognitive work analysis (Bisantz and Roth, 2008) and the like -- are applicable to astronauts, mission control, operational medicine, Space Shuttle manufacturing and assembly operations, and space suit designers as they are in other work domains (e.g., Bloomberg, 2003; Bos et al, 2006; Brooks and Ince, 1992; Casler and Cook, 1999; Jones, 1994; McCurdy et ai, 2006; Neerincx et aI., 2006; Olofinboba and Dorneich, 2005; Patterson, Watts-Perotti and Woods, 1999; Patterson and Woods, 2001; Seagull et ai, 2007; Sierhuis, Clancey and Sims, 2002). The human exploration of space also has unique challenges of particular interest to human factors research and practice. This chapter provides an overview of those issues and reports on sorne of the latest research results as well as the latest challenges still facing the field.

  20. Human Factors Model

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  1. Human factors workplace considerations

    NASA Technical Reports Server (NTRS)

    Haines, Richard F.

    1988-01-01

    Computer workstations assume many different forms and play different functions today. In order for them to assume the effective interface role which they should play they must be properly designed to take into account the ubiguitous human factor. In addition, the entire workplace in which they are used should be properly configured so as to enhance the operational features of the individual workstation where possible. A number of general human factors workplace considerations are presented. This ongoing series of notes covers such topics as achieving comfort and good screen visibility, hardware issues (e.g., mouse maintenance), screen symbology features (e.g., labels, cursors, prompts), and various miscellaneous subjects. These notes are presented here in order to: (1) illustrate how one's workstation can be used to support telescience activities of many other people working within an organization, and (2) provide a single complete set of considerations for future reference.

  2. Human factors in aviation

    NASA Technical Reports Server (NTRS)

    Wiener, Earl L. (Editor); Nagel, David C. (Editor)

    1988-01-01

    The fundamental principles of human-factors (HF) analysis for aviation applications are examined in a collection of reviews by leading experts, with an emphasis on recent developments. The aim is to provide information and guidance to the aviation community outside the HF field itself. Topics addressed include the systems approach to HF, system safety considerations, the human senses in flight, information processing, aviation workloads, group interaction and crew performance, flight training and simulation, human error in aviation operations, and aircrew fatigue and circadian rhythms. Also discussed are pilot control; aviation displays; cockpit automation; HF aspects of software interfaces; the design and integration of cockpit-crew systems; and HF issues for airline pilots, general aviation, helicopters, and ATC.

  3. Helicopter Human Factors

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.; Sridhar, Banavar (Technical Monitor)

    1995-01-01

    Even under optimal conditions, helicopter flight is a most demanding form of human-machine interaction, imposing continuous manual, visual, communications, and mental demands on pilots. It is made even more challenging by small margins for error created by the close proximity of terrain in NOE flight and missions flown at night and in low visibility. Although technology advances have satisfied some current and proposed requirements, hardware solutions alone are not sufficient to ensure acceptable system performance and pilot workload. However, human factors data needed to improve the design and use of helicopters lag behind advances in sensor, display, and control technology. Thus, it is difficult for designers to consider human capabilities and limitations when making design decisions. This results in costly accidents, design mistakes, unrealistic mission requirements, excessive training costs, and challenge human adaptability. NASA, in collaboration with DOD, industry, and academia, has initiated a program of research to develop scientific data bases and design principles to improve the pilot/vehicle interface, optimize training time and cost, and maintain pilot workload and system performance at an acceptable level. Work performed at Ames, and by other research laboratories, will be reviewed to summarize the most critical helicopter human factors problems and the results of research that has been performed to: (1) Quantify/model pilots use of visual cues for vehicle control; (2) Improve pilots' performance with helmet displays of thermal imagery and night vision goggles for situation awareness and vehicle control; (3) Model the processes by which pilots encode maps and compare them to the visual scene to develop perceptually and cognitively compatible electronic map formats; (4) Evaluate the use of spatially localized auditory displays for geographical orientation, target localization, radio frequency separation; (5) Develop and flight test control

  4. Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex

    PubMed Central

    Kolumam, Ganesh; Chen, Mark Z.; Tong, Raymond; Zavala-Solorio, Jose; Kates, Lance; van Bruggen, Nicholas; Ross, Jed; Wyatt, Shelby K.; Gandham, Vineela D.; Carano, Richard A.D.; Dunshee, Diana Ronai; Wu, Ai-Luen; Haley, Benjamin; Anderson, Keith; Warming, Søren; Rairdan, Xin Y.; Lewin-Koh, Nicholas; Zhang, Yingnan; Gutierrez, Johnny; Baruch, Amos; Gelzleichter, Thomas R.; Stevens, Dale; Rajan, Sharmila; Bainbridge, Travis W.; Vernes, Jean-Michel; Meng, Y. Gloria; Ziai, James; Soriano, Robert H.; Brauer, Matthew J.; Chen, Yongmei; Stawicki, Scott; Kim, Hok Seon; Comps-Agrar, Laëtitia; Luis, Elizabeth; Spiess, Christoph; Wu, Yan; Ernst, James A.; McGuinness, Owen P.; Peterson, Andrew S.; Sonoda, Junichiro

    2015-01-01

    Dissipating excess calories as heat through therapeutic stimulation of brown adipose tissues (BAT) has been proposed as a potential treatment for obesity-linked disorders. Here, we describe the generation of a humanized effector-less bispecific antibody that activates fibroblast growth factor receptor (FGFR) 1/βKlotho complex, a common receptor for FGF21 and FGF19. Using this molecule, we show that antibody-mediated activation of FGFR1/βKlotho complex in mice induces sustained energy expenditure in BAT, browning of white adipose tissue, weight loss, and improvements in obesity-associated metabolic derangements including insulin resistance, hyperglycemia, dyslipidemia and hepatosteatosis. In mice and cynomolgus monkeys, FGFR1/βKlotho activation increased serum high-molecular-weight adiponectin, which appears to contribute over time by enhancing the amplitude of the metabolic benefits. At the same time, insulin sensitization by FGFR1/βKlotho activation occurs even before the onset of weight loss in a manner that is independent of adiponectin. Together, selective activation of FGFR1/βKlotho complex with a long acting therapeutic antibody represents an attractive approach for the treatment of type 2 diabetes and other obesity-linked disorders through enhanced energy expenditure, insulin sensitization and induction of high-molecular-weight adiponectin. PMID:26288846

  5. SARSCEST (human factors)

    NASA Technical Reports Server (NTRS)

    Parsons, H. Mcilvaine

    1988-01-01

    People interact with the processes and products of contemporary technology. Individuals are affected by these in various ways and individuals shape them. Such interactions come under the label 'human factors'. To expand the understanding of those to whom the term is relatively unfamiliar, its domain includes both an applied science and applications of knowledge. It means both research and development, with implications of research both for basic science and for development. It encompasses not only design and testing but also training and personnel requirements, even though some unwisely try to split these apart both by name and institutionally. The territory includes more than performance at work, though concentration on that aspect, epitomized in the derivation of the term ergonomics, has overshadowed human factors interest in interactions between technology and the home, health, safety, consumers, children and later life, the handicapped, sports and recreation education, and travel. Two aspects of technology considered most significant for work performance, systems and automation, and several approaches to these, are discussed.

  6. Helicopter human factors research

    NASA Technical Reports Server (NTRS)

    Nagel, David C.; Hart, Sandra G.

    1988-01-01

    Helicopter flight is among the most demanding of all human-machine integrations. The inherent manual control complexities of rotorcraft are made even more challenging by the small margin for error created in certain operations, such as nap-of-the-Earth (NOE) flight, by the proximity of the terrain. Accident data recount numerous examples of unintended conflict between helicopters and terrain and attest to the perceptual and control difficulties associated with low altitude flight tasks. Ames Research Center, in cooperation with the U.S. Army Aeroflightdynamics Directorate, has initiated an ambitious research program aimed at increasing safety margins for both civilian and military rotorcraft operations. The program is broad, fundamental, and focused on the development of scientific understandings and technological countermeasures. Research being conducted in several areas is reviewed: workload assessment, prediction, and measure validation; development of advanced displays and effective pilot/automation interfaces; identification of visual cues necessary for low-level, low-visibility flight and modeling of visual flight-path control; and pilot training.

  7. Virulence factors of the Mycobacterium tuberculosis complex

    PubMed Central

    Forrellad, Marina A.; Klepp, Laura I.; Gioffré, Andrea; Sabio y García, Julia; Morbidoni, Hector R.; Santangelo, María de la Paz; Cataldi, Angel A.; Bigi, Fabiana

    2013-01-01

    The Mycobacterium tuberculosis complex (MTBC) consists of closely related species that cause tuberculosis in both humans and animals. This illness, still today, remains to be one of the leading causes of morbidity and mortality throughout the world. The mycobacteria enter the host by air, and, once in the lungs, are phagocytated by macrophages. This may lead to the rapid elimination of the bacillus or to the triggering of an active tuberculosis infection. A large number of different virulence factors have evolved in MTBC members as a response to the host immune reaction. The aim of this review is to describe the bacterial genes/proteins that are essential for the virulence of MTBC species, and that have been demonstrated in an in vivo model of infection. Knowledge of MTBC virulence factors is essential for the development of new vaccines and drugs to help manage the disease toward an increasingly more tuberculosis-free world. PMID:23076359

  8. Fundamentals of systems ergonomics/human factors.

    PubMed

    Wilson, John R

    2014-01-01

    Ergonomics/human factors is, above anything else, a systems discipline and profession, applying a systems philosophy and systems approaches. Many things are labelled as system in today's world, and this paper specifies just what attributes and notions define ergonomics/human factors in systems terms. These are obviously a systems focus, but also concern for context, acknowledgement of interactions and complexity, a holistic approach, recognition of emergence and embedding of the professional effort involved within organization system. These six notions are illustrated with examples from a large body of work on rail human factors.

  9. Human factors challenges for advanced process control

    SciTech Connect

    Stubler, W.F.; O`Hara, J..M.

    1996-08-01

    New human-system interface technologies provide opportunities for improving operator and plant performance. However, if these technologies are not properly implemented, they may introduce new challenges to performance and safety. This paper reports the results from a survey of human factors considerations that arise in the implementation of advanced human-system interface technologies in process control and other complex systems. General trends were identified for several areas based on a review of technical literature and a combination of interviews and site visits with process control organizations. Human factors considerations are discussed for two of these areas, automation and controls.

  10. Human Factors In Aircraft Automation

    NASA Technical Reports Server (NTRS)

    Billings, Charles

    1995-01-01

    Report presents survey of state of art in human factors in automation of aircraft operation. Presents examination of aircraft automation and effects on flight crews in relation to human error and aircraft accidents.

  11. Understanding adverse events: human factors.

    PubMed Central

    Reason, J

    1995-01-01

    (1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with

  12. Understanding adverse events: human factors.

    PubMed

    Reason, J

    1995-06-01

    (1) Human rather than technical failures now represent the greatest threat to complex and potentially hazardous systems. This includes healthcare systems. (2) Managing the human risks will never be 100% effective. Human fallibility can be moderated, but it cannot be eliminated. (3) Different error types have different underlying mechanisms, occur in different parts of the organisation, and require different methods of risk management. The basic distinctions are between: Slips, lapses, trips, and fumbles (execution failures) and mistakes (planning or problem solving failures). Mistakes are divided into rule based mistakes and knowledge based mistakes. Errors (information-handling problems) and violations (motivational problems) Active versus latent failures. Active failures are committed by those in direct contact with the patient, latent failures arise in organisational and managerial spheres and their adverse effects may take a long time to become evident. (4) Safety significant errors occur at all levels of the system, not just at the sharp end. Decisions made in the upper echelons of the organisation create the conditions in the workplace that subsequently promote individual errors and violations. Latent failures are present long before an accident and are hence prime candidates for principled risk management. (5) Measures that involve sanctions and exhortations (that is, moralistic measures directed to those at the sharp end) have only very limited effectiveness, especially so in the case of highly trained professionals. (6) Human factors problems are a product of a chain of causes in which the individual psychological factors (that is, momentary inattention, forgetting, etc) are the last and least manageable links. Attentional "capture" (preoccupation or distraction) is a necessary condition for the commission of slips and lapses. Yet, its occurrence is almost impossible to predict or control effectively. The same is true of the factors associated with

  13. NASA Space Human Factors Program

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This booklet briefly and succinctly treats 23 topics of particular interest to the NASA Space Human Factors Program. Most articles are by different authors who are mainly NASA Johnson or NASA Ames personnel. Representative topics covered include mental workload and performance in space, light effects on Circadian rhythms, human sleep, human reasoning, microgravity effects and automation and crew performance.

  14. Structure of a human translation termination complex

    PubMed Central

    Matheisl, Sarah; Berninghausen, Otto; Becker, Thomas; Beckmann, Roland

    2015-01-01

    In contrast to bacteria that have two release factors, RF1 and RF2, eukaryotes only possess one unrelated release factor eRF1, which recognizes all three stop codons of the mRNA and hydrolyses the peptidyl-tRNA bond. While the molecular basis for bacterial termination has been elucidated, high-resolution structures of eukaryotic termination complexes have been lacking. Here we present a 3.8 Å structure of a human translation termination complex with eRF1 decoding a UAA(A) stop codon. The complex was formed using the human cytomegalovirus (hCMV) stalling peptide, which perturbs the peptidyltransferase center (PTC) to silence the hydrolysis activity of eRF1. Moreover, unlike sense codons or bacterial stop codons, the UAA stop codon adopts a U-turn-like conformation within a pocket formed by eRF1 and the ribosome. Inducing the U-turn conformation for stop codon recognition rationalizes how decoding by eRF1 includes monitoring geometry in order to discriminate against sense codons. PMID:26384426

  15. Teleoperator Human Factors Study

    NASA Technical Reports Server (NTRS)

    1986-01-01

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

  16. Modeling the human prothrombinase complex components

    NASA Astrophysics Data System (ADS)

    Orban, Tivadar

    Thrombin generation is the culminating stage of the blood coagulation process. Thrombin is obtained from prothrombin (the substrate) in a reaction catalyzed by the prothrombinase complex (the enzyme). The prothrombinase complex is composed of factor Xa (the enzyme), factor Va (the cofactor) associated in the presence of calcium ions on a negatively charged cell membrane. Factor Xa, alone, can activate prothrombin to thrombin; however, the rate of conversion is not physiologically relevant for survival. Incorporation of factor Va into prothrombinase accelerates the rate of prothrombinase activity by 300,000-fold, and provides the physiological pathway of thrombin generation. The long-term goal of the current proposal is to provide the necessary support for the advancing of studies to design potential drug candidates that may be used to avoid development of deep venous thrombosis in high-risk patients. The short-term goals of the present proposal are to (1) to propose a model of a mixed asymmetric phospholipid bilayer, (2) expand the incomplete model of human coagulation factor Va and study its interaction with the phospholipid bilayer, (3) to create a homology model of prothrombin (4) to study the dynamics of interaction between prothrombin and the phospholipid bilayer.

  17. DSN human factors project

    NASA Technical Reports Server (NTRS)

    Chafin, R. L.; Martin, T. H.

    1980-01-01

    The project plan was to hold focus groups to identify the factors influencing the ease of use characteristics of software and to bond the problem. A questionnaire survey was conducted to evaluate those factors which were more appropriately measured with that method. The performance oriented factors were analyzed and relationships hypothesized. The hypotheses were put to test in the experimental phase of the project. In summary, the initial analysis indicates that there is an initial performance effect favoring computer controlled dialogue but the advantage fades fast as operators become experienced. The user documentation style is seen to have a significant effect on performance. The menu and prompt command formats are preferred by inexperienced operators. The short form mnemonic is least favored. There is no clear best command format but the short form mnemonic is clearly the worst.

  18. The genetic basis of complex human behaviors.

    PubMed

    Plomin, R; Owen, M J; McGuffin, P

    1994-06-17

    Quantitative genetic research has built a strong case for the importance of genetic factors in many complex behavioral disorders and dimensions in the domains of psychopathology, personality, and cognitive abilities. Quantitative genetics can also provide an empirical guide and a conceptual framework for the application of molecular genetics. The success of molecular genetics in elucidating the genetic basis of behavioral disorders has largely relied on a reductionistic one gene, one disorder (OGOD) approach in which a single gene is necessary and sufficient to develop a disorder. In contrast, a quantitative trait loci (QTL) approach involves the search for multiple genes, each of which is neither necessary nor sufficient for the development of a trait. The OGOD and QTL approaches have both advantages and disadvantages for identifying genes that affect complex human behaviors.

  19. Human factors of visual displays

    NASA Technical Reports Server (NTRS)

    Snyder, H. L.

    1984-01-01

    Several human factors issues in visual displays are addressed in this report. They are as follows: (1) the importance of luminance range and contrast; (2) uniformity of visual displays; (3) image quality; (4) color contrast; and (5) dot matrix fonts.

  20. In vitro synthesis of human protein synthesis initiation factor 4 gamma and its localization on 43 and 48 S initiation complexes.

    PubMed

    Joshi, B; Yan, R; Rhoads, R E

    1994-01-21

    The rate of protein synthesis is controlled in a large number of physiological situations at the stage of 48 S initiation complex formation, a phase that involves the recruitment of mRNA to the 40 S ribosomal subunit. This process is mediated by the eukaryotic initiation factor-4 (eIF-4) group of translation initiation factors consisting of eIF-4E, eIF-4A, eIF-4B, and eIF-4 gamma. In order to develop a new tool to study this process, we have produced radiolabeled eIF-4 gamma by in vitro transcription and translation. Despite the fact that eIF-4 gamma is predicted from the cDNA sequence to be 154 kDa, the major synthetic product migrated on SDS-polyacrylamide gel electrophoresis at 205 kDa. Although this is similar to the migration of the fastest polypeptide of authentic eIF-4 gamma (approximately 206 kDa), no products were found to co-migrate with the slowest forms of authentic eIF-4 gamma (210-220 kDa), suggesting that these forms derive from extensive modification of the initial polypeptide. The in vitro product also formed a complex with eIF-4E, as judged by its ability to bind to m7GTP-Sepharose. Sucrose gradient sedimentation studies demonstrated that eIF-4 gamma was present on both 43 and 48 S initiation complexes but not 80 S complexes. This supports a model in which free eIF-4E binds to mRNA followed by binding of the eIF-4E.mRNA complex to a 43 S initiation complex already containing eIF-4 gamma.

  1. Reconstitution of the human cytoplasmic dynein complex.

    PubMed

    Trokter, Martina; Mücke, Norbert; Surrey, Thomas

    2012-12-18

    Cytoplasmic dynein is the major motor protein responsible for microtubule minus-end-directed movements in most eukaryotic cells. It transports a variety of cargoes and has numerous functions during spindle assembly and chromosome segregation. It is a large complex of about 1.4 MDa composed of six different subunits, interacting with a multitude of different partners. Most biochemical studies have been performed either with the native mammalian cytoplasmic dynein complex purified from tissue or, more recently, with recombinant dynein fragments from budding yeast and Dictyostelium. Hardly any information exists about the properties of human dynein. Moreover, experiments with an entire human dynein complex prepared from recombinant subunits with a well-defined composition are lacking. Here, we reconstitute a complete cytoplasmic dynein complex using recombinant human subunits and characterize its biochemical and motile properties. Using analytical gel filtration, sedimentation-velocity ultracentrifugation, and negative-stain electron microscopy, we demonstrate that the smaller subunits of the complex have an important structural function for complex integrity. Fluorescence microscopy experiments reveal that while engaged in collective microtubule transport, the recombinant human cytoplasmic dynein complex is an active, microtubule minus-end-directed motor, as expected. However, in contrast to recombinant dynein of nonmetazoans, individual reconstituted human dynein complexes did not show robust processive motility, suggesting a more intricate mechanism of processivity regulation for the human dynein complex. In the future, the comparison of reconstituted dynein complexes from different species promises to provide molecular insight into the mechanisms regulating the various functions of these large molecular machines.

  2. Space operations and the human factor

    NASA Astrophysics Data System (ADS)

    Brody, Adam R.

    1993-10-01

    Although space flight does not put the public at high risk, billions of dollars in hardware are destroyed and the space program halted when an accident occurs. Researchers are therefore applying human-factors techniques similar to those used in the aircraft industry, albeit at a greatly reduced level, to the spacecraft environment. The intent is to reduce the likelihood of catastrophic failure. To increase safety and efficiency, space human factors researchers have simulated spacecraft docking and extravehicular activity rescue. Engineers have also studied EVA suit mobility and aids. Other basic human-factors issues that have been applied to the space environment include antropometry, biomechanics, and ergonomics. Workstation design, workload, and task analysis currently receive much attention, as do habitability and other aspects of confined environments. Much work also focuses on individual payloads, as each presents its own complexities.

  3. New Anthocyanin-Human Salivary Protein Complexes.

    PubMed

    Ferrer-Gallego, Raúl; Soares, Susana; Mateus, Nuno; Rivas-Gonzalo, Julián; Escribano-Bailón, M Teresa; de Freitas, Victor

    2015-08-01

    The interaction between phenolic compounds and salivary proteins is considered the basis of the poorly understood phenomenon of astringency. Furthermore, this interaction is an important factor in relation to their bioavailability. In this work, interactions between anthocyanin and human salivary protein fraction were studied by mass spectrometry (MALDI-TOF-MS and FIA-ESI-MS) and saturation-transfer difference (STD) NMR spectroscopy. Anthocyanins were able to interact with saliva proteins. The dissociation constant (KD) between malvidin 3-glucoside and salivary proline-rich proteins was 1.92 mM for the hemiketal form (pH 3.4) and 1.83 mM for the flavylium cation (pH 1.0). New soluble complexes between these salivary proteins and malvidin 3-glucoside were identified for the first time.

  4. Human factors in underwater systems.

    PubMed

    Crosson, D

    1993-10-01

    Applications of human factors to undersea engineering and the relationship to aerospace science are explored. Cooperative ventures include the TEKTITE underwater habitat and development of better procedures to prevent decompression sickness. Other research involved the use of alternate gases in diving systems, remote-operation vehicles, and diving system tests.

  5. HUMAN PROSTATE CANCER RISK FACTORS

    EPA Science Inventory

    Prostate cancer has the highest prevalence of any non-skin cancer in the human body, with similar likelihood of neoplastic foci found within the prostates of men around the world regardless of diet, occupation, lifestyle, or other factors. Essentially all men with circulating an...

  6. Human factors in software development

    SciTech Connect

    Curtis, B.

    1986-01-01

    This book presents an overview of ergonomics/human factors in software development, recent research, and classic papers. Articles are drawn from the following areas of psychological research on programming: cognitive ergonomics, cognitive psychology, and psycholinguistics. Topics examined include: theoretical models of how programmers solve technical problems, the characteristics of programming languages, specification formats in behavioral research and psychological aspects of fault diagnosis.

  7. Human factors in underwater systems.

    PubMed

    Crosson, D

    1993-10-01

    Applications of human factors to undersea engineering and the relationship to aerospace science are explored. Cooperative ventures include the TEKTITE underwater habitat and development of better procedures to prevent decompression sickness. Other research involved the use of alternate gases in diving systems, remote-operation vehicles, and diving system tests. PMID:11541030

  8. Human Factors in Financial Trading

    PubMed Central

    Leaver, Meghan; Reader, Tom W.

    2016-01-01

    Objective This study tests the reliability of a system (FINANS) to collect and analyze incident reports in the financial trading domain and is guided by a human factors taxonomy used to describe error in the trading domain. Background Research indicates the utility of applying human factors theory to understand error in finance, yet empirical research is lacking. We report on the development of the first system for capturing and analyzing human factors–related issues in operational trading incidents. Method In the first study, 20 incidents are analyzed by an expert user group against a referent standard to establish the reliability of FINANS. In the second study, 750 incidents are analyzed using distribution, mean, pathway, and associative analysis to describe the data. Results Kappa scores indicate that categories within FINANS can be reliably used to identify and extract data on human factors–related problems underlying trading incidents. Approximately 1% of trades (n = 750) lead to an incident. Slip/lapse (61%), situation awareness (51%), and teamwork (40%) were found to be the most common problems underlying incidents. For the most serious incidents, problems in situation awareness and teamwork were most common. Conclusion We show that (a) experts in the trading domain can reliably and accurately code human factors in incidents, (b) 1% of trades incur error, and (c) poor teamwork skills and situation awareness underpin the most critical incidents. Application This research provides data crucial for ameliorating risk within financial trading organizations, with implications for regulation and policy. PMID:27142394

  9. Intestinal trefoil factor controls the expression of the adenomatous polyposis coli-catenin and the E-cadherin-catenin complexes in human colon carcinoma cells.

    PubMed

    Efstathiou, J A; Noda, M; Rowan, A; Dixon, C; Chinery, R; Jawhari, A; Hattori, T; Wright, N A; Bodmer, W F; Pignatelli, M

    1998-03-17

    Intestinal trefoil factor 3 (TFF3) is a member of the trefoil family of peptides, small molecules constitutively expressed in epithelial tissues, including the gastrointestinal tract. TFF3 has been shown to promote migration of intestinal epithelial cells in vitro and to enhance mucosal healing and epithelial restitution in vivo. In this study, we evaluated the effect of recombinant TFF3 (rTFF3) stimulation on the expression and cellular localization of the epithelial (E)-cadherin-catenin complex, a prime mediator of Ca2+ dependent cell-cell adhesion, and the adenomatous polyposis coli (APC)-catenin complex in HT29, HCT116, and SW480 colorectal carcinoma cell lines. Stimulation by rTFF3 (10(-9) M and 10(-8) M) for 20-24 hr led to cell detachment and to a reduction in intercellular adhesion in HT29 and HCT116 cells. In both cell lines, E-cadherin expression was down-regulated. The expression of APC, alpha-catenin and beta-catenin also was decreased in HT29 cells, with a translocation of APC into the nucleus. No change in either cell adhesion or in the expression of E-cadherin, the catenins, and APC was detected in SW480 cells. In addition, TFF3 induced DNA fragmentation and morphological changes characteristic of apoptosis in HT29. Tyrphostin, a competitive inhibitor of protein tyrosine kinases, inhibited the effects of TFF3. Our results indicate that by perturbing the complexes between E-cadherin, beta-catenin, and associated proteins, TFF3 may modulate epithelial cell adhesion, migration, and survival.

  10. Environmental Factors Inducing Human Cancers

    PubMed Central

    Parsa, N

    2012-01-01

    Background An explosion of research has been done in discovering how human health is affected by environmental factors. I will discuss the impacts of environmental cancer causing factors and how they continue to cause multiple disruptions in cellular networking. Some risk factors may not cause cancer. Other factors initiate consecutive genetic mutations that would eventually alter the normal pathway of cellular proliferations and differentiation. Genetic mutations in four groups of genes; (Oncogenes, Tumor suppressor genes, Apoptosis genes and DNA repairing genes) play a vital role in altering the normal cell division. In recent years, molecular genetics have greatly increased our understanding of the basic mechanisms in cancer development and utilizing these molecular techniques for cancer screening, diagnosis, prognosis and therapies. Inhibition of carcinogenic exposures wherever possible should be the goal of cancer prevention programs to reduce exposures from all environmental carcinogens. PMID:23304670

  11. Human factors in spacecraft design.

    PubMed

    Harrison, A A; Connors, M M

    1990-01-01

    This paper describes some of the salient implications of evolving mission parameters for spacecraft design. Among the requirements for future spacecraft are new, higher standards of living, increased support of human productivity, and greater accommodation of physical and cultural variability. Design issues include volumetric allowances, architecture and layouts, closed life support systems, health maintenance systems, recreational facilities, automation, privacy, and decor. An understanding of behavioral responses to design elements is a precondition for critical design decisions. Human factors research results must be taken into account early in the course of the design process.

  12. Human factors in spacecraft design

    NASA Technical Reports Server (NTRS)

    Harrison, Albert A.; Connors, Mary M.

    1990-01-01

    This paper describes some of the salient implications of evolving mission parameters for spacecraft design. Among the requirements for future spacecraft are new, higher standards of living, increased support of human productivity, and greater accommodation of physical and cultural variability. Design issues include volumetric allowances, architecture and layouts, closed life support systems, health maintenance systems, recreational facilities, automation, privacy, and decor. An understanding of behavioral responses to design elements is a precondition for critical design decisions. Human factors research results must be taken into account early in the course of the design process.

  13. Approaching human language with complex networks

    NASA Astrophysics Data System (ADS)

    Cong, Jin; Liu, Haitao

    2014-12-01

    The interest in modeling and analyzing human language with complex networks is on the rise in recent years and a considerable body of research in this area has already been accumulated. We survey three major lines of linguistic research from the complex network approach: 1) characterization of human language as a multi-level system with complex network analysis; 2) linguistic typological research with the application of linguistic networks and their quantitative measures; and 3) relationships between the system-level complexity of human language (determined by the topology of linguistic networks) and microscopic linguistic (e.g., syntactic) features (as the traditional concern of linguistics). We show that the models and quantitative tools of complex networks, when exploited properly, can constitute an operational methodology for linguistic inquiry, which contributes to the understanding of human language and the development of linguistics. We conclude our review with suggestions for future linguistic research from the complex network approach: 1) relationships between the system-level complexity of human language and microscopic linguistic features; 2) expansion of research scope from the global properties to other levels of granularity of linguistic networks; and 3) combination of linguistic network analysis with other quantitative studies of language (such as quantitative linguistics).

  14. Approaching human language with complex networks.

    PubMed

    Cong, Jin; Liu, Haitao

    2014-12-01

    The interest in modeling and analyzing human language with complex networks is on the rise in recent years and a considerable body of research in this area has already been accumulated. We survey three major lines of linguistic research from the complex network approach: 1) characterization of human language as a multi-level system with complex network analysis; 2) linguistic typological research with the application of linguistic networks and their quantitative measures; and 3) relationships between the system-level complexity of human language (determined by the topology of linguistic networks) and microscopic linguistic (e.g., syntactic) features (as the traditional concern of linguistics). We show that the models and quantitative tools of complex networks, when exploited properly, can constitute an operational methodology for linguistic inquiry, which contributes to the understanding of human language and the development of linguistics. We conclude our review with suggestions for future linguistic research from the complex network approach: 1) relationships between the system-level complexity of human language and microscopic linguistic features; 2) expansion of research scope from the global properties to other levels of granularity of linguistic networks; and 3) combination of linguistic network analysis with other quantitative studies of language (such as quantitative linguistics).

  15. Approaching human language with complex networks.

    PubMed

    Cong, Jin; Liu, Haitao

    2014-12-01

    The interest in modeling and analyzing human language with complex networks is on the rise in recent years and a considerable body of research in this area has already been accumulated. We survey three major lines of linguistic research from the complex network approach: 1) characterization of human language as a multi-level system with complex network analysis; 2) linguistic typological research with the application of linguistic networks and their quantitative measures; and 3) relationships between the system-level complexity of human language (determined by the topology of linguistic networks) and microscopic linguistic (e.g., syntactic) features (as the traditional concern of linguistics). We show that the models and quantitative tools of complex networks, when exploited properly, can constitute an operational methodology for linguistic inquiry, which contributes to the understanding of human language and the development of linguistics. We conclude our review with suggestions for future linguistic research from the complex network approach: 1) relationships between the system-level complexity of human language and microscopic linguistic features; 2) expansion of research scope from the global properties to other levels of granularity of linguistic networks; and 3) combination of linguistic network analysis with other quantitative studies of language (such as quantitative linguistics). PMID:24794524

  16. Human Factors Inputs to the Training Device Design Process.

    ERIC Educational Resources Information Center

    Smode, Alfred F.

    Guidelines are presented for achieving human factors inputs to the design of synthetic training systems. A method is developed for design and organization of training concepts and data supportive to the human factors specialist in deriving the functional specifications for the design of any complex training device. Three major sections are…

  17. Consanguinity, human evolution, and complex diseases

    PubMed Central

    Bittles, A. H.; Black, M. L.

    2010-01-01

    There is little information on inbreeding during the critical early years of human existence. However, given the small founding group sizes and restricted mate choices it seems inevitable that intrafamilial reproduction occurred and the resultant levels of inbreeding would have been substantial. Currently, couples related as second cousins or closer (F ≥ 0.0156) and their progeny account for an estimated 10.4% of the global population. The highest rates of consanguineous marriage occur in north and sub-Saharan Africa, the Middle East, and west, central, and south Asia. In these regions even couples who regard themselves as unrelated may exhibit high levels of homozygosity, because marriage within clan, tribe, caste, or biraderi boundaries has been a long-established tradition. Mortality in first-cousin progeny is ≈3.5% higher than in nonconsanguineous offspring, although demographic, social, and economic factors can significantly influence the outcome. Improving socioeconomic conditions and better access to health care will impact the effects of consanguinity, with a shift from infant and childhood mortality to extended morbidity. At the same time, a range of primarily social factors, including urbanization, improved female education, and smaller family sizes indicate that the global prevalence of consanguineous unions will decline. This shift in marriage patterns will initially result in decreased homozygosity, accompanied by a reduction in the expression of recessive single-gene disorders. Although the roles of common and rare gene variants in the etiology of complex disease remain contentious, it would be expected that declining consanguinity would also be reflected in reduced prevalence of complex diseases, especially in population isolates. PMID:19805052

  18. 14 CFR 460.15 - Human factors.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Human factors. 460.15 Section 460.15... TRANSPORTATION LICENSING HUMAN SPACE FLIGHT REQUIREMENTS Launch and Reentry with Crew § 460.15 Human factors. An operator must take the precautions necessary to account for human factors that can affect a crew's...

  19. 14 CFR 460.15 - Human factors.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 4 2011-01-01 2011-01-01 false Human factors. 460.15 Section 460.15... TRANSPORTATION LICENSING HUMAN SPACE FLIGHT REQUIREMENTS Launch and Reentry with Crew § 460.15 Human factors. An operator must take the precautions necessary to account for human factors that can affect a crew's...

  20. 14 CFR 460.15 - Human factors.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 14 Aeronautics and Space 4 2014-01-01 2014-01-01 false Human factors. 460.15 Section 460.15... TRANSPORTATION LICENSING HUMAN SPACE FLIGHT REQUIREMENTS Launch and Reentry with Crew § 460.15 Human factors. An operator must take the precautions necessary to account for human factors that can affect a crew's...

  1. 14 CFR 460.15 - Human factors.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 4 2012-01-01 2012-01-01 false Human factors. 460.15 Section 460.15... TRANSPORTATION LICENSING HUMAN SPACE FLIGHT REQUIREMENTS Launch and Reentry with Crew § 460.15 Human factors. An operator must take the precautions necessary to account for human factors that can affect a crew's...

  2. 14 CFR 460.15 - Human factors.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 14 Aeronautics and Space 4 2013-01-01 2013-01-01 false Human factors. 460.15 Section 460.15... TRANSPORTATION LICENSING HUMAN SPACE FLIGHT REQUIREMENTS Launch and Reentry with Crew § 460.15 Human factors. An operator must take the precautions necessary to account for human factors that can affect a crew's...

  3. Human factors engineering of enhanced spaceport procedures

    NASA Astrophysics Data System (ADS)

    Kanki, Barbara G.; Barth, Tim; Blankmann-Alexander, Donna; Parker, D. Blake; Coan, Hester

    2001-02-01

    Because operational procedures provide a first line of defense against human error, human-centered design is key for streamlining work processes, standardizing work practices, and providing invaluable reminders and cautions during high risk, complex operations. In contrast, inaccurate or poorly designed operational procedures and documentation can impede the work process, encourage unsafe work practices, and confuse or mislead operators during safety critical steps. In response to several internal KSC studies that concluded that operational procedures (work instructions) were the leading contributors to Shuttle ground processing incidents and inefficiencies, the Shuttle Work Instruction Task Team (WITT) was chartered to develop a vision for a new work instruction system. This paper describes some of the original WITT recommendations and activities, as well as collaborative human factors engineering projects supporting the WITT efforts. Past achievements as well as ongoing and planned initiatives to provide continued support for the enhancement of spaceport procedures are described. .

  4. Elimination capacity of a TSE-model agent in the manufacturing process of Alphanate/Fanhdi, a human factor VIII/VWF complex concentrate.

    PubMed

    Diez, J M; Caballero, S; Belda, F J; Otegui, M; Gajardo, R; Jorquera, J I

    2009-11-01

    The variant Creutzfeldt-Jakob disease (vCJD) is a transmissible spongiform encephalopathy (TSE), mainly present in the UK and is associated with the ingestion of bovine products affected with bovine spongiform encephalopathy. Manufacturers of biological products must investigate the ability of their production processes to remove TSE agents. We studied the purification steps in the manufacturing process of two FVIII/VWF concentrates (Alphanate) and Fanhdi in their ability to eliminate an experimental TSE-model agent. Hamster scrapie strain 263K brain-derived materials were spiked into samples of the solutions taken before various stages during its production: 3.5% polyethylene glycol (PEG) precipitation, heparin affinity chromatography and saline precipitation/final filtrations. PEG precipitation and affinity chromatography were studied both as isolated and combined steps. TSE agent removal was determined using a laboratory scale model representative of the industrial manufacturing process. The prion protein (PrP(Sc)) was measured with Western blot and TSE infectivity was measured with bioassay. Western blot results were in agreement with those obtained by bioassay, showing a significant removal capacity in the production process: 3.21-3.43 log(10) for the PEG precipitation; about 3.45 log(10) for the affinity chromatography; and around 2.0 log(10) for the saline precipitation plus final filtrations. PEG precipitation and heparin affinity chromatography were demonstrated to be two complementary TSE-model agent removal mechanisms with total removal being the sum of the two. An overall reduction factor of around 8 log(10) can be deduced. The tests from the production process of FVIII/VWF complex concentrates have demonstrated their potential for eliminating TSE agents.

  5. Elimination capacity of a TSE-model agent in the manufacturing process of Alphanate/Fanhdi, a human factor VIII/VWF complex concentrate.

    PubMed

    Diez, J M; Caballero, S; Belda, F J; Otegui, M; Gajardo, R; Jorquera, J I

    2009-11-01

    The variant Creutzfeldt-Jakob disease (vCJD) is a transmissible spongiform encephalopathy (TSE), mainly present in the UK and is associated with the ingestion of bovine products affected with bovine spongiform encephalopathy. Manufacturers of biological products must investigate the ability of their production processes to remove TSE agents. We studied the purification steps in the manufacturing process of two FVIII/VWF concentrates (Alphanate) and Fanhdi in their ability to eliminate an experimental TSE-model agent. Hamster scrapie strain 263K brain-derived materials were spiked into samples of the solutions taken before various stages during its production: 3.5% polyethylene glycol (PEG) precipitation, heparin affinity chromatography and saline precipitation/final filtrations. PEG precipitation and affinity chromatography were studied both as isolated and combined steps. TSE agent removal was determined using a laboratory scale model representative of the industrial manufacturing process. The prion protein (PrP(Sc)) was measured with Western blot and TSE infectivity was measured with bioassay. Western blot results were in agreement with those obtained by bioassay, showing a significant removal capacity in the production process: 3.21-3.43 log(10) for the PEG precipitation; about 3.45 log(10) for the affinity chromatography; and around 2.0 log(10) for the saline precipitation plus final filtrations. PEG precipitation and heparin affinity chromatography were demonstrated to be two complementary TSE-model agent removal mechanisms with total removal being the sum of the two. An overall reduction factor of around 8 log(10) can be deduced. The tests from the production process of FVIII/VWF complex concentrates have demonstrated their potential for eliminating TSE agents. PMID:19563480

  6. Human Factors Considerations in System Design

    NASA Technical Reports Server (NTRS)

    Mitchell, C. M. (Editor); Vanbalen, P. M. (Editor); Moe, K. L. (Editor)

    1983-01-01

    Human factors considerations in systems design was examined. Human factors in automated command and control, in the efficiency of the human computer interface and system effectiveness are outlined. The following topics are discussed: human factors aspects of control room design; design of interactive systems; human computer dialogue, interaction tasks and techniques; guidelines on ergonomic aspects of control rooms and highly automated environments; system engineering for control by humans; conceptual models of information processing; information display and interaction in real time environments.

  7. Human factors in space telepresence

    NASA Technical Reports Server (NTRS)

    Akin, D. L.; Howard, R. D.; Oliveria, J. S.

    1983-01-01

    The problems of interfacing a human with a teleoperation system, for work in space are discussed. Much of the information presented here is the result of experience gained by the M.I.T. Space Systems Laboratory during the past two years of work on the ARAMIS (Automation, Robotics, and Machine Intelligence Systems) project. Many factors impact the design of the man-machine interface for a teleoperator. The effects of each are described in turn. An annotated bibliography gives the key references that were used. No conclusions are presented as a best design, since much depends on the particular application desired, and the relevant technology is swiftly changing.

  8. Proteomic characterization of the human FTSJ3 preribosomal complexes.

    PubMed

    Simabuco, Fernando M; Morello, Luis G; Aragão, Annelize Zambon Barbosa; Paes Leme, Adriana Franco; Zanchin, Nilson I T

    2012-06-01

    In eukaryotes, ribosome biogenesis involves excision of transcribed spacer sequences from the preribosomal RNA, base and ribose covalent modification at specific sites, assembly of ribosomal proteins, and transport of subunits from the nucleolus to the cytoplasm where mature ribosomes engage in mRNA translation. The biochemical reactions throughout ribosome synthesis are mediated by factors that associate transiently to the preribosomal complexes. In this work, we describe the complexes containing the human protein FTSJ3. This protein functions in association with NIP7 in ribosome synthesis and contains a putative RNA-methyl-transferase domain (FtsJ) in the N-terminal region and two uncharacterized domains in the central (DUF3381) and C-terminal (Spb1_C) regions. FLAG-tagged FTSJ3 coimmunoprecipitates both RPS and RPL proteins, ribosome synthesis factors, and proteins whose function in ribosome synthesis has not been demonstrated yet. A similar set of proteins coimmunoprecipitates with the Spb1_C domain, suggesting that FTSJ3 interaction with the preribosome complexes is mediated by the Spb1_C domain. Approximately 50% of the components of FTSJ3 complexes are shared by complexes described for RPS19, Par14, nucleolin, and NOP56. A significant number of factors are also found in complexes described for nucleophosmin, SBDS, ISG20L2, and NIP7. These findings provide information on the dynamics of preribosome complexes in human cells.

  9. A human transcription factor in search mode

    PubMed Central

    Hauser, Kevin; Essuman, Bernard; He, Yiqing; Coutsias, Evangelos; Garcia-Diaz, Miguel; Simmerling, Carlos

    2016-01-01

    Transcription factors (TF) can change shape to bind and recognize DNA, shifting the energy landscape from a weak binding, rapid search mode to a higher affinity recognition mode. However, the mechanism(s) driving this conformational change remains unresolved and in most cases high-resolution structures of the non-specific complexes are unavailable. Here, we investigate the conformational switch of the human mitochondrial transcription termination factor MTERF1, which has a modular, superhelical topology complementary to DNA. Our goal was to characterize the details of the non-specific search mode to complement the crystal structure of the specific binding complex, providing a basis for understanding the recognition mechanism. In the specific complex, MTERF1 binds a significantly distorted and unwound DNA structure, exhibiting a protein conformation incompatible with binding to B-form DNA. In contrast, our simulations of apo MTERF1 revealed significant flexibility, sampling structures with superhelical pitch and radius complementary to the major groove of B-DNA. Docking these structures to B-DNA followed by unrestrained MD simulations led to a stable complex in which MTERF1 was observed to undergo spontaneous diffusion on the DNA. Overall, the data support an MTERF1-DNA binding and recognition mechanism driven by intrinsic dynamics of the MTERF1 superhelical topology. PMID:26673724

  10. Human Factors Checklist: Think Human Factors - Focus on the People

    NASA Technical Reports Server (NTRS)

    Miller, Darcy; Stelges, Katrine; Barth, Timothy; Stambolian, Damon; Henderson, Gena; Dischinger, Charles; Kanki, Barbara; Kramer, Ian

    2016-01-01

    A quick-look Human Factors (HF) Checklist condenses industry and NASA Agency standards consisting of thousands of requirements into 14 main categories. With support from contractor HF and Safety Practitioners, NASA developed a means to share key HF messages with Design, Engineering, Safety, Project Management, and others. It is often difficult to complete timely assessments due to the large volume of HF information. The HF Checklist evolved over time into a simple way to consider the most important concepts. A wide audience can apply the checklist early in design or through planning phases, even before hardware or processes are finalized or implemented. The checklist is a good place to start to supplement formal HF evaluation. The HF Checklist was based on many Space Shuttle processing experiences and lessons learned. It is now being applied to ground processing of new space vehicles and adjusted for new facilities and systems.

  11. A comparison of human prothrombin, factor IX (Christmas factor), factor X (Stuart factor), and protein S.

    PubMed

    Di Scipio, R G; Hermodson, M A; Yates, S G; Davie, E W

    1977-02-22

    Human prothrombin, factor IX, and factor X have been idolated in high yield and characterized as the their amino-terminal sequence, molecular weight, amino acid composition, and migration in sodium dodecyl sulfate-polyacrylamide gel electrophoresis. An additional human plasma protein, called protein S, has also been purified and its properties have been compared with those of prothrombin, factor IX, and factor X. Prothrombin (mol wt 72 000), factor IX (mol wt 57 000), and protein S (mol wt 69 000) are single-chain glycoproteins, while factor X (mol wt 59 000) is a glycoprotein composed of two polypeptide chains held together by a disulfide bond(s). The amino-terminal sequence of the light chain of human factor X is homologous with prothrombin, factor IX, and protein S. The heavy chain of human factor X is slightly larger than the heavy chain of bovine factor X and differs from bovine factor X in its amino-terminal sequence.

  12. Human Factors in Human-Systems Integration

    NASA Technical Reports Server (NTRS)

    Fitts, David J.; Sandor, Aniko; Litaker, Harry L., Jr.; Tillman, Barry

    2008-01-01

    Any large organization whose mission is to design and develop systems for humans, and train humans needs a well-developed integration and process plan to deal with the challenges that arise from managing multiple subsystems. Human capabilities, skills, and needs must be considered early in the design and development process, and must be continuously considered throughout the development lifecycle. This integration of human needs within system design is typically formalized through a Human-Systems Integration (HSI) program. By having an HSI program, an institution or organization can reduce lifecycle costs and increase the efficiency, usability, and quality of its products because human needs have been considered from the beginning.

  13. Step Complexity Measure for Emergency Operating Procedures - Determining Weighting Factors

    SciTech Connect

    Park, Jinkyun; Jung, Wondea; Kim, Jaewhan; Ha, Jaejoo

    2003-09-15

    In complex systems, such as nuclear power plants (NPPs) or airplane control systems, human error has been regarded as the primary cause of many events. Therefore, to ensure system safety, extensive effort has been made to identify the significant factors that can cause human error. According to related studies, written manuals or operating procedures are revealed as one of the important factors, and the understandability is pointed out as one of the major reasons for procedure-related human errors.Many qualitative checklists have been suggested to evaluate emergency operating procedures (EOPs) of NPPs so as to minimize procedure-related human errors. However, since qualitative evaluations using checklists have some drawbacks, a quantitative measure that can quantify the complexity of EOPs is indispensable.From this necessity, Park et al. suggested the step complexity (SC) measure to quantify the complexity of procedural steps included in EOPs. To verify the appropriateness of the SC measure, averaged step performance time data obtained from emergency training records of the loss-of-coolant accident (LOCA) and the excess steam demand event were compared with estimated SC scores. However, although averaged step performance time data and estimated SC scores show meaningful correlation, some important issues such as determining proper weighting factors have to be clarified to ensure the appropriateness of the SC measure. These were not properly dealt with due to a lack of backup data.In this paper, to resolve one of the important issues, emergency training records are additionally collected and analyzed in order to determine proper weighting factors. The total number of collected records is 66, and the training scenarios cover five emergency conditions including the LOCA, the steam generator tube rupture, the loss of all feedwater, the loss of off-site power, and the station blackout. From these records, average step performance time data are retrieved, and new

  14. Habitability and Human Factors Contributions to Human Space Flight

    NASA Technical Reports Server (NTRS)

    Sumaya, Jennifer Boyer

    2011-01-01

    This slide presentation reviews the work of the Habitability and Human Factors Branch in support of human space flight in two main areas: Applied support to major space programs, and Space research. The field of Human Factors applies knowledge of human characteristics for the design of safer, more effective, and more efficient systems. This work is in several areas of the human space program: (1) Human-System Integration (HSI), (2) Orion Crew Exploration Vehicle, (3) Extravehicular Activity (EVA), (4) Lunar Surface Systems, (5) International Space Station (ISS), and (6) Human Research Program (HRP). After detailing the work done in these areas, the facilities that are available for human factors work are shown.

  15. Complex assembly on the human CYP17 promoter

    PubMed Central

    Sewer, Marion B.; Jagarlapudi, Srinath

    2009-01-01

    Optimal steroid hormone biosynthesis occurs via the integration of multiple regulatory processes, one of which entails a coordinate increase in the transcription of all genes required for steroidogenesis. In the human adrenal cortex adrenocorticotropin (ACTH) activates a signaling cascade that promotes the dynamic assembly of protein complexes on the promoters of steroidogenic genes. For CYP17, multiple transcription factors, including steroidogenic factor-1 (SF-1), GATA-6, and sterol regulatory binding protein 1 (SREBP1), are recruited to the promoter during activated transcription. The ability of these factors to increase CYP17 mRNA expression requires the formation of higher order coregulatory complexes, many of which contain enzymatic activities that post-translationally modify both the transcription factors and histones. We discuss the mechanisms by which transcription factors and coregulatory proteins regulate CYP17 transcription and summarize the role of kinases, phosphatases, acetyltransferases, and histone deacetylases in controlling CYP17 mRNA expression. PMID:19007851

  16. Trends in human factors research.

    PubMed

    Cohen, A

    1982-06-01

    As just described, NIOSH's ongoing and new activities offer varied approaches and opportunities for gaining insights into human factor and ergonomic aspects of workplace hazards and their control. They represent a blend of surveillance work (re, the prevalence survey of chronic trauma risk), in-depth studies of known workplace problems emphasizing undue physical and psychological job demands and their consequences (re, stress from machine-paced work and musculoskeletal problems from repeated lifting), first evaluations of the consequences of new technology (re, use of video display terminals), and finally problem-solving efforts (re, the evaluation and field testing of the work practice guide for reducing lifting hazards and control technology assessment). Taken together, these efforts signal an important new commitment by NIOSH in making workplaces safe for our working men and women. PMID:6896907

  17. Social complexity as a proximate and ultimate factor in communicative complexity

    PubMed Central

    Freeberg, Todd M.; Dunbar, Robin I. M.; Ord, Terry J.

    2012-01-01

    The ‘social complexity hypothesis’ for communication posits that groups with complex social systems require more complex communicative systems to regulate interactions and relations among group members. Complex social systems, compared with simple social systems, are those in which individuals frequently interact in many different contexts with many different individuals, and often repeatedly interact with many of the same individuals in networks over time. Complex communicative systems, compared with simple communicative systems, are those that contain a large number of structurally and functionally distinct elements or possess a high amount of bits of information. Here, we describe some of the historical arguments that led to the social complexity hypothesis, and review evidence in support of the hypothesis. We discuss social complexity as a driver of communication and possible causal factor in human language origins. Finally, we discuss some of the key current limitations to the social complexity hypothesis—the lack of tests against alternative hypotheses for communicative complexity and evidence corroborating the hypothesis from modalities other than the vocal signalling channel. PMID:22641818

  18. ERBS human factors analysis: A case study

    NASA Technical Reports Server (NTRS)

    Moe, K. L.; Weger, C.

    1983-01-01

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

  19. Development of an Integrated Human Factors Toolkit

    NASA Technical Reports Server (NTRS)

    Resnick, Marc L.

    2003-01-01

    An effective integration of human abilities and limitations is crucial to the success of all NASA missions. The Integrated Human Factors Toolkit facilitates this integration by assisting system designers and analysts to select the human factors tools that are most appropriate for the needs of each project. The HF Toolkit contains information about a broad variety of human factors tools addressing human requirements in the physical, information processing and human reliability domains. Analysis of each tool includes consideration of the most appropriate design stage, the amount of expertise in human factors that is required, the amount of experience with the tool and the target job tasks that are needed, and other factors that are critical for successful use of the tool. The benefits of the Toolkit include improved safety, reliability and effectiveness of NASA systems throughout the agency. This report outlines the initial stages of development for the Integrated Human Factors Toolkit.

  20. Human driven transitions in complex model ecosystems

    NASA Astrophysics Data System (ADS)

    Harfoot, Mike; Newbold, Tim; Tittinsor, Derek; Purves, Drew

    2015-04-01

    Human activities have been observed to be impacting ecosystems across the globe, leading to reduced ecosystem functioning, altered trophic and biomass structure and ultimately ecosystem collapse. Previous attempts to understand global human impacts on ecosystems have usually relied on statistical models, which do not explicitly model the processes underlying the functioning of ecosystems, represent only a small proportion of organisms and do not adequately capture complex non-linear and dynamic responses of ecosystems to perturbations. We use a mechanistic ecosystem model (1), which simulates the underlying processes structuring ecosystems and can thus capture complex and dynamic interactions, to investigate boundaries of complex ecosystems to human perturbation. We explore several drivers including human appropriation of net primary production and harvesting of animal biomass. We also present an analysis of the key interactions between biotic, societal and abiotic earth system components, considering why and how we might think about these couplings. References: M. B. J. Harfoot et al., Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model., PLoS Biol. 12, e1001841 (2014).

  1. Human Factors in Space Flight

    NASA Technical Reports Server (NTRS)

    Woolford, Barbara J.; Mount, Frances

    2005-01-01

    After forty years of experience with human space flight (Table 1), the current emphasis is on the design of space vehicles, habitats, and missions to ensure mission success. What lessons have we learned that will affect the design of spacecraft for future space exploration, leading up to exploring Mars? This chapter addresses this issue in four sections: Anthropometry and Biomechanics; Environmental Factors; Habitability and Architecture; and Crew Personal Sustenance. This introductory section introduces factors unique to space flight. A unique consideration for design of a habitable volume in a space vehicle is the lack of gravity during a space flight, referred to as microgravity. This affects all aspects of life, and drives special features in the habitat, equipment, tools, and procedures. The difference in gravity during a space mission requires designing for posture and motion differences. In Earth s gravity, or even with partial gravity, orientation is not a variable because the direction in which gravity acts defines up and down. In a microgravity environment the working position is arbitrary; there is no gravity cue. Orientation is defined primarily through visual cues. The orientation within a particular crew station or work area is referred to as local vertical, and should be consistent within a module to increase crew productivity. Equipment was intentionally arranged in various orientations in one module on Skylab to assess the efficiency in use of space versus the effects of inconsistent layout. The effects of that arrangement were confusion on entering the module, time spent in re-orientation, and conflicts in crew space requirements when multiple crew members were in the module. Design of a space vehicle is constrained by the three major mission drivers: mass, volume and power. Each of these factors drives the cost of a mission. Mass and volume determine the size of the launch vehicle directly; they can limit consumables such as air, water, and

  2. The novel complement inhibitor human CUB and Sushi multiple domains 1 (CSMD1) protein promotes factor I-mediated degradation of C4b and C3b and inhibits the membrane attack complex assembly.

    PubMed

    Escudero-Esparza, Astrid; Kalchishkova, Nikolina; Kurbasic, Emila; Jiang, Wen G; Blom, Anna M

    2013-12-01

    CUB and Sushi multiple domains 1 (CSMD1) is a transmembrane protein containing 15 consecutive complement control protein (CCP) domains, which are characteristic for complement inhibitors. We expressed a membrane-bound fragment of human CSMD1 composed of the 15 C-terminal CCP domains and demonstrated that it inhibits deposition of C3b by the classical pathway on the surface of Chinese hamster ovary cells by 70% at 6% serum and of C9 (component of membrane attack complex) by 90% at 1.25% serum. Furthermore, this fragment of CSMD1 served as a cofactor to factor I-mediated degradation of C3b. In all functional assays performed, well-characterized complement inhibitors were used as positive controls, whereas Coxsackie adenovirus receptor, a protein with no effect on complement, was a negative control. Moreover, attenuation of expression in human T47 breast cancer cells that express endogenous CSMD1 significantly increased C3b deposition on these cells by 45% at 8% serum compared with that for the controls. Furthermore, by expressing a soluble 17-21 CCP fragment of CSMD1, we found that CSMD1 inhibits complement by promoting factor I-mediated C4b/C3b degradation and inhibition of MAC assembly at the level of C7. Our results revealed a novel complement inhibitor for the classical and lectin pathways.

  3. The novel complement inhibitor human CUB and Sushi multiple domains 1 (CSMD1) protein promotes factor I-mediated degradation of C4b and C3b and inhibits the membrane attack complex assembly.

    PubMed

    Escudero-Esparza, Astrid; Kalchishkova, Nikolina; Kurbasic, Emila; Jiang, Wen G; Blom, Anna M

    2013-12-01

    CUB and Sushi multiple domains 1 (CSMD1) is a transmembrane protein containing 15 consecutive complement control protein (CCP) domains, which are characteristic for complement inhibitors. We expressed a membrane-bound fragment of human CSMD1 composed of the 15 C-terminal CCP domains and demonstrated that it inhibits deposition of C3b by the classical pathway on the surface of Chinese hamster ovary cells by 70% at 6% serum and of C9 (component of membrane attack complex) by 90% at 1.25% serum. Furthermore, this fragment of CSMD1 served as a cofactor to factor I-mediated degradation of C3b. In all functional assays performed, well-characterized complement inhibitors were used as positive controls, whereas Coxsackie adenovirus receptor, a protein with no effect on complement, was a negative control. Moreover, attenuation of expression in human T47 breast cancer cells that express endogenous CSMD1 significantly increased C3b deposition on these cells by 45% at 8% serum compared with that for the controls. Furthermore, by expressing a soluble 17-21 CCP fragment of CSMD1, we found that CSMD1 inhibits complement by promoting factor I-mediated C4b/C3b degradation and inhibition of MAC assembly at the level of C7. Our results revealed a novel complement inhibitor for the classical and lectin pathways. PMID:23964079

  4. The Brain Prize 2014: complex human functions.

    PubMed

    Grigaityte, Kristina; Iacoboni, Marco

    2014-11-01

    Giacomo Rizzolatti, Stanislas Dehaene, and Trevor Robbins were recently awarded the 2014 Grete Lundbeck European Brain Research Prize for their 'pioneering research on higher brain mechanisms underpinning such complex human functions as literacy, numeracy, motivated behavior and social cognition, and for their effort to understand cognitive and behavioral disorders'. Why was their work highlighted? Is there anything that links together these seemingly disparate lines of research?

  5. Structure of human PNP complexed with ligands.

    PubMed

    Canduri, Fernanda; Silva, Rafael Guimarães; dos Santos, Denis Marangoni; Palma, Mário Sérgio; Basso, Luiz Augusto; Santos, Diógenes Santiago; de Azevedo, Walter Filgueira

    2005-07-01

    Purine nucleoside phosphorylase (PNP) is a key enzyme in the purine-salvage pathway, which allows cells to utilize preformed bases and nucleosides in order to synthesize nucleotides. PNP is specific for purine nucleosides in the beta-configuration and exhibits a strong preference for purines containing a 6-keto group and ribosyl-containing nucleosides relative to the corresponding analogues. PNP was crystallized in complex with ligands and data collection was performed using synchrotron radiation. This work reports the structure of human PNP in complex with guanosine (at 2.80 A resolution), 3'-deoxyguanosine (at 2.86 A resolution) and 8-azaguanine (at 2.85 A resolution). These structures were compared with the PNP-guanine, PNP-inosine and PNP-immucillin-H complexes solved previously.

  6. Human factors in agile manufacturing

    SciTech Connect

    Forsythe, C.

    1995-03-01

    As industries position themselves for the competitive markets of today, and the increasingly competitive global markets of the 21st century, agility, or the ability to rapidly develop and produce new products, represents a common trend. Agility manifests itself in many different forms, with the agile manufacturing paradigm proposed by the Iacocca Institute offering a generally accepted, long-term vision. In its many forms, common elements of agility or agile manufacturing include: changes in business, engineering and production practices, seamless information flow from design through production, integration of computer and information technologies into all facets of the product development and production process, application of communications technologies to enable collaborative work between geographically dispersed product development team members and introduction of flexible automation of production processes. Industry has rarely experienced as dramatic an infusion of new technologies or as extensive a change in culture and work practices. Human factors will not only play a vital role in accomplishing the technical and social objectives of agile manufacturing. but has an opportunity to participate in shaping the evolution of industry paradigms for the 21st century.

  7. HL-20 Vertical Human Factors

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The HL-20 space taxi, Langley's candidate personnel launch system, is one of several designs being considered by NASA as a complement to the Space Shuttle. Human factors studies, using Langley volunteers as subjects, have been ongoing since March 1991 to verify crew seating arrangements, habitability, ingress and egress, equipment layout and maintenance and handling operations, and to determine visibility requirements during docking and landing operations. Langley volunteers, wearing flight suits and helmets, were put through a series of tests with the craft placed both vertically and horizontally to simulate launch and landing attitudes, The HL-20 would be launched into a low orbit by an expendable rocket and then use its own propulsion system to boost itself to the space station. Following exchange of crews or delivery of small payload, the HL-20 would return to Earth like the space shuttle, making a runway landing near the launch site, The full-scale engineering research model of the HL-20 design was constructed by students and faculty at North Carolina State University and North Carolina A&T State University with the Mars Mission Research Center under a grant from NASA Langley.

  8. Sicca complex and infection with human immunodeficiency virus.

    PubMed

    Couderc, L J; D'Agay, M F; Danon, F; Harzic, M; Brocheriou, C; Clauvel, J P

    1987-05-01

    Five male patients with the persistent generalized lymphadenopathy syndrome also had a sicca complex. Salivary gland biopsy specimens showed diffuse lymphocytic infiltration of the glandular parenchyma. Serum autoantibodies and rheumatoid factor were not detected. All patients had IgG antibodies to human immunodeficiency virus and IgG to the viral capsid antigen of Epstein-Barr virus. These five patients had benign lymphocytic infiltrates in other organs (lung, liver, and kidneys). Sicca complex may be one of the various manifestations of the lymphoid hyperplasia noted in human immunodeficiency virus-infected patients. In these patients, the sicca complex showed specific features related to male predominance, lack of serum autoantibodies, and peripheral-blood T-lymphocyte subset distribution.

  9. Accounting for the Human Factor.

    ERIC Educational Resources Information Center

    Ginsburg, Sigmund G.

    1994-01-01

    College governing boards must address six areas of campus human resources management: composition of the new workforce; leadership and motivation; quality of work life; performance evaluation; compensation; and the role of the campus human resource management department. (MSE)

  10. NASA Information Sciences and Human Factors Program

    NASA Technical Reports Server (NTRS)

    Holcomb, Lee; Hood, Ray; Montemerlo, Melvin; Jenkins, James; Smith, Paul; Dibattista, John; Depaula, Ramon; Hunter, Paul

    1990-01-01

    Fiscal year 1989 descriptions of technical accomplishments in seven sections are presented: automation and robotics; communications; computer sciences; controls and guidance; data systems; human factors; and sensor technology.

  11. NASA information sciences and human factors program

    NASA Technical Reports Server (NTRS)

    Holcomb, Lee; Hood, Ray; Montemerlo, Melvin; Jenkins, James; Smith, Paul; Dibattista, John; Depaula, Ramon; Hunter, Paul; Lavery, David

    1991-01-01

    The FY-90 descriptions of technical accomplishments are contained in seven sections: Automation and Robotics, Communications, Computer Sciences, Controls and Guidance, Data Systems, Human Factors, and Sensor Technology.

  12. NASA Information Sciences and Human Factors Program

    NASA Technical Reports Server (NTRS)

    Holcomb, Lee B.; Mciver, Duncan E.; Dibattista, John D.; Larsen, Ronald L.; Montemerlo, Melvin D.; Wallgren, Ken; Sokoloski, Marty; Wasicko, Dick

    1985-01-01

    This report contains FY 1984/85 descriptions and accomplishments in six sections: Computer Science and Automation, Controls and Guidance, Data Systems, Human Factors, Sensor Technology, and Communications.

  13. Factors Determining Nestedness in Complex Networks

    PubMed Central

    Jonhson, Samuel; Domínguez-García, Virginia; Muñoz, Miguel A.

    2013-01-01

    Understanding the causes and effects of network structural features is a key task in deciphering complex systems. In this context, the property of network nestedness has aroused a fair amount of interest as regards ecological networks. Indeed, Bastolla et al. introduced a simple measure of network nestedness which opened the door to analytical understanding, allowing them to conclude that biodiversity is strongly enhanced in highly nested mutualistic networks. Here, we suggest a slightly refined version of such a measure of nestedness and study how it is influenced by the most basic structural properties of networks, such as degree distribution and degree-degree correlations (i.e. assortativity). We find that most of the empirically found nestedness stems from heterogeneity in the degree distribution. Once such an influence has been discounted – as a second factor – we find that nestedness is strongly correlated with disassortativity and hence – as random networks have been recently found to be naturally disassortative – they also tend to be naturally nested just as the result of chance. PMID:24069264

  14. Organizational crisis management: the human factor.

    PubMed

    Lewis, Gerald

    2005-01-01

    While many professionals are quite competent when dealing with operational aspects of organizational continuity, often the "human factor" does not receive adequate attention. This article provides a brief overview of a soon to be published book by the same title. It provides a comprehensive understanding of the ubiquitous yet complex reactions of the workforce to a wide array of organizational disruptions. It goes beyond the short term intervention of debriefings to describe the more extensive pre and post incident strategies required to mitigate the impact of crises on the workforce. It is important to remember: "An organization can get its phone lines back up and have its computers backed up...but its workers may still be messed up."

  15. Human Factors in Aeronautics at NASA

    NASA Technical Reports Server (NTRS)

    Mogford, Richard

    2016-01-01

    This is a briefing to a regularly meeting DoD group called the Human Systems Community of Interest: Mission Effectiveness. I was asked to address human factors in aeronautics at NASA. (Exploration (space) human factors has apparently already been covered.) The briefing describes human factors organizations at NASA Ames and Langley. It then summarizes some aeronautics tasks that involve the application of human factors in the development of specific tools and capabilities. The tasks covered include aircrew checklists, dispatch operations, Playbook, Dynamic Weather Routes, Traffic Aware Strategic Aircrew Requests, and Airplane State Awareness and Prediction Technologies. I mention that most of our aeronautics work involves human factors as embedded in development tasks rather than basic research.

  16. Human Modeling for Ground Processing Human Factors Engineering Analysis

    NASA Technical Reports Server (NTRS)

    Stambolian, Damon B.; Lawrence, Brad A.; Stelges, Katrine S.; Steady, Marie-Jeanne O.; Ridgwell, Lora C.; Mills, Robert E.; Henderson, Gena; Tran, Donald; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over the last few years using human modeling for human factors engineering analysis for design of spacecraft. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the human modeling currently used at Kennedy Space Center (KSC), and to explain the future plans for human modeling for future spacecraft designs

  17. Human Factors Simulation in Construction Management Education

    ERIC Educational Resources Information Center

    Jaeger, M.; Adair, D.

    2010-01-01

    Successful construction management depends primarily on the representatives of the involved construction project parties. In addition to effective application of construction management tools and concepts, human factors impact significantly on the processes of any construction management endeavour. How can human factors in construction management…

  18. Human Factors Research and Nuclear Safety.

    ERIC Educational Resources Information Center

    Moray, Neville P., Ed.; Huey, Beverly M., Ed.

    The Panel on Human Factors Research Needs in Nuclear Regulatory Research was formed by the National Research Council in response to a request from the Nuclear Regulatory Commission (NRC). The NRC asked the research council to conduct an 18-month study of human factors research needs for the safe operation of nuclear power plants. This report…

  19. Human Factors and the International Space Station

    NASA Technical Reports Server (NTRS)

    Peacock, Brian; Rajulu, Sudhakar; Novak, Jennifer; Rathjen, Thomas; Whitmore, Mihriban; Maida, James; Woolford, Barbara

    2001-01-01

    The purposes of this panel are to inform the human factors community regarding the challenges of designing the International Space Station (ISS) and to stimulate the broader human factors community into participating in the various basic and applied research opportunities associated with the ISS. This panel describes the variety of techniques used to plan and evaluate human factors for living and working in space. The panel members have contributed to many different aspects of the ISS design and operations. Architecture, equipment, and human physical performance requirements for various tasks have all been tailored to the requirements of operating in microgravity.

  20. Human factors in general aviation

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The relation of the pilot to the aircraft in general aviation is considered. The human component is analyzed, along with general aviation facilities. The man-machine interface, and the man-environment interface are discussed.

  1. Implementing human factors in clinical practice

    PubMed Central

    Timmons, Stephen; Baxendale, Bryn; Buttery, Andrew; Miles, Giulia; Roe, Bridget; Browes, Simon

    2015-01-01

    Objectives To understand whether aviation-derived human factors training is acceptable and useful to healthcare professionals. To understand whether and how healthcare professionals have been able to implement human factors approaches to patient safety in their own area of clinical practice. Methods Qualitative, longitudinal study using semi-structured interviews and focus groups, of a multiprofessional group of UK NHS staff (from the emergency department and operating theatres) who have received aviation-derived human factors training. Results The human factors training was evaluated positively, and thought to be both acceptable and relevant to practice. However, the staff found it harder to implement what they had learned in their own clinical areas, and this was principally attributed to features of the informal organisational cultures. Conclusions In order to successfully apply human factors approaches in hospital, careful consideration needs to be given to the local context and informal culture of clinical practice. PMID:24631959

  2. Human Factors in Cabin Accident Investigations

    NASA Technical Reports Server (NTRS)

    Chute, Rebecca D.; Rosekind, Mark R. (Technical Monitor)

    1996-01-01

    Human factors has become an integral part of the accident investigation protocol. However, much of the investigative process remains focussed on the flight deck, airframe, and power plant systems. As a consequence, little data has been collected regarding the human factors issues within and involving the cabin during an accident. Therefore, the possibility exists that contributing factors that lie within that domain may be overlooked. The FAA Office of Accident Investigation is sponsoring a two-day workshop on cabin safety accident investigation. This course, within the workshop, will be of two hours duration and will explore relevant areas of human factors research. Specifically, the three areas of discussion are: Information transfer and resource management, fatigue and other physical stressors, and the human/machine interface. Integration of these areas will be accomplished by providing a suggested checklist of specific cabin-related human factors questions for investigators to probe following an accident.

  3. Human factors engineering for designing the next in medicine.

    PubMed

    Lai, Fuji

    2007-01-01

    Good design of emerging medical technology in an increasingly complex clinical and technological environment requires an understanding of the context of use, workload, and environment as well as appreciation for ease of use, fit into clinical workflow, and the need for user feedback in the design process. This is where human factors engineering can come into play for good design. Human factors engineering involves the application of principles about human behaviors, abilities, and limitations to the design of tools, devices, environments, and training in order to optimize human performance and safety. The human factors engineering process should be an integral part of the emerging technology development process and needs to be included upfront. This can help ensure that the new product is safe, functional, natural to use, seamlessly integrated into existing clinical workflow, and embraced by users to be incorporated into practice for maximum benefit to patient safety and healthcare quality.

  4. The importance of residues 195-206 of human blood clotting factor VII in the interaction of factor VII with tissue factor

    SciTech Connect

    Wildgoose, P.; Kisiel, W.; Kazim, A.L. )

    1990-09-01

    Previous studies indicated that human and bovine factor VII exhibit 71% amino acid sequence identity. In the present study, competition binding experiments revealed that the interaction of human factor VII with cell-surface human tissue factor was not inhibited by 100-fold molar excess of bovine factor VII. This finding indicated that bovine and human factor VII are not structurally homologous in the region(s) where human factor VII interacts with human tissue factor. On this premise, the authors synthesized three peptides corresponding to regions of human factor VII that exhibited marked structural dissimilarity to bovine factor VII; these regions of dissimilarity included residues 195-206, 263-274, and 314-326. Peptide 195-206 inhibited the interaction of factor VII with cell-surface tissue factor and the activation of factor X by a complex of factor VIIa and tissue factor half-maximally at concentrations of 1-2 mM. A structurally rearranged form of peptide 195-206 containing an aspartimide residue inhibited these reactions half-maximally at concentrations of 250-300 {mu}M. In contrast, neither peptide 263-274 nor peptide 314-326, at 2 mM concentration, significantly affected either factor VIIa interaction with tissue factor or factor VIIa-mediated activation of factor X. The data provide presumptive evidence that residues 195-206 of human factor VII are involved in the interaction of human factor VII with the extracellular domain of human tissue factor apoprotein.

  5. Human factors for Mars missions

    NASA Technical Reports Server (NTRS)

    Nicogossian, Arnauld E.

    1988-01-01

    The implications of human participation in Mars missions are reviewed. The psychological effects of long-term confinement, tension, and boredom are examined. The medical implications of travel to Mars, including the effects of low gravity and exposure to radiation, are discussed. The difficulty of providing sufficient consumables, such as air, food, and water, is considered.

  6. Human factors in safety and business management.

    PubMed

    Vogt, Joachim; Leonhardt, Jorg; Koper, Birgit; Pennig, Stefan

    2010-02-01

    Human factors in safety is concerned with all those factors that influence people and their behaviour in safety-critical situations. In aviation these are, for example, environmental factors in the cockpit, organisational factors such as shift work, human characteristics such as ability and motivation of staff. Careful consideration of human factors is necessary to improve health and safety at work by optimising the interaction of humans with their technical and social (team, supervisor) work environment. This provides considerable benefits for business by increasing efficiency and by preventing incidents/accidents. The aim of this paper is to suggest management tools for this purpose. Management tools such as balanced scorecards (BSC) are widespread instruments and also well known in aviation organisations. Only a few aviation organisations utilise management tools for human factors although they are the most important conditions in the safety management systems of aviation organisations. One reason for this is that human factors are difficult to measure and therefore also difficult to manage. Studies in other domains, such as workplace health promotion, indicate that BSC-based tools are useful for human factor management. Their mission is to develop a set of indicators that are sensitive to organisational performance and help identify driving forces as well as bottlenecks. Another tool presented in this paper is the Human Resources Performance Model (HPM). HPM facilitates the integrative assessment of human factors programmes on the basis of a systematic performance analysis of the whole system. Cause-effect relationships between system elements are defined in process models in a first step and validated empirically in a second step. Thus, a specific representation of the performance processes is developed, which ranges from individual behaviour to system performance. HPM is more analytic than BSC-based tools because HPM also asks why a certain factor is

  7. Human factors in safety and business management.

    PubMed

    Vogt, Joachim; Leonhardt, Jorg; Koper, Birgit; Pennig, Stefan

    2010-02-01

    Human factors in safety is concerned with all those factors that influence people and their behaviour in safety-critical situations. In aviation these are, for example, environmental factors in the cockpit, organisational factors such as shift work, human characteristics such as ability and motivation of staff. Careful consideration of human factors is necessary to improve health and safety at work by optimising the interaction of humans with their technical and social (team, supervisor) work environment. This provides considerable benefits for business by increasing efficiency and by preventing incidents/accidents. The aim of this paper is to suggest management tools for this purpose. Management tools such as balanced scorecards (BSC) are widespread instruments and also well known in aviation organisations. Only a few aviation organisations utilise management tools for human factors although they are the most important conditions in the safety management systems of aviation organisations. One reason for this is that human factors are difficult to measure and therefore also difficult to manage. Studies in other domains, such as workplace health promotion, indicate that BSC-based tools are useful for human factor management. Their mission is to develop a set of indicators that are sensitive to organisational performance and help identify driving forces as well as bottlenecks. Another tool presented in this paper is the Human Resources Performance Model (HPM). HPM facilitates the integrative assessment of human factors programmes on the basis of a systematic performance analysis of the whole system. Cause-effect relationships between system elements are defined in process models in a first step and validated empirically in a second step. Thus, a specific representation of the performance processes is developed, which ranges from individual behaviour to system performance. HPM is more analytic than BSC-based tools because HPM also asks why a certain factor is

  8. Human Factors Directions for Civil Aviation

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.

    2002-01-01

    Despite considerable progress in understanding human capabilities and limitations, incorporating human factors into aircraft design, operation, and certification, and the emergence of new technologies designed to reduce workload and enhance human performance in the system, most aviation accidents still involve human errors. Such errors occur as a direct or indirect result of untimely, inappropriate, or erroneous actions (or inactions) by apparently well-trained and experienced pilots, controllers, and maintainers. The field of human factors has solved many of the more tractable problems related to simple ergonomics, cockpit layout, symbology, and so on. We have learned much about the relationships between people and machines, but know less about how to form successful partnerships between humans and the information technologies that are beginning to play a central role in aviation. Significant changes envisioned in the structure of the airspace, pilots and controllers' roles and responsibilities, and air/ground technologies will require a similarly significant investment in human factors during the next few decades to ensure the effective integration of pilots, controllers, dispatchers, and maintainers into the new system. Many of the topics that will be addressed are not new because progress in crucial areas, such as eliminating human error, has been slow. A multidisciplinary approach that capitalizes upon human studies and new classes of information, computational models, intelligent analytical tools, and close collaborations with organizations that build, operate, and regulate aviation technology will ensure that the field of human factors meets the challenge.

  9. Osteosarcoma cell-calcium signaling through tissue factor-factor VIIa complex and factor Xa.

    PubMed

    Daubie, Valéry; De Decker, Robert; Nicaise, Charles; Pochet, Roland

    2007-06-12

    The cells responsible for bone formation express protease-activated receptors. Although serine protease thrombin has been shown to elicit functional responses in bone cells that impact on cell survival and alkaline phosphatase activity, nothing is known about tissue factor, factor VIIa, and factor Xa, the serine proteases that act upstream of thrombin in the coagulation cascade. This paper demonstrates that tissue factor is expressed in the osteoblast-like cell line SaOS-2 and, that tissue factor in a factor VIIa-bound complex induces a transient intracellular Ca(2+) increase through protease-activated receptor-2. In SaOS-2 cells, factor Xa induced a sustained intracellular Ca(2+) response, as does SLIGRL, a PAR2-activating peptide, and PAR-1-dependent cell viability. PMID:17509570

  10. Human factors certification: A useful concept?

    NASA Technical Reports Server (NTRS)

    Jackson, Alistair

    1994-01-01

    This paper considers what is involved in certification processes and their relation to human factors aspects of systems. It derives from recognition of a lack of understanding of the processes and purposes of certification. This was encountered when attempting to address the workshop topic by integrating an understanding of human factors with the observed processes of certification. The paper considers what human factors (HF) certification might be and then develops a simple model of the elements of a certification process. It then tries to relate these elements to the needs of the aviation communities and other parties with an interest in the certification of advance aviation technologies.

  11. Microgravity human factors workstation development

    NASA Technical Reports Server (NTRS)

    Whitmore, Mihriban; Wilmington, Robert P.; Morris, Randy B.; Jensen, Dean G.

    1992-01-01

    Microgravity evaluations of workstation hardware as well as its system components were found to be very useful for determining the expected needs of the Space Station crew and for refining overall workstation design. Research at the Johnson Space Center has been carried out to provide optimal workstation design and human interface. The research included evaluations of hand controller configurations for robots and free flyers, the identification of cursor control device requirements, and the examination of anthropometric issues of workstation design such as reach, viewing distance, and head clearance.

  12. The complexity-cost factor in bilingualism.

    PubMed

    Festman, Julia

    2013-08-01

    Language processing changes with the knowledge and use of two languages. The advantage of being bilingual comes at the expense of increased processing demands and processing costs. I suggest considering bilingual complexity including these demands and costs. The proposed model claims effortless monolingual processing. By integrating individual and situational variability, the model would lose its idealistic touch, even for monolinguals.

  13. pH sensitivity of epidermal growth factor receptor complexes.

    PubMed

    Nunez, M; Mayo, K H; Starbuck, C; Lauffenburger, D

    1993-03-01

    The association/dissociation binding kinetics of 125I-labeled mouse epidermal growth factor (EGF) to receptors on human fibroblast cells in monolayer culture have been measured at 4 degrees C as a function of extracellular pH from pH 5-9. At pH 8, steady-state total binding is maximal. As pH is lowered to 6.5, total binding monotonically decreases dramatically. It changes further only slightly between pH 6.5 and 5 to about 20% of the maximum binding value. Scatchard binding plots at pH 7.5 and above show the commonly observed concave-upward, non-linear curve; as pH is lowered, this plot becomes much more linear, indicating that the "high affinity" bound receptor population is greatly diminished. Application of our ternary complex binding model [Mayo et al., J Biol Chem 264:17838-17844, 1989], which hypothesizes complexation of the EGF-bound receptor with a cell surface interaction molecule, indicates that pH may have some direct effects on ternary complex formation, but the major effect is on EGF-receptor dissociation. PMID:8501133

  14. NASA Information Sciences and Human Factors Program

    NASA Technical Reports Server (NTRS)

    Holcomb, Lee (Editor); Hood, Ray (Editor); Montemerlo, Melvin (Editor); Sokoloski, Martin M. (Editor); Jenkins, James P. (Editor); Smith, Paul H. (Editor); Dibattista, John D. (Editor)

    1988-01-01

    The FY 1987 descriptions of technical accomplishments are contained for seven areas: automation and robotics, communications systems, computer sciences, controls and guidance, data systems, human factors, and sensor technology.

  15. NASA information sciences and human factors program

    NASA Technical Reports Server (NTRS)

    Holcomb, Lee; Hood, Ray; Montemerlo, Melvin; Sokoloski, Martin; Jenkins, James; Smith, Paul; Dibattista, John

    1989-01-01

    The FY 1988 descriptions of technical accomplishments is presented in seven sections: Automation and Robotics, Communications Systems, Computer Sciences, Controls and Guidance, Data Systems, Human Factors, and Sensor Technology.

  16. Human factors issues for interstellar spacecraft

    NASA Technical Reports Server (NTRS)

    Cohen, Marc M.; Brody, Adam R.

    1991-01-01

    Developments in research on space human factors are reviewed in the context of a self-sustaining interstellar spacecraft based on the notion of traveling space settlements. Assumptions about interstellar travel are set forth addressing costs, mission durations, and the need for multigenerational space colonies. The model of human motivation by Maslow (1970) is examined and directly related to the design of space habitat architecture. Human-factors technology issues encompass the human-machine interface, crew selection and training, and the development of spaceship infrastructure during transtellar flight. A scenario for feasible instellar travel is based on a speed of 0.5c, a timeframe of about 100 yr, and an expandable multigenerational crew of about 100 members. Crew training is identified as a critical human-factors issue requiring the development of perceptual and cognitive aids such as expert systems and virtual reality.

  17. Induction of nerve growth factor receptors on cultured human melanocytes

    SciTech Connect

    Peacocke, M.; Yaar, M.; Mansur, C.P.; Chao, M.V.; Gilchrest, B.A. )

    1988-07-01

    Normal differentiation and malignant transformation of human melanocytes involve a complex series of interactions during which both genetic and environmental factors play roles. At present, the regulation of these processes is poorly understood. The authors have induced the expression of nerve growth factor (NGF) receptors on cultured human melanocytes with phorbol 12-tetradecanoate 13-acetate and have correlated this event with the appearance of a more differentiated, dendritic morphology. Criteria for NGF receptor expression included protein accumulation and cell-surface immunofluorescent staining with a monoclonal antibody directed against the human receptor and induction of the messenger RNA species as determined by blot-hybridization studies. The presence of the receptor could also be induced by UV irradiation or growth factor deprivation. The NGF receptor is inducible in cultured human melanocytes, and they suggest that NGF may modulate the behavior of this neural crest-derived cell in the skin.

  18. Organization of the human mitochondrial transcription initiation complex

    PubMed Central

    Yakubovskaya, Elena; Guja, Kip E.; Eng, Edward T.; Choi, Woo Suk; Mejia, Edison; Beglov, Dmitri; Lukin, Mark; Kozakov, Dima; Garcia-Diaz, Miguel

    2014-01-01

    Initiation of transcription in human mitochondria involves two factors, TFAM and TFB2M, in addition to the mitochondrial RNA polymerase, POLRMT. We have investigated the organization of the human mitochondrial transcription initiation complex on the light-strand promoter (LSP) through solution X-ray scattering, electron microscopy (EM) and biochemical studies. Our EM results demonstrate a compact organization of the initiation complex, suggesting that protein–protein interactions might help mediate initiation. We demonstrate that, in the absence of DNA, only POLRMT and TFAM form a stable interaction, albeit one with low affinity. This is consistent with the expected transient nature of the interactions necessary for initiation and implies that the promoter DNA acts as a scaffold that enables formation of the full initiation complex. Docking of known crystal structures into our EM maps results in a model for transcriptional initiation that strongly correlates with new and existing biochemical observations. Our results reveal the organization of TFAM, POLRMT and TFB2M around the LSP and represent the first structural characterization of the entire mitochondrial transcriptional initiation complex. PMID:24413562

  19. Human factors in cockpit automation

    NASA Technical Reports Server (NTRS)

    Wiener, E. L.

    1984-01-01

    The rapid advance in microprocessor technology has made it possible to automate many functions that were previously performed manually. Several research areas have been identified which are basic to the question of the implementation of automation in the cockpit. One of the identified areas deserving further research is warning and alerting systems. Modern transport aircraft have had one after another warning and alerting systems added, and computer-based cockpit systems make it possible to add even more. Three major areas of concern are: input methods (including voice, keyboard, touch panel, etc.), output methods and displays (from traditional instruments to CRTs, to exotic displays including the human voice), and training for automation. Training for operating highly automatic systems requires considerably more attention than it has been given in the past. Training methods have not kept pace with the advent of flight-deck automation.

  20. Transforming growth factor beta stabilizes p15INK4B protein, increases p15INK4B-cdk4 complexes, and inhibits cyclin D1-cdk4 association in human mammary epithelial cells.

    PubMed Central

    Sandhu, C; Garbe, J; Bhattacharya, N; Daksis, J; Pan, C H; Yaswen, P; Koh, J; Slingerland, J M; Stampfer, M R

    1997-01-01

    The effects of transforming growth factor beta (TGF-beta) were studied in closely related human mammary epithelial cells (HMEC), both finite-life-span 184 cells and immortal derivatives, 184A1S, and 184A1L5R, which differ in their cell cycle responses to TGF-beta but express type I and type II TGF-beta receptors and retain TGF-beta induction of extracellular matrix. The arrest-resistant phenotype was not due to loss of cyclin-dependent kinase (cdk) inhibitors. TGF-beta was shown to regulate p15INK4B expression at at least two levels: mRNA accumulation and protein stability. In TGF-beta-arrested HMEC, there was not only an increase in p15 mRNA but also a major increase in p5INK4B protein stability. As cdk4- and cdk6-associated p15INK4B increased during TGF-beta arrest of sensitive cells, there was a loss of cyclin D1, p21Cip1, and p27Kip1 from these kinase complexes, and cyclin E-cdk2-associated p27Kip1 increased. In HMEC, p15INK4B complexes did not contain detectable cyclin. p15INK4B from both sensitive and resistant cells could displace in vitro cyclin D1, p21Cip1, and p27Kip1 from cdk4 isolated from sensitive cells. Cyclin D1 could not be displaced from cdk4 in the resistant 184A1L5R cell lysates. Thus, in TGF-beta arrest, p15INK4B may displace already associated cyclin D1 from cdks and prevent new cyclin D1-cdk complexes from forming. Furthermore, p27Kip1 binding shifts from cdk4 to cyclin E-cdk2 during TGF-beta-mediated arrest. The importance of posttranslational regulation of p15INK4B by TGF-beta is underlined by the observation that in TGF-beta-resistant 184A1L5R, although the p15 transcript increased, p15INK4B protein was not stabilized and did not accumulate, and cyclin D1-cdk association and kinase activation were not inhibited. PMID:9111314

  1. Human Factors Throughout the Life Cycle: Lessons Learned from the Shuttle Program. [Human Factors in Ground Processing

    NASA Technical Reports Server (NTRS)

    Kanki, Barbara G.

    2011-01-01

    With the ending of the Space Shuttle Program, it is critical that we not forget the Human Factors lessons we have learned over the years. At every phase of the life cycle, from manufacturing, processing and integrating vehicle and payload, to launch, flight operations, mission control and landing, hundreds of teams have worked together to achieve mission success in one of the most complex, high-risk socio-technical enterprises ever designed. Just as there was great diversity in the types of operations performed at every stage, there was a myriad of human factors that could further complicate these human systems. A single mishap or close call could point to issues at the individual level (perceptual or workload limitations, training, fatigue, human error susceptibilities), the task level (design of tools, procedures and aspects of the workplace), as well as the organizational level (appropriate resources, safety policies, information access and communication channels). While we have often had to learn through human mistakes and technological failures, we have also begun to understand how to design human systems in which individuals can excel, where tasks and procedures are not only safe but efficient, and how organizations can foster a proactive approach to managing risk and supporting human enterprises. Panelists will talk about their experiences as they relate human factors to a particular phase of the shuttle life cycle. They will conclude with a framework for tying together human factors lessons-learned into system-level risk management strategies.

  2. Space Human Factors: Research to Application

    NASA Technical Reports Server (NTRS)

    Woolford, Barbara

    2008-01-01

    Human Factors has been instrumental in preventing potential on-orbit hazards and increasing overall crew safety. Poor performance & operational learning curves on-orbit are mitigated. Human-centered design is applied to optimize design and minimize potentially hazardous conditions, especially with larger crew sizes and habitat constraints. Lunar and Mars requirements and design developments are enhanced, based on ISS Lessons Learned.

  3. Space Human Factors Engineering Gap Analysis Project Final Report

    NASA Technical Reports Server (NTRS)

    Hudy, Cynthia; Woolford, Barbara

    2006-01-01

    Humans perform critical functions throughout each phase of every space mission, beginning with the mission concept and continuing to post-mission analysis (Life Sciences Division, 1996). Space missions present humans with many challenges - the microgravity environment, relative isolation, and inherent dangers of the mission all present unique issues. As mission duration and distance from Earth increases, in-flight crew autonomy will increase along with increased complexity. As efforts for exploring the moon and Mars advance, there is a need for space human factors research and technology development to play a significant role in both on-orbit human-system interaction, as well as the development of mission requirements and needs before and after the mission. As part of the Space Human Factors Engineering (SHFE) Project within the Human Research Program (HRP), a six-month Gap Analysis Project (GAP) was funded to identify any human factors research gaps or knowledge needs. The overall aim of the project was to review the current state of human factors topic areas and requirements to determine what data, processes, or tools are needed to aid in the planning and development of future exploration missions, and also to prioritize proposals for future research and technology development.

  4. Reducing the Complexity Gap: Expanding the Period of Human Nurturance

    ERIC Educational Resources Information Center

    Kiel, L. Douglas

    2014-01-01

    Socio-techno-cultural reality, in the current historical era, evolves at a faster rate than do human brain or human institutions. This reality creates a "complexity gap" that reduces human and institutional capacities to adapt to the challenges of late modernity. New insights from the neurosciences may help to reduce the complexity gap.…

  5. Human factors and safety in emergency medicine

    NASA Technical Reports Server (NTRS)

    Schaefer, H. G.; Helmreich, R. L.; Scheidegger, D.

    1994-01-01

    A model based on an input process and outcome conceptualisation is suggested to address safety-relevant factors in emergency medicine. As shown in other dynamic and demanding environments, human factors play a decisive role in attaining high quality service. Attitudes held by health-care providers, organisational shells and work-cultural parameters determine communication, conflict resolution and workload distribution within and between teams. These factors should be taken into account to improve outcomes such as operational integrity, job satisfaction and morale.

  6. The motion commotion: Human factors in transportation

    NASA Technical Reports Server (NTRS)

    Millar, A. E., Jr. (Editor); Rosen, R. L. (Editor); Gibson, J. D. (Editor); Crum, R. G. (Editor)

    1972-01-01

    The program for a systems approach to the problem of incorporating human factors in designing transportation systems is summarized. The importance of the human side of transportation is discussed along with the three major factors related to maintaining a mobile and quality life. These factors are (1) people, as individuals and groups, (2) society as a whole, and (3) the natural environment and man-made environs. The problems and bottlenecks are presented along with approaches to their solutions through systems analysis. Specific recommendations essential to achieving improved mobility within environmental constraints are presented.

  7. Minimization of Boolean complexity in human concept learning.

    PubMed

    Feldman, J

    2000-10-01

    One of the unsolved problems in the field of human concept learning concerns the factors that determine the subjective difficulty of concepts: why are some concepts psychologically simple and easy to learn, while others seem difficult, complex or incoherent? This question was much studied in the 1960s but was never answered, and more recent characterizations of concepts as prototypes rather than logical rules leave it unsolved. Here I investigate this question in the domain of Boolean concepts (categories defined by logical rules). A series of experiments measured the subjective difficulty of a wide range of logical varieties of concepts (41 mathematically distinct types in six families--a far wider range than has been tested previously). The data reveal a surprisingly simple empirical 'law': the subjective difficulty of a concept is directly proportional to its Boolean complexity (the length of the shortest logically equivalent propositional formula)--that is, to its logical incompressibility. PMID:11034211

  8. Rendezvous Integration Complexities of NASA Human Flight Vehicles

    NASA Technical Reports Server (NTRS)

    Brazzel, Jack P.; Goodman, John L.

    2009-01-01

    Propellant-optimal trajectories, relative sensors and navigation, and docking/capture mechanisms are rendezvous disciplines that receive much attention in the technical literature. However, other areas must be considered. These include absolute navigation, maneuver targeting, attitude control, power generation, software development and verification, redundancy management, thermal control, avionics integration, robotics, communications, lighting, human factors, crew timeline, procedure development, orbital debris risk mitigation, structures, plume impingement, logistics, and in some cases extravehicular activity. While current and future spaceflight programs will introduce new technologies and operations concepts, the complexity of integrating multiple systems on multiple spacecraft will remain. The systems integration task may become more difficult as increasingly complex software is used to meet current and future automation, autonomy, and robotic operation requirements.

  9. Cleavage and activation of human factor IX by serine proteases

    SciTech Connect

    Enfield, D.L.; Thompson, A.R.

    1984-10-01

    Human factor IX circulates as a single-chain glycoprotein. Upon activation in vitro, it is cleaved into disulfide-linked light and heavy chains and an activation peptide. After reduction of activated /sup 125/I-factor IX, the heavy and light chains are readily identified by gel electrophoresis. A direct, immunoradiometric assay for factor IXa was developed to assess activation of factor IX for proteases that cleaved it. The assay utilized radiolabeled antithrombin III with heparin to identify the active site and antibodies to distinguish factor IX. After cleavage of factor IX by factor XIa, factor VIIa-tissue thromboplastin complex, or the factor X-activating enzyme from Russell's viper venom, antithrombin III bound readily to factor IXa. Cleavage of /sup 125/I-factor IX by trypsin, chymotrypsin, and granulocyte elastase in the presence of calcium yielded major polypeptide fragments of the sizes of the factor XIa-generated light and heavy chains. When the immunoradiometric assay was used to assess trypsin-cleaved factor IX, the product bound antithrombin III, but not maximally. After digesting with insolubilized trypsin, clotting activity confirmed activation. In evaluating activation of factor IX, physical evidence of activation cleavages does not necessarily correlate with generation of an active site.

  10. Human factors of the high technology cockpit

    NASA Technical Reports Server (NTRS)

    Wiener, Earl L.

    1990-01-01

    The rapid advance of cockpit automation in the last decade has outstripped the ability of the human factors profession to understand the changes in human functions required. High technology cockpits require less physical (observable) workload, but are highly demanding of cognitive functions such as planning, alternative selection, and monitoring. Furthermore, automation creates opportunity for new and more serious forms of human error, and many pilots are concerned about the possibility of complacency affecting their performance. On the positive side, the equipment works as advertized with high reliability, offering highly efficient, computer-based flight. These findings from the cockpit studies probably apply equally to other industries, such as nuclear power production, other modes of transportation, medicine, and manufacturing, all of which traditionally have looked to aviation for technological leadership. The challenge to the human factors profession is to aid designers, operators, and training departments in exploiting the positive side of automation, while seeking solutions to the negative side. Viewgraphs are given.

  11. Human Factors Engineering Guidelines for Overhead Cranes

    NASA Technical Reports Server (NTRS)

    Chandler, Faith; Delgado, H. (Technical Monitor)

    2001-01-01

    This guideline provides standards for overhead crane cabs that can be applied to the design and modification of crane cabs to reduce the potential for human error due to design. This guideline serves as an aid during the development of a specification for purchases of cranes or for an engineering support request for crane design modification. It aids human factors engineers in evaluating existing cranes during accident investigations or safety reviews.

  12. Information sciences and human factors overview

    NASA Technical Reports Server (NTRS)

    Holcomb, Lee B.

    1988-01-01

    An overview of program objectives of the Information Sciences and Human Factors Division of NASA's Office of Aeronautics and Space Technology is given in viewgraph form. Information is given on the organizational structure, goals, the research and technology base, telerobotics, systems autonomy in space operations, space sensors, humans in space, space communications, space data systems, transportation vehicle guidance and control, spacecraft control, and major program directions in space.

  13. Human Factors Interface with Systems Engineering for NASA Human Spaceflights

    NASA Technical Reports Server (NTRS)

    Wong, Douglas T.

    2009-01-01

    This paper summarizes the past and present successes of the Habitability and Human Factors Branch (HHFB) at NASA Johnson Space Center s Space Life Sciences Directorate (SLSD) in including the Human-As-A-System (HAAS) model in many NASA programs and what steps to be taken to integrate the Human-Centered Design Philosophy (HCDP) into NASA s Systems Engineering (SE) process. The HAAS model stresses systems are ultimately designed for the humans; the humans should therefore be considered as a system within the systems. Therefore, the model places strong emphasis on human factors engineering. Since 1987, the HHFB has been engaging with many major NASA programs with much success. The HHFB helped create the NASA Standard 3000 (a human factors engineering practice guide) and the Human Systems Integration Requirements document. These efforts resulted in the HAAS model being included in many NASA programs. As an example, the HAAS model has been successfully introduced into the programmatic and systems engineering structures of the International Space Station Program (ISSP). Success in the ISSP caused other NASA programs to recognize the importance of the HAAS concept. Also due to this success, the HHFB helped update NASA s Systems Engineering Handbook in December 2007 to include HAAS as a recommended practice. Nonetheless, the HAAS model has yet to become an integral part of the NASA SE process. Besides continuing in integrating HAAS into current and future NASA programs, the HHFB will investigate incorporating the Human-Centered Design Philosophy (HCDP) into the NASA SE Handbook. The HCDP goes further than the HAAS model by emphasizing a holistic and iterative human-centered systems design concept.

  14. Annotated bibliography of human factors applications literature

    SciTech Connect

    McCafferty, D.B.

    1984-09-30

    This bibliography was prepared as part of the Human Factors Technology Project, FY 1984, sponsored by the Office of Nuclear Safety, US Department of Energy. The project was conducted by Lawrence Livermore National Laboratory, with Essex Corporation as a subcontractor. The material presented here is a revision and expansion of the bibliographic material developed in FY 1982 as part of a previous Human Factors Technology Project. The previous bibliography was published September 30, 1982, as Attachment 1 to the FY 1982 Project Status Report.

  15. Human Research Program: Space Human Factors and Habitability Element

    NASA Technical Reports Server (NTRS)

    Russo, Dane M.

    2007-01-01

    The three project areas of the Space Human Factors and Habitability Element work together to achieve a working and living environment that will keep crews healthy, safe, and productive throughout all missions -- from Earth orbit to Mars expeditions. The Advanced Environmental Health (AEH) Project develops and evaluates advanced habitability systems and establishes requirements and health standards for exploration missions. The Space Human Factors Engineering (SHFE) Project s goal is to ensure a safe and productive environment for humans in space. With missions using new technologies at an ever-increasing rate, it is imperative that these advances enhance crew performance without increasing stress or risk. The ultimate goal of Advanced Food Technology (AFT) Project is to develop and deliver technologies for human centered spacecraft that will support crews on missions to the moon, Mars, and beyond.

  16. Dissecting complex epigenetic alterations in human lupus.

    PubMed

    Patel, Dipak R; Richardson, Bruce C

    2013-01-01

    Systemic lupus erythematosus is a chronic relapsing autoimmune disease that primarily afflicts women, and both a genetic predisposition and appropriate environmental exposures are required for lupus to develop and flare. The genetic requirement is evidenced by an increased concordance in identical twins and by the validation of at least 35 single-nucleotide polymorphisms predisposing patients to lupus. Genes alone, though, are not enough. The concordance of lupus in identical twins is often incomplete, and when concordant, the age of onset is usually different. Lupus is also not present at birth, but once the disease develops, it typically follows a chronic relapsing course. Thus, genes alone are insufficient to cause human lupus, and additional factors encountered in the environment and over time are required to initiate the disease and subsequent flares. The nature of the environmental contribution, though, and the mechanisms by which environmental agents modify the immune response to cause lupus onset and flares in genetically predisposed people have been controversial. Reports that the lupus-inducing drugs procainamide and hydralazine are epigenetic modifiers, that epigenetically modified T cells are sufficient to cause lupus-like autoimmunity in animal models, and that patients with active lupus have epigenetic changes similar to those caused by procainamide and hydralazine have prompted a growing interest in how epigenetic alterations contribute to this disease. Understanding how epigenetic mechanisms modify T cells to contribute to lupus requires an understanding of how epigenetic mechanisms regulate gene expression. The roles of DNA methylation, histone modifications, and microRNAs in lupus pathogenesis will be reviewed here. PMID:23374884

  17. Human factors and productivity on Space Station Freedom

    NASA Technical Reports Server (NTRS)

    Leach, C. S.; Brown, J. W.; Santy, P. A.

    1989-01-01

    Three main facets of man systems are investigated with reference to the Space Station Freedom program: specific hardware systems that focus on the human element; requirements definition for man-systems integration; and crew interface and operations analysis. Three key criteria have been identified for selecting individuals to constitute the human system or crew for Space Station Freedom missions: aptitude for mission specific skills, motivation, and sensitivity to self and others. Integration of the human system into the complex engineering and science systems planned on Space Station Freedom will require the close collaboration of engineers, physicians, psychologists, and human factors experts. Ground-based research and experiments on the KC-135 aircraft are providing information about how human systems will function on a space station and how to design other systems to interact with the crew. A laboratory for further research will be provided onboard Space Station Freedom.

  18. The human factors of workstation telepresence

    NASA Technical Reports Server (NTRS)

    Smith, Thomas J.; Smith, Karl U.

    1990-01-01

    The term workstation telepresence has been introduced to describe human-telerobot compliance, which enables the human operator to effectively project his/her body image and behavioral skills to control of the telerobot itself. Major human-factors considerations for establishing high fidelity workstation telepresence during human-telerobot operation are discussed. Telerobot workstation telepresence is defined by the proficiency and skill with which the operator is able to control sensory feedback from direct interaction with the workstation itself, and from workstation-mediated interaction with the telerobot. Numerous conditions influencing such control have been identified. This raises the question as to what specific factors most critically influence the realization of high fidelity workstation telepresence. The thesis advanced here is that perturbations in sensory feedback represent a major source of variability in human performance during interactive telerobot operation. Perturbed sensory feedback research over the past three decades has established that spatial transformations or temporal delays in sensory feedback engender substantial decrements in interactive task performance, which training does not completely overcome. A recently developed social cybernetic model of human-computer interaction can be used to guide this approach, based on computer-mediated tracking and control of sensory feedback. How the social cybernetic model can be employed for evaluating the various modes, patterns, and integrations of interpersonal, team, and human-computer interactions which play a central role is workstation telepresence are discussed.

  19. Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors.

    PubMed

    Vafai, Scott B; Mevers, Emily; Higgins, Kathleen W; Fomina, Yevgenia; Zhang, Jianming; Mandinova, Anna; Newman, David; Shaw, Stanley Y; Clardy, Jon; Mootha, Vamsi K

    2016-01-01

    Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS). Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as "complex I bypass." In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology. PMID:27622560

  20. Natural Product Screening Reveals Naphthoquinone Complex I Bypass Factors

    PubMed Central

    Mevers, Emily; Higgins, Kathleen W.; Fomina, Yevgenia; Zhang, Jianming; Mandinova, Anna; Newman, David; Shaw, Stanley Y.; Clardy, Jon; Mootha, Vamsi K.

    2016-01-01

    Deficiency of mitochondrial complex I is encountered in both rare and common diseases, but we have limited therapeutic options to treat this lesion to the oxidative phosphorylation system (OXPHOS). Idebenone and menadione are redox-active molecules capable of rescuing OXPHOS activity by engaging complex I-independent pathways of entry, often referred to as “complex I bypass.” In the present study, we created a cellular model of complex I deficiency by using CRISPR genome editing to knock out Ndufa9 in mouse myoblasts, and utilized this cell line to develop a high-throughput screening platform for novel complex I bypass factors. We screened a library of ~40,000 natural product extracts and performed bioassay-guided fractionation on a subset of the top scoring hits. We isolated four plant-derived 1,4-naphthoquinone complex I bypass factors with structural similarity to menadione: chimaphilin and 3-chloro-chimaphilin from Chimaphila umbellata and dehydro-α-lapachone and dehydroiso-α-lapachone from Stereospermum euphoroides. We also tested a small number of structurally related naphthoquinones from commercial sources and identified two additional compounds with complex I bypass activity: 2-methoxy-1,4-naphthoquinone and 2-methoxy-3-methyl-1,4,-naphthoquinone. The six novel complex I bypass factors reported here expand this class of molecules and will be useful as tool compounds for investigating complex I disease biology. PMID:27622560

  1. Human and Mechanical Factors in Ergometry.

    ERIC Educational Resources Information Center

    Ellis, M. J.; Hubbard, R. P.

    Analysis of the human and mechanical factors inherent in ergometry suggest many strategies for the improvement of experiments related to exertion. The resistive principles of gravitation, friction, elasticity, viscosity, magnetism, and inertia used in ergometers impose different restraints on experiments. The suitability of different resistive…

  2. Integrating Data and Networks: Human Factors

    NASA Astrophysics Data System (ADS)

    Chen, R. S.

    2012-12-01

    The development of technical linkages and interoperability between scientific networks is a necessary but not sufficient step towards integrated use and application of networked data and information for scientific and societal benefit. A range of "human factors" must also be addressed to ensure the long-term integration, sustainability, and utility of both the interoperable networks themselves and the scientific data and information to which they provide access. These human factors encompass the behavior of both individual humans and human institutions, and include system governance, a common framework for intellectual property rights and data sharing, consensus on terminology, metadata, and quality control processes, agreement on key system metrics and milestones, the compatibility of "business models" in the short and long term, harmonization of incentives for cooperation, and minimization of disincentives. Experience with several national and international initiatives and research programs such as the International Polar Year, the Group on Earth Observations, the NASA Earth Observing Data and Information System, the U.S. National Spatial Data Infrastructure, the Global Earthquake Model, and the United Nations Spatial Data Infrastructure provide a range of lessons regarding these human factors. Ongoing changes in science, technology, institutions, relationships, and even culture are creating both opportunities and challenges for expanded interoperability of scientific networks and significant improvement in data integration to advance science and the use of scientific data and information to achieve benefits for society as a whole.

  3. Applications of Human Factors in Space

    NASA Technical Reports Server (NTRS)

    Rajulu, Sudhakar; Margerum, Sarah

    2008-01-01

    The main question for human factors practitioners is to determine if the user population can be accommodated within a design. Given the wide range of variables feeding into a design, just one of which is human factors, oftentimes designers will have restrictions that may potentially impact the level of accommodation. This paper focuses on two case studies where there have been impacts at the design level that may be detrimental to the ability of the design to meet certain criteria. The studies use novel approaches to determine what, if any, changes in population accommodation levels have occurred and what factors are important when manipulating the design in the future. The results of these studies provide a backbone for future analyses when working with design considerations.

  4. Synchronization in human musical rhythms and mutually interacting complex systems

    PubMed Central

    Hennig, Holger

    2014-01-01

    Though the music produced by an ensemble is influenced by multiple factors, including musical genre, musician skill, and individual interpretation, rhythmic synchronization is at the foundation of musical interaction. Here, we study the statistical nature of the mutual interaction between two humans synchronizing rhythms. We find that the interbeat intervals of both laypeople and professional musicians exhibit scale-free (power law) cross-correlations. Surprisingly, the next beat to be played by one person is dependent on the entire history of the other person’s interbeat intervals on timescales up to several minutes. To understand this finding, we propose a general stochastic model for mutually interacting complex systems, which suggests a physiologically motivated explanation for the occurrence of scale-free cross-correlations. We show that the observed long-term memory phenomenon in rhythmic synchronization can be imitated by fractal coupling of separately recorded or synthesized audio tracks and thus applied in electronic music. Though this study provides an understanding of fundamental characteristics of timing and synchronization at the interbrain level, the mutually interacting complex systems model may also be applied to study the dynamics of other complex systems where scale-free cross-correlations have been observed, including econophysics, physiological time series, and collective behavior of animal flocks. PMID:25114228

  5. The human factor: enhancing women's rights.

    PubMed

    Steinzor, N

    1995-01-01

    The Universal Declaration of Human Rights, adopted by the UN in 1948, declares that all human beings are born free and equal in dignity and rights, and that everyone has the right to life, liberty, and security of person. In practice, however, far from everyone has these rights, especially women. Many women worldwide have neither the awareness of nor access to family planning methods with which they could regulate their fertility and childbearing. Thus deprived of their reproductive freedom, these women cannot pursue education, employment, and other life options which would otherwise be readily available to them were they not saddled with poor reproductive health and too many children. Expanded choices enhance the status of women, which in turn helps them to reduce fertility rates and stabilize population growth. The author discusses how the wide range of cultural and social norms, and economic and political systems worldwide make it very difficult and complex to actually implement universal human rights.

  6. Human factors in high consequence manufacturing systems

    SciTech Connect

    Forsythe, C.; Grose, E.

    1997-11-01

    A high consequence system is often defined as one in which the potential exists for severe or catastrophic accidents. Familiar examples include nuclear power plants, airline and other mass transportation, dams and reservoirs, and large-scale food processing. Many manufacturing systems also qualify as high consequence systems. Much of the authors` experience with high consequence systems derives from work associated with the surveillance and dismantlement of nuclear weapons for the US Department of Energy. With such operations, there exists a risk of high explosive detonation accompanied by radiological dispersal and, potentially, nuclear detonation. Analysis of major industrial accidents such as Three Mile Island, Chernobyl and Bhopal have revealed that these incidents were not attributable to a single event or direct cause, but were the result of multiple factors that combined to create a condition ripe for an accident. In each case, human error was a critical factor contributing to the accident. Consequently, many authors have emphasized the need for greater appreciation of systematic factors and in particular, human activities. This paper discusses approaches used in hazard analysis of US nuclear weapons operations to assess risk associated with human factors.

  7. Mycobacterium abscessus Complex Infections in Humans.

    PubMed

    Lee, Meng-Rui; Sheng, Wang-Huei; Hung, Chien-Ching; Yu, Chong-Jen; Lee, Li-Na; Hsueh, Po-Ren

    2015-09-01

    Mycobacterium abscessus complex comprises a group of rapidly growing, multidrug-resistant, nontuberculous mycobacteria that are responsible for a wide spectrum of skin and soft tissue diseases, central nervous system infections, bacteremia, and ocular and other infections. M. abscessus complex is differentiated into 3 subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. The 2 major subspecies, M. abscessus subsp. abscessus and M. abscessus subsp. massiliense, have different erm(41) gene patterns. This gene provides intrinsic resistance to macrolides, so the different patterns lead to different treatment outcomes. M. abscessus complex outbreaks associated with cosmetic procedures and nosocomial transmissions are not uncommon. Clarithromycin, amikacin, and cefoxitin are the current antimicrobial drugs of choice for treatment. However, new treatment regimens are urgently needed, as are rapid and inexpensive identification methods and measures to contain nosocomial transmission and outbreaks. PMID:26295364

  8. Mycobacterium abscessus Complex Infections in Humans

    PubMed Central

    Lee, Meng-Rui; Sheng, Wang-Huei; Hung, Chien-Ching; Yu, Chong-Jen; Lee, Li-Na

    2015-01-01

    Mycobacterium abscessus complex comprises a group of rapidly growing, multidrug-resistant, nontuberculous mycobacteria that are responsible for a wide spectrum of skin and soft tissue diseases, central nervous system infections, bacteremia, and ocular and other infections. M. abscessus complex is differentiated into 3 subspecies: M. abscessus subsp. abscessus, M. abscessus subsp. massiliense, and M. abscessus subsp. bolletii. The 2 major subspecies, M. abscessus subsp. abscessus and M. abscessus subsp. massiliense, have different erm(41) gene patterns. This gene provides intrinsic resistance to macrolides, so the different patterns lead to different treatment outcomes. M. abscessus complex outbreaks associated with cosmetic procedures and nosocomial transmissions are not uncommon. Clarithromycin, amikacin, and cefoxitin are the current antimicrobial drugs of choice for treatment. However, new treatment regimens are urgently needed, as are rapid and inexpensive identification methods and measures to contain nosocomial transmission and outbreaks. PMID:26295364

  9. Space human factors publications: 1980-1990

    NASA Technical Reports Server (NTRS)

    Dickson, Katherine J.

    1991-01-01

    A 10 year cummulative bibliography of publications resulting from research supported by the NASA Space Human Factors Program of the Life Science Division is provided. The goal of this program is to understand the basic mechanisms underlying behavioral adaptation to space and to develop and validate system design requirements, protocols, and countermeasures to ensure the psychological well-being, safety, and productivity of crewmembers. Subjects encompassed by this bibliography include selection and training, group dynamics, psychophysiological interactions, habitability issues, human-machine interactions, psychological support measures, and anthropometric data. Principal Investigators whose research tasks resulted in publication are identified by asterisk.

  10. Critical Questions for Space Human Factors

    NASA Technical Reports Server (NTRS)

    Woolford, Barbara; Bagian, Tandi

    2000-01-01

    Traditional human factors contributions to NASA's crewed space programs have been rooted in the classic approaches to quantifying human physical and cognitive capabilities and limitations in the environment of interest, and producing recommendations and standards for the selection or design of mission equipment. Crews then evaluate the interfaces, displays, or equipment, and with the assistance of human factors experts, improvements are made as funds, time, control documentation, and weight allow. We have come a long way from the early spaceflight days, where men with the ' right stuff were the solution to operating whatever equipment was given to them. The large and diverse Shuttle astronaut corps has impacted mission designs to accommodate a wide range of human capabilities and preferences. Yet with existing long duration experience, we have seen the need to address a different set of dynamics when designing for optimal crew performance: critical equipment and mission situations degrade, and human function changes with mission environment, situation, and duration. Strategies for quantifying the critical nature of human factors requirements are being worked by NASA. Any exploration-class mission will place new responsibilities on mission designers to provide the crew with the information and resources to accomplish the mission. The current duties of a Mission Control Center to monitor system status, detect degradation or malfunction, and provide a proven solution, will need to be incorporated into on-board systems to allow the crew autonomous decision-making. The current option to resupply and replace mission systems and resources, including both vehicle equipment and human operators, will be removed, so considerations of maintenance, onboard training, and proficiency assessment are critical to providing a self-sufficient crew. As we 'move in' to the International Space Station, there are tremendous opportunities to investigate our ability to design for autonomous

  11. Social complexity parallels vocal complexity: a comparison of three non-human primate species

    PubMed Central

    Bouchet, Hélène; Blois-Heulin, Catherine; Lemasson, Alban

    2013-01-01

    Social factors play a key role in the structuring of vocal repertoires at the individual level, notably in non-human primates. Some authors suggested that, at the species level too, social life may have driven the evolution of communicative complexity, but this has rarely been empirically tested. Here, we use a comparative approach to address this issue. We investigated vocal variability, at both the call type and the repertoire levels, in three forest-dwelling species of Cercopithecinae presenting striking differences in their social systems, in terms of social organization as well as social structure. We collected female call recordings from twelve De Brazza's monkeys (Cercopithecus neglectus), six Campbell's monkeys (Cercopithecus campbelli) and seven red-capped mangabeys (Cercocebus torquatus) housed in similar conditions. First, we noted that the level of acoustic variability and individual distinctiveness found in several call types was related to their importance in social functioning. Contact calls, essential to intra-group cohesion, were the most individually distinctive regardless of the species, while threat calls were more structurally variable in mangabeys, the most “despotic” of our three species. Second, we found a parallel between the degree of complexity of the species' social structure and the size, diversity, and usage of its vocal repertoire. Mangabeys (most complex social structure) called twice as often as guenons and displayed the largest and most complex repertoire. De Brazza's monkeys (simplest social structure) displayed the smallest and simplest repertoire. Campbell's monkeys displayed an intermediate pattern. Providing evidence of higher levels of vocal variability in species presenting a more complex social system, our results are in line with the theory of a social-vocal coevolution of communicative abilities, opening new perspectives for comparative research on the evolution of communication systems in different animal taxa. PMID

  12. Introduction to human factors considerations in system design

    NASA Technical Reports Server (NTRS)

    Chapanis, A.

    1983-01-01

    A definition for human factors or ergonomics and its industrial and domestic application is presented. Human factors engineering, which discovers and applies information about human abilities, limitations, and other characteristics to the design of tools, machines, systems, tasks, jobs, and environments for safe, comfortable, and effective human use, is outlined. The origins of human factors and ergonomics, the philosophy of human factors, goals and objectives, systems development and design, are reviewed.

  13. The space station: Human factors and productivity

    NASA Technical Reports Server (NTRS)

    Gillan, D. J.; Burns, M. J.; Nicodemus, C. L.; Smith, R. L.

    1986-01-01

    Human factor researchers and engineers are making inputs into the early stages of the design of the Space Station to improve both the quality of life and work on-orbit. Effective integration of the human factors information related to various Intravehicular Activity (IVA), Extravehicular Activity (EVA), and teletobotics systems during the Space Station design will result in increased productivity, increased flexibility of the Space Stations systems, lower cost of operations, improved reliability, and increased safety for the crew onboard the Space Station. The major features of productivity examined include the cognitive and physical effort involved in work, the accuracy of worker output and ability to maintain performance at a high level of accuracy, the speed and temporal efficiency with which a worker performs, crewmember satisfaction with their work environment, and the relation between performance and cost.

  14. Analog environments in space human factors

    NASA Technical Reports Server (NTRS)

    Connors, Mary M.

    1992-01-01

    An account is given of what has been learned from space analog environments, which mimic such significant features of space as isolation, confinement, risk, and deprivation; emphasis is placed on the especially successful environments constituted by extended submarine research, undersea habitats, and Antarctic station wintering. Attention is also given to the advantages and limitations of the use of analog environments for space human factors research, and possibilities for such research efforts' management.

  15. Humanism as a common factor in psychotherapy.

    PubMed

    Wampold, Bruce E

    2012-12-01

    There are many forms of psychotherapies, each distinctive in its own way. From the origins of psychotherapy, it has been suggested that psychotherapy is effective through factors that are common to all therapies. In this article, I suggest that the commonalities that are at the core of psychotherapy are related to evolved human characteristics, which include (a) making sense of the world, (b) influencing through social means, and (c) connectedness, expectation, and mastery. In this way, all psychotherapies are humanistic.

  16. Isolation of human serum spreading factor.

    PubMed

    Barnes, D W; Silnutzer, J

    1983-10-25

    Serum spreading factor (SF) was isolated from human serum by a four-step procedure employing affinity chromatography on glass beads, concanavalin A-Sepharose, DEAE-agarose, and heparin-agarose. The final product was purified approximately 260-fold from the starting material and was maximally active in assays of cell spreading-promoting activity at 300 ng/ml. The isolated human SF preparation consisted of two proteins of apparent molecular weights approximately 65,000 (SF65) and 75,000 (SF75). Both SF65 and SF75 have been shown previously to exhibit cell spreading-promoting activity and to bind monoclonal antibody to human serum SF. PMID:6630199

  17. Human factors engineers as change agents

    SciTech Connect

    Hallbert, B.P.; Harbour, G.L.; Caccamise, D.J.; Francis, L.C.

    1992-01-01

    This presentation describes a case study and the lessons learned when a Human Factors Engineering (HFE) Department was enlisted as technical experts but gradually assumed a much larger role as change agents in transforming outdated job practices into streamlined processes that promoted a safety culture. At Rocky Flats Nuclear Weapons processing plant in Colorado, a workforce of over 7000 people support or directly operate a myriad of processes that range from laboratory analysis to typical foundry activities, greatly complicated by the presence of fissile, radioactive materials. Safe handling of these materials was governed by detailed discussions contained in Nuclear Material Safety limits (NMSLs). In spite of this rather extensive documentation, operators were committing an unacceptable number of safety infractions. Analysis revealed NMSLs were difficult to comprehend and not practical for use in operational settings. New job performance aids, called Criticality Safety Operating Limits (CSOLs) were developed to solve these problems. However, the solution involved more than applying good human factors principles to this job-aid. Following the classic Lewin Force Field Model of Change, safety infractions made change imperative; the forces operating against it were tradition, and perceived irrelevance of new expertise. Historically, Criticality Engineering dictated safety limits to Operations. In the course of Human Factoring'' the CSOLs, the HFE, through an iterative process, became the team integrator of this development process. Using Quality concepts such as buy-in, empowerment, and ownership, HFE was able to instantiate and receive enthusiastic acceptance of their products.

  18. Space Station crew safety - Human factors model

    NASA Technical Reports Server (NTRS)

    Cohen, M. M.; Junge, M. K.

    1984-01-01

    A model of the various human factors issues and interactions that might affect crew safety is developed. The first step addressed systematically the central question: How is this Space Station different from all other spacecraft? A wide range of possible issue was identified and researched. Five major topics of human factors issues that interacted with crew safety resulted: Protocols, Critical Habitability, Work Related Issues, Crew Incapacitation and Personal Choice. Second, an interaction model was developed that would show some degree of cause and effect between objective environmental or operational conditions and the creation of potential safety hazards. The intermediary steps between these two extremes of causality were the effects on human performance and the results of degraded performance. The model contains three milestones: stressor, human performance (degraded) and safety hazard threshold. Between these milestones are two countermeasure intervention points. The first opportunity for intervention is the countermeasure against stress. If this countermeasure fails, performance degrades. The second opportunity for intervention is the countermeasure against error. If this second countermeasure fails, the threshold of a potential safety hazard may be crossed.

  19. Safe surgery, the human factors approach.

    PubMed

    O'Connor, Tony; Papanikolaou, V; Keogh, I

    2010-04-01

    Studies estimate that a degree of error occurs in 5-15% of all hospital admissions, with 45% of errors occurring in the operating theatre. Staffing limitations, high turnover rates, site and side-specific surgical procedures, make operating theatres a high-risk environment. Valuable lessons may be learned from the aviation experience with error management. With over 70% of air-crashes occurring due to human rather than technical error, the Human Factors Approach to error recognises the potential for errors occurring due to human limitations, such as stress and fatigue. It encourages error reporting in a non-punitive environment, where it is seen as a valuable source of information, facilitating education and future error prevention. Errors in healthcare and surgery however, have been traditionally associated with secrecy and embarrassment, often reaching an unsatisfactory endpoint with no resultant education. Application of the Human Factors Approach to error management in healthcare, can only serve to improve safety standards in our hospitals and satisfy ever-increasing public expectations.

  20. Human factors for a sustainable future.

    PubMed

    Thatcher, Andrew; Yeow, Paul H P

    2016-11-01

    Current human activities are seriously eroding the ability of natural and social systems to cope. Clearly we cannot continue along our current path without seriously damaging our own ability to survive as a species. This problem is usually framed as one of sustainability. As concerned professionals, citizens, and humans there is a strong collective will to address what we see as a failure to protect the natural and social environments that supports us. While acknowledging that we cannot do this alone, human factors and ergonomics needs to apply its relevant skills and knowledge to assist where it can in addressing the commonly identified problem areas. These problems include pollution, climate change, renewable energy, land transformation, and social unrest amongst numerous other emerging global problems. The issue of sustainability raises two fundamental questions for human factors and ergonomics: which system requires sustaining and what length of time is considered sustainable? In this paper we apply Wilson (2014) parent-sibling-child model to understanding what is required of an HFE sustainability response. This model is used to frame the papers that appear in this Special Issue.

  1. Human factors in modern traffic systems.

    PubMed

    Noy, Y I

    1997-10-01

    Traffic systems are undergoing enormous change with the advent of Intelligent Transport Systems (ITS). Although productivity and quality of mobility are emerging interests, safety remains the predominant preoccupation of ITS human factors. It should be evident that while intelligent technologies may have the potential to improve traffic safety, they also have the potential to adversely affect it. Ultimately, the effect on safety depends on the specific technologies that are invoked and the manner in which they are incorporated within the vehicle as well as within the larger road transportation system. Current automotive developments can be characterized as technology-centred solutions rather than user-centred solutions. Greater effort must be directed at understanding and accommodating the human element in the road transportation system in order that future transportation objectives can be achieved. There is a need to expand the scope of traditional human factors to include macro-level effects as well as to place greater emphasis on understanding human interactions with other elements of the system. There is also increasing recognition of the urgent need for systematic procedures and criteria for testing the safety of ITS prior to large-scale market penetration.

  2. Human factors in modern traffic systems.

    PubMed

    Noy, Y I

    1997-10-01

    Traffic systems are undergoing enormous change with the advent of Intelligent Transport Systems (ITS). Although productivity and quality of mobility are emerging interests, safety remains the predominant preoccupation of ITS human factors. It should be evident that while intelligent technologies may have the potential to improve traffic safety, they also have the potential to adversely affect it. Ultimately, the effect on safety depends on the specific technologies that are invoked and the manner in which they are incorporated within the vehicle as well as within the larger road transportation system. Current automotive developments can be characterized as technology-centred solutions rather than user-centred solutions. Greater effort must be directed at understanding and accommodating the human element in the road transportation system in order that future transportation objectives can be achieved. There is a need to expand the scope of traditional human factors to include macro-level effects as well as to place greater emphasis on understanding human interactions with other elements of the system. There is also increasing recognition of the urgent need for systematic procedures and criteria for testing the safety of ITS prior to large-scale market penetration. PMID:9339139

  3. Human factors for a sustainable future.

    PubMed

    Thatcher, Andrew; Yeow, Paul H P

    2016-11-01

    Current human activities are seriously eroding the ability of natural and social systems to cope. Clearly we cannot continue along our current path without seriously damaging our own ability to survive as a species. This problem is usually framed as one of sustainability. As concerned professionals, citizens, and humans there is a strong collective will to address what we see as a failure to protect the natural and social environments that supports us. While acknowledging that we cannot do this alone, human factors and ergonomics needs to apply its relevant skills and knowledge to assist where it can in addressing the commonly identified problem areas. These problems include pollution, climate change, renewable energy, land transformation, and social unrest amongst numerous other emerging global problems. The issue of sustainability raises two fundamental questions for human factors and ergonomics: which system requires sustaining and what length of time is considered sustainable? In this paper we apply Wilson (2014) parent-sibling-child model to understanding what is required of an HFE sustainability response. This model is used to frame the papers that appear in this Special Issue. PMID:27234806

  4. Human epidermal growth factor and the proliferation of human fibroblasts.

    PubMed

    Carpenter, G; Cohen, S

    1976-06-01

    The effect of human epidermal growth factor (hEGF), a 5,400 molecular weight polypeptide isolated from human urine, on the growth of human foreskin fibroblasts (HF cells) was studied by measuring cell numbers and the incorporation of labeled thymidine. The addition of hEGF to HF cells growing in a medium containing 10% calf serum resulted in a 4-fold increase in the final density. The presence of hEGF also promoted the growth of HF cells in media containing either 1% calf serum or 10% gamma globulin-free serum. The addition of hEGF to quiescent confluent monolayers of HF cells, maintained in a medium with 1% calf serum for 48 hours, resulted in a 10- to 20-fold increase in the amount of 3H-thymidine incorporation after 20-24 hours. The stimulation of thymidine incorporation was maximal at an hEGF concentration of 2 ng/ml, was dependent on the presence of serum, and was enhanced by the addition of ascorbic acid. In confluent cultures of HF cells, subject to density dependent inhibition of growth, hEGF was able to stimulate DNA synthesis more effectively than fresh calf serum. Human EGF stimulated DNA synthesis in quiescent cultures, however, regardless of cell density. The addition of rabbit anti-hEGF inhibited all effects of this growth factor on HF cells.

  5. The Gla domain of factor IXa binds to factor VIIIa in the tenase complex.

    PubMed

    Blostein, Mark D; Furie, Barbara C; Rajotte, Isabelle; Furie, Bruce

    2003-08-15

    During blood coagulation factor IXa binds to factor VIIIa on phospholipid membranes to form an enzymatic complex, the tenase complex. To test whether there is a protein-protein contact site between the gamma-carboxyglutamic acid (Gla) domain of factor IXa and factor VIIIa, we demonstrated that an antibody to the Gla domain of factor IXa inhibited factor VIIIa-dependent factor IXa activity, suggesting an interaction of the factor IXa Gla domain with factor VIIIa. To study this interaction, we synthesized three analogs of the factor IXa Gla domain (FIX1-47) with Phe-9, Phe-25, or Val-46 replaced, respectively, with benzoylphenylalanine (BPA), a photoactivatable cross-linking reagent. These factor IX Gla domain analogs maintain native tertiary structure, as demonstrated by calcium-induced fluorescence quenching and phospholipid binding studies. In the absence of phospholipid membranes, FIX1-47 was able to inhibit factor IXa activity. This inhibition is dependent on the presence of factor VIIIa, suggesting a contact site between the factor IXa Gla domain and factor VIIIa. To demonstrate a direct interaction we did cross-linking experiments with FIX1-479BPA, FIX1-4725BPA, and FIX1-4746BPA. Covalent cross-linking to factor VIIIa was observed primarily with FIX1-4725BPA and to a much lesser degree with FIX1-4746BPA. Immunoprecipitation experiments with an antibody to the C2 domain of factor VIIIa indicate that the factor IX Gla domain cross-links to the A3-C1-C2 domain of factor VIIIa. These results suggest that the factor IXa Gla domain contacts factor VIIIa in the tenase complex through a contact site that includes phenylalanine 25 and perhaps valine 46.

  6. Improving Safety through Human Factors Engineering.

    PubMed

    Siewert, Bettina; Hochman, Mary G

    2015-10-01

    Human factors engineering (HFE) focuses on the design and analysis of interactive systems that involve people, technical equipment, and work environment. HFE is informed by knowledge of human characteristics. It complements existing patient safety efforts by specifically taking into consideration that, as humans, frontline staff will inevitably make mistakes. Therefore, the systems with which they interact should be designed for the anticipation and mitigation of human errors. The goal of HFE is to optimize the interaction of humans with their work environment and technical equipment to maximize safety and efficiency. Special safeguards include usability testing, standardization of processes, and use of checklists and forcing functions. However, the effectiveness of the safety program and resiliency of the organization depend on timely reporting of all safety events independent of patient harm, including perceived potential risks, bad outcomes that occur even when proper protocols have been followed, and episodes of "improvisation" when formal guidelines are found not to exist. Therefore, an institution must adopt a robust culture of safety, where the focus is shifted from blaming individuals for errors to preventing future errors, and where barriers to speaking up-including barriers introduced by steep authority gradients-are minimized. This requires creation of formal guidelines to address safety concerns, establishment of unified teams with open communication and shared responsibility for patient safety, and education of managers and senior physicians to perceive the reporting of safety concerns as a benefit rather than a threat. PMID:26466179

  7. Human Factors in Accidents Involving Remotely Piloted Aircraft

    NASA Technical Reports Server (NTRS)

    Merlin, Peter William

    2013-01-01

    This presentation examines human factors that contribute to RPA mishaps and provides analysis of lessons learned. RPA accident data from U.S. military and government agencies were reviewed and analyzed to identify human factors issues. Common contributors to RPA mishaps fell into several major categories: cognitive factors (pilot workload), physiological factors (fatigue and stress), environmental factors (situational awareness), staffing factors (training and crew coordination), and design factors (human machine interface).

  8. Constructing the S-matrix With Complex Factorization

    SciTech Connect

    Schuster, Philip C.; Toro, Natalia; /Stanford U., ITP

    2009-06-19

    A remarkable connection between BCFW recursion relations and constraints on the S-matrix was made by Benincasa and Cachazo in 0705.4305, who noted that mutual consistency of different BCFW constructions of four-particle amplitudes generates nontrivial (but familiar) constraints on three-particle coupling constants - these include gauge invariance, the equivalence principle, and the lack of non-trivial couplings for spins > 2. These constraints can also be derived with weaker assumptions, by demanding the existence of four-point amplitudes that factorize properly in all unitarity limits with complex momenta. From this starting point, we show that the BCFW prescription can be interpreted as an algorithm for fully constructing a tree-level S-matrix, and that complex factorization of general BCFW amplitudes follows from the factorization of four-particle amplitudes. The allowed set of BCFW deformations is identified, formulated entirely as a statement on the three-particle sector, and using only complex factorization as a guide. Consequently, our analysis based on the physical consistency of the S-matrix is entirely independent of field theory. We analyze the case of pure Yang-Mills, and outline a proof for gravity. For Yang-Mills, we also show that the well-known scaling behavior of BCFW-deformed amplitudes at large z is a simple consequence of factorization. For gravity, factorization in certain channels requires asymptotic behavior {approx} 1/z{sup 2}.

  9. Human Factors Technologies: Past Promises, Future Issues. Final Technical Paper.

    ERIC Educational Resources Information Center

    Alluisi, Earl A.

    This discussion of the major issues confronting the human factors profession begins by pointing out that the concepts of systems and system design are central to the roles and functions of the human factors specialist. Three related disciplines--human factors engineering, ergonomics, and human skilled performance--are briefly described, and the…

  10. Expression of active human factor IX in transfected cells.

    PubMed

    Busby, S; Kumar, A; Joseph, M; Halfpap, L; Insley, M; Berkner, K; Kurachi, K; Woodbury, R

    Factor IX is the precursor of a serine protease that functions in the intrinsic blood clotting pathway. Deficiencies in this plasma glycoprotein result in haemophilia B (or Christmas disease) and occur in about 1 in 30,000 males. Patients are currently treated with fresh frozen plasma or prothrombin complex concentrates prepared from pooled plasma from normal individuals. There are several problems with this method of treatment, including the probable exposure of the patients to contaminants such as the viral agents responsible for hepatitis and AIDS (acquired immune deficiency syndrome). As a first step towards an alternative source of pure human factor IX, we report here on the use of recombinant DNA techniques to produce biologically active factor IX in cultured mammalian cells. Stable cell lines were produced by cotransfecting a baby hamster kidney (BHK) cell line with a plasmid containing a gene for factor IX and a plasmid containing a selectable marker. Protein secreted by these cell lines reduces the clotting time of plasma from factor IX-deficient patients. We present additional evidence that this protein is authentic human factor IX.

  11. Investigating the Effect of Complexity Factors in Gas Law Problems

    ERIC Educational Resources Information Center

    Schuttlefield, Jennifer D.; Kirk, John; Pienta, Norbert J.; Tang, Hui

    2012-01-01

    Undergraduate students were asked to complete gas law questions using a Web-based tool as a first step in our understanding of the role of cognitive load in chemistry word questions and in helping us assess student problem-solving. Each question contained five different complexity factors, which were randomly assigned by the tool so that a…

  12. Conglutinin-like factors in human saliva--relation to other salivary aggregating factors--.

    PubMed

    Murai, Y

    1980-12-01

    This study was conducted to examine the relation between conglutinin-like factors and other bacterial aggregating factors in human saliva. Human and guinea pig complement intermediate cells (EAC4b,3b) were prepared by using and anticomplementary agent K-76 COONa. Conglutinin-like factors and agglutinins for sensitized sheep erythrocytes in parotid and whole saliva from seven subjects were examined. Whole saliva from the subjects with a periodontal disease showed a lower activity than that from the subjects with a clinically normal gingiva. It seems, therefore, that some strum component from the gingival crevice inhibit the aggregation of sensitized sheep erthrocytes by saliva as in the case of the conglutination of EAC4b, 3b cells. Conglutinin-like factors appeard over a wide region including both the void volume and the secretory IgA region in gel filtration of human whole saliva on Sepharose 4B. The void volume fractions contained a high conglutinin-like factor activity but no Iga activity. These data suggest that conglutinin-like factors are not polymers of IgA but complexes of glycoproteins or those on which IgA is bound furthermore. PMID:6936093

  13. Hemoglobin enhances tissue factor expression on human malignant cells.

    PubMed

    Siddiqui, F A; Amirkhosravi, A; Amaya, M; Meyer, T; Biggerstaff, J; Desai, H; Francis, J L

    2001-04-01

    Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined.

  14. Hemoglobin enhances tissue factor expression on human malignant cells.

    PubMed

    Siddiqui, F A; Amirkhosravi, A; Amaya, M; Meyer, T; Biggerstaff, J; Desai, H; Francis, J L

    2001-04-01

    Tissue Factor (TF) is a transmembrane glycoprotein that complexes with factor VII/activated factor VII to initiate blood coagulation. TF may be expressed on the surface of various cells including monocytes and endothelial cells. Over-expression of TF in human tumor cell lines promotes metastasis. We recently showed that hemoglobin (Hb) forms a specific complex with TF purified from human malignant melanoma cells and enhances its procoagulant activity (PCA). To further study this interaction, we examined the effect of Hb on the expression of TF on human malignant (TF+) cells and KG1 myeloid leukemia (TF-) cells. Human melanoma A375 and J82 bladder carcinoma cells, which express TF at moderate and relatively high levels, respectively, were incubated with varying concentrations (0-1.5 mg/ml) of Hb. After washing, cells were analyzed for Hb binding and TF expression using flow cytometry and confocal microscopy. Hb bound to the cells in a concentration-dependent manner, and increased both TF expression and PCA. The human A375 malignant melanoma cells incubated with Hb (1 mg/ml) expressed up to six times more TF antigen than cells without Hb. This increase in TF expression and PCA of intact cells incubated with Hb was significantly inhibited by cycloheximide at a concentration of 10 microg/ml (P < 0.01). An increase in total cellular TF antigen content was demonstrated by specific immunoassay. In contrast, Hb (5 mg/ml) did not induce TF expression and PCA on KG1 cells as determined by flow cytometry and TF (FXAA) activity. We conclude that Hb specifically binds to TF-bearing malignant cells and increases their PCA. This effect seems to be at least partly due to de novo synthesis of TF and increased surface expression. However, the exact mechanism by which Hb binds and upregulates TF expression remains to be determined. PMID:11414630

  15. Human factors engineering program review model

    SciTech Connect

    Not Available

    1994-07-01

    The staff of the Nuclear Regulatory Commission is performing nuclear power plant design certification reviews based on a design process plan that describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification and an acceptable implemented design. There are two principal reasons for this approach. First, the initial design certification applications submitted for staff review did not include detailed design information. Second, since human performance literature and industry experiences have shown that many significant human factors issues arise early in the design process, review of the design process activities and results is important to the evaluation of an overall design. However, current regulations and guidance documents do not address the criteria for design process review. Therefore, the HFE Program Review Model (HFE PRM) was developed as a basis for performing design certification reviews that include design process evaluations as well as review of the final design. A central tenet of the HFE PRM is that the HFE aspects of the plant should be developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The HFE PRM consists of ten component elements. Each element in divided into four sections: Background, Objective, Applicant Submittals, and Review Criteria. This report describes the development of the HFE PRM and gives a detailed description of each HFE review element.

  16. [Asthma: a complex disease determined by genetic and environmental factors].

    PubMed

    Louis, R; Schleich, F; Corhay, J-L; Louis, E

    2012-01-01

    Asthma is a complex disease highly dependent of environmental exposure and genetic background. Through linkage analysis, positional cloning and genome wide association studies, novel asthma genes have come out such as ADAM-33 or ORMLD3. Important environmental factors include allergenic exposure, pollutants and especially particulate matters, tobacco, aerosol exposure, viral infections and level of exposure to endotoxin. The effects of environmental factors are modulated by the genetic sequence and numerous single nucleotide polymorphisms (SNPs). Recently, it has also become clear that environmental factors may alter gene expression by DNA methylation or histone methylation/acetylation without changing the gene sequence and thereby changing asthmatic phenotype.

  17. Understanding complexity in the human brain

    PubMed Central

    Bassett, Danielle S.; Gazzaniga, Michael S.

    2011-01-01

    Although the ultimate aim of neuroscientific enquiry is to gain an understanding of the brain and how its workings relate to the mind, the majority of current efforts are largely focused on small questions using increasingly detailed data. However, it might be possible to successfully address the larger question of mind–brain mechanisms if the cumulative findings from these neuroscientific studies are coupled with complementary approaches from physics and philosophy. The brain, we argue, can be understood as a complex system or network, in which mental states emerge from the interaction between multiple physical and functional levels. Achieving further conceptual progress will crucially depend on broad-scale discussions regarding the properties of cognition and the tools that are currently available or must be developed in order to study mind–brain mechanisms. PMID:21497128

  18. Human factors for pleasure in product use.

    PubMed

    Jordan, P W

    1998-02-01

    Traditionally, human factors have tended to concentrate on making products 'usable'--focusing on utilitarian, functional product benefits. This paper reports an interview-based study looking at the issue of 'pleasure' in product use. The study was a 'first pass' at addressing the hedonic and experiential benefits and penalties associated with product use, and at identifying the properties of a product that influence how pleasurable or displeasurable it is to use. Feelings associated with using pleasurable products included security, confidence, pride, excitement and satisfaction. Displeasurable products, meanwhile, were associated with feelings that included annoyance, anxiety, contempt and frustration. The properties of products that were salient in terms of influencing the level of pleasure/displeasure with a product included features, usability, aesthetics, performance and reliability. Responses to questions investigating behavioural correlates to pleasure in product use suggested that pleasurable products were used more regularly and that future purchase choices would be affected by the level of pleasure in product use. It is concluded that the issue of pleasure in product use involves more than usability alone. As the user's representative in the product creation process, the human factors specialist should consider many other factors in order to ensure that the user's experience of product use is maximised.

  19. Understanding the complexity of human gait dynamics

    NASA Astrophysics Data System (ADS)

    Scafetta, Nicola; Marchi, Damiano; West, Bruce J.

    2009-06-01

    Time series of human gait stride intervals exhibit fractal and multifractal properties under several conditions. Records from subjects walking at normal, slow, and fast pace speed are analyzed to determine changes in the fractal scalings as a function of the stress condition of the system. Records from subjects with different age from children to elderly and patients suffering from neurodegenerative disease are analyzed to determine changes in the fractal scalings as a function of the physical maturation or degeneration of the system. A supercentral pattern generator model is presented to simulate the above two properties that are typically found in dynamical network performance: that is, how a dynamical network responds to stress and to evolution.

  20. Understanding the complexity of human gait dynamics.

    PubMed

    Scafetta, Nicola; Marchi, Damiano; West, Bruce J

    2009-06-01

    Time series of human gait stride intervals exhibit fractal and multifractal properties under several conditions. Records from subjects walking at normal, slow, and fast pace speed are analyzed to determine changes in the fractal scalings as a function of the stress condition of the system. Records from subjects with different age from children to elderly and patients suffering from neurodegenerative disease are analyzed to determine changes in the fractal scalings as a function of the physical maturation or degeneration of the system. A supercentral pattern generator model is presented to simulate the above two properties that are typically found in dynamical network performance: that is, how a dynamical network responds to stress and to evolution. PMID:19566268

  1. Epidermal growth factor (urogastrone) in human tissues.

    PubMed

    Hirata, Y; Orth, D N

    1979-04-01

    Human epidermal growth factor (hEGF), which stimulates the growth of a variety of tissues, was first isolated from mouse submandibular glands, but is also excreted in large amounts (about 50 micrograms/day) in human urine and is probably identical to human beta-urogastrone (hUG), a potent inhibitor of stimulated gastric acid secretion. However, the primary tissue source of hEGF/hUG is as yet unknown. The hEGF/hUG in homogenates of human salivary glands and a wide variety of other endocrine and nonendocrine tissues was extracted by Amberlite CG-50 cation exchange chromatography and immune affinity chromatography using the immunoglobulin fraction of rabbit anti-hEGF serum covalently bound to agarose. The extracts were subjected to homologous hEGF RIA. Immunoreactive hEGF was found in extracts of adult submandibular gland, thyroid gland, duodenum, jejunum, and kidney, but not in several fetal tissues. The tissue immunoreactive hEGF was similar to standard hEGF in terms of immunoreactivity and elution from Sephadex G-50 Fine resin, but its concentrations were very low (1.3-5.5 ng/g wet tissue). Thus, it is not certain that these tissues represent the only source of the large amounts of hEGF/hUG that appear to be filtered by the kidneys each day.

  2. Space human factors discipline science plan

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The purpose of this Discipline Science Plan is to provide a conceptual strategy for NASA's Life Sciences Division research and development activities in the comprehensive areas of behavior, performance, and human factors. This document summarizes the current status of the program, outlines available knowledge, establishes goals and objectives, defines critical questions in the subdiscipline areas, and identifies technological priorities. It covers the significant research areas critical to NASA's programmatic requirements for the Extended Duration Orbiter, Space Station Freedom, and Exploration mission science activities. These science activities include ground-based and flight; basic, applied and operational; and animal and human research and development. This document contains a general plan that will be used by both NASA Headquarters program offices and the field centers to review and plan basic, applied, and operational research and development activities, both intramural and extramural, in this area.

  3. Vestibular reactions to spaceflight: human factors issues.

    PubMed

    Young, L R

    2000-09-01

    Vestibular function, along with other sensory systems influencing spatial orientation, can have a profound influence on the ability of astronauts to function effectively. Beyond the well-known problems of space motion sickness, vestibular effects can influence astronaut well-being and performance during all phases of a space mission. This paper discusses some of the major vestibular reactions affecting human factors encountered in all space missions, and covers them chronologically in the following sequence: launch, early on-orbit, late on-orbit, EVA, artificial gravity, re-entry, and post-landing.

  4. Review of EPRI Nuclear Human Factors Program

    SciTech Connect

    Hanes, L.F.; O`Brien, J.F.

    1996-03-01

    The Electric Power Research Institute (EPRI) Human Factors Program, which is part of the EPRI Nuclear Power Group, was established in 1975. Over the years, the Program has changed emphasis based on the shifting priorities and needs of the commercial nuclear power industry. The Program has produced many important products that provide significant safety and economic benefits for EPRI member utilities. This presentation will provide a brief history of the Program and products. Current projects and products that have been released recently will be mentioned.

  5. Chiral heterobimetallic complexes targeting human DNA-topoisomerase Iα.

    PubMed

    Tabassum, Sartaj; Asim, Ahmad; Khan, Rais Ahmad; Hussain, Zahid; Srivastav, Saurabh; Srikrishna, Saripella; Arjmand, Farukh

    2013-12-28

    The chiral monometallic Cu(II) (1) and Zn(II) (2) and heterobimetallic Cu(II)-Sn(IV) and Zn(II)-Sn(IV) complexes with tridentate chiral Schiff base -ONO-ligand in the presence of nitrogen donor heterocyclic ligand imidazole; were prepared and characterized by various physico-chemical and spectroscopic methods. Preliminary complex-DNA interaction studies employing optical methods revealed that 3 displayed a higher propensity towards the drug target DNA double helix and recommended predominantly an electrostatic mode of interaction as well as a groove binding affinity of the complex with CT-DNA. This was quantified by Kb and KSV values of complexes 1-4, which demonstrated a multifold increase in complex 3 binding to CT DNA and clearly demonstrates its potency to act as a chemotherapeutic agent. Furthermore, the gel electrophoretic patterns of supercoiled pBR322 DNA with varying concentrations of complex 3 exhibits the ability to cleave DNA and follow a freely diffusible radical mechanism. The antiproliferative effects of complex 3 on human hepatoma cancer cells (Huh7) was investigated. Human Topo I inhibition assay by complex 3 was performed and results confirmed significantly good activity at lower concentrations than some of the classical Topo I inhibitors. Additionally, complex 3 was investigated for the expression of MMP-2 and TGF-β by real time PCR. The cellular uptake of complex 3 by HeLa cells was studied by confocal microscopy. PMID:24077532

  6. Time to accelerate integration of human factors and ergonomics in patient safety.

    PubMed

    Gurses, Ayse P; Ozok, A Ant; Pronovost, Peter J

    2012-04-01

    Progress toward improving patient safety has been slow despite engagement of the health care community in improvement efforts. A potential reason for this sluggish pace is the inadequate integration of human factors and ergonomics principles and methods in these efforts. Patient safety problems are complex and rarely caused by one factor or component of a work system. Thus, health care would benefit from human factors and ergonomics evaluations to systematically identify the problems, prioritize the right ones, and develop effective and practical solutions. This paper gives an overview of the discipline of human factors and ergonomics and describes its role in improving patient safety. We provide examples of how human factors and ergonomics principles and methods have improved both care processes and patient outcomes. We provide five major recommendations to better integrate human factors and ergonomics in patient safety improvement efforts: build capacity among health care workers to understand human factors and ergonomics, create market forces that demand the integration of human factors and ergonomics design principles into medical technologies, increase the number of human factors and ergonomic practitioners in health care organizations, expand investments in improvement efforts informed by human factors and ergonomics, and support interdisciplinary research to improve patient safety. In conclusion, human factors and ergonomics must play a more prominent role in health care if we want to increase the pace in improving patient safety.

  7. Human Factors of Remotely Piloted Aircraft

    NASA Technical Reports Server (NTRS)

    Hobbs, Alan Neville

    2014-01-01

    The civilian use of remotely piloted, or unmanned aircraft is expected to increase rapidly in the years ahead. Despite being referred to as unmanned some of the major challenges confronting this emerging sector relate to human factors. As unmanned aircraft systems (UAS) are introduced into civil airspace, a failure to adequately consider human factors could result in preventable accidents that may not only result in loss of life, but may also undermine public confidence in remotely piloted operations. Key issues include pilot situational awareness, collision avoidance in the absence of an out-the-window view, the effects of time delays in communication and control systems, control handovers, the challenges of very long duration flights, and the design of the control station. Problems have included poor physical layout of controls, non-intuitive automation interfaces, an over-reliance on text displays, and complicated sequences of menu selection to perform routine tasks. Some of the interface problems may have been prevented had an existing regulation or cockpit design principle been applied. In other cases, the design problems may indicate a lack of suitable guidance material.

  8. An integrated approach to rotorcraft human factors research

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.; Hartzell, E. James; Voorhees, James W.; Bucher, Nancy M.; Shively, R. Jay

    1988-01-01

    As the potential of civil and military helicopters has increased, more complex and demanding missions in increasingly hostile environments have been required. Users, designers, and manufacturers have an urgent need for information about human behavior and function to create systems that take advantage of human capabilities, without overloading them. Because there is a large gap between what is known about human behavior and the information needed to predict pilot workload and performance in the complex missions projected for pilots of advanced helicopters, Army and NASA scientists are actively engaged in Human Factors Research at Ames. The research ranges from laboratory experiments to computational modeling, simulation evaluation, and inflight testing. Information obtained in highly controlled but simpler environments generates predictions which can be tested in more realistic situations. These results are used, in turn, to refine theoretical models, provide the focus for subsequent research, and ensure operational relevance, while maintaining predictive advantages. The advantages and disadvantages of each type of research are described along with examples of experimental results.

  9. [Growth factors in human tooth development].

    PubMed

    Bellone, C; Barni, T; Pagni, L; Balboni, G C; Vannelli, G B

    1990-03-01

    Our research concerns the immunohistochemical localization of EGF and IGF-I receptors in the tooth germ, using monoclonal antibodies. The results show that in the early phases of human tooth development EGF and IGF-I receptors are present. At bud stage both receptors are localized at dental laminae level, in some epithelial cells of the tooth bud and in some mesenchymal cells. At cap stage the receptors are present in the outer and inner enamel epithelium, and in some cells of stellate reticulum. As far as concerns the mesenchymal cells, some cells of dental papilla in contact with enamel organ, are intensely positive. The immunopositivity is present also in some mesenchymal cells at follicular level. At late cap stage and at early bell stage receptors are not present at inner enamel epithelium level but they can be detectable in the mesenchyma of dental papilla and in some cells of the follicle. On the basis of these results it may be hypothesized that EGF and IGF-I can act as growth factors in the modulation of cellular proliferation and differentiation during the human tooth morphogenesis. Moreover, it is possible that these substances can play a role in the mesenchymal-epithelial interaction in the developing human tooth.

  10. Functional analysis of a growth factor-responsive transcription factor complex.

    PubMed

    Hill, C S; Marais, R; John, S; Wynne, J; Dalton, S; Treisman, R

    1993-04-23

    Serum response factor (SRF) forms a ternary complex at the c-fos serum response element (SRE) with an accessory factor, Elk-1. We constructed altered-binding specificity derivatives of SRF and Elk-1 that form a ternary complex at a mutated, inactive SRE; like Elk-1, the Elk-1 variant only binds its target as part of a ternary complex with SRF. Simultaneous expression of these SRF and Elk-1 derivatives restores serum-regulated activity to the mutated SRE in transfected cells. Efficient transcriptional activation is dependent on the regulated phosphorylation of Elk-1 C-terminal MAP kinase sites and requires the C-terminal sequences of SRF as well as SRF sequences that mediate ternary complex formation. These experiments provide direct evidence that SRF and Elk-1 functionally cooperate in the ternary complex at the SRE to regulate transcription.

  11. Prioritizing protein complexes implicated in human diseases by network optimization

    PubMed Central

    2014-01-01

    Background The detection of associations between protein complexes and human inherited diseases is of great importance in understanding mechanisms of diseases. Dysfunctions of a protein complex are usually defined by its member disturbance and consequently result in certain diseases. Although individual disease proteins have been widely predicted, computational methods are still absent for systematically investigating disease-related protein complexes. Results We propose a method, MAXCOM, for the prioritization of candidate protein complexes. MAXCOM performs a maximum information flow algorithm to optimize relationships between a query disease and candidate protein complexes through a heterogeneous network that is constructed by combining protein-protein interactions and disease phenotypic similarities. Cross-validation experiments on 539 protein complexes show that MAXCOM can rank 382 (70.87%) protein complexes at the top against protein complexes constructed at random. Permutation experiments further confirm that MAXCOM is robust to the network structure and parameters involved. We further analyze protein complexes ranked among top ten for breast cancer and demonstrate that the SWI/SNF complex is potentially associated with breast cancer. Conclusions MAXCOM is an effective method for the discovery of disease-related protein complexes based on network optimization. The high performance and robustness of this approach can facilitate not only pathologic studies of diseases, but also the design of drugs targeting on multiple proteins. PMID:24565064

  12. Identifying influential nodes in complex networks based on expansion factor

    NASA Astrophysics Data System (ADS)

    Liu, Dong; Jing, Yun; Chang, Baofang

    2016-03-01

    Identifying the top influential spreaders in a network has practical significance. In this paper, we propose a novel centrality to identify influential spreaders based on expansion factor. Nodes with high expansion factor centrality (EFC) have strong spreading capability. During the course of the work, an improved strategy is proposed to reduce the time complexity of EFC. We discuss the correlations between EFC and the other five classical indicators. Simulation results on the Susceptible-Infected-Removed (SIR) model manifest that EFC can identify influential nodes and find some critical influential nodes neglected by other indicators.

  13. Humanism Factors and Islam Viewpoint from Motahri's Point of View

    ERIC Educational Resources Information Center

    Yousefi, Zargham; Yousefy, Alireza; Keshtiaray, Narges

    2015-01-01

    The aim of this research is to criticize liberal humanism based on Islam viewpoint emphasizing Motahri's point of view. In this paper, the researchers tried to identify liberalism humanism factors with analytical look in order to present a new categorization called "main factor of liberal humanism". Then, each factor was studied and…

  14. The N2-P3 complex of the evoked potential and human performance

    NASA Technical Reports Server (NTRS)

    Odonnell, Brian F.; Cohen, Ronald A.

    1988-01-01

    The N2-P3 complex and other endogenous components of human evoked potential provide a set of tools for the investigation of human perceptual and cognitive processes. These multidimensional measures of central nervous system bioelectrical activity respond to a variety of environmental and internal factors which have been experimentally characterized. Their application to the analysis of human performance in naturalistic task environments is just beginning. Converging evidence suggests that the N2-P3 complex reflects processes of stimulus evaluation, perceptual resource allocation, and decision making that proceed in parallel, rather than in series, with response generation. Utilization of these EP components may provide insights into the central nervous system mechanisms modulating task performance unavailable from behavioral measures alone. The sensitivity of the N2-P3 complex to neuropathology, psychopathology, and pharmacological manipulation suggests that these components might provide sensitive markers for the effects of environmental stressors on the human central nervous system.

  15. Probabilistic Multi-Factor Interaction Model for Complex Material Behavior

    NASA Technical Reports Server (NTRS)

    Abumeri, Galib H.; Chamis, Christos C.

    2010-01-01

    Complex material behavior is represented by a single equation of product form to account for interaction among the various factors. The factors are selected by the physics of the problem and the environment that the model is to represent. For example, different factors will be required for each to represent temperature, moisture, erosion, corrosion, etc. It is important that the equation represent the physics of the behavior in its entirety accurately. The Multi-Factor Interaction Model (MFIM) is used to evaluate the divot weight (foam weight ejected) from the external launch tanks. The multi-factor has sufficient degrees of freedom to evaluate a large number of factors that may contribute to the divot ejection. It also accommodates all interactions by its product form. Each factor has an exponent that satisfies only two points - the initial and final points. The exponent describes a monotonic path from the initial condition to the final. The exponent values are selected so that the described path makes sense in the absence of experimental data. In the present investigation, the data used were obtained by testing simulated specimens in launching conditions. Results show that the MFIM is an effective method of describing the divot weight ejected under the conditions investigated. The problem lies in how to represent the divot weight with a single equation. A unique solution to this problem is a multi-factor equation of product form. Each factor is of the following form (1 xi/xf)ei, where xi is the initial value, usually at ambient conditions, xf the final value, and ei the exponent that makes the curve represented unimodal that meets the initial and final values. The exponents are either evaluated by test data or by technical judgment. A minor disadvantage may be the selection of exponents in the absence of any empirical data. This form has been used successfully in describing the foam ejected in simulated space environmental conditions. Seven factors were required

  16. Cognitive human factors for telemedicine systems.

    PubMed

    Piazza, Matteo; Giorgino, Toni; Azzini, Ivano; Stefanelli, Mario; Luo, Roger

    2004-01-01

    The recent integration of telephony systems with information and communication technology (ICT) enables the development of innovative tools for telemedicine. The dissemination and widespread acceptance of telephone-based care monitoring systems challenge the researcher to deal with the cognitive factors involved in the patient-physician interaction, and the way they should be to shape up the technological solutions. This paper proposes a model that describes the impact of socio-cognitive factors in the complex process of health care management. The model has been used to design and develop a telephone system for the management of hypertensive patient within the EU funded Homey project. The knowledge existed in a widely accepted guideline for the care of hypertension has been represented and augmented through the proposed cognitive model. The final product is an intelligent system able to manage an adaptive dialogue. It monitors patients' adherence and increases their involvement by promoting self-care through frequent virtual visits, which is complementary to the traditional face-to-face encounters with their primary care physicians.

  17. Converging strategies in expression of human complex retroviruses.

    PubMed

    Cavallari, Ilaria; Rende, Francesca; D'Agostino, Donna M; Ciminale, Vincenzo

    2011-08-01

    The discovery of human retroviruses in the early 1980s revealed the existence of viral-encoded non-structural genes that were not evident in previously described animal retroviruses. Based on the absence or presence of these additional genes retroviruses were classified as 'simple' and 'complex', respectively. Expression of most of these extra genes is achieved through the generation of alternatively spliced mRNAs. The present review summarizes the genetic organization and expression strategies of human complex retroviruses and highlights the converging mechanisms controlling their life cycles.

  18. Human Factors in Virtual Reality Development

    NASA Technical Reports Server (NTRS)

    Kaiser, Mary K.; Proffitt, Dennis R.; Null, Cynthia H. (Technical Monitor)

    1995-01-01

    This half-day tutorial will provide an overview of basic perceptual functioning as it relates to the design of virtual environment systems. The tutorial consists of three parts. First, basic issues in visual perception will be presented, including discussions of the visual sensations of brightness and color, and the visual perception of depth relationships in three-dimensional space (with a special emphasis on motion -specified depth). The second section will discuss the importance of conducting human-factors user studies and evaluations. Examples and suggestions on how best to get help with user studies will be provided. Finally, we will discuss how, by drawing on their complementary competencies, perceptual psychologists and computer engineers can work as a team to develop optimal VR systems, technologies, and techniques.

  19. Human factors and error in perinatal care: the interplay between nurses, machines, and the work environment.

    PubMed

    Mahlmeister, Laura R

    2010-01-01

    Perinatal nurses work with intricate systems requiring frequent interface with complex technology. This interplay is strongly influenced by the work environment and systems operations. The interplay among worker, technology, and the environment increases the risk of medical error, adverse patient outcomes, and in some instances, healthcare team member injury. Human factors engineering is an applied science that provides the study of the interface between people and machines. Human factors engineers design operations and systems that recognize the capacities and limitations of human beings and make it difficult for errors to occur. This article discusses the role of human factors research in healthcare design and the application of human factors engineering to perinatal settings. Recommendations are offered for the development of ultrasafe, high-reliability operations based on knowledge accrued through human factors research.

  20. Human Factors Tools for Improving Simulation Activities in Continuing Medical Education

    ERIC Educational Resources Information Center

    Seagull, F. Jacob

    2012-01-01

    Human factors (HF) is a discipline often drawn upon when there is a need to train people to perform complex, high-stakes tasks and effectively assess their performance. Complex tasks often present unique challenges for training and assessment. HF has developed specialized techniques that have been effective in overcoming several of these…

  1. Complexity and human health: the case for a transdisciplinary paradigm.

    PubMed

    Albrecht, G; Freeman, S; Higginbotham, N

    1998-03-01

    Transdisciplinary thinking is an emerging philosophy underpinning health social science. We advance a definition of transdisciplinary thinking and link it with complexity theory. Complexity theory's concern with non-linear relationships, interactive causality and emergent properties of systems compels researchers to adopt a transdisciplinary perspective. We construct a generic framework for analyzing health processes from diverse disciplines and apply it to coronary heart disease in the Australian Coalfields. Insights from this analysis support our argument that transdisciplinary thinking maximizes understanding of the complexity of human health.

  2. Background complexity and the detectability of camouflaged targets by birds and humans.

    PubMed

    Xiao, Feng; Cuthill, Innes C

    2016-09-14

    Remaining undetected is often key to survival, and camouflage is a widespread solution. However, extrinsic to the animal itself, the complexity of the background may be important. This has been shown in laboratory experiments using artificially patterned prey and backgrounds, but the mechanism remains obscure (not least because 'complexity' is a multifaceted concept). In this study, we determined the best predictors of detection by wild birds and human participants searching for the same cryptic targets on trees in the field. We compared detection success to metrics of background complexity and 'visual clutter' adapted from the human visual salience literature. For both birds and humans, the factor that explained most of the variation in detectability was the textural complexity of the tree bark as measured by a metric of feature congestion (specifically, many nearby edges in the background). For birds, this swamped any effects of colour match to the local surroundings, although for humans, local luminance disparities between the target and tree became important. For both taxa, a more abstract measure of complexity, entropy, was a poorer predictor. Our results point to the common features of background complexity that affect visual search in birds and humans, and how to quantify them. PMID:27629039

  3. Structure-aided prediction of mammalian transcription factor complexes in conserved non-coding elements.

    PubMed

    Guturu, Harendra; Doxey, Andrew C; Wenger, Aaron M; Bejerano, Gill

    2013-12-19

    Mapping the DNA-binding preferences of transcription factor (TF) complexes is critical for deciphering the functions of cis-regulatory elements. Here, we developed a computational method that compares co-occurring motif spacings in conserved versus unconserved regions of the human genome to detect evolutionarily constrained binding sites of rigid TF complexes. Structural data were used to estimate TF complex physical plausibility, explore overlapping motif arrangements seldom tackled by non-structure-aware methods, and generate and analyse three-dimensional models of the predicted complexes bound to DNA. Using this approach, we predicted 422 physically realistic TF complex motifs at 18% false discovery rate, the majority of which (326, 77%) contain some sequence overlap between binding sites. The set of mostly novel complexes is enriched in known composite motifs, predictive of binding site configurations in TF-TF-DNA crystal structures, and supported by ChIP-seq datasets. Structural modelling revealed three cooperativity mechanisms: direct protein-protein interactions, potentially indirect interactions and 'through-DNA' interactions. Indeed, 38% of the predicted complexes were found to contain four or more bases in which TF pairs appear to synergize through overlapping binding to the same DNA base pairs in opposite grooves or strands. Our TF complex and associated binding site predictions are available as a web resource at http://bejerano.stanford.edu/complex.

  4. Roles of Human Factors and Ergonomics in Meeting the Challenge of Terrorism

    ERIC Educational Resources Information Center

    Nickerson, Raymond S.

    2011-01-01

    Human factors and ergonomics research focuses on questions pertaining to the design of devices, systems, and procedures with the goal of making sure that they are well suited to human use and focuses on studies of the interaction of people with simple and complex systems and machines. Problem areas studied include the allocation of function to…

  5. Medical error and human factors engineering: where are we now?

    PubMed

    Gawron, Valerie J; Drury, Colin G; Fairbanks, Rollin J; Berger, Roseanne C

    2006-01-01

    The goal of human factors engineering is to optimize the relationship between humans and systems by studying human behavior, abilities, and limitations and using this knowledge to design systems for safe and effective human use. With the assumption that the human component of any system will inevitably produce errors, human factors engineers design systems and human/machine interfaces that are robust enough to reduce error rates and the effect of the inevitable error within the system. In this article, we review the extent and nature of medical error and then discuss human factors engineering tools that have potential applicability. These tools include taxonomies of human and system error and error data collection and analysis methods. Finally, we describe studies that have examined medical error, and on the basis of these studies, present conclusions about how human factors engineering can significantly reduce medical errors and their effects.

  6. Kinetics of Factor X activation by the membrane-bound complex of Factor IXa and Factor VIIIa.

    PubMed

    Panteleev, Mikhail A; Saenko, Evgueni L; Ananyeva, Natalya M; Ataullakhanov, Fazoil I

    2004-08-01

    Intrinsic tenase consists of activated Factors IX (IXa) and VIII (VIIIa) assembled on a negatively charged phospholipid surface. In vivo, this surface is mainly provided by activated platelets. In vitro, phosphatidylcholine/phosphatidylserine vesicles are often used to mimic natural pro-coagulant membranes. In the present study, we developed a quantitative mathematical model of Factor X activation by intrinsic tenase. We considered two situations, when complex assembly occurs on either the membrane of phospholipid vesicles or the surface of activated platelets. On the basis of existing experimental evidence, the following mechanism for the complex assembly on activated platelets was suggested: (i) Factors IXa, VIIIa and X bind to their specific platelet receptors; (ii) bound factors form complexes on the membrane: platelet-bound Factor VIIIa provides a high-affinity site for Factor X and platelet-bound Factor IXa provides a high-affinity site for Factor VIIIa; (iii) the enzyme-cofactor-substrate complex is assembled. This mechanism allowed the explanation of co-operative effects in the binding of Factors IXa, VIIIa and X to platelets. The model was reduced to obtain a single equation for the Factor X activation rate as a function of concentrations of Factors IXa, VIIIa, X and phospholipids (or platelets). The equation had a Michaelis-Menten form, where apparent V(max) and K(m) were functions of the factors' concentrations and the internal kinetic constants of the system. The equation obtained can be used in both experimental studies of intrinsic tenase and mathematical modelling of the coagulation cascade. The approach of the present study can be applied to research of other membrane-dependent enzymic reactions.

  7. Active gamma-carboxylated human factor IX expressed using recombinant DNA techniques.

    PubMed

    de la Salle, H; Altenburger, W; Elkaim, R; Dott, K; Dieterlé, A; Drillien, R; Cazenave, J P; Tolstoshev, P; Lecocq, J P

    Factor IX (Christmas factor), a vitamin K-dependent plasma protein made in the liver, functions in the middle phase of the intrinsic pathway of blood coagulation. A functional deficiency of factor IX underlies haemophilia B, a chromosome X-linked recessive disease for which the major therapeutic approach is replacement treatment using factor IX concentrates. The cloning and characterization of the gene for human factor IX would mean that human factor IX could be produced in greater yield and purity through using recombinant DNA techniques. We have now used a human factor IX cDNA clone, inserted into a vaccinia virus-derived vector, to infect human hepatoma cells which normally produce no factor IX, and mouse fibroblasts. Fully active factor IX was produced by the hepatoma cells, whereas the fibroblasts produced a protein less active than natural factor IX, even in the presence of high levels of vitamin K. Human factor IX is extensively post-translationally modified, and thus represents probably the most complex protein produced in active form by recombinant DNA techniques to date. Our study also illustrates the potential of vaccinia virus-based vectors for expressing significant amounts of complex, clinically useful proteins in eukaryotic cells, in addition to its already demonstrated usefulness for producing live recombinant vaccines.

  8. In situ structural analysis of the human nuclear pore complex.

    PubMed

    von Appen, Alexander; Kosinski, Jan; Sparks, Lenore; Ori, Alessandro; DiGuilio, Amanda L; Vollmer, Benjamin; Mackmull, Marie-Therese; Banterle, Niccolo; Parca, Luca; Kastritis, Panagiotis; Buczak, Katarzyna; Mosalaganti, Shyamal; Hagen, Wim; Andres-Pons, Amparo; Lemke, Edward A; Bork, Peer; Antonin, Wolfram; Glavy, Joseph S; Bui, Khanh Huy; Beck, Martin

    2015-10-01

    Nuclear pore complexes are fundamental components of all eukaryotic cells that mediate nucleocytoplasmic exchange. Determining their 110-megadalton structure imposes a formidable challenge and requires in situ structural biology approaches. Of approximately 30 nucleoporins (Nups), 15 are structured and form the Y and inner-ring complexes. These two major scaffolding modules assemble in multiple copies into an eight-fold rotationally symmetric structure that fuses the inner and outer nuclear membranes to form a central channel of ~60 nm in diameter. The scaffold is decorated with transport-channel Nups that often contain phenylalanine-repeat sequences and mediate the interaction with cargo complexes. Although the architectural arrangement of parts of the Y complex has been elucidated, it is unclear how exactly it oligomerizes in situ. Here we combine cryo-electron tomography with mass spectrometry, biochemical analysis, perturbation experiments and structural modelling to generate, to our knowledge, the most comprehensive architectural model of the human nuclear pore complex to date. Our data suggest previously unknown protein interfaces across Y complexes and to inner-ring complex members. We show that the transport-channel Nup358 (also known as Ranbp2) has a previously unanticipated role in Y-complex oligomerization. Our findings blur the established boundaries between scaffold and transport-channel Nups. We conclude that, similar to coated vesicles, several copies of the same structural building block--although compositionally identical--engage in different local sets of interactions and conformations.

  9. Purification and analysis of endogenous human RNA exosome complexes

    PubMed Central

    Domanski, Michal; Upla, Paula; Rice, William J.; Molloy, Kelly R.; Ketaren, Natalia E.; Stokes, David L.; Jensen, Torben Heick; Rout, Michael P.

    2016-01-01

    As a result of its importance in key RNA metabolic processes, the ribonucleolytic RNA exosome complex has been the focus of intense study for almost two decades. Research on exosome subunit assembly, cofactor and substrate interaction, enzymatic catalysis and structure have largely been conducted using complexes produced in the yeast Saccharomyces cerevisiae or in bacteria. Here, we examine different populations of endogenous exosomes from human embryonic kidney (HEK) 293 cells and test their enzymatic activity and structural integrity. We describe methods to prepare EXOSC10-containing, enzymatically active endogenous human exosomes at suitable yield and purity for in vitro biochemistry and negative stain transmission electron microscopy. This opens the door for assays designed to test the in vitro effects of putative cofactors on human exosome activity and will enable structural studies of preparations from endogenous sources. PMID:27402899

  10. Development of biomechanical models for human factors evaluations

    NASA Technical Reports Server (NTRS)

    Woolford, Barbara; Pandya, Abhilash; Maida, James

    1993-01-01

    Computer aided design (CAD) techniques are now well established and have become the norm in many aspects of aerospace engineering. They enable analytical studies, such as finite element analysis, to be performed to measure performance characteristics of the aircraft or spacecraft long before a physical model is built. However, because of the complexity of human performance, CAD systems for human factors are not in widespread use. The purpose of such a program would be to analyze the performance capability of a crew member given a particular environment and task. This requires the design capabilities to describe the environment's geometry and to describe the task's requirements, which may involve motion and strength. This in turn requires extensive data on human physical performance which can be generalized to many different physical configurations. PLAID is developing into such a program. Begun at Johnson Space Center in 1977, it was started to model only the geometry of the environment. The physical appearance of a human body was generated, and the tool took on a new meaning as fit, access, and reach could be checked. Specification of fields-of-view soon followed. This allowed PLAID to be used to predict what the Space Shuttle cameras or crew could see from a given point.

  11. Probabilistic simulation of the human factor in structural reliability

    NASA Technical Reports Server (NTRS)

    Shah, Ashwin R.; Chamis, Christos C.

    1991-01-01

    Many structural failures have occasionally been attributed to human factors in engineering design, analyses maintenance, and fabrication processes. Every facet of the engineering process is heavily governed by human factors and the degree of uncertainty associated with them. Factors such as societal, physical, professional, psychological, and many others introduce uncertainties that significantly influence the reliability of human performance. Quantifying human factors and associated uncertainties in structural reliability require: (1) identification of the fundamental factors that influence human performance, and (2) models to describe the interaction of these factors. An approach is being developed to quantify the uncertainties associated with the human performance. This approach consists of a multi factor model in conjunction with direct Monte-Carlo simulation.

  12. A Human Factors Perspective on Alarm System Research and Development 2000 to 2010

    SciTech Connect

    Curt Braun; John Grimes; Eric Shaver; Ronald Boring

    2011-09-01

    By definition, alarms serve to notify human operators of out-of-parameter conditions that could threaten equipment, the environment, product quality and, of course, human life. Given the complexities of industrial systems, human machine interfaces, and the human operator, the understanding of how alarms and humans can best work together to prevent disaster is continually developing. This review examines advances in alarm research and development from 2000 to 2010 and includes the writings of trade professionals, engineering and human factors researchers, and standards organizations with the goal of documenting advances in alarms system design, research, and implementation.

  13. Human Factors and Robotics: Current Status and Future Prospects.

    ERIC Educational Resources Information Center

    Parsons, H. McIlvaine; Kearsley, Greg P.

    The principal human factors engineering issue in robotics is the division of labor between automation (robots) and human beings. This issue reflects a prime human factors engineering consideration in systems design--what equipment should do and what operators and maintainers should do. Understanding of capabilities and limitations of robots and…

  14. Emergence of dynamical complexity related to human heart rate variability

    NASA Astrophysics Data System (ADS)

    Chang, Mei-Chu; Peng, C.-K.; Stanley, H. Eugene

    2014-12-01

    We apply the refined composite multiscale entropy (MSE) method to a one-dimensional directed small-world network composed of nodes whose states are binary and whose dynamics obey the majority rule. We find that the resulting fluctuating signal becomes dynamically complex. This dynamical complexity is caused (i) by the presence of both short-range connections and long-range shortcuts and (ii) by how well the system can adapt to the noisy environment. By tuning the adaptability of the environment and the long-range shortcuts we can increase or decrease the dynamical complexity, thereby modeling trends found in the MSE of a healthy human heart rate in different physiological states. When the shortcut and adaptability values increase, the complexity in the system dynamics becomes uncorrelated.

  15. Information Presentation: Human Research Program - Space Human Factors and Habitability, Space Human Factors Engineering Project

    NASA Technical Reports Server (NTRS)

    Holden, Kristina L.; Sandor, Aniko; Thompson, Shelby G.; Kaiser, Mary K.; McCann, Robert S.; Begault, D. R.; Adelstein, B. D.; Beutter, B. R.; Wenzel, E. M.; Godfroy, M.; Stone, L. S.

    2010-01-01

    The goal of the Information Presentation Directed Research Project (DRP) is to address design questions related to the presentation of information to the crew. The major areas of work, or subtasks, within this DRP are: 1) Displays, 2) Controls, 3) Electronic Procedures and Fault Management, and 4) Human Performance Modeling. This DRP is a collaborative effort between researchers atJohnson Space Center and Ames Research Center. T

  16. Human Factors Aspects of Operating Small Reactors

    SciTech Connect

    OHara, J.M.; Higgins, J.; Deem, R.; Xing, J.; DAgostino, A.

    2010-11-07

    The nuclear-power community has reached the stage of proposing advanced reactor designs to support power generation for decades to come. They are considering small modular reactors (SMRs) as one approach to meet these energy needs. While the power output of individual reactor modules is relatively small, they can be grouped to produce reactor sites with different outputs. Also, they can be designed to generate hydrogen, or to process heat. Many characteristics of SMRs are quite different from those of current plants, and so may require a concept of operations (ConOps) that also is different. The U.S. Nuclear Regulatory Commission (NRC) has begun examining the human factors engineering- (HFE) and ConOps- aspects of SMRs; if needed, they will formulate guidance to support SMR licensing reviews. We developed a ConOps model, consisting of the following dimensions: Plant mission; roles and responsibilities of all agents; staffing, qualifications, and training; management of normal operations; management of off-normal conditions and emergencies; and, management of maintenance and modifications. We are reviewing information on SMR design to obtain data about each of these dimensions, and have identified several preliminary issues. In addition, we are obtaining operations-related information from other types of multi-module systems, such as refineries, to identify lessons learned from their experience. Here, we describe the project's methodology and our preliminary findings.

  17. Enhanced vision simulator for human factors evaluations

    NASA Astrophysics Data System (ADS)

    Suiter, James M.

    1995-06-01

    A low-cost Operational Development and Evaluation System (ODES) was developed for evaluating and demonstrating Head Up Display (HUD) technology, including projected out the window graphics. This consisted of commercial workstations and PC's, a prototype autopilot control panel and an engineering F-15 HUD unit. Software utilized functional partitioning to provide maximum flexibility for modification, expansion and rehosting of software functions. For human factors evaluation of Enhanced Vision Systems (EVS), a real-time simulation was needed for subjects to respond to. Real-time simulated enhanced vision, such as that using millimeter wave radar, is not possible without supercomputers or oversimplification of the radar simulation. We solved this problem by defining operational scenarios for evaluation, generating the EVS radar simulation off-line, transferring simulation run results to a Silicon Graphics (SG) machine for B-scope to C-scope conversion and contrast enhancement and recording the SG images on an optical disk, a frame at a time. For real-time simulation, an ODES system was modified to control the playback of the optical disk recorder through the HUD raster subsystem in coordination with the aircraft model position as driven by the autopilot. The system was first put to use in a study of EVS raster obscuration issues.

  18. Requirement of the eukaryotic translation initiation factor 4F complex in hepatitis E virus replication.

    PubMed

    Zhou, Xinying; Xu, Lei; Wang, Yijin; Wang, Wenshi; Sprengers, Dave; Metselaar, Herold J; Peppelenbosch, Maikel P; Pan, Qiuwei

    2015-12-01

    Hepatitis E virus (HEV) infection, one of the foremost causes of acute hepatitis, is becoming a health problem of increasing magnitude. As other viruses, HEV exploits elements from host cell biochemistry, but we understand little as to which components of the human hepatocellular machinery are perverted for HEV multiplication. It is, however, known that the eukaryotic translation initiation factors 4F (eIF4F) complex, the key regulator of the mRNA-ribosome recruitment phase of translation initiation, serves as an important component for the translation and replication of many viruses. Here we aim to investigate the role of three subunits of the eIF4F complex: eukaryotic translation initiation factor 4A (eIF4A), eukaryotic translation initiation factor 4G (eIF4G) and eukaryotic translation initiation factor 4E (eIF4E) in HEV replication. We found that efficient replication of HEV requires eIF4A, eIF4G and eIF4E. Consistently, the negative regulatory factors of this complex: programmed cell death 4 (PDCD4) and eIF4E-binding protein 1 (4E-BP1) exert anti-HEV activities, which further illustrates the requirement for eIF4A and eIF4E in supporting HEV replication. Notably, phosphorylation of eIF4E induced by MNK1/2 activation is not involved in HEV replication. Although ribavirin and interferon-α (IFN-α), the most often-used off-label drugs for treating hepatitis E, interact with this complex, their antiviral activities are independent of eIF4E. In contrast, eIF4E silencing provokes enhanced anti-HEV activity of these compounds. Thus, HEV replication requires eIF4F complex and targeting essential elements of this complex provides important clues for the development of novel antiviral therapy against HEV.

  19. Dynamic analysis of the human brain with complex cerebral sulci.

    PubMed

    Tseng, Jung-Ge; Huang, Bo-Wun; Ou, Yi-Wen; Yen, Ke-Tien; Wu, Yi-Te

    2016-07-01

    The brain is one of the most vulnerable organs inside the human body. Head accidents often appear in daily life and are easy to cause different level of brain damage inside the skull. Once the brain suffered intense locomotive impact, external injuries, falls, or other accidents, it will result in different degrees of concussion. This study employs finite element analysis to compare the dynamic characteristics between the geometric models of an assumed simple brain tissue and a brain tissue with complex cerebral sulci. It is aimed to understand the free vibration of the internal brain tissue and then to protect the brain from injury caused by external influences. Reverse engineering method is used for a Classic 5-Part Brain (C18) model produced by 3B Scientific Corporation. 3D optical scanner is employed to scan the human brain structure model with complex cerebral sulci and imported into 3D graphics software to construct a solid brain model to simulate the real complex brain tissue. Obtaining the normal mode analysis by inputting the material properties of the true human brain into finite element analysis software, and then to compare the simplified and the complex of brain models. PMID:27459595

  20. Social scale and structural complexity in human languages

    PubMed Central

    Nettle, Daniel

    2012-01-01

    The complexity of different components of the grammars of human languages can be quantified. For example, languages vary greatly in the size of their phonological inventories, and in the degree to which they make use of inflectional morphology. Recent studies have shown that there are relationships between these types of grammatical complexity and the number of speakers a language has. Languages spoken by large populations have been found to have larger phonological inventories, but simpler morphology, than languages spoken by small populations. The results require further investigation, and, most importantly, the mechanism whereby the social context of learning and use affects the grammatical evolution of a language needs elucidation. PMID:22641821

  1. Proteolytic processing of human coagulation factor IX by plasmin.

    PubMed

    Samis, J A; Ramsey, G D; Walker, J B; Nesheim, M E; Giles, A R

    2000-02-01

    Previous studies have shown that thrombin generation in vivo caused a 92% decrease in factor IX (F.IX) activity and the appearance of a cleavage product after immunoblotting that comigrated with activated F.IX (F.IXa). Under these conditions, the fibrinolytic system was clearly activated, suggesting plasmin may have altered F.IX. Thus, the effect(s) of plasmin on human F.IX was determined in vitro. Plasmin (50 nM) decreased the 1-stage clotting activity of F.IX (4 microM) by 80% and the activity of F.IXa (4 microM) by 50% after 30 minutes at 37 degrees C. Plasmin hydrolysis of F.IX yields products of 45, 30, 20, and 14 kd on reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and 2 products of 52 and 14 kd under nonreducing conditions. Plasmin-treated F.IX did not bind the active site probe, p-aminobenzamidine, or form an SDS-stable complex with antithrombin. It only marginally activated human factor X in the presence of phospholipid and activated factor VIII. Although dansyl-Glu-Gly-Arg-chloromethyl ketone inactivated-F. IXa inhibited the clotting activity of F.IXa, plasmin-treated F.IX did not. Plasmin cleaves F.IX after Lys43, Arg145, Arg180, Lys316, and Arg318, but F.IXa is not appreciably generated despite cleavage at the 2 normal activation sites (Arg145 and Arg180). Tissue plasminogen activator-catalyzed lysis of fibrin formed in human plasma results in generation of the 45- and 30-kd fragments of F.IX and decreased F.IX clotting activity. Collectively, the results suggest that plasmin is able to down-regulate coagulation by inactivating F.IX. PMID:10648407

  2. Terminal Area Productivity Program: Dynamic Spacing Human Factors

    NASA Technical Reports Server (NTRS)

    Kanki, Barbara G.

    1997-01-01

    Dynamic spacing human factors deals with the following human factors issues: define controller limits to incorporating dynamic changes in separation standards; identify timing, planning, and coordination strategies; and consider consistency with current practices, policies, and regulations. The AVOSS technologies will make it possible to reduce separation standards in the terminal area under certain meteorological conditions. This paper contains the following sections: Dynamic space human factors overview, Preliminary tests, and current research status & plans.

  3. Human milk composition: nutrients and bioactive factors.

    PubMed

    Ballard, Olivia; Morrow, Ardythe L

    2013-02-01

    This article provides an overview of the composition of human milk, its variation, and its clinical relevance. The composition of human milk is the biological norm for infant nutrition. Human milk also contains many hundreds to thousands of distinct bioactive molecules that protect against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. Some of these molecules (eg, lactoferrin) are being investigated as novel therapeutic agents. Human milk changes in composition from colostrum to late lactation, within feeds, by gestational age, diurnally, and between mothers. Feeding infants with expressed human milk is increasing.

  4. Human Factors Research for Space Exploration: Measurement, Modeling, and Mitigation

    NASA Technical Reports Server (NTRS)

    Kaiser, Mary K.; Allen, Christopher S.; Barshi, Immanuel; Billman, Dorrit; Holden, Kritina L.

    2010-01-01

    As part of NASA's Human Research Program, the Space Human Factors Engineering Project serves as the bridge between Human Factors research and Human Spaceflight applications. Our goal is to be responsive to the operational community while addressing issues at a sufficient level of abstraction to ensure that our tools and solutions generalize beyond the point design. In this panel, representatives from four of our research domains will discuss the challenges they face in solving current problems while also enabling future capabilities.

  5. Converging Strategies in Expression of Human Complex Retroviruses

    PubMed Central

    Cavallari, Ilaria; Rende, Francesca; D'Agostino, Donna M.; Ciminale, Vincenzo

    2011-01-01

    The discovery of human retroviruses in the early 1980s revealed the existence of viral-encoded non-structural genes that were not evident in previously described animal retroviruses. Based on the absence or presence of these additional genes retroviruses were classified as ‘simple’ and ‘complex’, respectively. Expression of most of these extra genes is achieved through the generation of alternatively spliced mRNAs. The present review summarizes the genetic organization and expression strategies of human complex retroviruses and highlights the converging mechanisms controlling their life cycles. PMID:21994786

  6. Developing human factors/ergonomics as a design discipline.

    PubMed

    Norros, Leena

    2014-01-01

    This paper deals with internal challenges that the human factors/ergonomics (HFE) research faces when wishing to strengthen its contribution to development of work systems. Three established characteristics of high-quality HFE, i.e., HFE takes a systems approach, HFE is design-driven, and HFE focuses on two closely related outcomes, performance and well-being, are taken as a starting point of a methodological discussion, in which conceptual innovations, e.g. adopting the technology-in-use perspective, are proposed to support development of HFE towards the high-quality aims. The feasibility of the proposed conceptual choices is demonstrated by introducing a naturalistic HFE analysis approach including four HFE functions. The gained experience of the use of this approach in a number of complex work domains allows the conclusion that becoming design-driven appears as that most difficult quality target for HFE to reach. Creating an own design discipline identity in a multi-voiced collaboration is the key internal challenge for human factors/ergonomics.

  7. Is schizophrenia the price of human central nervous system complexity?

    PubMed

    Dean, Brian

    2009-01-01

    The purpose of the present study was to determine if there is evidence to support the hypothesis that schizophrenia is a human-specific disorder associated with the need for highly complex central nervous system (CNS) development. A review was therefore undertaken of published literature relevant to the identification of human-specific CNS development. There was no clear evidence found at the macroscopic, microscopic or molecular level that suggests unique changes have occurred in the evolution of the human CNS. Rather, highly significant changes in the size of the frontal lobe, increases in numbers of specific cell types, changes in gene expression and changes in genome sequence all seem to be involved in the evolution of the human CNS. Human-specific changes in CNS development are wide ranging. The modification in CNS structure and function that has resulted from these changes affects many pathways and behaviours that appear to be also affected in subjects with schizophrenia. Therefore there is evidence to support the hypothesis that schizophrenia is a disease that develops because of derangements to human-specific CNS functions that have emerged since our species diverged from non-human primates. PMID:19085524

  8. Establishing Causality in Complex Human Interactions: Identifying Breakdowns of Intentionality

    NASA Astrophysics Data System (ADS)

    Goodison, Peter; Johnson, Peter; Thoms, Joanne

    People in complex scenarios face the challenge of understanding the purpose and effect of other human and computational behaviour on their own goals through intent recognition. They are left asking what caused person or system ‘x’ to do that? The necessity to provide this support human-computer interaction has increased alongside the deployment of autonomous systems that are to some degree unsupervised. This paper aims to examine intent recognition as a form of decision making about causality in complex systems. By finding the needs and limitations of this decision mechanism it is hoped this can be applied to the design of systems to support the awareness of information cues and reduce the number of intent recognition breakdowns between people and autonomous systems. The paper outlines theoretical foundations for this approach using simulation theory and process models of intention. The notion of breakdowns is then applied to intent recognition breakdowns in a diary study to gain insight into the phenomena.

  9. Human Factors Report: TMA Operational Evaluations 1996 and 1998

    NASA Technical Reports Server (NTRS)

    Lee, Katharine K.; Quinn, Cheryl M.; Hoang, Ty; Sanford, Beverly D.

    2000-01-01

    The Traffic Management Advisor (TMA) is a component of the Center-TRACON Automation System (CTAS), a suite of decision-support tools for the air traffic control (ATC) environment which is being developed at NASA Ames Research Center. TMA has been operational at the ATC facilities in Dallas/Fort Worth, Texas, since an operational field evaluation in 1996. The Operational Evaluation demonstrated significant benefits, including an approximately 5 percent increase in airport capacity. This report describes the human factors results from the 1996 Operational Evaluation and an investigation of TMA usage performed two years later, during the 1998 TMA Daily Use Field Survey. The results described are instructive for CTAS focused development, and provide valuable lessons for future research in ATC decision-support tools where it is critical to merge a well-defined, complex work environment with advanced automation.

  10. Human Health Risk Assessment of Trichloroethylene from Industrial Complex A

    PubMed Central

    Sin, Saemi

    2012-01-01

    This study investigated the human health risks of trichloroethylene from Industrial Complex A. The excessive carcinogenic risks for central tendency exposure were 1.40 × 10?5 for male and female residents in the vicinity of Industrial Complex A. The excessive cancers risk for reasonable maximum exposure were 2.88 × 10?5 and 1.97 × 10?5 for males and females, respectively. These values indicate that there are potential cancer risks for exposure to these concentrations. The hazard index for central tendency exposure to trichloroethylene was 1.71 for male and female residents. The hazard indexes for reasonable maximum exposure were 3.27 and 2.41 for males and females, respectively. These values were over one, which is equivalent to the threshold value. This result showed that adverse cancer and non-cancer health effects may occur and that some risk management of trichloroethylene from Industrial Complex A was needed. PMID:24278607

  11. Electronic cigarettes: incorporating human factors engineering into risk assessments

    PubMed Central

    Yang, Ling; Rudy, Susan F; Cheng, James M; Durmowicz, Elizabeth L

    2014-01-01

    Objective A systematic review was conducted to evaluate the impact of human factors (HF) on the risks associated with electronic cigarettes (e-cigarettes) and to identify research gaps. HF is the evaluation of human interactions with products and includes the analysis of user, environment and product complexity. Consideration of HF may mitigate known and potential hazards from the use and misuse of a consumer product, including e-cigarettes. Methods Five databases were searched through January 2014 and publications relevant to HF were incorporated. Voluntary adverse event (AE) reports submitted to the US Food and Drug Administration (FDA) and the package labelling of 12 e-cigarette products were analysed. Results No studies specifically addressing the impact of HF on e-cigarette use risks were identified. Most e-cigarette users are smokers, but data on the user population are inconsistent. No articles focused specifically on e-cigarette use environments, storage conditions, product operational requirements, product complexities, user errors or misuse. Twelve published studies analysed e-cigarette labelling and concluded that labelling was inadequate or misleading. FDA labelling analysis revealed similar concerns described in the literature. AE reports related to design concerns are increasing and fatalities related to accidental exposure and misuse have occurred; however, no publications evaluating the relationship between AEs and HF were identified. Conclusions The HF impacting e-cigarette use and related hazards are inadequately characterised. Thorough analyses of user–product–environment interfaces, product complexities and AEs associated with typical and atypical use are needed to better incorporate HF engineering principles to inform and potentially reduce or mitigate the emerging hazards associated with e-cigarette products. PMID:24732164

  12. Activated human platelets induce factor XIIa-mediated contact activation.

    PubMed

    Bäck, Jennie; Sanchez, Javier; Elgue, Graciela; Ekdahl, Kristina Nilsson; Nilsson, Bo

    2010-01-01

    Earlier studies have shown that isolated platelets in buffer systems can promote activation of FXII or amplify contact activation, in the presence of a negatively charge substance or material. Still proof is lacking that FXII is activated by platelets in a more physiological environment. In this study we investigate if activated platelets can induce FXII-mediated contact activation and whether this activation affects clot formation in human blood. Human platelets were activated with a thrombin receptor-activating peptide, SFLLRN-amide, in platelet-rich plasma or in whole blood. FXIIa and FXIa in complex with preferentially antithrombin (AT) and to some extent C1-inhibitor (C1INH) were generated in response to TRAP stimulation. This contact activation was independent of surface-mediated contact activation, tissue factor pathway or thrombin. In clotting whole blood FXIIa-AT and FXIa-AT complexes were specifically formed, demonstrating that AT is a potent inhibitor of FXIIa and FXIa generated by platelet activation. Contact activation proteins were analyzed by flow cytometry and FXII, FXI, high-molecular weight kininogen, and prekallikrein were detected on activated platelets. Using chromogenic assays, enzymatic activity of platelet-associated FXIIa, FXIa, and kallikrein were demonstrated. Inhibition of FXIIa in non-anticoagulated blood also prolonged the clotting time. We conclude that platelet activation triggers FXII-mediated contact activation on the surface and in the vicinity of activated platelets. This leads specifically to generation of FXIIa-AT and FXIa-AT complexes, and contributes to clot formation. Activated platelets may thereby constitute an intravascular locus for contact activation, which may explain the recently reported importance of FXII in thrombus formation. PMID:19878657

  13. Pedigree models for complex human traits involving the mitochrondrial genome

    SciTech Connect

    Schork, N.J.; Guo, S.W. )

    1993-12-01

    Recent biochemical and molecular-genetic discoveries concerning variations in human mtDNA have suggested a role for mtDNA mutations in a number of human traits and disorders. Although the importance of these discoveries cannot be emphasized enough, the complex natures of mitochondrial biogenesis, mutant mtDNA phenotype expression, and the maternal inheritance pattern exhibited by mtDNA transmission make it difficult to develop models that can be used routinely in pedigree analyses to quantify and test hypotheses about the role of mtDNA in the expression of a trait. In the present paper, the authors describe complexities inherent in mitochondrial biogenesis and genetic transmission and show how these complexities can be incorporated into appropriate mathematical models. The authors offer a variety of likelihood-based models which account for the complexities discussed. The derivation of the models is meant to stimulate the construction of statistical tests for putative mtDNA contribution to a trait. Results of simulation studies which make use of the proposed models are described. The results of the simulation studies suggest that, although pedigree models of mtDNA effects can be reliable, success in mapping chromosomal determinants of a trait does not preclude the possibility that mtDNA determinants exist for the trait as well. Shortcomings inherent in the proposed models are described in an effort to expose areas in need of additional research. 58 refs., 5 figs., 2 tabs.

  14. The multiple complexes formed by the interaction of platelet factor 4 with heparin.

    PubMed Central

    Bock, P E; Luscombe, M; Marshall, S E; Pepper, D S; Holbrook, J J

    1980-01-01

    The anisotropy of the fluorescence of dansyl (5-dimethylaminonaphthalene-1- sulphonyl) groups covalently attached to human platelet factor 4 was used to detect the macromolecular compounds formed when the factor was mixed with heparin. At low heparin/protein ratios a very-high-molecular-weight compound (1) was formed that dissociated to give a smaller compound (2) when excess heparin was added. 2. A large complex was also detected as a precipitate that formed at high protein concentrations in chloride buffer. It contained 15.7% (w/w) polysaccharide, equivalent to four or five heparin tetrasaccharide units per protein tetramer. In this complex, more than one molecule of protein binds to each heparin molecule of molecular weight greater than about 6 X 10(3).3. The stability of these complexes varied with pH, salt concentration and the chain length of the heparin. The limit complexes found in excess of the larger heparins consisted of only one heparin molecule per protein tetramer, and the failure to observe complexes with four heparin molecules/protein tetramer is discussed. PMID:7283972

  15. A stable transcription factor complex nucleated by oligomeric AML1–ETO controls leukaemogenesis

    SciTech Connect

    Sun, Xiao-Jian; Wang, Zhanxin; Wang, Lan; Jiang, Yanwen; Kost, Nils; Soong, T. David; Chen, Wei-Yi; Tang, Zhanyun; Nakadai, Tomoyoshi; Elemento, Olivier; Fischle, Wolfgang; Melnick, Ari; Patel, Dinshaw J.; Nimer, Stephen D.; Roeder, Robert G.

    2013-06-30

    Transcription factors are frequently altered in leukaemia through chromosomal translocation, mutation or aberrant expression. AML1–ETO, a fusion protein generated by the t(8;21) translocation in acute myeloid leukaemia, is a transcription factor implicated in both gene repression and activation. AML1–ETO oligomerization, mediated by the NHR2 domain, is critical for leukaemogenesis, making it important to identify co-regulatory factors that ‘read’ the NHR2 oligomerization and contribute to leukaemogenesis. Here we show that, in human leukaemic cells, AML1–ETO resides in and functions through a stable AML1–ETO-containing transcription factor complex (AETFC) that contains several haematopoietic transcription (co)factors. These AETFC components stabilize the complex through multivalent interactions, provide multiple DNA-binding domains for diverse target genes, co-localize genome wide, cooperatively regulate gene expression, and contribute to leukaemogenesis. Within the AETFC complex, AML1–ETO oligomerization is required for a specific interaction between the oligomerized NHR2 domain and a novel NHR2-binding (N2B) motif in E proteins. Crystallographic analysis of the NHR2–N2B complex reveals a unique interaction pattern in which an N2B peptide makes direct contact with side chains of two NHR2 domains as a dimer, providing a novel model of how dimeric/oligomeric transcription factors create a new protein-binding interface through dimerization/oligomerization. Intriguingly, disruption of this interaction by point mutations abrogates AML1–ETO-induced haematopoietic stem/progenitor cell self-renewal and leukaemogenesis. These results reveal new mechanisms of action of AML1–ETO, and provide a potential therapeutic target in t(8;21)-positive acute myeloid leukaemia.

  16. Human factors in space station architecture 1: Space station program implications for human factors research

    NASA Technical Reports Server (NTRS)

    Cohen, M. M.

    1985-01-01

    The space station program is based on a set of premises on mission requirements and the operational capabilities of the space shuttle. These premises will influence the human behavioral factors and conditions on board the space station. These include: launch in the STS Orbiter payload bay, orbital characteristics, power supply, microgravity environment, autonomy from the ground, crew make-up and organization, distributed command control, safety, and logistics resupply. The most immediate design impacts of these premises will be upon the architectural organization and internal environment of the space station.

  17. High-Resolution NMR Studies of Human Tissue Factor

    PubMed Central

    Nuzzio, Kristin M.; Watt, Eric D.; Boettcher, John M.; Gajsiewicz, Joshua M.; Morrissey, James H.; Rienstra, Chad M.

    2016-01-01

    In normal hemostasis, the blood clotting cascade is initiated when factor VIIa (fVIIa, other clotting factors are named similarly) binds to the integral membrane protein, human tissue factor (TF). The TF/fVIIa complex in turn activates fX and fIX, eventually concluding with clot formation. Several X-ray crystal structures of the soluble extracellular domain of TF (sTF) exist; however, these structures are missing electron density in functionally relevant regions of the protein. In this context, NMR can provide complementary structural information as well as dynamic insights into enzyme activity. The resolution and sensitivity for NMR studies are greatly enhanced by the ability to prepare multiple milligrams of protein with various isotopic labeling patterns. Here, we demonstrate high-yield production of several isotopically labeled forms of recombinant sTF, allowing for high-resolution NMR studies both in the solid and solution state. We also report solution NMR spectra at sub-mM concentrations of sTF, ensuring the presence of dispersed monomer, as well as the first solid-state NMR spectra of sTF. Our improved sample preparation and precipitation conditions have enabled the acquisition of multidimensional NMR data sets for TF chemical shift assignment and provide a benchmark for TF structure elucidation. PMID:27657719

  18. A Qualitative Model of Human Interaction with Complex Dynamic Systems

    NASA Technical Reports Server (NTRS)

    Hess, Ronald A.

    1987-01-01

    A qualitative model describing human interaction with complex dynamic systems is developed. The model is hierarchical in nature and consists of three parts: a behavior generator, an internal model, and a sensory information processor. The behavior generator is responsible for action decomposition, turning higher level goals or missions into physical action at the human-machine interface. The internal model is an internal representation of the environment which the human is assumed to possess and is divided into four submodel categories. The sensory information processor is responsible for sensory composition. All three parts of the model act in consort to allow anticipatory behavior on the part of the human in goal-directed interaction with dynamic systems. Human workload and error are interpreted in this framework, and the familiar example of an automobile commute is used to illustrate the nature of the activity in the three model elements. Finally, with the qualitative model as a guide, verbal protocols from a manned simulation study of a helicopter instrument landing task are analyzed with particular emphasis on the effect of automation on human-machine performance.

  19. A qualitative model of human interaction with complex dynamic systems

    NASA Technical Reports Server (NTRS)

    Hess, Ronald A.

    1987-01-01

    A qualitative model describing human interaction with complex dynamic systems is developed. The model is hierarchical in nature and consists of three parts: a behavior generator, an internal model, and a sensory information processor. The behavior generator is responsible for action decomposition, turning higher level goals or missions into physical action at the human-machine interface. The internal model is an internal representation of the environment which the human is assumed to possess and is divided into four submodel categories. The sensory information processor is responsible for sensory composition. All three parts of the model act in consort to allow anticipatory behavior on the part of the human in goal-directed interaction with dynamic systems. Human workload and error are interpreted in this framework, and the familiar example of an automobile commute is used to illustrate the nature of the activity in the three model elements. Finally, with the qualitative model as a guide, verbal protocols from a manned simulation study of a helicopter instrument landing task are analyzed with particular emphasis on the effect of automation on human-machine performance.

  20. Lunar microcosmos. [human factors of lunar habitat

    NASA Technical Reports Server (NTRS)

    Pirie, N.

    1974-01-01

    A human habitat on the lunar surface requires energy recycling metabolites based on the utilization of vegetative plants that are good photosynthesizers. Selection criteria involve reactions to fertilization by human excrements, suitability as food for man (with or without fractionation), physiological effects of prolonged ingestion of these plants, and technical methods for returning inedible portions back into the cycle.

  1. Environmental layout complexity affects neural activity during navigation in humans.

    PubMed

    Slone, Edward; Burles, Ford; Iaria, Giuseppe

    2016-05-01

    Navigating large-scale surroundings is a fundamental ability. In humans, it is commonly assumed that navigational performance is affected by individual differences, such as age, sex, and cognitive strategies adopted for orientation. We recently showed that the layout of the environment itself also influences how well people are able to find their way within it, yet it remains unclear whether differences in environmental complexity are associated with changes in brain activity during navigation. We used functional magnetic resonance imaging to investigate how the brain responds to a change in environmental complexity by asking participants to perform a navigation task in two large-scale virtual environments that differed solely in interconnection density, a measure of complexity defined as the average number of directional choices at decision points. The results showed that navigation in the simpler, less interconnected environment was faster and more accurate relative to the complex environment, and such performance was associated with increased activity in a number of brain areas (i.e. precuneus, retrosplenial cortex, and hippocampus) known to be involved in mental imagery, navigation, and memory. These findings provide novel evidence that environmental complexity not only affects navigational behaviour, but also modulates activity in brain regions that are important for successful orientation and navigation.

  2. Environmental layout complexity affects neural activity during navigation in humans.

    PubMed

    Slone, Edward; Burles, Ford; Iaria, Giuseppe

    2016-05-01

    Navigating large-scale surroundings is a fundamental ability. In humans, it is commonly assumed that navigational performance is affected by individual differences, such as age, sex, and cognitive strategies adopted for orientation. We recently showed that the layout of the environment itself also influences how well people are able to find their way within it, yet it remains unclear whether differences in environmental complexity are associated with changes in brain activity during navigation. We used functional magnetic resonance imaging to investigate how the brain responds to a change in environmental complexity by asking participants to perform a navigation task in two large-scale virtual environments that differed solely in interconnection density, a measure of complexity defined as the average number of directional choices at decision points. The results showed that navigation in the simpler, less interconnected environment was faster and more accurate relative to the complex environment, and such performance was associated with increased activity in a number of brain areas (i.e. precuneus, retrosplenial cortex, and hippocampus) known to be involved in mental imagery, navigation, and memory. These findings provide novel evidence that environmental complexity not only affects navigational behaviour, but also modulates activity in brain regions that are important for successful orientation and navigation. PMID:26990572

  3. Validating cognitive support for operators of complex human-machine systems

    SciTech Connect

    O`Hara, J.; Wachtel, J.

    1995-10-01

    Modem nuclear power plants (NPPs) are complex systems whose performance is the result of an intricate interaction of human and system control. A complex system may be defined as one which supports a dynamic process involving a large number of elements that interact in many different ways. Safety is addressed through defense-in-depth design and preplanning; i.e., designers consider the types of failures that are most likely to occur and those of high consequence, and design their solutions in advance. However, complex interactions and their failure modes cannot always be anticipated by the designer and may be unfamiliar to plant personnel. These situations may pose cognitive demands on plant personnel, both individually and as a crew. Other factors may contribute to the cognitive challenges of NPP operation as well, including hierarchal processes, dynamic pace, system redundancy and reliability, and conflicting objectives. These factors are discussed in this paper.

  4. WHO DOES WHAT IN HUMAN FACTORS/ERGONOMICS IN MALAYSIA?

    PubMed

    Ahasan, Rabiul

    2014-12-01

    Individuals' expertise in human factors and ergonomics in Malaysia was studied with a view to aiding in gauging the confusion and conjectures of the expertise in this area. The choices and preferences of individuals in dealing with the current issues of human factors and ergonomics were examined. The authors suggest the ways to meet ethical challenges in their work and professions.

  5. Simulation for human factors research. A central question: Fidelity

    NASA Technical Reports Server (NTRS)

    Nagel, D.

    1985-01-01

    Generalized outlines are presented for simulation in human factors research. Recent trends in aeronautical simulation are given. Some criteria for effective training devices are also given. Full system/full mission simulation in aviation and in space human factors research is presented.

  6. Some NASA contributions to human factors engineering: A survey

    NASA Technical Reports Server (NTRS)

    Behan, R. A.; Wendhausen, H. W.

    1973-01-01

    This survey presents the NASA contributions to the state of the art of human factors engineering, and indicates that these contributions have a variety of applications to nonaerospace activities. Emphasis is placed on contributions relative to man's sensory, motor, decisionmaking, and cognitive behavior and on applications that advance human factors technology.

  7. Complex formation with nucleic acids and aptamers alters the antigenic properties of platelet factor 4

    PubMed Central

    Jaax, Miriam E.; Krauel, Krystin; Marschall, Thomas; Brandt, Sven; Gansler, Julia; Fürll, Birgitt; Appel, Bettina; Fischer, Silvia; Block, Stephan; Helm, Christiane A.; Müller, Sabine; Preissner, Klaus T.

    2013-01-01

    The tight electrostatic binding of the chemokine platelet factor 4 (PF4) to polyanions induces heparin-induced thrombocytopenia, a prothrombotic adverse drug reaction caused by immunoglobulin G directed against PF4/polyanion complexes. This study demonstrates that nucleic acids, including aptamers, also bind to PF4 and enhance PF4 binding to platelets. Systematic assessment of RNA and DNA constructs, as well as 4 aptamers of different lengths and secondary structures, revealed that increasing length and double-stranded segments of nucleic acids augment complex formation with PF4, while single nucleotides or single-stranded polyA or polyC constructs do not. Aptamers were shown by circular dichroism spectroscopy to induce structural changes in PF4 that resemble those induced by heparin. Moreover, heparin-induced anti-human–PF4/heparin antibodies cross-reacted with human PF4/nucleic acid and PF4/aptamer complexes, as shown by an enzyme immunoassay and a functional platelet activation assay. Finally, administration of PF4/44mer–DNA protein C aptamer complexes in mice induced anti–PF4/aptamer antibodies, which cross-reacted with murine PF4/heparin complexes. These data indicate that the formation of anti-PF4/heparin antibodies in postoperative patients may be augmented by PF4/nucleic acid complexes. Moreover, administration of therapeutic aptamers has the potential to induce anti-PF4/polyanion antibodies and a prothrombotic diathesis. PMID:23673861

  8. Dynamics of Major Histocompatibility Complex Class I Association with the Human Peptide-loading Complex*

    PubMed Central

    Panter, Michaela S.; Jain, Ankur; Leonhardt, Ralf M.; Ha, Taekjip; Cresswell, Peter

    2012-01-01

    Although the human peptide-loading complex (PLC) is required for optimal major histocompatibility complex class I (MHC I) antigen presentation, its composition is still incompletely understood. The ratio of the transporter associated with antigen processing (TAP) and MHC I to tapasin, which is responsible for MHC I recruitment and peptide binding optimization, is particularly critical for modeling of the PLC. Here, we characterized the stoichiometry of the human PLC using both biophysical and biochemical approaches. By means of single-molecule pulldown (SiMPull), we determined a TAP/tapasin ratio of 1:2, consistent with previous studies of insect-cell microsomes, rat-human chimeric cells, and HeLa cells expressing truncated TAP subunits. We also report that the tapasin/MHC I ratio varies, with the PLC population comprising both 2:1 and 2:2 complexes, based on mutational and co-precipitation studies. The MHC I-saturated PLC may be particularly prevalent among peptide-selective alleles, such as HLA-C4. Additionally, MHC I association with the PLC increases when its peptide supply is reduced by inhibiting the proteasome or by blocking TAP-mediated peptide transport using viral inhibitors. Taken together, our results indicate that the composition of the human PLC varies under normal conditions and dynamically adapts to alterations in peptide supply that may arise during viral infection. These findings improve our understanding of the quality control of MHC I peptide loading and may aid the structural and functional modeling of the human PLC. PMID:22829594

  9. NASA: Model development for human factors interfacing

    NASA Technical Reports Server (NTRS)

    Smith, L. L.

    1984-01-01

    The results of an intensive literature review in the general topics of human error analysis, stress and job performance, and accident and safety analysis revealed no usable techniques or approaches for analyzing human error in ground or space operations tasks. A task review model is described and proposed to be developed in order to reduce the degree of labor intensiveness in ground and space operations tasks. An extensive number of annotated references are provided.

  10. Human Serum Albumin Complexed with Myristate and AZT

    SciTech Connect

    Zhu, Lili; Yang, Feng; Chen, Liqing; Meehan, Edward J.; Huang, Mingdong

    2008-06-16

    3'-Azido-3'-deoxythymidine (AZT) is the first clinically effective drug for the treatment of human immunodeficiency virus infection. The drug interaction with human serum albumin (HSA) has been an important component in understanding its mechanism of action, especially in drug distribution and in drug-drug interaction on HSA in the case of multi-drug therapy. We present here crystal structures of a ternary HSA-Myr-AZT complex and a quaternary HSA-Myr-AZT-SAL complex (Myr, myristate; SAL, salicylic acid). From this study, a new drug binding subsite on HSA Sudlow site 1 was identified. The presence of fatty acid is needed for the creation of this subsite due to fatty acid induced conformational changes of HSA. Thus, the Sudlow site 1 of HSA can be divided into three non-overlapped subsites: a SAL subsite, an indomethacin subsite and an AZT subsite. Binding of a drug to HSA often influences simultaneous binding of other drugs. From the HSA-Myr-AZT-SAL complex structure, we observed the coexistence of two drugs (AZT and SAL) in Sudlow site 1 and the competition between these two drugs in subdomain IB. These results provide new structural information on HSA-drug interaction and drug-drug interaction on HSA.

  11. Human Factors and Computer Interfaces--Implications for Artificial Intelligence.

    ERIC Educational Resources Information Center

    Norris, Cathleen A.

    1987-01-01

    This second in a series of articles on artificial intelligence emphasizes human factors. The design of video display units and keyboards is discussed, the organizational structure of human memory is described, humans are examined as information processors using inductive and deductive reasoning, and educational implications are explored. (LRW)

  12. Human Reliability Analysis for Design: Using Reliability Methods for Human Factors Issues

    SciTech Connect

    Ronald Laurids Boring

    2010-11-01

    This paper reviews the application of human reliability analysis methods to human factors design issues. An application framework is sketched in which aspects of modeling typically found in human reliability analysis are used in a complementary fashion to the existing human factors phases of design and testing. The paper provides best achievable practices for design, testing, and modeling. Such best achievable practices may be used to evaluate and human system interface in the context of design safety certifications.

  13. Space Human Factors Engineering Challenges in Long Duration Space Flight

    NASA Technical Reports Server (NTRS)

    Garland, Daniel J.; Endsley, Mica R.; Ellison, June; Caldwell, Barrett S.; Mount, Frances E.; Bond, Robert L. (Technical Monitor)

    1999-01-01

    The focus of this panel is on identifying and discussing the critical human factors challenges facing long duration space flight. Living and working aboard the International Space Station (ISS) will build on the experience humans have had to date aboard the Shuttle and MIR. More extended missions, involving lunar and planetary missions to Mars are being planned. These missions will involve many human factors challenges regarding a number of issues on which more research is needed.

  14. Human factors aspects of advanced instrumentation in the nuclear industry

    SciTech Connect

    Carter, R.J.

    1989-01-01

    An important consideration in regards to the use of advanced instrumentation in the nuclear industry is the interface between the instrumentation system and the human. A survey, oriented towards identifying the human factors aspects of digital instrumentation, was conducted at a number of United States (US) and Canadian nuclear vendors and utilities. Human factors issues, subsumed under the categories of computer-generated displays, controls, organizational support, training, and related topics were identified. 20 refs., 2 tabs.

  15. INTERACTION OF THE RHEUMATOID FACTOR WITH ANTIGEN-ANTIBODY COMPLEXES AND AGGREGATED GAMMA GLOBULIN

    PubMed Central

    Edelman, G. M.; Kunkel, H. G.; Franklin, E. C.

    1958-01-01

    The effect of highly purified rheumatoid factor on the precipitin reactions of various antigen-antibody systems was determined. The amount of nitrogen precipitated was increased over a broad range when the factor was added to ovalbumin, human albumin, or human gamma globulin, and the corresponding rabbit antibodies. In the zone of antigen excess, soluble antigen-antibody complexes were precipitated by rheumatoid factor. Soluble aggregates of human and rabbit gamma globulin, produced by heating at 63°C., treatment with urea plus mercaptoethanol or treatment with guanidine, also precipitated with rheumatoid factor. Ultracentrifugal analysis of dissolved specific precipitates showed the presence of aggregated gamma globulin. The sedimentation rate of reactive aggregates was greater than 20 S, and concentrated preparations free of the non-reactive 7 S gamma globulin could be prepared by various procedures of zone centrifugation. These aggregates showed a high inhibitory capacity in the sensitized sheep cell agglutination reaction. Solid gamma globulin, prepared by heat denaturation, also selectively adsorbed the rheumatoid factor, and removed or decreased the activity in the various precipitation and agglutination reactions. Elution of highly purified active preparations from the solid gamma globulin could be carried out with urea or acid buffers. Evidence for interaction between rheumatoid factor and low molecular weight gamma globulin without precipitation, was also obtained. This interaction appears to occur in the circulation of patients with rheumatoid arthritis. The question of whether the rheumatoid factor represents an antibody to gamma globulin was discussed. Points of similarity to the behavior of complement also were cited. PMID:13549644

  16. Hybrid Structural Model of the Complete Human ESCRT-0 Complex

    SciTech Connect

    Ren, Xuefeng; Kloer, Daniel P.; Kim, Young C.; Ghirlando, Rodolfo; Saidi, Layla F.; Hummer, Gerhard; Hurley, James H.

    2009-03-31

    The human Hrs and STAM proteins comprise the ESCRT-0 complex, which sorts ubiquitinated cell surface receptors to lysosomes for degradation. Here we report a model for the complete ESCRT-0 complex based on the crystal structure of the Hrs-STAM core complex, previously solved domain structures, hydrodynamic measurements, and Monte Carlo simulations. ESCRT-0 expressed in insect cells has a hydrodynamic radius of R{sub H} = 7.9 nm and is a 1:1 heterodimer. The 2.3 {angstrom} crystal structure of the ESCRT-0 core complex reveals two domain-swapped GAT domains and an antiparallel two-stranded coiled-coil, similar to yeast ESCRT-0. ESCRT-0 typifies a class of biomolecular assemblies that combine structured and unstructured elements, and have dynamic and open conformations to ensure versatility in target recognition. Coarse-grained Monte Carlo simulations constrained by experimental R{sub H} values for ESCRT-0 reveal a dynamic ensemble of conformations well suited for diverse functions.

  17. AFRICAN GENETIC DIVERSITY: Implications for Human Demographic History, Modern Human Origins, and Complex Disease Mapping

    PubMed Central

    Campbell, Michael C.; Tishkoff, Sarah A.

    2010-01-01

    Comparative studies of ethnically diverse human populations, particularly in Africa, are important for reconstructing human evolutionary history and for understanding the genetic basis of phenotypic adaptation and complex disease. African populations are characterized by greater levels of genetic diversity, extensive population substructure, and less linkage disequilibrium (LD) among loci compared to non-African populations. Africans also possess a number of genetic adaptations that have evolved in response to diverse climates and diets, as well as exposure to infectious disease. This review summarizes patterns and the evolutionary origins of genetic diversity present in African populations, as well as their implications for the mapping of complex traits, including disease susceptibility. PMID:18593304

  18. The heparin-binding exosite is critical to allosteric activation of factor IXa in the intrinsic tenase complex: the role of arginine 165 and factor X.

    PubMed

    Misenheimer, Tina M; Buyue, Yang; Sheehan, John P

    2007-07-01

    Heparin inhibits the intrinsic tenase complex (factor IXa-factor VIIIa) via interaction with a factor IXa exosite. To define the role of this exosite, human factor IXa with alanine substituted for conserved surface residues (R126, N129, K132, R165, N178) was characterized. Chromogenic substrate hydrolysis by the mutant proteases was reduced 20-30% relative to factor IXa wild type. Coagulant activity was moderately (N129A, K132A, K126A) or dramatically (R165A) reduced relative to factor IXa wild type. Kinetic analysis demonstrated a marked reduction in apparent cofactor affinity (23-fold) for factor IXa R165, and an inability to stabilize cofactor activity. Factor IXa K126A, N129A, and K132A demonstrated modest reductions ( approximately 2-fold) in apparent cofactor affinity, and accelerated decay of intrinsic tenase activity. In the absence of factor VIIIa, factor IXa N178A and R165A demonstrated a defective Vmax(app) for factor X activation. In the presence of factor VIIIa, Vmax(app) varied in proportion to the predicted factor IXa-factor VIIIa concentration. However, factor IXa R165A had a 65% reduction in the kcat for factor X, suggesting an additional effect on catalysis. The ability of factor IXa to compete for physical assembly into the intrinsic tenase complex was enhanced by EGR-chloromethylketone bound to the factor IXa active site or addition of factor X, and reduced by selected mutations in the heparin-binding exosite (N178A, K126A, R165A). These results suggest that the factor IXa heparin-binding exosite participates in both cofactor binding and protease activation, and cofactor affinity is linked to active site conformation and factor X interaction during enzyme assembly.

  19. Our Complex Universe: A Human Understanding through Art

    NASA Astrophysics Data System (ADS)

    Kaler, J. B.

    2013-04-01

    Nature, in all its aspects, provides us with a foundation for creating art in all its forms. Among the most inspirational of these aspects are those of the sky, from sunsets to stars to galaxies. But it works both ways. While we can strive to know the Universe through physics and mathematics, the unending complexity of the structures we examine overwhelms the senses and hinders our ability to appreciate the beauty and meaning of our surroundings. The arts provide avenues for understanding and interpreting the complexity of nature in human terms. In doing so, they reveal more of nature's aesthetics and thereby have the power to inspire scientists to look ever deeper into our Universe.

  20. Pluripotent stem cell transcription factors during human odontogenesis.

    PubMed

    da Cunha, Juliana Malta; da Costa-Neves, Adriana; Kerkis, Irina; da Silva, Marcelo Cavenaghi Pereira

    2013-09-01

    Stem cells are capable of generating various cell lines and can be obtained from adult or embryonic tissues for clinical therapies. Stem cells from deciduous dental pulp are among those that are easily obtainable from adult tissues and have been widely studied because of their ability to differentiate into a variety of cell lines in the presence of various chemical mediators. We have analyze the expression of several proteins related to the differentiation and proliferative potential of cell populations that compose the tooth germ of human fetuses. We evaluate 20 human fetuses of both genders. After being paraffin-embedded, cap and bell stages of tooth germ development were subjected to immunohistochemistry for the following markers: Oct-4, Nanog, Stat-3 and Sox-2. The studied antibodies showed nuclear or cytoplasmic immunnostaining within various anatomical structures and with various degrees of expression, indicating the action of these proteins during tooth development. We conclude that the interrelationship between these transcription factors is complex and associated with self-renewal and cell differentiation. Our results suggest that the expression of Oct-4, Nanog, Sox-2 and Stat-3 are related to differentiation in ameloblasts and odontoblasts.

  1. Human disease and drug pharmacology, complex as real life.

    PubMed

    Viayna, E; Sola, I; Di Pietro, O; Muñoz-Torrero, D

    2013-01-01

    In the past decades drug discovery practice has escaped from the complexity of the formerly used phenotypic screening in animals to focus on assessing drug effects on isolated protein targets in the search for drugs that exclusively and potently hit one selected target, thought to be critical for a given disease, while not affecting at all any other target to avoid the occurrence of side-effects. However, reality does not conform to these expectations, and, conversely, this approach has been concurrent with increased attrition figures in late-stage clinical trials, precisely due to lack of efficacy and safety. In this context, a network biology perspective of human disease and treatment has burst into the drug discovery scenario to bring it back to the consideration of the complexity of living organisms and particularly of the (patho)physiological environment where protein targets are (mal)functioning and where drugs have to exert their restoring action. Under this perspective, it has been found that usually there is not one but several disease-causing genes and, therefore, not one but several relevant protein targets to be hit, which do not work on isolation but in a highly interconnected manner, and that most known drugs are inherently promiscuous. In this light, the rationale behind the currently prevailing single-target-based drug discovery approach might even seem a Utopia, while, conversely, the notion that the complexity of human disease must be tackled with complex polypharmacological therapeutic interventions constitutes a difficult-to-refuse argument that is spurring the development of multitarget therapies. PMID:23410162

  2. Human disease and drug pharmacology, complex as real life.

    PubMed

    Viayna, E; Sola, I; Di Pietro, O; Muñoz-Torrero, D

    2013-01-01

    In the past decades drug discovery practice has escaped from the complexity of the formerly used phenotypic screening in animals to focus on assessing drug effects on isolated protein targets in the search for drugs that exclusively and potently hit one selected target, thought to be critical for a given disease, while not affecting at all any other target to avoid the occurrence of side-effects. However, reality does not conform to these expectations, and, conversely, this approach has been concurrent with increased attrition figures in late-stage clinical trials, precisely due to lack of efficacy and safety. In this context, a network biology perspective of human disease and treatment has burst into the drug discovery scenario to bring it back to the consideration of the complexity of living organisms and particularly of the (patho)physiological environment where protein targets are (mal)functioning and where drugs have to exert their restoring action. Under this perspective, it has been found that usually there is not one but several disease-causing genes and, therefore, not one but several relevant protein targets to be hit, which do not work on isolation but in a highly interconnected manner, and that most known drugs are inherently promiscuous. In this light, the rationale behind the currently prevailing single-target-based drug discovery approach might even seem a Utopia, while, conversely, the notion that the complexity of human disease must be tackled with complex polypharmacological therapeutic interventions constitutes a difficult-to-refuse argument that is spurring the development of multitarget therapies.

  3. Applying Human Factors during the SIS Life Cycle

    SciTech Connect

    Avery, K.

    2010-05-05

    Safety Instrumented Systems (SIS) are widely used in U.S. Department of Energy's (DOE) nonreactor nuclear facilities for safety-critical applications. Although use of the SIS technology and computer-based digital controls, can improve performance and safety, it potentially introduces additional complexities, such as failure modes that are not readily detectable. Either automated actions or manual (operator) actions may be required to complete the safety instrumented function to place the process in a safe state or mitigate a hazard in response to an alarm or indication. DOE will issue a new standard, Application of Safety Instrumented Systems Used at DOE Nonreactor Nuclear Facilities, to provide guidance for the design, procurement, installation, testing, maintenance, operation, and quality assurance of SIS used in safety significant functions at DOE nonreactor nuclear facilities. The DOE standard focuses on utilizing the process industry consensus standard, American National Standards Institute/ International Society of Automation (ANSI/ISA) 84.00.01, Functional Safety: Safety Instrumented Systems for the Process Industry Sector, to support reliable SIS design throughout the DOE complex. SIS design must take into account human-machine interfaces and their limitations and follow good human factors engineering (HFE) practices. HFE encompasses many diverse areas (e.g., information display, user-system interaction, alarm management, operator response, control room design, and system maintainability), which affect all aspects of system development and modification. This paper presents how the HFE processes and principles apply throughout the SIS life cycle to support the design and use of SIS at DOE nonreactor nuclear facilities.

  4. Human opinion dynamics: an inspiration to solve complex optimization problems.

    PubMed

    Kaur, Rishemjit; Kumar, Ritesh; Bhondekar, Amol P; Kapur, Pawan

    2013-01-01

    Human interactions give rise to the formation of different kinds of opinions in a society. The study of formations and dynamics of opinions has been one of the most important areas in social physics. The opinion dynamics and associated social structure leads to decision making or so called opinion consensus. Opinion formation is a process of collective intelligence evolving from the integrative tendencies of social influence with the disintegrative effects of individualisation, and therefore could be exploited for developing search strategies. Here, we demonstrate that human opinion dynamics can be utilised to solve complex mathematical optimization problems. The results have been compared with a standard algorithm inspired from bird flocking behaviour and the comparison proves the efficacy of the proposed approach in general. Our investigation may open new avenues towards understanding the collective decision making. PMID:24141795

  5. Human opinion dynamics: An inspiration to solve complex optimization problems

    PubMed Central

    Kaur, Rishemjit; Kumar, Ritesh; Bhondekar, Amol P.; Kapur, Pawan

    2013-01-01

    Human interactions give rise to the formation of different kinds of opinions in a society. The study of formations and dynamics of opinions has been one of the most important areas in social physics. The opinion dynamics and associated social structure leads to decision making or so called opinion consensus. Opinion formation is a process of collective intelligence evolving from the integrative tendencies of social influence with the disintegrative effects of individualisation, and therefore could be exploited for developing search strategies. Here, we demonstrate that human opinion dynamics can be utilised to solve complex mathematical optimization problems. The results have been compared with a standard algorithm inspired from bird flocking behaviour and the comparison proves the efficacy of the proposed approach in general. Our investigation may open new avenues towards understanding the collective decision making. PMID:24141795

  6. Human opinion dynamics: An inspiration to solve complex optimization problems

    NASA Astrophysics Data System (ADS)

    Kaur, Rishemjit; Kumar, Ritesh; Bhondekar, Amol P.; Kapur, Pawan

    2013-10-01

    Human interactions give rise to the formation of different kinds of opinions in a society. The study of formations and dynamics of opinions has been one of the most important areas in social physics. The opinion dynamics and associated social structure leads to decision making or so called opinion consensus. Opinion formation is a process of collective intelligence evolving from the integrative tendencies of social influence with the disintegrative effects of individualisation, and therefore could be exploited for developing search strategies. Here, we demonstrate that human opinion dynamics can be utilised to solve complex mathematical optimization problems. The results have been compared with a standard algorithm inspired from bird flocking behaviour and the comparison proves the efficacy of the proposed approach in general. Our investigation may open new avenues towards understanding the collective decision making.

  7. Human Factors in Library Administration. Revised Edition.

    ERIC Educational Resources Information Center

    Barnhard, Neil

    Intended for the beginning or inexperienced supervisor, this continuing education course syllabus presents basic information on the development of human relations skills, particularly in the areas of leadership, communication, conflict, and motivation. Role playing situations set in various types of medical libraries are also outlined to provide…

  8. Human Factors Lessons Learned from Flight Testing Wingless Lifting Body Vehicles

    NASA Technical Reports Server (NTRS)

    Merlin, Peter William

    2014-01-01

    Since the 1960s, NASA, the Air Force, and now private industry have attempted to develop an operational human crewed reusable spacecraft with a wingless, lifting body configuration. This type of vehicle offers increased mission flexibility and greater reentry cross range than capsule type craft, and is particularly attractive due to the capability to land on a runway. That capability, however, adds complexity to the human factors engineering requirements of developing such aircraft.

  9. Status of human factors engineering system design in Europe

    SciTech Connect

    Ives, G. )

    1990-01-01

    A review of the European status of human factors engineering has been carried out covering a wide scope of activities which includes psychology, cognitive science, ergonomics, design, training, procedure writing, operating, artificial intelligence and expert systems. There is an increasing awareness of the part that human factors play in major nuclear power plant accidents. The emphasis of attention in human factors is changing. In some areas there are encouraging signs of progress and development, but in other areas there is still scope for improvement.

  10. Human factor design of habitable space facilities

    NASA Technical Reports Server (NTRS)

    Clearwater, Yvonne A.

    1987-01-01

    Current fundamental and applied habitability research conducted as part of the U.S. space program is reviewed with emphasis on methods, findings, and applications of the results to the planning and design of the International Space Station. The discussion covers the following six concurrent directions of habitability research: operational simulation, functional interior decor research, space crew privacy requirements, interior layout and configuration analysis, human spatial habitability model, and analogous environments research.

  11. Recent technology products from Space Human Factors research

    NASA Technical Reports Server (NTRS)

    Jenkins, James P.

    1991-01-01

    The goals of the NASA Space Human Factors program and the research carried out concerning human factors are discussed with emphasis given to the development of human performance models, data, and tools. The major products from this program are described, which include the Laser Anthropometric Mapping System; a model of the human body for evaluating the kinematics and dynamics of human motion and strength in microgravity environment; an operational experience data base for verifying and validating the data repository of manned space flights; the Operational Experience Database Taxonomy; and a human-computer interaction laboratory whose products are the display softaware and requirements and the guideline documents and standards for applications on human-computer interaction. Special attention is given to the 'Convoltron', a prototype version of a signal processor for synthesizing the head-related transfer functions.

  12. Usability: Human Research Program - Space Human Factors and Habitability

    NASA Technical Reports Server (NTRS)

    Sandor, Aniko; Holden, Kritina L.

    2009-01-01

    The Usability project addresses the need for research in the area of metrics and methodologies used in hardware and software usability testing in order to define quantifiable and verifiable usability requirements. A usability test is a human-in-the-loop evaluation where a participant works through a realistic set of representative tasks using the hardware/software under investigation. The purpose of this research is to define metrics and methodologies for measuring and verifying usability in the aerospace domain in accordance with FY09 focus on errors, consistency, and mobility/maneuverability. Usability metrics must be predictive of success with the interfaces, must be easy to obtain and/or calculate, and must meet the intent of current Human Systems Integration Requirements (HSIR). Methodologies must work within the constraints of the aerospace domain, be cost and time efficient, and be able to be applied without extensive specialized training.

  13. Structure of transportin SR2, a karyopherin involved in human disease, in complex with Ran

    PubMed Central

    Tsirkone, Vicky G.; Beutels, Katrien G.; Demeulemeester, Jonas; Debyser, Zeger; Christ, Frauke; Strelkov, Sergei V.

    2014-01-01

    Transportin SR2 (TRN-SR2) is a β-type karyopherin responsible for the nuclear import of specific cargoes, including serine/arginine-rich splicing factors. The protein has been implicated in a variety of human diseases, including HIV infection, primary biliary cirrhosis and limb-girdle muscular dystrophy 1F. Towards understanding its molecular mechanism, a 2.9 Å resolution crystal structure of human TRN-SR2 complexed with the small GTPase Ran has been determined. TRN-SR2 is composed of 20 α-helical HEAT repeats forming a solenoid-like fold. The first nine repeats form a ‘cradle’ for the binding of RanGTP, revealing similarities but also differences with respect to the related importin 13 complex. PMID:24915079

  14. Human factors survey of advanced instrumentation and controls

    SciTech Connect

    Carter, R.J.

    1989-01-01

    A survey oriented towards identifying the human factors issues in regard to the use of advanced instrumentation and controls (I C) in the nuclear industry was conducted. A number of United States (US) and Canadian nuclear vendors and utilities were participants in the survey. Human factors items, subsumed under the categories of computer-generated displays (CGD), controls, organizational support, training, and related topics, were discussed. The survey found the industry to be concerned about the human factors issues related to the implementation of advanced I C. Fifteen potential human factors problems were identified. They include: the need for an advanced I C guideline equivalent to NUREG-0700; a role change in the control room from operator to supervisor; information overload; adequacy of existing training technology for advanced I C; and operator acceptance and trust. 11 refs., 1 tab.

  15. Architecture of the human XPC DNA repair and stem cell coactivator complex

    PubMed Central

    He, Yuan; Grob, Patricia; Fong, Yick W.; Nogales, Eva; Tjian, Robert

    2015-01-01

    The Xeroderma pigmentosum complementation group C (XPC) complex is a versatile factor involved in both nucleotide excision repair and transcriptional coactivation as a critical component of the NANOG, OCT4, and SOX2 pluripotency gene regulatory network. Here we present the structure of the human holo-XPC complex determined by single-particle electron microscopy to reveal a flexible, ear-shaped structure that undergoes localized loss of order upon DNA binding. We also determined the structure of the complete yeast homolog Rad4 holo-complex to find a similar overall architecture to the human complex, consistent with their shared DNA repair functions. Localized differences between these structures reflect an intriguing phylogenetic divergence in transcriptional capabilities that we present here. Having positioned the constituent subunits by tagging and deletion, we propose a model of key interaction interfaces that reveals the structural basis for this difference in functional conservation. Together, our findings establish a framework for understanding the structure-function relationships of the XPC complex in the interplay between transcription and DNA repair. PMID:26627236

  16. Advanced automated glass cockpit certification: Being wary of human factors

    NASA Technical Reports Server (NTRS)

    Amalberti, Rene; Wilbaux, Florence

    1994-01-01

    This paper presents some facets of the French experience with human factors in the process of certification of advanced automated cockpits. Three types of difficulties are described: first, the difficulties concerning the hotly debated concept of human error and its non-linear relationship to risk of accident; a typology of errors to be taken into account in the certification process is put forward to respond to this issue. Next, the difficulties connected to the basically gradual and evolving nature of pilot expertise on a given type of aircraft, which contrasts with the immediate and definitive style of certifying systems. The last difficulties to be considered are those related to the goals of certification itself on these new aircraft and the status of findings from human factor analyses (in particular, what should be done with disappointing results, how much can the changes induced by human factors investigation economically affect aircraft design, how many errors do we need to accumulate before we revise the system, what should be remedied when human factor problems are discovered at the certification stage: the machine? pilot training? the rules? or everything?). The growth of advanced-automated glass cockpits has forced the international aeronautical community to pay more attention to human factors during the design phase, the certification phase and pilot training. The recent creation of a human factor desk at the DGAC-SFACT (Official French services) is a direct consequence of this. The paper is divided into three parts. Part one debates human error and its relationship with system design and accident risk. Part two describes difficulties connected to the basically gradual and evolving nature of pilot expertise on a given type of aircraft, which contrasts with the immediate and definitive style of certifying systems. Part three focuses on concrete outcomes of human factors for certification purposes.

  17. Postcrystallization Analysis of the Irreproducibility of the Human Intrinsic Factor−Cobalamin Complex Crystals

    SciTech Connect

    Sukumar,N.; Mathews, F.S.; Gordon, M.M.; Ealick, S.E.; Alpers, D.H.

    2009-01-23

    Approximately 15% (w/w) of human intrinsic factor (IF) is comprised of carbohydrate side chains, making crystallization problematic. In addition, IF is sensitive to proteolysis. To understand the role of these factors in crystallization, we carried out dynamic light scattering studies and assessed their correlation with crystallization. The packing of the IF-cobalamin complex and the known properties of the protein in solution were also analyzed to explore the irreproducibility of the IF-cobalamin complex crystals and the difficulty in obtaining apo-IF crystals suitable for crystallographic analysis. The results indicate that although glycosylation may in general be inhibitory for crystallization, time-dependent proteolysis appears to play a much more important role in the process of crystallization of IF. Thus, the presence of cobalamin and of domain fragments that can form incomplete dimers lacking one of two {beta}-domains appears to promote the crystallization of IF.

  18. A human factors evaluation using tools for automated knowledge engineering

    NASA Technical Reports Server (NTRS)

    Gomes, Marie E.; Lind, Stephanie

    1994-01-01

    A human factors evaluation of the MH-53J helicopter cockpit is described. This evaluation was an application and futher development of Tools for Automated Knowledge Engineering (TAKE). TAKE is used to acquire and analyze knowledge from domain experts (aircrew members, system designers, maintenance personnel, human factors engineers, or others). TAKE was successfully utilized for the purpose of recommending improvements for the man-machine interfaces (MMI) in the MH-53J cockpit.

  19. Kinetics of the Factor XIa catalyzed activation of human blood coagulation Factor IX

    SciTech Connect

    Walsh, P.N.; Bradford, H.; Sinha, D.; Piperno, J.R.; Tuszynski, G.P.

    1984-05-01

    The kinetics of activation of human Factor IX by human Factor XIa was studied by measuring the release of a trichloroacetic acid-soluble tritium-labeled activation peptide from Factor IX. Initial rates of trichloroacetic acid-soluble /sup 3/H-release were linear over 10-30 min of incubation of Factor IX (88 nM) with CaCl/sub 2/ (5 mM) and with pure (greater than 98%) Factor XIa (0.06-1.3 nM), which was prepared by incubating human Factor XI with bovine Factor XIIa. Release of /sup 3/H preceded the appearance of Factor IXa activity, and the percentage of /sup 3/H released remained constant when the mole fraction of /sup 3/H-labeled and unlabeled Factor IX was varied and the total Factor IX concentration remained constant. A linear correlation (r greater than 0.98, P less than 0.001) was observed between initial rates of /sup 3/H-release and the concentration of Factor XIa, measured by chromogenic assay and by radioimmunoassay and added at a Factor IX:Factor XIa molar ratio of 70-5,600. Kinetic parameters, determined by Lineweaver-Burk analysis, include K/sub m/ (0.49 microM) of about five- to sixfold higher than the plasma Factor IX concentration, which could therefore regulate the reaction. The catalytic constant (k/sub cat/) (7.7/s) is approximately 20-50 times higher than that reported by Zur and Nemerson for Factor IX activation by Factor VIIa plus tissue factor. Therefore, depending on the relative amounts of Factor XIa and Factor VIIa generated in vivo and other factors which may influence reaction rates, these kinetic parameters provide part of the information required for assessing the relative contributions of the intrinsic and extrinsic pathways to Factor IX activation, and suggest that the Factor XIa catalyzed reaction is physiologically significant.

  20. Three-dimensional structure of human chromatin accessibility complex hCHRAC by electron microscopy

    SciTech Connect

    Hu, M.; Hainfeld, J.; Zhang, Y.-B.; Qian, L.; Brinas, R. P.; Kuznetsova, L.

    2008-12-01

    ATP-dependent chromatin remodeling complexes modulate the dynamic assembly and remodeling of chromatin involved in DNA transcription, replication, and repair. There is little structural detail known about these important multiple-subunit enzymes that catalyze chromatin remodeling processes. Here we report a three-dimensional structure of the human chromatin accessibility complex, hCHRAC, using single particle reconstruction by negative stain electron microscopy. This structure shows an asymmetric 15 x 10 x 12 nm disk shape with several lobes protruding out of its surfaces. Based on the factors of larger contact area, smaller steric hindrance, and direct involvement of hCHRAC in interactions with the nucleosome, we propose that four lobes on one side form a multiple-site contact surface 10 nm in diameter for nucleosome binding. This work provides the first determination of the three-dimensional structure of the ISWI-family of chromatin remodeling complexes.

  1. Cancer-relevant Splicing Factor CAPERα Engages the Essential Splicing Factor SF3b155 in a Specific Ternary Complex*

    PubMed Central

    Loerch, Sarah; Maucuer, Alexandre; Manceau, Valérie; Green, Michael R.; Kielkopf, Clara L.

    2014-01-01

    U2AF homology motifs (UHMs) mediate protein-protein interactions with U2AF ligand motifs (ULMs) of pre-mRNA splicing factors. The UHM-containing alternative splicing factor CAPERα regulates splicing of tumor-promoting VEGF isoforms, yet the molecular target of the CAPERα UHM is unknown. Here we present structures of the CAPERα UHM bound to a representative SF3b155 ULM at 1.7 Å resolution and, for comparison, in the absence of ligand at 2.2 Å resolution. The prototypical UHM/ULM interactions authenticate CAPERα as a bona fide member of the UHM family of proteins. We identify SF3b155 as the relevant ULM-containing partner of full-length CAPERα in human cell extracts. Isothermal titration calorimetry comparisons of the purified CAPERα UHM binding known ULM-containing proteins demonstrate that high affinity interactions depend on the presence of an intact, intrinsically unstructured SF3b155 domain containing seven ULM-like motifs. The interplay among bound CAPERα molecules gives rise to the appearance of two high affinity sites in the SF3b155 ULM-containing domain. In conjunction with the previously identified, UHM/ULM-mediated complexes of U2AF65 and SPF45 with SF3b155, this work demonstrates the capacity of SF3b155 to offer a platform for coordinated recruitment of UHM-containing splicing factors. PMID:24795046

  2. Human factors in automatic image retrieval system design and evaluation

    NASA Astrophysics Data System (ADS)

    Jaimes, Alejandro

    2006-01-01

    Image retrieval is a human-centered task: images are created by people and are ultimately accessed and used by people for human-related activities. In designing image retrieval systems and algorithms, or measuring their performance, it is therefore imperative to consider the conditions that surround both the indexing of image content and the retrieval. This includes examining the different levels of interpretation for retrieval, possible search strategies, and image uses. Furthermore, we must consider different levels of similarity and the role of human factors such as culture, memory, and personal context. This paper takes a human-centered perspective in outlining levels of description, types of users, search strategies, image uses, and human factors that affect the construction and evaluation of automatic content-based retrieval systems, such as human memory, context, and subjectivity.

  3. Human Factors In The Design Of Video Displays

    NASA Technical Reports Server (NTRS)

    Kaiser, Mary K.; Proffitt, Dennis R.

    1990-01-01

    Good designs take account of perceptual tendencies and conceptual biases in observers. Report presents overview of evolving knowledge of interactions between video displays and human observers. Discusses relative advantages and disadvantages of static and dynamic displays, with attention to human factors combining with characteristics of video-display medium to affect observer's percepts.

  4. Human Factors of Queuing: A Library Circulation Model.

    ERIC Educational Resources Information Center

    Mansfield, Jerry W.

    1981-01-01

    Classical queuing theories and their accompanying service facilities totally disregard the human factors in the name of efficiency. As library managers we need to be more responsive to human needs in the design of service points and make every effort to minimize queuing and queue frustration. Five references are listed. (Author/RAA)

  5. A NEW LEVEL OF ARCHITECTURAL COMPLEXITY IN THE HUMAN PYRUVATE DEHYDROGENASE COMPLEX

    PubMed Central

    Smolle, Michaela; Prior, Alison Elizabeth; Brown, Audrey Elaine; Cooper, Alan; Byron, Olwyn; Lindsay, John Gordon

    2006-01-01

    SUMMARY Mammalian pyruvate dehydrogenase multi-enzyme complex (PDC) is a key metabolic assembly comprising a 60- meric pentagonal dodecahedral E2 core attached to which are 30 E1 heterotetramers and 6 E3 homodimers at maximal occupancy. Stable E3 integration is mediated by an accessory E3 binding protein (E3BP) located on each of the 12 E2 icosahedral faces. Here, we present evidence for a novel subunit organisation in which dihydrolipoamide dehydrogenase (E3) and E3BP form subcomplexes with a 1:2 stoichiometry implying the existence of a network of E3 ‘cross-bridges’ linking pairs of E3BPs across the surface of the E2 core assembly. We have also determined a low resolution structure for a truncated E3BP/E3 subcomplex using small angle xray scattering showing one of the E3BP lipoyl domains docked into the E3 active site. This new level of architectural complexity in mammalian PDC contrasts with the recently published crystal structure of human E3 complexed with its cognate subunit binding domain and provides important new insights into subunit organisation, its catalytic mechanism and regulation by the intrinsic PDC kinase. PMID:16679318

  6. Human Factors for Situation Assessment in Grid Operations

    SciTech Connect

    Guttromson, Ross T.; Schur, Anne; Greitzer, Frank L.; Paget, Mia L.

    2007-08-08

    Executive Summary Despite advances in technology, power system operators must assimilate overwhelming amounts of data to keep the grid operating. Analyses of recent blackouts have clearly demonstrated the need to enhance the operator’s situation awareness (SA). The long-term objective of this research is to integrate valuable technologies into the grid operator environment that support decision making under normal and abnormal operating conditions and remove non-technical barriers to enable the optimum use of these technologies by individuals working alone and as a team. More specifically, the research aims to identify methods and principles to increase SA of grid operators in the context of system conditions that are representative or common across many operating entities and develop operationally relevant experimental methods for studying technologies and operational practices which contribute to SA. With increasing complexity and interconnectivity of the grid, the scope and complexity of situation awareness have grown. New paradigms are needed to guide research and tool development aimed to enhance and improve operations. In reviewing related research, operating practices, systems, and tools, the present study established a taxonomy that provides a perspective on research and development surrounding power grid situation awareness and clarifies the field of human factors/SA for grid operations. Information sources that we used to identify critical factors underlying SA included interviews with experienced operational personnel, available historical summaries and transcripts of abnormal conditions and outages (e.g., the August 14, 2003 blackout), scientific literature, and operational policies/procedures and other documentation. Our analysis of August 2003 blackout transcripts and interviews adopted a different perspective than previous analyses of this material, and we complemented this analysis with additional interviews. Based on our analysis and a broad

  7. Mutations in Complex I Assembly Factor TMEM126B Result in Muscle Weakness and Isolated Complex I Deficiency.

    PubMed

    Sánchez-Caballero, Laura; Ruzzenente, Benedetta; Bianchi, Lucas; Assouline, Zahra; Barcia, Giulia; Metodiev, Metodi D; Rio, Marlène; Funalot, Benoît; van den Brand, Mariël A M; Guerrero-Castillo, Sergio; Molenaar, Joery P; Koolen, David; Brandt, Ulrich; Rodenburg, Richard J; Nijtmans, Leo G; Rötig, Agnès

    2016-07-01

    Mitochondrial complex I deficiency results in a plethora of often severe clinical phenotypes manifesting in early childhood. Here, we report on three complex-I-deficient adult subjects with relatively mild clinical symptoms, including isolated, progressive exercise-induced myalgia and exercise intolerance but with normal later development. Exome sequencing and targeted exome sequencing revealed compound-heterozygous mutations in TMEM126B, encoding a complex I assembly factor. Further biochemical analysis of subject fibroblasts revealed a severe complex I deficiency caused by defective assembly. Lentiviral complementation with the wild-type cDNA restored the complex I deficiency, demonstrating the pathogenic nature of these mutations. Further complexome analysis of one subject indicated that the complex I assembly defect occurred during assembly of its membrane module. Our results show that TMEM126B defects can lead to complex I deficiencies and, interestingly, that symptoms can occur only after exercise. PMID:27374773

  8. Recombinant Human Factor IX Produced from Transgenic Porcine Milk

    PubMed Central

    Lee, Meng-Hwan; Lin, Yin-Shen; Tu, Ching-Fu; Yen, Chon-Ho

    2014-01-01

    Production of biopharmaceuticals from transgenic animal milk is a cost-effective method for highly complex proteins that cannot be efficiently produced using conventional systems such as microorganisms or animal cells. Yields of recombinant human factor IX (rhFIX) produced from transgenic porcine milk under the control of the bovine α-lactalbumin promoter reached 0.25 mg/mL. The rhFIX protein was purified from transgenic porcine milk using a three-column purification scheme after a precipitation step to remove casein. The purified protein had high specific activity and a low ratio of the active form (FIXa). The purified rhFIX had 11.9 γ-carboxyglutamic acid (Gla) residues/mol protein, which approached full occupancy of the 12 potential sites in the Gla domain. The rhFIX was shown to have a higher isoelectric point and lower sialic acid content than plasma-derived FIX (pdFIX). The rhFIX had the same N-glycosylation sites and phosphorylation sites as pdFIX, but had a higher specific activity. These results suggest that rhFIX produced from porcine milk is physiologically active and they support the use of transgenic animals as bioreactors for industrial scale production in milk. PMID:24955355

  9. An evaluation of human factors research for ultrasonic inservice inspection

    SciTech Connect

    Pond, D.J.; Donohoo, D.T.; Harris, R.V. Jr.

    1998-03-01

    This work was undertaken to determine if human factors research has yielded information applicable to upgrading requirements in ASME Boiler and Pressure Vessel Code Section XI, improving methods and techniques in Section V, and/or suggesting relevant research. A preference was established for information and recommendations which have become accepted and standard practice. Manual Ultrasonic Testing/Inservice Inspection (UT/ISI) is a complex task subject to influence by dozens of variables. This review frequently revealed equivocal findings regarding effects of environmental variables as well as repeated indications that inspection performance may be more, and more reliably, influenced by the workers` social environment, including managerial practices, than by other situational variables. Also of significance are each inspector`s relevant knowledge, skills, and abilities, and determination of these is seen as a necessary first step in upgrading requirements, methods, and techniques as well as in focusing research in support of such programs, While understanding the effects and mediating mechanisms of the variables impacting inspection performance is a worthwhile pursuit for researchers, initial improvements in industrial UTASI performance may be achieved by implementing practices already known to mitigate the effects of potentially adverse conditions. 52 refs., 2 tabs.

  10. The pursuit of better diagnostic performance: a human factors perspective

    PubMed Central

    Henriksen, Kerm; Brady, Jeff

    2013-01-01

    Despite the relatively slow start in treating diagnostic error as an amenable research topic at the beginning of the patient safety movement, interest has steadily increased over the past few years in the form of solicitations for research, regularly scheduled conferences, an expanding literature and even a new professional society. Yet improving diagnostic performance increasingly is recognised as a multifaceted challenge. With the aid of a human factors perspective, this paper addresses a few of these challenges, including questions that focus on who owns the problem, treating cognitive and system shortcomings as separate issues, why knowledge in the head is not enough, and what we are learning from health information technology (IT) and the use of checklists. To encourage empirical testing of interventions that aim to improve diagnostic performance, a systems engineering approach making use of rapid-cycle prototyping and simulation is proposed. To gain a fuller understanding of the complexity of the sociotechnical space where diagnostic work is performed, a final note calls for the formation of substantive partnerships with those in disciplines beyond the clinical domain. PMID:23704082

  11. Polyelectrolyte Complex for Heparin Binding Domain Osteogenic Growth Factor Delivery.

    PubMed

    Wing Moon Lam, Raymond; Abbah, Sunny Akogwu; Ming, Wang; Naidu, Mathanapriya; Ng, Felly; Tao, Hu; Goh Cho Hong, James; Ting, Kang; Hee Kit, Wong

    2016-01-01

    During reconstructive bone surgeries, supraphysiological amounts of growth factors are empirically loaded onto scaffolds to promote successful bone fusion. Large doses of highly potent biological agents are required due to growth factor instability as a result of rapid enzymatic degradation as well as carrier inefficiencies in localizing sufficient amounts of growth factor at implant sites. Hence, strategies that prolong the stability of growth factors such as BMP-2/NELL-1, and control their release could actually lower their efficacious dose and thus reduce the need for larger doses during future bone regeneration surgeries. This in turn will reduce side effects and growth factor costs. Self-assembled PECs have been fabricated to provide better control of BMP-2/NELL-1 delivery via heparin binding and further potentiate growth factor bioactivity by enhancing in vivo stability. Here we illustrate the simplicity of PEC fabrication which aids in the delivery of a variety of growth factors during reconstructive bone surgeries. PMID:27585207

  12. An Integrated Suite of Tools to support Human Factors Engineering

    SciTech Connect

    Jacques V Hugo

    2001-08-01

    Human Factors Engineering (HFE) work for the nuclear industry imposes special demands on the practitioner in terms of the scope, complexity and safety requirements for humans in nuclear installations. Unfortunately HFE lags behind other engineering disciplines in the development and use of modern, powerful tools for the full range of analysis and design processes. HFE does not appear to be an attractive market for software and hardware developers and as a result, HFE practitioners usually have to rely on inefficient general-purpose tools like standard office software, or they have to use expensive special-purpose tools that offer only part of the solution they require and which also do not easily integrate with other tools. There have been attempts to develop generic software tools to support the HFE analyst and also to achieve some order and consistency in format and presentation. However, in spite of many years of development, very few tools have emerged that have achieved these goals. This would suggest the need for special tools, but existing commercial products have been found inadequate and to date not a single tool has been developed that adequately supports the special requirements of HFE work for the nuclear industry. This paper describes an integrated suite of generic as well as purpose-built tools that facilitate information solicitation, issues tracking, work domain analysis, functional requirements analysis, function allocation, operational sequence analysis, task analysis and development of HSI design requirements. In combination, this suite of tools supports the analytical as well as the representational aspects of key HFE activities primarily for new NPPs, including capturing information from subject matter experts and various source documents directly into the appropriate tool and then linking, analyzing and extending that information further to represent detailed functional and task information, and ultimately HSI design requirements. The paper

  13. The impact of the human genome project on complex disease.

    PubMed

    Bailey, Jessica N Cooke; Pericak-Vance, Margaret A; Haines, Jonathan L

    2014-07-16

    In the decade that has passed since the initial release of the Human Genome, numerous advancements in science and technology within and beyond genetics and genomics have been encouraged and enhanced by the availability of this vast and remarkable data resource. Progress in understanding three common, complex diseases: age-related macular degeneration (AMD), Alzheimer's disease (AD), and multiple sclerosis (MS), are three exemplars of the incredible impact on the elucidation of the genetic architecture of disease. The approaches used in these diseases have been successfully applied to numerous other complex diseases. For example, the heritability of AMD was confirmed upon the release of the first genome-wide association study (GWAS) along with confirmatory reports that supported the findings of that state-of-the art method, thus setting the foundation for future GWAS in other heritable diseases. Following this seminal discovery and applying it to other diseases including AD and MS, the genetic knowledge of AD expanded far beyond the well-known APOE locus and now includes more than 20 loci. MS genetics saw a similar increase beyond the HLA loci and now has more than 100 known risk loci. Ongoing and future efforts will seek to define the remaining heritability of these diseases; the next decade could very well hold the key to attaining this goal.

  14. Algorithmic complexity of growth hormone release in humans.

    PubMed

    Prank, K; Wagner, M; Brabant, G

    1997-01-01

    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation.

  15. Algorithmic complexity of growth hormone release in humans

    SciTech Connect

    Prank, K.; Wagner, M.; Brabant, G.

    1996-12-31

    Most hormones are secreted in an pulsatile rather than in a constant manner. This temporal pattern of pulsatile hormone release plays an important role in the regulation of cellular function and structure. In healthy humans growth hormone (GH) secretion is characterized by distinct pulses whereas patients bearing a GH producing tumor accompanied with excessive secretion (acromegaly) exhibit a highly irregular pattern of GH release. It has been hypothesized that this highly disorderly pattern of GH release in acromegaly arises from random events in the GH-producing tumor under decreased normal control of GH secretion. Using a context-free grammar complexity measure (algorithmic complexity) in conjunction with random surrogate data sets we demonstrate that the temporal pattern of GH release in acromegaly is not significantly different from a variety of stochastic processes. In contrast, normal subjects clearly exhibit deterministic structure in their temporal patterns of GH secretion. Our results support the hypothesis that GH release in acromegaly is due to random events in the GH-producing tumorous cells which might become independent from hypothalamic regulation. 17 refs., 1 fig., 2 tabs.

  16. On the Characterization of Revisitation Patterns in Complex Human Dynamics - A Data Science Approach

    NASA Astrophysics Data System (ADS)

    Barbosa Filho, Hugo Serrano

    When it comes to visitation patterns, humans beings are extremely regular and predictable, with recurrent activities responsible for most of our movements. In recent years, we have seen scientists attempt to model and explain human dynamics and in particular human movement. Akin to other human behaviors, traveling patterns evolve from the convolution between internal and external factors. A better understanding on the mechanisms responsible for transforming and incorporating individual events into regular patterns is of fundamental importance. Many aspects of our complex lives are affected by human movements such as disease spread and epidemics modeling, city planning, wireless network development, and disaster relief, to name a few. Given the myriad of applications, it is clear that a complete understanding of how people move in space can lead to considerable benefits to our society. In most of the recent works, scientists have focused on the idea that people movements are biased towards frequently-visited locations. According to them, human movement is based on a exploration/exploitation dichotomy in which individuals choose new locations (exploration) or return to frequently-visited locations (exploitation). In this dissertation we present some of our contributions to the field, such as the presence of a recency effect in human mobility and Web browsing behaviors as well as the Returner vs. Explorers dichotomy in Web browsing trajectories.

  17. Complexity of human and ecosystem interactions in an agricultural landscape

    USGS Publications Warehouse

    Coupe, Richard H.; Barlow, Jeannie R.; Capel, Paul D.

    2012-01-01

    The complexity of human interaction in the commercial agricultural landscape and the resulting impacts on the ecosystem services of water quality and quantity is largely ignored by the current agricultural paradigm that maximizes crop production over other ecosystem services. Three examples at different spatial scales (local, regional, and global) are presented where human and ecosystem interactions in a commercial agricultural landscape adversely affect water quality and quantity in unintended ways in the Delta of northwestern Mississippi. In the first example, little to no regulation of groundwater use for irrigation has caused declines in groundwater levels resulting in loss of baseflow to streams and threatening future water supply. In the second example, federal policy which subsidizes corn for biofuel production has encouraged many producers to switch from cotton to corn, which requires more nutrients and water, counter to national efforts to reduce nutrient loads to the Gulf of Mexico and exacerbating groundwater level declines. The third example is the wholesale adoption of a system for weed control that relies on a single chemical, initially providing many benefits and ultimately leading to the widespread occurrence of glyphosate and its degradates in Delta streams and necessitating higher application rates of glyphosate as well as the use of other herbicides due to increasing weed resistance. Although these examples are specific to the Mississippi Delta, analogous situations exist throughout the world and point to the need for change in how we grow our food, fuel, and fiber, and manage our soil and water resources.

  18. Complex history of admixture between modern humans and Neandertals.

    PubMed

    Vernot, Benjamin; Akey, Joshua M

    2015-03-01

    Recent analyses have found that a substantial amount of the Neandertal genome persists in the genomes of contemporary non-African individuals. East Asians have, on average, higher levels of Neandertal ancestry than do Europeans, which might be due to differences in the efficiency of purifying selection, an additional pulse of introgression into East Asians, or other unexplored scenarios. To better define the scope of plausible models of archaic admixture between Neandertals and anatomically modern humans, we analyzed patterns of introgressed sequence in whole-genome data of 379 Europeans and 286 East Asians. We found that inferences of demographic history restricted to neutrally evolving genomic regions allowed a simple one-pulse model to be robustly rejected, suggesting that differences in selection cannot explain the differences in Neandertal ancestry. We show that two additional demographic models, involving either a second pulse of Neandertal gene flow into the ancestors of East Asians or a dilution of Neandertal lineages in Europeans by admixture with an unknown ancestral population, are consistent with the data. Thus, the history of admixture between modern humans and Neandertals is most likely more complex than previously thought.

  19. Perception of complex motion in humans and pigeons (Columba livia).

    PubMed

    Nankoo, Jean-François; Madan, Christopher R; Spetch, Marcia L; Wylie, Douglas R

    2014-06-01

    In the primate visual system, local motion signals are pooled to create a global motion percept. Like primates, many birds are highly dependent on vision for their survival, yet relatively little is known about motion perception in birds. We used random-dot stimuli to investigate pigeons' ability to detect complex motion (radial, rotation, and spiral) compared to humans. Our human participants had a significantly lower threshold for rotational and radial motion when compared to spiral motion. The data from the pigeons, however, showed that the pigeons were most sensitive to rotational motion and least sensitive to radial motion, while sensitivity for spiral motion was intermediate. We followed up the pigeon results with an investigation of the effect of display aperture shape for rotational motion and velocity gradient for radial motion. We found no effect of shape of the aperture on thresholds, but did observe that radial motion containing accelerating dots improved thresholds. However, this improvement did not reach the thresholds levels observed for rotational motion. In sum, our experiments demonstrate that the pooling mechanism in the pigeon motion system is most efficient for rotation.

  20. Complex history of admixture between modern humans and Neandertals.

    PubMed

    Vernot, Benjamin; Akey, Joshua M

    2015-03-01

    Recent analyses have found that a substantial amount of the Neandertal genome persists in the genomes of contemporary non-African individuals. East Asians have, on average, higher levels of Neandertal ancestry than do Europeans, which might be due to differences in the efficiency of purifying selection, an additional pulse of introgression into East Asians, or other unexplored scenarios. To better define the scope of plausible models of archaic admixture between Neandertals and anatomically modern humans, we analyzed patterns of introgressed sequence in whole-genome data of 379 Europeans and 286 East Asians. We found that inferences of demographic history restricted to neutrally evolving genomic regions allowed a simple one-pulse model to be robustly rejected, suggesting that differences in selection cannot explain the differences in Neandertal ancestry. We show that two additional demographic models, involving either a second pulse of Neandertal gene flow into the ancestors of East Asians or a dilution of Neandertal lineages in Europeans by admixture with an unknown ancestral population, are consistent with the data. Thus, the history of admixture between modern humans and Neandertals is most likely more complex than previously thought. PMID:25683119

  1. Probabilistic Simulation of the Human Factor in Structural Reliability

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.; Singhal, Surendra N.

    1994-01-01

    The formal approach described herein computationally simulates the probable ranges of uncertainties for the human factor in probabilistic assessments of structural reliability. Human factors such as marital status, professional status, home life, job satisfaction, work load, and health are studied by using a multifactor interaction equation (MFIE) model to demonstrate the approach. Parametric studies in conjunction with judgment are used to select reasonable values for the participating factors (primitive variables). Subsequently performed probabilistic sensitivity studies assess the suitability of the MFIE as well as the validity of the whole approach. Results show that uncertainties range from 5 to 30 percent for the most optimistic case, assuming 100 percent for no error (perfect performance).

  2. An overview of a nuclear reprocessing plant Human Factors programme.

    PubMed

    Kirwan, Barry

    2003-09-01

    This paper presents a case study of a large Human Factors programme applied in the nuclear fuel reprocessing industry (1987-1991). The paper outlines the key Human Factors issues addressed, as well as the impacts achieved, and gives an indication of the resources utilised (approximately 15 person-years of effort). It also considers the starting point of the programme, in terms of the factors that led to the need for such an extensive programme. Some general lessons learned are given at the end of the paper. PMID:12963330

  3. 2014 Space Human Factors Engineering Standing Review Panel

    NASA Technical Reports Server (NTRS)

    Steinberg, Susan

    2014-01-01

    The 2014 Space Human Factors Engineering (SHFE) Standing Review Panel (from here on referred to as the SRP) participated in a WebEx/teleconference with members of the Space Human Factors and Habitability (SHFH) Element, representatives from the Human Research Program (HRP), the National Space Biomedical Research Institute (NSBRI), and NASA Headquarters on November 17, 2014 (list of participants is in Section XI of this report). The SRP reviewed the updated research plans for the Risk of Incompatible Vehicle/Habitat Design (HAB Risk) and the Risk of Performance Errors Due to Training Deficiencies (Train Risk). The SRP also received a status update on the Risk of Inadequate Critical Task Design (Task Risk), the Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI Risk), and the Risk of Inadequate Human-Computer Interaction (HCI Risk).

  4. Design, Development, Testing, and Evaluation: Human Factors Engineering

    NASA Technical Reports Server (NTRS)

    Adelstein, Bernard; Hobbs, Alan; OHara, John; Null, Cynthia

    2006-01-01

    While human-system interaction occurs in all phases of system development and operation, this chapter on Human Factors in the DDT&E for Reliable Spacecraft Systems is restricted to the elements that involve "direct contact" with spacecraft systems. Such interactions will encompass all phases of human activity during the design, fabrication, testing, operation, and maintenance phases of the spacecraft lifespan. This section will therefore consider practices that would accommodate and promote effective, safe, reliable, and robust human interaction with spacecraft systems. By restricting this chapter to what the team terms "direct contact" with the spacecraft, "remote" factors not directly involved in the development and operation of the vehicle, such as management and organizational issues, have been purposely excluded. However, the design of vehicle elements that enable and promote ground control activities such as monitoring, feedback, correction and reversal (override) of on-board human and automation process are considered as per NPR8705.2A, Section 3.3.

  5. Crystal structure of HIV-1 Tat complexed with human P-TEFb

    SciTech Connect

    Tahirov, Tahir H.; Babayeva, Nigar D.; Varzavand, Katayoun; Cooper, Jeffrey J.; Sedore, Stanley C.; Price, David H.

    2010-08-23

    Regulation of the expression of the human immunodeficiency virus (HIV) genome is accomplished in large part by controlling transcription elongation. The viral protein Tat hijacks the host cell's RNA polymerase II elongation control machinery through interaction with the positive transcription elongation factor, P-TEFb, and directs the factor to promote productive elongation of HIV mRNA. Here we describe the crystal structure of the Tat-P-TEFb complex containing HIV-1 Tat, human Cdk9 (also known as CDK9), and human cyclin T1 (also known as CCNT1). Tat adopts a structure complementary to the surface of P-TEFb and makes extensive contacts, mainly with the cyclin T1 subunit of P-TEFb, but also with the T-loop of the Cdk9 subunit. The structure provides a plausible explanation for the tolerance of Tat to sequence variations at certain sites. Importantly, Tat induces significant conformational changes in P-TEFb. This finding lays a foundation for the design of compounds that would specifically inhibit the Tat-P-TEFb complex and block HIV replication.

  6. Structural and Functional Analysis of the Human Nuclear Xenobiotic Receptor PXR in Complex with RXRα

    PubMed Central

    Wallace, Bret D.; Betts, Laurie; Talmage, Garrick; Pollet, Rebecca M.; Holman, Natalie S.; Redinbo, Matthew R.

    2013-01-01

    The human nuclear xenobiotic receptor PXR recognizes a range of potentially harmful drugs and endobiotic chemicals, but must complex with the nuclear receptor RXRα to control the expression of numerous drug metabolism genes. To date, the structural basis and functional consequences of this interaction have remained unclear. Here we present 2.8 Å resolution crystal structures of the heterodimeric complex formed between the ligand binding domains (LBDs) of human PXR and RXRα. These structures establish that PXR and RXRα form a heterotetramer unprecedented in the nuclear receptor family of ligand-regulated transcription factors. We further show that both PXR and RXRα bind to the transcriptional coregulator SRC-1 with higher affinity when they are part of the PXR-RXRα heterotetramer complex than they do when each LBD is examined alone. Furthermore, we purify the full-length forms of each receptor from recombinant bacterial expression systems, and characterize their interactions with a range of direct and everted repeat DNA elements. Taken together, these data advance our understanding of PXR, the master regulator of drug metabolism gene expression in humans, in its functional partnership with RXRα. PMID:23602807

  7. Sociopsychological factors affecting the human response to noise exposure.

    PubMed

    Borsky, P N

    1979-08-01

    Community noise is reported to be the most often mentioned undesirable neighborhood condition in a recent U.S. Census survey. Understanding community response to noise involves the measurement of a number of complex acoustic and nonacoustic variables and establishing the chain of relationships between physical exposure, perception, annoyance, and acceptability responses and finally complaint behavior. The perceived loudness of a noise is the most important acoustic parameter influencing annoyance and complaints, and the simple dBA unit can be used to integrate spectral characteristics of complex sounds in community studies. Although energy averaging such as Leq or Ldn can be used to describe multiple noise exposures over time, the variable trade-off relationships between number and level of exposures are somewhat obscured by such summary measures. However, they are still the best available descriptors and, until more accurate ones are developed, can be used to measure community noise environments. Perception of an identical noise exposure can vary according to the physiological noise sensitivity of a person and the activity context in which the noise is heard. Although the acoustic quality of the noise itself usually explains about 10 to 25 per cent of the variability in annoyance responses, sociopsychological variables measured in field studies account for 35 to 50 per cent of the variations in human annoyance responses. Three of the most important nonacoustic factors are the connotative fear effects of the noise signal, the feeling that those responsible for the noise are misfeasant in not reducing the noise, and the feeling that harmful health effects are produced by the noise. When residents report great fear, a high misfeasance, and marked health effects, about 90 per cent report a high annoyance level whether their noise exposure level is above 90 Ldn or 65 to 70 Ldn. In contrast, if the feelings are a low fear level, a low degree of misfeasance, and minimal

  8. Dynamics of Human Mitochondrial Complex I Assembly: Implications for Neurodegenerative Diseases.

    PubMed

    Giachin, Gabriele; Bouverot, Romain; Acajjaoui, Samira; Pantalone, Serena; Soler-López, Montserrat

    2016-01-01

    Neurons are extremely energy demanding cells and highly dependent on the mitochondrial oxidative phosphorylation (OXPHOS) system. Mitochondria generate the energetic potential via the respiratory complexes I to IV, which constitute the electron transport chain (ETC), together with complex V. These redox reactions release energy in the form of ATP and also generate reactive oxygen species (ROS) that are involved in cell signaling but can eventually lead to oxidative stress. Complex I (CI or NADH:ubiquinone oxidoreductase) is the largest ETC enzyme, containing 44 subunits and the main contributor to ROS production. In recent years, the structure of the CI has become available and has provided new insights into CI assembly. A number of chaperones have been identified in the assembly and stability of the mature holo-CI, although they are not part of its final structure. Interestingly, CI dysfunction is the most common OXPHOS disorder in humans and defects in the CI assembly process are often observed. However, the dynamics of the events leading to CI biogenesis remain elusive, which precludes our understanding of how ETC malfunctioning affects neuronal integrity. Here, we review the current knowledge of the structural features of CI and its assembly factors and the potential role of CI misassembly in human disorders such as Complex I Deficiencies or Alzheimer's and Parkinson's diseases. PMID:27597947

  9. Dynamics of Human Mitochondrial Complex I Assembly: Implications for Neurodegenerative Diseases

    PubMed Central

    Giachin, Gabriele; Bouverot, Romain; Acajjaoui, Samira; Pantalone, Serena; Soler-López, Montserrat

    2016-01-01

    Neurons are extremely energy demanding cells and highly dependent on the mitochondrial oxidative phosphorylation (OXPHOS) system. Mitochondria generate the energetic potential via the respiratory complexes I to IV, which constitute the electron transport chain (ETC), together with complex V. These redox reactions release energy in the form of ATP and also generate reactive oxygen species (ROS) that are involved in cell signaling but can eventually lead to oxidative stress. Complex I (CI or NADH:ubiquinone oxidoreductase) is the largest ETC enzyme, containing 44 subunits and the main contributor to ROS production. In recent years, the structure of the CI has become available and has provided new insights into CI assembly. A number of chaperones have been identified in the assembly and stability of the mature holo-CI, although they are not part of its final structure. Interestingly, CI dysfunction is the most common OXPHOS disorder in humans and defects in the CI assembly process are often observed. However, the dynamics of the events leading to CI biogenesis remain elusive, which precludes our understanding of how ETC malfunctioning affects neuronal integrity. Here, we review the current knowledge of the structural features of CI and its assembly factors and the potential role of CI misassembly in human disorders such as Complex I Deficiencies or Alzheimer's and Parkinson's diseases.

  10. Dynamics of Human Mitochondrial Complex I Assembly: Implications for Neurodegenerative Diseases

    PubMed Central

    Giachin, Gabriele; Bouverot, Romain; Acajjaoui, Samira; Pantalone, Serena; Soler-López, Montserrat

    2016-01-01

    Neurons are extremely energy demanding cells and highly dependent on the mitochondrial oxidative phosphorylation (OXPHOS) system. Mitochondria generate the energetic potential via the respiratory complexes I to IV, which constitute the electron transport chain (ETC), together with complex V. These redox reactions release energy in the form of ATP and also generate reactive oxygen species (ROS) that are involved in cell signaling but can eventually lead to oxidative stress. Complex I (CI or NADH:ubiquinone oxidoreductase) is the largest ETC enzyme, containing 44 subunits and the main contributor to ROS production. In recent years, the structure of the CI has become available and has provided new insights into CI assembly. A number of chaperones have been identified in the assembly and stability of the mature holo-CI, although they are not part of its final structure. Interestingly, CI dysfunction is the most common OXPHOS disorder in humans and defects in the CI assembly process are often observed. However, the dynamics of the events leading to CI biogenesis remain elusive, which precludes our understanding of how ETC malfunctioning affects neuronal integrity. Here, we review the current knowledge of the structural features of CI and its assembly factors and the potential role of CI misassembly in human disorders such as Complex I Deficiencies or Alzheimer's and Parkinson's diseases. PMID:27597947

  11. 49 CFR 225.12 - Rail Equipment Accident/Incident Reports alleging employee human factor as cause; Employee Human...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... employee human factor as cause; Employee Human Factor Attachment; notice to employee; employee supplement..., AND INVESTIGATIONS § 225.12 Rail Equipment Accident/Incident Reports alleging employee human factor as cause; Employee Human Factor Attachment; notice to employee; employee supplement. (a) Rail...

  12. 49 CFR 225.12 - Rail Equipment Accident/Incident Reports alleging employee human factor as cause; Employee Human...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... employee human factor as cause; Employee Human Factor Attachment; notice to employee; employee supplement..., AND INVESTIGATIONS § 225.12 Rail Equipment Accident/Incident Reports alleging employee human factor as cause; Employee Human Factor Attachment; notice to employee; employee supplement. (a) Rail...

  13. Human Factors Research for Space Exploration: Measurement, Modeling, and Mitigation

    NASA Technical Reports Server (NTRS)

    Kaiser, Mary K.; Allen, Christopher S.; Barshi, Immanuel; Billman, Dorrit; Holden, Kritina L.

    2010-01-01

    As part of NASA's Human Research Program, the Space Human Factors Engineering Project serves as the bridge between Human Factors research and Human Spaceflight applications. Our goal is to be responsive to the operational community while addressing issues at a sufficient level of abstraction to ensure that our tools and solutions generalize beyond the point design. In this panel, representatives from four of our research domains will discuss the challenges they face in solving current problems while also enabling future capabilities. Historically, engineering-dominated organizations have tended to view good Human Factors (HF) as a desire rather than a requirement in system design and development. Our field has made significant gains in the past decade, however; the Department of Defense, for example, now recognizes Human-System Integration (HSI), of which HF is a component, as an integral part of their divisions hardware acquisition processes. And our own agency was far more accepting of HF/HSI requirements during the most recent vehicle systems definition than in any prior cycle. Nonetheless, HF subject matter experts at NASA often find themselves in catch up mode... coping with legacy systems (hardware and software) and procedures that were designed with little regard for the human element, and too often with an attitude of we can deal with any operator issues during training. Our challenge, then, is to segregate the true knowledge gaps in Space Human Factors from the prior failures to incorporate best (or even good) HF design principles. Further, we strive to extract the overarching core HF issues from the point-design-specific concerns that capture the operators (and managers) attention. Generally, our approach embraces a 3M approach to Human Factors: Measurement, Modeling, and Mitigation. Our first step is to measure human performance, to move from subjective anecdotes to objective, quantified data. Next we model the phenomenon, using appropriate methods in

  14. Discovery of insect and human dengue virus host factors.

    PubMed

    Sessions, October M; Barrows, Nicholas J; Souza-Neto, Jayme A; Robinson, Timothy J; Hershey, Christine L; Rodgers, Mary A; Ramirez, Jose L; Dimopoulos, George; Yang, Priscilla L; Pearson, James L; Garcia-Blanco, Mariano A

    2009-04-23

    Dengue fever is the most frequent arthropod-borne viral disease of humans, with almost half of the world's population at risk of infection. The high prevalence, lack of an effective vaccine, and absence of specific treatment conspire to make dengue fever a global public health threat. Given their compact genomes, dengue viruses (DENV-1-4) and other flaviviruses probably require an extensive number of host factors; however, only a limited number of human, and an even smaller number of insect host factors, have been identified. Here we identify insect host factors required for DENV-2 propagation, by carrying out a genome-wide RNA interference screen in Drosophila melanogaster cells using a well-established 22,632 double-stranded RNA library. This screen identified 116 candidate dengue virus host factors (DVHFs). Although some were previously associated with flaviviruses (for example, V-ATPases and alpha-glucosidases), most of the DVHFs were newly implicated in dengue virus propagation. The dipteran DVHFs had 82 readily recognizable human homologues and, using a targeted short-interfering-RNA screen, we showed that 42 of these are human DVHFs. This indicates notable conservation of required factors between dipteran and human hosts. This work suggests new approaches to control infection in the insect vector and the mammalian host.

  15. Heparin inhibits the intrinsic tenase complex by interacting with an exosite on factor IXa.

    PubMed

    Sheehan, John P; Kobbervig, Catherine E; Kirkpatrick, Heidi M

    2003-09-30

    The specific molecular target for direct heparin inhibition of factor X activation by intrinsic tenase (factor IXa-factor VIIIa) was investigated. Comparison of size-fractionated oligosaccharides demonstrated that an octasaccharide was sufficient to inhibit intrinsic tenase. Substitution of soluble dihexanoic phosphatidylserine (C6PS) for phospholipid (PL) vesicles demonstrated that inhibition by low-molecular weight heparin (LMWH) was independent of factor IXa-factor VIIIa membrane assembly. LMWH also inhibited factor X activation by the factor IXa-PL complex via a distinct mechanism that required longer oligosaccharides and was independent of substrate concentrations. The apparent affinity of LMWH for the factor IXa-PL complex was higher in the absence of factor VIIIa, suggesting that the cofactor adversely affected the interaction of heparin with factor IXa-phospholipid. LMWH did not interact directly with the active site, as it failed to inhibit chromogenic substrate cleavage by the factor IXa-PL complex. LMWH induced a modest decrease in factor IXa-factor VIIIa affinity [K(D(app))] on PL vesicles that did not account for the inhibition. In contrast, LMWH caused a substantial reduction in factor IXa-factor VIIIa affinity in the presence of C6PS that fully accounted for the inhibition. Factor IXa bound LMWH with significantly higher affinity than factor X by competition solution affinity analysis, and the K(D(app)) for the factor IXa-LMWH complex agreed with the K(I) for inhibition of the factor IXa-PL complex by LMWH. Thus, LMWH binds to an exosite on factor IXa that antagonizes cofactor activity without disrupting factor IXa-factor VIIIa assembly on the PL surface. This exosite may contribute to the clinical efficacy of heparin and represents a novel target for antithrombotic therapy.

  16. Discrimination of Complex Human Behavior by Pigeons (Columba livia) and Humans

    PubMed Central

    Qadri, Muhammad A. J.; Sayde, Justin M.; Cook, Robert G.

    2014-01-01

    The cognitive and neural mechanisms for recognizing and categorizing behavior are not well understood in non-human animals. In the current experiments, pigeons and humans learned to categorize two non-repeating, complex human behaviors (“martial arts” vs. “Indian dance”). Using multiple video exemplars of a digital human model, pigeons discriminated these behaviors in a go/no-go task and humans in a choice task. Experiment 1 found that pigeons already experienced with discriminating the locomotive actions of digital animals acquired the discrimination more rapidly when action information was available than when only pose information was available. Experiments 2 and 3 found this same dynamic superiority effect with naïve pigeons and human participants. Both species used the same combination of immediately available static pose information and more slowly perceived dynamic action cues to discriminate the behavioral categories. Theories based on generalized visual mechanisms, as opposed to embodied, species-specific action networks, offer a parsimonious account of how these different animals recognize behavior across and within species. PMID:25379777

  17. Some human factors issues in the development and evaluation of cockpit alerting and warning systems

    NASA Technical Reports Server (NTRS)

    Randle, R. J., Jr.; Larsen, W. E.; Williams, D. H.

    1980-01-01

    A set of general guidelines for evaluating a newly developed cockpit alerting and warning system in terms of human factors issues are provided. Although the discussion centers around a general methodology, it is made specifically to the issues involved in alerting systems. An overall statement of the current operational problem is presented. Human factors problems with reference to existing alerting and warning systems are described. The methodology for proceeding through system development to system test is discussed. The differences between traditional human factors laboratory evaluations and those required for evaluation of complex man-machine systems under development are emphasized. Performance evaluation in the alerting and warning subsystem using a hypothetical sample system is explained.

  18. Applied human factors research at the NASA Johnson Space Center Human-Computer Interaction Laboratory

    NASA Technical Reports Server (NTRS)

    Rudisill, Marianne; Mckay, Timothy D.

    1990-01-01

    The applied human factors research program performed at the NASA Johnson Space Center's Human-Computer Interaction Laboratory is discussed. Research is conducted to advance knowledge in human interaction with computer systems during space crew tasks. In addition, the Laboratory is directly involved in the specification of the human-computer interface (HCI) for space systems in development (e.g., Space Station Freedom) and is providing guidelines and support for HCI design to current and future space missions.

  19. Production of recombinant human factor VIII in different cell lines and the effect of human XBP1 co-expression.

    PubMed

    Campos-da-Paz, Mariana; Costa, Christiane Silva; Quilici, Luana Salgado; de Carmo Simões, Isabella; Kyaw, Cynthia Maria; Maranhão, Andrea Queiroz; Brigido, Marcelo Macedo

    2008-06-01

    Recombinant factor VIII is one of the most complex mammalian proteins and a biotechnology venture required for the treatment of hemophilia A. The complexity of the protein, post-translational modifications and limitations of expression elements make the production of active recombinant FVIII a challenge. Here we report the production of biologically active Factor VIII in two different cell lines, CHO and HepG2, by transient transfection. Two expression vectors based on the CMV promoter were used: one harboring CMV Intron A (InA) and the other without it. To bypass difficulties in secretion, we also studied the influence of co-expression of the human splice isoform of the XBP1 gene. We report the production of recombinant FVIII possessing bioengineered FVIII heavy and light chains, linked by a minimal B domain. In our study, HepG2, a human hepatocyte cell line, expressed Factor VIII ten-fold more than a CHO cell line, and in HepG2 cells, the expression of XBP1 improved Factor VIII activity. For CHO cells, expression was improved by the presence of InA, but no further improvement was noted with XBP1 co-expression. These data suggest that the minimal B domain rFVIII preserves Factor VIII biological activity and that different expression elements can be used to improve its production.

  20. Aviation Safety: Modeling and Analyzing Complex Interactions between Humans and Automated Systems

    NASA Technical Reports Server (NTRS)

    Rungta, Neha; Brat, Guillaume; Clancey, William J.; Linde, Charlotte; Raimondi, Franco; Seah, Chin; Shafto, Michael

    2013-01-01

    The on-going transformation from the current US Air Traffic System (ATS) to the Next Generation Air Traffic System (NextGen) will force the introduction of new automated systems and most likely will cause automation to migrate from ground to air. This will yield new function allocations between humans and automation and therefore change the roles and responsibilities in the ATS. Yet, safety in NextGen is required to be at least as good as in the current system. We therefore need techniques to evaluate the safety of the interactions between humans and automation. We think that current human factor studies and simulation-based techniques will fall short in front of the ATS complexity, and that we need to add more automated techniques to simulations, such as model checking, which offers exhaustive coverage of the non-deterministic behaviors in nominal and off-nominal scenarios. In this work, we present a verification approach based both on simulations and on model checking for evaluating the roles and responsibilities of humans and automation. Models are created using Brahms (a multi-agent framework) and we show that the traditional Brahms simulations can be integrated with automated exploration techniques based on model checking, thus offering a complete exploration of the behavioral space of the scenario. Our formal analysis supports the notion of beliefs and probabilities to reason about human behavior. We demonstrate the technique with the Ueberligen accident since it exemplifies authority problems when receiving conflicting advices from human and automated systems.

  1. Pentamethylpyrromethene boron difluoride complexes in human ovarian cancer photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Morgan, Lee R.; Chaudhuri, Aulena; Gillen, Laura E.; Boyer, Joseph H.; Wolford, Lionel T.

    1990-07-01

    Quasiaromatic heterocycles (QAM) such as substituted 1 , 3 , 5 , 7 , 8-pentamethylpyrromethene boron difluorides (PMP-BF2) and - (dimethoxyphosphinylmethyl, methyl) bimane have been evaluated for their abilities to produce cellular toxicities when used in photodynamic therapy (PDT) for ovarian cancer. The most active QAH tested to date has been the disodiuxn salt of PMP-2,6-disulfonate--BF2 (PMPDS-BF2). Human ovarian cancer cells from fifteen different patients have been grown in culture. Cells were obtained from biopsy material and grown in RPMI medium with 10% FBA plus penicillin and streptomycin. Cells were harvested and as single cell suspensions exposed to PMP-BF2 complexes or bimanes in concentrations of 0.004-0.4 ug/106 cells/ml of medium. Initially the cells were exposed to the chemicals for 30 minutes in a 5% CO2 incubator (37°C) with gentle shaking. The cells were washed with plain RPMI medium, then resuspended in the enriched RPMI medium and exposed to a sunlamp for 10-20 minutes. Cells were then allowed to grow in an soft agar culture media at 37°C (5% C02) for 14 days. When compared to controls (only light or only chemicals) there was 100% inhibition of all cellular growth for PMPDSBF2 at the 0.4 ug/mi concentrations. There was variations in concentrations of the chemical needed to produce 100% inhibition when the 15 different ovarian cancer cell specimens were compared at all concentrations. PMP-BF2 complexes are characterized by extremely high extinction coefficients, superior laser activity and little if any triplet-triplet absorption. The biamanes share these properties however are less active in ovarian cancer cell The lasing properties of PMP-BF2, and bimanes will be compared to their PDT effectiveness.

  2. Probabilistic Multi-Factor Interaction Model for Complex Material Behavior

    NASA Technical Reports Server (NTRS)

    Chamis, Christos C.; Abumeri, Galib H.

    2008-01-01

    The Multi-Factor Interaction Model (MFIM) is used to evaluate the divot weight (foam weight ejected) from the launch external tanks. The multi-factor has sufficient degrees of freedom to evaluate a large number of factors that may contribute to the divot ejection. It also accommodates all interactions by its product form. Each factor has an exponent that satisfies only two points the initial and final points. The exponent describes a monotonic path from the initial condition to the final. The exponent values are selected so that the described path makes sense in the absence of experimental data. In the present investigation, the data used was obtained by testing simulated specimens in launching conditions. Results show that the MFIM is an effective method of describing the divot weight ejected under the conditions investigated.

  3. Coagulation factor X activates innate immunity to human species C adenovirus.

    PubMed

    Doronin, Konstantin; Flatt, Justin W; Di Paolo, Nelson C; Khare, Reeti; Kalyuzhniy, Oleksandr; Acchione, Mauro; Sumida, John P; Ohto, Umeharu; Shimizu, Toshiyuki; Akashi-Takamura, Sachiko; Miyake, Kensuke; MacDonald, James W; Bammler, Theo K; Beyer, Richard P; Farin, Frederico M; Stewart, Phoebe L; Shayakhmetov, Dmitry M

    2012-11-01

    Although coagulation factors play a role in host defense for "living fossils" such as horseshoe crabs, the role of the coagulation system in immunity in higher organisms remains unclear. We modeled the interface of human species C adenovirus (HAdv) interaction with coagulation factor X (FX) and introduced a mutation that abrogated formation of the HAdv-FX complex. In vivo genome-wide transcriptional profiling revealed that FX-binding-ablated virus failed to activate a distinct network of nuclear factor κB-dependent early-response genes that are activated by HAdv-FX complex downstream of TLR4/MyD88/TRIF/TRAF6 signaling. Our study implicates host factor "decoration" of the virus as a mechanism to trigger an innate immune sensor that responds to a misplacement of coagulation FX from the blood into intracellular macrophage compartments upon virus entry into the cell. PMID:23019612

  4. NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly of Human Complex I.

    PubMed

    Rhein, Virginie F; Carroll, Joe; Ding, Shujing; Fearnley, Ian M; Walker, John E

    2016-07-01

    Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 45 proteins. One arm lies in the inner membrane, and the other extends about 100 Å into the matrix of the organelle. The extrinsic arm contains binding sites for NADH, the primary electron acceptor FMN, and seven iron-sulfur clusters that form a pathway for electrons linking FMN to the terminal electron acceptor, ubiquinone, which is bound in a tunnel in the region of the junction between the arms. The membrane arm contains four antiporter-like domains, energetically coupled to the quinone site and involved in pumping protons from the matrix into the intermembrane space contributing to the proton motive force. Seven of the subunits, forming the core of the membrane arm, are translated from mitochondrial genes, and the remaining subunits, the products of nuclear genes, are imported from the cytosol. Their assembly is coordinated by at least thirteen extrinsic assembly factor proteins that are not part of the fully assembled complex. They assist in insertion of co-factors and in building up the complex from smaller sub-assemblies. One such factor, NDUFAF5, belongs to the family of seven-β-strand S-adenosylmethionine-dependent methyltransferases. However, similar to another family member, RdmB, it catalyzes the introduction of a hydroxyl group, in the case of NDUFAF5, into Arg-73 in the NDUFS7 subunit of human complex I. This modification occurs early in the pathway of assembly of complex I, before the formation of the juncture between peripheral and membrane arms. PMID:27226634

  5. NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly of Human Complex I.

    PubMed

    Rhein, Virginie F; Carroll, Joe; Ding, Shujing; Fearnley, Ian M; Walker, John E

    2016-07-01

    Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 45 proteins. One arm lies in the inner membrane, and the other extends about 100 Å into the matrix of the organelle. The extrinsic arm contains binding sites for NADH, the primary electron acceptor FMN, and seven iron-sulfur clusters that form a pathway for electrons linking FMN to the terminal electron acceptor, ubiquinone, which is bound in a tunnel in the region of the junction between the arms. The membrane arm contains four antiporter-like domains, energetically coupled to the quinone site and involved in pumping protons from the matrix into the intermembrane space contributing to the proton motive force. Seven of the subunits, forming the core of the membrane arm, are translated from mitochondrial genes, and the remaining subunits, the products of nuclear genes, are imported from the cytosol. Their assembly is coordinated by at least thirteen extrinsic assembly factor proteins that are not part of the fully assembled complex. They assist in insertion of co-factors and in building up the complex from smaller sub-assemblies. One such factor, NDUFAF5, belongs to the family of seven-β-strand S-adenosylmethionine-dependent methyltransferases. However, similar to another family member, RdmB, it catalyzes the introduction of a hydroxyl group, in the case of NDUFAF5, into Arg-73 in the NDUFS7 subunit of human complex I. This modification occurs early in the pathway of assembly of complex I, before the formation of the juncture between peripheral and membrane arms.

  6. NDUFAF5 Hydroxylates NDUFS7 at an Early Stage in the Assembly of Human Complex I*

    PubMed Central

    Rhein, Virginie F.; Carroll, Joe; Ding, Shujing; Fearnley, Ian M.; Walker, John E.

    2016-01-01

    Complex I (NADH ubiquinone oxidoreductase) in mammalian mitochondria is an L-shaped assembly of 45 proteins. One arm lies in the inner membrane, and the other extends about 100 Å into the matrix of the organelle. The extrinsic arm contains binding sites for NADH, the primary electron acceptor FMN, and seven iron-sulfur clusters that form a pathway for electrons linking FMN to the terminal electron acceptor, ubiquinone, which is bound in a tunnel in the region of the junction between the arms. The membrane arm contains four antiporter-like domains, energetically coupled to the quinone site and involved in pumping protons from the matrix into the intermembrane space contributing to the proton motive force. Seven of the subunits, forming the core of the membrane arm, are translated from mitochondrial genes, and the remaining subunits, the products of nuclear genes, are imported from the cytosol. Their assembly is coordinated by at least thirteen extrinsic assembly factor proteins that are not part of the fully assembled complex. They assist in insertion of co-factors and in building up the complex from smaller sub-assemblies. One such factor, NDUFAF5, belongs to the family of seven-β-strand S-adenosylmethionine-dependent methyltransferases. However, similar to another family member, RdmB, it catalyzes the introduction of a hydroxyl group, in the case of NDUFAF5, into Arg-73 in the NDUFS7 subunit of human complex I. This modification occurs early in the pathway of assembly of complex I, before the formation of the juncture between peripheral and membrane arms. PMID:27226634

  7. Human factors of intelligent computer aided display design

    NASA Technical Reports Server (NTRS)

    Hunt, R. M.

    1985-01-01

    Design concepts for a decision support system being studied at NASA Langley as an aid to visual display unit (VDU) designers are described. Ideally, human factors should be taken into account by VDU designers. In reality, although the human factors database on VDUs is small, such systems must be constantly developed. Human factors are therefore a secondary consideration. An expert system will thus serve mainly in an advisory capacity. Functions can include facilitating the design process by shortening the time to generate and alter drawings, enhancing the capability of breaking design requirements down into simpler functions, and providing visual displays equivalent to the final product. The VDU system could also discriminate, and display the difference, between designer decisions and machine inferences. The system could also aid in analyzing the effects of designer choices on future options and in ennunciating when there are data available on a design selections.

  8. A human factors methodology for real-time support applications

    NASA Technical Reports Server (NTRS)

    Murphy, E. D.; Vanbalen, P. M.; Mitchell, C. M.

    1983-01-01

    A general approach to the human factors (HF) analysis of new or existing projects at NASA/Goddard is delineated. Because the methodology evolved from HF evaluations of the Mission Planning Terminal (MPT) and the Earth Radiation Budget Satellite Mission Operations Room (ERBS MOR), it is directed specifically to the HF analysis of real-time support applications. Major topics included for discussion are the process of establishing a working relationship between the Human Factors Group (HFG) and the project, orientation of HF analysts to the project, human factors analysis and review, and coordination with major cycles of system development. Sub-topics include specific areas for analysis and appropriate HF tools. Management support functions are outlined. References provide a guide to sources of further information.

  9. The effect of tripeptide-copper complex on human hair growth in vitro.

    PubMed

    Pyo, Hyun Keol; Yoo, Hyeon Gyeong; Won, Chong Hyun; Lee, Seung Ho; Kang, Yong Jung; Eun, Hee Chul; Cho, Kwang Hyun; Kim, Kyu Han

    2007-07-01

    The tripeptide-copper complex, described as a growth factor for various kinds of differentiated cells, stimulates the proliferation of dermal fibroblasts and elevates the production of vascular endothelial growth factor, but decreased the secretion of transforming growth factor-beta1 by dermal fibroblasts. Dermal papilla cells (DPCs) are specialized fibroblasts, which are important in the morphogenesis and growth of hair follicles. In the present study, the effects of L-alanyl-L-histidyl-L-lysine-Cu2+ (AHK-Cu) on human hair growth ex vivo and cultured dermal papilla cells were evaluated. AHK-Cu (10(-12) - 10(-9) M) stimulated the elongation of human hair follicles ex vivo and the proliferation of DPCs in vitro. Annexin V-fluorescein isothiocyanate/propidium iodide labeling and flow cytometric analysis showed that 10(-9) M AHK-Cu reduced the number of apoptotic DPCs, but this decrease was not statistically significant. The ratio of Bcl-2/Bax was elevated, and the levels of the cleaved forms of caspase-3 and PARP were reduced by treatment with 10(-9) M AHK-Cu. The present study proposed that AHK-Cu promotes the growth of human hair follicles, and this stimulatory effect may occur due to stimulation of the proliferation and the preclusion of the apoptosis of DPCs. PMID:17703734

  10. Addressing the human factors issues associated with control room modifications

    SciTech Connect

    O`Hara, J.; Stubler, W.; Kramer, J.

    1998-03-01

    Advanced human-system interface (HSI) technology is being integrated into existing nuclear plants as part of plant modifications and upgrades. The result of this trend is that hybrid HSIs are created, i.e., HSIs containing a mixture of conventional (analog) and advanced (digital) technology. The purpose of the present research is to define the potential effects of hybrid HSIs on personnel performance and plant safety and to develop human factors guidance for safety reviews of them where necessary. In support of this objective, human factors issues associated with hybrid HSIs were identified. The issues were evaluated for their potential significance to plant safety, i.e., their human performance concerns have the potential to compromise plant safety. The issues were then prioritized and a subset was selected for design review guidance development.

  11. Investigating the Effect of Complexity Factors in Stoichiometry Problems Using Logistic Regression and Eye Tracking

    ERIC Educational Resources Information Center

    Tang, Hui; Kirk, John; Pienta, Norbert J.

    2014-01-01

    This paper includes two experiments, one investigating complexity factors in stoichiometry word problems, and the other identifying students' problem-solving protocols by using eye-tracking technology. The word problems used in this study had five different complexity factors, which were randomly assigned by a Web-based tool that we…

  12. Human Factors and Habitability Challenges for Mars Missions

    NASA Technical Reports Server (NTRS)

    Whitmore, Mihriban

    2015-01-01

    As NASA is planning to send humans deeper into space than ever before, adequate crew health and performance will be critical for mission success. Within the NASA Human Research Program (HRP), the Space Human Factors and Habitability (SHFH) team is responsible for characterizing the risks associated with human capabilities and limitations with respect to long-duration spaceflight, and for providing mitigations (e.g., guidelines, technologies, and tools) to promote safe, reliable and productive missions. SHFH research includes three domains: Advanced Environmental Health (AEH), Advanced Food Technology (AFT), and Space Human Factors Engineering (SHFE). The AEH portfolio focuses on understanding the risk of microbial contamination of the spacecraft and on the development of standards for exposure to potential toxins such as chemicals, bacteria, fungus, and lunar/Martian dust. The two risks that the environmental health project focuses on are adverse health effects due to changes in host-microbe interactions, and risks associated with exposure to dust in planetary surface habitats. This portfolio also proposes countermeasures to these risks by making recommendations that relate to requirements for environmental quality, foods, and crew health on spacecraft and space missions. The AFT portfolio focuses on reducing the mass, volume, and waste of the entire integrated food system to be used in exploration missions, and investigating processing methods to extend the shelf life of food items up to five years, while assuring that exploration crews will have nutritious and palatable foods. The portfolio also delivers improvements in both the food itself and the technologies for storing and preparing it. SHFE sponsors research to establish human factors and habitability standards and guidelines in five risk areas, and provides improved design concepts for advanced crew interfaces and habitability systems. These risk areas include: Incompatible vehicle/habitat design

  13. Human factors - Man-machine symbiosis in space

    NASA Technical Reports Server (NTRS)

    Brown, Jeri W.

    1987-01-01

    The relation between man and machine in space is studied. Early spaceflight and the goal of establishing a permanent space presence are described. The need to consider the physiological, psychological, and social integration of humans for each space mission is examined. Human factors must also be considered in the design of spacecraft. The effective utilization of man and machine capabilities, and research in anthropometry and biomechanics aimed at determining the limitations of spacecrews are discussed.

  14. Human Health/Human Factors Considerations in Trans-Lunar Space

    NASA Technical Reports Server (NTRS)

    Moore, E. Cherice; Howard, Robert; Mendeck, Gavin

    2014-01-01

    The human factors insights of how they are incorporated into the vehicle are crucial towards designing and planning the internal designs necessary for future spacecraft and missions. The adjusted mission concept of supporting the Asteroid Redirect Crewed Mission will drive some human factors changes on how the Orion will be used and will be reassessed so as to best contribute to missions success. Recognizing what the human factors and health functional needs are early in the design process and how to integrate them will improve this and future generations of space vehicles to achieve mission success and continue to minimize risks.

  15. Modulation of human neutrophil apoptosis by immune complexes.

    PubMed

    Gamberale, R; Giordano, M; Trevani, A S; Andonegui, G; Geffner, J R

    1998-10-01

    In the present study we examined whether immune complexes (IC) are able to modulate human neutrophil apoptosis. We observed different effects depending on the type of IC employed. Precipitating IC (pIC) and Ab-coated erythrocytes (E-IgG) triggered a marked stimulation of apoptosis, while heat-aggregated IgG and soluble IC, significantly delayed spontaneous apoptosis. Blocking Abs directed to Fcgamma receptor type II (FcgammaRII), but not to FcgammaRIII, markedly diminished the acceleration of apoptosis triggered by either pIC or E-IgG, supporting a critical role for FcgammaRII in apoptosis stimulation. This phenomenon, on the other hand, does not appear to involve IC phagocytosis or the participation of CR3. Acceleration of neutrophil apoptosis triggered by either pIC or E-IgG seems to require the activation of the respiratory burst, as suggested by 1) the ability of catalase to prevent apoptosis stimulation; 2) the effect of azide, an heme enzyme inhibitor, which dramatically enhanced apoptosis induced by pIC or E-IgG; and 3) the inability of pIC or E-IgG to accelerate apoptosis of neutrophils isolated from CGD patients. It is well established that IC affect the course of inflammation by inducing the release of inflammatory cytokines, proteolytic enzymes, oxidative agents, and other toxic molecules. Our results suggest that IC may also affect the course of inflammation by virtue of their ability to modulate neutrophil apoptosis.

  16. Subunit composition of the human cytoplasmic dynein-2 complex

    PubMed Central

    Asante, David; Stevenson, Nicola L.; Stephens, David J.

    2014-01-01

    ABSTRACT Cytoplasmic dynein-2 is the motor for retrograde intraflagellar transport (IFT), and mutations in dynein-2 are known to cause skeletal ciliopathies. Here, we define for the first time the composition of the human cytoplasmic dynein-2 complex. We show that the proteins encoded by the ciliopathy genes WDR34 and WDR60 are bona fide dynein-2 intermediate chains and are both required for dynein-2 function. In addition, we identify TCTEX1D2 as a unique dynein-2 light chain that is itself required for cilia function. We define several subunits common to both dynein-1 and dynein-2, including TCTEX-1 (also known as DYNLT1) and TCTEX-3 (also known as DYNLT3), roadblock-1 (also known as DYNLRB1) and roadblock-2 (also known as DYNLRB2), and LC8-1 and LC8-2 light chains (DYNLL1 and DYNLL2, respectively). We also find that NudCD3 associates with dynein-2 as it does with dynein-1. By contrast, the common dynein-1 regulators dynactin, LIS1 (also known as PAFAH1B1) and BICD2 are not found in association with dynein-2. These data explain why mutations in either WDR34 or WDR60 cause disease, as well as identifying TCTEX1D2 as a candidate ciliopathy gene. PMID:25205765

  17. Model of human collective decision-making in complex environments

    NASA Astrophysics Data System (ADS)

    Carbone, Giuseppe; Giannoccaro, Ilaria

    2015-12-01

    A continuous-time Markov process is proposed to analyze how a group of humans solves a complex task, consisting in the search of the optimal set of decisions on a fitness landscape. Individuals change their opinions driven by two different forces: (i) the self-interest, which pushes them to increase their own fitness values, and (ii) the social interactions, which push individuals to reduce the diversity of their opinions in order to reach consensus. Results show that the performance of the group is strongly affected by the strength of social interactions and by the level of knowledge of the individuals. Increasing the strength of social interactions improves the performance of the team. However, too strong social interactions slow down the search of the optimal solution and worsen the performance of the group. In particular, we find that the threshold value of the social interaction strength, which leads to the emergence of a superior intelligence of the group, is just the critical threshold at which the consensus among the members sets in. We also prove that a moderate level of knowledge is already enough to guarantee high performance of the group in making decisions.

  18. Subunit composition of the human cytoplasmic dynein-2 complex.

    PubMed

    Asante, David; Stevenson, Nicola L; Stephens, David J

    2014-11-01

    Cytoplasmic dynein-2 is the motor for retrograde intraflagellar transport (IFT), and mutations in dynein-2 are known to cause skeletal ciliopathies. Here, we define for the first time the composition of the human cytoplasmic dynein-2 complex. We show that the proteins encoded by the ciliopathy genes WDR34 and WDR60 are bona fide dynein-2 intermediate chains and are both required for dynein-2 function. In addition, we identify TCTEX1D2 as a unique dynein-2 light chain that is itself required for cilia function. We define several subunits common to both dynein-1 and dynein-2, including TCTEX-1 (also known as DYNLT1) and TCTEX-3 (also known as DYNLT3), roadblock-1 (also known as DYNLRB1) and roadblock-2 (also known as DYNLRB2), and LC8-1 and LC8-2 light chains (DYNLL1 and DYNLL2, respectively). We also find that NudCD3 associates with dynein-2 as it does with dynein-1. By contrast, the common dynein-1 regulators dynactin, LIS1 (also known as PAFAH1B1) and BICD2 are not found in association with dynein-2. These data explain why mutations in either WDR34 or WDR60 cause disease, as well as identifying TCTEX1D2 as a candidate ciliopathy gene.

  19. Meeting Human Reliability Requirements through Human Factors Design, Testing, and Modeling

    SciTech Connect

    R. L. Boring

    2007-06-01

    In the design of novel systems, it is important for the human factors engineer to work in parallel with the human reliability analyst to arrive at the safest achievable design that meets design team safety goals and certification or regulatory requirements. This paper introduces the System Development Safety Triptych, a checklist of considerations for the interplay of human factors and human reliability through design, testing, and modeling in product development. This paper also explores three phases of safe system development, corresponding to the conception, design, and implementation of a system.

  20. NASA Space Flight Human-System Standard Human Factors, Habitability, and Environmental Health

    NASA Technical Reports Server (NTRS)

    Holubec, Keith; Connolly, Janis

    2010-01-01

    This slide presentation reviews the history, and development of NASA-STD-3001, NASA Space Flight Human-System Standard Human Factors, Habitability, and Environmental Health, and the related Human Integration Design Handbook. Currently being developed from NASA-STD-3000, this project standard currently in review will be available in two volumes, (i.e., Volume 1 -- VCrew Health and Volume 2 -- Human Factors, Habitability, and Environmental Health) and the handbook will be both available as a pdf file and as a interactive website.

  1. A Human Factors Framework for Payload Display Design

    NASA Technical Reports Server (NTRS)

    Dunn, Mariea C.; Hutchinson, Sonya L.

    1998-01-01

    During missions to space, one charge of the astronaut crew is to conduct research experiments. These experiments, referred to as payloads, typically are controlled by computers. Crewmembers interact with payload computers by using visual interfaces or displays. To enhance the safety, productivity, and efficiency of crewmember interaction with payload displays, particular attention must be paid to the usability of these displays. Enhancing display usability requires adoption of a design process that incorporates human factors engineering principles at each stage. This paper presents a proposed framework for incorporating human factors engineering principles into the payload display design process.

  2. Human Factors Vehicle Displacement Analysis: Engineering In Motion

    NASA Technical Reports Server (NTRS)

    Atencio, Laura Ashley; Reynolds, David; Robertson, Clay

    2010-01-01

    While positioned on the launch pad at the Kennedy Space Center, tall stacked launch vehicles are exposed to the natural environment. Varying directional winds and vortex shedding causes the vehicle to sway in an oscillating motion. The Human Factors team recognizes that vehicle sway may hinder ground crew operation, impact the ground system designs, and ultimately affect launch availability . The objective of this study is to physically simulate predicted oscillation envelopes identified by analysis. and conduct a Human Factors Analysis to assess the ability to carry out essential Upper Stage (US) ground operator tasks based on predicted vehicle motion.

  3. Human factors systems approach to healthcare quality and patient safety

    PubMed Central

    Carayon, Pascale; Wetterneck, Tosha B.; Rivera-Rodriguez, A. Joy; Hundt, Ann Schoofs; Hoonakker, Peter; Holden, Richard; Gurses, Ayse P.

    2013-01-01

    Human factors systems approaches are critical for improving healthcare quality and patient safety. The SEIPS (Systems Engineering Initiative for Patient Safety) model of work system and patient safety is a human factors systems approach that has been successfully applied in healthcare research and practice. Several research and practical applications of the SEIPS model are described. Important implications of the SEIPS model for healthcare system and process redesign are highlighted. Principles for redesigning healthcare systems using the SEIPS model are described. Balancing the work system and encouraging the active and adaptive role of workers are key principles for improving healthcare quality and patient safety. PMID:23845724

  4. Human factors engineering report for the cold vacuum drying facility

    SciTech Connect

    IMKER, F.W.

    1999-06-30

    The purpose of this report is to present the results and findings of the final Human Factors Engineering (HFE) technical analysis and evaluation of the Cold Vacuum Drying Facility (CVDF). Ergonomics issues are also addressed in this report, as appropriate. This report follows up and completes the preliminary work accomplished and reported by the Preliminary HFE Analysis report (SNF-2825, Spent Nuclear Fuel Project Cold Vacuum Drying Facility Human Factors Engineering Analysis: Results and Findings). This analysis avoids redundancy of effort except for ensuring that previously recommended HFE design changes have not affected other parts of the system. Changes in one part of the system may affect other parts of the system where those changes were not applied. The final HFE analysis and evaluation of the CVDF human-machine interactions (HMI) was expanded to include: the physical work environment, human-computer interface (HCI) including workstation and software, operator tasks, tools, maintainability, communications, staffing, training, and the overall ability of humans to accomplish their responsibilities, as appropriate. Key focal areas for this report are the process bay operations, process water conditioning (PWC) skid, tank room, and Central Control Room operations. These key areas contain the system safety-class components and are the foundation for the human factors design basis of the CVDF.

  5. Probabilistic simulation of the human factor in structural reliability

    NASA Technical Reports Server (NTRS)

    Chamis, C. C.

    1993-01-01

    A formal approach is described in an attempt to computationally simulate the probable ranges of uncertainties of the human factor in structural probabilistic assessments. A multi-factor interaction equation (MFIE) model has been adopted for this purpose. Human factors such as marital status, professional status, home life, job satisfaction, work load and health, are considered to demonstrate the concept. Parametric studies in conjunction with judgment are used to select reasonable values for the participating factors (primitive variables). Suitability of the MFIE in the subsequently probabilistic sensitivity studies are performed to assess the validity of the whole approach. Results obtained show that the uncertainties for no error range from five to thirty percent for the most optimistic case.

  6. Human factors evaluation of teletherapy: Literature review. Volume 5

    SciTech Connect

    Henriksen, K.; Kaye, R.D.; Jones, R.; Morisseau, D.S.; Serig, D.L.

    1995-07-01

    A series of human factors evaluations were undertaken to better understand the contributing factors to human error in the teletherapy environment. Teletherapy is a multidisciplinary methodology for treating cancerous tissue through selective exposure to an external beam of ionizing radiation. A team of human factors specialists, assisted by a panel of radiation oncologists, medical physicists, and radiation therapists, conducted site visits to radiation oncology departments at community hospitals, university centers, and free-standing clinics. A function and task analysis was performed initially to guide subsequent evaluations in the areas of workplace environment, system-user interfaces, procedures, training, and organizational practices. To further acquire an in-depth and up-to-date understanding of the practice of teletherapy in support of these evaluations, a systematic literature review was conducted. Factors that have a potential impact on the accuracy of treatment delivery were of primary concern. The present volume is the literature review. The volume starts with an overview of the multiphased nature of teletherapy, and then examines the requirement for precision, the increasing role of quality assurance, current conceptualizations of human error, and the role of system factors such as the workplace environment, user-system interfaces, procedures, training, and organizational practices.

  7. Requirements for Receptor Engagement during Infection by Adenovirus Complexed with Blood Coagulation Factor X

    PubMed Central

    Bradshaw, Angela C.; Parker, Alan L.; Duffy, Margaret R.; Coughlan, Lynda; van Rooijen, Nico; Kähäri, Veli-Matti; Nicklin, Stuart A.; Baker, Andrew H.

    2010-01-01

    Human adenoviruses from multiple species bind to coagulation factor X (FX), yet the importance of this interaction in adenovirus dissemination is unknown. Upon contact with blood, vectors based on adenovirus serotype 5 (Ad5) binds to FX via the hexon protein with nanomolar affinity, leading to selective uptake of the complex into the liver and spleen. The Ad5:FX complex putatively targets heparan sulfate proteoglycans (HSPGs). The aim of this study was to elucidate the specific requirements for Ad5:FX-mediated cellular uptake in this high-affinity pathway, specifically the HSPG receptor requirements as well as the role of penton base-mediated integrin engagement in subsequent internalisation. Removal of HS sidechains by enzymatic digestion or competition with highly-sulfated heparins/heparan sulfates significantly decreased FX-mediated Ad5 cell binding in vitro and ex vivo. Removal of N-linked and, in particular, O-linked sulfate groups significantly attenuated the inhibitory capabilities of heparin, while the chemical inhibition of endogenous HSPG sulfation dose-dependently reduced FX-mediated Ad5 cellular uptake. Unlike native heparin, modified heparins lacking O- or N-linked sulfate groups were unable to inhibit Ad5 accumulation in the liver 1h after intravascular administration of adenovirus. Similar results were observed in vitro using Ad5 vectors possessing mutations ablating CAR- and/or αv integrin binding, demonstrating that attachment of the Ad5:FX complex to the cell surface involves HSPG sulfation. Interestingly, Ad5 vectors ablated for αv integrin binding showed markedly delayed cell entry, highlighting the need for an efficient post-attachment internalisation signal for optimal Ad5 uptake and transport following surface binding mediated through FX. This study therefore integrates the established model of αv integrin-dependent adenoviral infection with the high-affinity FX-mediated pathway. This has important implications for mechanisms that define

  8. Human factors issues in the use of night vision devices

    NASA Technical Reports Server (NTRS)

    Kaiser, Mary K.; Foyle, David C.

    1991-01-01

    An account is given of the critical human factors that arise in field data on the differences between night vision displays and unaided day vision. Attention is given to the findings of empirical studies of performance on rotorcraft-flight-relevant perceptual tasks in which depth and distance perception are critical factors. Suggestions are made for man-machine-critical component design modifications in current night vision systems.

  9. Crystal Structure of Human Plasma Platelet-Activating Factor Acetylhydrolase

    SciTech Connect

    Samanta, U.; Bahnson, B

    2008-01-01

    Human plasma platelet-activating factor (PAF) acetylhydrolase functions by reducing PAF levels as a general anti-inflammatory scavenger and is linked to anaphylactic shock, asthma, and allergic reactions. The enzyme has also been implicated in hydrolytic activities of other pro-inflammatory agents, such as sn-2 oxidatively fragmented phospholipids. This plasma enzyme is tightly bound to low and high density lipoprotein particles and is also referred to as lipoprotein-associated phospholipase A{sub 2}. The crystal structure of this enzyme has been solved from x-ray diffraction data collected to a resolution of 1.5{angstrom}. It has a classic lipase {alpha}/{beta}-hydrolase fold, and it contains a catalytic triad of Ser{sup 273}, His{sup 351}, and Asp{sup 296}. Two clusters of hydrophobic residues define the probable interface-binding region, and a prediction is given of how the enzyme is bound to lipoproteins. Additionally, an acidic patch of 10 carboxylate residues and a neighboring basic patch of three residues are suggested to play a role in high density lipoprotein/low density lipoprotein partitioning. A crystal structure is also presented of PAF acetylhydrolase reacted with the organophosphate compound paraoxon via its active site Ser{sup 273}. The resulting diethyl phosphoryl complex was used to model the tetrahedral intermediate of the substrate PAF to the active site. The model of interface binding begins to explain the known specificity of lipoprotein-bound substrates and how the active site can be both close to the hydrophobic-hydrophilic interface and at the same time be accessible to the aqueous phase.

  10. TIMMDC1/C3orf1 Functions as a Membrane-Embedded Mitochondrial Complex I Assembly Factor through Association with the MCIA Complex

    PubMed Central

    Guarani, Virginia; Paulo, Joao; Zhai, Bo; Huttlin, Edward L.; Gygi, Steven P.

    2014-01-01

    Complex I (CI) of the electron transport chain, a large membrane-embedded NADH dehydrogenase, couples electron transfer to the release of protons into the mitochondrial inner membrane space to promote ATP production through ATP synthase. In addition to being a central conduit for ATP production, CI activity has been linked to neurodegenerative disorders, including Parkinson's disease. CI is built in a stepwise fashion through the actions of several assembly factors. We employed interaction proteomics to interrogate the molecular associations of 15 core subunits and assembly factors previously linked to human CI deficiency, resulting in a network of 101 proteins and 335 interactions (edges). TIMMDC1, a predicted 4-pass membrane protein, reciprocally associated with multiple members of the MCIA CI assembly factor complex and core CI subunits and was localized in the mitochondrial inner membrane, and its depletion resulted in reduced CI activity and cellular respiration. Quantitative proteomics demonstrated a role for TIMMDC1 in assembly of membrane-embedded and soluble arms of the complex. This study defines a new membrane-embedded CI assembly factor and provides a resource for further analysis of CI biology. PMID:24344204

  11. Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection.

    PubMed

    Blackburn, Elizabeth H; Epel, Elissa S; Lin, Jue

    2015-12-01

    Telomeres are the protective end-complexes at the termini of eukaryotic chromosomes. Telomere attrition can lead to potentially maladaptive cellular changes, block cell division, and interfere with tissue replenishment. Recent advances in the understanding of human disease processes have clarified the roles of telomere biology, especially in diseases of human aging and in some aging-related processes. Greater overall telomere attrition predicts mortality and aging-related diseases in inherited telomere syndrome patients, and also in general human cohorts. However, genetically caused variations in telomere maintenance either raise or lower risks and progression of cancers, in a highly cancer type-specific fashion. Telomere maintenance is determined by genetic factors and is also cumulatively shaped by nongenetic influences throughout human life; both can interact. These and other recent findings highlight both causal and potentiating roles for telomere attrition in human diseases.

  12. Circuitry and dynamics of human transcription factor regulatory networks

    PubMed Central

    Neph, Shane; Stergachis, Andrew B.; Reynolds, Alex; Sandstrom, Richard; Borenstein, Elhanan; Stamatoyannopoulos, John A.

    2012-01-01

    SUMMARY The combinatorial cross-regulation of hundreds of sequence-specific transcription factors defines a regulatory network that underlies cellular identity and function. Here we use genome-wide maps of in vivo DNaseI footprints to assemble an extensive core human regulatory network comprising connections among 475 sequence-specific transcription factors, and to analyze the dynamics of these connections across 41 diverse cell and tissue types. We find that human transcription factor networks are highly cell-selective and are driven by cohorts of factors that include regulators with previously unrecognized roles in control of cellular identity. Moreover, we identify many widely expressed factors that impact transcriptional regulatory networks in a cell-selective manner. Strikingly, in spite of their inherent diversity, all cell type regulatory networks independently converge on a common architecture that closely resembles the topology of living neuronal networks. Together, our results provide the first description of the circuitry, dynamics, and organizing principles of the human transcription factor regulatory network. PMID:22959076

  13. Human factors/ergonomics as a systems discipline? "The human use of human beings" revisited.

    PubMed

    Hollnagel, Erik

    2014-01-01

    Discussions of the possible future of Human factors/ergonomics (HFE) usually take the past for granted in the sense that the future of HFE is assumed to be more of the same. This paper argues that the nature of work in the early 2010s is so different from the nature of work when HFE was formulated 60-70 years ago that a critical reassessment of the basis for HFE is needed. If HFE should be a systems discipline, it should be a soft systems rather than a hard systems discipline. It is not enough for HFE to seek to improve performance and well-being through systems design, since any change to the work environment in principle alters the very basis for the change. Instead HFE should try to anticipate how the nature of work will change so that it can both foresee what work will be and propose what work should be.

  14. Human factors review for Severe Accident Sequence Analysis (SASA)

    SciTech Connect

    Krois, P.A.; Haas, P.M.; Manning, J.J.; Bovell, C.R.

    1984-01-01

    The paper will discuss work being conducted during this human factors review including: (1) support of the Severe Accident Sequence Analysis (SASA) Program based on an assessment of operator actions, and (2) development of a descriptive model of operator severe accident management. Research by SASA analysts on the Browns Ferry Unit One (BF1) anticipated transient without scram (ATWS) was supported through a concurrent assessment of operator performance to demonstrate contributions to SASA analyses from human factors data and methods. A descriptive model was developed called the Function Oriented Accident Management (FOAM) model, which serves as a structure for bridging human factors, operations, and engineering expertise and which is useful for identifying needs/deficiencies in the area of accident management. The assessment of human factors issues related to ATWS required extensive coordination with SASA analysts. The analysis was consolidated primarily to six operator actions identified in the Emergency Procedure Guidelines (EPGs) as being the most critical to the accident sequence. These actions were assessed through simulator exercises, qualitative reviews, and quantitative human reliability analyses. The FOAM descriptive model assumes as a starting point that multiple operator/system failures exceed the scope of procedures and necessitates a knowledge-based emergency response by the operators. The FOAM model provides a functionally-oriented structure for assembling human factors, operations, and engineering data and expertise into operator guidance for unconventional emergency responses to mitigate severe accident progression and avoid/minimize core degradation. Operators must also respond to potential radiological release beyond plant protective barriers. Research needs in accident management and potential uses of the FOAM model are described. 11 references, 1 figure.

  15. Human factors with nonhumans - Factors that affect computer-task performance

    NASA Technical Reports Server (NTRS)

    Washburn, David A.

    1992-01-01

    There are two general strategies that may be employed for 'doing human factors research with nonhuman animals'. First, one may use the methods of traditional human factors investigations to examine the nonhuman animal-to-machine interface. Alternatively, one might use performance by nonhuman animals as a surrogate for or model of performance by a human operator. Each of these approaches is illustrated with data in the present review. Chronic ambient noise was found to have a significant but inconsequential effect on computer-task performance by rhesus monkeys (Macaca mulatta). Additional data supported the generality of findings such as these to humans, showing that rhesus monkeys are appropriate models of human psychomotor performance. It is argued that ultimately the interface between comparative psychology and technology will depend on the coordinated use of both strategies of investigation.

  16. Tissue Factor Residues That Modulate Magnesium-Dependent Rate Enhancements of the Tissue Factor/Factor VIIa Complex

    PubMed Central

    Gajsiewicz, Joshua M.; Nuzzio, Kristin M.; Rienstra, Chad M.; Morrissey, James H.

    2016-01-01

    The blood coagulation cascade is initiated when the cell-surface complex of factor VIIa (FVIIa, a trypsin-like serine protease) and tissue factor (TF, an integral-membrane protein) proteolytically activates factor X (FX). Both FVIIa and FX bind to membranes via their γ-carboxyglutamate-rich domains (GLA domains). GLA domains contain seven to nine bound Ca2+ ions that are critical for their folding and function, and most biochemical studies of blood clotting have employed supraphysiologic Ca2+ concentrations to ensure saturation of these domains with bound Ca2+. Recently, it has become clear that, at plasma concentrations of metal ions, Mg2+ actually occupies two or three of the divalent metal ion-binding sites in GLA domains, and that these bound Mg2+ ions are required for full function of these clotting proteins. In this study, we investigated how Mg2+ influences FVIIa enzymatic activity. We found that the presence of TF was required for Mg2+ to enhance the rate of FX activation by FVIIa, and we used alanine-scanning mutagenesis to identify TF residues important for mediating this response to Mg2+. Several TF mutations, including those at residues G164, K166, and Y185, blunted the ability of Mg2+ to enhance the activity of the TF/FVIIa conplex. Our results suggest that these TF residues interact with the GLA domain of FX in a Mg2+-dependent manner (although effects of Mg2+ on the FVIIa GLA domain cannot be ruled out). Notably, these TF residues are located within or immediately adjacent to the putative substrate-binding exosite of TF. PMID:26169722

  17. Hydroxyl radical scavenging mechanism of human erythrocytes by quercetin-germanium (IV) complex.

    PubMed

    Li, Sheng-Pu; Xie, Wei-Ling; Cai, Huai-Hong; Cai, Ji-Ye; Yang, Pei-Hui

    2012-08-30

    Quercetin is a popular flavonoid in plant foods, herbs, and dietary supplement. Germanium, a kind of trace elements, can enhance the body immunity. This study investigated the hydroxyl-radical-scavenging mechanism of the quercertin-germanium (IV) (Qu-Ge) complex to human erythrocytes, especially the effects on ultrastructure and mechanical properties of cell membrane, plasma membrane potential and intracellular free Ca(2+) concentration. Results showed that QuGe(2), a kind of the Qu-Ge complex, could reduce the oxidative damage of erythrocytes, change the cell-surface morphology, and partly recover the disruption of plasma membrane potential and intracellular free Ca(2+) level. Atomic force microscopy (AFM) was used to characterize the changes of the cell morphology, cell-membrane ultrastructure and biophysical properties at nanoscalar level. QuGe(2) has triggered the antioxidative factor to inhibit cellular damage. These results can improve the understanding of hydroxyl-radical-scavenging mechanism of human erythrocytes induced by the Qu-Ge complex, which can be potentially developed as a new antioxidant for treatment of oxidative damage.

  18. Human replication protein A binds single-stranded DNA in two distinct complexes.

    PubMed Central

    Blackwell, L J; Borowiec, J A

    1994-01-01

    Human replication protein A, a single-stranded DNA (ssDNA)-binding protein, is a required factor in eukaryotic DNA replication and DNA repair systems and has been suggested to function during DNA recombination. The protein is also a target of interaction for a variety of proteins that control replication, transcription, and cell growth. To understand the role of hRPA in these processes, we examined the binding of hRPA to defined ssDNA molecules. Employing gel shift assays that "titrated" the length of ssDNA, hRPA was found to form distinct multimeric complexes that could be detected by glutaraldehyde cross-linking. Within these complexes, monomers of hRPA utilized a minimum binding site size on ssDNA of 8 to 10 nucleotides (the hRPA8-10nt complex) and appeared to bind ssDNA cooperatively. Intriguingly, alteration of gel shift conditions revealed the formation of a second, distinctly different complex that bound ssDNA in roughly 30-nucleotide steps (the hRPA30nt complex), a complex similar to that described by Kim et al. (C. Kim, R. O. Snyder, and M. S. Wold, Mol. Cell. Biol. 12:3050-3059, 1992). Both the hRPA8-10nt and hRPA30nt complexes can coexist in solution. We speculate that the role of hRPA in DNA metabolism may be modulated through the ability of hRPA to bind ssDNA in these two modes. Images PMID:8196638

  19. Development of a sensitive enzyme immunoassay for human epidermal growth factor (urogastrone).

    PubMed

    Kurobe, M; Tokida, N; Furukawa, S; Ishikawa, E; Hayashi, K

    1986-04-15

    A sensitive two-site enzyme immunoassay (EIA) for human epidermal growth factor (hEGF) was developed, based on the sandwiching of an antigen between anti-hEGF IgG-coated polystyrene beads and anti-hEGF Fab'-linked peroxidase complex (horseradish peroxidase, EC. 1.11.1.7). This method has four advantages: the anti-hEGF Fab'-linked peroxidase complex is more stable than 125I-labelled antibody; the procedure is simple and rapid compared to bioassay; its discriminatory sensitivity is as low as 0.1 pg/assay tube; and serial dilution curves of unextracted human serum and urine samples all paralleled that of standard hEGF. The validity of the measurement of hEGF-like immunoreactivity in human serum and plasma is discussed.

  20. With eloquence and humanity? Human factors/ergonomics in sustainable human development.

    PubMed

    Moore, Dave; Barnard, Tim

    2012-12-01

    This article is based on a keynote presentation given at the 18th Congress of the International Ergonomics Association in Recife, Brazil, February 2012. It considers new, and not so new, approaches and practical roles for the emerging field of human factors/ergonomics (HFE) in sustainable development (SD).The material for this article was largely drawn from the literature in the fields of human development, sustainability, climate change mitigation and adaptation, and social/environmental impact assessment. Identifying the role of HFE in SD is not a simple one and from the outset is complicated by the widely differing ideas in the sustainability literature about what exactly it is we are hoping to sustain. Is it individual companies, business models, cultures, or the carrying capacity of our planet? Or combinations of these? For the purposes of this article, certain assumptions are made, and various emerging opportunities and responsibilities associated with our changing world of work are introduced. First, there are new versions of traditional tasks for us, such as working with the people and companies in the renewable energy sectors. Beyond this, however, it is suggested that there are emerging roles for HFE professionals in transdisciplinary work where we might play our part, for example, in tackling the twinned issues of climate change and human development in areas of significant poverty. In particular we have the tools and capabilities to help define and measure what groups have reason to value, and wish to sustain. It is suggested, that to do this effectively, however, will require a philosophical shift, or perhaps just a philosophical restatement at a collective level, regarding who and what we ultimately serve.

  1. With eloquence and humanity? Human factors/ergonomics in sustainable human development.

    PubMed

    Moore, Dave; Barnard, Tim

    2012-12-01

    This article is based on a keynote presentation given at the 18th Congress of the International Ergonomics Association in Recife, Brazil, February 2012. It considers new, and not so new, approaches and practical roles for the emerging field of human factors/ergonomics (HFE) in sustainable development (SD).The material for this article was largely drawn from the literature in the fields of human development, sustainability, climate change mitigation and adaptation, and social/environmental impact assessment. Identifying the role of HFE in SD is not a simple one and from the outset is complicated by the widely differing ideas in the sustainability literature about what exactly it is we are hoping to sustain. Is it individual companies, business models, cultures, or the carrying capacity of our planet? Or combinations of these? For the purposes of this article, certain assumptions are made, and various emerging opportunities and responsibilities associated with our changing world of work are introduced. First, there are new versions of traditional tasks for us, such as working with the people and companies in the renewable energy sectors. Beyond this, however, it is suggested that there are emerging roles for HFE professionals in transdisciplinary work where we might play our part, for example, in tackling the twinned issues of climate change and human development in areas of significant poverty. In particular we have the tools and capabilities to help define and measure what groups have reason to value, and wish to sustain. It is suggested, that to do this effectively, however, will require a philosophical shift, or perhaps just a philosophical restatement at a collective level, regarding who and what we ultimately serve. PMID:23397805

  2. Pharmacological NAD-Boosting Strategies Improve Mitochondrial Homeostasis in Human Complex I-Mutant Fibroblasts.

    PubMed

    Felici, Roberta; Lapucci, Andrea; Cavone, Leonardo; Pratesi, Sara; Berlinguer-Palmini, Rolando; Chiarugi, Alberto

    2015-06-01

    Mitochondrial disorders are devastating genetic diseases for which efficacious therapies are still an unmet need. Recent studies report that increased availability of intracellular NAD obtained by inhibition of the NAD-consuming enzyme poly(ADP-ribose) polymerase (PARP)-1 or supplementation with the NAD-precursor nicotinamide riboside (NR) ameliorates energetic derangement and symptoms in mouse models of mitochondrial disorders. Whether these pharmacological approaches also improve bioenergetics of human cells harboring mitochondrial defects is unknown. It is also unclear whether the same signaling cascade is prompted by PARP-1 inhibitors and NR supplementation to improve mitochondrial homeostasis. Here, we show that human fibroblasts mutant for the NADH dehydrogenase (ubiquinone) Fe-S protein 1 (NDUFS1) subunit of respiratory complex I have similar ATP, NAD, and mitochondrial content compared with control cells, but show reduced mitochondrial membrane potential. Interestingly, mutant cells also show increased transcript levels of mitochondrial DNA but not nuclear DNA respiratory complex subunits, suggesting activation of a compensatory response. At variance with prior work in mice, however, NR supplementation, but not PARP-1 inhibition, increased intracellular NAD content in NDUFS1 mutant human fibroblasts. Conversely, PARP-1 inhibitors, but not NR supplementation, increased transcription of mitochondrial transcription factor A and mitochondrial DNA-encoded respiratory complexes constitutively induced in mutant cells. Still, both NR and PARP-1 inhibitors restored mitochondrial membrane potential and increased organelle content as well as oxidative activity of NDUFS1-deficient fibroblasts. Overall, data provide the first evidence that in human cells harboring a mitochondrial respiratory defect exposure to NR or PARP-1, inhibitors activate different signaling pathways that are not invariantly prompted by NAD increases, but equally able to improve energetic

  3. [COMPLEX ASSESSMENT OF ENVIRONMENTAL FACTORS AND POSTVACCINAL IMMUNE STATE].

    PubMed

    Kryazhev, D A; Boev, M V; Tulina, L M; Neplokhov, A A; Boev, V M

    2016-01-01

    This article was written on the base of the analysis of data of protocols of annual serological sturdies of the post-vaccination immunity status in indicator groups of populations, the analysis of samples of drinking water air and soil with the assessment of the socio-economic development of mono-towns and rural settlements. In the article there is reflected the comprehensive assessment of environmental factors and specific features of the formation of socio-economic conditions of rural communities and mono towns. There was performed a comparative assessment of the status of post-vaccination immunity to infections controlled by specific means of prevention, in different age groups in mono towns and rural settlements. There was established a dependence of the formation of post-vaccination immunity on the state of environmental factors. PMID:27266020

  4. Human Factors Engineering at Marshall Space Flight Center

    NASA Technical Reports Server (NTRS)

    Dunn, M. C.; Hutchinson, Sonya L.

    1999-01-01

    The mission of NASA Marshall Space Flight Center (MSFC) is to develop, implement, and maintain systems for space transportation and microgravity research. Factors impacting the MSFC position as a leader in advancing science and technology include: (1) heightened emphasis on safety; (2) increased interest in effective resource utilization; and (3) growing importance of employing systems and procedures that pragmatically support mission science. In light of these factors, MSFC is integrating human factors engineering (HFE) into the systems engineering process. This paper describes the HFE program, applications of HFE in MSFC projects, and the future of HFE at MSFC.

  5. Biological characterization of human fibroblast-derived mitogenic factors for human melanocytes.

    PubMed Central

    Imokawa, G; Yada, Y; Morisaki, N; Kimura, M

    1998-01-01

    To clarify the paracrine linkage between human fibroblasts and melanocytes in cutaneous pigmentation, we studied the effects of human fibroblast-derived factors on the proliferation of human melanocytes. In medium conditioned for 4 days with human fibroblast culture, factors were produced that markedly stimulated DNA synthesis of human melanocytes. The stimulatory effect was higher in medium conditioned with fibroblasts from aged skin than in medium conditioned with fibroblasts from young skin, and was interrupted by inhibitors of tyrosine kinase, such as tyrphostin, genistein and herbimycin, but not by inhibitors of protein kinases C and A, such as H-7 and phloretin. The conditioned medium was also capable of activating mitogen-activated protein kinase of human melanocytes, with old fibroblasts being more effective than young ones. Analysis of factors released into the conditioned medium revealed that levels of hepatocyte growth factor (HGF) and stem cell factor (SCF) were increased in old-fibroblast-conditioned medium compared with young-fibroblast-conditioned medium. In contrast, levels of basic fibroblast growth factor (bFGF) were similar in both media. When the conditioned medium was treated with HGF antibody with or without SCF antibody, the increase in DNA synthesis by human melanocytes was decreased to 20% of the elevated level, whereas antibodies to bFGF had no effect. Analysis of the medium conditioned for 4 days after cytokine application demonstrated that, of the cytokines tested, interleukin 1alpha and tumour necrosis factor alpha are highly effective in stimulating HGF secretion by old fibroblasts. HGF and SCF, but not bFGF, were markedly increased in culture medium in the presence of IL-1alpha, and this stimulatory effect was confined to young human fibroblasts. These findings suggest that SCF and HGF derived from human fibroblasts may play a part in regulating cutaneous pigmentation during inflammation and aging. PMID:9494091

  6. Microtomography of the human tooth-alveolar bone complex

    NASA Astrophysics Data System (ADS)

    Dalstra, Michel; Cattaneo, Paolo M.; Beckmann, Felix; Sakima, Maurício T.; Lemor, Carsten; Laursen, Morten G.; Melsen, Birte

    2006-08-01

    In this study the structure of the adult human dentoalveolar process is examined using conventional and synchrotron radiation-based microtomography (SRμCT). Mandibular and maxillary segments containing two to five adjacent teeth were harvested at autopsy from 49 adult donors. These segments were embedded in blocks of methylmetacrylate and scanned using a conventional table-top μCT-scanner at a pixel size and slice thickness of 35 μm. A few segments were also scanned at a synchrotron facility at an initial pixel size of 16.4 μm, which was binned by a factor 2 to result in an effective voxel size of almost 32.8 μm. The three-dimensional reconstructions revealed how intricately the teeth are supported by the alveolar bone. Furthermore, this support is highly inhomogeneous with respect to the buccal, mesial, lingual and distal quadrants. Reflecting their various degrees of mineralization, tissues like bone, dentine, enamel and cementum, could well be identified, especially in the scans made with SRμCT. Despite comparable voxel sizes, the reconstructed data-sets obtained with conventional μCT were less detailed and somewhat fuzzy in appearance compared to the data-sets of SRμCT. However, for quantification of macroscopical features like the thickness of the alveolar wall or the presence of dehiscences/fenestrations this seemed sufficient.

  7. A Virtual Campus Based on Human Factor Engineering

    ERIC Educational Resources Information Center

    Yang, Yuting; Kang, Houliang

    2014-01-01

    Three Dimensional or 3D virtual reality has become increasingly popular in many areas, especially in building a digital campus. This paper introduces a virtual campus, which is based on a 3D model of The Tourism and Culture College of Yunnan University (TCYU). Production of the virtual campus was aided by Human Factor and Ergonomics (HF&E), an…

  8. Some Human Factors Issues in Bringing Jobs to Confined Persons.

    ERIC Educational Resources Information Center

    Overby, Charles

    This paper explores several human factors and other issues associated with taking jobs to disabled persons using computer-telecommunications technology and systems. General concepts of the transportation communications tradeoff are discussed. Legal and institutional dimensions of handicapped employments are addressed. A variety of research and…

  9. The Human Factor: A Key to Excellence in Education.

    ERIC Educational Resources Information Center

    Mintzies, Paula; Hare, Isadora

    This document contends that efforts designed to determine how schools can educate children for the nation of tomorrow, by focusing primarily on curriculum issues, instruction, and teachers, may have overlooked the interpersonal factors which contribute to excellence and those human and social forces which may interfere with the attainment of…

  10. Interviewer as Instrument: Accounting for Human Factors in Evaluation Research

    ERIC Educational Resources Information Center

    Brown, Joel H.

    2006-01-01

    This methodological study examines an original data collection model designed to incorporate human factors and enhance data richness in qualitative and evaluation research. Evidence supporting this model is drawn from in-depth youth and adult interviews in one of the largest policy/program evaluations undertaken in the United States, the Drug,…

  11. Investigation of Multiple Human Factors in Personalized Learning

    ERIC Educational Resources Information Center

    Chen, Sherry Y.; Huang, Pei-Ren; Shih, Yu-Cheng; Chang, Li-Ping

    2016-01-01

    In the past decade, a number of personalized learning systems have been developed and they mainly focus on learners' prior knowledge. On the other hand, previous research suggested that gender differences and cognitive styles have great effects on student learning. To this end, this study examines how human factors, especially gender differences…

  12. Human Factor Management in a Region Under Industrialization - A Concept.

    ERIC Educational Resources Information Center

    Muszynski, Marek; Kowalewski, Andrzej

    Numerous studies conducted by the Committee for Studies on Regions under Industrialization of the Polish Academy of Sciences provide the basis for historical analysis and regional comparison relative to concept formation, program guidelines, and program implementation procedures for rational human factor management. The exhaustion of Poland's…

  13. Human Factors Evaluation of Advanced Electric Power Grid Visualization Tools

    SciTech Connect

    Greitzer, Frank L.; Dauenhauer, Peter M.; Wierks, Tamara G.; Podmore, Robin

    2009-04-01

    This report describes initial human factors evaluation of four visualization tools (Graphical Contingency Analysis, Force Directed Graphs, Phasor State Estimator and Mode Meter/ Mode Shapes) developed by PNNL, and proposed test plans that may be implemented to evaluate their utility in scenario-based experiments.

  14. Critical Human Factors in Emerging Library Technology Centers.

    ERIC Educational Resources Information Center

    Lamont, Melissa

    1999-01-01

    Discusses new services that academic librarians are offering to users involving digital data, such as geographic information systems laboratories and electronic text centers. Suggests that human factors, such as management, organizational climate among the staff, and the development of a user community will determine the success or failure of the…

  15. The Complex Exogenous RNA Spectra in Human Plasma: An Interface with Human Gut Biota?

    PubMed Central

    Wang, Kai; Li, Hong; Yuan, Yue; Etheridge, Alton; Zhou, Yong; Huang, David; Wilmes, Paul; Galas, David

    2012-01-01

    Human plasma has long been a rich source for biomarker discovery. It has recently become clear that plasma RNA molecules, such as microRNA, in addition to proteins are common and can serve as biomarkers. Surveying human plasma for microRNA biomarkers using next generation sequencing technology, we observed that a significant fraction of the circulating RNA appear to originate from exogenous species. With careful analysis of sequence error statistics and other controls, we demonstrated that there is a wide range of RNA from many different organisms, including bacteria and fungi as well as from other species. These RNAs may be associated with protein, lipid or other molecules protecting them from RNase activity in plasma. Some of these RNAs are detected in intracellular complexes and may be able to influence cellular activities under in vitro conditions. These findings raise the possibility that plasma RNAs of exogenous origin may serve as signaling molecules mediating for example the human-microbiome interaction and may affect and/or indicate the state of human health. PMID:23251414

  16. Similarities between GCS and human motor cortex: complex movement coordination

    NASA Astrophysics Data System (ADS)

    Rodríguez, Jose A.; Macias, Rosa; Molgo, Jordi; Guerra, Dailos

    2014-07-01

    The "Gran Telescopio de Canarias" (GTC1) is an optical-infrared 10-meter segmented mirror telescope at the ORM observatory in Canary Islands (Spain). The GTC control system (GCS), the brain of the telescope, is is a distributed object & component oriented system based on RT-CORBA and it is responsible for the management and operation of the telescope, including its instrumentation. On the other hand, the Human motor cortex (HMC) is a region of the cerebrum responsible for the coordination of planning, control, and executing voluntary movements. If we analyze both systems, as far as the movement control of their mechanisms and body parts is concerned, we can find extraordinary similarities in their architectures. Both are structured in layers, and their functionalities are comparable from the movement conception until the movement action itself: In the GCS we can enumerate the Sequencer high level components, the Coordination libraries, the Control Kit library and the Device Driver library as the subsystems involved in the telescope movement control. If we look at the motor cortex, we can also enumerate the primary motor cortex, the secondary motor cortices, which include the posterior parietal cortex, the premotor cortex, and the supplementary motor area (SMA), the motor units, the sensory organs and the basal ganglia. From all these components/areas we will analyze in depth the several subcortical regions, of the the motor cortex, that are involved in organizing motor programs for complex movements and the GCS coordination framework, which is composed by a set of classes that allow to the high level components to transparently control a group of mechanisms simultaneously.

  17. Evidence for the formation of a heterotrimeric complex of leukaemia inhibitory factor with its receptor subunits in solution.

    PubMed Central

    Zhang, J G; Owczarek, C M; Ward, L D; Howlett, G J; Fabri, L J; Roberts, B A; Nicola, N A

    1997-01-01

    Leukaemia inhibitory factor (LIF) is a polyfunctional cytokine that is known to require at least two distinct receptor components (LIF receptor alpha-chain and gp130) in order to form a high-affinity, functional, receptor complex. Human LIF binds with unusually high affinity to a naturally occurring mouse soluble LIF receptor alpha-chain, and this property was used to purify a stable complex of human LIF and mouse LIF receptor alpha-chain from pregnant-mouse serum. Recombinant soluble human gp130 was expressed, with a FLAG(R) epitope (DYKDDDDK) at the N-terminus, in the methylotropic yeast Pichia pastoris and purified using affinity chromatography. The formation of a trimeric complex in solution was established by native gel electrophoresis, gel-filtration chromatography, sedimentation equilibrium analysis, surface plasmon resonance spectroscopy and chemical cross-linking. The stoichiometry of this solution complex was 1:1:1, in contrast with that of the complex of interleukin-6, the interleukin-6-specific low-affinity receptor subunit and gp130, which is 2:2:2. PMID:9271090

  18. Effectiveness of Shrinkage and Variable Selection Methods for the Prediction of Complex Human Traits using Data from Distantly Related Individuals

    PubMed Central

    Pérez‐Rodríguez, Paulino; Veturi, Yogasudha; Simianer, Henner; de los Campos, Gustavo

    2015-01-01

    Summary Genome‐wide association studies (GWAS) have detected large numbers of variants associated with complex human traits and diseases. However, the proportion of variance explained by GWAS‐significant single nucleotide polymorphisms has been usually small. This brought interest in the use of whole‐genome regression (WGR) methods. However, there has been limited research on the factors that affect prediction accuracy (PA) of WGRs when applied to human data of distantly related individuals. Here, we examine, using real human genotypes and simulated phenotypes, how trait complexity, marker‐quantitative trait loci (QTL) linkage disequilibrium (LD), and the model used affect the performance of WGRs. Our results indicated that the estimated rate of missing heritability is dependent on the extent of marker‐QTL LD. However, this parameter was not greatly affected by trait complexity. Regarding PA our results indicated that: (a) under perfect marker‐QTL LD WGR can achieve moderately high prediction accuracy, and with simple genetic architectures variable selection methods outperform shrinkage procedures and (b) under imperfect marker‐QTL LD, variable selection methods can achieved reasonably good PA with simple or moderately complex genetic architectures; however, the PA of these methods deteriorated as trait complexity increases and with highly complex traits variable selection and shrinkage methods both performed poorly. This was confirmed with an analysis of human height. PMID:25600682

  19. Factors Affecting Grammatical and Lexical Complexity of Long-Term L2 Speakers' Oral Proficiency

    ERIC Educational Resources Information Center

    Lahmann, Cornelia; Steinkrauss, Rasmus; Schmid, Monika S.

    2016-01-01

    There remains considerable disagreement about which factors drive second language (L2) ultimate attainment. Age of onset (AO) appears to be a robust factor, lending support to theories of maturational constraints on L2 acquisition. The present study is an investigation of factors that influence grammatical and lexical complexity at the stage of L2…

  20. Exploring the potential relevance of human-specific genes to complex disease

    PubMed Central

    2011-01-01

    Although human disease genes generally tend to be evolutionarily more ancient than non-disease genes, complex disease genes appear to be represented more frequently than Mendelian disease genes among genes of more recent evolutionary origin. It is therefore proposed that the analysis of human-specific genes might provide new insights into the genetics of complex disease. Cross-comparison with the Human Gene Mutation Database (http://www.hgmd.org) revealed a number of examples of disease-causing and disease-associated mutations in putatively human-specific genes. A sizeable proportion of these were missense polymorphisms associated with complex disease. Since both human-specific genes and genes associated with complex disease have often experienced particularly rapid rates of evolutionary change, either due to weaker purifying selection or positive selection, it is proposed that a significant number of human-specific genes may play a role in complex disease. PMID:21296743

  1. The human TREX-2 complex is stably associated with the nuclear pore basket.

    PubMed

    Umlauf, David; Bonnet, Jacques; Waharte, François; Fournier, Marjorie; Stierle, Matthieu; Fischer, Benoit; Brino, Laurent; Devys, Didier; Tora, László

    2013-06-15

    In eukaryotes, mRNA export involves many evolutionarily conserved factors that carry the nascent transcript to the nuclear pore complex (NPC). The THO/TREX complex couples transcription to mRNA export and recruits the mRNA export receptor NXF1 for the transport of messenger ribonucleoprotein particles (mRNP) to the NPC. The transcription and export complex 2 (TREX-2) was suggested to interact with NXF1 and to shuttle between transcription sites and the NPC. Here, we characterize the dynamics of human TREX-2 and show that it stably associates with the NPC basket. Moreover, the association of TREX-2 with the NPC requires the basket nucleoporins NUP153 and TPR, but is independent of transcription. Differential profiles of mRNA nuclear accumulation reveal that TREX-2 functions similarly to basket nucleoporins, but differently from NXF1. Thus, our results show that TREX-2 is an NPC-associated complex in mammalian cells and suggest that it is involved in putative NPC basket-related functions.

  2. Radioimmunoassay of factor V in human plasma and platelets

    SciTech Connect

    Tracy, P.B.; Eide, L.L.; Bowie, E.J.W.; Mann, K.G.

    1982-07-01

    Homogeneous, single-chain human factor V was used to develop a double antibody competition radioimmunoassay to measure factor V concentrations in plasma and platelets. Standard curves were constructed that allow for the detection of as little as 20 ng factor V/ml of plasma. Normal factor V concentrations range from 4 to 14 ..mu..g/ml of plasma with an average value of 7.0 +/- 2.0 ..mu..g/ml (n = 64). No correlation was observed between antigen levels and age or sex. The radioimmunoassay data are consistent with factor V clotting assays, providing freshly drawn plasma is used in the bioassay. Radioimmunoassay of washed platelets indicate that 0.63-1.93 ..mu..g of factor V is present per 2.5 X 10/sup 8/ platelets (6412-14128 molecules of factor V per platelet). When normalized to individual hematocrits and platelet count, the data indicated that platelets contribute approximately 18%-25% of the factor V found in whole blood. In addition, two individuals with functionally deficient factor V were examined and found to be deficient in both antigen and activity.

  3. Varying levels of complexity in transcription factor binding motifs

    PubMed Central

    Keilwagen, Jens; Grau, Jan

    2015-01-01

    Binding of transcription factors to DNA is one of the keystones of gene regulation. The existence of statistical dependencies between binding site positions is widely accepted, while their relevance for computational predictions has been debated. Building probabilistic models of binding sites that may capture dependencies is still challenging, since the most successful motif discovery approaches require numerical optimization techniques, which are not suited for selecting dependency structures. To overcome this issue, we propose sparse local inhomogeneous mixture (Slim) models that combine putative dependency structures in a weighted manner allowing for numerical optimization of dependency structure and model parameters simultaneously. We find that Slim models yield a substantially better prediction performance than previous models on genomic context protein binding microarray data sets and on ChIP-seq data sets. To elucidate the reasons for the improved performance, we develop dependency logos, which allow for visual inspection of dependency structures within binding sites. We find that the dependency structures discovered by Slim models are highly diverse and highly transcription factor-specific, which emphasizes the need for flexible dependency models. The observed dependency structures range from broad heterogeneities to sparse dependencies between neighboring and non-neighboring binding site positions. PMID:26116565

  4. 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.

  5. Multiscale factors affecting human attitudes toward snow leopards and wolves.

    PubMed

    Suryawanshi, Kulbhushansingh R; Bhatia, Saloni; Bhatnagar, Yash Veer; Redpath, Stephen; Mishra, Charudutt

    2014-12-01

    The threat posed by large carnivores to livestock and humans makes peaceful coexistence between them difficult. Effective implementation of conservation laws and policies depends on the attitudes of local residents toward the target species. There are many known correlates of human attitudes toward carnivores, but they have only been assessed at the scale of the individual. Because human societies are organized hierarchically, attitudes are presumably influenced by different factors at different scales of social organization, but this scale dependence has not been examined. We used structured interview surveys to quantitatively assess the attitudes of a Buddhist pastoral community toward snow leopards (Panthera uncia) and wolves (Canis lupus). We interviewed 381 individuals from 24 villages within 6 study sites across the high-elevation Spiti Valley in the Indian Trans-Himalaya. We gathered information on key explanatory variables that together captured variation in individual and village-level socioeconomic factors. We used hierarchical linear models to examine how the effect of these factors on human attitudes changed with the scale of analysis from the individual to the community. Factors significant at the individual level were gender, education, and age of the respondent (for wolves and snow leopards), number of income sources in the family (wolves), agricultural production, and large-bodied livestock holdings (snow leopards). At the community level, the significant factors included the number of smaller-bodied herded livestock killed by wolves and mean agricultural production (wolves) and village size and large livestock holdings (snow leopards). Our results show that scaling up from the individual to higher levels of social organization can highlight important factors that influence attitudes of people toward wildlife and toward formal conservation efforts in general. Such scale-specific information can help managers apply conservation measures at

  6. Multiscale factors affecting human attitudes toward snow leopards and wolves.

    PubMed

    Suryawanshi, Kulbhushansingh R; Bhatia, Saloni; Bhatnagar, Yash Veer; Redpath, Stephen; Mishra, Charudutt

    2014-12-01

    The threat posed by large carnivores to livestock and humans makes peaceful coexistence between them difficult. Effective implementation of conservation laws and policies depends on the attitudes of local residents toward the target species. There are many known correlates of human attitudes toward carnivores, but they have only been assessed at the scale of the individual. Because human societies are organized hierarchically, attitudes are presumably influenced by different factors at different scales of social organization, but this scale dependence has not been examined. We used structured interview surveys to quantitatively assess the attitudes of a Buddhist pastoral community toward snow leopards (Panthera uncia) and wolves (Canis lupus). We interviewed 381 individuals from 24 villages within 6 study sites across the high-elevation Spiti Valley in the Indian Trans-Himalaya. We gathered information on key explanatory variables that together captured variation in individual and village-level socioeconomic factors. We used hierarchical linear models to examine how the effect of these factors on human attitudes changed with the scale of analysis from the individual to the community. Factors significant at the individual level were gender, education, and age of the respondent (for wolves and snow leopards), number of income sources in the family (wolves), agricultural production, and large-bodied livestock holdings (snow leopards). At the community level, the significant factors included the number of smaller-bodied herded livestock killed by wolves and mean agricultural production (wolves) and village size and large livestock holdings (snow leopards). Our results show that scaling up from the individual to higher levels of social organization can highlight important factors that influence attitudes of people toward wildlife and toward formal conservation efforts in general. Such scale-specific information can help managers apply conservation measures at

  7. Human factors in surgery: from Three Mile Island to the operating room.

    PubMed

    D'Addessi, Alessandro; Bongiovanni, Luca; Volpe, Andrea; Pinto, Francesco; Bassi, PierFrancesco

    2009-01-01

    Human factors is a definition that includes the science of understanding the properties of human capability, the application of this understanding to the design and development of systems and services, the art of ensuring their successful applications to a program. The field of human factors traces its origins to the Second World War, but Three Mile Island has been the best example of how groups of people react and make decisions under stress: this nuclear accident was exacerbated by wrong decisions made because the operators were overwhelmed with irrelevant, misleading or incorrect information. Errors and their nature are the same in all human activities. The predisposition for error is so intrinsic to human nature that scientifically it is best considered as inherently biologic. The causes of error in medical care may not be easily generalized. Surgery differs in important ways: most errors occur in the operating room and are technical in nature. Commonly, surgical error has been thought of as the consequence of lack of skill or ability, and is the result of thoughtless actions. Moreover the 'operating theatre' has a unique set of team dynamics: professionals from multiple disciplines are required to work in a closely coordinated fashion. This complex environment provides multiple opportunities for unclear communication, clashing motivations, errors arising not from technical incompetence but from poor interpersonal skills. Surgeons have to work closely with human factors specialists in future studies. By improving processes already in place in many operating rooms, safety will be enhanced and quality increased. PMID:19829020

  8. Factors leading to the formation of arc cloud complexes

    NASA Technical Reports Server (NTRS)

    Welshinger, Mark John; Brundidge, Kenneth C.

    1987-01-01

    A total of 12 mesoscale convective systems (MCSs) were investigated. The duration of the gust front, produced by each MCS, was used to classify the MCSs. Category 1 MCSs were defined as ones that produced a gust front and the gust front lasted for more than 6 h. There were 7 category 1 MCSs in the sample. Category 2 MCSs were defined as ones that produced a gust front and the gust front lasted for 6 h or less. There were 4 category 2 MCSs. The MCS of Case 12 was not categorized because the precipitation characteristics were similar to a squall line, rather than an MCS. All of the category 1 MCSs produced arc cloud complexes (ACCs), while only one of the category 2 MCSs produced an ACC. To determine if there were any differences in the characteristics between the MCSs of the two categories, composite analyses were accomplished. The analyses showed that there were significant differences in the characteristics of category 1 and 2 MCSs. Category 1 MCSs, on average, had higher thunderstorm heights, greater precipitation intensities, colder cloud top temperatures and produced larger magnitudes of surface divergence than category 2 MCSs.

  9. Factors forming the BRCA1-A complex orchestrate BRCA1 recruitment to the sites of DNA damage.

    PubMed

    Her, Joonyoung; Soo Lee, Nam; Kim, Yonghwan; Kim, Hongtae

    2016-07-01

    Sustaining genomic integrity is essential for preventing onset of cancers. Therefore, human cells evolve to have refined biological pathways to defend genetic materials from various genomic insults. DNA damage response and DNA repair pathways essential for genome maintenance are accomplished by cooperative executions of multiple factors including breast cancer type 1 susceptibility protein (BRCA1). BRCA1 is initially identified as an altered gene in the hereditary breast cancer patients. Since then, tremendous efforts to understand the functions of BRAC1 reveal that BRCA1 is found in distinct complexes, including BRCA1-A, BRCA1-B, BRCA1-C, and the BRCA1/PALB2/BRCA2 complex, and plays diverse roles in a context-dependent manner. Among the complexes, BRCA1-A is critical for BRCA1 recruitment to the sites of DNA damage. Factors comprising the BRCA1-A include RAP80, CCDC98/Abraxas, BRCC36, BRCC45, BARD1, BRCA1, and MERIT40, a RAP80-associated factor. In this review, we summarize recent findings of the factors that form the BRCA1-A complex.

  10. Factors forming the BRCA1-A complex orchestrate BRCA1 recruitment to the sites of DNA damage.

    PubMed

    Her, Joonyoung; Soo Lee, Nam; Kim, Yonghwan; Kim, Hongtae

    2016-07-01

    Sustaining genomic integrity is essential for preventing onset of cancers. Therefore, human cells evolve to have refined biological pathways to defend genetic materials from various genomic insults. DNA damage response and DNA repair pathways essential for genome maintenance are accomplished by cooperative executions of multiple factors including breast cancer type 1 susceptibility protein (BRCA1). BRCA1 is initially identified as an altered gene in the hereditary breast cancer patients. Since then, tremendous efforts to understand the functions of BRAC1 reveal that BRCA1 is found in distinct complexes, including BRCA1-A, BRCA1-B, BRCA1-C, and the BRCA1/PALB2/BRCA2 complex, and plays diverse roles in a context-dependent manner. Among the complexes, BRCA1-A is critical for BRCA1 recruitment to the sites of DNA damage. Factors comprising the BRCA1-A include RAP80, CCDC98/Abraxas, BRCC36, BRCC45, BARD1, BRCA1, and MERIT40, a RAP80-associated factor. In this review, we summarize recent findings of the factors that form the BRCA1-A complex. PMID:27325824

  11. Immunodetection of human topoisomerase I-DNA covalent complexes.

    PubMed

    Patel, Anand G; Flatten, Karen S; Peterson, Kevin L; Beito, Thomas G; Schneider, Paula A; Perkins, Angela L; Harki, Daniel A; Kaufmann, Scott H

    2016-04-01

    A number of established and investigational anticancer drugs slow the religation step of DNA topoisomerase I (topo I). These agents induce cytotoxicity by stabilizing topo I-DNA covalent complexes, which in turn interact with advancing replication forks or transcription complexes to generate lethal lesions. Despite the importance of topo I-DNA covalent complexes, it has been difficult to detect these lesions within intact cells and tumors. Here, we report development of a monoclonal antibody that specifically recognizes covalent topo I-DNA complexes, but not free topo I or DNA, by immunoblotting, immunofluorescence or flow cytometry. Utilizing this antibody, we demonstrate readily detectable topo I-DNA covalent complexes after treatment with camptothecins, indenoisoquinolines and cisplatin but not nucleoside analogues. Topotecan-induced topo I-DNA complexes peak at 15-30 min after drug addition and then decrease, whereas indotecan-induced complexes persist for at least 4 h. Interestingly, simultaneous staining for covalent topo I-DNA complexes, phospho-H2AX and Rad51 suggests that topotecan-induced DNA double-strand breaks occur at sites distinct from stabilized topo I-DNA covalent complexes. These studies not only provide new insight into the action of topo I-directed agents, but also illustrate a strategy that can be applied to study additional topoisomerases and their inhibitors in vitro and in vivo.

  12. National plan to enhance aviation safety through human factors improvements

    NASA Technical Reports Server (NTRS)

    Foushee, Clay

    1990-01-01

    The purpose of this section of the plan is to establish a development and implementation strategy plan for improving safety and efficiency in the Air Traffic Control (ATC) system. These improvements will be achieved through the proper applications of human factors considerations to the present and future systems. The program will have four basic goals: (1) prepare for the future system through proper hiring and training; (2) develop a controller work station team concept (managing human errors); (3) understand and address the human factors implications of negative system results; and (4) define the proper division of responsibilities and interactions between the human and the machine in ATC systems. This plan addresses six program elements which together address the overall purpose. The six program elements are: (1) determine principles of human-centered automation that will enhance aviation safety and the efficiency of the air traffic controller; (2) provide new and/or enhanced methods and techniques to measure, assess, and improve human performance in the ATC environment; (3) determine system needs and methods for information transfer between and within controller teams and between controller teams and the cockpit; (4) determine how new controller work station technology can optimally be applied and integrated to enhance safety and efficiency; (5) assess training needs and develop improved techniques and strategies for selection, training, and evaluation of controllers; and (6) develop standards, methods, and procedures for the certification and validation of human engineering in the design, testing, and implementation of any hardware or software system element which affects information flow to or from the human.

  13. 1H NMR studies of reactions of copper complexes with human blood plasma and urine.

    PubMed

    Bligh, S W; Boyle, H A; McEwen, A B; Sadler, P J; Woodham, R H

    1992-01-22

    Reactions of the copper complexes Cu(II)Cl2, [Cu(II)(EDTA)]2-, [Cu(II)2(DIPS)4] and [Cu(I)(DMP)2]+ (where DIPS is 3,5-diisopropylsalicylate and DMP is 2,9-dimethylphenanthroline) with human blood plasma and urine have been studied by 500 MHz 1H NMR spectroscopy, and CD spectroscopy has been used to monitor the transfer of Cu(II) onto albumin in plasma. The rate of transfer of Cu(II) from [Cu(II)(EDTA)]2- onto albumin as measured by CD (T1/2 26 min, 0.5 mM Cu, 21 degrees), was similar to the rate of Cu(II) binding to amino acids and citrate, and to the rate of formation of [Ca(II)(EDTA)]2- in plasma. Reactions of Cu(II)Cl2 and [Cu(II)2(DIPS)4] in plasma followed a similar course, but were more rapid. The latter complex also appeared to give rise to the displacement of lactate from protein binding. Reactions of copper complexes in plasma therefore involve a range of low Mr ligands as well as albumin, and the ligands play a major role in determining the kinetics of the reactions. These factors, as well as the partitioning of both complexes and displaced ligands into lipoproteins, are likely to play important roles in the molecular pharmacology of copper-containing drugs. In urine, His and formate were involved in EDTA and DIPS displacement from their respective copper complexes, and peaks for free DIPS and [Ca(II)(EDTA)]2- were observed. The complex (Cu(I)(DMP)2]+ appeared to be relatively stable in both plasma and urine. PMID:1739401

  14. Human Factors Engineering: Current and Emerging Dual-Use Applications

    NASA Technical Reports Server (NTRS)

    Chandlee, G. O.; Goldsberry, B. S.

    1994-01-01

    Human Factors Engineering is a multidisciplinary endeavor in which information pertaining to human characteristics is used in the development of systems and machines. Six representatives considered to be experts from the public and private sectors were surveyed in an effort to identify the potential dual-use of human factors technology. Each individual was asked to provide a rating as to the dual-use of 85 identified NASA technologies. Results of the survey were as follows: nearly 75 percent of the technologies were identified at least once as high dual-use by one of the six survey respondents, and nearly 25 percent of the identified NASA technologies were identified as high dual-use technologies by a majority of the respondents. The perceived level of dual-use appeared to be independent of the technology category. Successful identification of dual-use technology requires expanded input from industry. As an adjunct, cost-benefit analysis should be conducted to identify the feasibility of the dual-use technology. Concurrent with this effort should be an examination of precedents established by other technologies in other industrial settings. Advances in human factors and systems engineering are critical to reduce risk in any workplace and to enhance industrial competitiveness.

  15. Human factors engineering checklists for application in the SAR process

    SciTech Connect

    Overlin, T.K.; Romero, H.A.; Ryan, T.G.

    1995-03-01

    This technical report was produced to assist the preparers and reviewers of the human factors portions of the SAR in completing their assigned tasks regarding analysis and/or review of completed analyses. The checklists, which are the main body of the report, and the subsequent tables, were developed to assist analysts in generating the needed analysis data to complete the human engineering analysis for the SAR. The technical report provides a series of 19 human factors engineering (HFE) checklists which support the safety analyses of the US Department of Energy`s (DOE) reactor and nonreactor facilities and activities. The results generated using these checklists and in the preparation of the concluding analyses provide the technical basis for preparing the human factors chapter, and subsequent inputs to other chapters, required by DOE as a part of the safety analysis reports (SARs). This document is divided into four main sections. The first part explains the origin of the checklists, the sources utilized, and other information pertaining to the purpose and scope of the report. The second part, subdivided into 19 sections, is the checklists themselves. The third section is the glossary which defines terms that could either be unfamiliar or have specific meanings within the context of these checklists. The final section is the subject index in which the glossary terms are referenced back to the specific checklist and page the term is encountered.

  16. Human Factors Issues For Multi-Modular Reactor Units

    SciTech Connect

    Tuan Q Tran; Humberto E. Garcia; Ronald L. Boring; Jeffrey C. Joe; Bruce P. Hallbert

    2007-08-01

    Smaller and multi-modular reactor (MMR) will be highly technologically-advanced systems allowing more system flexibility to reactors configurations (e.g., addition/deletion of reactor units). While the technical and financial advantages of systems may be numerous, MMR presents many human factors challenges that may pose vulnerability to plant safety. An important human factors challenge in MMR operation and performance is the monitoring of data from multiple plants from centralized control rooms where human operators are responsible for interpreting, assessing, and responding to different system’s states and failures (e.g., simultaneously monitoring refueling at one plant while keeping an eye on another plant’s normal operating state). Furthermore, the operational, safety, and performance requirements for MMR can seriously change current staffing models and roles, the mode in which information is displayed, procedures and training to support and guide operators, and risk analysis. For these reasons, addressing human factors concerns in MMR are essential in reducing plant risk.

  17. Importance of endothelium-derived hyperpolarizing factor in human arteries.

    PubMed Central

    Urakami-Harasawa, L; Shimokawa, H; Nakashima, M; Egashira, K; Takeshita, A

    1997-01-01

    The endothelium plays an important role in maintaining the vascular homeostasis by releasing vasodilator substances, including prostacyclin (PGI2), nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). Although the former two substances have been investigated extensively, the importance of EDHF still remains unclear, especially in human arteries. Thus we tested our hypothesis that EDHF plays an important role in human arteries, particularly with reference to the effect of vessel size, its vasodilating mechanism, and the influences of risk factors for atherosclerosis. Isometric tension and membrane potentials were recorded in isolated human gastroepiploic arteries and distal microvessels (100-150 microm in diameter). The contribution of PGI2, NO, and EDHF to endothelium-dependent relaxations was analyzed by inhibitory effects of indomethacin, NG-nitro- L-arginine, and KCl, respectively. The nature of and hyperpolarizing mechanism by EDHF were examined by the inhibitory effects of inhibitors of cytochrome P450 pathway and of various K channels. The effects of atherosclerosis risk factors on EDHF-mediated relaxations were also analyzed. The results showed that (a) the contribution of EDHF to endothelium-dependent relaxations is significantly larger in microvessels than in large arteries; (b) the nature of EDHF may not be a product of cytochrome P450 pathway, while EDHF-induced hyperpolarization is partially mediated by calcium-activated K channels; and (c) aging and hypercholesterolemia significantly impair EDHF-mediated relaxations. These results demonstrate that EDHF also plays an important role in human arteries. PMID:9389744

  18. Human factors for the Moon: the gap in anthropometric data.

    NASA Astrophysics Data System (ADS)

    Lia Schlacht, Irene; Foing, Bernard H.; Rittweger, Joern; Masali, Melchiorre; Stevenin, Hervé

    2016-07-01

    Since the space era began, we learned first to survive and then to live in space. In the state of the art, we know how important human factors research and development is to guarantee maximum safety and performance for human missions. With the extension of the duration of space missions, we also need to learn how habitability and comfort factors are closely related to safety and performance. Humanities disciplines such as design, architecture, anthropometry, and anthropology are now involved in mission design from the start. Actual plans for building a simulated Moon village in order to simulate and test Moon missions are now being carried out using a holistic approach, involving multidisciplinary experts cooperating concurrently with regard to the interactions among humans, technology, and the environment. However, in order to implement such plans, we need basic anthropometrical data, which is still missing. In other words: to optimize performance, we need to create doors and ceilings with dimensions that support a natural human movement in the reduced gravity environment of the Moon, but we are lacking detailed anthropometrical data on human movement on the Moon. In the Apollo missions more than 50 years ago, no anthropometrical studies were carried in hypogravity out as far as we know. The necessity to collect data is very consistent with state-of-the-art research. We still have little knowledge of how people will interact with the Moon environment. Specifically, it is not known exactly which posture, which kind of walking and running motions astronauts will use both inside and outside a Moon station. Considering recent plans for a Moon mission where humans will spend extensive time in reduced gravity conditions, the need for anthropometric, biomechanics and kinematics field data is a priority in order to be able to design the right architecture, infrastructure, and interfaces. Objective of this paper: Bring knowledge on the relevance of anthropometrical and

  19. [Structure and function of the factor VIII/von Willebrand factor complex].

    PubMed

    Müller, G

    1990-03-01

    In the blood plasma factor VIII is bound to the von Willebrand factor. The primary structure of the two proteins were clarified by gene clonation. Factor VIII descends from a precursor protein with 2,351 amino acids by splitting of 19 amino acid residues and is activated by partial proteolysis. In the blood coagulation factor VIII acts as co-factor for the activation of factor X by factor IX in the presence of phospholipids and Ca++ within the intrinsic coagulation system. The formation of the von Willebrand factor takes place by splitting of 22 and 741 amino acid residues, respectively, from pre-pro-von Willebrand factor via pro-von Willebrand factor. The subunits of the von Willebrand factor consist od 2,050 amino acid residues. In the blood plasma the von Willebrand factor is existing as a mixture of multimeres. Receptors of the von Willebrand factor on the thrombocytic membrane are the glycoproteins GPIb and GPIIb/GPIIIa, by means of which the adhesion of thrombocytes at the subendoethelium of the vascular wall and the aggregation of thrombocytes are mediated. PMID:2159676

  20. Capturing the Value: Earth Applications of Space Human Factors Research

    NASA Technical Reports Server (NTRS)

    Connors, Mary M.; Shafto, Michael G. (Technical Monitor)

    1995-01-01

    This paper details how the Space Human Factors/Life Sciences program at Ames Research Center (ARC) has provided, and continues to provide, a variety of Earth-based benefits. These benefits will be considered under five categories: aeronautics, space-like environments, general applications, human/automation interaction, and methodology. The human factors work at ARC includes a range of activities whose products serve the aerospace community. Some areas of research focus specifically on aeronautical requirements; others are driven by space needs. However, the symbiosis between these two domains allows a sharing of resources, and the insights and experimental results gathered in one domain can often be applied in the other. Aeronautics is an industry whose survival is generally viewed as critical to American competitiveness, and where benefits can result in a very high payoff. The ability to apply space-initiated research to aeronautical requirements represents one example of bringing space benefits down to Earth. The second-order value of space human factors research goes well beyond the aerospace community. Spaceflight shares with a number of other activities certain environmental characteristics that drive human factors engineering design and procedural specification. Spaceflight is an isolated activity, conducted under severely confined conditions, with a high level of risk, and where provisions are restricted and opportunities for outside help are limited. A number of Earth-based activities including submarines and other naval vessels, oil rigs, remote weather stations, and scientific and polar expeditions, share many of these characteristics. These activities serve as testbeds for space-related research and, in turn, space-related research provides beneficial insight to the conduct of these activities.

  1. Human Factors Guidelines for UAS in the National Airspace System

    NASA Technical Reports Server (NTRS)

    Hobbs, Alan; Shively, R. Jay

    2013-01-01

    The ground control stations (GCS) of some UAS have been characterized by less-than-adequate human-system interfaces. In some cases this may reflect a failure to apply an existing regulation or human factors standard. In other cases, the problem may indicate a lack of suitable guidance material. NASA is leading a community effort to develop recommendations for human factors guidelines for GCS to support routine beyond-line-of-sight UAS operations in the national airspace system (NAS). In contrast to regulations, guidelines are not mandatory requirements. However, by encapsulating solutions to identified problems or areas of risk, guidelines can provide assistance to system developers, users and regulatory agencies. To be effective, guidelines must be relevant to a wide range of systems, must not be overly prescriptive, and must not impose premature standardization on evolving technologies. By assuming that a pilot will be responsible for each UAS operating in the NAS, and that the aircraft will be required to operate in a manner comparable to conventionally piloted aircraft, it is possible to identify a generic set of pilot tasks and the information, control and communication requirements needed to support these tasks. Areas where guidelines will be useful can then be identified, utilizing information from simulations, operational experience and the human factors literature. In developing guidelines, we recognize that existing regulatory and guidance material will, at times, provide adequate coverage of an area. In other cases suitable guidelines may be found in existing military or industry human factors standards. In cases where appropriate existing standards cannot be identified, original guidelines will be proposed.

  2. Synthesis of Antihemophilic Factor Antigen by Cultured Human Endothelial Cells

    PubMed Central

    Jaffe, Eric A.; Hoyer, Leon W.; Nachman, Ralph L.

    1973-01-01

    Antihemophilic factor (AHF, Factor VIII) antigen has been demonstrated in cultured human endothelial cells by immunofluorescence studies using monospecific rabbit antibody to human AHF. Control studies with cultured human smooth muscle cells and human fibroblasts were negative. By radioimmunoassay it was demonstrated that cultured human endothelial cells contain AHF antigen which is released into the culture medium. Cultured smooth muscle cells and fibroblasts did not have this property. Cultured endothelial cells incorporated radioactive amino acids into high molecular weight, AHF antigen-rich protein fractions prepared from the culture media, 7% of the radioactive amino acid counts incorporated into this material were precipitated by globulin prepared from rabbit anti-AHF whereas normal rabbit globulin precipitated only 1.5% of the counts. Although cultured endothelial cells actively synthesize AHF antigen, AHF procoagulant activity was not detected in the culture medium. Studies seeking a basis for the lack of procoagulant activity have not clarified this deficiency, but they have established that exogenous AHF procoagulant activity is not inactivated by the tissue culture system. Images PMID:4583980

  3. Characterization of a human antigen specific helper factor

    SciTech Connect

    Richardson, B.

    1986-03-01

    While antigen (Ag) specific helper factors have been characterized in mice, similar molecules have not been identified in humans. To characterize human antigen specific helper molecules, an IL-2 dependent tetanus toxoid (T.T.) reactive T cell line was fused with a 6-thioguanine resistant CEM line, and hybrids selected in medium containing hypoxanthine and azaserine. Hybrids were screened by culturing the cells with /sup 35/S-Met then reacting the supernatants with T.T. or hepatitis vaccine immobilized on nitrocellulose. One hybrid, TT6BA-O, was identified which secreted a Met-containing molecule which bound T.T. but not hepatitis vaccine. Supernatants from TT6BA-O, but not the parent CEM line, when added to autologous peripheral blood mononuclear cells (PBMC's) stimulated secretion of T.T. specific antibodies (Abs). Specificity controls demonstrated that TT6BA-O supernatant did not induce antibodies to diphtheria toxoid, hepatitis vaccine or pneumococcal polysaccharide, and total immunoglobulin (lg) synthesis was minimally increased. In contrast, pokeweed mitogen stimulated significant lg synthesis as well as Ab's to pneumococcal polysaccharide and T.T. TT6BA-O supernatant induced anti-T.T.Ab's in autologous PBMC's but not PBMC's from 3 unrelated donors, suggesting that the activity of the helper factor is restricted, possibly by the MHC. The molecular weight of the helper factor was estimated at 100,000-150,000 by Sephacryl S-300 chromatography. Finally, the helper factor could be demonstrated to bind and elute from sephorose-immobilized T.T. and anti-DR antisera, but not anti-lg antisera or the T40/25 monoclonal antibody, which binds a nonpolymorphic determinant on the human T cell receptor. These results demonstrate that human Ag specific helper factors exist, bind antigen and bear class II MHC determinants.

  4. The Staphylococcus aureus Protein Sbi Acts as a Complement Inhibitor and Forms a Tripartite Complex with Host Complement Factor H and C3b

    PubMed Central

    van den Elsen, Jean; Burman, Julia; Hälbich, Steffi; Richter, Julia; Skerka, Christine; Zipfel, Peter F.

    2008-01-01

    The Gram-positive bacterium Staphylococcus aureus, similar to other pathogens, binds human complement regulators Factor H and Factor H related protein 1 (FHR-1) from human serum. Here we identify the secreted protein Sbi (Staphylococcus aureus binder of IgG) as a ligand that interacts with Factor H by a—to our knowledge—new type of interaction. Factor H binds to Sbi in combination with C3b or C3d, and forms tripartite Sbi∶C3∶Factor H complexes. Apparently, the type of C3 influences the stability of the complex; surface plasmon resonance studies revealed a higher stability of C3d complexed to Sbi, as compared to C3b or C3. As part of this tripartite complex, Factor H is functionally active and displays complement regulatory activity. Sbi, by recruiting Factor H and C3b, acts as a potent complement inhibitor, and inhibits alternative pathway-mediated lyses of rabbit erythrocytes by human serum and sera of other species. Thus, Sbi is a multifunctional bacterial protein, which binds host complement components Factor H and C3 as well as IgG and β2-glycoprotein I and interferes with innate immune recognition. PMID:19112495

  5. SM-TF: A structural database of small molecule-transcription factor complexes.

    PubMed

    Xu, Xianjin; Ma, Zhiwei; Sun, Hongmin; Zou, Xiaoqin

    2016-06-30

    Transcription factors (TFs) are the proteins involved in the transcription process, ensuring the correct expression of specific genes. Numerous diseases arise from the dysfunction of specific TFs. In fact, over 30 TFs have been identified as therapeutic targets of about 9% of the approved drugs. In this study, we created a structural database of small molecule-transcription factor (SM-TF) complexes, available online at http://zoulab.dalton.missouri.edu/SM-TF. The 3D structures of the co-bound small molecule and the corresponding binding sites on TFs are provided in the database, serving as a valuable resource to assist structure-based drug design related to TFs. Currently, the SM-TF database contains 934 entries covering 176 TFs from a variety of species. The database is further classified into several subsets by species and organisms. The entries in the SM-TF database are linked to the UniProt database and other sequence-based TF databases. Furthermore, the druggable TFs from human and the corresponding approved drugs are linked to the DrugBank. © 2016 Wiley Periodicals, Inc.

  6. Quantitative analysis of binding of transcription factor complex to biotinylated DNA probe by a streptavidin-agarose pulldown assay.

    PubMed

    Deng, Wu-Guo; Zhu, Ying; Montero, Alberto; Wu, Kenneth K

    2003-12-01

    Gene expression is regulated by a large complex of proteins that bind to the promoter/enhancer region of a gene. We determined whether a streptavidin-bead binding assay might be useful in detecting individual proteins in the complex comprising transactivators, coactivators, mediators, and general transcription factors. We used biotinylated cyclooxygenase-2 promoter probes as a model. Nuclear extracts obtained from human fibroblasts treated with or without an agonist were incubated with a 5(')-biotinylated probe and streptavidin-agarose beads at room temperature for 1h. After centrifugation, the pellet was washed and proteins in the complex were assessed by immunoblots. An array of transcription factors was detectable concurrently in the same batch of pellets at basal state. p300 and its associated factor PCAF levels but not Srb7, Med7, or TFII(B) were increased by phorbol ester or tumor necrosis factor alpha stimulation. Only trace of CREB-binding protein was detected. These results suggest that p300 and PCAF are the predominant coactivators for COX-2 promoter activation. Our findings indicate that the streptavidin-bead pulldown assay is valuable for determining the binding of a large number of transcription factors to promoter/enhancer and evaluating the relationship of protein binding with regulation of gene expression.

  7. Factors influencing trace element composition in human teeth

    SciTech Connect

    Tandon, L.; Iyengar, G.V.

    1997-12-01

    The authors recently compiled and reviewed the literature published in or after 1978 for 45 major, minor, and trace elements in human teeth as a part of an International Atomic Energy Agency (IAEA) study. The purpose of this paper is to discuss the various factors that influence the concentration levels of certain trace elements in human teeth. The sampling practices and analytical techniques that are applicable for trace element analysis are also discussed. It is also our intention to identify reference range of values, where data permit such conclusions. The scrutiny was designed to identify only the healthy permanent teeth, and values from teeth with fillings, caries, or periodontal diseases were eliminated.

  8. Equivalent circuit with complex physical constants and equivalent-parameters-expressed dissipation factors of piezoelectric materials

    NASA Astrophysics Data System (ADS)

    Chen, Yu; Wen, Yu-Mei; Li, Ping

    2006-06-01

    The equivalent circuit with complex physical constants for a piezoelectric ceramic in thickness mode is established. In the equivalent circuit, electric components (equivalent circuit parameters) are connected to real and imaginary parts of complex physical coefficients of piezoelectric materials. Based on definitions of dissipation factors, three of them (dielectric, elastic and piezoelectric dissipation factors) are represented by equivalent circuit parameters. Since the equivalent circuit parameters are detectable, the dissipation factors can be easily obtained. In the experiments, the temperature and the stress responses of the three dissipation factors are measured.

  9. Selective inhibition of the prothrombinase complex: factor Va alters macromolecular recognition of a tick anticoagulant peptide mutant by factor Xa.

    PubMed

    Betz, A; Vlasuk, G P; Bergum, P W; Krishnaswamy, S

    1997-01-01

    The prothrombinase complex assembles through reversible interactions between the protease, factor Xa, the cofactor, factor Va, and acidic phospholipid membranes in the presence of calcium ions. Changes in macromolecular recognition by factor Xa which may result from its interaction with factor Va in the prothrombinase complex have been probed using a recombinant derivative of tick anticoagulant peptide where Arg3 has been replaced with Ala (R3A-TAP). In contrast to the wild type inhibitor, R3A-TAP was a weak competitive inhibitor of factor Xa (Ki = 794 nM). The inhibition of the prothrombinase complex by R3A-TAP was characterized by slow, tight-binding kinetics with an increased affinity of approximately 4000-fold (Ki* = 0.195 nM) relative to that of solution-phase factor Xa. Stopped-flow measurements using p-aminobenzamidine (PAB) demonstrated that the reaction between solution-phase factor Xa and R3A-TAP could be adequately described by a single reversible step with rate constants that were consistent with equilibrium binding measurements. The rate-limiting bimolecular combination of R3A-TAP and factor Xa was competitive with PAB binding of the protease. In contrast, the reaction of R3A-TAP with prothrombinase measured using PAB yielded biphasic stopped-flow traces, indicating a multistep pathway for the reaction of the inhibitor with the enzyme complex. The kinetic measurements were consistent with the initial formation of a ternary complex between R3A-TAP, prothrombinase, and PAB followed by two unimolecular steps which lead to PAB dissociation from the enzyme. In this case, prior occupation of the active site by PAB had no effect on the bimolecular reaction between R3A-TAP and prothrombinase. Thus, the interaction of factor Xa with factor Va on the membrane surface alters recognition of R3A-TAP by the protease, leading to changes in the thermodynamics as well as in the observed kinetic mechanism for the reaction. Therefore, a single amino acid substitution in

  10. Space Flight Human System Standards (SFHSS). Volume 2; Human Factors, Habitability and Environmental Factors" and Human Integration Design Handbook (HIDH)

    NASA Technical Reports Server (NTRS)

    Davis, Jeffrey R.; Fitts, David J.

    2009-01-01

    This viewgraph presentation reviews the standards for space flight hardware based on human capabilities and limitations. The contents include: 1) Scope; 2) Applicable documents; 3) General; 4) Human Physical Characteristics and Capabilities; 5) Human Performance and Cognition; 6) Natural and Induced Environments; 7) Habitability Functions; 8) Architecture; 9) Hardware and Equipment; 10) Crew Interfaces; 11) Spacesuits; 12) Operatons: Reserved; 13) Ground Maintenance and Assembly: Reserved; 14) Appendix A-Reference Documents; 15) Appendix N-Acronyms and 16) Appendix C-Definition. Volume 2 is supported by the Human Integration Design Handbook (HIDH)s.

  11. The Impact of Evolutionary Driving Forces on Human Complex Diseases: A Population Genetics Approach.

    PubMed

    Saeb, Amr T M; Al-Naqeb, Dhekra

    2016-01-01

    Investigating the molecular evolution of human genome has paved the way to understand genetic adaptation of humans to the environmental changes and corresponding complex diseases. In this review, we discussed the historical origin of genetic diversity among human populations, the evolutionary driving forces that can affect genetic diversity among populations, and the effects of human movement into new environments and gene flow on population genetic diversity. Furthermore, we presented the role of natural selection on genetic diversity and complex diseases. Then we reviewed the disadvantageous consequences of historical selection events in modern time and their relation to the development of complex diseases. In addition, we discussed the effect of consanguinity on the incidence of complex diseases in human populations. Finally, we presented the latest information about the role of ancient genes acquired from interbreeding with ancient hominids in the development of complex diseases. PMID:27313952

  12. The Impact of Evolutionary Driving Forces on Human Complex Diseases: A Population Genetics Approach

    PubMed Central

    Saeb, Amr T. M.; Al-Naqeb, Dhekra

    2016-01-01

    Investigating the molecular evolution of human genome has paved the way to understand genetic adaptation of humans to the environmental changes and corresponding complex diseases. In this review, we discussed the historical origin of genetic diversity among human populations, the evolutionary driving forces that can affect genetic diversity among populations, and the effects of human movement into new environments and gene flow on population genetic diversity. Furthermore, we presented the role of natural selection on genetic diversity and complex diseases. Then we reviewed the disadvantageous consequences of historical selection events in modern time and their relation to the development of complex diseases. In addition, we discussed the effect of consanguinity on the incidence of complex diseases in human populations. Finally, we presented the latest information about the role of ancient genes acquired from interbreeding with ancient hominids in the development of complex diseases. PMID:27313952

  13. Formation of tissue factor activity following incubation of recombinant human tissue factor apoprotein with plasma lipoproteins

    SciTech Connect

    Sakai, T.; Kisiel, W. )

    1990-11-01

    Incubation of recombinant human tissue factor apoprotein (Apo-TF) with human plasma decreased the recalcified clotting time of this plasma in a time-and dose-dependent manner suggesting relipidation of the Apo-TF by plasma lipoproteins. Incubation of Apo-TF with purified preparations of human very low density, low density and high density lipoproteins resulted in tissue factor activity in a clotting assay. The order of effectiveness was VLDL greater than LDL much greater than HDL. Tissue factor activity generated by incubation of a fixed amount of Apo-TF with plasma lipoproteins was lipoprotein concentration-dependent and saturable. The association of Apo-TF with lipoprotein particles was supported by gel filtration studies in which {sup 125}I-Apo-TF coeluted with the plasma lipoprotein in the void volume of a Superose 6 column in the presence and absence of calcium ions. In addition, void-volume Apo-TF-lipoprotein fractions exhibited tissue factor activity. These results suggest that the factor VIII-bypassing activity of bovine Apo-TF observed in a canine hemophilic model may be due, in part, to its association with plasma lipoproteins and expression of functional tissue factor activity.

  14. Systematic Discovery of Complex Indels in Human Cancers

    PubMed Central

    Ye, Kai; Wang, Jiayin; Jayasinghe, Reyka; Lameijer, Eric-Wubbo; McMichael, Joshua F.; Ning, Jie; McLellan, Michael D.; Xie, Mingchao; Cao, Song; Yellapantula, Venkata; Huang, Kuan-lin; Scott, Adam; Foltz, Steven; Niu, Beifang; Johnson, Kimberly J.; Moed, Matthijs; Slagboom, P. Eline; Chen, Feng; Wendl, Michael C.; Ding, Li

    2016-01-01

    Complex indels are formed by simultaneously deleting and inserting DNA fragments of different sizes at a common genomic location. Here, we present a systematic analysis of somatic complex indels in the coding sequences of over 8,000 cancer cases using Pindel-C. We discovered 285 complex indels in cancer genes (e.g., PIK3R1, TP53, ARID1A, GATA3, and KMT2D) in approximately 3.5% of cases analyzed; nearly all instances of complex indels were overlooked (81.1%) or mis-annotated (17.6%) in 2,199 samples previously reported. In-frame complex indels are enriched in PIK3R1 and EGFR while frameshifts are prevalent in VHL, GATA3, TP53, ARID1A, PTEN, and ATRX. Further, complex indels display strong tissue specificity (e.g., VHL from kidney cancer and GATA3 from breast cancer). Finally, structural analyses support findings of previously missed, but potentially druggable mutations in EGFR, MET, and KIT oncogenes. This study indicates the critical importance of improving complex indel discovery and interpretation in medical research. PMID:26657142

  15. Systematic discovery of complex insertions and deletions in human cancers.

    PubMed

    Ye, Kai; Wang, Jiayin; Jayasinghe, Reyka; Lameijer, Eric-Wubbo; McMichael, Joshua F; Ning, Jie; McLellan, Michael D; Xie, Mingchao; Cao, Song; Yellapantula, Venkata; Huang, Kuan-lin; Scott, Adam; Foltz, Steven; Niu, Beifang; Johnson, Kimberly J; Moed, Matthijs; Slagboom, P Eline; Chen, Feng; Wendl, Michael C; Ding, Li

    2016-01-01

    Complex insertions and deletions (indels) are formed by simultaneously deleting and inserting DNA fragments of different sizes at a common genomic location. Here we present a systematic analysis of somatic complex indels in the coding sequences of samples from over 8,000 cancer cases using Pindel-C. We discovered 285 complex indels in cancer-associated genes (such as PIK3R1, TP53, ARID1A, GATA3 and KMT2D) in approximately 3.5% of cases analyzed; nearly all instances of complex indels were overlooked (81.1%) or misannotated (17.6%) in previous reports of 2,199 samples. In-frame complex indels are enriched in PIK3R1 and EGFR, whereas frameshifts are prevalent in VHL, GATA3, TP53, ARID1A, PTEN and ATRX. Furthermore, complex indels display strong tissue specificity (such as VHL in kidney cancer samples and GATA3 in breast cancer samples). Finally, structural analyses support findings of previously missed, but potentially druggable, mutations in the EGFR, MET and KIT oncogenes. This study indicates the critical importance of improving complex indel discovery and interpretation in medical research. PMID:26657142

  16. In situ structural analysis of the human nuclear pore complex

    PubMed Central

    Ori, Alessandro; DiGuilio, Amanda L.; Vollmer, Benjamin; Mackmull, Marie-Therese; Banterle, Niccolo; Parca, Luca; Kastritis, Panagiotis; Buczak, Katarzyna; Mosalaganti, Shyamal; Hagen, Wim; Andres-Pons, Amparo; Lemke, Edward A.; Bork, Peer; Antonin, Wolfram; Glavy, Joseph S.; Bui, Khanh Huy; Beck, Martin

    2016-01-01

    Summary Nuclear pore complexes (NPCs) are fundamental components of all eukaryotic cells that mediate nucleocytoplasmic exchange. Elucidating their 110 MDa structure imposes a formidable challenge and requires in situ structural biology approaches. Fifteen out of about thirty nucleoporins (Nups) are structured and form the Y- and inner ring complexes. These two major scaffolding modules assemble in multiple copies into an eight-fold rotationally symmetric structure that fuses the inner and outer nuclear membranes to form a central channel of ∼60 nm in diameter 1. The scaffold is decorated with transport channel Nups that often contain phenylalanine (FG)-repeat sequences and mediate the interaction with cargo complexes. Although the architectural arrangement of parts of the Y-complex has been elucidated, it is unclear how exactly it oligomerizes in situ. Here, we combined cryo electron tomography with mass spectrometry, biochemical analysis, perturbation experiments and structural modeling to generate the most comprehensive architectural model of the NPC to date. Our data suggest previously unknown protein interfaces across Y-complexes and to inner ring complex members. We demonstrate that the higher eukaryotic transport channel Nup358 (RanBP2) has a previously unanticipated role in Y-complex oligomerization. Our findings blur the established boundaries between scaffold and transport channel Nups. We conclude that, similarly to coated vesicles, multiple copies of the same structural building block - although compositionally identical - engage in different local sets of interactions and conformations. PMID:26416747

  17. Vestibular factors influencing the biomedical support of humans in space

    NASA Technical Reports Server (NTRS)

    Lichtenberg, B. K.

    1988-01-01

    This paper will describe the biomedical support aspects of humans in space with respect to the vestibular system. The vestibular system is thought to be the primary sensory system involved in the short-term effects of space motion sickness although there is increasing evidence that many factors play a role in this complex set of symptoms. There is the possibility that an individual's inner sense of orientation may be strongly coupled with the susceptibility to space motion sickness. A variety of suggested countermeasures for space motion sickness will be described. Although there are no known ground-based tests that can predict space motion sickness, the search should go on. The long term effects of the vestibular system in weightlessness are still relatively unknown. Some preliminary data has shown that the otoconia are irregular in size and distribution following extended periods of weightlessness. The ramifications of this data are not yet known and because the data was obtained on lower order animals, definitive studies and results must wait until the space station era when higher primates can be studied for long durations. This leads us to artificial gravity, the last topic of this paper. The vestibular system is intimately tied to this question since it has been shown on Earth that exposure to a slow rotating room causes motion sickness for some period of time before adaptation occurs. If the artificial gravity is intermittent, will this mean that people will get sick every time they experience it? The data from many astronauts returning to Earth indicates that a variety of sensory illusions are present, especially immediately upon return to a 1-g environment. Oscillopsia or apparent motion of the visual surround upon head motion along with inappropriate eye motions for a given head motion, all indicate that there is much to be studied yet about the vestibular and CNS systems reaction to a sudden application of a steady state acceleration field like 1-g. From

  18. Matriptase Complexes and Prostasin Complexes with HAI-1 and HAI-2 in Human Milk: Significant Proteolysis in Lactation.

    PubMed

    Lai, Chih-Hsin; Lai, Ying-Jung J; Chou, Feng-Pai; Chang, Hsiang-Hua D; Tseng, Chun-Che; Johnson, Michael D; Wang, Jehng-Kang; Lin, Chen-Yong

    2016-01-01

    Significant proteolysis may occur during milk synthesis and secretion, as evidenced by the presence of protease-protease inhibitor complex containing the activated form of the type 2 transmembrane serine protease matriptase and the transmembrane Kunitz-type serine protease inhibitor HAI-1. In order to identify other proteolysis events that may occur during lactation, human milk was analyzed for species containing HAI-1 and HAI-2 which is closely related to HAI-1. In addition to the previously demonstrated matriptase-HAI-1 complex, HAI-1 was also detected in complex with prostasin, a glycosylphosphatidylinositol (GPI)-anchored serine protease. HAI-2 was also detected in complexes, the majority of which appear to be part of higher-order complexes, which do not bind to ionic exchange columns or immunoaffinity columns, suggesting that HAI-2 and its target proteases may be incorporated into special protein structures during lactation. The small proportion HAI-2 species that could be purified contain matriptase or prostasin. Human mammary epithelial cells are the likely cellular sources for these HAI-1 and HAI-2 complexes with matriptase and prostasin given that these protease-inhibitor complexes with the exception of prostasin-HAI-2 complex were detected in milk-derived mammary epithelial cells. The presence of these protease-inhibitor complexes in human milk provides in vivo evidence that the proteolytic activity of matriptase and prostasin are significantly elevated at least during lactation, and possibly contribute to the process of lactation, and that they are under tight control by HAI-1 and HAI-2.

  19. Matriptase Complexes and Prostasin Complexes with HAI-1 and HAI-2 in Human Milk: Significant Proteolysis in Lactation

    PubMed Central

    Lai, Chih-Hsin; Lai, Ying-Jung J.; Chou, Feng-Pai; Chang, Hsiang-Hua D.; Tseng, Chun-Che; Johnson, Michael D.; Wang, Jehng-Kang; Lin, Chen-Yong

    2016-01-01

    Significant proteolysis may occur during milk synthesis and secretion, as evidenced by the presence of protease-protease inhibitor complex containing the activated form of the type 2 transmembrane serine protease matriptase and the transmembrane Kunitz-type serine protease inhibitor HAI-1. In order to identify other proteolysis events that may occur during lactation, human milk was analyzed for species containing HAI-1 and HAI-2 which is closely related to HAI-1. In addition to the previously demonstrated matriptase-HAI-1 complex, HAI-1 was also detected in complex with prostasin, a glycosylphosphatidylinositol (GPI)-anchored serine protease. HAI-2 was also detected in complexes, the majority of which appear to be part of higher-order complexes, which do not bind to ionic exchange columns or immunoaffinity columns, suggesting that HAI-2 and its target proteases may be incorporated into special protein structures during lactation. The small proportion HAI-2 species that could be purified contain matriptase or prostasin. Human mammary epithelial cells are the likely cellular sources for these HAI-1 and HAI-2 complexes with matriptase and prostasin given that these protease-inhibitor complexes with the exception of prostasin-HAI-2 complex were detected in milk-derived mammary epithelial cells. The presence of these protease-inhibitor complexes in human milk provides in vivo evidence that the proteolytic activity of matriptase and prostasin are significantly elevated at least during lactation, and possibly contribute to the process of lactation, and that they are under tight control by HAI-1 and HAI-2. PMID:27043831

  20. Collaborating with human factors when designing an electronic textbook

    SciTech Connect

    Ratner, J.A.; Zadoks, R.I.; Attaway, S.W.

    1996-04-01

    The development of on-line engineering textbooks presents new challenges to authors to effectively integrate text and tools in an electronic environment. By incorporating human factors principles of interface design and cognitive psychology early in the design process, a team at Sandia National Laboratories was able to make the end product more usable and shorten the prototyping and editing phases. A critical issue was simultaneous development of paper and on-line versions of the textbook. In addition, interface consistency presented difficulties with distinct goals and limitations for each media. Many of these problems were resolved swiftly with human factors input using templates, style guides and iterative usability testing of both paper and on-line versions. Writing style continuity was also problematic with numerous authors contributing to the text.

  1. Human Factors Evaluations of Two-Dimensional Spacecraft Conceptual Layouts

    NASA Technical Reports Server (NTRS)

    Kennedy, Kriss J.; Toups, Larry D.; Rudisill, Marianne

    2010-01-01

    Much of the human factors work done in support of the NASA Constellation lunar program has been with low fidelity mockups. These volumetric replicas of the future lunar spacecraft allow researchers to insert test subjects from the engineering and astronaut population and evaluate the vehicle design as the test subjects perform simulations of various operational tasks. However, lunar outpost designs must be evaluated without the use of mockups, creating a need for evaluation tools that can be performed on two-dimension conceptual spacecraft layouts, such as floor plans. A tool based on the Cooper- Harper scale was developed and applied to one lunar scenario, enabling engineers to select between two competing floor plan layouts. Keywords: Constellation, human factors, tools, processes, habitat, outpost, Net Habitable Volume, Cooper-Harper.

  2. Human Factors Considerations for Performance-Based Navigation

    NASA Technical Reports Server (NTRS)

    Barhydt, Richard; Adams, Catherine A.

    2006-01-01

    A transition toward a performance-based navigation system is currently underway in both the United States and around the world. Performance-based navigation incorporates Area Navigation (RNAV) and Required Navigation Performance (RNP) procedures that do not rely on the location of ground-based navigation aids. These procedures offer significant benefits to both operators and air traffic managers. Under sponsorship from the Federal Aviation Administration (FAA), the National Aeronautics and Space Administration (NASA) has undertaken a project to document human factors issues that have emerged during RNAV and RNP operations and propose areas for further consideration. Issues were found to include aspects of air traffic control and airline procedures, aircraft systems, and procedure design. Major findings suggest the need for human factors-specific instrument procedure design guidelines. Ongoing industry and government activities to address air-ground communication terminology, procedure design improvements, and chart-database commonality are strongly encouraged.

  3. Autocrine growth factors for human tumor clonogenic cells.

    PubMed

    Hamburger, A W; White, C P

    1985-11-01

    A human epithelial-derived cell line, SW-13, releases a soluble substance that functions as an autocrine growth factor. SW-13 cells, derived from a human adenocarcinoma of the adrenal cortex, form a few small colonies when suspended in soft agar at low densities. The number of colonies increased significantly when either viable SW-13 cells or serum-free medium conditioned by SW-13 cells (CM) was added to agar underlayers. CM increased colony formation in a dose-dependent fashion. Clonal growth at low cell densities was dependent on the presence of both horse serum and SW-13 CM. Neither activity alone was capable of sustaining growth. Even when cells were plated at high densities CM could not substitute for serum, but could reduce the threshold serum concentration. The results suggest that autocrine and serum-derived factors act in concert to maintain clonal growth of epithelial tumor cells in soft agar.

  4. Insulin-like substance and insulin-degrading complex of hemolysate of human erythrocytes

    SciTech Connect

    Matulyavichyus, V.A.; Vareikis, E.I.; Lashas, L.V.

    1986-08-20

    A lysate of human erythrocytes was fractionated on gel-filtration resins of different types and immunoreactive insulin, the insulinase activity and the effect of individual fractions on the insulinase activity was determined in the fractions obtained. It was established that the hemolysate contains a complex of insulin-metabolizing compounds, including an insulin-like substance, insulinase, and an inhibitor and activator of the insulinase activity. The insulin-like substance coincided with native insulin in site of elution from a column of Sephadex G-50 and its concentration in the lysate exceeded that of insulin in the blood plasma. Insulinase, which has a molecular weight of about 100,000, cleaved (/sup 125/I) insulin to fragments soluble in trichloroacetic acid, but had no effect on hypophyseal proteins and glycoprotein hormones. The insulinase activity was inhibited by low temperatures, atropine, and a newly discovered intraerythrocytic proteinase inhibitor, which also inhibits the serine proteinases trypsin and chymotrypsin. A substance eluted from a column of Sephadex G-100 in the region of low-molecular-weight substances increased the insulinase activity. The elution curve of substances with proteinase-inhibiting and insulinase-activating activities indicates that there is more than one inhibitory and activating factor. The results of the studies suggest that the insulin-degrading complex in human erythrocytes acts as a regulator of the insulin level in the blood plasma. It is also possible that the insulin-like substance is produced in the cytosol of the erythrocytes.

  5. Roles of human factors and ergonomics in meeting the challenge of terrorism.

    PubMed

    Nickerson, Raymond S

    2011-09-01

    Human factors and ergonomics research focuses on questions pertaining to the design of devices, systems, and procedures with the goal of making sure that they are well suited to human use and focuses on studies of the interaction of people with simple and complex systems and machines. Problem areas studied include the allocation of function to people and machines, person-system interface design, accident prevention, risk assessment, human performance under various types of stress, crisis management, search and rescue operations, decision aiding, the training and coordination of teams, and negotiation and conflict resolution, among many others. Much human factors and ergonomics work has been directed at responding to accidents (train wrecks, airplane crashes, nuclear plant mishaps) and natural disasters (hurricanes, earthquakes, floods). Although most of this work has not been motivated by the reality of terrorism or, in particular, by the attacks of 9/11, much of it is relevant to one or another aspect of terrorism in its various manifestations, and human factors and ergonomics researchers are increasingly making the connection. The purpose of this article is to illustrate this relevance by noting a few studies, from among the many that could be cited, that have implications for helping to prevent terrorism or for dealing with the effects of terrorist incidents when they occur.

  6. Roles of human factors and ergonomics in meeting the challenge of terrorism.

    PubMed

    Nickerson, Raymond S

    2011-09-01

    Human factors and ergonomics research focuses on questions pertaining to the design of devices, systems, and procedures with the goal of making sure that they are well suited to human use and focuses on studies of the interaction of people with simple and complex systems and machines. Problem areas studied include the allocation of function to people and machines, person-system interface design, accident prevention, risk assessment, human performance under various types of stress, crisis management, search and rescue operations, decision aiding, the training and coordination of teams, and negotiation and conflict resolution, among many others. Much human factors and ergonomics work has been directed at responding to accidents (train wrecks, airplane crashes, nuclear plant mishaps) and natural disasters (hurricanes, earthquakes, floods). Although most of this work has not been motivated by the reality of terrorism or, in particular, by the attacks of 9/11, much of it is relevant to one or another aspect of terrorism in its various manifestations, and human factors and ergonomics researchers are increasingly making the connection. The purpose of this article is to illustrate this relevance by noting a few studies, from among the many that could be cited, that have implications for helping to prevent terrorism or for dealing with the effects of terrorist incidents when they occur. PMID:21823775

  7. 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.

  8. Simulation: Moving from Technology Challenge to Human Factors Success

    SciTech Connect

    Gould, Derek A.; Chalmers, Nicholas; Johnson, Sheena J.; Kilkenny, Caroline; White, Mark D.; Bech, Bo; Lonn, Lars; Bello, Fernando

    2012-06-15

    Recognition of the many limitations of traditional apprenticeship training is driving new approaches to learning medical procedural skills. Among simulation technologies and methods available today, computer-based systems are topical and bring the benefits of automated, repeatable, and reliable performance assessments. Human factors research is central to simulator model development that is relevant to real-world imaging-guided interventional tasks and to the credentialing programs in which it would be used.

  9. The development of human factors research objectives for civil aviation

    NASA Technical Reports Server (NTRS)

    Post, T. J.

    1970-01-01

    Human factors research programs which would support civil aviation and be suitable for accomplishment by NASA research centers are identified. Aviation problems formed the basis for the research program recommendations and, accordingly, problems were identified, ranked and briefly defined in an informal report to the project monitor and other cognizant NASA personnel. The sources for this problem foundation were literature reviews and extensive interviews with NASA and non-NASA personnel. An overview of these findings is presented.

  10. Functional roles of alternative splicing factors in human disease

    PubMed Central

    Cieply, Benjamin; Carstens, Russ P

    2015-01-01

    Alternative splicing (AS) is an important mechanism used to generate greater transcriptomic and proteomic diversity from a finite genome. Nearly all human gene transcripts are alternatively spliced and can produce protein isoforms with divergent and even antagonistic properties that impact cell functions. Many AS events are tightly regulated in a cell-type or tissue-specific manner, and at different developmental stages. AS is regulated by RNA-binding proteins, including cell- or tissue-specific splicing factors. In the past few years, technological advances have defined genome-wide programs of AS regulated by increasing numbers of splicing factors. These splicing regulatory networks (SRNs) consist of transcripts that encode proteins that function in coordinated and related processes that impact the development and phenotypes of different cell types. As such, it is increasingly recognized that disruption of normal programs of splicing regulated by different splicing factors can lead to human diseases. We will summarize examples of diseases in which altered expression or function of splicing regulatory proteins has been implicated in human disease pathophysiology. As the role of AS continues to be unveiled in human disease and disease risk, it is hoped that further investigations into the functions of numerous splicing factors and their regulated targets will enable the development of novel therapies that are directed at specific AS events as well as the biological pathways they impact. WIREs RNA 2015, 6:311–326. doi: 10.1002/wrna.1276 For further resources related to this article, please visit the http://wires.wiley.com/remdoi.cgi?doi=10.1002/wrna.1276WIREs website. Conflict of interest: The authors have declared no conflicts of interest for this article. PMID:25630614

  11. E-Education Applications: Human Factors and Innovative Approaches

    ERIC Educational Resources Information Center

    Ghaoui, Claude, Ed.

    2004-01-01

    "E-Education Applications: Human Factors and Innovative Approaches" enforces the need to take multi-disciplinary and/or inter-disciplinary approaches, when solutions for e-education (or online-, e-learning) are introduced. By focusing on the issues that have impact on the usability of e-learning, the book specifically fills-in a gap in this area,…

  12. TFCat: the curated catalog of mouse and human transcription factors

    PubMed Central

    Fulton, Debra L; Sundararajan, Saravanan; Badis, Gwenael; Hughes, Timothy R; Wasserman, Wyeth W; Roach, Jared C; Sladek, Rob

    2009-01-01

    Unravelling regulatory programs governed by transcription factors (TFs) is fundamental to understanding biological systems. TFCat is a catalog of mouse and human TFs based on a reliable core collection of annotations obtained by expert review of the scientific literature. The collection, including proven and homology-based candidate TFs, is annotated within a function-based taxonomy and DNA-binding proteins are organized within a classification system. All data and user-feedback mechanisms are available at the TFCat portal . PMID:19284633

  13. Human factors analysis and design methods for nuclear waste retrieval systems. Human factors design methodology and integration plan

    SciTech Connect

    Casey, S.M.

    1980-06-01

    The purpose of this document is to provide an overview of the recommended activities and methods to be employed by a team of human factors engineers during the development of a nuclear waste retrieval system. This system, as it is presently conceptualized, is intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository. This document, and the others in this series, have been developed for the purpose of implementing human factors engineering principles during the design and construction of the retrieval system facilities and equipment. The methodology presented has been structured around a basic systems development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Within each of these phases, the recommended activities of the human engineering team have been stated, along with descriptions of the human factors engineering design techniques applicable to the specific design issues. Explicit examples of how the techniques might be used in the analysis of human tasks and equipment required in the removal of spent fuel canisters have been provided. Only those techniques having possible relevance to the design of the waste retrieval system have been reviewed. This document is intended to provide the framework for integrating human engineering with the rest of the system development effort. The activities and methodologies reviewed in this document have been discussed in the general order in which they will occur, although the time frame (the total duration of the development program in years and months) in which they should be performed has not been discussed.

  14. STRIPAK complexes: structure, biological function, and involvement in human diseases.

    PubMed

    Hwang, Juyeon; Pallas, David C

    2014-02-01

    The mammalian striatin family consists of three proteins, striatin, S/G2 nuclear autoantigen, and zinedin. Striatin family members have no intrinsic catalytic activity, but rather function as scaffolding proteins. Remarkably, they organize multiple diverse, large signaling complexes that participate in a variety of cellular processes. Moreover, they appear to be regulatory/targeting subunits for the major eukaryotic serine/threonine protein phosphatase 2A. In addition, striatin family members associate with germinal center kinase III kinases as well as other novel components, earning these assemblies the name striatin-interacting phosphatase and kinase (STRIPAK) complexes. Recently, there has been a great increase in functional and mechanistic studies aimed at identifying and understanding the roles of STRIPAK and STRIPAK-like complexes in cellular processes of multiple organisms. These studies have identified novel STRIPAK and STRIPAK-like complexes and have explored their roles in specific signaling pathways. Together, the results of these studies have sparked increased interest in striatin family complexes because they have revealed roles in signaling, cell cycle control, apoptosis, vesicular trafficking, Golgi assembly, cell polarity, cell migration, neural and vascular development, and cardiac function. Moreover, STRIPAK complexes have been connected to clinical conditions, including cardiac disease, diabetes, autism, and cerebral cavernous malformation. In this review, we discuss the expression, localization, and protein domain structure of striatin family members. Then we consider the diverse complexes these proteins and their homologs form in various organisms, emphasizing what is known regarding function and regulation. Finally, we explore possible roles of striatin family complexes in disease, especially cerebral cavernous malformation.

  15. STRIPAK Complexes: structure, biological function, and involvement in human diseases

    PubMed Central

    Hwang, Juyeon; Pallas, David C.

    2014-01-01

    The mammalian striatin family consists of three proteins, striatin, S/G2 nuclear autoantigen, and zinedin. Striatin family members have no intrinsic catalytic activity, but rather function as scaffolding proteins. Remarkably, they organize multiple diverse, large signaling complexes that participate in a variety of cellular processes. Moreover, they appear to be regulatory/targeting subunits for the major eukaryotic serine/threonine protein phosphatase 2A. In addition, striatin family members associate with germinal center kinase III kinases as well as other novel components, earning these assemblies the name striatin-interacting phosphatase and kinase (STRIPAK) complexes. Recently, there has been a great increase in functional and mechanistic studies aimed at identifying and understanding the roles of STRIPAK–like complexes in cellular processes of multiple organisms. These studies have identified novel STRIPAK or STRIPAK-like complexes and have explored their roles in specific signaling pathways. Together, the results of these studies have sparked increased interest in striatin family complexes because they have revealed roles in signaling, cell cycle control, apoptosis, vesicular trafficking, Golgi assembly, cell polarity, cell migration, neural and vascular development, and cardiac function. Moreover, STRIPAK complexes have been connected to clinical conditions, including cardiac disease, diabetes, autism, and cerebral cavernous malformation. In this review, we discuss the expression, localization, and protein domain structure of striatin family members. Then we consider the diverse complexes these proteins and their homologs form in various organisms, emphasizing what is known regarding function and regulation. Finally, we will explore possible roles of striatin family complexes in disease, especially cerebral cavernous malformation. PMID:24333164

  16. A human factors approach to range scheduling for satellite control

    NASA Technical Reports Server (NTRS)

    Wright, Cameron H. G.; Aitken, Donald J.

    1991-01-01

    Range scheduling for satellite control presents a classical problem: supervisory control of a large-scale dynamic system, with unwieldy amounts of interrelated data used as inputs to the decision process. Increased automation of the task, with the appropriate human-computer interface, is highly desirable. The development and user evaluation of a semi-automated network range scheduling system is described. The system incorporates a synergistic human-computer interface consisting of a large screen color display, voice input/output, a 'sonic pen' pointing device, a touchscreen color CRT, and a standard keyboard. From a human factors standpoint, this development represents the first major improvement in almost 30 years to the satellite control network scheduling task.

  17. Space station proximity operations windows: Human factors design guidelines

    NASA Technical Reports Server (NTRS)

    Haines, Richard F.

    1987-01-01

    Proximity operations refers to all activities outside the Space Station which take place within a 1-km radius. Since there will be a large number of different operations involving manned and unmanned vehicles, single- and multiperson crews, automated and manually controlled flight, a wide variety of cargo, and construction/repair activities, accurate and continuous human monitoring of these operations from a specially designed control station on Space Station will be required. Total situational awareness will be required. This paper presents numerous human factors design guidelines and related background information for control windows which will support proximity operations. Separate sections deal with natural and artificial illumination geometry; all basic rendezvous vector approaches; window field-of-view requirements; window size; shape and placement criteria; window optical characteristics as they relate to human perception; maintenance and protection issues; and a comprehensive review of windows installed on U.S. and U.S.S.R. manned vehicles.

  18. A human factors analysis of EVA time requirements

    NASA Technical Reports Server (NTRS)

    Pate, D. W.

    1996-01-01

    Human Factors Engineering (HFE), also known as Ergonomics, is a discipline whose goal is to engineer a safer, more efficient interface between humans and machines. HFE makes use of a wide range of tools and techniques to fulfill this goal. One of these tools is known as motion and time study, a technique used to develop time standards for given tasks. A human factors motion and time study was initiated with the goal of developing a database of EVA task times and a method of utilizing the database to predict how long an ExtraVehicular Activity (EVA) should take. Initial development relied on the EVA activities performed during the STS-61 mission (Hubble repair). The first step of the analysis was to become familiar with EVAs and with the previous studies and documents produced on EVAs. After reviewing these documents, an initial set of task primitives and task time modifiers was developed. Videotaped footage of STS-61 EVAs were analyzed using these primitives and task time modifiers. Data for two entire EVA missions and portions of several others, each with two EVA astronauts, was collected for analysis. Feedback from the analysis of the data will be used to further refine the primitives and task time modifiers used. Analysis of variance techniques for categorical data will be used to determine which factors may, individually or by interactions, effect the primitive times and how much of an effect they have.

  19. Transforming growth factor (TGF)-. alpha. in human milk

    SciTech Connect

    Okada, Masaki; Wakai, Kae; Shizume, Kazuo ); Iwashita, Mitsutoshi ); Ohmura, Eiji; Kamiya, Yoshinobu; Murakami, Hitomi; Onoda, Noritaka; Tsushima, Toshio

    1991-01-01

    Transforming growth factor (TGF)-{alpha} and epidermal growth factor (EGF) were measured in human milk by means of homologous radioimmunoassay. As previously reported, EGF concentration in the colostrum was approximately 200 ng/ml and decreased to 50 ng/ml by day 7 postpartum. The value of immunoreactive (IR)-TGF-{alpha} was 2.2-7.2 ng/ml, much lower than that of EGF. In contrast to EGF, the concentration of IR-TGF-{alpha} was fairly stable during the 7 postpartum days. There was no relationship between the concentrations of IR-TGF-{alpha} and IR-EGF, suggesting that the regulatory mechanism in the release of the two growth factors is different. On gel-chromatography using a Sephadex G-50 column, IR-EGF appeared in the fraction corresponding to that of authentic human EGF, while 70%-80% of the IR-TGF-{alpha} was eluted as a species with a molecular weight greater than that of authentic human TGF-{alpha}. Although the physiological role of TGF-{alpha} in milk is not known, it is possible that it is involved in the development of the mammary gland and/or the growth of newborn infants.

  20. Human risk factors associated with pilots in runway excursions.

    PubMed

    Chang, Yu-Hern; Yang, Hui-Hua; Hsiao, Yu-Jung

    2016-09-01

    A breakdown analysis of civil aviation accidents worldwide indicates that the occurrence of runway excursions represents the largest portion among all aviation occurrence categories. This study examines the human risk factors associated with pilots in runway excursions, by applying a SHELLO model to categorize the human risk factors and to evaluate the importance based on the opinions of 145 airline pilots. This study integrates aviation management level expert opinions on relative weighting and improvement-achievability in order to develop four kinds of priority risk management strategies for airline pilots to reduce runway excursions. The empirical study based on experts' evaluation suggests that the most important dimension is the liveware/pilot's core ability. From the perspective of front-line pilots, the most important risk factors are the environment, wet/containment runways, and weather issues like rain/thunderstorms. Finally, this study develops practical strategies for helping management authorities to improve major operational and managerial weaknesses so as to reduce the human risks related to runway excursions. PMID:27344128

  1. Human Factors Considerations for Area Navigation Departure and Arrival Procedures

    NASA Technical Reports Server (NTRS)

    Barhydt, Richard; Adams, Catherine A.

    2006-01-01

    Area navigation (RNAV) procedures are being implemented in the United States and around the world as part of a transition to a performance-based navigation system. These procedures are providing significant benefits and have also caused some human factors issues to emerge. Under sponsorship from the Federal Aviation Administration (FAA), the National Aeronautics and Space Administration (NASA) has undertaken a project to document RNAV-related human factors issues and propose areas for further consideration. The component focusing on RNAV Departure and Arrival Procedures involved discussions with expert users, a literature review, and a focused review of the NASA Aviation Safety Reporting System (ASRS) database. Issues were found to include aspects of air traffic control and airline procedures, aircraft systems, and procedure design. Major findings suggest the need for specific instrument procedure design guidelines that consider the effects of human performance. Ongoing industry and government activities to address air-ground communication terminology, design improvements, and chart-database commonality are strongly encouraged. A review of factors contributing to RNAV in-service errors would likely lead to improved system design and operational performance.

  2. Linguistic complex networks: Rationale, application, interpretation, and directions. Reply to comments on "Approaching human language with complex networks"

    NASA Astrophysics Data System (ADS)

    Cong, Jin; Liu, Haitao

    2014-12-01

    Amid the enthusiasm for real-world networks of the new millennium, the enquiry into linguistic networks is flourishing not only as a productive branch of the new networks science but also as a promising approach to linguistic research. Although the complex network approach constitutes a potential opportunity to make linguistics a science, the world of linguistics seems unprepared to embrace it. For one thing, linguistics has been largely unaffected by quantitative methods. Those who are accustomed to qualitative linguistic methods may find it hard to appreciate the application of quantitative properties of language such as frequency and length, not to mention quantitative properties of language modeled as networks. With this in mind, in our review [1] we restrict ourselves to the basics of complex networks and the new insights into human language with the application of complex networks. For another, while breaking new grounds and posing new challenges for linguistics, the complex network approach to human language as a new tradition of linguistic research is faced with challenges and unsolved issues of its own. It is no surprise that the comments on our review, especially their skepticism and suggestions, focus on various different aspects of the complex network approach to human language. We are grateful to all the insightful and penetrating comments, which, together with our review, mark a significant impetus to linguistic research from the complex network approach. In this reply, we would like to address four major issues of the complex network approach to human language, namely, a) its theoretical rationale, b) its application in linguistic research, c) interpretation of the results, and d) directions of future research.

  3. A Human Factors Approach to Bridging Systems and Introducing New Technologies

    NASA Technical Reports Server (NTRS)

    Kanki, Barbara G.

    2011-01-01

    The application of human factors in aviation has grown to cover a wide range of disciplines and methods capable of assessing human-systems integration at many levels. For example, at the individual level, pilot workload may be studied while at the team level, coordinated workload distribution may be the focal point. At the organizational level, the way in which individuals and teams are supported by training and standards, policies and procedures may introduce additional, relevant topics. A consideration of human factors at each level contributes to our understanding of successes and failures in pilot performance, but this system focused on the flight deck alone -- is only one part of the airspace system. In the FAA's NextGen plan to overhaul the National Airspace System (NAS), new capabilities will enhance flightdeck systems (pilots), flight operations centers (dispatchers) and air traffic control systems (controllers and air traffic managers). At a minimum, the current roles and responsibilities of these three systems are likely to change. Since increased automation will be central to many of the enhancements, the role of automation is also likely to change. Using NextGen examples, a human factors approach for bridging complex airspace systems will be the main focus of this presentation. It is still crucial to consider the human factors within each system, but the successful implementation of new technologies in the NAS requires an understanding of the collaborations that occur when these systems intersect. This human factors approach to studying collaborative systems begins with detailed task descriptions within each system to establish a baseline of the current operations. The collaborative content and context are delineated through the review of regulatory and advisory materials, letters of agreement, policies, procedures and documented practices. Field observations and interviews also help to fill out the picture. Key collaborative functions across systems

  4. Space station crew safety: Human factors interaction model

    NASA Technical Reports Server (NTRS)

    Cohen, M. M.; Junge, M. K.

    1985-01-01

    A model of the various human factors issues and interactions that might affect crew safety is developed. The first step addressed systematically the central question: How is this space station different from all other spacecraft? A wide range of possible issue was identified and researched. Five major topics of human factors issues that interacted with crew safety resulted: Protocols, Critical Habitability, Work Related Issues, Crew Incapacitation and Personal Choice. Second, an interaction model was developed that would show some degree of cause and effect between objective environmental or operational conditions and the creation of potential safety hazards. The intermediary steps between these two extremes of causality were the effects on human performance and the results of degraded performance. The model contains three milestones: stressor, human performance (degraded) and safety hazard threshold. Between these milestones are two countermeasure intervention points. The first opportunity for intervention is the countermeasure against stress. If this countermeasure fails, performance degrades. The second opportunity for intervention is the countermeasure against error. If this second countermeasure fails, the threshold of a potential safety hazard may be crossed.

  5. Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF)

    PubMed Central

    He, Yonghua; Schmidt, Monica A.; Erwin, Christopher; Guo, Jun; Sun, Raphael; Pendarvis, Ken; Warner, Brad W.; Herman, Eliot M.

    2016-01-01

    Necrotizing enterocolitis (NEC) is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF), typically found in bodily fluids, such as amniotic fluid, salvia and mother’s breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N’ terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform. PMID:27314851

  6. Helmet-mounted pilot night vision systems: Human factors issues

    NASA Technical Reports Server (NTRS)

    Hart, Sandra G.; Brickner, Michael S.

    1989-01-01

    Helmet-mounted displays of infrared imagery (forward-looking infrared (FLIR)) allow helicopter pilots to perform low level missions at night and in low visibility. However, pilots experience high visual and cognitive workload during these missions, and their performance capabilities may be reduced. Human factors problems inherent in existing systems stem from three primary sources: the nature of thermal imagery; the characteristics of specific FLIR systems; and the difficulty of using FLIR system for flying and/or visually acquiring and tracking objects in the environment. The pilot night vision system (PNVS) in the Apache AH-64 provides a monochrome, 30 by 40 deg helmet-mounted display of infrared imagery. Thermal imagery is inferior to television imagery in both resolution and contrast ratio. Gray shades represent temperatures differences rather than brightness variability, and images undergo significant changes over time. The limited field of view, displacement of the sensor from the pilot's eye position, and monocular presentation of a bright FLIR image (while the other eye remains dark-adapted) are all potential sources of disorientation, limitations in depth and distance estimation, sensations of apparent motion, and difficulties in target and obstacle detection. Insufficient information about human perceptual and performance limitations restrains the ability of human factors specialists to provide significantly improved specifications, training programs, or alternative designs. Additional research is required to determine the most critical problem areas and to propose solutions that consider the human as well as the development of technology.

  7. Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF).

    PubMed

    He, Yonghua; Schmidt, Monica A; Erwin, Christopher; Guo, Jun; Sun, Raphael; Pendarvis, Ken; Warner, Brad W; Herman, Eliot M

    2016-01-01

    Necrotizing enterocolitis (NEC) is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF), typically found in bodily fluids, such as amniotic fluid, salvia and mother's breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N' terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform. PMID:27314851

  8. Novel factors modulating human β-cell proliferation.

    PubMed

    Shirakawa, J; Kulkarni, R N

    2016-09-01

    β-Cell dysfunction in type 1 and type 2 diabetes is accompanied by a progressive loss of β-cells, and an understanding of the cellular mechanism(s) that regulate β-cell mass will enable approaches to enhance hormone secretion. It is becoming increasingly recognized that enhancement of human β-cell proliferation is one potential approach to restore β-cell mass to prevent and/or cure type 1 and type 2 diabetes. While several reports describe the factor(s) that enhance β-cell replication in animal models or cell lines, promoting effective human β-cell proliferation continues to be a challenge in the field. In this review, we discuss recent studies reporting successful human β-cell proliferation including WS6, an IkB kinase and EBP1 inhibitor; harmine and 5-IT, both DYRK1A inhibitors; GNF7156 and GNF4877, GSK-3β and DYRK1A inhibitors; osteoprotegrin and Denosmab, receptor activator of NF-kB (RANK) inhibitors; and SerpinB1, a protease inhibitor. These studies provide important examples of proteins and pathways that may prove useful for designing therapeutic strategies to counter the different forms of human diabetes. PMID:27615134

  9. Functional analysis of Cobra Venom Factor/human C3 chimeras transiently expressed in mammalian cells.

    PubMed

    Kölln, Johanna; Matzas, Mark; Jänner, Nathalie; Mix, Thorsten; Klensang, Katrin; Bredehorst, Reinhard; Spillner, Edzard

    2004-05-01

    The complement activating venom component Cobra Venom Factor (CVF), a functional and structural homologue of the human complement component C3, forms a stable CVF-dependent C3 convertase complex, which, in contrast to C3-dependent convertase effects continuous activation of the complement and, thereby, decomplementation. In order to elucidate the mechanism underlying the enhanced activity of CVF compared to human C3, we generated two CVF/C3 chimeras and established different affinity-based assay systems for functional analysis of these constructs. To allow for convenient expression and subsequent functional characterisation, the CVF/C3 chimeras as well as CVF and C3 were transiently expressed in mammalian cells. Problems due to the low concentration of the recombinant proteins in the supernatants of transient expressions were circumvented by fusion to peptide tags enabling their efficient immobilisation onto suitable surfaces and subsequent characterisation. In an alternative approach monoclonal antibody fragments generated from a semisynthetic phage display scFv library were employed for concentrating the recombinant proteins by immunoprecipitation. Utilising both approaches all transiently expressed proteins could be characterised for their complement consumption activity. The data obtained with the CVF/C3 chimeras demonstrate that the increased stability of the CVFBb complex is independent of the domains in CVF corresponding to binding sites of factor B and H and the cleavage sites of factor I in the human C3 molecule. PMID:15140572

  10. A Complex Genome-MicroRNA Interplay in Human Mitochondria

    PubMed Central

    Shinde, Santosh; Bhadra, Utpal

    2015-01-01

    Small noncoding regulatory RNA exist in wide spectrum of organisms ranging from prokaryote bacteria to humans. In human, a systematic search for noncoding RNA is mainly limited to the nuclear and cytosolic compartments. To investigate whether endogenous small regulatory RNA are present in cell organelles, human mitochondrial genome was also explored for prediction of precursor microRNA (pre-miRNA) and mature miRNA (miRNA) sequences. Six novel miRNA were predicted from the organelle genome by bioinformatics analysis. The structures are conserved in other five mammals including chimp, orangutan, mouse, rat, and rhesus genome. Experimentally, six human miRNA are well accumulated or deposited in human mitochondria. Three of them are expressed less prominently in Northern analysis. To ascertain their presence in human skeletal muscles, total RNA was extracted from enriched mitochondria by an immunomagnetic method. The expression of six novel pre-miRNA and miRNA was confirmed by Northern blot analysis; however, low level of remaining miRNA was found by sensitive Northern analysis. Their presence is further confirmed by real time RT-PCR. The six miRNA find their multiple targets throughout the human genome in three different types of software. The luciferase assay was used to confirm that MT-RNR2 gene was the potential target of hsa-miR-mit3 and hsa-miR-mit4. PMID:25695052

  11. Preparation of the Human Cytomegalovirus Nuclear Egress Complex and Associated Proteins.

    PubMed

    Sharma, Mayuri; Kamil, Jeremy P; Coen, Donald M

    2016-01-01

    Herpesviruses, like most DNA viruses, replicate their genomes in the host cell nucleus. Their DNA is then packaged and assembled into viral nucleocapsids, which, in most cases, are too large to pass through the nuclear pore complex. Instead, herpesviruses use a complex multistep pathway, termed nuclear egress, to exit the nucleus. Key players in this process include two conserved viral proteins that form the nuclear egress complex (NEC). In human cytomegalovirus, these NEC proteins are UL50, embedded in the inner nuclear membrane, and its nucleoplasmic partner UL53. Both are essential for viral nuclear egress. However, other viral components as well as host nuclear envelope proteins may also participate in nuclear egress. Identifying these viral and cellular factors may provide important insight into the herpesvirus lifecycle and its relationship to the underlying, yet still-mysterious, host nuclear egress pathway. We developed an immunoprecipitation-based protocol, described herein, to identify protein-protein interactions involving the NEC from the nuclear fraction of infected cells that express an epitope-tagged version of NEC subunit UL53.

  12. Human genome-wide RNAi screen reveals host factors required for enterovirus 71 replication

    PubMed Central

    Wu, Kan Xing; Phuektes, Patchara; Kumar, Pankaj; Goh, Germaine Yen Lin; Moreau, Dimitri; Chow, Vincent Tak Kwong; Bard, Frederic; Chu, Justin Jang Hann

    2016-01-01

    Enterovirus 71 (EV71) is a neurotropic enterovirus without antivirals or vaccine, and its host-pathogen interactions remain poorly understood. Here we use a human genome-wide RNAi screen to identify 256 host factors involved in EV71 replication in human rhabdomyosarcoma cells. Enrichment analyses reveal overrepresentation in processes like mitotic cell cycle and transcriptional regulation. We have carried out orthogonal experiments to characterize the roles of selected factors involved in cell cycle regulation and endoplasmatic reticulum-associated degradation. We demonstrate nuclear egress of CDK6 in EV71 infected cells, and identify CDK6 and AURKB as resistance factors. NGLY1, which co-localizes with EV71 replication complexes at the endoplasmatic reticulum, supports EV71 replication. We confirm importance of these factors for EV71 replication in a human neuronal cell line and for coxsackievirus A16 infection. A small molecule inhibitor of NGLY1 reduces EV71 replication. This study provides a comprehensive map of EV71 host factors and reveals potential antiviral targets. PMID:27748395

  13. Secreted Factors from Human Vestibular Schwannomas Can Cause Cochlear Damage

    PubMed Central

    Dilwali, Sonam; Landegger, Lukas D.; Soares, Vitor Y. R.; Deschler, Daniel G.; Stankovic, Konstantina M.

    2015-01-01

    Vestibular schwannomas (VSs) are the most common tumours of the cerebellopontine angle. Ninety-five percent of people with VS present with sensorineural hearing loss (SNHL); the mechanism of this SNHL is currently unknown. To establish the first model to study the role of VS-secreted factors in causing SNHL, murine cochlear explant cultures were treated with human tumour secretions from thirteen different unilateral, sporadic VSs of subjects demonstrating varied degrees of ipsilateral SNHL. The extent of cochlear explant damage due to secretion application roughly correlated with the subjects’ degree of SNHL. Secretions from tumours associated with most substantial SNHL resulted in most significant hair cell loss and neuronal fibre disorganization. Secretions from VSs associated with good hearing or from healthy human nerves led to either no effect or solely fibre disorganization. Our results are the first to demonstrate that secreted factors from VSs can lead to cochlear damage. Further, we identified tumour necrosis factor alpha (TNFα) as an ototoxic molecule and fibroblast growth factor 2 (FGF2) as an otoprotective molecule in VS secretions. Antibody-mediated TNFα neutralization in VS secretions partially prevented hair cell loss due to the secretions. Taken together, we have identified a new mechanism responsible for SNHL due to VSs. PMID:26690506

  14. Secreted Factors from Human Vestibular Schwannomas Can Cause Cochlear Damage.

    PubMed

    Dilwali, Sonam; Landegger, Lukas D; Soares, Vitor Y R; Deschler, Daniel G; Stankovic, Konstantina M

    2015-12-22

    Vestibular schwannomas (VSs) are the most common tumours of the cerebellopontine angle. Ninety-five percent of people with VS present with sensorineural hearing loss (SNHL); the mechanism of this SNHL is currently unknown. To establish the first model to study the role of VS-secreted factors in causing SNHL, murine cochlear explant cultures were treated with human tumour secretions from thirteen different unilateral, sporadic VSs of subjects demonstrating varied degrees of ipsilateral SNHL. The extent of cochlear explant damage due to secretion application roughly correlated with the subjects' degree of SNHL. Secretions from tumours associated with most substantial SNHL resulted in most significant hair cell loss and neuronal fibre disorganization. Secretions from VSs associated with good hearing or from healthy human nerves led to either no effect or solely fibre disorganization. Our results are the first to demonstrate that secreted factors from VSs can lead to cochlear damage. Further, we identified tumour necrosis factor alpha (TNFα) as an ototoxic molecule and fibroblast growth factor 2 (FGF2) as an otoprotective molecule in VS secretions. Antibody-mediated TNFα neutralization in VS secretions partially prevented hair cell loss due to the secretions. Taken together, we have identified a new mechanism responsible for SNHL due to VSs.

  15. Secreted Factors from Human Vestibular Schwannomas Can Cause Cochlear Damage.

    PubMed

    Dilwali, Sonam; Landegger, Lukas D; Soares, Vitor Y R; Deschler, Daniel G; Stankovic, Konstantina M

    2015-01-01

    Vestibular schwannomas (VSs) are the most common tumours of the cerebellopontine angle. Ninety-five percent of people with VS present with sensorineural hearing loss (SNHL); the mechanism of this SNHL is currently unknown. To establish the first model to study the role of VS-secreted factors in causing SNHL, murine cochlear explant cultures were treated with human tumour secretions from thirteen different unilateral, sporadic VSs of subjects demonstrating varied degrees of ipsilateral SNHL. The extent of cochlear explant damage due to secretion application roughly correlated with the subjects' degree of SNHL. Secretions from tumours associated with most substantial SNHL resulted in most significant hair cell loss and neuronal fibre disorganization. Secretions from VSs associated with good hearing or from healthy human nerves led to either no effect or solely fibre disorganization. Our results are the first to demonstrate that secreted factors from VSs can lead to cochlear damage. Further, we identified tumour necrosis factor alpha (TNFα) as an ototoxic molecule and fibroblast growth factor 2 (FGF2) as an otoprotective molecule in VS secretions. Antibody-mediated TNFα neutralization in VS secretions partially prevented hair cell loss due to the secretions. Taken together, we have identified a new mechanism responsible for SNHL due to VSs. PMID:26690506

  16. The gene structure of human anti-haemophilic factor IX.

    PubMed

    Anson, D S; Choo, K H; Rees, D J; Giannelli, F; Gould, K; Huddleston, J A; Brownlee, G G

    1984-05-01

    The mRNA sequence of the human intrinsic clotting factor IX (Christmas factor) has been completed and is 2802 residues long, including a 29 residue long 5' non-coding and a 1390 residue long 3' non-coding region, but excluding the poly(A) tail. The factor IX gene is approximately 34 kb long and we define, by the sequencing of 5280 residues, the presumed promoter region, all eight exons, and some intron and flanking sequence. Introns account for 92% of the gene length and the longest is estimated to be 10 100 residues. Exons conform roughly to previously designated protein regions, but the catalytic region of the protein is coded by two separate exons. This differs from the arrangement in the other characterized serine protease genes which are further subdivided in this region.

  17. Significance of respirasomes for the assembly/stability of human respiratory chain complex I.

    PubMed

    Schägger, Hermann; de Coo, René; Bauer, Matthias F; Hofmann, Sabine; Godinot, Catherine; Brandt, Ulrich

    2004-08-27

    We showed that the human respiratory chain is organized in supramolecular assemblies of respiratory chain complexes, the respirasomes. The mitochondrial complexes I (NADH dehydrogenase) and III (cytochrome c reductase) form a stable core respirasome to which complex IV (cytochrome c oxidase) can also bind. An analysis of the state of respirasomes in patients with an isolated deficiency of single complexes provided evidence that the formation of respirasomes is essential for the assembly/stability of complex I, the major entry point of respiratory chain substrates. Genetic alterations leading to a loss of complex III prevented respirasome formation and led to the secondary loss of complex I. Therefore, primary complex III assembly deficiencies presented as combined complex III/I defects. This dependence of complex I assembly/stability on respirasome formation has important implications for the diagnosis of mitochondrial respiratory chain disorders.

  18. Complexity analysis of human physiological signals based on case studies

    NASA Astrophysics Data System (ADS)

    Angelova, Maia; Holloway, Philip; Ellis, Jason

    2015-04-01

    This work focuses on methods for investigation of physiological time series based on complexity analysis. It is a part of a wider programme to determine non-invasive markers for healthy ageing. We consider two case studies investigated with actigraphy: (a) sleep and alternations with insomnia, and (b) ageing effects on mobility patterns. We illustrate, using these case studies, the application of fractal analysis to the investigation of regulation patterns and control, and change of physiological function. In the first case study, fractal analysis techniques were implemented to study the correlations present in sleep actigraphy for individuals suffering from acute insomnia in comparison with healthy controls. The aim was to investigate if complexity analysis can detect the onset of adverse health-related events. The subjects with acute insomnia displayed significantly higher levels of complexity, possibly a result of too much activity in the underlying regulatory systems. The second case study considered mobility patterns during night time and their variations with age. It showed that complexity metrics can identify change in physiological function with ageing. Both studies demonstrated that complexity analysis can be used to investigate markers of health, disease and healthy ageing.

  19. MTO1-deficient mouse model mirrors the human phenotype showing complex I defect and cardiomyopathy.

    PubMed

    Becker, Lore; Kling, Eva; Schiller, Evelyn; Zeh, Ramona; Schrewe, Anja; Hölter, Sabine M; Mossbrugger, Ilona; Calzada-Wack, Julia; Strecker, Valentina; Wittig, Ilka; Dumitru, Iulia; Wenz, Tina; Bender, Andreas; Aichler, Michaela; Janik, Dirk; Neff, Frauke; Walch, Axel; Quintanilla-Fend, Leticia; Floss, Thomas; Bekeredjian, Raffi; Gailus-Durner, Valérie; Fuchs, Helmut; Wurst, Wolfgang; Meitinger, Thomas; Prokisch, Holger; de Angelis, Martin Hrabě; Klopstock, Thomas

    2014-01-01

    Recently, mutations in the mitochondrial translation optimization factor 1 gene (MTO1) were identified as causative in children with hypertrophic cardiomyopathy, lactic acidosis and respiratory chain defect. Here, we describe an MTO1-deficient mouse model generated by gene trap mutagenesis that mirrors the human phenotype remarkably well. As in patients, the most prominent signs and symptoms were cardiovascular and included bradycardia and cardiomyopathy. In addition, the mutant mice showed a marked worsening of arrhythmias during induction and reversal of anaesthesia. The detailed morphological and biochemical workup of murine hearts indicated that the myocardial damage was due to complex I deficiency and mitochondrial dysfunction. In contrast, neurological examination was largely normal in Mto1-deficient mice. A translational consequence of this mouse model may be to caution against anaesthesia-related cardiac arrhythmias which may be fatal in patients.

  20. Structure of human enterovirus 71 in complex with a capsid-binding inhibitor

    PubMed Central

    Plevka, Pavel; Perera, Rushika; Yap, Moh Lan; Cardosa, Jane; Kuhn, Richard J.; Rossmann, Michael G.

    2013-01-01

    Human enterovirus 71 is a picornavirus causing hand, foot, and mouth disease that may progress to fatal encephalitis in infants and small children. As of now, no cure is available for enterovirus 71 infections. Small molecule inhibitors binding into a hydrophobic pocket within capsid viral protein 1 were previously shown to effectively limit infectivity of many picornaviruses. Here we report a 3.2-Å-resolution X-ray structure of the enterovirus 71 virion complexed with the capsid-binding inhibitor WIN 51711. The inhibitor replaced the natural pocket factor within the viral protein 1 pocket without inducing any detectable rearrangements in the structure of the capsid. Furthermore, we show that the compound stabilizes enterovirus 71 virions and limits its infectivity, probably through restricting dynamics of the capsid necessary for genome release. Thus, our results provide a structural basis for development of antienterovirus 71 capsid-binding drugs. PMID:23509286

  1. Genetic complexity of the human surfactant-associated proteins SP-A1 and SP-A2

    PubMed Central

    Silveyra, Patricia; Floros, Joanna

    2012-01-01

    Pulmonary surfactant protein A (SP-A) plays a key role in innate lung host defense, in surfactant-related functions, and in parturition. In the course of evolution, the genetic complexity of SP-A has increased, particularly in the regulatory regions (i.e. promoter, untranslated regions). Although most species have a single SP-A gene, two genes encode SP-A in humans and primates (SFTPA1and SFTPA2). This may account for the multiple functions attributed to human SP-A, as well as the regulatory complexity of its expression by a relatively diverse set of protein and non-protein cellular factors. The interplay between enhancer cis-acting DNA sequences and trans-acting proteins that recognize these DNA elements is essential for gene regulation, primarily at the transcription initiation level. Furthermore, regulation at the mRNA level is essential to ensure proper physiological levels of SP-A under different conditions. To date, numerous studies have shown significant complexity of the regulation of SP-A expression at different levels, including transcription, splicing, mRNA decay, and translation. A number of trans-acting factors have also been described to play a role in the control of SP-A expression. The aim of this report is to describe the genetic complexity of the SFTPA1 and SFTPA2 genes, as well as to review regulatory mechanisms that control SP-A expression in humans and other animal species. PMID:23069847

  2. Consensus Genome-Wide Expression Quantitative Trait Loci and Their Relationship with Human Complex Trait Disease.

    PubMed

    Yu, Chen-Hsin; Pal, Lipika R; Moult, John

    2016-07-01

    Most of the risk loci identified from genome-wide association (GWA) studies do not provide direct information on the biological basis of a disease or on the underlying mechanisms. Recent expression quantitative trait locus (eQTL) association studies have provided information on genetic factors associated with gene expression variation. These eQTLs might contribute to phenotype diversity and disease susceptibility, but interpretation is handicapped by low reproducibility of the expression results. To address this issue, we have generated a set of consensus eQTLs by integrating publicly available data for specific human populations and cell types. Overall, we find over 4000 genes that are involved in high-confidence eQTL relationships. To elucidate the role that eQTLs play in human common diseases, we matched the high-confidence eQTLs to a set of 335 disease risk loci identified from the Wellcome Trust Case Control Consortium GWA study and follow-up studies for 7 human complex trait diseases-bipolar disorder (BD), coronary artery disease (CAD), Crohn's disease (CD), hypertension (HT), rheumatoid arthritis (RA), type 1 diabetes (T1D), and type 2 diabetes (T2D). The results show that the data are consistent with ∼50% of these disease loci arising from an underlying expression change mechanism. PMID:27428252

  3. A Human Factors Analysis of EVA Time Requirements

    NASA Technical Reports Server (NTRS)

    Pate, Dennis W.

    1997-01-01

    Human Factors Engineering (HFE) is a discipline whose goal is to engineer a safer, more efficient interface between humans and machines. HFE makes use of a wide range of tools and techniques to fulfill this goal. One of these tools is known as motion and time study, a technique used to develop time standards for given tasks. During the summer of 1995, a human factors motion and time study was initiated with the goals of developing a database of EVA task times and developing a method of utilizing the database to predict how long an EVA should take. Initial development relied on the EVA activities performed during the STS-61 (Hubble) mission. The first step of the study was to become familiar with EVA's, the previous task-time studies, and documents produced on EVA's. After reviewing these documents, an initial set of task primitives and task-time modifiers was developed. Data was collected from videotaped footage of two entire STS-61 EVA missions and portions of several others, each with two EVA astronauts. Feedback from the analysis of the data was used to further refine the primitives and modifiers used. The project was continued during the summer of 1996, during which data on human errors was also collected and analyzed. Additional data from the STS-71 mission was also collected. Analysis of variance techniques for categorical data was used to determine which factors may affect the primitive times and how much of an effect they have. Probability distributions for the various task were also generated. Further analysis of the modifiers and interactions is planned.

  4. Human Factors Lessons Learned on the International Space Station

    NASA Technical Reports Server (NTRS)

    Woolford, Barbara; Mount, Frances E.

    2006-01-01

    Experience on International Space Station (ISS) provides many important lessons for future space flight. NASA human factors engineers have been systematically collecting lessons learned from crew debriefs, as well as working with ground support teams to continuously improve crew operations. This paper describes the methods for collecting data from debriefs, lessons learned through that process, and an example of a technology development task funded through the Space Human Factors Engineering (SHFE) program element in response to an identified operational need. Each ISS increment crew spends many hours after the flight answering questions from the various subsystem leads. The Flight Crew Integration subsystem lead asks questions specific to human factors and habitability issues. In addition, crew comments on many other subsystems provide insight into interface designs, operability and maintainability. The debrief comments are unique to each crew, and must be categorized to provide operational lessons learned. Personal identifiers are removed and comments aggregated to separate consistent issues from personal preferences. Examples will be given, and the procedure for incorporating the lessons into requirements and guidelines for the next human space vehicle will be described. In flight, very few astronauts are medical doctors. Written medical procedures during flight need to be easy to follow and quick to understand. The problem was analyzed as part of a SHFE task. Organization was analyzed and reorganizations were created and tested. Results will be reported. The ISS is a very important analog for planning future long-term missions. Collection of data from debriefs, studying the lessons learned and focusing on requirements for future missions are examples of the accomplishments through the SHFE program.

  5. Does human cognition allow Human Factors (HF) certification of advanced aircrew systems?

    NASA Technical Reports Server (NTRS)

    Macleod, Iain S.; Taylor, Robert M.

    1994-01-01

    This paper has examined the requirements of HF specification and certification within advanced or complex aircrew systems. It suggests reasons for current inadequacies in the use of HF in the design process, giving some examples in support, and suggesting an avenue towards the improvement of the HF certification process. The importance of human cognition to the operation and performance of advanced aircrew systems has been stressed. Many of the shortfalls of advanced aircrew systems must be attributed to over automated designs that show little consideration on either the mental limits or the cognitive capabilities of the human system component. Traditional approaches to system design and HF certification are set within an over physicalistic foundation. Also, traditionally it was assumed that physicalistic system functions could be attributed to either the human or the machine on a one to one basis. Moreover, any problems associated with the parallel needs, or promoting human understanding alongside system operation and direction, were generally equated in reality by the natural flexibility and adaptability of human skills. The consideration of the human component of a complex system is seen as being primarily based on manifestations of human behavior to the almost total exclusion of any appreciation of unobservable human mental and cognitive processes. The argument of this paper is that the considered functionality of any complex human-machine system must contain functions that are purely human and purely cognitive. Human-machine system reliability ultimately depends on human reliability and dependability and, therefore, on the form and frequency of cognitive processes that have to be conducted to support system performance. The greater the demand placed by an advanced aircraft system on the human component's basic knowledge processes or cognition, rather than on skill, the more insiduous the effects the human may have on that system. This paper discusses one

  6. Involvement of Polycomb Repressive Complex 2 in Maturation of Induced Pluripotent Stem Cells during Reprogramming of Mouse and Human Fibroblasts.

    PubMed

    Khazaie, Niusha; Massumi, Mohammad; Wee, Ping; Salimi, Mahdieh; Mohammadnia, Abdulshakour; Yaqubi, Moein

    2016-01-01

    Induced pluripotent stem cells (iPSCs) provide a reliable source for the study of regenerative medicine, drug discovery, and developmental biology. Despite extensive studies on the reprogramming of mouse and human fibroblasts into iPSCs, the efficiency of reprogramming is still low. Here, we used a bioinformatics and systems biology approach to study the two gene regulatory waves governing the reprogramming of mouse and human fibroblasts into iPSCs. Our results revealed that the maturation phase of reprogramming was regulated by a more complex regulatory network of transcription factors compared to the initiation phase. Interestingly, in addition to pluripotency factors, the polycomb repressive complex 2 (PRC2) members Ezh2, Eed, Jarid2, Mtf2, and Suz12 are crucially recruited during the maturation phase of reprogramming. Moreover, we found that during the maturation phase of reprogramming, pluripotency factors, via the expression and induction of PRC2 complex members, could silence the lineage-specific gene expression program and maintain a ground state of pluripotency in human and mouse naïve iPSCs. The findings obtained here provide us a better understanding of the gene regulatory network (GRN) that governs reprogramming, and the maintenance of the naïve state of iPSCs.

  7. Involvement of Polycomb Repressive Complex 2 in Maturation of Induced Pluripotent Stem Cells during Reprogramming of Mouse and Human Fibroblasts

    PubMed Central

    Khazaie, Niusha; Massumi, Mohammad; Wee, Ping; Salimi, Mahdieh; Mohammadnia, Abdulshakour; Yaqubi, Moein

    2016-01-01

    Induced pluripotent stem cells (iPSCs) provide a reliable source for the study of regenerative medicine, drug discovery, and developmental biology. Despite extensive studies on the reprogramming of mouse and human fibroblasts into iPSCs, the efficiency of reprogramming is still low. Here, we used a bioinformatics and systems biology approach to study the two gene regulatory waves governing the reprogramming of mouse and human fibroblasts into iPSCs. Our results revealed that the maturation phase of reprogramming was regulated by a more complex regulatory network of transcription factors compared to the initiation phase. Interestingly, in addition to pluripotency factors, the polycomb repressive complex 2 (PRC2) members Ezh2, Eed, Jarid2, Mtf2, and Suz12 are crucially recruited during the maturation phase of reprogramming. Moreover, we found that during the maturation phase of reprogramming, pluripotency factors, via the expression and induction of PRC2 complex members, could silence the lineage-specific gene expression program and maintain a ground state of pluripotency in human and mouse naïve iPSCs. The findings obtained here provide us a better understanding of the gene regulatory network (GRN) that governs reprogramming, and the maintenance of the naïve state of iPSCs. PMID:26938987

  8. Complex assembly, crystallization and preliminary X-ray crystallographic analysis of the human Rod–Zwilch–ZW10 (RZZ) complex

    SciTech Connect

    Altenfeld, Anika; Wohlgemuth, Sabine; Wehenkel, Annemarie; Musacchio, Andrea

    2015-03-20

    The 800 kDa complex of the human Rod, Zwilch and ZW10 proteins (the RZZ complex) was reconstituted in insect cells, purified, crystallized and subjected to preliminary X-ray diffraction analysis. The spindle-assembly checkpoint (SAC) monitors kinetochore–microtubule attachment during mitosis. In metazoans, the three-subunit Rod–Zwilch–ZW10 (RZZ) complex is a crucial SAC component that interacts with additional SAC-activating and SAC-silencing components, including the Mad1–Mad2 complex and cytoplasmic dynein. The RZZ complex contains two copies of each subunit and has a predicted molecular mass of ∼800 kDa. Given the low abundance of the RZZ complex in natural sources, its recombinant reconstitution was attempted by co-expression of its subunits in insect cells. The RZZ complex was purified to homogeneity and subjected to systematic crystallization attempts. Initial crystals containing the entire RZZ complex were obtained using the sitting-drop method and were subjected to optimization to improve the diffraction resolution limit. The crystals belonged to space group P3{sub 1} (No. 144) or P3{sub 2} (No. 145), with unit-cell parameters a = b = 215.45, c = 458.7 Å, α = β = 90.0, γ = 120.0°.

  9. Complexity of Human Circulation Design: Tips for Students

    ERIC Educational Resources Information Center

    Kurbel, Sven; Gros, Mario; Maric, Svjetlana

    2009-01-01

    Medical students are faced with a challenge to comprehend the enormous complexity of the circulatory systems. There is a gap between courses of anatomy, with detailed description of all normally present macroscopic vessels, and histology, which is focused on microscopic tissue architecture. Both courses leave arterioles, capillaries, and venules…

  10. Human Factors in Training - Space Medicine Proficiency Training

    NASA Technical Reports Server (NTRS)

    Connell, Erin; Arsintescu, Lucia

    2009-01-01

    The early Constellation space missions are expected to have medical capabilities very similar to those currently on the Space Shuttle and International Space Station (ISS). For Crew Exploration Vehicle (CEV) missions to ISS, medical equipment will be located on ISS, and carried into CEV in the event of an emergency. Flight Surgeons (FS) on the ground in Mission Control will be expected to direct the Crew Medical Officer (CMO) during medical situations. If there is a loss of signal and the crew is unable to communicate with the ground, a CMO would be expected to carry out medical procedures without the aid of a FS. In these situations, performance support tools can be used to reduce errors and time to perform emergency medical tasks. Work on medical training has been conducted in collaboration with the Medical Training Group at the Space Life Sciences Directorate and with Wyle Lab which provides medical training to crew members, Biomedical Engineers (BMEs), and to flight surgeons under the JSC Space Life Sciences Directorate s Bioastronautics contract. The space medical training work is part of the Human Factors in Training Directed Research Project (DRP) of the Space Human Factors Engineering (SHFE) Project under the Space Human Factors and Habitability (SHFH) Element of the Human Research Program (HRP). Human factors researchers at Johnson Space Center have recently investigated medical performance support tools for CMOs on-orbit, and FSs on the ground, and researchers at the Ames Research Center performed a literature review on medical errors. The work proposed for FY10 continues to build on this strong collaboration with the Space Medical Training Group and previous research. This abstract focuses on two areas of work involving Performance Support Tools for Space Medical Operations. One area of research building on activities from FY08, involved the feasibility of just-in-time (JIT) training techniques and concepts for real-time medical procedures. In Phase 1

  11. Human Factors in Training - Space Flight Resource Management Training

    NASA Technical Reports Server (NTRS)

    Bryne, Vicky; Connell, Erin; Barshi, Immanuel; Arsintescu, L.

    2009-01-01

    . Work on SFRM training has been conducted in collaboration with the Expedition Vehicle Division at the Mission Operations Directorate (MOD) and with United Space Alliance (USA) which provides training to Flight Controllers. The space flight resource management training work is part of the Human Factors in Training Directed Research Project (DRP) of the Space Human Factors Engineering (SHFE) Project under the Space Human Factors and Habitability (SHFH) Element of the Human Research Program (HRP). Human factors researchers at the Ames Research Center have been investigating team work and distributed decision making processes to develop a generic SFRM training framework for flight controllers. The work proposed for FY10 continues to build on this strong collaboration with MOD and the USA Training Group as well as previous research in relevant domains such as aviation. In FY10, the work focuses on documenting and analyzing problem solving strategies and decision making processes used in MCC by experienced FCers.

  12. Epidermal growth factor receptor in adult human dorsal root ganglia.

    PubMed

    Huerta, J J; Diaz-Trelles, R; Naves, F J; Llamosas, M M; Del Valle, M E; Vega, J A

    1996-09-01

    Transforming growth factor-alpha (TGFalpha) enhances neuronal survival and neurite outgrowth in cultured dorsal root ganglia (DRG) sensory neurons. It binds a membrane protein, denominated epidermal growth factor receptor (EGFr). EGFr has been localized in developing and adult human DRG. However, it remains to be elucidated whether all DRG neurons express EGFr or whether differences exist among neuronal subtypes. This study was undertaken to investigate these topics in adult human DRG using immunoblotting, and combined immunohistochemistry and image analysis techniques. A mouse monoclonal antibody (clone F4) mapping within the intracytoplasmic domain of EGFr was used. Immunoblotting revealed two main proteins with estimated molecular masses of approximately/equal to 65 kDa and 170 kDa, and thus consistent with the full-length EGFr. Additional protein bands were also encountered. Light immunohistochemistry revealed specific immunoreactivity (IR) for EGFr-like proteins in most (86%) primary sensory neurons, the intensity of immunostaining being stronger in the small- and intermediate-sized ones. Furthermore, EGFr-like IR was also observed in the satellite glial cells of the ganglia as well as in the intraganglionic and dorsal root Schwann cells. Taken together, our findings demonstrate that EGFr, and other related proteins containing the epitope labeled with the antibody F4, are responsible for the EGFr IR reported in DRG. Furthermore, we demonstrated heterogeneity in the expression of EGFr-like IR in adult human primary sensory neurons, which suggests different responsiveness to their ligands.

  13. Towards a sustainable world through human factors and ergonomics: it is all about values.

    PubMed

    Lange-Morales, Karen; Thatcher, Andrew; García-Acosta, Gabriel

    2014-01-01

    In this paper, we analyse two approaches that attempt to address how a human factors and ergonomics (HFE) perspective can contribute to the sustainability of the human race. We outline the principles, purposes and fields of application of ergoecology and green ergonomics, and thereafter deal with their context of emergence, and the overlaps in purpose, and principles. Shared values are deduced and related to socio-technical principles for systems' design. Social responsibility and environmental/ecospheric responsibility are the leading threads of ergoecology and green ergonomics, giving rise to the values of: respect for human rights, respect for the Earth, respect for ethical decision-making, appreciation of complexity, respect for transparency and openness, and respect for diversity. We discuss the consequences of considering these values in HFE theory and practice.

  14. Accommodating complexity and human behaviors in decision analysis.

    SciTech Connect

    Backus, George A.; Siirola, John Daniel; Schoenwald, David Alan; Strip, David R.; Hirsch, Gary B.; Bastian, Mark S.; Braithwaite, Karl R.; Homer, Jack

    2007-11-01

    This is the final report for a LDRD effort to address human behavior in decision support systems. One sister LDRD effort reports the extension of this work to include actual human choices and additional simulation analyses. Another provides the background for this effort and the programmatic directions for future work. This specific effort considered the feasibility of five aspects of model development required for analysis viability. To avoid the use of classified information, healthcare decisions and the system embedding them became the illustrative example for assessment.

  15. New polymorphic variants of human blood clotting factor IX

    SciTech Connect

    Surin, V.L.; Luk`yanenko, A.V.; Tagiev, A.F.; Smirnova, O.V.; Plutalov, O.V.; Berlin, Yu.A.

    1995-04-01

    The polymorphism of Alu-repeats, which are located in the introns of the human factor IX gene (copies 1-3), was studied. To identify polymorphic variants, direct sequencing of PCR products that contained appropriate repeats was used. In each case, 20 unrelated X chromosomes were studied. A polymorphic Dra I site was found near the 3{prime}-end of Alu copy 3 within the region of the polyA tract. A PCR-based testing system with internal control of restriction hydrolysis was suggested. Testing 81 unrelated X chromosomes revealed that the frequency of the polymorphic Dra I site is 0.23. Taq I polymorphism, which was revealed in Alu copy 4 of factor IX gene in our previous work, was found to be closely linked to Dra I polymorphism. Studies in linkage between different types of polymorphisms of the factor IX gene revealed the presence of a rare polymorphism in intron a that was located within the same minisatellite region as the known polymorphic insertion 50 bp/Dde I. However, the size of the insertion in our case was 26 bp. Only one polymorphic variant was found among over 150 unrelated X chromosomes derived from humans from Moscow and its vicinity. 10 refs., 4 figs., 1 tab.

  16. Human colon-derived soluble factors modulate gut microbiota composition.

    PubMed

    Hevia, Arancha; Bernardo, David; Montalvillo, Enrique; Al-Hassi, Hafid O; Fernández-Salazar, Luis; Garrote, Jose A; Milani, Christian; Ventura, Marco; Arranz, Eduardo; Knight, Stella C; Margolles, Abelardo; Sánchez, Borja

    2015-01-01

    The commensal microbiota modulates immunological and metabolic aspects of the intestinal mucosa contributing to development of human gut diseases including inflammatory bowel disease. The host/microbiota interaction often referred to as a crosstalk, mainly focuses on the effect of the microbiota on the host neglecting effects that the host could elicit on the commensals. Colonic microenvironments from three human healthy controls (obtained from the proximal and distal colon, both in resting conditions and after immune - IL-15- and microbiota - LPS-in vitro challenges) were used to condition a stable fecal population. Subsequent 16S rRNA gene-based analyses were performed to study the effect induced by the host on the microbiota composition and function. Non-supervised principal component analysis (PCA) showed that all microbiotas, which had been conditioned with colonic microenvironments clustered together in terms of relative microbial composition, suggesting that soluble factors were modulating a stable fecal population independently from the treatment or the origin. Our findings confirmed that the host intestinal microenvironment has the capacity to modulate the gut microbiota composition via yet unidentified soluble factors. These findings indicate that an appropriate understanding of the factors of the host mucosal microenvironment affecting microbiota composition and function could improve therapeutic manipulation of the microbiota composition. PMID:25918688

  17. Human Colon-Derived Soluble Factors Modulate Gut Microbiota Composition

    PubMed Central

    Hevia, Arancha; Bernardo, David; Montalvillo, Enrique; Al-Hassi, Hafid O.; Fernández-Salazar, Luis; Garrote, Jose A.; Milani, Christian; Ventura, Marco; Arranz, Eduardo; Knight, Stella C.; Margolles, Abelardo; Sánchez, Borja

    2015-01-01

    The commensal microbiota modulates immunological and metabolic aspects of the intestinal mucosa contributing to development of human gut diseases including inflammatory bowel disease. The host/microbiota interaction often referred to as a crosstalk, mainly focuses on the effect of the microbiota on the host neglecting effects that the host could elicit on the commensals. Colonic microenvironments from three human healthy controls (obtained from the proximal and distal colon, both in resting conditions and after immune – IL-15- and microbiota – LPS-in vitro challenges) were used to condition a stable fecal population. Subsequent 16S rRNA gene-based analyses were performed to study the effect induced by the host on the microbiota composition and function. Non-supervised principal component analysis (PCA) showed that all microbiotas, which had been conditioned with colonic microenvironments clustered together in terms of relative microbial composition, suggesting that soluble factors were modulating a stable fecal population independently from the treatment or the origin. Our findings confirmed that the host intestinal microenvironment has the capacity to modulate the gut microbiota composition via yet unidentified soluble factors. These findings indicate that an appropriate understanding of the factors of the host mucosal microenvironment affecting microbiota composition and function could improve therapeutic manipulation of the microbiota composition. PMID:25918688

  18. Human colon-derived soluble factors modulate gut microbiota composition.

    PubMed

    Hevia, Arancha; Bernardo, David; Montalvillo, Enrique; Al-Hassi, Hafid O; Fernández-Salazar, Luis; Garrote, Jose A; Milani, Christian; Ventura, Marco; Arranz, Eduardo; Knight, Stella C; Margolles, Abelardo; Sánchez, Borja

    2015-01-01

    The commensal microbiota modulates immunological and metabolic aspects of the intestinal mucosa contributing to development of human gut diseases including inflammatory bowel disease. The host/microbiota interaction often referred to as a crosstalk, mainly focuses on the effect of the microbiota on the host neglecting effects that the host could elicit on the commensals. Colonic microenvironments from three human healthy controls (obtained from the proximal and distal colon, both in resting conditions and after immune - IL-15- and microbiota - LPS-in vitro challenges) were used to condition a stable fecal population. Subsequent 16S rRNA gene-based analyses were performed to study the effect induced by the host on the microbiota composition and function. Non-supervised principal component analysis (PCA) showed that all microbiotas, which had been conditioned with colonic microenvironments clustered together in terms of relative microbial composition, suggesting that soluble factors were modulating a stable fecal population independently from the treatment or the origin. Our findings confirmed that the host intestinal microenvironment has the capacity to modulate the gut microbiota composition via yet unidentified soluble factors. These findings indicate that an appropriate understanding of the factors of the host mucosal microenvironment affecting microbiota composition and function could improve therapeutic manipulation of the microbiota composition.

  19. Identifying Human Factors Issues in Aircraft Maintenance Operations

    NASA Technical Reports Server (NTRS)

    Veinott, Elizabeth S.; Kanki, Barbara G.; Shafto, Michael G. (Technical Monitor)

    1995-01-01

    Maintenance operations incidents submitted to the Aviation Safety Reporting System (ASRS) between 1986-1992 were systematically analyzed in order to identify issues relevant to human factors and crew coordination. This exploratory analysis involved 95 ASRS reports which represented a wide range of maintenance incidents. The reports were coded and analyzed according to the type of error (e.g, wrong part, procedural error, non-procedural error), contributing factors (e.g., individual, within-team, cross-team, procedure, tools), result of the error (e.g., aircraft damage or not) as well as the operational impact (e.g., aircraft flown to destination, air return, delay at gate). The main findings indicate that procedural errors were most common (48.4%) and that individual and team actions contributed to the errors in more than 50% of the cases. As for operational results, most errors were either corrected after landing at the destination (51.6%) or required the flight crew to stop enroute (29.5%). Interactions among these variables are also discussed. This analysis is a first step toward developing a taxonomy of crew coordination problems in maintenance. By understanding what variables are important and how they are interrelated, we may develop intervention strategies that are better tailored to the human factor issues involved.

  20. Crystallization and biochemical characterization of the human spliceosomal Aar2-Prp8(RNaseH) complex.

    PubMed

    Santos, Karine; Preussner, Marco; Heroven, Anna Christina; Weber, Gert

    2015-11-01

    In eukaryotes, the removal of nuclear noncoding sequences (pre-mRNA splicing) is catalyzed by the spliceosome, which consists of five ribonucleoprotein particles (U1, U2, U4, U5 and U6 snRNPs, each with a respective snRNA) and a plethora of protein factors that aid spliceosomal maturation, assembly, activation and disassembly. Recently, the U5 snRNP maturation factor Aar2p from baker's yeast has been characterized structurally and biochemically. Aar2p binds to the RNaseH (RH) and Jab1/MPN domains of the highly conserved U5-specific Prp8p, which forms a framework for the spliceosomal catalytic centre. Thereby, Aar2p sterically excludes Brr2p, a helicase essential for the catalytic activation of the spliceosome, from Prp8p binding. At the same time, Aar2p blocks U4/U6 di-snRNA binding to Prp8p. Aar2p therefore prevents premature spliceosome activation and its functions are regulated by reversible phosphorylation. To date, little is known about the hypothetical human Aar2 (hsAar2) orthologue C20ORF4. This study identifies C20ORF4 (i) as part of the HeLa proteome by Western blotting and (ii) as a true Aar2 orthologue which binds to the RH domain (hsRH) of Prp8 and corroborates an evolutionary link between yeast and human Aar2 function. An elaborate strategy was devised to crystallize hsAar2 in complex with hsRH. The analysis of initial weakly diffracting crystals obtained by in situ proteolysis and homology modelling guided the design of an hsAar2 construct in which an internal loop was replaced by three serines (hsAar2(Δloop)). A complex of hsAar2(Δloop) and hsRH crystallized in space group C2; the crystals diffracted to 2.35 Å resolution and were suitable for structure determination by molecular-replacement approaches. The study presented here suggests a connection between Aar2 and the spliceosome in human cells and paves the way for structural studies of human Aar2. PMID:26527271