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Sample records for factor complex human

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. Human transforming growth factor. beta. -. cap alpha. /sub 2/-macroglobulin complex is a latent form of transforming growth factor. beta

    SciTech Connect

    Huang, S.S.; O'Grady, P.; Huang, J.S.

    1987-05-01

    Human platelet-derived transforming growth factor ..beta.. (TGF..beta..) has been shown to be present as a high molecular weight latent form in human serum. Appearance of transforming growth factor activity, along with the change from high molecular weight form to low molecular weight form, was observed following treatment of the latent form of TGF..beta.. with acid or urea, suggesting that the latent form of TGF..beta.. is a complex of TGF..beta.. and a high molecular weight binding protein. Human ..cap alpha../sub 2/-M has been found to be a plasma binding protein for platelet-derived growth factor (PDGF) in serum or plasma. TGF..beta.. and PDGF share similar properties. They, therefore, investigated the interaction between /sup 125/I-TGF..beta.. and ..cap alpha../sub 2/M. /sup 125/I-TGF..beta.. and purified human ..cap alpha../sub 2/M formed a complex as demonstrated by polyacrylamide gel electrophoresis. Most of the /sup 125/I-TGF..beta..-..cap alpha../sub 2/M complex could be dissociated by acid or urea treatment. These results suggest that ..cap alpha../sub 2/M is a binding protein for TGF..beta.. and that TGF..beta..-..cap alpha../sub 2/M complex may be the latent form of TGF..beta.. in serum.

  6. 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.

  7. Clinical heterogeneity of human neurocysticercosis results from complex interactions among parasite, host and environmental factors.

    PubMed

    Fleury, Agnès; Escobar, Alfonso; Fragoso, Gladis; Sciutto, Edda; Larralde, Carlos

    2010-04-01

    Human neurocysticercosis (NC) is endemic in most countries of Latin America, Asia and Africa and is re-emerging in some industrialized nations. Both within and among endemic countries, NC is very variable in its clinical and radiological features, as well as in the intensity of the immuno-inflammatory reactions of the hosts. This review, focusing on the Mexican experience, describes and interprets the heterogeneity of NC as the result of different combinations among factors associated with the parasite, host and environment. The review may serve to foster similar descriptive efforts in other endemic areas of the world in order to facilitate the identification of the distinct factors that participate in the complex pathogenesis and diverse clinical outcomes of NC. In particular, it is necessary to understand the precise physiopathology of the inflammatory reaction associated with NC, as inflammation is one of the characteristics of those NC cases that are clinically more severe and less responsive to current treatments. Devising new medical interventions through the use of molecular regulators of the innate and adaptive immune responses of the host is a largely unexplored approach that could improve the existing forms of treatment.

  8. 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.

  9. Latent physiological factors of complex human diseases revealed by independent component analysis of clinarrays

    PubMed Central

    2010-01-01

    Background Diagnosis and treatment of patients in the clinical setting is often driven by known symptomatic factors that distinguish one particular condition from another. Treatment based on noticeable symptoms, however, is limited to the types of clinical biomarkers collected, and is prone to overlooking dysfunctions in physiological factors not easily evident to medical practitioners. We used a vector-based representation of patient clinical biomarkers, or clinarrays, to search for latent physiological factors that underlie human diseases directly from clinical laboratory data. Knowledge of these factors could be used to improve assessment of disease severity and help to refine strategies for diagnosis and monitoring disease progression. Results Applying Independent Component Analysis on clinarrays built from patient laboratory measurements revealed both known and novel concomitant physiological factors for asthma, types 1 and 2 diabetes, cystic fibrosis, and Duchenne muscular dystrophy. Serum sodium was found to be the most significant factor for both type 1 and type 2 diabetes, and was also significant in asthma. TSH3, a measure of thyroid function, and blood urea nitrogen, indicative of kidney function, were factors unique to type 1 diabetes respective to type 2 diabetes. Platelet count was significant across all the diseases analyzed. Conclusions The results demonstrate that large-scale analyses of clinical biomarkers using unsupervised methods can offer novel insights into the pathophysiological basis of human disease, and suggest novel clinical utility of established laboratory measurements. PMID:21044362

  10. 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.

  11. Introduction to human factors.

    PubMed

    Bergman, Eric

    2012-03-01

    This paper provides an introduction to "human factors engineering," an applied science that seeks to optimize usability and safety of systems. Human factors engineering pursues this goal by aligning system design with the perceptual, cognitive, and physical capabilities of users. Human factors issues loom large in the diabetes management domain because patients and health care professionals interact with a complex variety of systems, including medical device hardware and software, which are themselves embedded within larger systems of institutions, people, and processes. Usability considerations must be addressed in these systems and devices to ensure safe and effective diabetes management.

  12. Analysis of human factors case studies of complex military systems: surely we can do better

    NASA Astrophysics Data System (ADS)

    Hutchins, Susan G.

    2000-11-01

    People in nearly ever occupational setting can provide examples of poor system design. The focus for this paper is on an analysis of design problems found in complex military command and control systems and the ways in which these types of problems can be avoided in future system design. The source of data for this analysis was a group of case studies of sixteen U.S. military systems written by officer-students at the Naval Postgraduate School, Monterey, CA. Systems analyzed span the four military services and include aircraft systems, communications systems, the M-16 rifle, a missile defense system, a message processing system, weapon systems, and decision support systems. Documented problems with system use were categorized according to the following measures of effectiveness: Performance, Safety, Usability, Reliability, Maintainability, Time and Cost to Train, and Workload. The number of problems encountered per system ranged from one to nine; the mean number of reported problems per system was 4.9 IEEE 1220-1998 includes a revised systems engineering approach with an increased emphasis on engineering the system for the human. Adhering to a user-centered design approach should have a positive impact on system design by significantly reducing the types of system problems described in this paper.

  13. 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.

  14. 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.

  15. PTP1B Dephosphorylates N-Ethylmaleimide-sensitive Factor and Elicits SNARE Complex Disassembly during Human Sperm Exocytosis*

    PubMed Central

    Zarelli, Valeria E. P.; Ruete, Maria C.; Roggero, Carlos M.; Mayorga, Luis S.; Tomes, Claudia N.

    2009-01-01

    The reversible phosphorylation of tyrosyl residues in proteins is a cornerstone of the signaling pathways that regulate numerous cellular responses. Protein tyrosine phosphorylation is controlled through the concerted actions of protein-tyrosine kinases and phosphatases. The goal of the present study was to unveil the mechanisms by which protein tyrosine dephosphorylation modulates secretion. The acrosome reaction, a specialized type of regulated exocytosis undergone by sperm, is initiated by calcium and carried out by a number of players, including tyrosine kinases and phosphatases, and fusion-related proteins such as Rab3A, α-SNAP, N-ethylmaleimide-sensitive factor (NSF), SNAREs, complexin, and synaptotagmin VI. We report here that inducers were unable to elicit the acrosome reaction when permeabilized human sperm were loaded with anti-PTP1B antibodies or with the dominant-negative mutant PTP1B D181A; subsequent introduction of wild type PTP1B or NSF rescued exocytosis. Wild type PTP1B, but not PTP1B D181A, caused cis SNARE complex dissociation during the acrosome reaction through a mechanism involving NSF. Unlike its non-phosphorylated counterpart, recombinant phospho-NSF failed to dissociate SNARE complexes from rat brain membranes. These results strengthen our previous observation that NSF activity is regulated rather than constitutive during sperm exocytosis and indicate that NSF must be dephosphorylated by PTP1B to disassemble SNARE complexes. Interestingly, phospho-NSF served as a substrate for PTP1B in an in vitro assay. Our findings demonstrate that phosphorylation of NSF on tyrosine residues prevents its SNARE complex dissociation activity and establish for the first time a role for PTP1B in the modulation of the membrane fusion machinery. PMID:19208619

  16. Mapping the human translation elongation factor eEF1H complex using the yeast two-hybrid system.

    PubMed Central

    Mansilla, Francisco; Friis, Irene; Jadidi, Mandana; Nielsen, Karen M; Clark, Brian F C; Knudsen, Charlotte R

    2002-01-01

    In eukaryotes, the eukaryotic translation elongation factor eEF1A responsible for transporting amino-acylated tRNA to the ribosome forms a higher-order complex, eEF1H, with its guanine-nucleotide-exchange factor eEF1B. In metazoans, eEF1B consists of three subunits: eEF1B alpha, eEF1B eta and eEF1B gamma. The first two subunits possess the nucleotide-exchange activity, whereas the role of the last remains poorly defined. In mammals, two active tissue-specific isoforms of eEF1A have been identified. The reason for this pattern of differential expression is unknown. Several models on the basis of in vitro experiments have been proposed for the macromolecular organization of the eEF1H complex. However, these models differ in various aspects. This might be due to the difficulties of handling, particularly the eEF1B beta and eEF1B gamma subunits in vitro. Here, the human eEF1H complex is for the first time mapped using the yeast two-hybrid system, which is a powerful in vivo technique for analysing protein-protein interactions. The following complexes were observed: eEF1A1:eEF1B alpha, eEF1A1:eEF1B beta, eEF1B beta:eEF1B beta, eEF1B alpha:eEF1B gamma, eEF1B beta:eEF1B gamma and eEF1B alpha:eEF1B gamma:eEF1B beta, where the last was observed using a three-hybrid approach. Surprisingly, eEF1A2 showed no or only little affinity for the guanine-nucleotide-exchange factors. Truncated versions of the subunits of eEF1B were used to orientate these subunits within the resulting model. The model unit is a pentamer composed of two molecules of eEF1A, each interacting with either eEF1B alpha or eEF1B beta held together by eEF1B gamma. These units can dimerize via eEF1B beta. Our model is compared with other models, and structural as well as functional aspects of the model are discussed. PMID:11985494

  17. 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.

  18. 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)

  19. Trigramin: Primary structure and its inhibition of von Willebrand factor binding to glycoprotein IIb/IIIa complex on human platelets

    SciTech Connect

    Huang, Turfu; Holt, J.C.; Kirby, E.P.; Niewiarowski, S.

    1989-01-24

    Trigramin, a naturally occurring peptide purified from Trimeresurus gramineus snake venom, inhibits platelet aggregation and the binding of {sup 125}I-fibrinogen to ADP-stimulated platelets without affecting the platelet-release reaction. {sup 125}I-trigramin binds to ADP-stimulated and to chymotrypsin-treated normal platelets but not to thrombasthenic platelets. {sup 125}I-trigramin binding to platelets is blocked by monoclonal antibodies directed against the glycoprotein IIb/IIIa complex and by Arg-Gly-Asp-Ser (RGDS). The authors determined the primary structure of trigramin, which is composed of a single polypeptide chain of 72 amino acid residues and six disulfide bridges. The molecular weight of trigramin calculated on the basis of amino acid sequence was 7500, and the average pI was 5.61. An RGD sequence appeared in the carboxy-terminal domain of trigramin. An amino-terminal fragment (7-33) of trigramin showed 39% homology with a region (1555-1581) of von Willebrand factor (vWF). Trigramin also showed 36% identity in a 42 amino acid overlap and 53% identity in a 15 amino acid overlap when compared with two adhesive proteins, collagen {alpha}{sub 1} (I) and laminin B{sub 1}, respectively. Trigramin blocked binding of human vWF to the glycoprotein IIb/IIIa complex in thrombin-activated platelets in a dose-dependent manner. In conclusion, the data suggest that the biological activity of trigramin may depend upon the presence of an RGD sequence, the secondary structure of the molecule, and perhaps some other sequences that it shares with adhesive proteins.

  20. 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.

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

    DOE PAGES

    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

  2. Structure of the Human Factor VIII C2 Domain in Complex with the 3E6 Inhibitory Antibody.

    PubMed

    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. 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.

  3. Recombinant human hepatocyte growth factor (HGF), but not rat HGF, elicits glomerular injury and albuminuria in normal rats via an immune complex-dependent mechanism.

    PubMed

    Mizuno, Shinya; Ikebuchi, Fumie; Fukuta, Kazuhiro; Kato, Takashi; Matsumoto, Kunio; Adachi, Kiichi; Abe, Tetsushi; Nakamura, Toshikazu

    2011-03-01

    1. Hepatocyte growth factor (HGF) has the therapeutic potential to improve renal fibrosis and proteinuria in rodents with chronic kidney disease. In contrast, long-term administration of human HGF to normal rats reportedly elicits proteinuria. Thus, the role of HGF during proteinuria remains contentious. The aim of the present study was to demonstrate that human HGF is antigenic to rodents and that immune complex formation causes proteinuria. 2. We administered either human or rat HGF to normal rats for 28 days. Albuminuria was evaluated by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The renal phenotypes of the two HGF treatments were examined using histological techniques. 3. Administration of human HGF (1 mg/kg per day, i.v.) to rats led to severe albuminuria and glomerular hypertrophy in association with increased blood levels of anti-human HGF IgG and IgG deposition in mesangial areas. Furthermore, an immune complex between human HGF and anti-human HGF IgG stimulated the production of proteinuric cytokines (including transforming growth factor-β) in rat cultured mesangial cells. In contrast, treatment of healthy rats with rat HGF for 4 weeks caused neither mesangial IgG deposition nor elevated anti-HGF IgG in the blood. Overall, rat HGF did not provoke albuminuria. 4. We conclude that human HGF produces pseudotoxic effects in normal rat kidneys via an immune complex-mediated pathway, whereas syngenic HGF is safe due to less deposition of glomerular IgG. Our results affirm the safety of the repeated use of syngenic HGF for the treatment of chronic organ diseases, such as renal fibrosis and liver cirrhosis.

  4. 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.

  5. Mixed real/complex factorization

    SciTech Connect

    Lima, L.T.G. . Dept. of Electrical Engineering); Martines, N.; Pinto, H.J.C.P. . Centro de Pesquisas de Energia Electrica)

    1993-02-01

    This paper describes a mixed real/complex sparse matrix factorization and solution scheme applied to a large matrix problem. Large system eigenanalysis and frequency domain methods will directly benefit from the proposed scheme, which can reduce both memory and CPU time requirements when compared to conventional complex-only solutions. The application in hand is the small signal electromechanical stability analysis of large power systems. The savings obtained are significant considering the CPU intensive nature of these matrix problems.

  6. 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)

  7. 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

  8. 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.

  9. 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.

  10. Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex.

    PubMed

    Cao, Qing-Fu; Yamamoto, Junichi; Isobe, Tomoyasu; Tateno, Shumpei; Murase, Yuki; Chen, Yexi; Handa, Hiroshi; Yamaguchi, Yuki

    2015-10-01

    Restores TBP function 1 (Rtf1) is generally considered to be a subunit of the Paf1 complex (PAF1C), a multifunctional protein complex involved in histone modification and transcriptional or posttranscriptional regulation. Rtf1, however, is not stably associated with the PAF1C in most species except Saccharomyces cerevisiae, and its biochemical functions are not well understood. Here, we show that human Rtf1 is a transcription elongation factor that may function independently of the PAF1C. Rtf1 requires "Rtf1 coactivator" activity, which is most likely unrelated to the PAF1C or DSIF, for transcriptional activation in vitro. A mutational study revealed that the Plus3 domain of human Rtf1 is critical for its coactivator-dependent function. Transcriptome sequencing (RNA-seq) and chromatin immunoprecipitation studies in HeLa cells showed that Rtf1 and the PAF1C play distinct roles in regulating the expression of a subset of genes. Moreover, contrary to the finding in S. cerevisiae, the PAF1C was apparently recruited to the genes examined in an Rtf1-independent manner. The present study establishes a role for human Rtf1 as a transcription elongation factor and highlights the similarities and differences between the S. cerevisiae and human Rtf1 proteins.

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

    PubMed Central

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

    1978-01-01

    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

  12. Transcriptional activation of human CYP17 in H295R adrenocortical cells depends on complex formation among p54(nrb)/NonO, protein-associated splicing factor, and SF-1, a complex that also participates in repression of transcription.

    PubMed

    Sewer, Marion B; Nguyen, Viet Q; Huang, Ching-Jung; Tucker, Philip W; Kagawa, Norio; Waterman, Michael R

    2002-04-01

    The first 57 bp upstream of the transcription initiation site of the human CYP17 (hCYP17) gene are essential for both basal and cAMP-dependent transcription. EMSA carried out by incubating H295R adrenocortical cell nuclear extracts with radiolabeled -57/-38 probe from the hCYP17 promoter showed the formation of three DNA-protein complexes. The fastest complex contained steroidogenic factor (SF-1) and p54(nrb)/NonO, the intermediate complex contained p54(nrb)/NonO and polypyrimidine tract-binding protein-associated splicing factor (PSF), and the slowest complex contained an SF-1/PSF/p54(nrb)/NonO complex. (Bu)(2)cAMP treatment resulted in a cAMP-inducible increase in the binding intensity of only the upper complex and also activated hCYP17 gene transcription. SF-1 coimmunoprecipitated with p54(nrb)/NonO, indicating direct interaction between these proteins. Functional assays revealed that PSF represses basal transcription. Further, the repression of hCYP17 promoter-reporter construct luciferase activity resulted from PSF interacting with the corepressor mSin3A. Trichostatin A attenuated the inhibition of basal transcription, suggesting that a histone deacetylase interacts with the SF-1/PSF/p54(nrb)/NonO/mSin3A complex. Our studies lend support to the idea that the balance between transcriptional activation and repression is essential in the control of adrenocortical steroid hormone biosynthesis.

  13. 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.

  14. 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

  15. 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.

  16. Disorder in Complex Human System

    NASA Astrophysics Data System (ADS)

    Akdeniz, K. Gediz

    2011-11-01

    Since the world of human and whose life becomes more and more complex every day because of the digital technology and under the storm of knowledge (media, internet, governmental and non-governmental organizations, etc...) the simulation is rapidly growing in the social systems and in human behaviors. The formation of the body and mutual interactions are left to digital technological, communication mechanisms and coding the techno genetics of the body. Deconstruction begins everywhere. The linear simulation mechanism with modern realities are replaced by the disorder simulation of human behaviors with awareness realities. In this paper I would like to introduce simulation theory of "Disorder Sensitive Human Behaviors". I recently proposed this theory to critique the role of disorder human behaviors in social systems. In this theory the principle of realty is the chaotic awareness of the complexity of human systems inside of principle of modern thinking in Baudrillard's simulation theory. Proper examples will be also considered to investigate the theory.

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. A computational modeling and molecular dynamics study of the Michaelis complex of human protein Z-dependent protease inhibitor (ZPI) and factor Xa (FXa)

    PubMed Central

    Chandrasekaran, Vasudevan; Lee, Chang Jun; Lin, Ping; Duke, Robert E.

    2009-01-01

    Protein Z-dependent protease inhibitor (ZPI) and antithrombin III (AT3) are members of the serpin superfamily of protease inhibitors that inhibit factor Xa (FXa) and other proteases in the coagulation pathway. While experimental structural information is available for the interaction of AT3 with FXa, at present there is no structural data regarding the interaction of ZPI with FXa, and the precise role of this interaction in the blood coagulation pathway is poorly understood. In an effort to gain a structural understanding of this system, we have built a solvent equilibrated three-dimensional structural model of the Michaelis complex of human ZPI/FXa using homology modeling, protein–protein docking and molecular dynamics simulation methods. Preliminary analysis of interactions at the complex interface from our simulations suggests that the interactions of the reactive center loop (RCL) and the exosite surface of ZPI with FXa are similar to those observed from X-ray crystal structure-based simulations of AT3/FXa. However, detailed comparison of our modeled structure of ZPI/FXa with that of AT3/FXa points to differences in interaction specificity at the reactive center and in the stability of the inhibitory complex, due to the presence of a tyrosine residue at the P1 position in ZPI, instead of the P1 arginine residue in AT3. The modeled structure also shows specific structural differences between AT3 and ZPI in the heparin-binding and flexible N-terminal tail regions. Our structural model of ZPI/FXa is also compatible with available experimental information regarding the importance for the inhibitory action of certain basic residues in FXa. PMID:19172319

  3. 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.

  4. 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

  5. Research Needs for Human Factors.

    ERIC Educational Resources Information Center

    Army Research Inst. for the Behavioral and Social Sciences, Arlington, VA.

    Human factors engineering can be defined as the application of scientific principles, methods, and data drawn from a variety of disciplines to the development of engineering systems in which people play a significant role. Since human factors issues arise in every domain in which humans interact with the products of a technological society, six…

  6. 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.

  7. 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.

  8. Human granulocyte-macrophage colony-stimulating factor DNA cationic-lipid complexed autologous tumour cell vaccination in the treatment of canine B-cell multicentric lymphoma.

    PubMed

    Turek, M M; Thamm, D H; Mitzey, A; Kurzman, I D; Huelsmeyer, M K; Dubielzig, R R; Vail, D M

    2007-12-01

    This study describes the development of an human granulocyte-macrophage colony-stimulating factor DNA cationic-lipid complexed autologous tumour cell vaccine (hGM-CSF CLDC ATCV) and its implementation, following a chemotherapy treatment protocol, in a randomized, placebo-controlled, double-blinded clinical trial in pet dogs with naturally occurring lymphoma. We hypothesized that the use of this vaccine would result in an antitumour immune response leading to improved first remission duration and overall survival in dogs with B-cell lymphoma when compared with chemotherapy alone. Immune stimulation generated by hGM-CSF CLDC ATCV was assessed by means of surrogate in vivo analysis (delayed-type hypersensitivity [DTH]) as well as an ex vivo cellular assay (lymphocyte proliferation assay). The vaccine approach considered in the current report did not result in clinically improved outcomes. A small measure of immunomodulation was documented by DTH and several modifications to the approach are suggested. This report illustrates the feasibility of clinical trials with vaccine strategies using companion animals with non-Hodgkin's lymphoma.

  9. An analysis of some factors determining the sporozoite rates, human blood indexes, and biting rates of members of the Anopheles punctulatus complex in Papua New Guinea.

    PubMed

    Burkot, T R; Dye, C; Graves, P M

    1989-03-01

    The degree to which Anopheles punctulatus complex members feed on humans in different Papua New Guinea villages has a significant effect on sporozoite rates. Among villages, the human blood index (HBI) of the members of the complex varied with the average number of persons sharing a bednet. Although dogs are the preferred hosts by the 3 malaria vector species, the number of dogs did not significantly affect the HBI. The HBI was dependent upon the human-biting rate, implying increased avoidance of anophelines by people relative to other hosts at times of greater mosquito numbers. Human-biting rates and HBIs were also influenced by the distribution of alternative hosts relative to people.

  10. 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

  11. Human factors in visualization research.

    PubMed

    Tory, Melanie; Möller, Torsten

    2004-01-01

    Visualization can provide valuable assistance for data analysis and decision making tasks. However, how people perceive and interact with a visualization tool can strongly influence their understanding of the data as well as the system's usefulness. Human factors therefore contribute significantly to the visualization process and should play an important role in the design and evaluation of visualization tools. Several research initiatives have begun to explore human factors in visualization, particularly in perception-based design. Nonetheless, visualization work involving human factors is in its infancy, and many potentially promising areas have yet to be explored. Therefore, this paper aims to 1) review known methodology for doing human factors research, with specific emphasis on visualization, 2) review current human factors research in visualization to provide a basis for future investigation, and 3) identify promising areas for future research.

  12. 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.

  13. Research Needs for Human Factors

    DTIC Science & Technology

    1983-01-01

    Research Note 83-07 RESEARCH NEEDS FOR HUMAN FACTORS Conmmittee on Human Factors Cot ittee on Behavioral and Social Sciences and Education National... Research Council IIJanuary 1983 i ~ Approvted for Dublit rellease; distribution unlimited. __ A N- This report, as submitted by the contractor, has...CATALOG NUMBE -- Research Note 83-07 A2{>/)/.2 ? ___ 4. TITLE (e 5110) S. TyPE of REPORT & PERIOD COVERED Renearch Needs for Human Facotrs S. PERFORMING

  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. 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.

  17. Human factors simulation in construction management education

    NASA Astrophysics Data System (ADS)

    Jaeger, M.; Adair, D.

    2010-06-01

    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 be taught effectively? Although simulations are applied in construction management education, they have not incorporated human factors sufficiently. The focus on human factors as part of the simulation of construction management situations increases students' learning effectiveness within a cross-cultural teaching setting. This paper shows the development of discrete-event human factors in construction management simulation. A description of the source code is given. Learning effectiveness in a cross-cultural education setting was analysed by evaluating data obtained through student questionnaire surveys. The mean score obtained by the students using the simulator was 32% better than those not exposed to the simulator. The spread of results was noticeably greater for the students not exposed to the simulator. The human factors simulation provides an effective means to teach students the complexities and dynamics of interpersonal relationships in construction management.

  18. Human Factors in CAI Design.

    ERIC Educational Resources Information Center

    Rambally, Gerard K.; Rambally, Rodney S.

    1987-01-01

    Identifies human factor issues involved in the student-computer interface in computer assisted instruction and makes specific recommendations for screen design. Factors considered include simplicity, spaciousness, relevance, standardization, changing display screen contents, color coding, shape and size coding, and brightness coding. (Author/LRW)

  19. The LINC complex and human disease.

    PubMed

    Meinke, Peter; Nguyen, Thuy Duong; Wehnert, Manfred S

    2011-12-01

    The LINC (linker of nucleoskeleton and cytoskeleton) complex is a proposed mechanical link tethering the nucleo- and cyto-skeleton via the NE (nuclear envelope). The LINC components emerin, lamin A/C, SUN1, SUN2, nesprin-1 and nesprin-2 interact with each other at the NE and also with other binding partners including actin filaments and B-type lamins. Besides the mechanostructural functions, the LINC complex is also involved in signalling pathways and gene regulation. Emerin was the first LINC component associated with a human disease, namely EDMD (Emery-Dreifuss muscular dystrophy). Later on, other components of the LINC complex, such as lamins A/C and small isoforms of nesprin-1 and nesprin-2, were found to be associated with EDMD, reflecting a genetic heterogeneity that has not been resolved so far. Only approximately 46% of the EDMD patients can be linked to genes of LINC and non-LINC components, pointing to further genes involved in the pathology of EDMD. Obvious candidates are the LINC proteins SUN1 and SUN2. Recently, screening of binding partners of LINC components as candidates identified LUMA (TMEM43), encoding a binding partner of emerin and lamins, as a gene involved in atypical EDMD. Nevertheless, such mutations contribute only to a very small fraction of EDMD patients. EDMD-causing mutations in STA/EMD (encoding emerin) that disrupt emerin binding to Btf (Bcl-2-associated transcription factor), GCL (germ cell-less) and BAF (barrier to autointegration factor) provide the first glimpses into LINC being involved in gene regulation and thus opening new avenues for functional studies. Thus the association of LINC with human disease provides tools for understanding its functions within the cell.

  20. Human Factors in Aircraft Maintenance

    DTIC Science & Technology

    2001-03-01

    significant effect on the design of new systems but it can also mitigate problems found in the sub-optimal designs of current systems. 2. Human Factors...and parts 3. Airplane design and configuration 4. Job and task 5. Technical knowledge and skills 6. Factors affecting individual performance-e.g...software failures (e.g. documentation design ) were found. Note that there are typically multiple latent failures for each hazard pattern, so that

  1. New Anthocyanin-Human Salivary Protein Complexes.

    PubMed

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

    2015-08-04

    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.

  2. 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.

  3. 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...

  4. 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

  5. Mammalian testis-determining factor SRY and the enigma of inherited human sex reversal: frustrated induced fit in a bent protein-DNA complex.

    PubMed

    Phillips, Nelson B; Racca, Joseph; Chen, Yen-Shan; Singh, Rupinder; Jancso-Radek, Agnes; Radek, James T; Wickramasinghe, Nalinda P; Haas, Elisha; Weiss, Michael A

    2011-10-21

    Mammalian testis-determining factor SRY contains a high mobility group box, a conserved eukaryotic motif of DNA bending. Mutations in SRY cause XY gonadal dysgenesis and somatic sex reversal. Although such mutations usually arise de novo in spermatogenesis, some are inherited and so specify male development in one genetic background (the father) but not another (the daughter). Here, we describe the biophysical properties of a representative inherited mutation, V60L, within the minor wing of the L-shaped domain (box position 5). Although the stability and DNA binding properties of the mutant domain are similar to those of wild type, studies of SRY-induced DNA bending by subnanosecond time-resolved fluorescence resonance energy transfer (FRET) revealed enhanced conformational fluctuations leading to long range variation in bend angle. (1)H NMR studies of the variant protein-DNA complex demonstrated only local perturbations near the mutation site. Because the minor wing of SRY folds on DNA binding, the inherited mutation presumably hinders induced fit. Stopped-flow FRET studies indicated that such frustrated packing leads to accelerated dissociation of the bent complex. Studies of SRY-directed transcriptional regulation in an embryonic gonadal cell line demonstrated partial activation of downstream target Sox9. Our results have demonstrated a nonlocal coupling between DNA-directed protein folding and protein-directed DNA bending. Perturbation of this coupling is associated with a genetic switch poised at the threshold of activity.

  6. Core-binding factor β increases the affinity between human Cullin 5 and HIV-1 Vif within an E3 ligase complex.

    PubMed

    Salter, Jason D; Lippa, Geoffrey M; Belashov, Ivan A; Wedekind, Joseph E

    2012-11-06

    HIV-1 Vif masquerades as a receptor for a cellular E3 ligase harboring Elongin B, Elongin C, and Cullin 5 (EloB/C/Cul5) proteins that facilitate degradation of the antiretroviral factor APOBEC3G (A3G). This Vif-mediated activity requires human core-binding factor β (CBFβ) in contrast to cellular substrate receptors. We observed calorimetrically that Cul5 binds tighter to full-length Vif((1-192))/EloB/C/CBFβ (K(d) = 5 ± 2 nM) than to Vif((95-192))/EloB/C (K(d) = 327 ± 40 nM), which cannot bind CBFβ. A comparison of heat capacity changes supports a model in which CBFβ prestabilizes Vif((1-192)) relative to Vif((95-192)), consistent with a stronger interaction of Cul5 with Vif's C-terminal Zn(2+)-binding motif. An additional interface between Cul5 and an N-terminal region of Vif appears to be plausible, which has therapeutic design implications.

  7. 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

  8. 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).

  9. 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).

  10. 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.

  11. 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.

  12. Human DNA Ligase I Interacts with and Is Targeted for Degradation by the DCAF7 Specificity Factor of the Cul4-DDB1 Ubiquitin Ligase Complex.

    PubMed

    Peng, Zhimin; Liao, Zhongping; Matsumoto, Yoshihiro; Yang, Austin; Tomkinson, Alan E

    2016-10-14

    The synthesis, processing, and joining of Okazaki fragments during DNA replication is complex, requiring the sequential action of a large number of proteins. Proliferating cell nuclear antigen, a DNA sliding clamp, interacts with and coordinates the activity of several DNA replication proteins, including the enzymes flap endonuclease 1 (FEN-1) and DNA ligase I that complete the processing and joining of Okazaki fragments, respectively. Although it is evident that maintaining the appropriate relative stoichiometry of FEN-1 and DNA ligase I, which compete for binding to proliferating cell nuclear antigen, is critical to prevent genomic instability, little is known about how the steady state levels of DNA replication proteins are regulated, in particular the proteolytic mechanisms involved in their turnover. Because DNA ligase I has been reported to be ubiquitylated, we used a proteomic approach to map ubiquitylation sites and screen for DNA ligase I-associated E3 ubiquitin ligases. We identified three ubiquitylated lysine residues and showed that DNA ligase I interacts with and is targeted for ubiquitylation by DCAF7, a specificity factor for the Cul4-DDB1 complex. Notably, knockdown of DCAF7 reduced the degradation of DNA ligase I in response to inhibition of proliferation and replacement of ubiquitylated lysine residues reduced the in vitro ubiquitylation of DNA ligase I by Cul4-DDB1 and DCAF7. In contrast, a different E3 ubiquitin ligase regulates FEN-1 turnover. Thus, although the expression of many of the genes encoding DNA replication proteins is coordinately regulated, our studies reveal that different mechanisms are involved in the turnover of these proteins.

  13. Human factors in contingency operations.

    PubMed

    Mercer, Simon J; Khan, M A; Scott, T; Matthews, J J; Henning, Dcw; Stapley, S

    2016-06-10

    The UK Defence Medical Services are currently supporting contingency operations following a period of intensive activity in relatively mature trauma systems in Iraq and Afghanistan. Among the key lessons identified, human factors or non-technical skills played an important role in the improvement of patient care. This article describes the importance of human factors on Role 2 Afloat, one of the Royal Navy's maritime contingency capabilities, and illustrates how they are vital to ensuring that correct decisions are made for patient care in a timely manner. Teamwork and communication are particularly important to ensure that limited resources such as blood products and other consumables are best used and that patients are evacuated promptly, allowing the facility to accept further casualties and therefore maintain operational capability. These ideas may be transferred to any small specialist team given a particular role to perform.

  14. Human factors in incident reporting

    NASA Technical Reports Server (NTRS)

    Jones, S. G.

    1993-01-01

    The paper proposes a cooperative research effort be undertaken by academic institutions and industry organizations toward the compilation of a human factors data base in conjunction with technical information. Team members in any discipline can benefit and learn from observing positive examples of decision making and performance by crews under stressful or less than optimal circumstances. The opportunity to note trends in interpersonal and interactive behaviors and to categorize them is terms of more or less desirable outcomes should not be missed.

  15. 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

  16. 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...

  17. 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...

  18. Human factors training for aviation personnel.

    PubMed

    Johnston, A N; Maurino, D E

    1990-05-01

    The authors examine the reasons for new human factors training requirements contained in the ICAO circular 227-AN/136, Training of Operational Personnel in Human Factors. The circular, produced by the ICAO Flight Safety and Human Factors Study Group, includes a philosophical approach, a conceptual approach, and a model of software, hardware, environment, and liveware or the human element (SHEL model). Guidelines for human factors training, curriculum development, and trainee performance appraisal are included.

  19. 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.

  20. Human immune responses to major human cytomegalovirus glycoprotein complexes.

    PubMed Central

    Liu, Y N; Kari, B; Gehrz, R C

    1988-01-01

    Sera from both human cytomegalovirus (HCMV)-seropositive adults and infants with congenital HCMV infection recognized two major HCMV glycoprotein complexes. However, proliferative responses of peripheral blood mononuclear cells to these complexes varied among seropositive adults and were not detected in any of the infants. Thus, these glycoproteins alone may not be sufficient to develop a subviral HCMV vaccine. Images PMID:2828655

  1. The Chromatin Assembly Factor Complex 1 (CAF1) and 5-Azacytidine (5-AzaC) Affect Cell Motility in Src-transformed Human Epithelial Cells*

    PubMed Central

    Endo, Akinori; Ly, Tony; Pippa, Raffaella; Bensaddek, Dalila; Nicolas, Armel; Lamond, Angus I.

    2017-01-01

    Tumor invasion into surrounding stromal tissue is a hallmark of high grade, metastatic cancers. Oncogenic transformation of human epithelial cells in culture can be triggered by activation of v-Src kinase, resulting in increased cell motility, invasiveness, and tumorigenicity and provides a valuable model for studying how changes in gene expression cause cancer phenotypes. Here, we show that epithelial cells transformed by activated Src show increased levels of DNA methylation and that the methylation inhibitor 5-azacytidine (5-AzaC) potently blocks the increased cell motility and invasiveness induced by Src activation. A proteomic screen for chromatin regulators acting downstream of activated Src identified the replication-dependent histone chaperone CAF1 as an important factor for Src-mediated increased cell motility and invasion. We show that Src causes a 5-AzaC-sensitive decrease in both mRNA and protein levels of the p150 (CHAF1A) and p60 (CHAF1B), subunits of CAF1. Depletion of CAF1 in untransformed epithelial cells using siRNA was sufficient to recapitulate the increased motility and invasive phenotypes characteristic of transformed cells without activation of Src. Maintaining high levels of CAF1 by exogenous expression suppressed the increased cell motility and invasiveness phenotypes when Src was activated. These data identify a critical role of CAF1 in the dysregulation of cell invasion and motility phenotypes seen in transformed cells and also highlight an important role for epigenetic remodeling through DNA methylation for Src-mediated induction of cancer phenotypes. PMID:27872192

  2. 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.

  3. Architecture of human translation initiation factor 3.

    PubMed

    Querol-Audi, Jordi; Sun, Chaomin; Vogan, Jacob M; Smith, M Duane; Gu, Yu; Cate, Jamie H D; Nogales, Eva

    2013-06-04

    Eukaryotic translation initiation factor 3 (eIF3) plays a central role in protein synthesis by organizing the formation of the 43S preinitiation complex. Using genetic tag visualization by electron microscopy, we reveal the molecular organization of ten human eIF3 subunits, including an octameric core. The structure of eIF3 bears a close resemblance to that of the proteasome lid, with a conserved spatial organization of eight core subunits containing PCI and MPN domains that coordinate functional interactions in both complexes. We further show that eIF3 subunits a and c interact with initiation factors eIF1 and eIF1A, which control the stringency of start codon selection. Finally, we find that subunit j, which modulates messenger RNA interactions with the small ribosomal subunit, makes multiple independent interactions with the eIF3 octameric core. These results highlight the conserved architecture of eIF3 and how it scaffolds key factors that control translation initiation in higher eukaryotes, including humans.

  4. Human Factors Engineering Standards at NASA

    NASA Technical Reports Server (NTRS)

    Russo, Dane; Tillman, Barry; Pickett, Lynn

    2008-01-01

    NASA has begun a new approach to human factors design standards. For years NASA-STD-3000, Manned Systems Integration Standards, has been a source of human factors design guidance for space systems. In order to better meet the needs of the system developers, NASA is revising its human factors standards system. NASA-STD-3000 will be replaced by two documents: set of broad human systems design standards (including both human factors and medical topics) and a human factors design handbook. At the present time the standards document is in final review with some disagreement on several critical issues. The handbook is progressing with November 2008 as the anticipated completion date.

  5. 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.

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. Characterization of the human GARP (Golgi associated retrograde protein) complex

    SciTech Connect

    Liewen, Heike; Meinhold-Heerlein, Ivo; Oliveira, Vasco; Schwarzenbacher, Robert; Luo Guorong; Wadle, Andreas; Jung, Martin; Pfreundschuh, Michael; Stenner-Liewen, Frank . E-mail: stenlie@t-online.de

    2005-05-15

    The Golgi associated retrograde protein complex (GARP) or Vps fifty-three (VFT) complex is part of cellular inter-compartmental transport systems. Here we report the identification of the VFT tethering factor complex and its interactions in mammalian cells. Subcellular fractionation shows that human Vps proteins are found in the smooth membrane/Golgi fraction but not in the cytosol. Immunostaining of human Vps proteins displays a vesicular distribution most concentrated at the perinuclear envelope. Co-staining experiments with endosomal markers imply an endosomal origin of these vesicles. Significant accumulation of VFT complex positive endosomes is found in the vicinity of the Trans Golgi Network area. This is in accordance with a putative role in Golgi associated transport processes. In Saccharomyces cerevisiae, GARP is the main effector of the small GTPase Ypt6p and interacts with the SNARE Tlg1p to facilitate membrane fusion. Accordingly, the human homologue of Ypt6p, Rab6, specifically binds hVps52. In human cells, the 'orphan' SNARE Syntaxin 10 is the genuine binding partner of GARP mediated by hVps52. This reveals a previously unknown function of human Syntaxin 10 in membrane docking and fusion events at the Golgi. Taken together, GARP shows significant conservation between various species but diversification and specialization result in important differences in human cells.

  12. 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).

  13. 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

  14. 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?

  15. 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 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION LICENSING HUMAN SPACE FLIGHT REQUIREMENTS Launch and Reentry with Crew § 460.15 Human factors....

  16. 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 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION LICENSING HUMAN SPACE FLIGHT REQUIREMENTS Launch and Reentry with Crew § 460.15 Human factors....

  17. 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 Aeronautics and Space COMMERCIAL SPACE TRANSPORTATION, FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION LICENSING HUMAN SPACE FLIGHT REQUIREMENTS Launch and Reentry with Crew § 460.15 Human factors....

  18. 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.

  19. 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.

  20. Mitochondrial network complexity and pathological decrease in complex I activity are tightly correlated in isolated human complex I deficiency.

    PubMed

    Koopman, Werner J H; Visch, Henk-Jan; Verkaart, Sjoerd; van den Heuvel, Lambertus W P J; Smeitink, Jan A M; Willems, Peter H G M

    2005-10-01

    Complex I (NADH:ubiquinone oxidoreductase) is the largest multisubunit assembly of the oxidative phosphorylation system, and its malfunction is associated with a wide variety of clinical syndromes ranging from highly progressive, often early lethal, encephalopathies to neurodegenerative disorders in adult life. The changes in mitochondrial structure and function that are at the basis of the clinical symptoms are poorly understood. Video-rate confocal microscopy of cells pulse-loaded with mitochondria-specific rhodamine 123 followed by automated analysis of form factor (combined measure of length and degree of branching), aspect ratio (measure of length), and number of revealed marked differences between primary cultures of skin fibroblasts from 13 patients with an isolated complex I deficiency. These differences were independent of the affected subunit, but plotting of the activity of complex I, normalized to that of complex IV, against the ratio of either form factor or aspect ratio to number revealed a linear relationship. Relatively small reductions in activity appeared to be associated with an increase in form factor and never with a decrease in number, whereas relatively large reductions occurred in association with a decrease in form factor and/or an increase in number. These results demonstrate that complex I activity and mitochondrial structure are tightly coupled in human isolated complex I deficiency. To further prove the relationship between aberrations in mitochondrial morphology and pathological condition, fibroblasts from two patients with a different mutation but a highly fragmented mitochondrial phenotype were fused. Full restoration of the mitochondrial network demonstrated that this change in mitochondrial morphology was indeed associated with human complex I deficiency.

  1. Human Factors Plan for Maritime Safety

    DTIC Science & Technology

    1993-02-01

    HUMAN FACTORS ISSUES IN THE MARITIME ENVIRONMENT .............. 13 2. 1 DEFINITION OF HUMAN FACTORS ISSUES ........................ 13 2.2 CONTENT...The dotted line around the human factors technical basis in Figure 1 signifies that it needs to be developed. Safety data Accidents ) Definition of...and activity surveys, but met with some resistance from the ship personnel, and so little quntitative data was available from this study. Subjective

  2. Factors determining nestedness in complex networks.

    PubMed

    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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Human Modeling For Ground Processing Human Factors Engineering Analysis

    NASA Technical Reports Server (NTRS)

    Tran, Donald; Stambolian, Damon; Henderson, Gena; Barth, Tim

    2011-01-01

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

  9. 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

  10. 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…

  11. 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…

  12. 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.

  13. 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

  14. Human factors considerations for contraindication alerts.

    PubMed

    van der Sijs, Heleen; Baboe, Imtiaaz; Phansalkar, Shobha

    2013-01-01

    Alert fatigue is a ubiquitous problem in clinical decision support systems. Several remedies to alert fatigue have been proposed including improving the specificity of alerts and compliance with human factors principles. Human factors principles that are relevant for drug safety alerting have been identified and operationalized for drug-drug interactions (DDIs), resulting in a previously developed and validated quantitative instrument. Such an instrument is lacking for contraindications. This study describes the operationalization of human factors principles for contraindication alerting. Thirty items associated with 10 human factors principles are included in the instrument: 4 items are new, 5 are similar, and 21 are equal to the DDI-instrument. The instrument was further operationalized to a test protocol. Three independent persons used the test protocol. Inter-rater reliability indicated moderate agreement (κ=0.540) It is feasible to test the implementation of human factors in contraindication alert design with the newly developed instrument.

  15. Coding Human Factors Observations in Surgery.

    PubMed

    Cohen, Tara N; Wiegmann, Douglas A; Reeves, Scott T; Boquet, Albert J; Shappell, Scott A

    2016-10-25

    The reliability of the Human Factors Analysis and Classification System (HFACS) for classifying retrospective observational human factors data in the cardiovascular operating room is examined. Three trained analysts independently used HFACS to categorize observational human factors data collected at a teaching and nonteaching hospital system. Results revealed that the framework was substantially reliable overall (Study I: k = 0.635; Study II: k = 0.642). Reliability increased when only preconditions for unsafe acts were investigated (Study I: k =0.660; Study II: k = 0.726). Preconditions for unsafe acts were the most commonly identified issues, with HFACS categories being similarly populated across both hospitals. HFACS is a reliable tool for systematically categorizing observational data of human factors issues in the operating room. Findings have implications for the development of a HFACS tool for proactively collecting observational human factors data, eliminating the necessity for classification post hoc.

  16. TNO Human Factors - The Netherlands

    DTIC Science & Technology

    2005-12-01

    making in naval command and control. SCI-129 Symposium on ‘Critical Design Issues for the Human- Machine Interface ’, Prague, Czech Republic, 19-21...System Interaction (Environnements virtuels dinteraction Homme -Système Intuitive)., The original document contains color images. 14. ABSTRACT 15...to develop and test new concepts of team organisation, human- system task integration and intelligent interfaces for efficient and effective command

  17. Space operations and the human factor.

    PubMed

    Brody, A R

    1993-10-01

    The effects of human error on aviation and space flight are discussed and the role of human factor engineering in aviation and aerospace safety is examined. Specific areas discussed are docking and extravehicular activity; quantification of human capacity for space station design; and measurement of habitability, workload, and task analysis.

  18. 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.

  19. 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.

  20. An Argument for the Use of Chaos Theory To Map the Complexity of Human Communication.

    ERIC Educational Resources Information Center

    Keaten, James A.; And Others

    Noting that the chance to utilize a new paradigm is an opportunity that rarely presents itself, this paper suggests that chaos theory and communication can be combined to help understand human communication. The paper begins by examining the complexity of human communication--that is, the internal and external factors that affect the complexity of…

  1. Basic Research in Human Factors

    DTIC Science & Technology

    1990-07-01

    in the fields of experimental psychology , bimeccanics, mathematical psychology , cognitive and information sciences, sociology, business...administration, organizational and industrial psychology , and engineering. Each of these experts serves on the ccmittee or its subgroup without reimbursement other...studies on macro models and has identified researh needed for the description and prediction of human performance. Its report, which will recammend

  2. 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.

  3. Human factors for Mars missions.

    NASA Astrophysics Data System (ADS)

    Nicogossian, A. E.

    A manned mission to Mars will challenge the human capacity to cope with extreme environments and solve new problems associated with them. Life support systems capable of preventing the accumulation of toxic chemicals will be necessary. Psychological issues may gain greater importance.

  4. 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

  5. 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.

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

    PubMed Central

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

    2010-01-01

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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Global landscape of HIV-human protein complexes.

    PubMed

    Jäger, Stefanie; Cimermancic, Peter; Gulbahce, Natali; Johnson, Jeffrey R; McGovern, Kathryn E; Clarke, Starlynn C; Shales, Michael; Mercenne, Gaelle; Pache, Lars; Li, Kathy; Hernandez, Hilda; Jang, Gwendolyn M; Roth, Shoshannah L; Akiva, Eyal; Marlett, John; Stephens, Melanie; D'Orso, Iván; Fernandes, Jason; Fahey, Marie; Mahon, Cathal; O'Donoghue, Anthony J; Todorovic, Aleksandar; Morris, John H; Maltby, David A; Alber, Tom; Cagney, Gerard; Bushman, Frederic D; Young, John A; Chanda, Sumit K; Sundquist, Wesley I; Kortemme, Tanja; Hernandez, Ryan D; Craik, Charles S; Burlingame, Alma; Sali, Andrej; Frankel, Alan D; Krogan, Nevan J

    2011-12-21

    Human immunodeficiency virus (HIV) has a small genome and therefore relies heavily on the host cellular machinery to replicate. Identifying which host proteins and complexes come into physical contact with the viral proteins is crucial for a comprehensive understanding of how HIV rewires the host's cellular machinery during the course of infection. Here we report the use of affinity tagging and purification mass spectrometry to determine systematically the physical interactions of all 18 HIV-1 proteins and polyproteins with host proteins in two different human cell lines (HEK293 and Jurkat). Using a quantitative scoring system that we call MiST, we identified with high confidence 497 HIV-human protein-protein interactions involving 435 individual human proteins, with ∼40% of the interactions being identified in both cell types. We found that the host proteins hijacked by HIV, especially those found interacting in both cell types, are highly conserved across primates. We uncovered a number of host complexes targeted by viral proteins, including the finding that HIV protease cleaves eIF3d, a subunit of eukaryotic translation initiation factor 3. This host protein is one of eleven identified in this analysis that act to inhibit HIV replication. This data set facilitates a more comprehensive and detailed understanding of how the host machinery is manipulated during the course of HIV infection.

  15. 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.

  16. Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS)

    NASA Technical Reports Server (NTRS)

    Alexander, Tiffaney Miller

    2017-01-01

    Research results have shown that more than half of aviation, aerospace and aeronautics mishaps incidents are attributed to human error. As a part of Quality within space exploration ground processing operations, the identification and or classification of underlying contributors and causes of human error must be identified, in order to manage human error.This presentation will provide a framework and methodology using the Human Error Assessment and Reduction Technique (HEART) and Human Factor Analysis and Classification System (HFACS), as an analysis tool to identify contributing factors, their impact on human error events, and predict the Human Error probabilities (HEPs) of future occurrences. This research methodology was applied (retrospectively) to six (6) NASA ground processing operations scenarios and thirty (30) years of Launch Vehicle related mishap data. This modifiable framework can be used and followed by other space and similar complex operations.

  17. Patient safety - the role of human factors and systems engineering.

    PubMed

    Carayon, Pascale; Wood, Kenneth E

    2010-01-01

    Patient safety is a global challenge that requires knowledge and skills in multiple areas, including human factors and systems engineering. In this chapter, numerous conceptual approaches and methods for analyzing, preventing and mitigating medical errors are described. Given the complexity of healthcare work systems and processes, we emphasize the need for increasing partnerships between the health sciences and human factors and systems engineering to improve patient safety. Those partnerships will be able to develop and implement the system redesigns that are necessary to improve healthcare work systems and processes for patient safety.

  18. 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.…

  19. Relationship of Complexity Factor Ratings With Operational Errors

    DTIC Science & Technology

    2007-05-01

    and their descriptions was initially derived from the 19 complexity factors identified by Mogford et al. (1994). Subject Matter Experts ( SMEs ) from...in Table 1. Note that only two extra factors were added by the SMEs , yet there are 22 factors in the list. The “mix of aircraft with different...performance characteristics” and “VFR versus IFR traffic” factors were combined in the original list but were separated into two distinct factors for

  20. 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.

  1. Human factors and operating room safety.

    PubMed

    ElBardissi, Andrew W; Sundt, Thoralf M

    2012-02-01

    A human factors model is used to highlight the nature of many systems factors that affect surgical performance, including the OR environment, teamwork and communication, technology and equipment, tasks and workload factors, and organizational variables. If further improvements in the success rate and reliability of cardiac surgery are to be realized, interventions need to be developed to reduce the negative impact that work system failures can have on surgical performance. Some recommendations are proposed here; however, several challenges remain.

  2. 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.

  3. 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.

  4. Human factors in the management of the critically ill patient.

    PubMed

    Bion, J F; Abrusci, T; Hibbert, P

    2010-07-01

    Unreliable delivery of best practice care is a major component of medical error. Critically ill patients are particularly susceptible to error and unreliable care. Human factors analysis, widely used in industry, provides insights into how interactions between organizations, tasks, and the individual worker impact on human behaviour and affect systems reliability. We adopt a human factors approach to examine determinants of clinical reliability in the management of critically ill patients. We conducted a narrative review based on a Medline search (1950-March 2010) combining intensive/critical care (units) with medical errors, patient safety, or delivery of healthcare; keyword and Internet search 'human factors' or 'ergonomics'. Critical illness represents a high-risk, complex system spanning speciality and geographical boundaries. Substantial opportunities exist for improving the safety and reliability of care of critically ill patients at the level of the task, the individual healthcare provider, and the organization or system. Task standardization (best practice guidelines) and simplification (bundling or checklists) should be implemented where scientific evidence is strong, or adopted subject to further research ('dynamic standardization'). Technical interventions should be embedded in everyday practice by the adjunctive use of non-technical (behavioural) interventions. These include executive 'adoption' of clinical areas, systematic methods for identifying hazards and reflective learning from error, and a range of techniques for improving teamworking and communication. Human factors analysis provides a useful framework for understanding and rectifying the causes of error and unreliability, particularly in complex systems such as critical care.

  5. Factors Influencing Haptic Perception of Complex Shapes.

    PubMed

    Ehrich, Jonathan M; Flanders, Martha; Soechting, John F

    2008-01-01

    Exploration of an object by arm movement and somatosensation is a serial process that relies on memories and expectations. The present experiments tested the hypothesis that this process involves breaking the object into component shapes (primitives). This was tested by having human subjects explore shapes composed of semicircular arcs, as well as quarter circles or quarter ellipses. The subjects' perception was reported using a visual display. In the first experiment, in which a series of semicircular arcs was presented, with offsets that differed from trial to trial, performance was consistent with the perception of two (left and right) semicircles. In the second experiment, subjects often failed to detect the quarter circles or quarter ellipses and again behaved as if the object was composed of two (top and bottom) semicircles. The results suggest that the synthesis of haptically sensed shapes is biased toward simple geometric objects and that it can be strongly influenced by expectations.

  6. Fidelity of a human cell DNA replication complex.

    PubMed Central

    Roberts, J D; Kunkel, T A

    1988-01-01

    We have measured the fidelity of bidirectional, semiconservative DNA synthesis by a human DNA replication complex in vitro. Replication was performed by extracts of HeLa cells in the presence of simian virus 40 (SV40) large tumor antigen by using a double-stranded phage M13mp2 DNA template containing the SV40 origin of replication and either of two different target sequences for scoring mutations in the lacZ alpha-complementation gene, which encodes the alpha region (specifying the amino-terminal portion) of beta-galactosidase. Replicative synthesis was substantially more accurate than synthesis by the human DNA polymerase alpha-DNA primase complex purified from HeLa cell extracts by immunoaffinity chromatography, suggesting that additional factors or activities in the extract may increase fidelity during bidirectional replication. However, by using a sensitive opal codon reversion assay, single-base substitution errors were readily detected in the replication products at frequencies significantly higher than estimated spontaneous mutation rates in vivo. These data suggest that additional fidelity factors may be present during chromosomal replication in vivo and/or that the fidelity of replication alone does not account for the low spontaneous mutation rates in eukaryotes. Images PMID:3174620

  7. Surgical Never Events and Contributing Human Factors

    PubMed Central

    Thiels, Cornelius A.; Lal, Tarun Mohan; Nienow, Joseph M.; Pasupathy, Kalyan S.; Blocker, Renaldo C.; Aho, Johnathon M.; Morgenthaler, Timothy I.; Cima, Robert R.; Hallbeck, Susan; Bingener, Juliane

    2015-01-01

    Introduction We report the first prospective analysis of human factors elements contributing to invasive procedural never events using a validated Human Factors Analysis and Classification System (HFACS). Methods From 8/2009 - 8/2014 surgical and invasive procedural “Never Events” (retained foreign object, wrong site/side procedure, wrong implant, wrong procedure) underwent systematic causation analysis promptly after the event. Contributing human factors were categorized using Reason's 4 levels of error causation and 161 HFACS subcategories (nano-codes). Results During the study approximately 1.5 million procedures were performed and 69 never events were identified. A total of 628 contributing human factors nano-codes were identified. Action-based errors (n=260) and preconditions to actions (n=296) accounted for the majority of the nano-codes across all four types of events, with individual cognitive factors contributing half of the nano-codes. The most common action nano-codes were confirmation bias (n=36) and failed to understand (n=36). The most common pre-condition nano-codes were channeled attention on a single issue (n=33) and inadequate communication (n=30). Conclusion Targeting quality and system improvement interventions addressing cognitive factors and team resource management as well as perceptual biases may reduce errors and further improve patient safety. These results delineate targets to further reduce never events from our healthcare system. PMID:26032826

  8. 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.

  9. Cumulative knowledge and progress in human factors.

    PubMed

    Proctor, Robert W; Vu, Kim-Phuong L

    2010-01-01

    This review provides a cumulative perspective on current human factors research by first briefly acknowledging previous Annual Review articles. We show that several recent conceptual advances are an outgrowth of the information-processing approach adopted by the field and present several areas of current research that are built directly on prior work. Topic areas that provide fundamental tools for human factors analyses are summarized, and several current application areas are reviewed. We end by considering alternatives to the information-processing approach that have been proposed and placing those alternatives in context. We argue that the information-processing language provides the foundation that has enabled much of the growth in human factors. This growth reflects a cumulative development of concepts and methods that continues today.

  10. Genetic and environmental factors influencing human diseases with telomere dysfunction

    PubMed Central

    Ly, Hinh

    2009-01-01

    Both genetic and environmental factors have been implicated in the mechanism underlying the pathogenesis of serious and fatal forms of human blood disorder (acquired aplastic anemia, AA) and lung disease (idiopathic pulmonary fibrosis, IPF). We and other researchers have recently shown that naturally occurring mutations in genes encoding the telomere maintenance complex (telomerase) may predispose patients to the development of AA or IPF. Epidemiological data have shown that environmental factors can also cause and/or exacerbate the pathogenesis of these diseases. The exact mechanisms that these germ-line mutations in telomere maintenance genes coupled with environmental insults lead to ineffective hematopoiesis in AA and lung scarring in IPF are not well understood, however. In this article, we provide a summary of evidence for environmental and genetic factors influencing the diseases. These studies provide important insights into the interplay between environmental and genetic factors leading to human diseases with telomere dysfunction. PMID:19684885

  11. HUMAN FACTORS GUIDANCE FOR CONTROL ROOM EVALUATION

    SciTech Connect

    OHARA,J.; BROWN,W.; STUBLER,W.; HIGGINS,J.; WACHTEL,J.; PERSENSKY,J.J.

    2000-07-30

    The Human-System Interface Design Review Guideline (NUREG-0700, Revision 1) was developed by the US Nuclear Regulatory Commission (NRC) to provide human factors guidance as a basis for the review of advanced human-system interface technologies. The guidance consists of three components: design review procedures, human factors engineering guidelines, and a software application to provide design review support called the ``Design Review Guideline.'' Since it was published in June 1996, Rev. 1 to NUREG-0700 has been used successfully by NRC staff, contractors and nuclear industry organizations, as well as by interested organizations outside the nuclear industry. The NRC has committed to the periodic update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool in the face of emerging and rapidly changing technology. This paper addresses the current research to update of NUREG-0700 based on the substantial work that has taken place since the publication of Revision 1.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Human factors considerations for unattended ground sensors

    NASA Astrophysics Data System (ADS)

    Johnson, Robert A.

    2009-05-01

    Even with traditional system design and development programs military systems are developed that end up being difficult for the target audience to use. Over the years the military has learned to incorporate human factors considerations and requirements in system requirements documents in order to minimize this problem. However in today's environment of procuring GOTS/COTS equipment to quickly field a needed capability, the human factors aspects are not always considered or they may have to be traded for other considerations. This occurs for a variety of reasons with the driving reason being the willingness of commanders and agencies to trade capabilities for speed of fielding. This paper addresses human factors considerations that should be observed in the design of unattended ground sensors (UGS) at the component, equipment and system levels. This is not an abstract paper on human factors engineering but an examination of current trends and applications. Lessons learned from recent fieldings and example designs from the Harris Falcon Watch system are provided. What Harris has found is that design considerations, development schedules, understanding of the target audience and the mission scenarios, and training are all key factors in determining whether a system will be found to have utility by a broad spectrum of users.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. Host resistance factors in human milk.

    PubMed

    Goldman, A S; Smith, C W

    1973-06-01

    This paper discusses the nature of host resistance factors in human milk and epidemiologic studies regarding infections and mortality rates in breastfed and nonbreastfed babies. The defense factors and their proposed modes of action are: 1) a growth enhancer of lactobacilli, which interferes with intestinal colonization of enteric pathogens; 2) antistaphylococcal factors, which inhibit staphylococci; 3) secretory IgA and other immunoglobulins, which protect the gut and respiratory tract; 4) C4 and C3 (complement components; C3 fragments have opsonic, chemotactic, and anaphylatoxic activities); 5) lysozome, lysis of bacterial cell wall; 6) lactoperoxidase, killing of streptococci; 7) lactoferrin, kills microorganism by chelating iron, and 8) macrophages and lymphocytes, phagocytosis and cell-mediated immunity. Although it can be postulated that the breastfed infant's resistance to infection would be superior on account of the greater presence of these factors in human milk compared to cow's milk, little is known about the effects of these defense factors on the infant. Epidemiologic studies have reported on the lower morbidity and mortality rates of breastfed infants as compared to bottlefed infants. Other studies have focused on the protective effects of human milk upon the infant, but these have been inconclusive. In countries with poor sanitation and high infection rates, the incidence of bacterial infections is lowest in breastfed infants. The advantages of human milk however are difficult to demonstrate in societies with high standards of sanitation and low infection rates. Infection and mortality rates in infants have in fact declined in developed countries as the practice of breastfeeding declined. Until it is established that immunity to common pathogens is transmitted to the infant by human milk, it will not be known whether human milk does have protective effects.

  4. [Human factors and heart surgery: a Cartesian dream].

    PubMed

    de Leval, M R

    1996-01-01

    It is postulated that high technology medicine can be assimilated to complex socio-technical systems such as the aviation industry, nuclear power or chemical plants etc. It is proposed to apply to cardiac surgery the techniques of human reliability and human error analysis that have been acquired over the past two decades to enhance safety in those areas of high technology. It is now widely accepted that in complex socio-technical systems accidents are due to human factors in 60-80% of the cases. Accident theories and, in particular theories of organisational accidents, have been applied prospectively to negative surgical outcomes in an attempt to understand their causation ad to establish defence mechanisms to prevent them or at least mitigate their consequences. The philosophical issues raised by this endeavour will be outlined.

  5. Genetic and Environmental Factors in Complex Neurodevelopmental Disorders

    PubMed Central

    van Loo, K.M.J; Martens, G.J.M

    2007-01-01

    Complex neurodevelopmental disorders, such as schizophrenia, autism, attention deficit (hyperactivity) disorder, (manic) depressive illness and addiction, are thought to result from an interaction between genetic and environmental factors. Association studies on candidate genes and genome-wide linkage analyses have identified many susceptibility chromosomal regions and genes, but considerable efforts to replicate association have been surprisingly often disappointing. Here, we summarize the current knowledge of the genetic contribution to complex neurodevelopmental disorders, focusing on the findings from association and linkage studies. Furthermore, the contribution of the interaction of the genetic with environmental and epigenetic factors to the aetiology of complex neurodevelopmental disorders as well as suggestions for future research are discussed. PMID:19412416

  6. Complex Systems and Human Performance Modeling

    DTIC Science & Technology

    2013-12-01

    human communication patterns can be implemented in a task network modeling tool. Although queues are a basic feature in many task network modeling...time. MODELING COMMUNICATIVE BEHAVIOR Barabasi (2010) argues that human communication patterns are “bursty”; that is, the inter-event arrival...Having implemented the methods advocated by Clauset et al. in C3TRACE, we have grown more confident that the human communication data discussed above

  7. Advanced Human Factors Engineering Tool Technologies.

    DTIC Science & Technology

    1988-03-01

    representing the government, the military, academe, and private industry were surveyed to identify those tools that are most frequently used or viewed...tools by HFE researchers and practitioners within the academic, industrial , and military settings. % .. J. &@ossion For XTIS GR&&I DTIC TAS 0...267 E. Human Factors Engineering Tools Questionnaire .. ......... . 279 F. Listing of Industry , Government, and Academe

  8. 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…

  9. 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.

  10. 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.

  11. 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

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

    PubMed

    Hennig, Holger

    2014-09-09

    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.

  13. 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.

  14. 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.

  15. 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

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

    PubMed

    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.

  17. 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

  18. 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.

  19. Human factors in aircraft maintenance and inspection

    NASA Technical Reports Server (NTRS)

    Shepherd, William T.

    1992-01-01

    The events which have led to the intensive study of aircraft structural problems have contributed in no less measure to the study of human factors which influence aircraft maintenance and inspection. Initial research emphasis on aging aircraft maintenance and inspection has since broadened to include all aircraft types. Technicians must be equally adept at repairing old and new aircraft. Their skills must include the ability to repair sheet metal and composite materials; control cable and fly-by-wire systems; round dials and glass cockpits. Their work performance is heavily influenced by others such as designers, technical writers, job card authors, schedulers, and trainers. This paper describes the activities concerning aircraft and maintenance human factors.

  20. 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.

  1. Human factors by descent energy management

    NASA Technical Reports Server (NTRS)

    Curry, R. E.

    1979-01-01

    This paper describes some of the results of a human factors study of energy management during descent using standard aircraft displays. Discussions with pilots highlighted the practical constraints involved and the techniques (algorithms) used to accomplish the descent. The advantages and disadvantages of these algorithms are examined with respect to workload and their sensitivity to disturbances. Vertical navigation and flight performance computers are discussed in terms of the information needed for effective pilot monitoring and takeover

  2. 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.

  3. Human Factors Engineering Program Review Model

    DTIC Science & Technology

    2004-02-01

    AA NUREG -0711,Rev. 2 Human Factors Engineering Program Review Model 20081009191 I i m To] Bi U.S. Nuclear Regulatory Commission Office of...Material As of November 1999, you may electronically access NUREG -series publications and other NRC records at NRC’s Public Electronic Reading Room at...http://www.nrc.qov/readinq-rm.html. Publicly released records include, to name a few, NUREG -series publications; Federal Register notices; applicant

  4. 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.

  5. 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.

  6. 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}.

  7. Stable interaction between the human proliferating cell nuclear antigen loader complex Ctf18-replication factor C (RFC) and DNA polymerase {epsilon} is mediated by the cohesion-specific subunits, Ctf18, Dcc1, and Ctf8.

    PubMed

    Murakami, Takeshi; Takano, Ryuji; Takeo, Satoshi; Taniguchi, Rina; Ogawa, Kaori; Ohashi, Eiji; Tsurimoto, Toshiki

    2010-11-05

    One of the proliferating cell nuclear antigen loader complexes, Ctf18-replication factor C (RFC), is involved in sister chromatid cohesion. To examine its relationship with factors involved in DNA replication, we performed a proteomics analysis of Ctf18-interacting proteins. We found that Ctf18 interacts with a replicative DNA polymerase, DNA polymerase ε (pol ε). Co-immunoprecipitation with recombinant Ctf18-RFC and pol ε demonstrated that their binding is direct and mediated by two distinct interactions, one weak and one stable. Three subunits that are specifically required for cohesion in yeast, Ctf18, Dcc1, and Ctf8, formed a trimeric complex (18-1-8) and together enabled stable binding with pol ε. The C-terminal 23-amino acid stretch of Ctf18 was necessary for the trimeric association of 18-1-8 and was required for the stable interaction. The weak interaction was observed with alternative loader complexes including Ctf18-RFC(5), which lacks Dcc1 and Ctf8, suggesting that the common loader structures, including the RFC small subunits (RFC2-5), are responsible for the weak interaction. The two interaction modes, mediated through distinguishable structures of Ctf18-RFC, both occurred through the N-terminal half of pol ε, which includes the catalytic domain. The addition of Ctf18-RFC or Ctf18-RFC(5) to the DNA synthesis reaction caused partial inhibition and stimulation, respectively. Thus, Ctf18-RFC has multiple interactions with pol ε that promote polymorphic modulation of DNA synthesis. We propose that their interaction alters the DNA synthesis mode to enable the replication fork to cooperate with the establishment of cohesion.

  8. 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).

  9. 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.

  10. 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…

  11. 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…

  12. 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.

  13. 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

  14. Human factors in primary care telemedicine encounters.

    PubMed

    Bulik, Robert J

    2008-01-01

    Traditional delivery of primary care takes place in a face-to-face transaction between provider and patient. In telemedicine, however, the transaction is 'filtered' by the distance and technology. The potential problem of filtered communication in a telemedicine encounter was examined from a human factors perspective. Patients with and without experience of telemedicine, and providers who had experience of telemedicine, were asked about patient-provider relationships in interviews and focus groups. Seven themes emerged: initial impressions, style of questions, field of view, physical interaction, social talk, control of encounter and ancillary services. This suggests that communication can be improved and better patient-provider relationships can be developed in a primary care telemedicine encounter if attention is paid to four areas of the interaction: verbal, non-verbal, relational and actions/transactional. The human factors dimension of telemedicine is an important element in delivery of health care at a distance - and is one of few factors over which the provider has direct control.

  15. My 20 years of experience in the human factors field

    SciTech Connect

    Carnino, A. )

    1992-01-01

    My first encounter with human factors happened in early 1973: I was performing a reliability assessment of the safety injection system of the Fessenheim reactor, and I found that the operators had to switch to the recirculation phase manually and had only 6 min between the low and low-low level alarm indicating that the water tank was empty. It of course led us to replace this manual action by an automatic positioning for the recirculation phase. In July of the same year, I attended a North Atlantic Treaty Organization workshop in Liverpool on reliability assessment, and I met Alan Swain from the United States and Jens Rasmussen from Denmark. During the long rainy evenings of the seminar, we had time to discuss human errors and human factors, and that was the beginning of a very fruitful collaboration between us. I realized then the complexity of the problem. Quantification needs were obvious for reliability and risk assessment studies, but, at the same time, there were needs for better understanding of human behavior and the mechanisms that could lead to human errors. Knowledge of the man-machine interface also seemed very poor, although some basic ergonomic rules were available and could be applied. But a major problem was the lack of data.

  16. Accessory subunits are integral for assembly and function of human mitochondrial complex I.

    PubMed

    Stroud, David A; Surgenor, Elliot E; Formosa, Luke E; Reljic, Boris; Frazier, Ann E; Dibley, Marris G; Osellame, Laura D; Stait, Tegan; Beilharz, Traude H; Thorburn, David R; Salim, Agus; Ryan, Michael T

    2016-10-06

    Complex I (NADH:ubiquinone oxidoreductase) is the first enzyme of the mitochondrial respiratory chain and is composed of 45 subunits in humans, making it one of the largest known multi-subunit membrane protein complexes. Complex I exists in supercomplex forms with respiratory chain complexes III and IV, which are together required for the generation of a transmembrane proton gradient used for the synthesis of ATP. Complex I is also a major source of damaging reactive oxygen species and its dysfunction is associated with mitochondrial disease, Parkinson's disease and ageing. Bacterial and human complex I share 14 core subunits that are essential for enzymatic function; however, the role and necessity of the remaining 31 human accessory subunits is unclear. The incorporation of accessory subunits into the complex increases the cellular energetic cost and has necessitated the involvement of numerous assembly factors for complex I biogenesis. Here we use gene editing to generate human knockout cell lines for each accessory subunit. We show that 25 subunits are strictly required for assembly of a functional complex and 1 subunit is essential for cell viability. Quantitative proteomic analysis of cell lines revealed that loss of each subunit affects the stability of other subunits residing in the same structural module. Analysis of proteomic changes after the loss of specific modules revealed that ATP5SL and DMAC1 are required for assembly of the distal portion of the complex I membrane arm. Our results demonstrate the broad importance of accessory subunits in the structure and function of human complex I. Coupling gene-editing technology with proteomics represents a powerful tool for dissecting large multi-subunit complexes and enables the study of complex dysfunction at a cellular level.

  17. 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.

  18. 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.

  19. 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.

  20. Job performance aids: Human factoring maintenance procedures

    SciTech Connect

    Macris, A.C.; Fleming, S.T

    1991-11-01

    Job performance aids (JPAs) are human factors engineering techniques used to strengthen operating, maintenance, and engineering procedures. They are not a new concept, but one whose time has come. This paper focuses on the application of JPAs to maintenance procedures. Job performance aids research originates from US Department of Defense (DOD) efforts, primarily in maintenance-oriented tasks. While at Connecticut Yankee power plant, the authors, an instructional consultant, and the training manager were investigating ways to enhance training effectiveness. Based on historic research efforts, there is strong evidence that JPAs have the potential to improve human performance and realize additional benefits of reduced training time and should be incorporated into the training time and should be incorporated into the training curriculum.

  1. In vitro reconstitution of the human RISC-loading complex.

    PubMed

    MacRae, Ian J; Ma, Enbo; Zhou, Min; Robinson, Carol V; Doudna, Jennifer A

    2008-01-15

    Targeted gene silencing by RNAi requires the RNA-induced silencing complex (RISC), whose core component is the protein Argonaute (Ago) bound to a microRNA (miRNA) or an siRNA. In humans, Ago2 is loaded with miRNAs by the action of a specialized assembly called the RISC-loading complex (RLC), comprising the proteins Ago2, Dicer, and TRBP. Here we show that the human RLC assembles spontaneously in vitro from purified components. No cofactors or chaperones are required for the complex to form. The reconstituted RLC, containing one copy of each protein, has the dicing, slicing, guide-strand selection, and Ago2-loading activities observed for the endogenous RLC. Furthermore, once Ago2 is loaded with an miRNA, it tends to dissociate from the rest of the complex. These results lay the groundwork for future structural and functional dissection of RISC loading in humans.

  2. 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.

  3. Diabetes technology and the human factor.

    PubMed

    Liberman, A; Buckingham, B; Phillip, M

    2011-02-01

    When developing new technologies for human use the developer should take into consideration not only the efficacy and safety of the technology but also the desire and capabilities of the potential user. Any chronic disease is a challenge for both the patient and his/her caregivers. This statement is especially true in the case of patients with type 1 diabetes mellitus (T1DM) where adherence to therapy is crucial 24 hours a day 365 days a year. No vacation days are possible for the T1DM patient. It is therefore obvious why any new technology which is developed for helping patients cope with the disease should take into consideration the 'human factor' before, during and after the production process starts. There is no doubt that technology has changed the life of patients with T1DM in the last few decades, but despite the availability of new meters, new syringes, new sophisticated insulin pumps and continuous glucose sensors and communication tools, these technologies have not been well utilised by many patients. It is therefore important to understand why the technology is not always utilised and to find new ways to maximise use and benefits from the technology to as many patients as possible. The present chapter will review papers published in the last year where the patient's ability or willingness was an important factor in the success of the technology. We will try to understand why insulin pumps, glucose sensors and self-monitoring of blood glucose (SMBG) are not used enough or appropriately, whether there is a specific group that finds it more difficult than others to adopt new technologies and what can be done to overcome that issue. For this chapter we chose articles from a Public Medicine review of the literature related to human factors affecting the outcome of studies and of user acceptance of continuous glucose monitoring, insulin infusion pump therapy. We also searched the literature in the field of psychology in order to accurately define the problems

  4. Human Factors Experimental Design and Analysis Reference

    DTIC Science & Technology

    2007-07-01

    and R2Adj – PRESS Statistic – Mallows C(p) A linear regression model that includes all predictors investigated may not be the best model in terms of...as the Adjusted Coefficient of Determination, R2Adj, the PRESS statistic, and Mallows C(p) value. Human Factors Experimental Design and Analysis...equations with highest R2 using R2Adj, PRESS, and Mallows C(p) • Evaluation – Cumbersome as number of X’s increase 10 X’s = (210-1) = 1,023 Regression

  5. 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.

  6. Crystal structure of human nuclear pore complex component NUP43.

    PubMed

    Xu, Chao; Li, Zhihong; He, Hao; Wernimont, Amy; Li, Yanjun; Loppnau, Peter; Min, Jinrong

    2015-10-24

    Nuclear pore complexes (NPC) form nuclear pores that cross the nuclear envelope and allow molecules to transport between the nucleus and the cytoplasm. We solved the crystal structure of human Nup43 (hNUP43), an important component in the Nup107 subcomplex of NPC. hNup43 adopts a seven-bladed β-propeller fold. We confirmed by ITC that neither human Nup37 (hNup37) nor human Nup133 (hNup133) interacts with hNup43. We demonstrated by analytical gel filtration that the human Nup85-Seh1L binary complex recruits hNup43 to form a ternary complex. Based on amino acid sequence analysis, we predicted the hNup85-hSeh1L binding surface of hNup43.

  7. 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.

  8. An International Survey of Maintenance Human Factors Programs

    DTIC Science & Technology

    2007-09-01

    maintenance and repair organizations. Questions focused on training, error management , fatigue management , and other human factors issues. An online link was... Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Fatgue... Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 human Factors Metrcs

  9. 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.

  10. Factors Leading to the Formation of Arc Cloud Complexes.

    DTIC Science & Technology

    1985-12-01

    I. M2i .16 MICROCnWY O TEST CHART NATIONAL BUREAU 0F STANDARDS-1963-A ils. ... TEXAS A&M UNIVERSITY DEPARTMENT OF R AOL mMETEOROLOGY FACTORS LEADING...PERFORMING ORGANIZATION NAME AND ADDRESS 10. PROGRAM ELEMENT, PROJECT, TASKAFIT STUDENT AT: AREA & WORK UNIT NUMBERS Texas A&M Univ II. CONTROLLING...to an ACC. /0 FACTORS LEADING TO THE FORMATION OF ARC CLOUD COMPLEXES A Thesis by MARK JOHN WELSHINGER Submitted to the Graduate College of Texas A&M

  11. [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.

  12. Direct inhibition of the NOTCH transcription factor complex.

    PubMed

    Moellering, Raymond E; Cornejo, Melanie; Davis, Tina N; Del Bianco, Cristina; Aster, Jon C; Blacklow, Stephen C; Kung, Andrew L; Gilliland, D Gary; Verdine, Gregory L; Bradner, James E

    2009-11-12

    Direct inhibition of transcription factor complexes remains a central challenge in the discipline of ligand discovery. In general, these proteins lack surface involutions suitable for high-affinity binding by small molecules. Here we report the design of synthetic, cell-permeable, stabilized alpha-helical peptides that target a critical protein-protein interface in the NOTCH transactivation complex. We demonstrate that direct, high-affinity binding of the hydrocarbon-stapled peptide SAHM1 prevents assembly of the active transcriptional complex. Inappropriate NOTCH activation is directly implicated in the pathogenesis of several disease states, including T-cell acute lymphoblastic leukaemia (T-ALL). The treatment of leukaemic cells with SAHM1 results in genome-wide suppression of NOTCH-activated genes. Direct antagonism of the NOTCH transcriptional program causes potent, NOTCH-specific anti-proliferative effects in cultured cells and in a mouse model of NOTCH1-driven T-ALL.

  13. Direct inhibition of the NOTCH transcription factor complex

    PubMed Central

    Moellering, Raymond E.; Cornejo, Melanie; Davis, Tina N.; Del Bianco, Cristina; Aster, Jon C.; Blacklow, Stephen C.; Kung, Andrew L.; Gilliland, D. Gary; Verdine, Gregory L.; Bradner, James E.

    2010-01-01

    Direct inhibition of transcription factor complexes remains a central challenge in the discipline of ligand discovery. In general, these proteins lack surface involutions suitable for high-affinity binding by small molecules. Here we report the design of synthetic, cell-permeable, stabilized α-helical peptides that target a critical protein–protein interface in the NOTCH transactivation complex. We demonstrate that direct, high-affinity binding of the hydrocarbon-stapled peptide SAHM1 prevents assembly of the active transcriptional complex. Inappropriate NOTCH activation is directly implicated in the pathogenesis of several disease states, including T-cell acute lymphoblastic leukaemia (T-ALL). The treatment of leukaemic cells with SAHM1 results in genome-wide suppression of NOTCH-activated genes. Direct antagonism of the NOTCH transcriptional program causes potent, NOTCH-specific anti-proliferative effects in cultured cells and in a mouse model of NOTCH1-driven T-ALL. PMID:19907488

  14. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

    SciTech Connect

    Ramasharma, K.; Li, C.H.

    1987-05-01

    Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and ..cap alpha..-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin.

  15. 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.

  16. 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…

  17. Assessment of Military Personnel for Complex Environment using Human Performance Modeling

    DTIC Science & Technology

    2010-10-01

    HBR (Human Behaviour Representation)-theory´s aim to create a computer program that simulates typical military or military related scenarios (i.e... HBR -assessment decision support system consists mainly of two different computer programs: 1) Assessment-Demonstrator: a 3D-simulation of realistic...BEHAVIOR REPRESENTATION ( HBR ) Human behaviour is highly complex in its structure. It is influenced by physical, emotional, cognitive and social factors

  18. 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

  19. The Measure of Human Vital Signals Complexity by Matrix Analysis

    NASA Astrophysics Data System (ADS)

    Bikulčienė, Liepa; Venskaitytė, Eurelija; Gargasas, Liudas; Jurkonis, Vidmantas

    The subject of investigation is extraction of information from vital signals (ECG, accelerometer, SpO2) and using it in diagnostics and assessment of status of human physiological state and complexity. The aim of this study is presentation of data recording system and the analytical methods designed for analysis of complexity and dynamic interrelations between different signal parameters. The results show that expressing of cardiac signals with Hankel and coherence matrices could be useful for diagnostic purposes.

  20. Complex spectral OCT in human eye imaging in vivo

    NASA Astrophysics Data System (ADS)

    Targowski, Piotr; Wojtkowski, Maciej; Kowalczyk, Andrzej; Bajraszewski, Tomasz; Szkulmowski, Maciej; Gorczyńska, Iwona

    2004-01-01

    Complex spectral optical coherence tomography in comparison to spectral optical coherence tomography produces images free of parasitic terms with extended measurement range. This technique requires stability of the object during at least three consecutive measurements. In this paper we present how to improve this technique to make measurements less sensitive to involuntary eye movements. The first images of human skin and anterior chamber of the eye in vivo based on complex spectral optical coherence tomography are presented.

  1. 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…

  2. Modeling complex neuropsychiatric disorders with human induced pluripotent stem cells.

    PubMed

    Tobe, Brian T D; Snyder, Evan Y; Nye, Jeffrey S

    2011-10-01

    Identifying the molecular and cellular basis of complex neuropsychiatric disorders (cNPDs) has been limited by the inaccessibility of central neurons, variability within broad diagnostic classifications, and the interplay of genetic and environmental factors. Recent work utilizing neuronally differentiated human induced pluripotent stem cells (hiPSCs) from Mendelian and polygenic cNPDs is beginning to illuminate neuritic, synaptic or cell body variations accompanied by specific gene or protein expression alterations largely mimicking known pathology. In some cases, phenotypes have only emerged after application of cellular stress or long duration of differentiation. Pathological and cellular expression features are fully or partially responsive to pharmacological treatment highlighting the potential utility of differentiated hiPSCs for discovery of personalized therapeutics and for identifying pathogenetically relevant targets in subgroups of patients within a broad syndromic classification. Because of the inherent variability in developing and differentiating hiPSC lines and the multiple comparisons implicit in 'omics' technologies, rigorous algorithms for assuring statistical significance and independent confirmation of results, will be required for robust modeling of cNPDs.

  3. Crystal structure of a human cleavage factor CFI(m)25/CFI(m)68/RNA complex provides an insight into poly(A) site recognition and RNA looping.

    PubMed

    Yang, Qin; Coseno, Molly; Gilmartin, Gregory M; Doublié, Sylvie

    2011-03-09

    Cleavage factor I(m) (CFI(m)) is a highly conserved component of the eukaryotic mRNA 3' processing machinery that functions in sequence-specific poly(A) site recognition through the collaboration of a 25 kDa subunit containing a Nudix domain and a larger subunit of 59, 68, or 72 kDa containing an RNA recognition motif (RRM). Our previous work demonstrated that CFI(m)25 is both necessary and sufficient for sequence-specific binding of the poly(A) site upstream element UGUA. Here, we report the crystal structure of CFI(m)25 complexed with the RRM domain of CFI(m)68 and RNA. The CFI(m)25 dimer is clasped on opposite sides by two CFI(m)68 RRM domains. Each CFI(m)25 subunit binds one UGUA element specifically. Biochemical analysis indicates that the CFI(m)68 RRMs serve to enhance RNA binding and facilitate RNA looping. The intrinsic ability of CFI(m) to direct RNA looping may provide a mechanism for its function in the regulation of alternative poly(A) site selection.

  4. Humanized birth in high risk pregnancy: barriers and facilitating factors.

    PubMed

    Behruzi, Roxana; Hatem, Marie; Goulet, Lise; Fraser, William; Leduc, Nicole; Misago, Chizuru

    2010-02-01

    The medical model of childbearing assumes that a pregnancy always has the potential to turn into a risky procedure. In order to advocate humanized birth in high risk pregnancy, an important step involves the enlightenment of the professional's preconceptions on humanized birth in such a situation. The goal of this paper is to identify the professionals' perception of the potential obstacles and facilitating factors for the implementation of humanized care in high risk pregnancies. Twenty-one midwives, obstetricians, and health administrator professionals from the clinical and academic fields were interviewed in nine different sites in Japan from June through August 2008. The interviews were audio taped, and transcribed with the participants' consent. Data was subsequently analyzed using content analysis qualitative methods. Professionals concurred with the concept that humanized birth is a changing and promising process, and can often bring normality to the midst of a high obstetric risk situation. No practice guidelines can be theoretically defined for humanized birth in a high risk pregnancy, as there is no conflict between humanized birth and medical intervention in such a situation. Barriers encountered in providing humanized birth in a high risk pregnancy include factors such as: the pressure of being responsible for the safety of the mother and the fetus, lack of the women's active involvement in the decision making process and the heavy burden of responsibility on the physician's shoulders, potential legal issues, and finally, the lack of midwifery authority in providing care at high risk pregnancy. The factors that facilitate humanized birth in a high risk include: the sharing of decision making and other various responsibilities between the physicians and the women; being caring; stress management, and the fact that the evolution of a better relationship and communication between the health professional and the patient will lead to a stress

  5. Human factors in Spacelab - Crew training

    NASA Technical Reports Server (NTRS)

    Junge, M. K.

    1983-01-01

    At NASA-Ames Research Center's Life Sciences Flight Experiments Project Office two payloads for the Shuttle Spacelab are currently in development. The first payload, Spacelab-3, will launch in November 1984. Unique life sciences hardware designed to support animals in 0-g will fly for the first time. Flight crew training sessions for the Spacelab-3 astronauts began in June 1982. Human factors involvement is extensive. A thorough understanding of both the 1-g and 0-g environments is necessary. The weightlessness of the space environment creates special conditions; e.g., the time required for a 1-g laboratory experiment significantly increases in 0-g. The transportation of objects in 0-g uses different techniques than on earth. These considerations, plus others, are incorporated into the design of the Spacelab-3 crew training program.

  6. 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.

  7. Human Factors in Patient Safety as an Innovation

    PubMed Central

    Carayon, Pascale

    2010-01-01

    The use of Human Factors and Ergonomics (HFE) tools, methods, concepts and theories has been advocated by many experts and organizations to improve patient safety. To facilitate and support the spread of HFE knowledge and skills in health care and patient safety, we propose to conceptualize HFE as innovations whose diffusion, dissemination, implementation and sustainability need to be understood and specified. Using Greenhalgh et al. (2004) model of innovation, we identified various factors that can either hinder or facilitate the spread of HFE innovations in healthcare organizations. Barriers include lack of systems thinking, complexity of HFE innovations and lack of understanding about the benefits of HFE innovations. Positive impact of HFE interventions on task performance and the presence of local champions can facilitate the adoption, implementation and sustainability of HFE innovations. This analysis concludes with a series of recommendations for HFE professionals, researchers and educators. PMID:20106468

  8. 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…

  9. 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.

  10. Isolation and mass spectrometry of transcription factor complexes.

    PubMed

    Sebastiaan Winkler, G; Lacomis, Lynne; Philip, John; Erdjument-Bromage, Hediye; Svejstrup, Jesper Q; Tempst, Paul

    2002-03-01

    Protocols are described that enable the isolation of novel proteins associated with a known protein and the subsequent identification of these proteins by mass spectrometry. We review the basics of nanosample handling and of two complementary approaches to mass analysis, and provide protocols for the entire process. The protein isolation procedure is rapid and based on two high-affinity chromatography steps. The method does not require previous knowledge of complex composition or activity and permits subsequent biochemical characterization of the isolated factor. As an example, we provide the procedures used to isolate and analyze yeast Elongator, a histone acetyltransferase complex important for transcript elongation, which led to the identification of three novel subunits.

  11. Factors underlying variable DNA methylation in a human community cohort

    PubMed Central

    Lam, Lucia L.; Emberly, Eldon; Fraser, Hunter B.; Neumann, Sarah M.; Chen, Edith; Miller, Gregory E.; Kobor, Michael S.

    2012-01-01

    Epigenetics is emerging as an attractive mechanism to explain the persistent genomic embedding of early-life experiences. Tightly linked to chromatin, which packages DNA into chromosomes, epigenetic marks primarily serve to regulate the activity of genes. DNA methylation is the most accessible and characterized component of the many chromatin marks that constitute the epigenome, making it an ideal target for epigenetic studies in human populations. Here, using peripheral blood mononuclear cells collected from a community-based cohort stratified for early-life socioeconomic status, we measured DNA methylation in the promoter regions of more than 14,000 human genes. Using this approach, we broadly assessed and characterized epigenetic variation, identified some of the factors that sculpt the epigenome, and determined its functional relation to gene expression. We found that the leukocyte composition of peripheral blood covaried with patterns of DNA methylation at many sites, as did demographic factors, such as sex, age, and ethnicity. Furthermore, psychosocial factors, such as perceived stress, and cortisol output were associated with DNA methylation, as was early-life socioeconomic status. Interestingly, we determined that DNA methylation was strongly correlated to the ex vivo inflammatory response of peripheral blood mononuclear cells to stimulation with microbial products that engage Toll-like receptors. In contrast, our work found limited effects of DNA methylation marks on the expression of associated genes across individuals, suggesting a more complex relationship than anticipated. PMID:23045638

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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…

  17. Mammalian SWI/SNF chromatin remodeling complexes and cancer: Mechanistic insights gained from human genomics

    PubMed Central

    Kadoch, Cigall; Crabtree, Gerald R.

    2015-01-01

    Over the past 4 years, nearly 100 exome sequencing studies have revealed the high frequency of mutations in the genes encoding the subunits of ATP-dependent chromatin remodelers in human cancer. Most of these mutations are within the genes encoding subunits of the BAF (Brg/Brahma-associated factors) or mSWI/SNF complex, which is one of two dozen predicted ATP-dependent chromatin remodeling complexes in mammals. Considering BAF complexes as a single entity, the 15 subunits encoded by 29 genes are mutated in >20% of human cancer, across a broad range of tumor types. These observations demonstrate that there is little redundancy in the oncogenic function of BAF complexes with the other remodeling complexes, underscoring their unique roles. Several important conclusions emerge from these genomic data: specific subunits appear to be mutated in specific cancers, highlighting tissue-specific protective roles; mutations can function as tumor suppressors or oncogenes; mutations can be homozygous or, more commonly, heterozygous, implying their dosage-sensitive roles in an unknown yet fundamental process used to suppress the genesis of cancer. These new human genetic findings paired with biochemical studies are challenging old ideas on how chromatin remodeling complexes function, generating new hypotheses with respect to their normal and oncogenic mechanisms and highlighting potential avenues for therapeutic intervention in human cancer. PMID:26601204

  18. 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

  19. 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.

  20. Assessing the value of human factors initiatives.

    PubMed

    Kerr, Micky P; Knott, David S; Moss, Michael A; Clegg, Chris W; Horton, Robin P

    2008-05-01

    This paper examines the effectiveness of human factors initiatives and addresses some difficulties reported in calculating the value of such interventions. Company representatives and researchers applied a novel probabilistic assessment tool to estimate the financial impact of two macro-ergonomic projects. Key benefits of the company intranet project include reduced administrative and operational costs compared to a paper-based system; time savings for users asking for, providing and receiving information; and improved system usability and higher levels of usage. The communities of practice project demonstrates value through more efficient distribution and retrieval of information; reduced duplication by re-using technical knowledge to solve similar problems and improved sharing of good working practices, lessons and resources. The strengths of the tool include transparency, being quick and easy to learn and the collaborative workshop format, involving researches and key representatives from the organization. It makes a useful contribution to the challenge of assessing the financial value of ergonomic interventions, and, by exploiting its diagnostic and planning capabilities, could be extended to other domains.

  1. 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

    2016-07-03

    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.

  2. Integrating human factors and operational research in a multidisciplinary investigation of road maintenance.

    PubMed

    Ryan, Brendan; Qu, Rong; Schock, Alex; Parry, Tony

    2011-05-01

    There has been limited collaboration between researchers in human factors and operational research disciplines, particularly in relation to work in complex, distributed systems. This study aimed to investigate work at the interface between human factors and operational research in the case example of road resurfacing work. Descriptive material on the factors affecting performance in road maintenance work was collected with support from a range of human factors-based methods and was used to inform operational research analyses. Investigation of the case example from a different perspective, for the supply of asphalt from a distribution centre to multiple work locations, gave a broader picture of the complexity and challenges for the improvement of road maintenance processes. Factors affecting performance in the road maintenance context have been assessed for their potential for further investigation using an integrated human factors and operational research approach. Relative strengths of the disciplines and a rationale for ongoing, collaborative work are described. STATEMENT OF RELEVANCE: The paper provides evidence of the potential benefits of greater collaboration across human factors and operational research disciplines, using investigation of a case example in the complex, distributed system of road resurfacing.

  3. Social scale and structural complexity in human languages.

    PubMed

    Nettle, Daniel

    2012-07-05

    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.

  4. The reconstituted human Chl12-RFC complex functions as a second PCNA loader.

    PubMed

    Shiomi, Yasushi; Shinozaki, Ayako; Sugimoto, Katsunori; Usukura, Jiro; Obuse, Chikashi; Tsurimoto, Toshiki

    2004-04-01

    The sister chromatid cohesion factor Chl12 shares amino acid sequence similarity with RFC1, the largest subunit of replication factor C (RFC), and forms a clamp loader complex in association with the RFC small subunits RFCs2-5. It has been shown that the human Chl12-RFC complex, reconstituted with a baculovirus expression system, specifically interacts with human proliferating cell nuclear antigen (PCNA). The purified Chl12-RFC complex is structurally indistinguishable from RFC, as shown by electron microscopy, and it exhibits DNA-stimulated ATPase activity that is further enhanced by PCNA, and by DNA binding activity on specific primer/template DNA structures. Furthermore, the complex loads PCNA onto a circular DNA substrate, and stimulates DNA polymerase delta DNA synthesis on a primed M13 single-stranded template in the presence of purified replication proteins. However, it cannot substitute for RFC in promoting simian virus 40 DNA replication in vitro with crude fractions. These results demonstrate that the human Chl12-RFC complex is a second PCNA loader and that its roles in replication are clearly distinguishable from those of RFC.

  5. 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.

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

    DTIC Science & Technology

    1981-10-01

    lIII L 36 11111125 Ifl4 1111.6 MICROCOPY RESOLUTION TEST CHART NATIONAL BUREAU f STANDARDS -163 A "___ /-un ~:R Human. Factors and Robotics ...TITLE (end Subtitle) S. TYPE OF REPORT & PERIOD COVEREO HUMAN FACTORS AND ROBOTICS : CURRENT STATUS AND FUTURE PROSPECTS 6. PERFORMING ORG. REPORT NUMBER...19. KEY WORDS (Continu. a reverse side If neeesar and Identify by block number) Human Factors Automation Robots Robotics Artificial Intelligence 20

  7. 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.

  8. 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.

  9. [Influence of genetic factors on human sexual orientation. Review].

    PubMed

    Rodríguez-Larralde, Alvaro; Paradisi, Irene

    2009-09-01

    Human sexual orientation is a complex trait, influenced by several genes, experiential and sociocultural factors. These elements interact and produce a typical pattern of sexual orientation towards the opposite sex. Some exceptions exist, like bisexuality and homosexuality, which seem to be more frequent in males than females. Traditional methods for the genetic study of behavior multifactorial characteristics consist in detecting the presence of familial aggregation. In order to identify the importance of genetic and environmental factors in this aggregation, the concordance of the trait for monozygotic and dizygotic twins and for adopted sibs, reared together and apart, is compared. These types of studies have shown that familial aggregation is stronger for male than for female homosexuality. Based on the threshold method for multifactorial traits, and varying the frequency of homosexuality in the population between 4 and 10%, heritability estimates between 0.27 and 0.76 have been obtained. In 1993, linkage between homosexuality and chromosomal region Xq28 based on molecular approaches was reported. Nevertheless, this was not confirmed in later studies. Recently, a wide search of the genome has given significant or close to significant linkage values with regions 7q36, 8p12 and 10q26, which need to be studied more closely. Deviation in the proportion of X chromosome inactivation in mothers of homosexuals seems to favor the presence of genes related with sexual orientation in this chromosome. There is still much to be known about the genetics of human homosexuality.

  10. 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.

  11. Molecular factors that determine Curie spin relaxation in dysprosium complexes.

    PubMed

    Caravan, P; Greenfield, M T; Bulte, J W

    2001-11-01

    Dysprosium complexes can serve as transverse relaxation (T(2)) agents for water protons through chemical exchange and the Curie spin relaxation mechanism. Using a pair of matched dysprosium(III) complexes, Dy-L1 (contains one inner-sphere water) and Dy-L2 (no inner-sphere water), it is shown that the transverse relaxation of bulk water is predominantly an inner-sphere effect. The kinetics of water exchange at Dy-L1 were determined by (17)O NMR. Proton transverse relaxation by Dy-L1 at high fields is governed primarily through a large chemical shift difference between free and bound water. Dy-L1 forms a noncovalent adduct with human serum albumin which dramatically lengthens the rotational correlation time, tau(R), causing the dipole-dipole component of the Curie spin mechanism to become significant and transverse relaxivity to increase by 3-8 times that of the unbound chelate. These findings aid in the design of new molecular species as efficient r(2) agents.

  12. 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.

  13. Structural characterization of human general transcription factor TFIIF in solution

    PubMed Central

    Akashi, Satoko; Nagakura, Shinjiro; Yamamoto, Seiji; Okuda, Masahiko; Ohkuma, Yoshiaki; Nishimura, Yoshifumi

    2008-01-01

    Human general transcription factor IIF (TFIIF), a component of the transcription pre-initiation complex (PIC) associated with RNA polymerase II (Pol II), was characterized by size-exclusion chromatography (SEC), electrospray ionization mass spectrometry (ESI-MS), and chemical cross-linking. Recombinant TFIIF, composed of an equimolar ratio of α and β subunits, was bacterially expressed, purified to homogeneity, and found to have a transcription activity similar to a natural one in the human in vitro transcription system. SEC of purified TFIIF, as previously reported, suggested that this protein has a size >200 kDa. In contrast, ESI-MS of the purified sample gave a molecular size of 87 kDa, indicating that TFIIF is an αβ heterodimer, which was confirmed by matrix-assisted laser desorption/ionization (MALDI) MS of the cross-linked TFIIF components. Recent electron microscopy (EM) and photo-cross-linking studies showed that the yeast TFIIF homolog containing Tfg1 and Tfg2, corresponding to the human α and β subunits, exists as a heterodimer in the PIC, so the human TFIIF is also likely to exist as a heterodimer even in the PIC. In the yeast PIC, EM and photo-cross-linking studies showed different results for the mutual location of TFIIE and TFIIF along DNA. We have examined the direct interaction between human TFIIF and TFIIE by ESI-MS, SEC, and chemical cross-linking; however, no direct interaction was observed, at least in solution. This is consistent with the previous photo-cross-linking observation that TFIIF and TFIIE flank DNA separately on both sides of the Pol II central cleft in the yeast PIC. PMID:18218714

  14. 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

  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. 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.

  17. Transcriptional Activation Domains of Human Heat Shock Factor 1 Recruit Human SWI/SNF

    PubMed Central

    Sullivan, E. Kelly; Weirich, Christine S.; Guyon, Jeffrey R.; Sif, Saïd; Kingston, Robert E.

    2001-01-01

    Chromatin remodeling complexes such as SWI/SNF use the energy of ATP hydrolysis to remodel nucleosomal DNA and increase transcription of nucleosomal templates. Human heat shock factor one (hHSF1) is a tightly regulated activator that stimulates transcriptional initiation and elongation using different portions of its activation domains. Here we demonstrate that hHSF1 associates with BRG1, the ATPase subunit of human SWI/SNF (hSWI/SNF) at endogenous protein concentrations. We also show that hHSF1 activation domains recruit hSWI/SNF to a chromatin template in a purified system. Mutation of hHSF1 residues responsible for activation of transcriptional elongation has the most severe effect on recruitment of SWI/SNF and association of hHSF1 with BRG1, suggesting that recruitment of chromatin remodeling activity might play a role in stimulation of elongation. PMID:11486022

  18. 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

  19. 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.

  20. Human copy number variation and complex genetic disease.

    PubMed

    Girirajan, Santhosh; Campbell, Catarina D; Eichler, Evan E

    2011-01-01

    Copy number variants (CNVs) play an important role in human disease and population diversity. Advancements in technology have allowed for the analysis of CNVs in thousands of individuals with disease in addition to thousands of controls. These studies have identified rare CNVs associated with neuropsychiatric diseases such as autism, schizophrenia, and intellectual disability. In addition, copy number polymorphisms (CNPs) are present at higher frequencies in the population, show high diversity in copy number, sequence, and structure, and have been associated with multiple phenotypes, primarily related to immune or environmental response. However, the landscape of copy number variation still remains largely unexplored, especially for smaller CNVs and those embedded within complex regions of the human genome. An integrated approach including characterization of single nucleotide variants and CNVs in a large number of individuals with disease and normal genomes holds the promise of thoroughly elucidating the genetic basis of human disease and diversity.

  1. Bibliometric analysis of Human Factors (1970-2000): a quantitative description of scientific impact.

    PubMed

    Dee, John D; Cassano-Pinché, Andrea; Vicente, Kim J

    2005-01-01

    Bibliometric analyses use the citation history of scientific articles as data to measure scientific impact. This paper describes a bibliometric analysis of the 1682 papers and 2413 authors published in Human Factors from 1970 to 2000. The results show that Human Factors has substantial relative scientific influence, as measured by impact, immediacy, and half-life, exceeding the influence of comparable journals. Like other scientific disciplines, human factors research is a highly stratified activity. Most authors have published only one paper, and many papers are cited infrequently, if ever. A small number of authors account for a disproportionately large number of the papers published and citations received. However, the degree of stratification is not as extreme as in many other disciplines, possibly reflecting the diversity of the human factors discipline. A consistent trend of more authors per paper parallels a similar trend in other fields and may reflect the increasingly interdisciplinary nature of human factors research and a trend toward addressing human-technology interaction in more complex systems. Ten of the most influential papers from each of the last 3 decades illustrate trends in human factors research. Actual or potential applications of this research include considerations for the publication and distribution policy of Human Factors.

  2. 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.

  3. Differential proteolytic activation of factor VIII-von Willebrand factor complex by thrombin

    SciTech Connect

    Hill-Eubanks, D.C.; Parker, C.G.; Lollar, P. )

    1989-09-01

    Blood coagulation factor VIII (fVIII) is a plasma protein that is decreased or absent in hemophilia A. It is isolated as a mixture of heterodimers that contain a variably sized heavy chain and a common light chain. Thrombin catalyzes the activation of fVIII in a reaction that is associated with cleavages in both types of chain. The authors isolated a serine protease from Bothrops jararacussu snake venom that catalyzes thrombin-like heavy-chain cleavage but not light-chain cleavage in porcine fVIII as judged by NaDodSO{sub 4}/PAGE and N-terminal sequence analysis. Using a plasma-free assay of the ability of activated {sup 125}I-fVIII to function as a cofactor in the activation of factor X by factor IXa, they found that fVIII is activated by the venom enzyme. The venom enzyme-activated fVIII was isolated in stable form by cation-exchange HPLC. von Willebrand factor inhibited venom enzyme-activated fVIII but not thrombin-activated fVIII. These results suggest that the binding of fVIII to von Willebrand factor depends on the presence of an intact light chain and that activated fVIII must dissociate from von Willebrand factor to exert its cofactor effect. Thus, proteolytic activation of fVIII-von Willebrand factor complex appears to be differentially regulated by light-chain cleavage to dissociate the complex and heavy-chain cleavage to activate the cofactor function.

  4. 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

  5. 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.

  6. The Driving Forces of Cultural Complexity : Neanderthals, Modern Humans, and the Question of Population Size.

    PubMed

    Fogarty, Laurel; Wakano, Joe Yuichiro; Feldman, Marcus W; Aoki, Kenichi

    2017-03-01

    The forces driving cultural accumulation in human populations, both modern and ancient, are hotly debated. Did genetic, demographic, or cognitive features of behaviorally modern humans (as opposed to, say, early modern humans or Neanderthals) allow culture to accumulate to its current, unprecedented levels of complexity? Theoretical explanations for patterns of accumulation often invoke demographic factors such as population size or density, whereas statistical analyses of variation in cultural complexity often point to the importance of environmental factors such as food stability, in determining cultural complexity. Here we use both an analytical model and an agent-based simulation model to show that a full understanding of the emergence of behavioral modernity, and the cultural evolution that has followed, depends on understanding and untangling the complex relationships among culture, genetically determined cognitive ability, and demographic history. For example, we show that a small but growing population could have a different number of cultural traits from a shrinking population with the same absolute number of individuals in some circumstances.

  7. A Voice-Radio Method for Collecting Human Factors Data.

    ERIC Educational Resources Information Center

    Askren, William B.; And Others

    Available methods for collecting human factors data rely heavily on observations, interviews, and questionnaires. A need exists for other methods. The feasibility of using two-way voice-radio for this purpose was studied. The data collection methodology consisted of a human factors analyst talking from a radio base station with technicians wearing…

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. A Systematic Approach to Human Factors Measurement

    DTIC Science & Technology

    1978-10-01

    that system. Previous Verification tests (see Askren and Newton , 1969) have examined the following: a. Human design considerations relative to...process. In actual maintenance operationm4 there Is, of course, a performance standard which is usually defined as mecan -time-to-repair (HTTR). However...Askren, W. B. and Newton , R. R. Review and analysis of personnel subsystem test and evaluation literature (AFHRL-TR-68-7). Air Force Human Resources

  13. 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.

  14. 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.

  15. Proceedings of the Human Factors Society 35th annual meeting

    SciTech Connect

    Not Available

    1991-01-01

    These volumes cover the proceedings of the 35th annual meeting of the Human Factors Society. Topics include: designing for the future of nuclear power plants international perspectives on advanced control room design; human performance assessment in the nuclear power industry; validity of strength tests for predicting endurance of coal miners, psychosocial issues in hazard management and nuclear power plants; and human factors at the DOE's national laboratories.

  16. 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.

  17. 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.

  18. Human erythrocytes inhibit complement-mediated solubilization of immune complexes by human serum

    SciTech Connect

    Dorval, B.L.

    1987-01-01

    The aim of this study was to develop an autologus human system to evaluate the effects of human erythrocytes on solubilization of immune complex precipitates (IC) by human serum. Incubation of IC with fresh human serum or guinea pig serum resulted in solubilization of IC. When packed erythrocytes were added to human serum or guinea pig serum binding of IC to the erythrocyte occurred and IC solubilization was inhibited significantly (p <.025). Sheep erythrocytes did not bind IC or inhibit IC solubilization. To evaluate the role of human erythrocyte complement receptor (CR1) on these findings, human erythrocytes were treated with trypsin or anti-CR1 antibodies. Both treatments abrogated IC binding to human erythrocytes but did not affect the ability of the human erythrocyte to inhibit IC solubilization. Radioimmunoassay was used to measure C3, C4 and C5 activation in human serum after incubation with IC, human erythrocytes, human erythrocytes plus IC, whole blood or in whole blood plus IC.

  19. Tissue Factor–Factor VII Complex As a Key Regulator of Ovarian Cancer Phenotypes

    PubMed Central

    Koizume, Shiro; Miyagi, Yohei

    2015-01-01

    Tissue factor (TF) is an integral membrane protein widely expressed in normal human cells. Blood coagulation factor VII (fVII) is a key enzyme in the extrinsic coagulation cascade that is predominantly secreted by hepatocytes and released into the bloodstream. The TF–fVII complex is aberrantly expressed on the surface of cancer cells, including ovarian cancer cells. This procoagulant complex can initiate intracellular signaling mechanisms, resulting in malignant phenotypes. Cancer tissues are chronically exposed to hypoxia. TF and fVII can be induced in response to hypoxia in ovarian cancer cells at the gene expression level, leading to the autonomous production of the TF–fVII complex. Here, we discuss the roles of the TF–fVII complex in the induction of malignant phenotypes in ovarian cancer cells. The hypoxic nature of ovarian cancer tissues and the roles of TF expression in endometriosis are discussed. Arguments will be extended to potential strategies to treat ovarian cancers based on our current knowledge of TF–fVII function. PMID:26396550

  20. 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.

  1. Neurophysiological Factors in Human Information Processing Capacity

    ERIC Educational Resources Information Center

    Ramsey, Nick F.; Jansma, J. M.; Jager, G.; Van Raalten, T.; Kahn, R. S.

    2004-01-01

    What determines how well an individual can manage the complexity of information processing demands when several tasks have to be executed simultaneously? Various theoretical frameworks address the mechanisms of information processing and the changes that take place when processes become automated, and brain regions involved in various types of…

  2. Integrated structural analysis of the human nuclear pore complex scaffold.

    PubMed

    Bui, Khanh Huy; von Appen, Alexander; DiGuilio, Amanda L; Ori, Alessandro; Sparks, Lenore; Mackmull, Marie-Therese; Bock, Thomas; Hagen, Wim; Andrés-Pons, Amparo; Glavy, Joseph S; Beck, Martin

    2013-12-05

    The nuclear pore complex (NPC) is a fundamental component of all eukaryotic cells that facilitates nucleocytoplasmic exchange of macromolecules. It is assembled from multiple copies of about 30 nucleoporins. Due to its size and complex composition, determining the structure of the NPC is an enormous challenge, and the overall architecture of the NPC scaffold remains elusive. In this study, we have used an integrated approach based on electron tomography, single-particle electron microscopy, and crosslinking mass spectrometry to determine the structure of a major scaffold motif of the human NPC, the Nup107 subcomplex, in both isolation and integrated into the NPC. We show that 32 copies of the Nup107 subcomplex assemble into two reticulated rings, one each at the cytoplasmic and nuclear face of the NPC. This arrangement may explain how changes of the diameter are realized that would accommodate transport of huge cargoes.

  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. Polyelectrolyte complexes stabilize and controllably release vascular endothelial growth factor.

    PubMed

    Huang, Min; Vitharana, Samadhi N; Peek, Laura J; Coop, Tina; Berkland, Cory

    2007-05-01

    Angiogenesis has long been a desired therapeutic approach to improve clinical outcomes of conditions typified by ischemia. Vascular endothelial growth factor (VEGF) has demonstrated the ability to generate new blood vessels in vivo, but trials using intravenous delivery have not yet produced clinical success. Localized, sustained delivery of VEGF has been proven necessary to generate blood vessels as demonstrated by implantable, controlled release devices. Ultimately, nanoparticles delivered by intravenous injection may be designed to accumulate in target tissues and sustain the local VEGF concentration; however, injectable nanosuspensions that control the release of stabilized VEGF must first be developed. In this study, we utilize the heparin binding domain of VEGF to bind the polyanion dextran sulfate, resulting in an enhanced thermal stability of VEGF. Coacervation of the VEGF-bound dextran sulfate with selected polycations (chitosan, polyethylenimine, or poly-L-lysine) produced nanoparticles approximately 250 nm in diameter with high VEGF encapsulation efficiency (50-85%). Release of VEGF from these formulations persisted for >10 days and maintained high VEGF activity as determined by ELISA and a mitogenic bioassay. Chitosan-dextran sulfate complexes were preferred because of their biodegradability, desirable particle size ( approximately 250 nm), entrapment efficiency ( approximately 85%), controlled release (near linear for 10 days), and mitogenic activity.

  5. Yeast and Human RNA Polymerase II Elongation Complexes: Evidence for Functional Differences and Postinitiation Recruitment of Factors†

    PubMed Central

    Pardee, Timothy S.; Ghazy, Mohamed A.; Ponticelli, Alfred S.

    2003-01-01

    Immobilized DNA templates, glycerol gradient centrifugation, and native gel analysis were utilized to isolate and compare functional RNA polymerase II (RNAPII) elongation complexes from Saccharomyces cerevisiae and human cell nuclear extracts. Yeast elongation complexes blocked by incorporation of 3′-O-methyl-GTP into the nascent transcript exhibited a sedimentation coefficient of 35S, were less tightly associated to the template than their human counterparts, and displayed no detectable 3′-5′ exonuclease activity on the associated transcript. In contrast, blocked human elongation complexes were more tightly bound to the template, and multiple forms were identified, with the largest exhibiting a sedimentation coefficient of 60S. Analysis of the associated transcripts revealed that a subset of the human elongation complexes exhibited strong 3′-5′ exonuclease activity. Although isolated human preinitiation complexes were competent for efficient transcription, their ability to generate 60S elongation complexes was strikingly impaired. These findings demonstrate functional and size differences between S. cerevisiae and human RNAPII elongation complexes and support the view that the formation of mature elongation complexes involves recruitment of nuclear factors after the initiation of transcription. PMID:12684381

  6. Cognitive work analysis: An influential legacy extending beyond human factors and engineering.

    PubMed

    Naikar, Neelam

    2017-03-01

    Jens Rasmussen's multifaceted legacy includes cognitive work analysis (CWA), a framework for the analysis, design, and evaluation of complex sociotechnical systems. After considering the framework's origins, this paper reviews its progress, predictably covering experimental research on ecological interface design, case studies of the application of CWA to human factors and engineering problems in industry, and methods and modelling tools for CWA. Emphasis is placed, however, on studying the nexus between some of the recent results obtained with CWA and the original field studies of human problem-solving that motivated the framework's development. Of particular interest is a case study of the use of CWA for military doctrine development, a problem commonly regarded as lying outside the fields of human factors and engineering. It is concluded that the value of CWA, even for such diverse problems, is likely to result from its conceptual grounding in empirical observations of patterns of human reasoning in complex systems.

  7. Genetics of human episodic memory: dealing with complexity.

    PubMed

    Papassotiropoulos, Andreas; de Quervain, Dominique J-F

    2011-09-01

    Episodic memory is a polygenic behavioral trait with substantial heritability estimates. Despite its complexity, recent empirical evidence supports the notion that behavioral genetic studies of episodic memory might successfully identify trait-associated molecules and pathways. The development of high-throughput genotyping methods, of elaborated statistical analyses and of phenotypic assessment methods at the neural systems level will facilitate the reliable identification of novel memory-related genes. Importantly, a necessary crosstalk between behavioral genetic studies and investigation of causality by molecular genetic studies will ultimately pave the way towards the identification of biologically important, and hopefully druggable, genes and molecular pathways related to human episodic memory.

  8. 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

  9. Mechanisms for recurrent and complex human genomic rearrangements

    PubMed Central

    Liu, Pengfei; Carvalho, Claudia M.B.; Hastings, P. J.; Lupski, James R.

    2012-01-01

    During the last two decades, the importance of human genome copy number variation (CNV) in disease has become widely recognized. However, much is not understood about underlying mechanisms. We show how, although model organism research guides molecular understanding, important insights are gained from study of the wealth of information available in the clinic. We describe progress in explaining nonallelic homologous recombination (NAHR), a major cause of copy number change occurring when control of allelic recombination fails, highlight the growing importance of replicative mechanisms to explain complex events, and describe progress in understanding extreme chromosome reorganization (chromothripsis). Both non-homologous end-joining and aberrant replication have significant roles in chromothripsis. As we study CNV, the processes underlying human genome evolution are revealed. PMID:22440479

  10. Human Factors in Command-and-Control System Procurement,

    DTIC Science & Technology

    1985-12-01

    requirement for the equipment designer to take account of the human operator in the design and development of systems. Accordingly, human factors...they fail to take account of software development and the flow of information between the human and the machine. There has been a growing awareness... account of the human operator in the design and development of systems. Meister and Rabideau (1965) indicated that the concern centred on the ability

  11. Modeling of human factor Va inactivation by activated protein C

    PubMed Central

    2012-01-01

    Background Because understanding of the inventory, connectivity and dynamics of the components characterizing the process of coagulation is relatively mature, it has become an attractive target for physiochemical modeling. Such models can potentially improve the design of therapeutics. The prothrombinase complex (composed of the protease factor (F)Xa and its cofactor FVa) plays a central role in this network as the main producer of thrombin, which catalyses both the activation of platelets and the conversion of fibrinogen to fibrin, the main substances of a clot. A key negative feedback loop that prevents clot propagation beyond the site of injury is the thrombin-dependent generation of activated protein C (APC), an enzyme that inactivates FVa, thus neutralizing the prothrombinase complex. APC inactivation of FVa is complex, involving the production of partially active intermediates and “protection” of FVa from APC by both FXa and prothrombin. An empirically validated mathematical model of this process would be useful in advancing the predictive capacity of comprehensive models of coagulation. Results A model of human APC inactivation of prothrombinase was constructed in a stepwise fashion by analyzing time courses of FVa inactivation in empirical reaction systems with increasing number of interacting components and generating corresponding model constructs of each reaction system. Reaction mechanisms, rate constants and equilibrium constants informing these model constructs were initially derived from various research groups reporting on APC inactivation of FVa in isolation, or in the presence of FXa or prothrombin. Model predictions were assessed against empirical data measuring the appearance and disappearance of multiple FVa degradation intermediates as well as prothrombinase activity changes, with plasma proteins derived from multiple preparations. Our work integrates previously published findings and through the cooperative analysis of in vitro

  12. Visualizing failure effects in complex human-machine systems

    NASA Astrophysics Data System (ADS)

    Price, Jana M.; Mathur, Amit; Morley, Rebecca M.; Scalzo, Richard C.

    2001-07-01

    The ability to understand a system's behavior in both normal and failed conditions is fundamental to the design of error-tolerant systems as well as to the development of diagnostics. The System Analysis for Failure and Error Reduction (SAFER) Project seeks to provide designers with tools to visualize potential sources of error and their effects early in the design of human-machine systems. The project is based on an existing technology that provides a failure-space modeling environment, analysis capabilities for troubleshooting, and error diagnostics using design data of machine systems. The SAFER Project extends the functionality of the existing technology in two significant ways. First, by adding a model of human error probability within the tool, designers are able to estimate the probabilities of human errors and the effects that these errors may have on system components and on the entire system. Second, the visual presentation of failure-related measures and metrics has been improved through a process of user-centered design. This paper will describe the process that was used to develop the human error probability model and will present novel metrics for assessing failure within complex systems.

  13. 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…

  14. Risk Factors for Relapse of Human Brucellosis

    PubMed Central

    Hasanjani Roushan, Mohammad Reza; Moulana, Zahra; Afshar, Zeinab Mohseni; Ebrahimpour, Soheil

    2016-01-01

    Background & Propose: Brucellosis is serious disease around the world, especially in underdeveloped countries. Relapse is major problem in therapy of brucellosis. This study aimed to evaluate risk factors of relapse after treatment in patients. Methods: It is a descriptive-analytic study from 1990 to 2014, in Ayatolla Rohani hospital in Babol, Iran. We studied 980 patients with brucellosis. The studied community included patients infected with brucellosis and the required information was gathered based on their hospital files. The base for recognizing Malta fever were clinical symptoms and Para-clinical sign congruent with infection like as, titer SAT>1:320 and 2-ME>1:160. Patients with relapse and patients without relapse were placed separately in two groups. The data were statistically compared with Spss 16, by Chi-square and Cox–regression tests. Results: Based on this study, treatment regimen is a preventive factor (P=0.000). Moreover, Based on some statistical methods, regimens no. 3 and 4 were introduce preventive factors (P=0.001) and (P=0.004). It should also be noted that findings the same statistical model, factors like gender, age, residence, professional contacts, complications and delay in treatment were also analyzed but none of them are considered as preventive factors. Conclusion: Based our finding, we suggest aminoglycosides (gentamicin or streptomycin with doxycycline) are associated with lower rate of relapse in brucellosis. PMID:26925907

  15. Human Factors Engineering. Part 2. HEDGE (Human Factors Engineering Data Guide for Evaluation)

    DTIC Science & Technology

    1983-11-30

    by color, sie Point%. provided. fibeled . 6 Jack. Toaist poinfts WWI d. sign advertising of trotanki othsn, lit I -s.. n Io,,-Ieho lin..a 6_ plosg. r.pfs...DATA r EmlL-sTo- I ’.712£ L C’ T 1y FIGURE 8.8.1 COUNTERS , FLAGS, PRINTERS, AND PLOTTERS ISAII AC~tMA84. o ~- -~1ACION LoY TVl 0T1l 11I.o 8IIOA 0.-. wo...IDRST-P70-0 Test Operations Procedure 1-2-610 AD I ," ( , HUMAN FACTORS ENG PAR I I ... ..... Reproduced From Best Available Copy . ,.frpbi ees;dsrbto

  16. 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.

  17. Human factors engineering approaches to patient identification armband design.

    PubMed

    Probst, C Adam; Wolf, Laurie; Bollini, Mara; Xiao, Yan

    2016-01-01

    The task of patient identification is performed many times each day by nurses and other members of the care team. Armbands are used for both direct verification and barcode scanning during patient identification. Armbands and information layout are critical to reducing patient identification errors and dangerous workarounds. We report the effort at two large, integrated healthcare systems that employed human factors engineering approaches to the information layout design of new patient identification armbands. The different methods used illustrate potential pathways to obtain standardized armbands across healthcare systems that incorporate human factors principles. By extension, how the designs have been adopted provides examples of how to incorporate human factors engineering into key clinical processes.

  18. 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.

  19. 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.

  20. 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.

  1. Disrupting Mitochondrial–Nuclear Coevolution Affects OXPHOS Complex I Integrity and Impacts Human Health

    PubMed Central

    Gershoni, Moran; Levin, Liron; Ovadia, Ofer; Toiw, Yasmin; Shani, Naama; Dadon, Sara; Barzilai, Nir; Bergman, Aviv; Atzmon, Gil; Wainstein, Julio; Tsur, Anat; Nijtmans, Leo; Glaser, Benjamin; Mishmar, Dan

    2014-01-01

    The mutation rate of the mitochondrial DNA (mtDNA), which is higher by an order of magnitude as compared with the nuclear genome, enforces tight mitonuclear coevolution to maintain mitochondrial activities. Interruption of such coevolution plays a role in interpopulation hybrid breakdown, speciation events, and disease susceptibility. Previously, we found an elevated amino acid replacement rate and positive selection in the nuclear DNA-encoded oxidative phosphorylation (OXPHOS) complex I subunit NDUFC2, a phenomenon important for the direct interaction of NDUFC2 with the mtDNA-encoded complex I subunit ND4. This finding underlines the importance of mitonuclear coevolution to physical interactions between mtDNA and nuclear DNA-encoded factors. Nevertheless, it remains unclear whether this interaction is important for the stability and activity of complex I. Here, we show that siRNA silencing of NDUFC2 reduced growth of human D-407 retinal pigment epithelial cells, significantly diminished mitochondrial membrane potential, and interfered with complex I integrity. Moreover, site-directed mutagenesis of a positively selected amino acid in NDUFC2 significantly interfered with the interaction of NDUFC2 with its mtDNA-encoded partner ND4. Finally, we show that a genotype combination involving this amino acid (NDUFC2 residue 46) and the mtDNA haplogroup HV likely altered susceptibility to type 2 diabetes mellitus in Ashkenazi Jews. Therefore, mitonuclear coevolution is important for maintaining mitonuclear factor interactions, OXPHOS, and for human health. PMID:25245408

  2. Activation and function of human Hageman factor. The role of high molecular weight kininogen and prekallikrein.

    PubMed Central

    Meier, H L; Pierce, J V; Colman, R W; Kaplan, A P

    1977-01-01

    The activation and function of surface-bound Hageman factor in human plasma are dependent upon both high molecular weight (HMW) kininogen and prekallikrein. HMW kininogen does not affect the binding of Hageman factor to surfaces, but it enhances the function of surface-bound Hageman factor as assessed by its ability to activate prekallikrein and Factor XI. The initial conversion of prekallikrein to kallikrein by the surface-bound Hageman factor in the presence of HMW kininogen is followed by a rapid enzymatic activation of Hageman factor by kallikrein. The latter interaction is also facilitated by HMW kininogen. Kallikrein therefore functions as an activator of Hageman factor by a positive feedback mechanism and generates most of the activated Hageman factor during brief exposure of plasma to activating surfaces. HMW kininogen is a cofactor in the enzymatic activation of Hageman factor by kallikrein and it also augments the function of the activated Hageman factor generated. The stoichiometry of the Hagman factor interaction with HMW kininogen suggests that it enhances the activity of the active site of Hageman factor. Since HMW kininogen and prekallikrein circulate as a complex, HMW kininogen may also place the prekallikrein in an optimal position for its reciprocal interaction with Hageman factor to proceed. The surface appears to play a passive role upon which bound Hageman factor and the prekallikrein-HMW kininogen complex can interact. PMID:874082

  3. Human factors aspects of control room design

    NASA Technical Reports Server (NTRS)

    Jenkins, J. P.

    1983-01-01

    A plan for the design and analysis of a multistation control room is reviewed. It is found that acceptance of the computer based information system by the uses in the control room is mandatory for mission and system success. Criteria to improve computer/user interface include: match of system input/output with user; reliability, compatibility and maintainability; easy to learn and little training needed; self descriptive system; system under user control; transparent language, format and organization; corresponds to user expectations; adaptable to user experience level; fault tolerant; dialog capability user communications needs reflected in flexibility, complexity, power and information load; integrated system; and documentation.

  4. Human serum albumin complexes with chlorophyll and chlorophyllin.

    PubMed

    Ouameur, A Ahmed; Marty, R; Tajmir-Riahi, H A

    2005-02-15

    Porphyrins and their metal derivatives are strong protein binders. Some of these compounds have been used for radiation sensitization therapy of cancer and are targeted to interact with cellular DNA and protein. The presence of several high-affinity binding sites on human serum albumin (HSA) makes it possible target for many organic and inorganic molecules. Chlorophyll a and chlorophyllin (a food-grade derivative of chlorophyll), the ubiquitous green plant pigment widely consumed by humans, are potent inhibitors of experimental carcinogenesis and interact with protein and DNA in many ways. This study was designed to examine the interaction of HSA with chlorophyll (Chl) and chlorophyllin (Chln) in aqueous solution at physiological conditions. Fourier transform infrared, UV-visible, and CD spectroscopic methods were used to determine the pigment binding mode, the binding constant, and the effects of porphyrin complexation on protein secondary structure. Spectroscopic results showed that chlorophyll and chlorophyllin are located along the polypeptide chains with no specific interaction. Stronger protein association was observed for Chl than for Chln, with overall binding constants of K(Chl) = 2.9 x 10(4)M(-1) and K(Chln) = 7.0 x 10(3)M(-1). The protein conformation was altered (infrared data) with reduction of alpha-helix from 55% (free HSA) to 41-40% and increase of beta-structure from 22% (free HSA) to 29-35% in the pigment-protein complexes. Using the CDSSTR program (CD data) also showed major reduction of alpha-helix from 66% (free HSA) to 58 and 55% upon complexation with Chl and Chln, respectively.

  5. 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.

  6. Using human factors engineering to improve the effectiveness of infection prevention and control.

    PubMed

    Anderson, Judith; Gosbee, Laura Lin; Bessesen, Mary; Williams, Linda

    2010-08-01

    Human factors engineering is a discipline that studies the capabilities and limitations of humans and the design of devices and systems for improved performance. The principles of human factors engineering can be applied to infection prevention and control to study the interaction between the healthcare worker and the system that he or she is working with, including the use of devices, the built environment, and the demands and complexities of patient care. Some key challenges in infection prevention, such as delayed feedback to healthcare workers, high cognitive workload, and poor ergonomic design, are explained, as is how human factors engineering can be used for improvement and increased compliance with practices to prevent hospital-acquired infections.

  7. The complexity of human walking: a knee osteoarthritis study.

    PubMed

    Kotti, Margarita; Duffell, Lynsey D; Faisal, Aldo A; McGregor, Alison H

    2014-01-01

    This study proposes a framework for deconstructing complex walking patterns to create a simple principal component space before checking whether the projection to this space is suitable for identifying changes from the normality. We focus on knee osteoarthritis, the most common knee joint disease and the second leading cause of disability. Knee osteoarthritis affects over 250 million people worldwide. The motivation for projecting the highly dimensional movements to a lower dimensional and simpler space is our belief that motor behaviour can be understood by identifying a simplicity via projection to a low principal component space, which may reflect upon the underlying mechanism. To study this, we recruited 180 subjects, 47 of which reported that they had knee osteoarthritis. They were asked to walk several times along a walkway equipped with two force plates that capture their ground reaction forces along 3 axes, namely vertical, anterior-posterior, and medio-lateral, at 1000 Hz. Data when the subject does not clearly strike the force plate were excluded, leaving 1-3 gait cycles per subject. To examine the complexity of human walking, we applied dimensionality reduction via Probabilistic Principal Component Analysis. The first principal component explains 34% of the variance in the data, whereas over 80% of the variance is explained by 8 principal components or more. This proves the complexity of the underlying structure of the ground reaction forces. To examine if our musculoskeletal system generates movements that are distinguishable between normal and pathological subjects in a low dimensional principal component space, we applied a Bayes classifier. For the tested cross-validated, subject-independent experimental protocol, the classification accuracy equals 82.62%. Also, a novel complexity measure is proposed, which can be used as an objective index to facilitate clinical decision making. This measure proves that knee osteoarthritis subjects exhibit more

  8. Complex Patterns of Association between Pleiotropy and Transcription Factor Evolution

    PubMed Central

    Chesmore, Kevin N.; Bartlett, Jacquelaine; Cheng, Chao; Williams, Scott M.

    2016-01-01

    Pleiotropy has been claimed to constrain gene evolution but specific mechanisms and extent of these constraints have been difficult to demonstrate. The expansion of molecular data makes it possible to investigate these pleiotropic effects. Few classes of genes have been characterized as intensely as human transcription factors (TFs). We therefore analyzed the evolutionary rates of full TF proteins, along with their DNA binding domains and protein-protein interacting domains (PID) in light of the degree of pleiotropy, measured by the number of TF–TF interactions, or the number of DNA-binding targets. Data were extracted from the ENCODE Chip-Seq dataset, the String v 9.2 database, and the NHGRI GWAS catalog. Evolutionary rates of proteins and domains were calculated using the PAML CodeML package. Our analysis shows that the numbers of TF-TF interactions and DNA binding targets associated with constrained gene evolution; however, the constraint caused by the number of DNA binding targets was restricted to the DNA binding domains, whereas the number of TF-TF interactions constrained the full protein and did so more strongly. Additionally, we found a positive correlation between the number of protein–PIDs and the evolutionary rates of the protein–PIDs. These findings show that not only does pleiotropy associate with constrained protein evolution but the constraint differs by domain function. Finally, we show that GWAS associated TF genes are more highly pleiotropic. The GWAS data illustrates that mutations in highly pleiotropic genes are more likely to be associated with disease phenotypes. PMID:27635052

  9. Overview: Human Factors Issues in Space Station Architecture

    NASA Technical Reports Server (NTRS)

    Cohen, M. M.

    1985-01-01

    An overview is presented of human factors issues in space station architecture. The status of the space station program is given. Habitability concerns such as vibroacoustics, lighting systems, privacy and work stations are discussed in detail.

  10. 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.

  11. 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.

  12. Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex.

    PubMed

    Janssen, Bert J C; Gomes, Lucio; Koning, Roman I; Svergun, Dmitri I; Koster, Abraham J; Fritzinger, David C; Vogel, Carl-Wilhelm; Gros, Piet

    2009-08-19

    Immune protection by the complement system critically depends on assembly of C3 convertases on the surface of pathogens and altered host cells. These short-lived protease complexes are formed through pro-convertases, which for the alternative pathway consist of the complement component C3b and the pro-enzyme factor B (FB). Here, we present the crystal structure at 2.2-A resolution, small-angle X-ray scattering and electron microscopy (EM) data of the pro-convertase formed by human FB and cobra venom factor (CVF), a potent homologue of C3b that generates more stable convertases. FB is loaded onto CVF through its pro-peptide Ba segment by specific contacts, which explain the specificity for the homologous C3b over the native C3 and inactive products iC3b and C3c. The protease segment Bb binds the carboxy terminus of CVF through the metal-ion dependent adhesion site of the Von Willebrand factor A-type domain. A possible dynamic equilibrium between a 'loading' and 'activation' state of the pro-convertase may explain the observed difference between the crystal structure of CVFB and the EM structure of C3bB. These insights into formation of convertases provide a basis for further development of complement therapeutics.

  13. 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.

  14. 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.

  15. 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.

  16. Surgical Technology Integration with Tools for Cognitive Human Factors (STITCH)

    DTIC Science & Technology

    2007-10-01

    Award Number: W81XWH-06-1-0761 TITLE: Surgical Technology Integration with Tools for Cognitive Human Factors (STITCH) PRINCIPAL INVESTIGATOR...23 JUL 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Surgical Technology Integration with Tools for Cognitive Human Factors (STITCH) 5b. GRANT...Accomplishments 5 Reportable Outcomes 14 Conclusions 15 Appendices 17 References (appendix B) 18 Surgical Technology Integration with Tools for

  17. 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.

  18. Research Directory for Manpower, Personnel, Training, and Human Factors.

    DTIC Science & Technology

    1991-01-01

    Design 89 * * * HUMAN FACTORS ENGINEERING (lIFE) * AIR FORCE Arnaiz J* Gentex Corp 717-282-3550 Support of the Evaluation of Night Vision Devices...Command 8 48 Armstrong R Mr Human Engineering Lab 10 76 Arnaiz J* Gentex Corp 10 90 Arnold D Office of the Chief of Naval Operations 6 41 Arnold L

  19. 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.

  20. 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)

  1. 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

  2. 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

  3. A20: linking a complex regulator of ubiquitylation to immunity and human disease

    PubMed Central

    Ma, Averil; Malynn, Barbara A.

    2013-01-01

    A20 (also known as TNFAIP3) is a potent anti-inflammatory signalling molecule that restricts multiple intracellular signalling cascades. Recent studies in three general areas have converged to highlight the clinical and biological importance of A20. First, human genetic studies have strongly linked polymorphisms and mutations in the gene encoding A20 to inflammatory, autoimmune and malignant diseases. Second, studies in gene-targeted mice have revealed that A20 regulates multiple immune cell functions and prevents experimental diseases that closely mimic human conditions. Third, biochemical studies have unveiled complex mechanisms by which A20 regulates ubiquitin-dependent nuclear factor-κB and cell-survival signals. Taken together, these studies are revealing the importance of A20-mediated regulation of ubiquitin-dependent signalling in human disease. PMID:23059429

  4. Training for planning tumour resection: augmented reality and human factors.

    PubMed

    Abhari, Kamyar; Baxter, John S H; Chen, Elvis C S; Khan, Ali R; Peters, Terry M; de Ribaupierre, Sandrine; Eagleson, Roy

    2015-06-01

    Planning surgical interventions is a complex task, demanding a high degree of perceptual, cognitive, and sensorimotor skills to reduce intra- and post-operative complications. This process requires spatial reasoning to coordinate between the preoperatively acquired medical images and patient reference frames. In the case of neurosurgical interventions, traditional approaches to planning tend to focus on providing a means for visualizing medical images, but rarely support transformation between different spatial reference frames. Thus, surgeons often rely on their previous experience and intuition as their sole guide is to perform mental transformation. In case of junior residents, this may lead to longer operation times or increased chance of error under additional cognitive demands. In this paper, we introduce a mixed augmented-/virtual-reality system to facilitate training for planning a common neurosurgical procedure, brain tumour resection. The proposed system is designed and evaluated with human factors explicitly in mind, alleviating the difficulty of mental transformation. Our results indicate that, compared to conventional planning environments, the proposed system greatly improves the nonclinicians' performance, independent of the sensorimotor tasks performed ( ). Furthermore, the use of the proposed system by clinicians resulted in a significant reduction in time to perform clinically relevant tasks ( ). These results demonstrate the role of mixed-reality systems in assisting residents to develop necessary spatial reasoning skills needed for planning brain tumour resection, improving patient outcomes.

  5. 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.

  6. 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

  7. [Physical factors in human ecology and environmental hygiene].

    PubMed

    Rakhmanin, Iu A

    2009-01-01

    The paper considers the problem while studying various physical factors of the environment. It presents prospects for further investigations of the influence of physical factors on human health and the quality of the environment. The paper also gives a detailed description of advances and promising lines of studies in the area under discussion.

  8. 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

  9. 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.

  10. Robotics and human factors: current status and future prospects

    SciTech Connect

    Mcilvaine Parsons, H.; Kearsley, G.P.

    1982-10-01

    From the perspective of human factors engineering, the most important question is the division of labor between robots and humans, who participate in robot systems in nine activities: surveillance, intervention, maintenance, backup, input, output, supervision, inspection, and synergy. Additional concerns include hardware and software design of interfaces with operators, procedure development, accident prevention, and training. There have been a few human factors studies but more are needed, drawing in part on research in artificial intelligence, to support robotics for industrial productivity and military requirements. 49 references.

  11. 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.

  12. 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.

  13. 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.

  14. 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).

  15. 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.

  16. Distribution of adenosine deaminase complexing protein (ADCP) in human tissues.

    PubMed

    Dinjens, W N; ten Kate, J; van der Linden, E P; Wijnen, J T; Khan, P M; Bosman, F T

    1989-12-01

    The normal distribution of adenosine deaminase complexing protein (ADCP) in the human body was investigated quantitatively by ADCP-specific radioimmunoassay (RIA) and qualitatively by immunohistochemistry. In these studies we used a specific rabbit anti-human ADCP antiserum. In all 19 investigated tissues, except erythrocytes, ADCP was found by RIA in the soluble and membrane fractions. From all tissues the membrane fractions contained more ADCP (expressed per mg protein) than the soluble fractions. High membrane ADCP concentrations were found in skin, renal cortex, gastrointestinal tract, and prostate. Immunoperoxidase staining confirmed the predominant membrane-associated localization of the protein. In serous sweat glands, convoluted tubules of renal cortex, bile canaliculi, gastrointestinal tract, lung, pancreas, prostate gland, salivary gland, gallbladder, mammary gland, and uterus, ADCP immunoreactivity was found confined to the luminal membranes of the epithelial cells. These data demonstrate that ADCP is present predominantly in exocrine glands and absorptive epithelia. The localization of ADCP at the secretory or absorptive apex of the cells suggests that the function of ADCP is related to the secretory and/or absorptive process.

  17. Identification of human autoantibodies to transcription factor IIB.

    PubMed Central

    Abendroth, F D; Peterson, S R; Galman, M; Suwa, A; Hardin, J A; Dynan, W S

    1995-01-01

    We have characterized the ability of various human autoimmune sera to react with RNA polymerase II transcription factors. One serum, which strongly inhibited transcription in a cell-free system, was shown to contain antibodies directed against human TFIIB. The serum did not show reactivity against the other general transcription factors, including human TBP, TFIIE and TFIIF. The inhibition of transcription was directly attributable to depletion of TFIIB activity, as demonstrated by reconstitution of activity with recombinant TFIIB. It has long been recognized that components of the RNA processing machinery are major human autoantigens. The present results show that at least one general transcription factor required for messenger RNA synthesis is an autoantigen as well. Images PMID:7651839

  18. 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.

  19. 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).

  20. 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.

  1. 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

  2. 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...

  3. 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...

  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. 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

  5. Research Progress on the Risk Factors and Outcomes of Human Carotid Atherosclerotic Plaques

    PubMed Central

    Xiong, Xiang-Dong; Xiong, Wei-Dong; Xiong, Shang-Shen; Chen, Gui-Hai

    2017-01-01

    Objective: Atherosclerosis is an inflammatory process that results in complex lesions or plaques that protrude into the arterial lumen. Carotid atherosclerotic plaque rupture, with distal atheromatous debris embolization, causes cerebrovascular events. This review aimed to explore research progress on the risk factors and outcomes of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention. Data Sources: We searched the PubMed database for recently published research articles up to June 2016, with the key words of “risk factors”, “outcomes”, “blood components”, “molecular mechanisms”, “cellular mechanisms”, and “human carotid atherosclerotic plaques”. Study Selection: The articles, regarding the latest developments related to the risk factors and outcomes, atherosclerotic plaque composition, blood components, and consequences of human carotid atherosclerotic plaques, and the molecular and cellular mechanisms of human carotid atherosclerotic plaque vulnerability for therapeutic intervention, were selected. Results: This review described the latest researches regarding the interactive effects of both traditional and novel risk factors for human carotid atherosclerotic plaques, novel insights into human carotid atherosclerotic plaque composition and blood components, and consequences of human carotid atherosclerotic plaque. Conclusion: Carotid plaque biology and serologic biomarkers of vulnerability can be used to predict the risk of cerebrovascular events. Furthermore, plaque composition, rather than lesion burden, seems to most predict rupture and subsequent thrombosis. PMID:28303857

  6. 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.

  7. Discovery of Insect and Human Dengue Virus Host Factors

    PubMed Central

    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.

    2012-01-01

    Dengue fever (DF) is the most frequent arthropod-borne viral disease of humans, with almost half of the world's population at risk of infection1. The high prevalence, lack of an effective vaccine, and absence of specific treatment conspire to make DF a global public health threat1, 2. Given their compact genomes, dengue viruses (DENV 1-4) and other flaviviruses likely 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 identified3-10. To discover insect host factors required for DENV-2 propagation, we carried out a genome-wide RNA interference screen in Drosophila melanogaster cells using a well-established 22,632 dsRNA library. This screen identified 116 candidate dengue virus host factors (DVHFs) (Supplementary Fig. 1). While some were previously associated with flaviviruses (e.g., V-ATPases and alpha-glucosidases)3-5, 7, 9, 10, most DVHFs were newly implicated in DENV propagation. The dipteran DVHFs had eighty-two readily recognizable human homologues and, using a targeted siRNA screen, we showed that forty-two of these are human DVHFs. This indicates remarkable conservation of required factors between dipteran and human hosts. This work suggests novel approaches to control infection in the insect vector and the mammalian host. PMID:19396146

  8. Human Mitochondrial Transcription Initiation Complexes Have Similar Topology on the Light and Heavy Strand Promoters.

    PubMed

    Morozov, Yaroslav I; Temiakov, Dmitry

    2016-06-24

    Transcription is a highly regulated process in all domains of life. In human mitochondria, transcription of the circular genome involves only two promoters, called light strand promoter (LSP) and heavy strand promoter (HSP), located in the opposite DNA strands. Initiation of transcription occurs upon sequential assembly of an initiation complex that includes mitochondrial RNA polymerase (mtRNAP) and the initiation factors mitochondrial transcription factor A (TFAM) and TFB2M. It has been recently suggested that the transcription initiation factor TFAM binds to HSP and LSP in opposite directions, implying that the mechanisms of transcription initiation are drastically dissimilar at these promoters. In contrast, we found that binding of TFAM to HSP and the subsequent recruitment of mtRNAP results in a pre-initiation complex that is remarkably similar in topology and properties to that formed at the LSP promoter. Our data suggest that assembly of the pre-initiation complexes on LSP and HSP brings these transcription units in close proximity, providing an opportunity for regulatory proteins to simultaneously control transcription initiation in both mtDNA strands.

  9. Algebraic approach to form factors in the complex sinh-Gordon theory

    NASA Astrophysics Data System (ADS)

    Lashkevich, Michael; Pugai, Yaroslav

    2017-01-01

    We study form factors of the quantum complex sinh-Gordon theory in the algebraic approach. In the case of exponential fields the form factors can be obtained from the known form factors of the ZN-symmetric Ising model. The algebraic construction also provides an Ansatz for form factors of descendant operators. We obtain generating functions of such form factors and establish their main properties: the cluster factorization and reflection equations.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 77 FR 3500 - VTECH Communications, Inc., Human Factors Department, Beaverton, OR; Amended Certification...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-24

    ... Communications, Inc., Human Factors Department, Beaverton, OR; Amended Certification Regarding Eligibility To... the subject firm should read VTech Communications, Inc., Human Factors Department, Beaverton, Oregon... VTech Communications, Inc., Human Factors Department, Beaverton, Oregon. The intent of the...

  15. 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.

  16. Human Cytomegalovirus UL97 Phosphorylates the Viral Nuclear Egress Complex

    PubMed Central

    Sharma, Mayuri; Bender, Brian J.; Kamil, Jeremy P.; Lye, Ming F.; Pesola, Jean M.; Reim, Natalia I.; Hogle, James M.

    2014-01-01

    ABSTRACT Herpesvirus nucleocapsids exit the host cell nucleus in an unusual process known as nuclear egress. The human cytomegalovirus (HCMV) UL97 protein kinase is required for efficient nuclear egress, which can be explained by its phosphorylation of the nuclear lamina component lamin A/C, which disrupts the nuclear lamina. We found that a dominant negative lamin A/C mutant complemented the replication defect of a virus lacking UL97 in dividing cells, validating this explanation. However, as complementation was incomplete, we investigated whether the HCMV nuclear egress complex (NEC) subunits UL50 and UL53, which are required for nuclear egress and recruit UL97 to the nuclear rim, are UL97 substrates. Using mass spectrometry, we detected UL97-dependent phosphorylation of UL50 residue S216 (UL50-S216) and UL53-S19 in infected cells. Moreover, UL53-S19 was specifically phosphorylated by UL97 in vitro. Notably, treatment of infected cells with the UL97 inhibitor maribavir or infection with a UL97 mutant led to a punctate rather than a continuous distribution of the NEC at the nuclear rim. Alanine substitutions in both UL50-S216 and UL53-S19 resulted in a punctate distribution of the NEC in infected cells and also decreased virus production and nuclear egress in the absence of maribavir. These results indicate that UL97 phosphorylates the NEC and suggest that this phosphorylation modulates nuclear egress. Thus, the UL97-NEC interaction appears to recruit UL97 to the nuclear rim both for disruption of the nuclear lamina and phosphorylation of the NEC. IMPORTANCE Human cytomegalovirus (HCMV) causes birth defects and it can cause life-threatening diseases in immunocompromised patients. HCMV assembles in the nucleus and then translocates to the cytoplasm in an unusual process termed nuclear egress, an attractive target for antiviral therapy. A viral enzyme, UL97, is important for nuclear egress. It has been proposed that this is due to its role in disruption of the

  17. Human Factors Society, Annual Meeting, 32nd, Anaheim, CA, Oct. 24-28, 1988. Proceedings. Volumes 1 and 2

    SciTech Connect

    Not Available

    1988-01-01

    Papers dealing with human factors in transportation are presented, covering topics such as pilot performance and simulation, Space Station design and performance, human factors design in special-purpose workstations for the Space Station, auditory spatial information and head-coupled display systems, situation awareness in aircraft systems, control and display issues, human factors in maintenance, aging, telephony and video teleconferencing, auditory and vocal communication, and aircrew station workload, design, and automation. Other subjects include approaches to user interface design, speech recognition systems, hypermedia and interfaces, the development of documentation in real time, computer screen and menu design, expert systems, human factors education, design of work environments, forensics issues, human factors and automobiles, industrial ergonomics, international technology transfer, organizational design and management, personality and human performance, mental models of complex performance, and gender, intelligence, and human performance. Additional topics include accident analysis, product safety, transportation safety, robotics/industrial safety, system development, the human-computer interface, human factors in navy systems, workload evaluation, training systems and data bases, skill aquisition, visual performance, information portrayal determinants of complex decision making, and advanced displays.

  18. 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 developed. The…

  19. 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

    2016-07-08

    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.

  20. A homologue of the human STRIPAK complex controls sexual development in fungi.

    PubMed

    Bloemendal, Sandra; Bernhards, Yasmine; Bartho, Kathrin; Dettmann, Anne; Voigt, Oliver; Teichert, Ines; Seiler, Stephan; Wolters, Dirk A; Pöggeler, Stefanie; Kück, Ulrich

    2012-04-01

    Sexual development in fungi is a complex process involving the generation of new cell types and tissues - an essential step for all eukaryotic life. The characterization of sterile mutants in the ascomycete Sordaria macrospora has led to a number of proteins involved in sexual development, but a link between these proteins is still missing. Using a combined tandem-affinity purification/mass spectrometry approach, we showed in vivo association of developmental protein PRO22 with PRO11, homologue of mammalian striatin, and SmPP2AA, scaffolding subunit of protein phosphatase 2A. Further experiments extended the protein network to the putative kinase activator SmMOB3, known to be involved in sexual development. Extensive yeast two-hybrid studies allowed us to pinpoint functional domains involved in protein-protein interaction. We show for the first time that a number of already known factors together with new components associate in vivo to form a highly conserved multi-subunit complex. Strikingly, a similar complex has been described in humans, but the function of this so-called striatin interacting phosphatase and kinase (STRIPAK) complex is largely unknown. In S. macrospora, truncation of PRO11 and PRO22 leads to distinct defects in sexual development and cell fusion, indicating a role for the fungal STRIPAK complex in both processes.

  1. Discontinuities in the Human Bone-PDL-Cementum Complex

    PubMed Central

    Hurng, Jonathan M.; Kurylo, Michael P.; Marshall, Grayson W.; Webb, Samuel M.; Ryder, Mark I.; Ho, Sunita P.

    2011-01-01

    A naturally graded interface due to functional demands can deviate toward a discontinuous interface, eventually decreasing the functional efficiency of a dynamic joint. It is this characteristic feature in a human fibrous joint i.e. bone-tooth complex that will be discussed through histochemistry, and site-specific high resolution microscopy, micro tomography, X-ray fluorescence imaging and wet nanoindentation techniques. Results demonstrated two causes for the occurrence of 5-50 μm narrowed PDL-space: 1) microscopic scalloped regions at the PDL-insertion sites and macroscale stratified layers of bone with rich basophilic lines, and 2) macroscopic bony protrusions. Narrowed PDL-complexes illustrated patchy appearance of asporin, and when imaged under wet conditions using an atomic force microscope (AFM), demonstrated structural reorganization of the PDL, collagen periodicity, organic-dominant areas at the PDL-cementum and PDL-bone entheses and within cementum and bone. Scanning electron microscopy (SEM) results confirmed AFM results. Despite the narrowed PDL, continuity between PDL and vasculature in endosteal spaces of bone was demonstrated using a Micro XCT™. The higher levels of Ca and P X-ray fluorescence using a microprobe were correlated with higher elastic modulus values of 0.1-1.4 and 0.1-1.2 GPa for PDL-bone and PDL-cementum using wet nanoindentation. The ranges in elastic modulus values for PDL-bone and PDL-cementum entheses in 150-380 μm wide PDL-complex were 0.1-1.0 and 0.1-0.6 GPa. Based on these results we propose that strain amplification at the entheses could be minimized with a gradual change in modulus profile, a characteristic of 150-380 μm wide functional PDL-space. However, a discontinuity in modulus profile, a characteristic of 5-50 μm narrowed PDL-space would cause compromised mechanotransduction. The constrictions or narrowed sites within the bone-tooth fibrous joint will become the new “load bearing sites” that eventually could

  2. 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.

  3. Human factors dealing with the International Asteroid Mission

    NASA Astrophysics Data System (ADS)

    Human factors encompass many concerns in the 2.83 year International Asteroid Mission (IAM) mission from the initial crew selection to the final readaptation to Earth environment. These factors include radiation, physical deconditioning, crew selection and interaction, psychosocial issues, and health maintenance. The main theme that runs throughout the group's work is the lack of current available research into the problem areas. This stems from the relatively short mission durations in the last 30 years of spaceflight and thus no heavy emphasis in the human factors area. In short, no one has been in space for 3 years and thus we do not know what the effects of a three year flight are. It will be one of the goals in the IAM mission to do some research that may contribute to the fundamental knowledge of preparing for how humans can live in space.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. Immunoassay of human platelet factor 4(PF4, antiheparin factor) by radial immunodiffusion.

    PubMed

    Niewiarowski, S; Lowery, C T; Hawiger, J; Millman, M; Timmons, S

    1976-04-01

    Human platelet factor 4 antigen (PF4 antigen) was measured in platelets and in plasma by means of single radial immunodiffusion. Anti-PF4 antibody obtained in rabbits by injecting highly purified human PF4 was monospecific in double immunodiffusion and in quantitative "rocket" immunoelectrophoresis. A high degree of correlation was observed between the precipitation zones in the radial immunodiffusion method and the amount of purified PF4 (in the range of 0.6 to 50.0 mug per milliliter) or the number of platelets in plasma (in the range of 5 x 10(6) to 1.6 x 10(8) platelets per milliliter applied. The sensitivity of the method was 30 to 125 times higher as compared with clotting assay (antiheparin activity) and the standard error of the method was 2.3 per cent. The method was specific for the antigen present in platelets since human leukocytes and erythrocytes gave negative results. Release of PF4 antigen from washed platelets challenged with thrombin, collagen, ADP, and antigen-antibody complexes was measured by the radial immunodiffusion assay. It usually paralleled the release of 3H-serotonin but PF4 antigen was a more sensitive marker for platelet release reaction. Release of PF4 antigen was usually 2 to 4 times higher than release of the antiheparin activity as measured by clotting assay when both were compared as percentage of total content in platelets. The level of PF4 antigen was determined in platelet-rich plasma (PRP) and platelet-free plasma (PFP) obtained from 12 healthy volunteers. While the mean level of extraplatelet pool of PF4 antigen in PFP was 0.72 +/- 0.92 mug per milliliter, PRP contained 80 +/- 22 mug of PF4 antigen per 10(9) platelets. Addition of thrombin (1 U. per milliliter) liberated all of the PF4 antigen (78 +/- 24 mug) present in PRP but ADP (50 muM) released only 31 +/- 22 mug of PF4 antigen per 10(9) platelets. The presence of heparin did not interfere with the assay of intraplatelet or extraplatelet PF4 by single radial

  10. 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.

  11. TIMMDC1/C3orf1 functions as a membrane-embedded mitochondrial complex I assembly factor through association with the MCIA complex.

    PubMed

    Guarani, Virginia; Paulo, Joao; Zhai, Bo; Huttlin, Edward L; Gygi, Steven P; Harper, J Wade

    2014-03-01

    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.

  12. 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

  13. 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.

  14. 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.

  15. Genetic and environmental factors in experimental and human cancer

    SciTech Connect

    Takayama, S.; Takebe, H.; Gelboin, H.V.; MaChahon, B.; Matsushima, T.; Sugimura, T.

    1980-01-01

    Recently technological advances in assaying mutagenic principles have revealed that there are many mutagens in the environment, some of which might be carcinogenic to human beings. Other advances in genetics have shown that genetic factors might play an important role in the induction of cancer in human beings, e.g., the high incidence of skin cancers in patients with xeroderma pigmentosum. These proceedings deal with the relationships between genetic and environmental factors in carcinogenesis. The contributors cover mixed-function oxidases, pharmacogenetics, twin studies, DNA repair, immunology, and epidemiology.

  16. 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

  17. 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.

  18. Improving the human-computer interface: a human factors engineering approach.

    PubMed

    Salvemini, A V

    1998-01-01

    Human factors engineering involves the application of information about human behavior and characteristics in the design and testing of products, systems, and environments. A computing system's interface is developed on the basis of potential users' capabilities and limitations, the users' tasks, and the environment in which those tasks are performed. When human factors engineers work with users, subject-matter experts, and developers to design and test a system, they analyze and document users' tasks and requirements and develop prototype designs. Usability studies are conducted and user errors are analyzed to identify problems and develop recommendations for improving the human-computer interface.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

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

    PubMed

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

    2015-12-04

    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.

  4. 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.

  5. 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.

  6. A Competition between Stimulators and Antagonists of Upf Complex Recruitment Governs Human Nonsense-Mediated mRNA Decay

    PubMed Central

    Singh, Guramrit; Rebbapragada, Indrani; Lykke-Andersen, Jens

    2008-01-01

    The nonsense-mediated decay (NMD) pathway subjects mRNAs with premature termination codons (PTCs) to rapid decay. The conserved Upf1–3 complex interacts with the eukaryotic translation release factors, eRF3 and eRF1, and triggers NMD when translation termination takes place at a PTC. Contrasting models postulate central roles in PTC-recognition for the exon junction complex in mammals versus the cytoplasmic poly(A)-binding protein (PABP) in other eukaryotes. Here we present evidence for a unified model for NMD, in which PTC recognition in human cells is mediated by a competition between 3′ UTR–associated factors that stimulate or antagonize recruitment of the Upf complex to the terminating ribosome. We identify cytoplasmic PABP as a human NMD antagonizing factor, which inhibits the interaction between eRF3 and Upf1 in vitro and prevents NMD in cells when positioned in proximity to the termination codon. Surprisingly, only when an extended 3′ UTR places cytoplasmic PABP distally to the termination codon does a downstream exon junction complex enhance NMD, likely through increasing the affinity of Upf proteins for the 3′ UTR. Interestingly, while an artificial 3′ UTR of >420 nucleotides triggers NMD, a large subset of human mRNAs contain longer 3′ UTRs but evade NMD. We speculate that these have evolved to concentrate NMD-inhibiting factors, such as PABP, in spatial proximity of the termination codon. PMID:18447585

  7. Maintainability of Digital Systems: Technical Basis and Human Factors Review Guidance

    DTIC Science & Technology

    2000-03-01

    Human Factors Review Guidance Manuscript Completed: January 2000 Date Published: March 2000 Prepared by W. F. Stabler, J. C . Higgins/BNL J. Kramer...the lack of support from vendors, and also the desire to enhance instrumentation and control (I& C ) capabilities, the plant’s performance, and...based processors, the key features of digital systems, add a degree of complexity that may not have existed in earlier I& C systems. Many

  8. Geminin Inhibits a Late Step in the Formation of Human Pre-replicative Complexes*

    PubMed Central

    Wu, Min; Lu, Wenyan; Santos, Ruth E.; Frattini, Mark G.; Kelly, Thomas J.

    2014-01-01

    The initial step in initiation of eukaryotic DNA replication involves the assembly of pre-replicative complexes (pre-RCs) at origins of replication during the G1 phase of the cell cycle. In metazoans initiation is inhibited by the regulatory factor Geminin. We have purified the human pre-RC proteins, studied their interactions in vitro with each other and with origin DNA, and analyzed the effects of HsGeminin on formation of DNA-protein complexes. The formation of an initial complex containing the human origin recognition complex (HsORC), HsCdt1, HsCdc6, and origin DNA is cooperative, involving all possible binary interactions among the components. Maximal association of HsMCM2–7, a component of the replicative helicase, requires HsORC, HsCdc6, HsCdt1, and ATP, and is driven by interactions of HsCdt1 and HsCdc6 with multiple HsMCM2–7 subunits. Formation of stable complexes, resistant to high salt, requires ATP hydrolysis. In the absence of HsMCM proteins, HsGeminin inhibits the association of HsCdt1 with DNA or with HsORC-HsCdc6-DNA complexes. However, HsGeminin does not inhibit recruitment of HsMCM2–7 to DNA to form complexes containing all of the pre-RC proteins. In fact, HsGeminin itself is a component of such complexes, and interacts directly with the HsMcm3 and HsMcm5 subunits of HsMCM2–7, as well as with HsCdt1. Although HsGeminin does not prevent the initial formation of DNA-protein complexes containing the pre-RC proteins, it strongly inhibits the formation of stable pre-RCs that are resistant to high salt. We suggest that bound HsGeminin prevents transition of the pre-RC to a state that is competent for initiation of DNA replication. PMID:25231993

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. A short splicing isoform of HBS1L links the cytoplasmic exosome and SKI complexes in humans.

    PubMed

    Kalisiak, Katarzyna; Kuliński, Tomasz M; Tomecki, Rafał; Cysewski, Dominik; Pietras, Zbigniew; Chlebowski, Aleksander; Kowalska, Katarzyna; Dziembowski, Andrzej

    2016-09-26

    The exosome complex is a major eukaryotic exoribonuclease that requires the SKI complex for its activity in the cytoplasm. In yeast, the Ski7 protein links both complexes, whereas a functional equivalent of the Ski7 has remained unknown in the human genome.Proteomic analysis revealed that a previously uncharacterized short splicing isoform of HBS1L (HBS1LV3) is the long-sought factor linking the exosome and SKI complexes in humans. In contrast, the canonical HBS1L variant, HBS1LV1, which acts as a ribosome dissociation factor, does not associate with the exosome and instead interacts with the mRNA surveillance factor PELOTA. Interestingly, both HBS1LV1 and HBS1LV3 interact with the SKI complex and HBS1LV1 seems to antagonize SKI/exosome supercomplex formation. HBS1LV3 contains a unique C-terminal region of unknown structure, with a conserved RxxxFxxxL motif responsible for exosome binding and may interact with the exosome core subunit RRP43 in a way that resembles the association between Rrp6 RNase and Rrp43 in yeast. HBS1LV3 or the SKI complex helicase (SKI2W) depletion similarly affected the transcriptome, deregulating multiple genes. Furthermore, half-lives of representative upregulated mRNAs were increased, supporting the involvement of HBS1LV3 and SKI2W in the same mRNA degradation pathway, essential for transcriptome homeostasis in the cytoplasm.

  14. [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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. 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…

  20. 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.

  1. 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…

  2. Implementing human factors training in technical operations and maintenance.

    PubMed

    Taggart, W R

    1995-01-01

    The author reports experience with design of human factors training for aircraft engineering operations and maintenance. The program was based on five principles: observable skills-based training; integration with policies, practices, and procedures; data-driven and performance focused material; training needs fit organizational and national cultures; and training must be useful and beneficial.

  3. 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…

  4. Multi-Function Displays: A Guide for Human Factors Evaluation

    DTIC Science & Technology

    2013-11-01

    mental workload in rotary wing aircraft . Ergonomics , 36, 1121 - 40. Smith, S., & Mosier, J. (1984). Design guidelines for the user interface for...Monterey Technologies, Inc., except one designated by (*), who is from CAMI. 16. Abstract This guide is designed to assist aircraft ...section. 17. Key Words 18. Distribution Statement Multi-Function Displays, Display Design , Avionics, Human Factors Criteria, Aircraft

  5. 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…

  6. Human Factors Engineering and School Furniture: A Circular Odyssey.

    ERIC Educational Resources Information Center

    Lane, Kenneth E.; Richardson, Michael D.

    1993-01-01

    A search reveals only six articles that concern human-factors engineering as it relates to student furniture. Contacts with five school-furniture manufacturers disclose that designs were basically unaltered for years and are claimed to reflect what schools want in furniture. Proposes recommendations to design and secure furniture to meet students'…

  7. Some Human Factors Considerations for Designing Mixed Reality Interfaces

    DTIC Science & Technology

    2006-06-01

    the viewer’s eyes must converge at one distance, VSG , but must accommodate at another, fSG. Such a conflict causes the viewer to reconcile the two...the binocular fDV fSG p disparity vSG Right-eye View Left-eye View Some Human Factors Considerations for Designing Mixed Reality Interfaces RTO-MP

  8. 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,…

  9. 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…

  10. Surgical Technology Integration with Tools for Cognitive Human Factors (STITCH)

    DTIC Science & Technology

    2008-10-24

    Award Number: W81XWH-06-1-0761 TITLE: Surgical Technology Integration with Tools for Cognitive Human Factors (STITCH) PRINCIPAL INVESTIGATOR: W...COVERED (From - To) 25 Sep 2007 - 24 Sep 2008 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Surgical Technology Integration with Tools for Cognitive

  11. 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.

  12. Factors Affecting Timely Completion of a PhD: A Complex Systems Approach

    ERIC Educational Resources Information Center

    Pitchforth, Jegar; Beames, Stephanie; Thomas, Aleysha; Falk, Matthew; Farr, Charisse; Gasson, Susan; Thamrin, Sri Astuti; Mengersen, Kerrie

    2012-01-01

    Completing a PhD on time is a complex process, influenced by many interacting factors. In this paper we take a Bayesian Network approach to analyzing the factors perceived to be important in achieving this aim. Focusing on a single research group in Mathematical Sciences, we develop a conceptual model to describe the factors considered to be…

  13. 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…

  14. 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.

  15. Serum factors involved in human microvascular endothelial cell morphogenesis.

    PubMed

    Harvey, Kevin; Siddiqui, Rafat A; Sliva, Daniel; Garcia, Joe G N; English, Denis

    2002-09-01

    Our previous studies have demonstrated that lipid and protein angiogenic factors operate in tandem to induce optimal angiogenic responses in vivo. This study was undertaken to clarify the nature of the substances in human serum that are responsible for its remarkable ability to promote capillary morphogenesis in vitro. The ability of dilute (2%) human serum to promote the morphogenic differentiation of human dermal microvascular endothelial cells on Matrigel supports was depleted by more than 50% by treatment of the serum with activated charcoal, a procedure that effectively removes biologically active lipid growth factors. The remainder of the activity within serum was lost on heating to 60 degrees C for 60 minutes, indicating the involvement of a protein in the response. The ability of charcoal-treated serum to promote capillary morphogenesis was completely restored by the addition of sphingosine 1-phosphate (SPP, 500 nmol/L), but other lipids thought to be released into serum during clotting were ineffective. In addition, basic fibroblast growth factor (bFGF) effectively restored the ability of heat-treated serum to promote endothelial cell morphogenesis, but other protein growth factors, including vascular endothelial growth factor and platelet-derived growth factor, were ineffective. Together, SPP and bFGF were as effective as whole serum in promoting capillary morphogenesis. Responses to purified SPP were entirely sensitive to the effects of preexposure of the cells to pertussis toxin, whereas responses to bFGF were entirely pertussis toxin-resistant. Consistent with our hypothesis that two distinct factors in serum play a role in promoting capillary morphogenesis, responses induced by serum were inhibited approximately 50% by preexposure of endothelial cells to pertussis toxin. We conclude that platelet-released SPP acts in conjunction with circulating bFGF to promote capillary formation by microvascular endothelial cells. Lipid and protein growth factors

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Transactivation of the parathyroid hormone promoter by specificity proteins and the nuclear factor Y complex.

    PubMed

    Alimov, Alexander P; Park-Sarge, Ok-Kyong; Sarge, Kevin D; Malluche, Hartmut H; Koszewski, Nicholas J

    2005-08-01

    We previously identified a highly conserved specificity protein 1 (Sp1) DNA element in mammalian PTH promoters that acted as an enhancer of gene transcription and bound Sp1 and Sp3 proteins present in parathyroid gland nuclear extracts. More recently, a nuclear factor (NF)-Y element (NF-Y(prox)) was also described by our group, which was located approximately 30 bp downstream from the Sp1 site in the human PTH (hPTH) promoter and by itself acted as a weak enhancer of gene transcription. We now report that Sp proteins and NF-Y can synergistically enhance transcription of a minimal hPTH promoter construct. Positioning of the Sp1 DNA element appears to be critical for this synergism because deviations of one half of a helical turn caused an approximate 60% decrease in transactivation. Finally, examination of the bovine PTH (bPTH) promoter also revealed Sp1/NF-Y synergism, in conjunction with the identification of an analogous NF-Y binding site similarly positioned downstream from the bPTH Sp1 element. In summary, synergistic transactivation of the hPTH and bPTH promoters is observed by Sp proteins and the NF-Y complex. The conservation of this transactivation in the human and bovine promoters suggests that this may be a principle means of enhancing PTH gene transcription.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Formation mechanism and biological activity of novel thiolated human-like collagen iron complex.

    PubMed

    Zhu, Chenhui; Liu, Lingyun; Deng, Jianjun; Ma, Xiaoxuan; Hui, Junfeng; Fan, Daidi

    2016-03-01

    To develop an iron supplement that is effectively absorbed and utilized, thiolated human-like collagen was created to improve the iron binding capacity of human-like collagen. A thiolated human-like collagen-iron complex was prepared in a phosphate buffer, and one mole of thiolated human-like collagen-iron possessed approximately 28.83 moles of iron. The characteristics of thiolated human-like collagen-iron were investigated by ultraviolet-visible absorption spectroscopy, Fourier transform infrared spectroscopy, circular dichroism, and differential scanning calorimetry. The results showed that the thiolated human-like collagen-iron complex retained the secondary structure of human-like collagen and had greater thermodynamic stability than human-like collagen, although interactions between iron ions and human-like collagen occurred during the formation of the complex. In addition, to evaluate the bioavailability of thiolated human-like collagen-iron, an in vitro Caco-2 cell model and an in vivo iron deficiency anemia mouse model were employed. The data demonstrated that the thiolated human-like collagen-iron complex exhibited greater bioavailability and was more easily utilized than FeSO4, ferric ammonium citrate, or ferrous glycinate. These results indicated that the thiolated human-like collagen-iron complex is a potential iron supplement in the biomedical field.

  12. Impaired Immunogenicity of Meningococcal Neisserial Surface Protein A in Human Complement Factor H Transgenic Mice.

    PubMed

    Lujan, Eduardo; Pajon, Rolando; Granoff, Dan M

    2015-11-23

    Neisserial surface protein A (NspA) is a highly conserved outer membrane protein previously investigated as a meningococcal vaccine candidate. Despite eliciting serum bactericidal activity in mice, a recombinant NspA vaccine failed to elicit serum bactericidal antibodies in a phase 1 clinical trial in humans. The discordant results may be explained by the recent discovery that NspA is a human-specific ligand of the complement inhibitor factor H (FH). Therefore, in humans but not mice, NspA would be expected to form a complex with FH, which could impair human anti-NspA protective antibody responses. To investigate this question, we immunized human FH transgenic BALB/c mice with three doses of recombinant NspA expressed in Escherichia coli microvesicles, with each dose being separated by 3 weeks. Three of 12 (25%) transgenic mice and 13 of 14 wild-type mice responded with bactericidal titers of ≥1:10 in postimmunization sera (P = 0.0008, Fisher's exact test). In contrast, human FH transgenic and wild-type mice immunized with a control meningococcal native outer membrane vesicle vaccine had similar serum bactericidal antibody responses directed at PorA, which is not known to bind human FH, and a mutant factor H binding protein (FHbp) antigen with a >50-fold lower level of FH binding than wild-type FHbp antigen binding.Thus, human FH can impair anti-NspA serum bactericidal antibody responses, which may explain the poor immunogenicity of the NspA vaccine previously tested in humans. A mutant NspA vaccine engineered to have decreased binding to human FH may increase protective antibody responses in humans.

  13. 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.

  14. Inhibitory action of amyloid precursor protein against human Hageman factor (factor XII).

    PubMed

    Niwano, H; Embury, P B; Greenberg, B D; Ratnoff, O D

    1995-02-01

    Amyloid precursor protein forms that contain Kunitz protease inhibitor domains are released from activated platelets, T-lymphocytes, and leukocytes and inhibit trypsin, plasmin, and activated factor XI. We investigated the effects of amyloid precursor protein isoforms on activated Hageman factor (factor XII), activated factor X (Stuart factor), and thrombin. Recombinant amyloid precursor proteins with or without the Kunitz domain, 770 and 695 amino acids, respectively, were produced in insect cells by Baculovirus expression (BAC770 and BAC695). Neither BAC695 nor BAC770 inhibited human alpha-thrombin or activated factor X. The partial thromboplastin time was prolonged by both amyloid precursor proteins, only one of which, BAC770, contains the Kunitz protease inhibitor domain. Both forms of amyloid precursor proteins inhibited ellagic acid-induced activation of Hageman factor but did not inhibit activated Hageman factor. Bismuth subgallate, which is an insoluble analog of ellagic acid, lost its ability to activate Hageman factor on being exposed to BAC770. Inhibition of ellagic acid-induced activation of Hageman factor by both forms of amyloid precursor protein was enhanced by heparin. These findings suggested that the heparin-binding domain of amyloid precursor proteins is not in the Kunitz domain. This heparin-binding domain may block the activation of Hageman factor by negatively charged agents. Thus, amyloid precursor proteins may be involved in the control of hemostasis, properties not all dependent on the Kunitz domain.

  15. Analyzing Chromatin Remodeling Complexes Using Shotgun Proteomics and Normalized Spectral Abundance Factors

    PubMed Central

    Florens, Laurence; Carozza, Michael J.; Swanson, Selene K; Fournier, Marjorie; Coleman, Michael K.; Workman, Jerry L.; Washburn, Michael P.

    2006-01-01

    Mass spectrometry based approaches are commonly used to identify proteins from multiprotein complexes, typically with the goal of identifying new complex members or identifying post translational modifications. However, with the recent demonstration that spectral counting is a powerful quantitative proteomic approach, the analysis of multiprotein complexes by mass spectrometry can be reconsidered in certain cases. Using the chromatography based approach named multidimensional protein identification technology, multiprotein complexes may be analyzed quantitatively using the normalized spectral abundance factor that allows comparison of multiple independent analyses of samples. This study describes an approach to visualize multiprotein complex datasets that provides structure function information that is superior to tabular lists of data. In this method review, we describe a reanalysis of the Rpd3/Sin3 small and large histone deacetylase complexes previously described in a tabular form to demonstrate the normalized spectral abundance factor approach. PMID:17101441

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Biochemical and proteomic analysis of spliceosome factors interacting with intron-1 of human papillomavirus type-16.

    PubMed

    Martínez-Salazar, Martha; López-Urrutia, Eduardo; Arechaga-Ocampo, Elena; Bonilla-Moreno, Raul; Martínez-Castillo, Macario; Díaz-Hernández, Job; Del Moral-Hernández, Oscar; Cedillo-Barrón, Leticia; Martines-Juarez, Víctor; De Nova-Ocampo, Monica; Valdes, Jesús; Berumen, Jaime; Villegas-Sepúlveda, Nicolás

    2014-12-05

    The human papillomavirus type 16 (HPV-16) E6/E7 spliced transcripts are heterogeneously expressed in cervical carcinoma. The heterogeneity of the E6/E7 splicing profile might be in part due to the intrinsic variation of splicing factors in tumor cells. However, the splicing factors that bind the E6/E7 intron 1 (In-1) have not been defined. Therefore, we aimed to identify these factors; we used HeLa nuclear extracts (NE) for in vitro spliceosome assembly. The proteins were allowed to bind to an RNA/DNA hybrid formed by the In-1 transcript and a 5'-biotinylated DNA oligonucleotide complementary to the upstream exon sequence, which prevented interference in protein binding to the intron. The hybrid probes bound with the nuclear proteins were coupled to streptavidin magnetic beads for chromatography affinity purification. Proteins were eluted and identified by mass spectrometry (MS). Approximately 170 proteins were identified by MS, 80% of which were RNA binding proteins, including canonical spliceosome core components, helicases and regulatory splicing factors. The canonical factors were identified as components of the spliceosomal B-complex. Although 35-40 of the identified factors were cognate splicing factors or helicases, they have not been previously detected in spliceosome complexes that were assembled using in vivo or in vitro models.

  1. 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

  2. Vestibular factors influencing the biomedical support of humans in space

    NASA Astrophysics Data System (ADS)

    Lichtenberg, Byron K.

    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

  3. Extracellular complexes of the hematopoietic human and mouse CSF-1 receptor are driven by common assembly principles.

    PubMed

    Elegheert, Jonathan; Desfosses, Ambroise; Shkumatov, Alexander V; Wu, Xiongwu; Bracke, Nathalie; Verstraete, Kenneth; Van Craenenbroeck, Kathleen; Brooks, Bernard R; Svergun, Dmitri I; Vergauwen, Bjorn; Gutsche, Irina; Savvides, Savvas N

    2011-12-07

    The hematopoietic colony stimulating factor-1 receptor (CSF-1R or FMS) is essential for the cellular repertoire of the mammalian immune system. Here, we report a structural and mechanistic consensus for the assembly of human and mouse CSF-1:CSF-1R complexes. The EM structure of the complete extracellular assembly of the human CSF-1:CSF-1R complex reveals how receptor dimerization by CSF-1 invokes a ternary complex featuring extensive homotypic receptor contacts and striking structural plasticity at the extremities of the complex. Studies by small-angle X-ray scattering of unliganded hCSF-1R point to large domain rearrangements upon CSF-1 binding, and provide structural evidence for the relevance of receptor predimerization at the cell surface. Comparative structural and binding studies aiming to dissect the assembly principles of human and mouse CSF-1R complexes, including a quantification of the CSF-1/CSF-1R species cross-reactivity, show that bivalent cytokine binding to receptor coupled to ensuing receptor-receptor interactions are common denominators in extracellular complex formation.

  4. Active site amino acid sequence of human factor D.

    PubMed

    Davis, A E

    1980-08-01

    Factor D was isolated from human plasma by chromatography on CM-Sephadex C50, Sephadex G-75, and hydroxylapatite. Digestion of reduced, S-carboxymethylated factor D with cyanogen bromide resulted in three peptides which were isolated by chromatography on Sephadex G-75 (superfine) equilibrated in 20% formic acid. NH2-Terminal sequences were determined by automated Edman degradation with a Beckman 890C sequencer using a 0.1 M Quadrol program. The smallest peptide (CNBr III) consisted of the NH2-terminal 14 amino acids. The other two peptides had molecular weights of 17,000 (CNBr I) and 7000 (CNBr II). Overlap of the NH2-terminal sequence of factor D with the NH2-terminal sequence of CNBr I established the order of the peptides. The NH2-terminal 53 residues of factor D are somewhat more homologous with the group-specific protease of rat intestine than with other serine proteases. The NH2-terminal sequence of CNBr II revealed the active site serine of factor D. The typical serine protease active site sequence (Gly-Asp-Ser-Gly-Gly-Pro was found at residues 12-17. The region surrounding the active site serine does not appear to be more highly homologous with any one of the other serine proteases. The structural data obtained point out the similarities between factor D and the other proteases. However, complete definition of the degree of relationship between factor D and other proteases will require determination of the remainder of the primary structure.

  5. Enhancer Complexes Located Downstream of Both Human Immunoglobulin Cα Genes

    PubMed Central

    Mills, Frederick C.; Harindranath, Nagaradona; Mitchell, Mary; Max, Edward E.

    1997-01-01

    To investigate regulation of human immunoglobulin heavy chain expression, we have cloned DNA downstream from the two human Cα genes, corresponding to the position in the mouse IgH cluster of a locus control region (LCR) that includes an enhancer which regulates isotype switching. Within 25 kb downstream of both the human immunoglobulin Cα1 and Cα2 genes we identified several segments of DNA which display B lymphoid–specific DNase I hypersensitivity as well as enhancer activity in transient transfections. The corresponding sequences downstream from each of the two human Cα genes are nearly identical to each other. These enhancers are also homologous to three regions which lie in similar positions downstream from the murine Cα gene and form the murine LCR. The strongest enhancers in both mouse and human have been designated HS12. Within a 135-bp core homology region, the human HS12 enhancers are ∼90% identical to the murine homolog and include several motifs previously demonstrated to be important for function of the murine enhancer; additional segments of high sequence conservation suggest the possibility of previously unrecognized functional motifs. On the other hand, certain functional elements in the murine enhancer, including a B cell–specific activator protein site, do not appear to be conserved in human HS12. The human homologs of the murine enhancers designated HS3 and HS4 show lower overall sequence conservation, but for at least two of the functional motifs in the murine HS4 (a κB site and an octamer motif  ) the human HS4 homologs are exactly conserved. An additional hypersensitivity site between human HS3 and HS12 in each human locus displays no enhancer activity on its own, but includes a region of high sequence conservation with mouse, suggesting the possibility of another novel functional element. PMID:9294139

  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.

  7. Cognitive Factors Affecting Freeze-like Behavior in Humans.

    PubMed

    Alban, Michael W; Pocknell, Victoria

    2017-01-01

    Contemporary research on survival-related defensive behaviors has identified physiological markers of freeze/flight/fight. Our research focused on cognitive factors associated with freeze-like behavior in humans. Study 1 tested if an explicit decision to freeze is associated with the psychophysiological state of freezing. Heart rate deceleration occurred when participants chose to freeze. Study 2 varied the efficacy of freezing relative to other defense options and found "freeze" was responsive to variations in the perceived effectiveness of alternative actions. Study 3 tested if individual differences in motivational orientation affect preference for a "freeze" option when the efficacy of options is held constant. A trend in the predicted direction suggested that naturally occurring cognitions led loss-avoiders to select "freeze" more often than reward-seekers. In combination, our attention to the cognitive factors affecting freeze-like behavior in humans represents a preliminary step in addressing an important but neglected research area.

  8. 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.

  9. 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.

  10. Purification of human platelet-derived growth factor.

    PubMed Central

    Antoniades, H N; Scher, C D; Stiles, C D

    1979-01-01

    Human platelets contain a polypeptide growth factor that stimulates the proliferation of connective tissue cells. Purification of this platelet-derived growth factor (PDGF) was accomplished by heat (100 degrees C) treatment of washed platelets and subsequent ion-exchange chromatography, gel filtration in 1 M acetic acid, isoelectric focusing, and preparative sodium dodecyl sulfate/polyacrylamide gel electrophoresis. PDGF has an isoelectric point of 9.8 and a molecular weight ranging from 13,000 to 16,000 as judged by gel filtration in 1 M acetic acid or analytical sodium dodecyl sulfate gel electrophoresis under reducing conditions. The specific activity of the purified PDGF is 20 million times greater than that found in unfractionated human serum. Purified PDGF stimulates replicative DNA synthesis and cell proliferation in quiescent density-arrested cultures of BALB/c 3T3 cells at concentrations of 1 ng/ml (0.1 nM). Images PMID:287022

  11. 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.

  12. Human factors: should your medical devices require intensive care?

    PubMed

    Hyman, William A

    2010-06-01

    The design of a medical device should include active consideration of the way in which real users will actually use the device in the real environment of use. This consideration must include making the way in which the user interfaces with the device, for example, the buttons, the displays, the connections, such that the user can complete their tasks without error and without undue burden. This consideration of realistic user needs is addressed by the discipline of human factors.

  13. 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.

  14. Birds of Prey: Training Solutions to Human Factors Issues

    DTIC Science & Technology

    2007-11-01

    Interservice/Industry Training, Simulation, and Education Conference (I/ITSEC) 2007 2007 Paper No. 7133 Page 1 of 12 Birds of Prey: Training...2007 2. REPORT TYPE Conference Proceedings 3. DATES COVERED 01-01-2006 to 30-11-2007 4. TITLE AND SUBTITLE Birds of Prey: Training Solutions...ITSEC) 2007 2007 Paper No. 7133 Page 3 of 12 Birds of Prey: Training Solutions to Human Factors Issues Robert T. Nullmeyer Air Force Research

  15. Mobile Augmented Reality: Applications and Human Factors Evaluations

    DTIC Science & Technology

    2006-06-01

    increased the difficulty in acquiring and maintaining situation awareness (SA). Augmented reality (AR) has the potential to meet some of these new...intuitive and unambiguous. In the training applications, the virtual OPFOR must appear and behave realistically. We discuss the development of our augmented ... reality system and the human factors testing we have performed. We apply the system to two military needs: situation awareness during operations and training.

  16. The Human Factors of Graphic Interaction: Tasks and Techniques

    DTIC Science & Technology

    1980-12-01

    adjectives, adverbs , prepositions) of the language. The commands are the semantics of the input language, while the collection of information...presentation is to bring out some of the human factors issues which are germane to the design of the techniques, and to discuss any experiments which are...anecdotal reports of draftsmen and designers using light pens for hours without problems. We have found no germane experiments. Learning of hand-eye

  17. Purification of human platelet-derived growth factor

    SciTech Connect

    Raines, E.W.; Ross, R.

    1985-01-01

    The paper describes a method for purification of human platelet-derived growth factor (PDGF) from outdated platelet-rich plasma (PRP) using commonly available laboratory reagents and yielding a mitogen purified 800,000-fold over the starting material. (/sup 3/H)thymidine incorporation into DNA of cultured cells responsive to PDGF represents the most readily available method to follow its purification and define the biological activity of a purified preparation. Other assays to quantitate PDGF include radioreceptor assay and radioimmunoassay.

  18. Improving the Representation of Human Factors in Operational Analysis

    DTIC Science & Technology

    2010-10-01

    Defence Equipment and Support (DE&S) via Human Factors Integration Defence Technology Centre ( HFI DTC) activities. In particular this study’s Theme...Framework has been exploited in the HFI DTC Social Organisational Framework study, and the study team has provided a short extract for contribution to...the HFI DTC Handbook. The study has also been explicitly referenced in support to future MOD OA research studies. 8 SUMMARY AND CONCLUSIONS This

  19. 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.

  20. 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,…

  1. A Human Factors Analysis of USAF Remotely Piloted Aircraft Mishaps

    DTIC Science & Technology

    2013-06-01

    research question was: Do the types of active failures (unsafe acts) and latent failures (preconditions, unsafe supervision, and organizational...Operations Research iv THIS PAGE INTENTIONALLY LEFT BLANK v ABSTRACT As the effort to demonstrate the viability and effectiveness of...error-related mishaps that were coded using the DoD Human Factors Analysis and Classification System. The specific research question was: Do the types of

  2. Soft Controls: Technical Basis and Human Factors Review Guidance

    DTIC Science & Technology

    2000-03-01

    Controlling Office is (insert controlling DoD office). NUREG /CR-6635 BNL- NUREG -52565 Soft Controls: Technical Basis and Human Factors Review Guidance...DC 20555-0001 AVAILABILITY NOTICE Availability of Reference Materials Cited in NRC Publications NRC publications in the NUREG series, NRC regu...Technical Information Service Springfield, VA 22161 -0002 <http://www.ntis.gov> 1 -800-553-6847 or locally 703-605-6000 The NUREG series

  3. 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.

  4. Computational human factors in human-machine engineering - The Army-NASA aircrew/aircraft integration (A3I) program

    NASA Technical Reports Server (NTRS)

    Hartzell, E. James; Lakowske, Stephen

    1988-01-01

    The A3I program is a joint US Army-NASA exploratory program to develop a rational predictive methodology for helicopter cockpit system design, including mission requirements and training-system implications, that integrates human factors engineering with other vehicle system design disciplines at an early stage in the development process. The program will produce a prototye human factors/computer-aided engineering (HF/CAE) workstation suite for use by design professionals. This interactive environment will include computational and expert systems for the analysis and estimation of the impact of cockpit design and mission specification on system performance by considering the performance consequences from the human component of the system, especially as an integral part of the overall system operation, and from the very beginning of the design process. The central issues of pilot workload, performance, and training needs, and appropriate uses of automation are interrelated to affect all integrated design considerations in future man-machine systems. The goal is to aid designers in understanding these complex interactions and in optimally matching human capabilities with advanced cockpit systems.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. TFClass: an expandable hierarchical classification of human transcription factors

    PubMed Central

    Wingender, Edgar; Schoeps, Torsten; Dönitz, Jürgen

    2013-01-01

    TFClass (http://tfclass.bioinf.med.uni-goettingen.de/) provides a comprehensive classification of human transcription factors based on their DNA-binding domains. Transcription factors constitute a large functional family of proteins directly regulating the activity of genes. Most of them are sequence-specific DNA-binding proteins, thus reading out the information encoded in cis-regulatory DNA elements of promoters, enhancers and other regulatory regions of a genome. TFClass is a database that classifies human transcription factors by a six-level classification schema, four of which are abstractions according to different criteria, while the fifth level represents TF genes and the sixth individual gene products. Altogether, nine superclasses have been identified, comprising 40 classes and 111 families. Counted by genes, 1558 human TFs have been classified so far or >2900 different TFs when including their isoforms generated by alternative splicing or protein processing events. With this classification, we hope to provide a basis for deciphering protein–DNA recognition codes; moreover, it can be used for constructing expanded transcriptional networks by inferring additional TF-target gene relations. PMID:23180794

  15. 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.

  16. 49 CFR 225.12 - Rail Equipment Accident/Incident Reports alleging employee human factor as cause; Employee Human...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... employee human factor as cause; Employee Human Factor Attachment; notice to employee; employee supplement... cause; Employee Human Factor Attachment; notice to employee; employee supplement. (a) Rail Equipment... Attachment. If, in reporting a rail equipment accident/incident to FRA, a railroad cites an employee...

  17. 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

  18. Transcription factor induction of human oligodendrocyte progenitor fate and differentiation

    PubMed Central

    Wang, Jing; Pol, Suyog U.; Haberman, Alexa K.; Wang, Chunming; O’Bara, Melanie A.; Sim, Fraser J.

    2014-01-01

    Human oligodendrocyte progenitor cell (OPC) specification and differentiation occurs slowly and limits the potential for cell-based treatment of demyelinating disease. In this study, using FACS-based isolation and microarray analysis, we identified a set of transcription factors expressed by human primary CD140a+O4+ OPCs relative to CD133+CD140a− neural stem/progenitor cells (NPCs). Among these, lentiviral overexpression of transcription factors ASCL1, SOX10, and NKX2.2 in NPCs was sufficient to induce Sox10 enhancer activity, OPC mRNA, and protein expression consistent with OPC fate; however, unlike ASCL1 and NKX2.2, only the transcriptome of SOX10-infected NPCs was induced to a human OPC gene expression signature. Furthermore, only SOX10 promoted oligodendrocyte commitment, and did so at quantitatively equivalent levels to native OPCs. In xenografts of shiverer/rag2 animals, SOX10 increased the rate of mature oligodendrocyte differentiation and axon ensheathment. Thus, SOX10 appears to be the principle and rate-limiting regulator of myelinogenic fate from human NPCs. PMID:24982138

  19. 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.

  20. 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.

  1. 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

  2. Genome-wide uniformity of human ‘open’ pre-initiation complexes

    PubMed Central

    Lai, William K.M.; Pugh, B. Franklin

    2017-01-01

    Transcription of protein-coding and noncoding DNA occurs pervasively throughout the mammalian genome. Their sites of initiation are generally inferred from transcript 5′ ends and are thought to be either locally dispersed or focused. How these two modes of initiation relate is unclear. Here, we apply permanganate treatment and chromatin immunoprecipitation (PIP-seq) of initiation factors to identify the precise location of melted DNA separately associated with the preinitiation complex (PIC) and the adjacent paused complex (PC). This approach revealed the two known modes of transcription initiation. However, in contrast to prevailing views, they co-occurred within the same promoter region: initiation originating from a focused PIC, and broad nucleosome-linked initiation. PIP-seq allowed transcriptional orientation of Pol II to be determined, which may be useful near promoters where sufficient sense/anti-sense transcript mapping information is lacking. PIP-seq detected divergently oriented Pol II at both coding and noncoding promoters, as well as at enhancers. Their occupancy levels were not necessarily coupled in the two orientations. DNA sequence and shape analysis of initiation complex sites suggest that both sequence and shape contribute to specificity, but in a context-restricted manner. That is, initiation sites have the locally “best” initiator (INR) sequence and/or shape. These findings reveal a common core to pervasive Pol II initiation throughout the human genome. PMID:27927716

  3. A complex genome-microRNA interplay in human mitochondria.

    PubMed

    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.

  4. 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

  5. MITOCHONDRIAL DISEASES PART I: MOUSE MODELS OF OXPHOS DEFICIENCIES CAUSED BY DEFECTS ON RESPIRATORY COMPLEX SUBUNITS OR ASSEMBLY FACTORS

    PubMed Central

    Torraco, Alessandra; Peralta, Susana; Iommarini, Luisa; Diaz, Francisca

    2015-01-01

    Mitochondrial disorders are the most common inborn errors of metabolism affecting the oxidative phosphorylation system (OXPHOS). Because the poor knowledge of the pathogenic mechanisms, a cure for these disorders is still unavailable and all the treatments currently in use are supportive more than curative. Therefore, in the past decade a great variety of mouse models have been developed to assess the in vivo function of several mitochondrial proteins involved in human diseases. Due to the genetic and physiological similarity to humans, mice represent reliable models to study the pathogenic mechanisms of mitochondrial disorders and are precious to test new therapeutic approaches. Here we summarize the features of several mouse models of mitochondrial diseases directly related to defects in subunits of the OXPHOS complexes or in assembly factors. We discuss how these models recapitulate many human conditions and how they have contributed to the understanding of mitochondrial function in health and disease. PMID:25660179

  6. MTO1-Deficient Mouse Model Mirrors the Human Phenotype Showing Complex I Defect and Cardiomyopathy

    PubMed Central

    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. PMID:25506927

  7. 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.

  8. Definition of the affinity of binding between human von Willebrand factor and coagulation factor VIII.

    PubMed

    Ganz, P R; Atkins, J S; Palmer, D S; Dudani, A K; Hashemi, S; Luison, F

    1991-10-15

    Factor VIII and von Willebrand factor are two plasma proteins essential for effective hemostasis. In vivo, they form a non-covalent complex whose association appears to be metal ion dependent. However, a precise definition of the nature of the molecular forces governing their association remains to be defined, as does their binding affinity. In this paper we have determined the dissociation constant and stoichiometry for Factor VIII binding to immobilized von Willebrand factor. The data demonstrate that these proteins interact saturably and with relatively high affinity. Computer assisted analyses of the Scatchard data favour a two site binding model. The higher affinity site was found to have a Kd of 62 (+/- 13) x 10(-12) M while that of the lower affinity site was 380 (+/- 92) x 10(-12) M. The density of Factor VIII binding sites (Bmax) present on von Willebrand factor was 31 (+/- 3) pM for the high affinity binding site and 46 (+/- 6) pM for the lower site, corresponding to a calculated Factor VIII: von Willebrand factor binding ratio of 1:33 and 1:23, respectively.

  9. Modeling Reduced Human Performance as a Complex Adaptive System

    DTIC Science & Technology

    2003-09-01

    impacts human performance in general. It has a degrading effect (Belenky 1994) that can, in certain circumstances, be counteracted with noise ( Loeb 1986...going into design details that have just been described. D. RHPM AND FERBER’S FORMULA Jacques Ferber describes the major elements of a multi...Vocabulary, and its Relation to Organizations." Emergence 1(1): 110-127. Loeb , M. (1986). Noise and Human Efficiency. Chichester, UK, John Wiley

  10. Genome-Wide Prediction of DNA Methylation Using DNA Composition and Sequence Complexity in Human

    PubMed Central

    Wu, Chengchao; Yao, Shixin; Li, Xinghao; Chen, Chujia; Hu, Xuehai

    2017-01-01

    DNA methylation plays a significant role in transcriptional regulation by repressing activity. Change of the DNA methylation level is an important factor affecting the expression of target genes and downstream phenotypes. Because current experimental technologies can only assay a small proportion of CpG sites in the human genome, it is urgent to develop reliable computational models for predicting genome-wide DNA methylation. Here, we proposed a novel algorithm that accurately extracted sequence complexity features (seven features) and developed a support-vector-machine-based prediction model with integration of the reported DNA composition features (trinucleotide frequency and GC content, 65 features) by utilizing the methylation profiles of embryonic stem cells in human. The prediction results from 22 human chromosomes with size-varied windows showed that the 600-bp window achieved the best average accuracy of 94.7%. Moreover, comparisons with two existing methods further showed the superiority of our model, and cross-species predictions on mouse data also demonstrated that our model has certain generalization ability. Finally, a statistical test of the experimental data and the predicted data on functional regions annotated by ChromHMM found that six out of 10 regions were consistent, which implies reliable prediction of unassayed CpG sites. Accordingly, we believe that our novel model will be useful and reliable in predicting DNA methylation. PMID:28212312

  11. 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°.

  12. An integrated map of HIV-human protein complexes that facilitate viral infection.

    PubMed

    Emig-Agius, Dorothea; Olivieri, Kevin; Pache, Lars; Shih, Hsin Ling; Pustovalova, Olga; Bessarabova, Marina; Young, John A T; Chanda, Sumit K; Ideker, Trey

    2014-01-01

    Recent proteomic and genetic studies have aimed to identify a complete network of interactions between HIV and human proteins and genes. This HIV-human interaction network provides invaluable information as to how HIV exploits the host machinery and can be used as a starting point for further functional analyses. We integrated this network with complementary datasets of protein function and interaction to nominate human protein complexes with likely roles in viral infection. Based on our approach we identified a global map of 40 HIV-human protein complexes with putative roles in HIV infection, some of which are involved in DNA replication and repair, transcription, translation, and cytoskeletal regulation. Targeted RNAi screens were used to validate several proteins and complexes for functional impact on viral infection. Thus, our HIV-human protein complex map provides a significant resource of potential HIV-host interactions for further study.

  13. 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

  14. 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.

  15. 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.

  16. Vascular endothelial growth factor, basic fibroblast growth factor, insulin-like growth factor-I and platelet-derived growth factor levels in human milk of mothers with term and preterm neonates.

    PubMed

    Ozgurtas, Taner; Aydin, Ibrahim; Turan, Ozden; Koc, Esin; Hirfanoglu, Ibrahim Murat; Acikel, Cengiz Han; Akyol, Mesut; Erbil, M Kemal

    2010-05-01

    Human milk is a complex biological fluid. It contains many nutrients, anti-infectious and biologically active substance. Human milk also contains many angiogenic polypeptides. We have determined four of these: Vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF), insulin-like growth factor- I (IGF-I) and platelet-derived growth factor (PDGF). The aim of this study was to compare the concentrations of VEGF, b-FGF, IGF-I and PDGF in human milk collected from mothers with preterm and term neonates. Human milk samples were collected from 29 mothers of preterm (<37 weeks) and from 29 mothers of term (38>weeks) infants at days 3, 7 and 28 postpartum. Milk samples were analyzed for VEGF, b-FGF and PDGF by enzyme-linked immunosorbent assay and IGF-I was measured by radioimmunoassay method. Human milk levels of VEGF, IGF-I and b-FGF were significantly higher (p<0.001). Furthermore, within-preterm group concentrations of VEGF, IGF-I and PDGF significantly differed during postpartum days 3-7-28 (p<0.001, p<0.05, p<0.001, respectively), but did not do so for b-FGF concentrations. In term groups, concentrations of IGF-I and VEGF significantly differed (p<0.05, p<0.001, respectively), but did not do so for concentrations of b-FGF and PDGF. This is the first report of simultaneous measurements of four major angiogenic factors in human milk collected from mothers with preterm and term. Our results suggest that three of four angiogenic factors, VEGF, b-FGF and IGF-I, are higher concentration in human milk which collected from preterm mothers than those of terms.

  17. Human factors analysis and design methods for nuclear waste retrieval systems: Human factors design methodology and integration plan

    NASA Astrophysics Data System (ADS)

    Casey, S. M.

    1980-06-01

    The nuclear waste retrieval system 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 is discussed. The implementation of human factors engineering principles during the design and construction of the retrieval system facilities and equipment is reported. The methodology is structured around a basic system development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Examples of application of the techniques in the analysis of human tasks, and equipment required in the removal of spent fuel canisters is provided. The framework for integrating human engineering with the rest of the system development effort is documented.

  18. Expression, purification and characterization of the human MTA2-RBBP7 complex.

    PubMed

    Brasen, Christoffer; Dorosz, Jerzy; Wiuf, Anders; Boesen, Thomas; Mirza, Osman; Gajhede, Michael

    2017-02-04

    The repressive Nucleosome Remodeling and histone Deacetylation (NuRD) complex remodels the chromatin structure by coupling ATP-dependent remodeling activity with histone deacetylase function and plays important roles in regulating gene transcription, DNA damage repair and chromatin assembly. The complex is composed of six subunits: Metastasis Associated proteins MTA1/2/3 initially recruit histone chaperones RBBP4/7 followed by the histone deacetylases HDAC1/2 forming a core complex. Further association of the CpG-binding protein MBD2/3, p66α/β and the ATP-dependent helicase CDH3/4 constitutes the NuRD complex. Recent structural studies on truncated human proteins or orthologous have revealed that the stoichiometry of the MTA1-RBBP4 complex is 2:4. This study reports expression and purification of the intact human MTA2-RBBP7 complex using HEK293F cells as expression system. In analogy with findings on the Drosophila NuRD complex, we find that also the human MTA-RBBP can be isolated in vitro. Taken together with previous findings this suggests, that MTA-RBBP is a stable complex, with a central role in the initial assembly of the human NuRD complex. Refined 3D volumes of the complex generated from negative stain electron microscopy (EM) data reveals an elongated architecture that is capable of hinge like motion around the center of the particle.

  19. 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.

  20. 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