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

    PubMed Central

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

    2015-01-01

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

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Human Polymerase-Associated Factor complex (PAFc) connects the Super Elongation Complex (SEC) to RNA polymerase II on chromatin.

    PubMed

    He, Nanhai; Chan, Caleb K; Sobhian, Bijan; Chou, Seemay; Xue, Yuhua; Liu, Min; Alber, Tom; Benkirane, Monsef; Zhou, Qiang

    2011-09-06

    The Super Elongation Complex (SEC), containing transcription elongation activators/coactivators P-TEFb, ELL2, AFF4/1, ENL, and AF9, is recruited by HIV-1 Tat and mixed lineage leukemia (MLL) proteins to activate the expression of HIV-1 and MLL-target genes, respectively. In the absence of Tat and MLL, however, it is unclear how SEC is targeted to RNA polymerase (Pol) II to stimulate elongation in general. Furthermore, although ENL and AF9 can bind the H3K79 methyltransferase Dot1L, it is unclear whether these bindings are required for SEC-mediated transcription. Here, we show that the homologous ENL and AF9 exist in separate SECs with similar but nonidentical functions. ENL/AF9 contacts the scaffolding protein AFF4 that uses separate domains to recruit different subunits into SEC. ENL/AF9 also exists outside SEC when bound to Dot1L, which is found to inhibit SEC function. The YEATS domain of ENL/AF9 targets SEC to Pol II on chromatin through contacting the human Polymerase-Associated Factor complex (PAFc) complex. This finding explains the YEATS domain's dispensability for leukemogenesis when ENL/AF9 is translocated to MLL, whose interactions with PAFc and DNA likely substitute for the PAFc/chromatin-targeting function of the YEATS domain.

  9. Mechanism of open complex and dual incision formation by human nucleotide excision repair factors.

    PubMed Central

    Evans, E; Moggs, J G; Hwang, J R; Egly, J M; Wood, R D

    1997-01-01

    During nucleotide excision repair in human cells, a damaged DNA strand is cleaved by two endonucleases, XPG on the 3' side of the lesion and ERCC1-XPF on the 5' side. These structure-specific enzymes act at junctions between duplex and single-stranded DNA. ATP-dependent formation of an open DNA structure of approximately 25 nt around the adduct precedes this dual incision. We investigated the mechanism of open complex formation and find that mutations in XPB or XPD, the DNA helicase subunits of the transcription and repair factor TFIIH, can completely prevent opening and dual incision in cell-free extracts. A deficiency in XPC protein also prevents opening. The absence of RPA, XPA or XPG activities leads to an intermediate level of strand separation. In contrast, XPF or ERCC1-defective extracts open normally and generate a 3' incision, but fail to form the 5' incision. This same repair defect was observed in extracts from human xeroderma pigmentosum cells with an alteration in the C-terminal domain of XPB, suggesting that XPB has an additional role in facilitating 5' incision by ERCC1-XPF nuclease. These data support a mechanism in which TFIIH-associated helicase activity and XPC protein catalyze initial formation of the key open intermediate, with full extension to the cleavage sites promoted by the other core nucleotide excision repair factors. Opening is followed by dual incision, with the 3' cleavage made first. PMID:9351836

  10. 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. Copyright 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.

  11. 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.

  12. Complexity of Complement Resistance Factors Expressed by Acinetobacter baumannii Needed for Survival in Human Serum.

    PubMed

    Sanchez-Larrayoz, Amaro F; Elhosseiny, Noha M; Chevrette, Marc G; Fu, Yang; Giunta, Peter; Spallanzani, Raúl G; Ravi, Keerthikka; Pier, Gerald B; Lory, Stephen; Maira-Litrán, Tomás

    2017-08-30

    Acinetobacter baumannii is a bacterial pathogen with increasing impact in healthcare settings, due in part to this organism's resistance to many antimicrobial agents, with pneumonia and bacteremia as the most common manifestations of disease. A significant proportion of clinically relevant A. baumannii strains are resistant to killing by normal human serum (NHS), an observation supported in this study by showing that 12 out of 15 genetically diverse strains of A. baumannii are resistant to NHS killing. To expand our understanding of the genetic basis of A. baumannii serum resistance, a transposon (Tn) sequencing (Tn-seq) approach was used to identify genes contributing to this trait. An ordered Tn library in strain AB5075 with insertions in every nonessential gene was subjected to selection in NHS. We identified 50 genes essential for the survival of A. baumannii in NHS, including already known serum resistance factors, and many novel genes not previously associated with serum resistance. This latter group included the maintenance of lipid asymmetry genetic pathway as a key determinant in protecting A. baumannii from the bactericidal activity of NHS via the alternative complement pathway. Follow-up studies validated the role of eight additional genes identified by Tn-seq in A. baumannii resistance to killing by NHS but not by normal mouse serum, highlighting the human species specificity of A. baumannii serum resistance. The identification of a large number of genes essential for serum resistance in A. baumannii indicates the degree of complexity needed for this phenotype, which might reflect a general pattern that pathogens rely on to cause serious infections. Copyright © 2017 by The American Association of Immunologists, Inc.

  13. 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.

  14. 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.

  15. 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.

  16. Assembly of the Prothrombinase Complex on the Surface of Human Foreskin Fibroblasts: Implications for Connective Tissue Growth Factor

    PubMed Central

    Rico, Mario C.; Rough, James J.; Manns, Joanne M.; Carpio-Cano, Fabiola Del; Safadi, Fayez F.; Kunapuli, Satya P.; Cadena, Raul A DeLa

    2011-01-01

    Activated factor X (FXa) and thrombin can up-regulate gene expression of connective tissue growth factor (CTGF/CCN2) on fibroblasts. Since tissue factor (TF) is expressed on these cells, we hypothesized that they may assemble the prothrombinase complex leading to CTGF/CCN2 upregulation. In addition, the effect of thrombospondin-1 (TSP1) on this reaction was evaluated. Human foreskin fibroblasts were incubated with purified factor VII (FVII), factor X (FX), factor V (FV), prothrombin and calcium in the presence and absence of TSP1. Generation of FXa and of thrombin were assessed using chromogenic substrates. SMAD pathway phosphorylation was detected via Western-blot analysis. Pre-incubation of fibroblasts with FVII led to its auto-activation by cell-surface expressed TF, which in turn in the presence of FX, FVa, prothrombin and calcium led to FXa (9.7 ± 0.8 nM) and thrombin (7.9 ± 0.04 U/mL × 10-3) generation. Addition of TSP1 significantly enhanced thrombin (23.3 ± 0.7 U/mL × 10-3) but not FXa (8.5 ± 0.6 nM) generation. FXa and thrombin generation leads to upregulation of CTGF/CCN2. TSP1 alone upregulated CTGF/CCN2, an effect mediated via activation of transforming growth factor beta (TGFβ) as showed by phosphorylation of the SMAD pathway an event blunted by using a TGFβ receptor I inhibitor (TGFβRI). FXa- and thrombin-induced upregulation of CTGF/CCN2 was not blocked by TGFβRI. In summary, assembly of the prothrombinase complex occurs on fibroblast’s surface leading to serine proteases generation, an event enhanced by TSP1 and associated with CTGF/CCN2 upregulation. These mechanisms may play an important role in human diseases associated with fibrosis. PMID:21889790

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

    SciTech Connect

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

    1988-05-03

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

  18. Relation of human and natural factors in the development of lakes according to a complex analysis of lake sediments

    NASA Astrophysics Data System (ADS)

    Sapelko, T. V.; Shemanaev, K. V.; Kuznetsov, D. D.; Ignatieva, N. V.

    2012-04-01

    The question of establishing the features of the anthropogenic factor in the development of lakes at different stages is particularly relevant at the present time due to the human activities on the lakes. Recently, the processes of eutrophication by the influence of anthropogenic factors are studying by the scientists. The mechanism of a natural eutrophication is still poorly understood. To understand this mechanism needs data of reconstruction of trophic status of lakes over a long period (few millenniums), and the reasons of changes of their productivity. We received new data from sediment core of the central part of Lake Ladoga (60°28'10'' N, 31°19'18'' E) from a depth of 72 m. The thickness of core is 47cm. Every centimeter of the core was studied by using the pollen analysis on the content of organic matter in sediments, metals (Fe, Mn, Cu, Ni, Pb, Zn, Cr, Co, V), general, mineral and organic phosphorus. Age sediments studied about 2500 years. We calculated rate of sedimentation. According to a complex analysis revealed the dynamics of all the studied components in pre-industrial and industrial periods. In the period 2500-500 years ago there was no human impact on the productivity of the lake. Only about a few hundred years ago, the anthropogenic factor has more important role in the development of the lake. Since the beginning of the industrial period, impact of anthropogenic factors exceeded the impact of natural. According to our results (of content of organic matter, metals and phosphorus) we developed a method of percentage ratio of influence of natural and anthropogenic factors. In consequence, we received the data that the pollutions of human activities are not as large as previously thought.

  19. 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.

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

    PubMed

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

    2013-08-22

    Mature ribosomal RNAs (rRNAs) are produced from polycistronic precursors following complex processing. Precursor (pre)-rRNA processing has been extensively characterized in yeast and was assumed to be conserved in humans. We functionally characterized 625 nucleolar proteins in HeLa cells and identified 286 required for processing, including 74 without a yeast homolog. For selected candidates, we demonstrated that pre-rRNA processing defects are conserved in different cell types (including primary cells), defects are not due to activation of a p53-dependent nucleolar tumor surveillance pathway, and they precede cell-cycle arrest and apoptosis. We also investigated the exosome's role in processing internal transcribed spacers (ITSs) and report that 3' end maturation of 18S rRNA involves EXOSC10/Rrp6, a yeast ITS2 processing factor. We conclude that human cells adopt unique strategies and recruit distinct trans-acting factors to carry out essential processing steps, posing fundamental implications for understanding ribosomopathies at the molecular level and developing effective therapeutic agents. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Complexes of Human Papillomavirus Type 16 E6 Proteins Form Pseudo-Death-Inducing Signaling Complex Structures during Tumor Necrosis Factor-Mediated Apoptosis▿

    PubMed Central

    Filippova, Maria; Filippov, Valery A.; Kagoda, Mercy; Garnett, Theodore; Fodor, Nadya; Duerksen-Hughes, Penelope J.

    2009-01-01

    High-risk strains of human papillomavirus (HPV) such as HPV type 16 (HPV16) and HPV18 are causative agents of most human cervical carcinomas. E6, one of the oncogenes encoded by HPV16, possesses a number of biological and transforming functions. We have previously shown that the binding of E6 to host apoptotic proteins such as tumor necrosis factor (TNF) R1, the adaptor protein FADD, and procaspase 8 results in a significant modification of the normal flow of apoptotic events. For example, E6 can bind to and accelerate the degradation of FADD. In addition, full-length E6 binds to the TNF R1 death domain and can also bind to and accelerate the degradation of procaspase 8. In contrast, the binding of small splice isoforms known as E6* results in the stabilization of procaspase 8. In this report, we propose a model for the ability of HPV16 E6 to both sensitize and protect cells from TNF as well as to protect cells from Fas. We demonstrate that both the level of E6 expression and the ratio between full-length E6 and E6* are important factors in the modification of the host extrinsic apoptotic pathways and show that at high levels of E6 expression, the further sensitization of U2OS, NOK, and Ca Ski cells to TNF-mediated apoptosis is most likely due to the formation of a pseudo-death-inducing signaling complex structure that includes complexes of E6 proteins. PMID:18842714

  2. 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

  3. Statistical Factors in Complexation Reactions.

    ERIC Educational Resources Information Center

    Chung, Chung-Sun

    1985-01-01

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

  4. Pathogen safety of a pasteurized four-factor human prothrombin complex concentrate preparation using serial 20N virus filtration.

    PubMed

    Nowak, Thomas; Popp, Birgit; Gröner, Albrecht; Schäfer, Wolfram; Kalina, Uwe; Enssle, Karlheinz; Roth, Nathan J

    2017-05-01

    Beriplex P/N/Kcentra/Coaplex/Confidex is a four-factor human prothrombin complex concentrate (PCC). Here, we describe the pathogen safety profile and biochemical characteristics of an improved manufacturing process that further enhances the virus safety of Beriplex P/N. Samples of product intermediates were spiked with test viruses, and prions were evaluated under routine production and robustness conditions of the scale-down version of the commercial manufacturing process for their capacity to inactivate or remove pathogens. The PCC was characterized by determining the activity of Factor (F)II, FVII, FIX, FX, protein C, and protein S and the concentration of heparin and antithrombin III in nine product lots. The manufacturing process had a very high virus reduction capacity for a broad variety of virus challenges (overall reduction factors ≥15.5 to ≥18.4 log for enveloped viruses and 11.5 to ≥11.9 log for nonenveloped viruses). The high virus clearance capacity was provided by two dedicated virus reduction steps (pasteurization and serial 20N virus filtration) that provided effective inactivation and removal of viruses and a purification step (ammonium sulfate precipitation and adsorption to calcium phosphate) that contributed to the overall virus removal capacity. The diethylaminoethyl (DEAE) chromatography and ammonium sulfate precipitation steps removed prions to below the limit of detection. The levels of different clotting factors in the final product were well balanced. The improved manufacturing process of Beriplex P/N further enhances the margin of pathogen safety based on its capacity to remove and inactivate a wide range of virus challenges. © 2017 The Authors. Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.

  5. 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.

  6. 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.

  7. Sequestration of anti-platelet GPIIIa antibody in rheumatoid factor immune complexes of human immunodeficiency virus 1 thrombocytopenic patients.

    PubMed Central

    Karpatkin, S; Nardi, M A; Hymes, K B

    1995-01-01

    Human immunodeficiency virus 1-related idiopathic thrombocytopenic purpura (HIV-1-ITP) patients have a 4-fold increased percentage of CD5+ B cells and a 4.8-fold increased percentage of serum immune complexes precipitated by polyethylene glycol (PEG-ICs) compared to control subjects, as reported previously. Since CD5+ B cells produce predominantly IgM rheumatoid factor (RF) vs. Fc of IgG and PEG-ICs contain high levels of IgM, we looked for the presence of RF in the immune complexes of HIV-1-ITP patients. PEG-ICs were adsorbed to protein A and dissociated with acid, and IgM and IgG were purified by gel filtration and affinity chromatography. Solid-phase ELISA was used to measure antibody specificity vs. platelets, Fc, and HIV-1 gp120, p24, and CD4. Dissociated IgG antibody reacted with platelets, HIV-1 gp120, p24, and CD4, but not with Fc. Serum IgG did not react with platelets or Fc but did react with HIV-1 gp120, p24, and CD4. Both PEG-IC IgM and serum IgM reacted with Fc as well as the other four antigens. Control IgM and IgG were unreactive. Isolated IgM from PEG-ICs relocated approximately 50% of the IgG preincubated with IgM to the Vo region of a G200 gel-filtration column. Anti-platelet IgG but not IgM could be affinity-purified from fixed platelets. Both F(ab')2 fragments of anti-platelet IgG and the total PEG-IC bound to platelets in a saturation-dependent manner. F(ab')2 of anti-platelet IgG inhibited 50% binding of PEG-IC to platelets at an F(ab')2/complex ratio of 3:1 (wt/wt). Scatchard analysis revealed two classes of binding sites: high-affinity Kd values of 0.8-1.8 nM and lower-affinity Kd values of 6.6-12.3 nM with respective numbers of binding sites of 44,000-57,000 and 122,000-256,000 (n = 4). Anti-platelet IgG of 6/6 patients precipitated GPIIIa from platelet lysates of surface 125I-labeled platelets. Platelet count correlated inversely with anti-platelet IgG (r = -0.73; P < 0.01; n = 27). Thus, PEG-ICs of HIV-1-ITP patients contain IgM RF, which

  8. 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

  9. 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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26598467

  11. 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.

  12. A model for the unique role of factor Va A2 domain extension in the human ternary thrombin-generating complex.

    PubMed

    Shim, Joong-Youn; Lee, Chang Jun; Wu, Sangwook; Pedersen, Lee G

    2015-04-01

    An all-atom human ternary model for the prothrombinase-prothrombin complex, including metal ions and post-translationally modified residues, was constructed from existing X-ray crystal structures. The factor Xa-prothrombin interface was taken from an existing ternary model, which locates the active site of factor Xa in the vicinity of prothrombin cleavage positions. The three sulfotyrosine residues at the C-terminal sequence of factor Va A2 domain are accommodated by modelling rational interactions with positively charged patches on the surface of prothrombin. The entire model is then solvent-equilibrated with molecular dynamics. This ternary model for the thrombin-generating complex provides an estimate as to the role of the C-terminus of the factor Va A2 domain: to establish an interface between FXa and prothrombin and to stabilize the orientation of this interface. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. 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.

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

    PubMed

    Sokabe, Masaaki; Fraser, Christopher S

    2014-11-14

    The formation of a stable 43 S preinitiation complex (PIC) must occur to enable successful mRNA recruitment. However, the contributions of eIF1, eIF1A, eIF3, and the eIF2-GTP-Met-tRNAi ternary complex (TC) in stabilizing the 43 S PIC are poorly defined. We have reconstituted the human 43 S PIC and used fluorescence anisotropy to systematically measure the affinity of eIF1, eIF1A, and eIF3j in the presence of different combinations of 43 S PIC components. Our data reveal a complicated network of interactions that result in high affinity binding of all 43 S PIC components with the 40 S subunit. Human eIF1 and eIF1A bind cooperatively to the 40 S subunit, revealing an evolutionarily conserved interaction. Negative cooperativity is observed between the binding of eIF3j and the binding of eIF1, eIF1A, and TC with the 40 S subunit. To overcome this, eIF3 dramatically increases the affinity of eIF1 and eIF3j for the 40 S subunit. Recruitment of TC also increases the affinity of eIF1 for the 40 S subunit, but this interaction has an important indirect role in increasing the affinity of eIF1A for the 40 S subunit. Together, our data provide a more complete thermodynamic framework of the human 43 S PIC and reveal important interactions between its components to maintain its stability. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Human Platelets and Factor XI

    PubMed Central

    Lipscomb, Myatt S.; Walsh, Peter N.

    1979-01-01

    Because human platelets participate in the contact phase of intrinsic coagulation and contain a Factor XI-like coagulant activity, the nature of the Factor XI-like activity was examined and compared with purified plasma Factor XI. The platelet factor XI-like activity was sedimented with the particulate fraction of a platelet lysate, was inactivated by heat (t1/2 3.5 min, 56°C), was not a nonspecific phospholipid activity, and was destroyed by treatment with Triton X-100. Isolated platelet membranes were four-fold enriched in Factor XI activity and similarly enriched in plasma membrane marker enzymes. The Factor XI-like activity of platelet membranes was detected only when assayed in the presence of kaolin, which suggests that it is present in an unactivated form and can participate in contact activation. Concanavalin A inhibited the Factor XI-like activity of platelet lysates and platelet membranes but not of plasma or purified Factor XI. A platelet membrane-Factor XI complex was isolated after incubation of membranes with purified Factor XI. The Factor XI activity of the platelet membrane-plasma Factor XI complex was inhibited by concanavalin A, whereas unbound plasma Factor XI retained activity. An antibody raised against plasma Factor XI inhibited the in vitro Factor XI activity of plasma and of the platelet membrane-plasma Factor XI complex but had no effect on the endogenous Factor XI-like activity of washed lysed platelets or isolated platelet membranes. Washed platelets and isolated platelet membranes obtained from a Factor XI-deficient donor without a history of excessive bleeding had normal quantities of platelet Factor XI-like activity and normal behavior in the contact phase of coagulation (collagen-induced coagulant activity). These results indicate that platelet membranes contain an endogenous Factor XI-like activity that is functionally distinct from plasma Factor XI. PMID:447822

  16. 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.

  17. 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.

  18. 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.

  19. 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)

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Human Error In Complex Systems

    NASA Technical Reports Server (NTRS)

    Morris, Nancy M.; Rouse, William B.

    1991-01-01

    Report presents results of research aimed at understanding causes of human error in such complex systems as aircraft, nuclear powerplants, and chemical processing plants. Research considered both slips (errors of action) and mistakes (errors of intention), and influence of workload on them. Results indicated that: humans respond to conditions in which errors expected by attempting to reduce incidence of errors; and adaptation to conditions potent influence on human behavior in discretionary situations.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Production of the Growth Factors GM-CSF, G-CSF, and VEGF by Human Peripheral Blood Cells Induced with Metal Complexes of Human Serum γ-Globulin Formed with Copper or Zinc Ions

    PubMed Central

    Cheknev, Sergey B.; Apresova, Maria A.; Moryakova, Nadezhda A.; Efremova, Irina E.; Mezdrokhina, Anna S.; Piskovskaya, Lidya S.; Babajanz, Alla A.

    2014-01-01

    As it was established in our previous studies, the proteins of human serum γ-globulin fraction could interact with copper or zinc ions distributed in the periglobular space, form metal complexes, and become able to perform effector functions differing due to the conformational shifts from those mediated by them in native conformation of their Fc regions. In the present work we have evaluated ability of the γ-globulin metal complexes formed with copper or zinc ions in the conditions like to the physiological ones to induce production or to regulate induction in the culture of freshly isolated human peripheral blood cells (PBC) of granulocyte (G) and granulocyte-macrophage (GM) colony-stimulating factors (CSF) as well as of vascular endothelial growth factor (VEGF). The γ-globulin metal complexes formed with both copper and zinc ions were found to similarly reduce production of GM-CSF, G-CSF, and VEGF induced in normal human PBC cultures by the control γ-globulins or by copper and zinc ions used alone. In context of theory and practice of inflammation the properties of the γ-globulin metal complexes might impact the basic knowledge in search of novel approaches to anti-inflammatory drugs development. PMID:25104881

  13. 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.

  14. 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.

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

    PubMed

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

    2015-07-01

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

  16. Human factors in aviation

    NASA Technical Reports Server (NTRS)

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

    1988-01-01

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

  17. 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

  18. 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

  19. Human RNA polymerase II associated factor 1 complex promotes tumorigenesis by activating c-MYC transcription in non-small cell lung cancer

    SciTech Connect

    Zhi, Xiuyi; Giroux-Leprieur, Etienne; Wislez, Marie; Hu, Mu; Zhang, Yi; Shi, Huaiyin; Du, Kaiqi; Wang, Lei

    2015-10-02

    Human RNA polymerase II (RNAPII)-associated factor 1 complex (hPAF1C) plays a crucial role in protein-coding gene transcription. Overexpression of hPAF1C has been implicated in the initiation and progression of various human cancers. However, the molecular pathways involved in tumorigenesis through hPAF1C remain to be elucidated. The current study suggested hPAF1C expression as a prognostic biomarker for early stage non-small cell lung cancer (NSCLC) and patients with low hPAF1C expression levels had significantly better overall survival. Furthermore, the expression of hPAF1C was found to be positively correlated with c-MYC expression in patient tumor samples and in cancer cell lines. Mechanistic studies indicated that hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription. These results demonstrated the prognostic value of hPAF1C in early-stage NSCLC and the role of hPAF1C in the transcriptional regulation of c-MYC oncogene during NSCLC tumorigenesis. - Highlights: • hPAF1C expression is a prognostic biomarker for early stage non-small cell lung cancer. • The expression of hPAF1C was positively correlated with c-MYC in tumor samples of patients and in several NSCLC cell lines. • hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription.

  20. Human RNA polymerase II associated factor 1 complex promotes tumorigenesis by activating c-MYC transcription in non-small cell lung cancer.

    PubMed

    Zhi, Xiuyi; Giroux-Leprieur, Etienne; Wislez, Marie; Hu, Mu; Zhang, Yi; Shi, Huaiyin; Du, Kaiqi; Wang, Lei

    2015-10-02

    Human RNA polymerase II (RNAPII)-associated factor 1 complex (hPAF1C) plays a crucial role in protein-coding gene transcription. Overexpression of hPAF1C has been implicated in the initiation and progression of various human cancers. However, the molecular pathways involved in tumorigenesis through hPAF1C remain to be elucidated. The current study suggested hPAF1C expression as a prognostic biomarker for early stage non-small cell lung cancer (NSCLC) and patients with low hPAF1C expression levels had significantly better overall survival. Furthermore, the expression of hPAF1C was found to be positively correlated with c-MYC expression in patient tumor samples and in cancer cell lines. Mechanistic studies indicated that hPAF1C could promote lung cancer cell proliferation through regulating c-MYC transcription. These results demonstrated the prognostic value of hPAF1C in early-stage NSCLC and the role of hPAF1C in the transcriptional regulation of c-MYC oncogene during NSCLC tumorigenesis. Copyright © 2015. Published by Elsevier Inc.

  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. 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

  4. 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.

  5. 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.

  6. 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.

  7. NASA human factors programmatic overview

    NASA Technical Reports Server (NTRS)

    Connors, Mary M.

    1992-01-01

    Human factors addresses humans in their active and interactive capacities, i.e., in the mental and physical activities that they perform and in the contributions they make to achieving the goals of the mission. The overall goal of space human factors in NASA is to support the safety, productivity, and reliability of both the on-board crew and the ground support staff. Safety and reliability are fundamental requirements that human factors shares with other disciplines, while productivity represents the defining contribution of the human factors discipline.

  8. 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…

  9. 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.

  10. 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.

  11. Human Factors In Aircraft Automation

    NASA Technical Reports Server (NTRS)

    Billings, Charles

    1995-01-01

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

  12. 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

  13. Modeling the human prothrombinase complex components

    NASA Astrophysics Data System (ADS)

    Orban, Tivadar

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

  14. Understanding adverse events: human factors.

    PubMed

    Reason, J

    1995-06-01

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

  15. 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

  16. Some Human Factors in Codebreaking

    DTIC Science & Technology

    2003-10-01

    thereafter. Some human factors that can lead to vital ‘breaks’ are highlighted. Bletchley Park’s current rôle in Anglo-Polish diplomatic relations...Human Factors in Codebreaking 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Human factors in resuscitation teaching.

    PubMed

    Norris, Elizabeth M; Lockey, Andrew S

    2012-04-01

    There is an increasing interest in human factors within the healthcare environment reflecting the understanding of their impact on safety. The aim of this paper is to explore how human factors might be taught on resuscitation courses, and improve course outcomes in terms of improved mortality and morbidity for patients. The delivery of human factors training is important and this review explores the work that has been delivered already and areas for future research and teaching. Medline was searched using MESH terms Resuscitation as a Major concept and Patient or Leadership as core terms. The abstracts were read and 25 full length articles reviewed. Critical incident reporting has shown four recurring problems: lack of organisation at an arrest, lack of equipment, non functioning equipment, and obstructions preventing good care. Of these, the first relates directly to the concept of human factors. Team dynamics for both team membership and leadership, management of stress, conflict and the role of debriefing are highlighted. Possible strategies for teaching them are discussed. Four strategies for improving human factors training are discussed: team dynamics (including team membership and leadership behaviour), the influence of stress, debriefing, and conflict within teams. This review illustrates how human factor training might be integrated further into life support training without jeopardising the core content and lengthening the courses. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. Purification and characterization of the human elongator complex.

    PubMed

    Hawkes, Nicola A; Otero, Gabriel; Winkler, G Sebastiaan; Marshall, Nick; Dahmus, Michael E; Krappmann, Daniel; Scheidereit, Claus; Thomas, Claire L; Schiavo, Giampietro; Erdjument-Bromage, Hediye; Tempst, Paul; Svejstrup, Jesper Q

    2002-01-25

    Human Elongator complex was purified to virtual homogeneity from HeLa cell extracts. The purified factor can exist in two forms: a six-subunit complex, holo-Elongator, which has histone acetyltransferase activity directed against histone H3 and H4, and a three-subunit core form, which does not have histone acetyltransferase activity despite containing the catalytic Elp3 subunit. Elongator is a component of early elongation complexes formed in HeLa nuclear extracts and can interact directly with RNA polymerase II in solution. Several human homologues of the yeast Elongator subunits were identified as subunits of the human Elongator complex, including StIP1 (STAT-interacting protein 1) and IKAP (IKK complex-associated protein). Mutations in IKAP can result in the severe human disorder familial dysautonomia, raising the possibility that this disease might be due to compromised Elongator function and therefore could be a transcription disorder.

  5. 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)

  6. 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.

  7. Complexity of Human Language Comprehension

    DTIC Science & Technology

    1988-12-01

    complexity theory. a theory of the absolute difficulty of solving computation~d problems. in terms of their natural parameters. The major techrical result...of the thesis is that these computational problems are all intractable and cannot be solved in practice. The greatest difficulty of the research ies in...a major conceptual problem with this approach to linguitic theory: TGs do not construct explicit representations. In a TG, linguistic relations are

  8. The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation.

    PubMed

    Li, Xianghong; Zhao, Qiping; Liao, Rong; Sun, Peiqing; Wu, Xiaohua

    2003-08-15

    DNA replication initiation is tightly controlled so that each origin only fires once per cell cycle. Cell cycle-dependent Cdt1 degradation plays an essential role in DNA replication control, as overexpression of Cdt1 leads to re-replication. In this study, we investigated the mechanisms of Cdt1 degradation in mammalian cells. We showed that the F-box protein Skp2 specifically interacted with human Cdt1 in a phosphorylation-dependent manner. The SCF(Skp2) complex ubiquitinated Cdt1 both in vivo and in vitro. Down-regulation of Skp2 or disruption of the interaction between Cdt1 and Skp2 resulted in a stabilization and accumulation of Cdt1. These results suggest that the SCF(Skp2)-mediated ubiquitination pathway may play an important role in the cell cycle-dependent Cdt1 degradation in mammalian cells.

  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. 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).

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. Human variants in the neuronal basic helix-loop-helix/Per-Arnt-Sim (bHLH/PAS) transcription factor complex NPAS4/ARNT2 disrupt function.

    PubMed

    Bersten, David C; Bruning, John B; Peet, Daniel J; Whitelaw, Murray L

    2014-01-01

    Neuronal Per-Arnt-Sim homology (PAS) Factor 4 (NPAS4) is a neuronal activity-dependent transcription factor which heterodimerises with ARNT2 to regulate genes involved in inhibitory synapse formation. NPAS4 functions to maintain excitatory/inhibitory balance in neurons, while mouse models have shown it to play roles in memory formation, social interaction and neurodegeneration. NPAS4 has therefore been implicated in a number of neuropsychiatric or neurodegenerative diseases which are underpinned by defects in excitatory/inhibitory balance. Here we have explored a broad set of non-synonymous human variants in NPAS4 and ARNT2 for disruption of NPAS4 function. We found two variants in NPAS4 (F147S and E257K) and two variants in ARNT2 (R46W and R107H) which significantly reduced transcriptional activity of the heterodimer on a luciferase reporter gene. Furthermore, we found that NPAS4.F147S was unable to activate expression of the NPAS4 target gene BDNF due to reduced dimerisation with ARNT2. Homology modelling predicts F147 in NPAS4 to lie at the dimer interface, where it appears to directly contribute to protein/protein interaction. We also found that reduced transcriptional activation by ARNT2 R46W was due to disruption of nuclear localisation. These results provide insight into the mechanisms of NPAS4/ARNT dimerisation and transcriptional activation and have potential implications for cognitive phenotypic variation and diseases such as autism, schizophrenia and dementia.

  16. 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

  17. 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...

  18. 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...

  19. 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.

  20. 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. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. [Effect of MT01/PEN complexes on the expression of osteoprotegerin and receptor activator of nuclear factor κB ligand in human osteoblast-like cell line MG63].

    PubMed

    Ye, Cui; Yi, Zheng; Yuqin, Shen; Xu, Hou; Yixin, Lou; Xinhua, Sun

    2016-02-01

    This study aims to synthesize MTO1 (a kind of oligodeoxynucleotides) and N-isopropylacrylamide-modified polyethylenimines (PEN) complexes (MT01/PEN) as well as to investigate the effect of the complexes on the expression of osteoprotegerin (OPG) and the receptor activator of nuclear factor κB ligand (RANKL) in the human osteoblast-like cell line MG63. MG63 cells were transfected by MT01/PEN complexes formed with three different mass ratios (1:2, 1:4, 1:6) of MT01 to PEN. MT01 and MT01-s were used as positive control. Enzyme-linked immunosorbent assay and real-time polymerase chain reaction were performed to estimate the amount of OPG and RANKL released into the culture media and in MG63 at 24, 48, 72 h. MG63 responded to the MT01/PEN complexes by significantly upregulating the OPG on the protein and mRNA levels (P < 0.05). The protein and mRNA levels of RANKL were lower in most of the groups with complexes, and the OPG/RANKL ratio were higher (P < 0.05). MG63 were affected by the MT01/PEN complexes with different mass ratios, particularly when the ratio was 1:6. MT01 can enhance the promotion of ossification by establishing the delivery system with PEN.

  2. Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence

    PubMed Central

    Gordon, Lavinia; Joo, Jihoon E.; Powell, Joseph E.; Ollikainen, Miina; Novakovic, Boris; Li, Xin; Andronikos, Roberta; Cruickshank, Mark N.; Conneely, Karen N.; Smith, Alicia K.; Alisch, Reid S.; Morley, Ruth; Visscher, Peter M.; Craig, Jeffrey M.; Saffery, Richard

    2012-01-01

    Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic and shared and nonshared environmental factors to phenotypic variability. Using DNA methylation profiling of ∼20,000 CpG sites as a phenotype, we have examined discordance levels in three neonatal tissues from 22 MZ and 12 DZ twin pairs. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of nonshared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic, and other complex diseases. Finally, comparison of our data with that of several older twins revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyze DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome. PMID:22800725

  3. Neonatal DNA methylation profile in human twins is specified by a complex interplay between intrauterine environmental and genetic factors, subject to tissue-specific influence.

    PubMed

    Gordon, Lavinia; Joo, Jihoon E; Powell, Joseph E; Ollikainen, Miina; Novakovic, Boris; Li, Xin; Andronikos, Roberta; Cruickshank, Mark N; Conneely, Karen N; Smith, Alicia K; Alisch, Reid S; Morley, Ruth; Visscher, Peter M; Craig, Jeffrey M; Saffery, Richard

    2012-08-01

    Comparison between groups of monozygotic (MZ) and dizygotic (DZ) twins enables an estimation of the relative contribution of genetic and shared and nonshared environmental factors to phenotypic variability. Using DNA methylation profiling of ∼20,000 CpG sites as a phenotype, we have examined discordance levels in three neonatal tissues from 22 MZ and 12 DZ twin pairs. MZ twins exhibit a wide range of within-pair differences at birth, but show discordance levels generally lower than DZ pairs. Within-pair methylation discordance was lowest in CpG islands in all twins and increased as a function of distance from islands. Variance component decomposition analysis of DNA methylation in MZ and DZ pairs revealed a low mean heritability across all tissues, although a wide range of heritabilities was detected for specific genomic CpG sites. The largest component of variation was attributed to the combined effects of nonshared intrauterine environment and stochastic factors. Regression analysis of methylation on birth weight revealed a general association between methylation of genes involved in metabolism and biosynthesis, providing further support for epigenetic change in the previously described link between low birth weight and increasing risk for cardiovascular, metabolic, and other complex diseases. Finally, comparison of our data with that of several older twins revealed little evidence for genome-wide epigenetic drift with increasing age. This is the first study to analyze DNA methylation on a genome scale in twins at birth, further highlighting the importance of the intrauterine environment on shaping the neonatal epigenome.

  4. 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

  5. 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.

  6. 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.

  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. 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.

  9. 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.

  10. 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.

  11. Human factors in waste management

    SciTech Connect

    Moray, N.

    1994-10-01

    This article examines the role of human factors in radioactive waste management. Although few problems and ergonomics are special to radioactive waste management, some problems are unique especially with long term storage. The entire sociotechnical system must be looked at in order to see where improvement can take place because operator errors, as seen in Chernobyl and Bhopal, are ultimately the result of management errors.

  12. Complexity of coupled human and natural systems.

    PubMed

    Liu, Jianguo; Dietz, Thomas; Carpenter, Stephen R; Alberti, Marina; Folke, Carl; Moran, Emilio; Pell, Alice N; Deadman, Peter; Kratz, Timothy; Lubchenco, Jane; Ostrom, Elinor; Ouyang, Zhiyun; Provencher, William; Redman, Charles L; Schneider, Stephen H; Taylor, William W

    2007-09-14

    Integrated studies of coupled human and natural systems reveal new and complex patterns and processes not evident when studied by social or natural scientists separately. Synthesis of six case studies from around the world shows that couplings between human and natural systems vary across space, time, and organizational units. They also exhibit nonlinear dynamics with thresholds, reciprocal feedback loops, time lags, resilience, heterogeneity, and surprises. Furthermore, past couplings have legacy effects on present conditions and future possibilities.

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

    PubMed

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

    2009-11-01

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

  14. 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

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

    PubMed

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

    2017-01-06

    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. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  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. 14 CFR 460.15 - Human factors.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

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

  19. 14 CFR 460.15 - Human factors.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

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

  20. 14 CFR 460.15 - Human factors.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

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

  1. 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.

  2. 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.

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

    SciTech Connect

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

    2003-09-15

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

  4. 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

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

    PubMed

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

    2012-07-05

    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.

  6. 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.

  7. Human factors in space telepresence

    NASA Technical Reports Server (NTRS)

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

    1983-01-01

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

  8. 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).

  9. 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.

  10. 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.

  11. 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.

  12. Human behavioral complexity peaks at age 25.

    PubMed

    Gauvrit, Nicolas; Zenil, Hector; Soler-Toscano, Fernando; Delahaye, Jean-Paul; Brugger, Peter

    2017-04-01

    Random Item Generation tasks (RIG) are commonly used to assess high cognitive abilities such as inhibition or sustained attention. They also draw upon our approximate sense of complexity. A detrimental effect of aging on pseudo-random productions has been demonstrated for some tasks, but little is as yet known about the developmental curve of cognitive complexity over the lifespan. We investigate the complexity trajectory across the lifespan of human responses to five common RIG tasks, using a large sample (n = 3429). Our main finding is that the developmental curve of the estimated algorithmic complexity of responses is similar to what may be expected of a measure of higher cognitive abilities, with a performance peak around 25 and a decline starting around 60, suggesting that RIG tasks yield good estimates of such cognitive abilities. Our study illustrates that very short strings of, i.e., 10 items, are sufficient to have their complexity reliably estimated and to allow the documentation of an age-dependent decline in the approximate sense of complexity.

  13. Human behavioral complexity peaks at age 25

    PubMed Central

    Brugger, Peter

    2017-01-01

    Random Item Generation tasks (RIG) are commonly used to assess high cognitive abilities such as inhibition or sustained attention. They also draw upon our approximate sense of complexity. A detrimental effect of aging on pseudo-random productions has been demonstrated for some tasks, but little is as yet known about the developmental curve of cognitive complexity over the lifespan. We investigate the complexity trajectory across the lifespan of human responses to five common RIG tasks, using a large sample (n = 3429). Our main finding is that the developmental curve of the estimated algorithmic complexity of responses is similar to what may be expected of a measure of higher cognitive abilities, with a performance peak around 25 and a decline starting around 60, suggesting that RIG tasks yield good estimates of such cognitive abilities. Our study illustrates that very short strings of, i.e., 10 items, are sufficient to have their complexity reliably estimated and to allow the documentation of an age-dependent decline in the approximate sense of complexity. PMID:28406953

  14. 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.

  15. 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?

  16. 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.

  17. 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.

  18. 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.

  19. Major Histocompatibility Complex Class II Transactivator CIITA Is a Viral Restriction Factor That Targets Human T-Cell Lymphotropic Virus Type 1 Tax-1 Function and Inhibits Viral Replication▿

    PubMed Central

    Tosi, Giovanna; Forlani, Greta; Andresen, Vibeke; Turci, Marco; Bertazzoni, Umberto; Franchini, Genoveffa; Poli, Guido; Accolla, Roberto S.

    2011-01-01

    Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of an aggressive malignancy of CD4+ T lymphocytes. Since the viral transactivator Tax-1 is a major player in T-cell transformation, targeting Tax-1 protein is regarded as a possible strategy to arrest viral replication and to counteract neoplastic transformation. We demonstrate that CIITA, the master regulator of major histocompatibility complex class II gene transcription, inhibits HTLV-1 replication by blocking the transactivating function of Tax-1 both when exogenously transfected in 293T cells and when endogenously expressed by a subset of U937 promonocytic cells. Tax-1 and CIITA physically interact in vivo via the first 108 amino acids of Tax-1 and two CIITA adjacent regions (amino acids 1 to 252 and 253 to 410). Interestingly, only CIITA 1-252 mediated Tax-1 inhibition, in agreement with the fact that CIITA residues from positions 64 to 124 were required to block Tax-1 transactivation. CIITA inhibitory action on Tax-1 correlated with the nuclear localization of CIITA and was independent of the transcription factor NF-YB, previously involved in CIITA-mediated inhibition of Tax-2 of HTLV-2. Instead, CIITA severely impaired the physical and functional interaction of Tax-1 with the cellular coactivators p300/CBP-associated factor (PCAF), cyclic AMP-responsive element binding protein (CREB), and activating transcription factor 1 (ATF1), which are required for the optimal activation of HTLV-1 promoter. Accordingly, the overexpression of PCAF, CREB, and ATF1 restored Tax-1-dependent transactivation of the viral long-terminal-repeat promoter inhibited by CIITA. These findings strongly support our original observation that CIITA, beside increasing the antigen-presenting function for pathogen antigens, acts as an endogenous restriction factor against human retroviruses by blocking virus replication and spreading. PMID:21813598

  20. 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.

  1. Heritability of the Human Craniofacial Complex.

    PubMed

    Šešelj, Maja; Duren, Dana L; Sherwood, Richard J

    2015-09-01

    Quantifying normal variation and the genetic underpinnings of anatomical structures is one of the main goals of modern morphological studies. However, the extent of genetic contributions to normal variation in craniofacial morphology in humans is still unclear. The current study addresses this gap by investigating the genetic underpinnings of normal craniofacial morphology. The sample under investigation consists of 75 linear and angular measurements spanning the entire craniofacial complex, recorded from lateral cephalographs of 1,379 participants in the Fels Longitudinal Study. Heritabilities for each trait were estimated using SOLAR, a maximum-likelihood variance components approach utilizing all pedigree information for parameter estimation. Trait means and mean effects of the covariates age, sex, age(2) , sex × age, and sex × age(2) were simultaneously estimated in the analytic models. All traits of the craniofacial complex were significantly heritable. Heritability estimates ranged from 0.10 to 0.60, with the majority being moderate. It is important to note that we found similar ranges of heritability occurring across the different functional/developmental components of the craniofacial complex, the splanchnocranium, the basicranium, and the neurocranium. This suggests that traits from different regions of the craniofacial complex are of comparable utility for the purposes of population history and phylogeny reconstruction. At the same time, this genetic influence on craniofacial morphology signals a caution to researchers of nongenetic studies to consider the implications of this finding when selecting samples for study given their project design and goals. © 2015 Wiley Periodicals, Inc.

  2. 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

  3. Complex Loci in human and mouse genomes.

    PubMed

    Engström, Pär G; Suzuki, Harukazu; Ninomiya, Noriko; Akalin, Altuna; Sessa, Luca; Lavorgna, Giovanni; Brozzi, Alessandro; Luzi, Lucilla; Tan, Sin Lam; Yang, Liang; Kunarso, Galih; Ng, Edwin Lian-Chong; Batalov, Serge; Wahlestedt, Claes; Kai, Chikatoshi; Kawai, Jun; Carninci, Piero; Hayashizaki, Yoshihide; Wells, Christine; Bajic, Vladimir B; Orlando, Valerio; Reid, James F; Lenhard, Boris; Lipovich, Leonard

    2006-04-01

    Mammalian genomes harbor a larger than expected number of complex loci, in which multiple genes are coupled by shared transcribed regions in antisense orientation and/or by bidirectional core promoters. To determine the incidence, functional significance, and evolutionary context of mammalian complex loci, we identified and characterized 5,248 cis-antisense pairs, 1,638 bidirectional promoters, and 1,153 chains of multiple cis-antisense and/or bidirectionally promoted pairs from 36,606 mouse transcriptional units (TUs), along with 6,141 cis-antisense pairs, 2,113 bidirectional promoters, and 1,480 chains from 42,887 human TUs. In both human and mouse, 25% of TUs resided in cis-antisense pairs, only 17% of which were conserved between the two organisms, indicating frequent species specificity of antisense gene arrangements. A sampling approach indicated that over 40% of all TUs might actually be in cis-antisense pairs, and that only a minority of these arrangements are likely to be conserved between human and mouse. Bidirectional promoters were characterized by variable transcriptional start sites and an identifiable midpoint at which overall sequence composition changed strand and the direction of transcriptional initiation switched. In microarray data covering a wide range of mouse tissues, genes in cis-antisense and bidirectionally promoted arrangement showed a higher probability of being coordinately expressed than random pairs of genes. In a case study on homeotic loci, we observed extensive transcription of nonconserved sequences on the noncoding strand, implying that the presence rather than the sequence of these transcripts is of functional importance. Complex loci are ubiquitous, host numerous nonconserved gene structures and lineage-specific exonification events, and may have a cis-regulatory impact on the member genes.

  4. 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.

  5. 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

  6. Human factors in agile manufacturing

    SciTech Connect

    Forsythe, C.

    1995-03-01

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

  7. HL-20 Vertical Human Factors

    NASA Technical Reports Server (NTRS)

    1992-01-01

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

  8. Accounting for the Human Factor.

    ERIC Educational Resources Information Center

    Ginsburg, Sigmund G.

    1994-01-01

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

  9. 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

  10. Addressing Human Factors Gaps in Cyber Defense

    DTIC Science & Technology

    2016-09-23

    Air Force Research Laboratory 711th Human Performance Wing Airman Systems Directorate Warfighter Interface Division Applied Neuroscience Branch...NOTES 88ABW Cleared 03/18/2016; 88ABW-2016-1329. Human Factors and Ergonomics Society 2016 Annual Meeting (HFES) 19 – 23 September 2016 14... Human Factors community has begun to address human -centered issues in cyber operations, but in comparison to technological communities, we have only

  11. NASA Information Sciences and Human Factors Program

    NASA Technical Reports Server (NTRS)

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

    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.

  12. 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.

  13. 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.

  14. 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…

  15. Human Factors in Aeronautics at NASA

    NASA Technical Reports Server (NTRS)

    Mogford, Richard

    2016-01-01

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

  16. Human Modeling For Ground Processing Human Factors Engineering Analysis

    NASA Technical Reports Server (NTRS)

    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.

  17. 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

  18. 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…

  19. 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…

  20. 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…

  1. Complex Stapes Motions in Human Ears

    PubMed Central

    Chatzimichalis, Michail; Lauxmann, Michael; Röösli, Christof; Eiber, Albrecht; Huber, Alexander M.

    2010-01-01

    It has been reported that the physiological motion of the stapes in human and several animals in response to acoustic stimulation is mainly piston-like at low frequencies. At higher frequencies, the pattern includes rocking motions around the long and short axes of the footplate in human and animal ears. Measurements of such extended stapes motions are highly sensitive to the exact angulation of the stapes in relation to the measurement devices and to measurement errors. In this study, velocity in a specific direction was measured at multiple points on the footplates of human temporal bones using a Scanning Laser Doppler Vibrometer (SLDV) system, and the elementary components of the stapes motions, which were the piston-like motion and the rocking motions about the short and long axes of the footplate, were calculated from the measurements. The angular position of a laser beam with respect to the stapes and coordinates of the measurement points on the footplate plane were calculated by correlation between the SLDV measurement frame and the footplate-fixed frame, which was obtained from micro-CT images. The ratios of the rocking motions relative to the piston-like motion increased with frequency and reached a maximum around 7 kHz. A novel method for quantitatively assessing measurements of complex stapes motions and error boundaries of the motion components is presented. In the frequency range of 0.5 to 8 kHz, the magnitudes of the piston-like and two rocking motions were larger than estimated values of the corresponding upper error bounds. PMID:20165895

  2. 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.

  3. 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

  4. Rail human factors: Past, present and future.

    PubMed

    Wilson, John R; Norris, Beverley J

    2005-11-01

    Rail human factors research has grown rapidly in both quantity and quality of output over the past few years. There was an early base of work at a few institutions carried out over the 1960s and 1970s, followed by a lull in the 1980s and early 1990s. The continual influences of safety concerns, new technical system opportunities, reorganisation of the business, needs to increase effective, reliable and safe use of capacity, and increased society, media and government interest have now accelerated rail human factors research programmes in several countries. In this paper we review the literature on rail human factors research, covering driving, signalling and control, maintenance, reporting systems, passenger interests, planning and technical systems change. Current major rail human factors programmes are summarised and future research needs proposed. It is asserted that general human factors models and methods are being re-assessed, and new ones developed, to meet the requirements of the railways.

  5. 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.

  6. 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.

  7. Human Factors in Cabin Accident Investigations

    NASA Technical Reports Server (NTRS)

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

    1996-01-01

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

  8. Human factors in general aviation

    NASA Technical Reports Server (NTRS)

    1975-01-01

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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Complex Interdependence Regulates Heterotypic Transcription Factor Distribution and Coordinates Cardiogenesis

    PubMed Central

    Luna-Zurita, Luis; Stirnimann, Christian U.; Glatt, Sebastian; Kaynak, Bogac L.; Thomas, Sean; Baudin, Florence; Samee, Md Abul Hassan; He, Daniel; Small, Eric M.; Mileikovsky, Maria; Nagy, Andras; Holloway, Alisha K.; Pollard, Katherine S.; Müller, Christoph W.; Bruneau, Benoit G.

    2016-01-01

    SUMMARY Transcription factors (TFs) are thought to function with partners to achieve specificity and precise quantitative outputs. In the developing heart, heterotypic TF interactions, such as between the T-box TF TBX5 and the homeodomain TF NKX2-5, have been proposed as a mechanism for human congenital heart defects. We report extensive and complex interdependent genomic occupancy of TBX5, NKX2-5, and the zinc finger TF GATA4, coordinately controlling cardiac gene expression, differentiation, and morphogenesis. Interdependent binding serves not only to co-regulate gene expression, but also to prevent TFs from distributing to ectopic loci and activate lineage-inappropriate genes. We define preferential motif arrangements for TBX5 and NKX2-5 cooperative binding sites, supported at the atomic level by their co-crystal structure bound to DNA, revealing direct interaction between the two factors, and induced DNA bending. Complex interdependent binding mechanisms reveal tightly regulated TF genomic distribution and define a combinatorial logic for heterotypic TF regulation of differentiation. PMID:26875865

  15. Human factors paradigm and customer care perceptions.

    PubMed

    Clarke, Colin; Eales-Reynolds, Lesley-Jane

    2015-01-01

    The purpose of this paper is to examine if customer care (CC) can be directly linked to patient safety through a human factors (HF) framework. Data from an online questionnaire, completed by a convenience healthcare worker sample (n=373), was interrogated using thematic analysis within Vincent et al.'s (1998) HF theoretical framework. This proposes seven areas affecting patient safety: institutional context, organisation and management, work environment, team factors, individual, task and patient. Analysis identified responses addressing all framework areas. Responses (597) principally focused on work environment 40.7 per cent (n=243), organisation and management 28.8 per cent (n=172). Nevertheless, reference to other framework areas were clearly visible within the data: teams 10.2 per cent (n=61), individual 6.7 per cent (n=40), patients 6.0 per cent (n=36), tasks 4.2 per cent (n=24) and institution 3.5 per cent (n=21). Findings demonstrate congruence between CC perceptions and patient safety within a HF framework. The questionnaire requested participants to identify barriers to rather than CC enablers. Although this was at a single site complex organisation, it was similar to those throughout the NHS and other international health systems. CC can be viewed as consonant with patient safety rather than the potentially dangerous consumerisation stance, which could ultimately compromise patient safety. This work provides an original perspective on the link between CC and patient safety and has the potential to re-focus healthcare perceptions.

  16. 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.…

  17. 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

  18. 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.

  19. 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.

  20. 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

  1. Human factors and simulation in emergency medicine.

    PubMed

    Hayden, Emily M; Wong, Ambrose H; Ackerman, Jeremy; Sande, Margaret K; Lei, Charles; Kobayashi, Leo; Cassara, Michael; Cooper, Dylan D; Perry, Kimberly; Lewandowski, William E; Scerbo, Mark W

    2017-09-19

    This consensus group from the 2017 Academic Emergency Medicine Consensus Conference "Catalyzing System Change through Health Care Simulation: Systems, Competency, and Outcomes" held in Orlando, Florida on May 16, 2017 focused on the use of human factors and simulation in the field of emergency medicine. The human factors discipline is often underutilized within emergency medicine but has significant potential in improving the interface between technologies and individuals in the field. The discussion explored the domain of human factors, its benefits in medicine, how simulation can be a catalyst for human factors work in emergency medicine, and how emergency medicine can collaborate with human factors professionals to affect change. Implementing human factors in emergency medicine through healthcare simulation will require a demonstration of clinical and safety outcomes, advocacy to stakeholders and administrators, and establishment of structured collaborations between human factors professionals and emergency medicine, such as in this breakout group. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  2. 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.

  3. Summary report of the Human Factors Committee

    NASA Technical Reports Server (NTRS)

    Cooper, G. E.

    1978-01-01

    Reduced visibility as a human factors problem was studied in terms of the number of lives lost and cost of aircraft accidents and incidents. Human factors in flight through turbulence in detection and avoidance techniques, pilot and crew procedures for handling workloads and distractions caused by turbulence, and aircraft handling techniques for safe flights through turbulence are investigated. Education and training were reviewed in icing problems on aircraft. Pilots failure to recognize and detect wind shear in severe storms is examined. The pilots avoidance of lightning is discussed from the human factors point of view.

  4. Human factors certification: A useful concept?

    NASA Technical Reports Server (NTRS)

    Jackson, Alistair

    1994-01-01

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

  5. Nitric oxide reduces SLC29A1 promoter activity and adenosine transport involving transcription factor complex hCHOP-C/EBPalpha in human umbilical vein endothelial cells from gestational diabetes.

    PubMed

    Farías, Marcelo; Puebla, Carlos; Westermeier, Francisco; Jo, Miguel J; Pastor-Anglada, Marçal; Casanello, Paola; Sobrevia, Luis

    2010-04-01

    Reduced expression of human equilibrative nucleoside transporter 1 (hENT1) results from nitric oxide (NO)-dependent reduced SLC29A1 transcriptional activity in human umbilical vein endothelial cells (HUVECs) from gestational diabetes. As expression of the transcription factor C/EBP homologous protein 10 (hCHOP, which forms heterodimers with C/EBPalpha transcription factor) is activated by NO and induced in diabetes mellitus, we hypothesize that hCHOP plays a role in the gestational diabetes-reduced hENT1 expression in HUVECs. HUVEC primary cultures from 42 normal and 42 gestational diabetic pregnancies were used for adenosine uptake assays. Real-time PCR (mRNA quantification), western blotting (protein abundance), and luciferase activity (SLC29A1 promoter activity) were used. hCHOP-C/EBPalpha activity was assayed by chromatin immunoprecipitation. Overlap extension mutagenesis was used to generate a mutated hCHOP-C/EBPalpha consensus site at the SLC29A1 promoter, and endothelial NO synthase (eNOS) siRNA recombinant adenovirus was used to knock down eNOS. hCHOP nuclear protein abundance and binding to DNA were higher in gestational diabetes, paralleled by reduced SLC29A1 promoter activity, hENT1 expression, and transport activity. These changes were blocked by hCHOP consensus sequence mutation (-1845G > T and -1844C > A), eNOS-siRNA-induced knockdown, and N(G)-nitro-L-arginine methyl ester (NOS inhibitor), and were mimicked by S-nitroso-N-acetyl-L, D-penicillamine (NO donor) in cells from normal pregnancies. hCHOP and C/EBPalpha overexpression mimicked gestational diabetes effects in cells from normal pregnancies, but did not alter SLC29A1 promoter activity or hENT1-adenosine transport in cells from gestational diabetes. The hCHOP-C/EBPalpha complex down-regulates SLC29A1 expression in an NO-dependent manner in HUVECs from gestational diabetes.

  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. 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.

  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. Human Factors in Network Security

    DTIC Science & Technology

    1991-03-21

    mentioned, two other factors stimulate interest in network data security. These are; extensive telecomunications systems binding networks together, and the...This is a procedure that increases security by providing multiple, overlapping controls. A physical analogy is a facility where a fence is used in...unavailable. A physical analogy (Figure 2), shows that with a LAN built in the star configuration, failure of the central node will mean the network is

  10. 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.

  11. Microgravity human factors workstation development

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  12. Human factors and information transfer

    NASA Technical Reports Server (NTRS)

    Lee, Alfred T.

    1989-01-01

    Key problem areas in the management and transfer of information in the National Airspace System, contributing to human errors are identified. Information-management aspects supporting the user's ability to assess prevailing situations accurately with adequate time to make an informed decision are considered. The relationship between judgment biases and requirements for managing weather information is illustrated by examining such hazardous weather phenomena as microbursts and windshears. The system of air-ground communication relying almost exclusively on voice transmissions is discussed, and recommendations in the areas of communications procedures and technology development are provided.

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. Humanized docking system for assembly of targeting drug delivery complexes.

    PubMed

    Backer, Marina V; Gaynutdinov, Timur I; Gorshkova, Inna I; Crouch, Robert J; Hu, Tao; Aloise, Renee; Arab, Mohamed; Przekop, Kristen; Backer, Joseph M

    2003-05-20

    Targeted drug delivery requires 'loading' drugs onto targeting proteins. Traditional technologies for loading drugs rely on chemical conjugation of drugs or drug carriers to targeting proteins. An alternative approach might rely on assembly of targeting complexes using a docking system that includes two components: a 'docking' tag fused to a targeting protein, and a 'payload' module containing an adapter protein for non-covalent binding to the docking tag. We describe here a fully humanized adapter/docking tag system based on non-covalent interaction between two fragments of human pancreatic RNase I. A 15 amino acid long N-terminal fragment of RNase I designed to serve as a docking tag, was fused to the N-terminus of human vascular endothelial growth factor that served as a targeting protein. An 18-125 and an 18-127 amino acid long fragments of RNase I were engineered, expressed and refolded into active conformations to serve as adapter proteins. Interactions between the targeting and adapter proteins were characterized using enzymatic analysis and surface plasmon resonance. Targeting DNA delivery complexes were assembled, characterized by dynamic light scattering, and found to be very effective in receptor-mediated DNA delivery.

  20. 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.

  1. Human factors in cockpit automation

    NASA Technical Reports Server (NTRS)

    Wiener, E. L.

    1984-01-01

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

  2. 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.

  3. Space Human Factors Engineering Gap Analysis Project Final Report

    NASA Technical Reports Server (NTRS)

    Hudy, Cynthia; Woolford, Barbara

    2006-01-01

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

  4. 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.

  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. Patient Safety: The Role of Human Factors and Systems Engineering

    PubMed Central

    Carayon, Pascale; Wood, Kenneth E.

    2011-01-01

    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. PMID:20543237

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Factors affecting the complexity of dental implant restoration - what is the current evidence and guidance?

    PubMed

    Wright, S P; Hayden, J; Lynd, J A; Walker-Finch, K; Willett, J; Ucer, C; Speechley, S D

    2016-11-18

    Objectives The aim of this paper is to identify the factors that affect the complexity of implant restoration and to explore the indices that help us to assess it. With this knowledge the growing number of clinicians restoring dental implants will have a better understanding of the available guidance and evidence base, and the differing levels of competence required.Study design A literature review was conducted. The selection of publications reporting on complexity was based on predetermined criteria and was agreed upon by the authors. After title and abstract screening 17 articles were reviewed. The articles that were utilised to form the ITI SAC tool and Cologne Risk Assessment we also included.Assessing complexity Two key guides are available: International Team for Implantology's Straight-forward Advanced Complex tool and the Cologne ABC risk score. While these guides help identify treatment complexity they do not provide a strong enough evidence base from which to solely base clinical decisions. The key patient factors are expectation, communication, the oral environment, aesthetic outcome, occlusion, soft tissue profile and the intra-arch distance, whereas the key technical factors are impression taking, type of retention, loading protocol and the need for provisional restorations. Human factors also have a significant effect on complexity, specifically, the experience and training of the clinician, team communication and the work environment.Conclusions There are many interconnecting factors that affect the complexity of dental implant restoration. Furthermore the two widely used indices for the assessment of complexity have been investigated, and although these offer a good guideline as to the level of complexity, there is a lack evidence to support their use. The development of evidence-based treatment and protocols is necessary to develop the current indices further, and these need to be expanded to include other critical areas, such as human factors. A

  7. 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.

  8. 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.

  9. Mycobacterium abscessus Complex Infections in Humans.

    PubMed

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

    2015-09-01

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

  10. Revolutions and shifting paradigms in human factors & ergonomics.

    PubMed

    Boff, Kenneth R

    2006-07-01

    The "Revolution in Information Technology" has spawned a series of transformational revolutions in the nature and practice of human factors and ergonomics (HFE). "Generation 1" HFE evolved with a focus on adapting equipment, workplace and tasks to human capabilities and limitations. Generation 2, focused on cognitive systems integration, arose in response to the need to manage automation and dynamic function allocation. Generation 3 is focused on symbiotic technologies that can amplify human physical and cognitive capabilities. Generation 4 is emergent and is focused on biological enhancement of physical or cognitive capabilities. The shift from HFE Generations 1 and 2 to Generations 3 and 4 profoundly alters accepted boundary constraints on the adaptability of humans in complex systems design. Furthermore, it has opened an ethical divide between those that see cognitive and physical enhancement as a great benefit to society and those who perceive this as tampering with the fundamentals of human nature.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. [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.

  16. 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

  17. 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.

  18. The human factors of workstation telepresence

    NASA Technical Reports Server (NTRS)

    Smith, Thomas J.; Smith, Karl U.

    1990-01-01

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

  19. Human genetic factors in tuberculosis: an update.

    PubMed

    van Tong, Hoang; Velavan, Thirumalaisamy P; Thye, Thorsten; Meyer, Christian G

    2017-09-01

    Tuberculosis (TB) is a major threat to human health, especially in many developing countries. Human genetic variability has been recognised to be of great relevance in host responses to Mycobacterium tuberculosis infection and in regulating both the establishment and the progression of the disease. An increasing number of candidate gene and genome-wide association studies (GWAS) have focused on human genetic factors contributing to susceptibility or resistance to TB. To update previous reviews on human genetic factors in TB we searched the MEDLINE database and PubMed for articles from 1 January 2014 through 31 March 2017 and reviewed the role of human genetic variability in TB. Search terms applied in various combinations were 'tuberculosis', 'human genetics', 'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium tuberculosis'. Articles in English retrieved and relevant references cited in these articles were reviewed. Abstracts and reports from meetings were also included. This review provides a recent summary of associations of polymorphisms of human genes with susceptibility/resistance to TB. © 2017 John Wiley & Sons Ltd.

  20. Signal- and Listener- Based Factors in Complex Auditory Pattern Perception

    DTIC Science & Technology

    1994-09-23

    auditory stimuli, or perhaps only on auditory signals from one ear, or only on signals with certain properties (e.g., musical sounds ), etc. To the extent...investigated various aspects of complex auditory perception. These research efforts largely focussed on perception of speech sounds , and provided...research effort made significant progress in clarifying how human listeners decode very .complex sounds . 20. OISTRIUTIONAVAILAILITY OP ABSTRACT 21

  1. 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.

  2. Integrating human factors research and surgery: a review.

    PubMed

    Shouhed, Daniel; Gewertz, Bruce; Wiegmann, Doug; Catchpole, Ken

    2012-12-01

    To provide a review of human factors research within the context of surgery. We searched PubMed for relevant studies published from the earliest available date through February 29, 2012. The search was performed using the following keywords: human factors, surgery, errors, teamwork, communication, stress, disruptions, interventions, checklists, briefings, and training. Additional articles were identified by a manual search of the references from the key articles. As 2 human factors specialists, a senior clinician, and a junior clinician, we carefully selected the most appropriate exemplars of research findings with specific relevance to surgical error and safety. Seventy-seven articles of relevance were selected and reviewed in detail. Opinion pieces and editorials were disregarded; the focus was solely on articles based on empirical evidence, with a particular emphasis on prospectively designed studies. The themes that emerged related to the development of human factors theories, the application of those theories within surgery, a specific interest in the concept of flow, and the theoretical basis and value of human-related interventions for improving safety and flow in surgery. Despite increased awareness of safety, errors routinely continue to occur in surgical care. Disruptions in the flow of an operation, such as teamwork and communication failures, contribute significantly to such adverse events. While it is apparent that some incidence of human error is unavoidable, there is much evidence in medicine and other fields that systems can be better designed to prevent or detect errors before a patient is harmed. The complexity of factors leading to surgical errors requires collaborations between surgeons and human factors experts to carry out the proper prospective and observational studies. Only when we are guided by this valid and real-world data can useful interventions be identified and implemented.

  3. 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.

  4. 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

  5. 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…

  6. 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.

  7. Human factors engineering and patient safety

    PubMed Central

    Gosbee, J

    2002-01-01

    

 The case study and analyses presented here illustrate the crucial role of human factors engineering (HFE) in patient safety. HFE is a framework for efficient and constructive thinking which includes methods and tools to help healthcare teams perform patient safety analyses, such as root cause analyses. The literature on HFE over several decades contains theories and applied studies to help to solve difficult patient safety problems and design issues. A case study is presented which illustrates the vulnerabilities of human factors design in a transport monitor. The subsequent analysis highlights how to move beyond the more obvious contributing factors like training to design problems and the establishment of informal norms. General advice is offered to address these issues and design issues specific to this case are discussed. PMID:12468696

  8. Human Factors Principles in Information Dashboard Design

    SciTech Connect

    Hugo, Jacques V.; St. Germain, Shawn

    2016-06-01

    When planning for control room upgrades, nuclear power plants have to deal with a multitude of engineering and operational impacts. This will inevitably include several human factors considerations, including physical ergonomics of workstations, viewing angles, lighting, seating, new communication requirements, and new concepts of operation. In helping nuclear power utilities to deal with these challenges, the Idaho National Laboratory (INL) has developed effective methods to manage the various phases of the upgrade life cycle. These methods focus on integrating human factors engineering processes with the plant’s systems engineering process, a large part of which is the development of end-state concepts for control room modernization. Such an end-state concept is a description of a set of required conditions that define the achievement of the plant’s objectives for the upgrade. Typically, the end-state concept describes the transition of a conventional control room, over time, to a facility that employs advanced digital automation technologies in a way that significantly improves system reliability, reduces human and control room-related hazards, reduces system and component obsolescence, and significantly improves operator performance. To make the various upgrade phases as concrete and as visible as possible, an end-state concept would include a set of visual representations of the control room before and after various upgrade phases to provide the context and a framework within which to consider the various options in the upgrade. This includes the various control systems, human-system interfaces to be replaced, and possible changes to operator workstations. This paper describes how this framework helps to ensure an integrated and cohesive outcome that is consistent with human factors engineering principles and also provide substantial improvement in operator performance. The paper further describes the application of this integrated approach in the

  9. A New Definition of Shape Complexity Factor in Forging

    NASA Astrophysics Data System (ADS)

    Ara, R. Hosseini; Poursina, M.; Golastanian, H.

    2007-04-01

    One of the main objectives of forging process design is to ensure adequate metal flow in the dies so that the desired finished part geometry can be obtained without any internal or external defects. This paper presents a preform design method which employs a new criterion based on shape complexity factor to determine the necessity of preform stages for axisymmetric forging parts. The presented criterion was tested on several examples using finite element method to verify the models. Comparison of the new shape complexity factor with the other ones shows that the new criterion is more accurate in estimating the number of preform stages.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. Simulation and analysis of complex human tasks for manufacturing

    NASA Astrophysics Data System (ADS)

    Badler, Norman I.; Becket, Welton M.; Webber, Bonnie L.

    1995-11-01

    We discuss how the combination of a realistic human figure with a high-level behavioral control interface allow the construction of detailed simulations of humans performing manual tasks from which inferences about human performance requirements can be made. The Jack human modeling environment facilitates the real-time simulation of humans performing sequences of tasks such as walking, lifting, reaching, and grasping in a complex simulation environment. Analysis capabilities include strength, reachability, and visibility; moreover results from these tests can affect an unfolding simulation.

  15. 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.

  16. 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.

  17. 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.

  18. 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}.

  19. 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.

  20. 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.

  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. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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…

  7. 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…

  8. Evaluating Human Factors in Augmented Reality Systems

    DTIC Science & Technology

    2005-12-01

    A ugmented reality (AR) has been part of computergraphics methodology for decades. A number of prototype AR systems have shown the possibilities this...and predicting what might happen in the near future in your environment. We per- formed a domain analysis to determine which AR capa- bilities most...user’s location and then per- forming the (cognitive) task of Mark A. Livingston Naval Research Laboratory Evaluating Human Factors in Augmented Reality

  9. 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

  10. Human Factors Representations for Combat Models

    DTIC Science & Technology

    1982-07-01

    decicion rules. Existing rules in most versions do not make such requests. 5-B. Based on user-specified decision tables. 6-A. Relocation of command posts...on such simu- lations. The report makes explicit the presently implicit assumptions re- e •lated to human factors and provides a structure within which...tasks under adverse conditions; (2) decision making ; and (3) recognition of features and patterns. vii ’ . vii a

  11. Human Factors Feedback: Brain Acoustic Monitor

    DTIC Science & Technology

    2012-02-01

    gloves (nitrile rubber or latex ) or working in extreme heat or cold could also impact the ease-of- use of the touchpad. To remedy this problem, a standard...considerations for improving the device’s functionality based on applied human factor domain principles assessed during subject testing. This report focuses...board is permanently integrated into the laptop, would be highly preferable to improve portability and ruggedness. Such a design would decrease

  12. Heresies: Brief Essays on Human Factors

    DTIC Science & Technology

    1977-03-01

    uncertain? Does this increasing experience of deJa vu (the experience of, I already know this) mean that HF (and other behavioral research) tends, as some...government. Industry and universities are unlikely to provide the necessary support for Human Factors research and application. 10. In addition to internal...might be considered a crude parallel to a sonar/radar classification task. Does the situation accurately represent a MIS? Does the CRT aifect the

  13. 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

  14. Human factors aspects of air traffic control

    NASA Technical Reports Server (NTRS)

    Older, H. J.; Cameron, B. J.

    1972-01-01

    An overview of human factors problems associated with the operation of present and future air traffic control systems is presented. A description is included of those activities and tasks performed by air traffic controllers at each operational position within the present system. Judgemental data obtained from controllers concerning psychological dimensions related to these tasks and activities are also presented. The analysis includes consideration of psychophysiological dimensions of human performance. The role of the human controller in present air traffic control systems and his predicted role in future systems is described, particularly as that role changes as the result of the system's evolution towards a more automated configuration. Special attention is directed towards problems of staffing, training, and system operation. A series of ten specific research and development projects are recommended and suggested work plans for their implementation are included.

  15. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. 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.

  17. Human factors in modern traffic systems.

    PubMed

    Noy, Y I

    1997-10-01

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

  18. Space Station crew safety - Human factors model

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

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

  19. Safe surgery, the human factors approach.

    PubMed

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

    2010-04-01

    Studies estimate that a degree of error occurs in 5-15% of all hospital admissions, with 45% of errors occurring in the operating theatre. Staffing limitations, high turnover rates, site and side-specific surgical procedures, make operating theatres a high-risk environment. Valuable lessons may be learned from the aviation experience with error management. With over 70% of air-crashes occurring due to human rather than technical error, the Human Factors Approach to error recognises the potential for errors occurring due to human limitations, such as stress and fatigue. It encourages error reporting in a non-punitive environment, where it is seen as a valuable source of information, facilitating education and future error prevention. Errors in healthcare and surgery however, have been traditionally associated with secrecy and embarrassment, often reaching an unsatisfactory endpoint with no resultant education. Application of the Human Factors Approach to error management in healthcare, can only serve to improve safety standards in our hospitals and satisfy ever-increasing public expectations. Copyright 2009 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

  20. 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. © RSNA, 2015.

  1. Linking human factors to corporate strategy with cognitive mapping techniques.

    PubMed

    Village, Judy; Greig, Michael; Salustri, Filippo A; Neumann, W Patrick

    2012-01-01

    For human factors (HF) to avoid being considered of "side-car" status, it needs to be positioned within the organization in such a way that it affects business strategies and their implementation. Tools are needed to support this effort. This paper explores the feasibility of applying a technique from operational research called cognitive mapping to link HF to corporate strategy. Using a single case study, a cognitive map is drawn to reveal the complex relationships between human factors and achieving an organization's strategic goals. Analysis of the map for central concepts and reinforcing loops enhances understanding that can lead to discrete initiatives to facilitate integration of HF. It is recommended that this technique be used with senior managers to understand the organizations` strategic goals and enhance understanding of the potential for HF to contribute to the strategic goals.

  2. Human factors in air traffic control: problems at the interfaces.

    PubMed

    Shouksmith, George

    2003-10-01

    The triangular ISIS model for describing the operation of human factors in complex sociotechnical organisations or systems is applied in this research to a large international air traffic control system. A large sample of senior Air Traffic Controllers were randomly assigned to small focus discussion groups, whose task was to identify problems occurring at the interfaces of the three major human factor components: individual, system impacts, and social. From these discussions, a number of significant interface problems, which could adversely affect the functioning of the Air Traffic Control System, emerged. The majority of these occurred at the Individual-System Impact and Individual-Social interfaces and involved a perceived need for further interface centered training.

  3. 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).

  4. Human adipocytes secrete mineralocorticoid-releasing factors.

    PubMed

    Ehrhart-Bornstein, M; Lamounier-Zepter, V; Schraven, A; Langenbach, J; Willenberg, H S; Barthel, A; Hauner, H; McCann, S M; Scherbaum, W A; Bornstein, S R

    2003-11-25

    Obesity has become an epidemic problem in western societies, contributing to metabolic diseases, hypertension, and cardiovascular disease. Overweight and obesity are frequently associated with increased plasma levels of aldosterone. Recent evidence suggests that human fat is a highly active endocrine tissue. Therefore, we tested the hypothesis that adipocyte secretory products directly stimulate adrenocortical aldosterone secretion. Secretory products from isolated human adipocytes strongly stimulated steroidogenesis in human adrenocortical cells (NCI-H295R) with a predominant effect on mineralocorticoid secretion. Aldosterone secretion increased 7-fold during 24 h of incubation. This stimulation was comparable to maximal stimulation of these cells with forskolin (2 x 10(-5) M). On the molecular level, there was a 10-fold increase in the expression of steroid acute regulatory peptide mRNA. This effect was independent of adipose angiotensin II as revealed by the stimulatory effect of fat cell-conditioned medium even in the presence of the angiotensin type 1 receptor antagonist, valsartan. None of the recently defined adipocytokines accounted for the effect. Mineralocorticoid-stimulating activity was heat sensitive and could be blunted by heating fat cell-conditioned medium to 99 degrees C. Centrifugal filtration based on molecular mass revealed at least two releasing factors: a heat sensitive fraction (molecular mass >50 kDa) representing 60% of total activity, and an inactive fraction (molecular mass <50 kDa). However, the recovery rate increased to 92% when combining these two fractions, indicating the interaction of at least two factors. In conclusion, human adipocytes secrete potent mineralocorticoid-releasing factors, suggesting a direct link between obesity and hypertension.

  5. 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…

  6. 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…

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

    PubMed

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

    2001-04-01

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

  8. 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.

  9. 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.

  10. HEMOGLOBIN PRODUCTION FACTORS IN THE HUMAN LIVER

    PubMed Central

    Whipple, G. H.; Robscheit-Robbins, F. S.

    1942-01-01

    Human liver tissue has been assayed to determine the amount of hemoglobin production factors in normal and abnormal states. Standardized dogs made anemic by blood removal have been used in this biological assay. Normal animal liver as control is rated as 100 per cent. Normal human liver tissue as compared with the normal animal control contains more of these hemoglobin production factors—a biological assay ratio of 120 to 160 per cent. Infections, acute and chronic, do not appear to modify these values, the concentration of hemoglobin-producing factors falling within the normal range. Pernicious anemia and aplastic anemia both show large liver stores of hemoglobin-producing factors—a biological assay ratio of 200 to 240 per cent. Therapy in pernicious anemia reduces these liver stores as new red cells are formed. Secondary anemia presents a low normal or subnormal liver store of hemoglobin-producing factors—an assay of 60 to 130 per cent. Hemochromatosis, erythroblastic anemia, and hemolytic icterus in spite of large iron deposits in the liver usually show a biological assay which is normal or close to normal. Polycythemia shows low reserve stores of hemoglobin-producing factors. Leukemias present a wide range of values discussed above. Hypoproteinemia almost always is associated with low reserve stores of hemoglobin-producing factors in the liver—biological assays of 60 to 80 per cent. Hypoproteinemia means a depletion of body protein reserve stores including the labile protein liver reserves—a strong indication that the prehemoglobin material (or globin) is related to these liver stores. Pregnancy, eclampsia, and lactation all may present subnormal liver stores of hemoglobin-producing factors. Exhaustion of protein stores lowers the barrier to infection and renders the liver very susceptible to many toxic substances. It should not be difficult to correct hypoproteinemia under these conditions and thus relieve the patient of a real hazard. PMID:19871236

  11. 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.

  12. Epidermal growth factor (urogastrone)-mediated phosphorylation of a 35-kDa substrate in human placental membranes: relationship to the. beta. subunit of the guanine nucleotide regulatory complex

    SciTech Connect

    Valentine-Braun, K.A.; Northup, J.K.; Hollenberg, M.D.

    1986-01-01

    The authors have identified a component of about 35 kDa (pp35), present in human placental membrane preparations, that is a substrate for epidermal growth factor urogastrone) (EGF(Uro))-mediated phosphorylation. The EGF(Uro)-stimulated phosphorylation of pp35 was calcium-dependent and was markedly enhanced in membranes prepared in the presence (but not in the absence) of calcium. The (/sup 32/P)-phosphate incorporated into pp35 in the presence of EGF(Uro) was alkali-stable and was present as O/sup 4/-phosphotyrosine. Under identical conditions, insulin did not stimulate pp35 phosphorylation. Either in its native or in its phosphorylated form, pp35 could be released from the membranes in the presence of calcium-chelating agents (EDTA/EGTA); and EGF(Uro)-stimulated phosphorylation was reconstituted by adding back EDTA/EGTA eluates to EDTA/EGTA-washed membranes in the presence of calcium. The properties of pp35 were similar if not identical to those of ..beta..-35, a 35-kDa polypeptide similar to the ..beta.. subunit of the guanine nucleotide-binding oligomers that stimulate (G/sub s/) or inhibit (G/sub i/) the adenylate cyclase system. In contrast, the addition of ..beta.. subunits derived from rabbit liver G/sub i/ or bovine transducin did not result in phosphorylation of a 35-kDa substrate in the reconstituted system. They conclude that the human placental pp35 substrate likely represents the placental equivalent of the ..beta..-35 protein. The data point to a possible link between those receptors involved in growth-factor action and the regulatory systems that utilize GTP-binding proteins as transducing elements.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. 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.

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

    PubMed

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

    1993-04-23

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

  5. DOT/FAA Human Factors Workshop on AVIATION. Transcript. Volume I.

    DTIC Science & Technology

    1980-11-01

    and better applications of present knowledge in human factors. Concerned groups have called for more attention to the root causes of so-called human...the avoidance next time through by changing methods, practices or applications of complex systems and hardware. I believe that there is general... application to helicopters, we also have underway or are planning a number of programs that relate specifically to the human factors problems associated

  6. 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

  7. 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. (c) 2012 APA, all rights reserved.

  8. 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.

  9. 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.

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

    PubMed

    Xiao, Feng; Cuthill, Innes C

    2016-09-14

    Remaining undetected is often key to survival, and camouflage is a widespread solution. However, extrinsic to the animal itself, the complexity of the background may be important. This has been shown in laboratory experiments using artificially patterned prey and backgrounds, but the mechanism remains obscure (not least because 'complexity' is a multifaceted concept). In this study, we determined the best predictors of detection by wild birds and human participants searching for the same cryptic targets on trees in the field. We compared detection success to metrics of background complexity and 'visual clutter' adapted from the human visual salience literature. For both birds and humans, the factor that explained most of the variation in detectability was the textural complexity of the tree bark as measured by a metric of feature congestion (specifically, many nearby edges in the background). For birds, this swamped any effects of colour match to the local surroundings, although for humans, local luminance disparities between the target and tree became important. For both taxa, a more abstract measure of complexity, entropy, was a poorer predictor. Our results point to the common features of background complexity that affect visual search in birds and humans, and how to quantify them. © 2016 The Author(s).

  11. 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.

  12. Isolation and characterization of human orthologs of yeast CCR4–NOT complex subunits

    PubMed Central

    Albert, Thomas K.; Lemaire, Marc; Berkum, Nynke L. van; Gentz, Reiner; Collart, Martine A.; Timmers, H. Th. Marc

    2000-01-01

    The yeast CCR4–NOT protein complex is a global regulator of RNA polymerase II transcription. It is comprised of yeast NOT1 to NOT5, yeast CCR4 and additional proteins like yeast CAF1. Here we report the isolation of cDNAs encoding human NOT2, NOT3, NOT4 and a CAF1-like factor, CALIF. Analysis of their mRNA levels in different human tissues reveals a common ubiquitous expression pattern. A multitude of two-hybrid interactions among the human cDNAs suggest that their encoded proteins also form a complex in mammalian cells. Functional conservation of these proteins throughout evolution is supported by the observation that the isolated human NOT3 and NOT4 cDNAs can partially complement corresponding not mutations in yeast. Interestingly, human CALIF is highly homologous to, although clearly different from, a recently described human CAF1 protein. Conserved interactions of this factor with both NOT and CCR4 proteins and co-immunoprecipitation experiments suggest that CALIF is a bona fide component of the human CCR4–NOT complex. PMID:10637334

  13. 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

  14. Where's the emotion? How sport psychology can inform research on emotion in human factors.

    PubMed

    Eccles, David W; Ward, Paul; Woodman, Tim; Janelle, Christopher M; Le Scanff, Christine; Ehrlinger, Joyce; Castanier, Carole; Coombes, Stephen A

    2011-04-01

    The aim of this study was to demonstrate how research on emotion in sport psychology might inform the field of human factors. Human factors historically has paid little attention to the role of emotion within the research on human-system relations. The theories, methods, and practices related to research on emotion within sport psychology might be informative for human factors because fundamentally, sport psychology and human factors are applied fields concerned with enhancing performance in complex, real-world domains. Reviews of three areas of theory and research on emotion in sport psychology are presented, and the relevancy of each area for human factors is proposed: (a) emotional preparation and regulation for performance, (b) an emotional trait explanation for risk taking in sport, and (c) the link between emotion and motor behavior. Finally, there are suggestions for how to continue cross-talk between human factors and sport psychology about research on emotion and related topics in the future. The relevance of theory and research on emotion in sport psychology for human factors is demonstrated. The human factors field and, in particular, research on human-system relations may benefit from a consideration of theory and research on emotion in sport psychology. Theories, methods, and practices from sport psychology might be applied usefully to human factors.

  15. 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.

  16. Human factors in anaesthesia: lessons from aviation.

    PubMed

    Toff, N J

    2010-07-01

    Aviation safety has evolved over more than a century and has achieved remarkable results. Applying some of the lessons learned may help make healthcare safer. From the perspective of an anaesthetic background and some thousands of hours of airline flying, I offer a personal perspective, try to give a sense of the place of human factors in airline operations and some of the current problems, and make some suggestions as to what the NHS and anaesthesia might learn from this. Although many of the ingredients for safe operation are frequently already present in our hospitals, and some individual clinical areas and departments achieve high levels of reliability and safety, I will emphasize my firm belief that we cannot expect improvements in human factors training and awareness to be fully effective in the healthcare setting without the parallel development of a simple and strong safety system across organizations. In the process, we may find that the safe hospital turns out somewhat differently to the safe airline.

  17. 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

  18. [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.

  19. 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.

  20. Implementing complex innovations: factors influencing middle manager support.

    PubMed

    Chuang, Emmeline; Jason, Kendra; Morgan, Jennifer Craft

    2011-01-01

    Middle manager resistance is often described as a major challenge for upper-level administrators seeking to implement complex innovations such as evidence-based protocols or new skills training. However, factors influencing middle manager support for innovation implementation are currently understudied in the U.S. health care literature. This article examined the factors that influence middle managers' support for and participation in the implementation of work-based learning, a complex innovation adopted by health care organizations to improve the jobs, educational pathways, skills, and/or credentials of their frontline workers. We conducted semistructured interviews and focus groups with 92 middle managers in 17 health care organizations. Questions focused on understanding middle managers' support for work-based learning as a complex innovation, facilitators and barriers to the implementation process, and the systems changes needed to support the implementation of this innovation. Factors that emerged as influential to middle manager support were similar to those found in broader models of innovation implementation within the health care literature. However, our findings extend previous research by developing an understanding about how middle managers perceived these constructs and by identifying specific strategies for how to influence middle manager support for the innovation implementation process. These findings were generally consistent across different types of health care organizations. Study findings suggest that middle manager support was highest when managers felt the innovation fit their workplace needs and priorities and when they had more discretion and control over how it was implemented. Leaders seeking to implement innovations should consider the interplay between middle managers' control and discretion, their narrow focus on the performance of their own departments or units, and the dedication of staff and other resources for empowering their

  1. Social factors in clinical complexity: reflections from a paediatric unit.

    PubMed

    Sarkar, Shruti; Sarkar, Dipankar

    2010-06-01

    Medical text books have taught us evaluation and diagnosis of disease based on patients' symptoms, signs and relevant investigations and treatment is then implemented according to the clinical condition and current best available evidence. There are objective scoring scales to assess the severity of the condition, progress and eventual outcome. These scales rarely if ever consider the impact of social factors on the course of treatment and eventual clinical outcome. But in a country like India with diverse cultural backgrounds and deep social structures social, cultural and economic factors have great ramifications on the clinical course, treatment and ultimate outcome. Diverse beliefs, faiths, social norms and cultural practices not only have a direct effect on a person's daily life but indirectly also effect educational, professional and health care access. The effects of these factors on families and their way of deciding on their child's management in complex systems show multifaceted dynamic interactions leading to at times unexpected outcomes.

  2. Human liver cytochrome P450 3A4 ubiquitination: molecular recognition by UBC7-gp78 autocrine motility factor receptor and UbcH5a-CHIP-Hsc70-Hsp40 E2-E3 ubiquitin ligase complexes.

    PubMed

    Wang, YongQiang; Kim, Sung-Mi; Trnka, Michael J; Liu, Yi; Burlingame, A L; Correia, Maria Almira

    2015-02-06

    CYP3A4 is an abundant and catalytically dominant human liver endoplasmic reticulum-anchored cytochrome P450 enzyme engaged in the biotransformation of endo- and xenobiotics, including >50% of clinically relevant drugs. Alterations of CYP3A4 protein turnover can influence clinically relevant drug metabolism and bioavailability and drug-drug interactions. This CYP3A4 turnover involves endoplasmic reticulum-associated degradation via the ubiquitin (Ub)-dependent 26 S proteasomal system that relies on two highly complementary E2 Ub-conjugating-E3 Ub-ligase (UBC7-gp78 and UbcH5a-C terminus of Hsc70-interacting protein (CHIP)-Hsc70-Hsp40) complexes, as well as protein kinases (PK) A and C. We have documented that CYP3A4 Ser/Thr phosphorylation (Ser(P)/Thr(P)) by PKA and/or PKC accelerates/enhances its Lys ubiquitination by either of these E2-E3 systems. Intriguingly, CYP3A4 Ser(P)/Thr(P) and ubiquitinated Lys residues reside within the cytosol-accessible surface loop and/or conformationally assembled acidic Asp/Glu clusters, leading us to propose that such post-translational Ser/Thr protein phosphorylation primes CYP3A4 for ubiquitination. Herein, this possibility was examined through various complementary approaches, including site-directed mutagenesis, chemical cross-linking, peptide mapping, and LC-MS/MS analyses. Our findings reveal that such CYP3A4 Asp/Glu/Ser(P)/Thr(P) surface clusters are indeed important for its intermolecular electrostatic interactions with each of these E2-E3 subcomponents. By imparting additional negative charge to these Asp/Glu clusters, such Ser/Thr phosphorylation would generate P450 phosphodegrons for molecular recognition by the E2-E3 complexes, thereby controlling the timing of CYP3A4 ubiquitination and endoplasmic reticulum-associated degradation. Although the importance of phosphodegrons in the CHIP targeting of its substrates is known, to our knowledge this is the first example of phosphodegron involvement in gp78-substrate

  3. Plant polyadenylation factors: conservation and variety in the polyadenylation complex in plants.

    PubMed

    Hunt, Arthur G; Xing, Denghui; Li, Qingshun Q

    2012-11-20

    Polyadenylation, an essential step in eukaryotic gene expression, requires both cis-elements and a plethora of trans-acting polyadenylation factors. The polyadenylation factors are largely conserved across mammals and fungi. The conservation seems also extended to plants based on the analyses of Arabidopsis polyadenylation factors. To extend this observation, we systemically identified the orthologs of yeast and human polyadenylation factors from 10 plant species chosen based on both the availability of their genome sequences and their positions in the evolutionary tree, which render them representatives of different plant lineages. The evolutionary trajectories revealed several interesting features of plant polyadenylation factors. First, the number of genes encoding plant polyadenylation factors was clearly increased from "lower" to "higher" plants. Second, the gene expansion in higher plants was biased to some polyadenylation factors, particularly those involved in RNA binding. Finally, while there are clear commonalities, the differences in the polyadenylation apparatus were obvious across different species, suggesting an ongoing process of evolutionary change. These features lead to a model in which the plant polyadenylation complex consists of a conserved core, which is rather rigid in terms of evolutionary conservation, and a panoply of peripheral subunits, which are less conserved and associated with the core in various combinations, forming a collection of somewhat distinct complex assemblies. The multiple forms of plant polyadenylation complex, together with the diversified polyA signals may explain the intensive alternative polyadenylation (APA) and its regulatory role in biological functions of higher plants.

  4. 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.

  5. 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…

  6. 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…

  7. 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…

  8. 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…

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

    PubMed

    Mahlmeister, Laura R

    2010-01-01

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

  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. 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

  12. 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

  13. 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.

  14. 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.

  15. 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.

  16. Human factors technology for America's space program

    NASA Technical Reports Server (NTRS)

    Montemerlo, M. D.

    1982-01-01

    NASA is initiating a space human factors research and technology development program in October 1982. The impetus for this program stems from: the frequent and economical access to space provided by the Shuttle, the advances in control and display hardware/software made possible through the recent explosion in microelectronics technology, heightened interest in a space station, heightened interest by the military in space operations, and the fact that the technology for long duration stay times for man in space has received relatively little attention since the Apollo and Skylab missions. The rationale for and issues in the five thrusts of the new program are described. The main thrusts are: basic methodology, crew station design, ground control/operations, teleoperations and extra vehicular activity.

  17. 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.

  18. Human Factors in Virtual Reality Development

    NASA Technical Reports Server (NTRS)

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

    1995-01-01

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

  19. Human factors and ergonomics for primary care.

    PubMed

    Bowie, Paul; Jeffcott, Shelly

    2016-03-01

    In the second paper of this series, we provide a brief overview of the scientific discipline of human factors and ergonomics (HFE). Traditionally the HFE focus in healthcare has been in acute hospital settings which are perceived to exhibit characteristics more similar to other high-risk industries already applying related principles and methods. This paper argues that primary care is an area which could benefit extensively from an HFE approach, specifically in improving the performance and well-being of people and organisations. To this end, we define the purpose of HFE, outline its three specialist sub-domains (physical, cognitive and organisational HFE) and provide examples of guiding HFE principles and practices. Additionally, we describe HFE issues of significance to primary care education, improvement and research and outline early plans for building capacity and capability in this setting.

  20. 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

  1. 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…

  2. 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…

  3. A Complex Network of Factors with Overlapping Affinities Repress Splicing through Intronic Elements

    PubMed Central

    Wang, Yang; Xiao, Xinshu; Zhang, Jianming; Choudhury, Rajarshi; Robertson, Alex; Li, Kai; Ma, Meng; Burge, Christopher B.; Wang, Zefeng

    2012-01-01

    To better understand splicing regulation, we used a cell-based screen to identify ten diverse motifs that inhibit splicing from intron. Each motif was validated in another human cell type and gene context, and their presence correlated with in vivo splicing changes. All motifs exhibited exonic splicing enhancer or silencer activity, and grouping these motifs based on their distributions yielded clusters with distinct patterns of context-dependent activity. Candidate regulatory factors associated with each motif were identified, recovering 24 known and novel splicing regulators. Specific domains in selected factors were sufficient to confer ISS activity. Many factors bound multiple distinct motifs with similar affinity, and all motifs were recognized by multiple factors, revealing a complex, overlapping network of protein:RNA interactions. This arrangement enables individual cis-element to function differently in distinct cellular contexts depending on the spectrum of regulatory factors present. PMID:23241926

  4. A biomedical informatics perspective on human factors - How human factors influence information technology adoption.

    PubMed

    Meyer, R

    2011-01-01

    to select and summarize excellent research published in 2010 in the field of bio-medical informatics human factors. we attempt to derive a synthetic overview of the activity and new trends in this field, from a selection of worldwide research papers published during 2010. this year again, healthcare information technology (HIT) adoption occupies a central role in the field and leads to research focused mainly on measuring impact and factors influencing it. One of the selected papers especially dissects the anatomy of a nationwide personal electronic health record adoption failure. Due to the vast and increasing amount of excellent works, choosing the best papers in human factors is a challenge. More and more the published work takes into account fundamental principles expressed in Grudin's Laws, one form of which is: "When those who beneût from a technology are not those who do the work, then the technology is likely to fail or be subverted.".

  5. 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.

  6. Leveraging Health Care Simulation Technology for Human Factors Research: Closing the Gap Between Lab and Bedside.

    PubMed

    Deutsch, Ellen S; Dong, Yue; Halamek, Louis P; Rosen, Michael A; Taekman, Jeffrey M; Rice, John

    2016-11-01

    We describe health care simulation, designed primarily for training, and provide examples of how human factors experts can collaborate with health care professionals and simulationists-experts in the design and implementation of simulation-to use contemporary simulation to improve health care delivery. The need-and the opportunity-to apply human factors expertise in efforts to achieve improved health outcomes has never been greater. Health care is a complex adaptive system, and simulation is an effective and flexible tool that can be used by human factors experts to better understand and improve individual, team, and system performance within health care. Expert opinion is presented, based on a panel delivered during the 2014 Human Factors and Ergonomics Society Health Care Symposium. Diverse simulators, physically or virtually representing humans or human organs, and simulation applications in education, research, and systems analysis that may be of use to human factors experts are presented. Examples of simulation designed to improve individual, team, and system performance are provided, as are applications in computational modeling, research, and lifelong learning. The adoption or adaptation of current and future training and assessment simulation technologies and facilities provides opportunities for human factors research and engineering, with benefits for health care safety, quality, resilience, and efficiency. Human factors experts, health care providers, and simulationists can use contemporary simulation equipment and techniques to study and improve health care delivery. © 2016, Human Factors and Ergonomics Society.

  7. 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.

  8. 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.

  9. Atrial natriuretic factor in human plasma

    SciTech Connect

    Gutkowska, J.; Bonan, R.; Roy, D.; Bourassa, M.; Garcia, R.; Thibault, G.; Genest, J.; Cantin, M.

    1986-08-29

    A reproducible and sensitive radioimmunoassay (RIA) was developed to measure ANF in human plasma. Immunoreactive ANF was extracted from plasma with Sep-Pak cartridges, using 0.2% ammonium acetate (pH 4) with acetonitrile. The sensitivity of the assay was 3.9 pg/ml. The coefficient of variance for inter-assay and intra-assay was 16.8% and 6.8%, respectively. In normal healthy subjects (n = 67), ANF content was 11.9 +/- 1.3 pg/ml (mean +/- SEM). Significantly-higher ANF concentrations were found in proximal coronary sinus blood, being 6 to 37 times greater than in the peripheral circulation. Comparison of the prior extraction method with direct RIA revealed a good correlation (r = 91) in samples containing higher than 100 pg/ml ANF. No correlation was observed with lower values. The elution profiles of reverse-phase HPLC of peripheral and coronary sinus plasma extracts were similar but somewhat complex, with the main immunoreactive peak corresponding to a low-molecular-weight peptide.

  10. 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

  11. The science of human factors: separating fact from fiction

    PubMed Central

    Russ, Alissa L; Fairbanks, Rollin J; Karsh, Ben-Tzion; Militello, Laura G; Saleem, Jason J; Wears, Robert L

    2013-01-01

    Background Interest in human factors has increased across healthcare communities and institutions as the value of human centred design in healthcare becomes increasingly clear. However, as human factors is becoming more prominent, there is growing evidence of confusion about human factors science, both anecdotally and in scientific literature. Some of the misconceptions about human factors may inadvertently create missed opportunities for healthcare improvement. Methods The objective of this article is to describe the scientific discipline of human factors and provide common ground for partnerships between healthcare and human factors communities. Results The primary goal of human factors science is to promote efficiency, safety and effectiveness by improving the design of technologies, processes and work systems. As described in this article, human factors also provides insight on when training is likely (or unlikely) to be effective for improving patient safety. Finally, we outline human factors specialty areas that may be particularly relevant for improving healthcare delivery and provide examples to demonstrate their value. Conclusions The human factors concepts presented in this article may foster interdisciplinary collaborations to yield new, sustainable solutions for healthcare quality and patient safety. PMID:23592760

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

    SciTech Connect

    Curt Braun; John Grimes; Eric Shaver; Ronald Boring

    2011-09-01

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

  13. Engineering Complex Human-Technological Work Systems: A Sensemaking Approach

    DTIC Science & Technology

    2007-06-01

    of the systems analyst. Here, the systems engineer must begin to consider various types of knowledge - based systems, including (1) work control...sequence of both formal and informal activities and knowledge products through which an organization projects and guides its actions into the future, and...system engineer with deeper insight into the structures and activities associated with knowledge creation. Complex human-technological work systems

  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. 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.

  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. 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.

  18. 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…

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

    NASA Technical Reports Server (NTRS)

    Hess, Ronald A.

    1987-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Hess, Ronald A.

    1987-01-01

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

  1. 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.

  2. 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.; hide

    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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Human Serum Albumin Complexed with Myristate and AZT

    SciTech Connect

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

    2008-06-16

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

  11. 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.

  12. 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.

  13. [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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Human factors assessments of innovative technologies: Robotics sector

    SciTech Connect

    Moran, J.B.

    1997-12-01

    The U.S. Department of Energy (DOE) has funded major environmental technology developments over the past several years. One area that received significant attention is robotics, which has resulted in the development of a wide range of unique robotic systems tailored to the many tasks unique to the DOE complex. These systems are often used in highly hazardous environments, which reduces or eliminates worker exposures. The DOE, concurrent with the technology development initiative, also established and funded a 5-yr cooperative agreement intended to interface with the technology development community-with specific attention to the occupational safety and health aspects associated with individual technologies through human factors and hazard assessments. This program is now in its third year.

  19. 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.

  20. Possible DNA Viral Factors of Human Breast Cancer

    PubMed Central

    Hsu, Chun-Ru; Lu, Tsong-Ming; Chin, Lengsu William; Yang, Chi-Chiang

    2010-01-01

    Viruses are considered to be one of the high-risk factors closely related to human breast cancer. However, different studies of viruses in breast cancer present conflicting results and some of these works remain in dispute. DNA viruses, such as specific types of human papillomaviruses (HPV), Epstein–Barr virus (EBV), human cytomegalovirus (HCMV), herpes simplex virus (HSV), and human herpes virus type 8 (HHV-8), have emerged as causal factors of some human cancers. These respective exogenous viruses and the possibility of multiple viral factors are discussed in this review. PMID:24281079

  1. 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

  2. Human RAD50 makes a functional DNA-binding complex.

    PubMed

    Kinoshita, Eri; van Rossum-Fikkert, Sari; Sanchez, Humberto; Kertokalio, Aryandi; Wyman, Claire

    2015-06-01

    The MRE11-RAD50-NBS1 (MRN) complex has several distinct functions in DNA repair including important roles in both non-homologous end-joining (NHEJ) and homologous recombination (HR). The biochemical activities of MR(N) have been well characterized implying specific functional roles for the components. The arrangement of proteins in the complex implies interdependence of their biochemical activities making it difficult to separate specific functions. We obtained purified human RAD50 and observed that it binds ATP, undergoes ATP-dependent conformational changes as well as having ATPase activity. Scanning force microscopy analysis clearly showed that RAD50 binds DNA although not as oligomers. RAD50 alone was not functional in tethering DNA molecules. ATP increased formation of RAD50 multimers which were however globular lacking extended coiled coils, in contrast to the MR complex where ATP induced oligomers have obvious coiled coils protruding from a central domain. These results suggest that MRE11 is important in maintaining the structural arrangement of RAD50 in the protein complex and perhaps has a role in reinforcing proper alignment of the coiled coils in the ATP-bound state. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  3. 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.

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

    PubMed Central

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

    2014-01-01

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

  5. 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

  6. 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.

  7. 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

  8. Protein anticoagulants targeting factor VIIa-tissue factor complex: a comprehensive review.

    PubMed

    Shah, Karna; Bayoumi, Riad; Banerjee, Yajnavalka

    2013-01-01

    Anticoagulants are pivotal for the treatment of debilitating thromboembolic and associated disorders. Current anticoagulants such as heparin and warfarin are non-specific and have a narrow therapeutic window. These limitations have provided the impetus to develop new anticoagulant therapies/strategies that target specific factors in the blood coagulation cascade, ideally those located upstream in the clotting process. Factor VIIa (FVIIa) presents an attractive target as it, in complex with tissue factor (TF), acts as the prima ballerina for the formation of blood clot. A comprehensive review delineating the structure-activity relationship of protein/peptide anticoagulants targeting FVIIa or TF-FVIIa complex is absent in the literature. In this article, we have addressed this deficit by appraising the peptide/protein anticoagulants that target FVIIa/TF-FVIIa complex. Further, the current status of these anticoagulants, with regard to their performance in different clinical trials has also been presented. Lastly, the unexplored domains of these unique proteins have also been highlighted, which will facilitate further translational research in this paradigm, to improve strategies to counter and treat thromboembolic disorders.

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

    PubMed Central

    Campbell, Michael C.; Tishkoff, Sarah A.

    2010-01-01

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

  10. 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.

  11. Shear stress is required for the endocytic uptake of the factor VIII-von Willebrand factor complex by macrophages.

    PubMed

    Castro-Núñez, L; Dienava-Verdoold, I; Herczenik, E; Mertens, K; Meijer, A B

    2012-09-01

    Low-density lipoprotein (LDL) receptor family members contribute to the cellular uptake of factor VIII. How von Willebrand factor fits into this endocytic pathway has remained poorly understood. It has been suggested that macrophages contribute to the clearance of the factor VIII (FVIII)-von Willebrand factor (VWF) complex. We now assessed the mechanisms of uptake employing human monocyte-derived macrophages. A confocal microscopy study was employed to study the uptake by monocyte-derived macrophages of a functional green fluorescent FVIII-GFP derivative in the presence and absence of VWF. The results revealed that FVIII-GFP is internalized by macrophages. We found that FVIII-GFP co-localizes with LDL receptor-related protein (LRP), and that the LRP antagonist Receptor Associated Protein (RAP) blocks the uptake of FVIII-GFP. However, FVIII-GFP was not detected in the macrophages in the presence of VWF, suggesting that the FVIII-VWF complex is not internalized by these cells at all. Apart from static conditions, we also investigated the effect of shear stress on the uptake of FVIII-GFP in presence of VWF. Immunofluorescence studies demonstrated that VWF does not block endocytosis of FVIII-GFP under flow conditions. Moreover, VWF itself was also internalized by the macrophages. Strikingly, in the presence of RAP, endocytosis of FVIII-GFP and VWF was inhibited. The results show that shear stress is required for macrophages to internalize both constituents of the FVIII-VWF complex. © 2012 International Society on Thrombosis and Haemostasis.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. High-Resolution NMR Studies of Human Tissue Factor

    PubMed Central

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

    2016-01-01

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

  18. 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.

  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. Lunar microcosmos. [human factors of lunar habitat

    NASA Technical Reports Server (NTRS)

    Pirie, N.

    1974-01-01

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

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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…

  7. Advanced Video Activity Analytics (AVAA): Human Factors Evaluation

    DTIC Science & Technology

    2015-05-01

    ARL-TR-7286 ● MAY 2015 US Army Research Laboratory Advanced Video Activity Analytics (AVAA): Human Factors Evaluation by...TR-7286 ● MAY 2015 US Army Research Laboratory Advanced Video Activity Analytics (AVAA): Human Factors Evaluation Patricia L McDermott...

  8. 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.

  9. Exocyst Complex Protein Expression in the Human Placenta

    PubMed Central

    Gonzalez, I.M.; Ackerman, W.E.; Vandre, D.D.; Robinson, J.M.

    2014-01-01

    Introduction Protein production and secretion are essential to syncytiotrophoblast function and are associated with cytotrophoblast cell fusion and differentiation. Syncytiotrophoblast hormone secretion is a crucial determinant of maternal-fetal health, and can be misregulated in pathological pregnancies. Although, polarized secretion is a key component of placental function, the mechanisms underlying this process are poorly understood. Objective While the octameric exocyst complex is classically regarded as a master regulator of secretion in various mammalian systems, its expression in the placenta remained unexplored. We hypothesized that the syncytiotrophoblast would express all exocyst complex components and effector proteins requisite for vesicle-mediated secretion more abundantly than cytotrophoblasts in tissue specimens. Methods A two-tiered immunobiological approach was utilized to characterize exocyst and ancillary proteins in normal, term human placentas. Exocyst protein expression and localization was documented in tissue homogenates via immunoblotting and immunofluorescence labeling of placental sections. Results The eight exocyst proteins, EXOC1, 2, 3, 4, 5, 6, 7, and 8, were found in the human placenta. In addition, RAB11, an important exocyst complex modulator, was also expressed. Exocyst and Rab protein expression appeared to be regulated during trophoblast differentiation, as the syncytiotrophoblast expressed these proteins with little, if any, expression in cytotrophoblast cells. Additionally, exocyst proteins were localized at or near the syncytiotrophoblast apical membrane, the major site of placental secretion Discussion/Conclusion Our findings highlight exocyst protein expression as novel indicators of trophoblast differentiation. The exocyst’s regulated localization within the syncytiotrophoblast in conjunction with its well known functions suggests a possible role in placental polarized secretion PMID:24856041

  10. Exocyst complex protein expression in the human placenta.

    PubMed

    Gonzalez, I M; Ackerman, W E; Vandre, D D; Robinson, J M

    2014-07-01

    Protein production and secretion are essential to syncytiotrophoblast function and are associated with cytotrophoblast cell fusion and differentiation. Syncytiotrophoblast hormone secretion is a crucial determinant of maternal-fetal health, and can be misregulated in pathological pregnancies. Although, polarized secretion is a key component of placental function, the mechanisms underlying this process are poorly understood. While the octameric exocyst complex is classically regarded as a master regulator of secretion in various mammalian systems, its expression in the placenta remained unexplored. We hypothesized that the syncytiotrophoblast would express all exocyst complex components and effector proteins requisite for vesicle-mediated secretion more abundantly than cytotrophoblasts in tissue specimens. A two-tiered immunobiological approach was utilized to characterize exocyst and ancillary proteins in normal, term human placentas. Exocyst protein expression and localization was documented in tissue homogenates via immunoblotting and immunofluorescence labeling of placental sections. The eight exocyst proteins, EXOC1, 2, 3, 4, 5, 6, 7, and 8, were found in the human placenta. In addition, RAB11, an important exocyst complex modulator, was also expressed. Exocyst and Rab protein expression appeared to be regulated during trophoblast differentiation, as the syncytiotrophoblast expressed these proteins with little, if any, expression in cytotrophoblast cells. Additionally, exocyst proteins were localized at or near the syncytiotrophoblast apical membrane, the major site of placental secretion. Our findings highlight exocyst protein expression as novel indicators of trophoblast differentiation. The exocyst's regulated localization within the syncytiotrophoblast in conjunction with its well known functions suggests a possible role in placental polarized secretion. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. 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.

  12. Complex carbohydrate utilization by the healthy human microbiome.

    PubMed

    Cantarel, Brandi L; Lombard, Vincent; Henrissat, Bernard

    2012-01-01

    The various ecological habitats in the human body provide microbes a wide array of nutrient sources and survival challenges. Advances in technology such as DNA sequencing have allowed a deeper perspective into the molecular function of the human microbiota than has been achievable in the past. Here we aimed to examine the enzymes that cleave complex carbohydrates (CAZymes) in the human microbiome in order to determine (i) whether the CAZyme profiles of bacterial genomes are more similar within body sites or bacterial families and (ii) the sugar degradation and utilization capabilities of microbial communities inhabiting various human habitats. Upon examination of 493 bacterial references genomes from 12 human habitats, we found that sugar degradation capabilities of taxa are more similar to others in the same bacterial family than to those inhabiting the same habitat. Yet, the analysis of 520 metagenomic samples from five major body sites show that even when the community composition varies the CAZyme profiles are very similar within a body site, suggesting that the observed functional profile and microbial habitation have adapted to the local carbohydrate composition. When broad sugar utilization was compared within the five major body sites, the gastrointestinal track contained the highest potential for total sugar degradation, while dextran and peptidoglycan degradation were highest in oral and vaginal sites respectively. Our analysis suggests that the carbohydrate composition of each body site has a profound influence and probably constitutes one of the major driving forces that shapes the community composition and therefore the CAZyme profile of the local microbial communities, which in turn reflects the microbiome fitness to a body site.

  13. 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

  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. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Pluripotent stem cell transcription factors during human odontogenesis.

    PubMed

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

    2013-09-01

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

  3. 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…

  4. 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.

  5. Human Milk Composition: Nutrients and Bioactive Factors

    PubMed Central

    Ballard, Olivia; Morrow, Ardythe L.

    2013-01-01

    Synopsis The composition of human milk is the biologic 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, e.g., lactoferrin, are being investigated as novel therapeutic agents. A dynamic, bioactive fluid, human milk changes in composition from colostrum to late lactation, and varies within feeds, diurnally, and between mothers. Feeding infants with expressed human milk is increasing. Pasteurized donor milk is now commonly provided to high risk infants and most mothers in the U.S. express and freeze their milk at some point in lactation for future infant feedings. Many milk proteins are degraded by heat treatment and freeze-thaw cycles may not have the same bioactivity after undergoing these treatments. This article provides an overview of the composition of human milk, sources of its variation, and its clinical relevance. PMID:23178060

  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. Hemoglobin Is a Co-Factor of Human Trypanosome Lytic Factor

    PubMed Central

    Widener, Justin; Nielsen, Marianne Jensby; Shiflett, April; Moestrup, Søren Kragh; Hajduk, Stephen

    2007-01-01

    Trypanosome lytic factor (TLF) is a high-density lipoprotein (HDL) subclass providing innate protection to humans against infection by the protozoan parasite Trypanosoma brucei brucei. Two primate-specific plasma proteins, haptoglobin-related protein (Hpr) and apolipoprotein L-1 (ApoL-1), have been proposed to kill T. b. brucei both singularly or when co-assembled into the same HDL. To better understand the mechanism of T. b. brucei killing by TLF, the protein composition of TLF was investigated using a gentle immunoaffinity purification technique that avoids the loss of weakly associated proteins. HDL particles recovered by immunoaffinity absorption, with either anti-Hpr or anti-ApoL-1, were identical in protein composition and specific activity for T. b. brucei killing. Here, we show that TLF-bound Hpr strongly binds Hb and that addition of Hb stimulates TLF killing of T. b. brucei by increasing the affinity of TLF for its receptor, and by inducing Fenton chemistry within the trypanosome lysosome. These findings suggest that TLF in uninfected humans may be inactive against T. b. brucei prior to initiation of infection. We propose that infection of humans by T. b. brucei causes hemolysis that triggers the activation of TLF by the formation of Hpr–Hb complexes, leading to enhanced binding, trypanolytic activity, and clearance of parasites. PMID:17845074

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

    PubMed

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

    2015-12-01

    Hepatitis E virus (HEV) infection, one of the foremost causes of acute hepatitis, is becoming a health problem of increasing magnitude. As other viruses, HEV exploits elements from host cell biochemistry, but we understand little as to which components of the human hepatocellular machinery are perverted for HEV multiplication. It is, however, known that the eukaryotic translation initiation factors 4F (eIF4F) complex, the key regulator of the mRNA-ribosome recruitment phase of translation initiation, serves as an important component for the translation and replication of many viruses. Here we aim to investigate the role of three subunits of the eIF4F complex: eukaryotic translation initiation factor 4A (eIF4A), eukaryotic translation initiation factor 4G (eIF4G) and eukaryotic translation initiation factor 4E (eIF4E) in HEV replication. We found that efficient replication of HEV requires eIF4A, eIF4G and eIF4E. Consistently, the negative regulatory factors of this complex: programmed cell death 4 (PDCD4) and eIF4E-binding protein 1 (4E-BP1) exert anti-HEV activities, which further illustrates the requirement for eIF4A and eIF4E in supporting HEV replication. Notably, phosphorylation of eIF4E induced by MNK1/2 activation is not involved in HEV replication. Although ribavirin and interferon-α (IFN-α), the most often-used off-label drugs for treating hepatitis E, interact with this complex, their antiviral activities are independent of eIF4E. In contrast, eIF4E silencing provokes enhanced anti-HEV activity of these compounds. Thus, HEV replication requires eIF4F complex and targeting essential elements of this complex provides important clues for the development of novel antiviral therapy against HEV. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. 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

  10. 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.

  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. 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

  13. Human Factors Considerations of Undergrounds in Insurgencies

    DTIC Science & Technology

    1966-09-01

    related to either the outbreak or the outcome of in- surgency. For instance, a country’s relative stage of economic advance- ment, as measured by its gross...other associated questions: Are there particular factors asso- ciated with the outbreak of insurgency? Are these factors related to the success or...surgency and that certain economic-social conditions are more conducive to the outbreak of insurgency than others. I t is commonly believed that

  14. Rapid Prototyping and the Human Factors Engineering Process

    DTIC Science & Technology

    2016-08-29

    qr-..2. 9 Rapid prototyping or ’virtual prototyping’ of human- machine interfaces offers the possibility of putting the human operator ’in the loop...facilitates an iterative approach to the development of the human- machine interface, and that is most applicable to the early stages of systems...factors engineering (HFE) process re- commended for the development of human- machine systems is based on a series of increasin¥ly detailed analyses of

  15. Human Factors Issues in Aircraft Maintenance and Inspection

    DTIC Science & Technology

    1989-10-01

    Unaided, Colin G. Drury , Ph.D .......................................... A-65 Vigilance and Inspection Performance, Earl L. Wiener, Ph.D .... A-72 Human...Inspection and Review A- 64 The Human Operator as an Inspector: Aided and Unaided Colin G. Drury , Ph.D. Professor of Industrial Engineering SUNY, Buffalo...Continued Ballroom A - HUMAN FACTORS TECHNOLOGY - 10:15 a.m. The Human Operator as an Inspector: Aided and Unaided Colin G. Drury , Ph.D. SUNY, Buffalo

  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. New Developments in Understanding the Complexity of Human Speech Production.

    PubMed

    Simonyan, Kristina; Ackermann, Hermann; Chang, Edward F; Greenlee, Jeremy D

    2016-11-09

    Speech is one of the most unique features of human communication. Our ability to articulate our thoughts by means of speech production depends critically on the integrity of the motor cortex. Long thought to be a low-order brain region, exciting work in the past years is overturning this notion. Here, we highlight some of major experimental advances in speech motor control research and discuss the emerging findings about the complexity of speech motocortical organization and its large-scale networks. This review summarizes the talks presented at a symposium at the Annual Meeting of the Society of Neuroscience; it does not represent a comprehensive review of contemporary literature in the broader field of speech motor control. Copyright © 2016 the authors 0270-6474/16/3611440-09$15.00/0.

  18. New Developments in Understanding the Complexity of Human Speech Production

    PubMed Central

    Ackermann, Hermann; Chang, Edward F.; Greenlee, Jeremy D.

    2016-01-01

    Speech is one of the most unique features of human communication. Our ability to articulate our thoughts by means of speech production depends critically on the integrity of the motor cortex. Long thought to be a low-order brain region, exciting work in the past years is overturning this notion. Here, we highlight some of major experimental advances in speech motor control research and discuss the emerging findings about the complexity of speech motocortical organization and its large-scale networks. This review summarizes the talks presented at a symposium at the Annual Meeting of the Society of Neuroscience; it does not represent a comprehensive review of contemporary literature in the broader field of speech motor control. PMID:27911747

  19. 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…

  20. Endoglin forms a heteromeric complex with the signaling receptors for transforming growth factor-beta.

    PubMed

    Yamashita, H; Ichijo, H; Grimsby, S; Morén, A; ten Dijke, P; Miyazono, K

    1994-01-21

    Human endoglin is a dimeric protein that binds transforming growth factor-beta (TGF-beta). A porcine cDNA clone for endoglin was obtained from a porcine uterus cDNA library. The deduced sequence of the primary translated product of endoglin consists of 643 amino acids with a high sequence identity (96%) to human endoglin in the transmembrane and intracellular domains, but with a lower sequence similarity (66%) in the extracellular domain. In contrast to human endoglin, porcine endoglin has no Arg-Gly-Asp tripeptide in its sequence. Antibodies, raised against a peptide corresponding to the intracellular domain of porcine endoglin, immunoprecipitated an 84-kDa protein under reducing condition and a 130-kDa protein under nonreducing condition in porcine aortic endothelial cells. Porcine endoglin bound TGF-beta 1 and -beta 3 efficiently, but TGF-beta 2 less efficiently. Endoglin was found to be coimmunoprecipitated with TGF-beta receptors type I and/or II by the endoglin antibodies or by TGF-beta receptor II antibodies in the presence of ligand. Thus, endoglin and TGF-beta receptors I and/or II most likely formed a heteromeric receptor complex. Endoglin was phosphorylated on serine residue(s), which did not change after stimulation by TGF-beta 1. These results revealed that endoglin is a phosphorylated protein which forms a heteromeric complex with signaling receptors for TGF-beta.

  1. 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

  2. Influence of von Willebrand factor on the reactivity of human factor VIII inhibitors with factor VIII.

    PubMed

    Gensana, M; Altisent, C; Aznar, J A; Casaña, P; Hernández, F; Jorquera, J I; Magallón, M; Massot, M; Puig, L

    2001-07-01

    In order to determine the difference in reactivity of factor (F) VIII inhibitors against the FVIII/von Willebrand factor (vWF) complex and against vWF-deficient FVIII, we investigated a panel of 10 antibodies to FVIII from multitransfused individuals with severe haemophilia A and other pathologies. Immunoblotting of purified FVIII and purified thrombin-cleaved FVIII revealed that in all cases inhibitor epitopes could be localized in the heavy chain (A2 subunit) while in four cases they were also present in the light chain. One of the FVIII inhibitors remained unclassified. The effect on FVIII:C of purified IgG from inhibitor plasmas was tested against a high purity FVIII/vWF concentrate and a monoclonally purified FVIII concentrate with only trace contents of vWF, by two different functional assays. Our results suggest that for those inhibitors showing A2 plus light chain (LC) reactivity, the IgG concentration required to inhibit 50% of FVIII activity in vitro is higher for the FVIII/vWF complex than for the vWF-deficient FVIII. We conclude that there might be a protective role of vWF (at least in vitro) against FVIII inhibitors with A2 and LC subunit specificity.

  3. 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

  4. 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.

  5. 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.

  6. 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

  7. Molecular determinants of the cell-cycle regulated Mcm1p-Fkh2p transcription factor complex.

    PubMed

    Boros, Joanna; Lim, Fei-Ling; Darieva, Zoulfia; Pic-Taylor, Aline; Harman, Ruth; Morgan, Brian A; Sharrocks, Andrew D

    2003-05-01

    The MADS-box transcription factor Mcm1p and forkhead (FKH) transcription factor Fkh2p act in a DNA-bound complex to regulate cell-cycle dependent expression of the CLB2 cluster in Saccharomyces cerevisiae. Binding of Fkh2p requires prior binding by Mcm1p. Here we have investigated the molecular determinants governing the formation of the Mcm1p- Fkh2p complex. Fkh2p exhibits cooperativity in complex formation with Mcm1p and we have mapped a small region of Fkh2p located immediately upstream of the FKH DNA binding domain that is required for this cooperativity. This region is lacking in the related protein Fkh1p that cannot form ternary complexes with Mcm1p. A second region is identified that inhibits Mcm1p-independent DNA binding by Fkh2p. The spacing between the Mcm1p and Fkh2p binding sites is also a critical determinant for complex formation. We also show that Fkh2p can form ternary complexes with the human counterpart of Mcm1p, serum response factor (SRF). Mutations at analogous positions in Mcm1p, which are known to affect SRF interaction with its partner protein Elk-1, abrogate complex formation with Fkh2p, demonstrating evolutionary conservation of coregulatory protein binding surfaces. Our data therefore provide molecular insights into the mechanisms of Mcm1p- Fkh2p complex formation and more generally aid our understanding of MADS-box protein function.

  8. Specificity-Determining DNA Triplet Code for Positioning of Human Preinitiation Complex

    NASA Astrophysics Data System (ADS)

    Goldshtein, Matan; Lukatsky, David B.

    2017-05-01

    The notion that transcription factors bind DNA only through specific, consensus binding sites has been recently questioned. In a pioneering study by Pugh and Venters no specific consensus motif for the positioning of the human pre-initiation complex (PIC) has been identified. Here, we reveal that nonconsensus, statistical, DNA triplet code provides specificity for the positioning of the human PIC. In particular, we reveal a highly non-random, statistical pattern of repetitive nucleotide triplets that correlates with the genome-wide binding preferences of PIC measured by Chip-exo. We analyze the triplet enrichment and depletion near the transcription start site (TSS) and identify triplets that have the strongest effect on PIC-DNA nonconsensus binding. Our results constitute a proof-of-concept for a new design principle for protein-DNA recognition in the human genome, which can lead to a better mechanistic understanding of transcriptional regulation.

  9. 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

  10. Complex History of Admixture between Modern Humans and Neandertals

    PubMed Central

    Vernot, Benjamin; Akey, Joshua M.

    2015-01-01

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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Transcription factor binding predicts histone modifications in human cell lines

    PubMed Central

    Benveniste, Dan; Sonntag, Hans-Joachim; Sanguinetti, Guido; Sproul, Duncan

    2014-01-01

    Gene expression in higher organisms is thought to be regulated by a complex network of transcription factor binding and chromatin modifications, yet the relative importance of these two factors remains a matter of debate. Here, we show that a computational approach allows surprisingly accurate prediction of histone modifications solely from knowledge of transcription factor binding both at promoters and at potential distal regulatory elements. This accuracy significantly and substantially exceeds what could be achieved by using DNA sequence as an input feature. Remarkably, we show that transcription factor binding enables strikingly accurate predictions across different cell lines. Analysis of the relative importance of specific transcription factors as predictors of specific histone marks recapitulated known interactions between transcription factors and histone modifiers. Our results demonstrate that reported associations between histone marks and gene expression may be indirect effects caused by interactions between transcription factors and histone-modifying complexes. PMID:25187560

  16. 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.

  17. 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.

  18. 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.

  19. The Human Factors of Sensor Fusion

    DTIC Science & Technology

    2008-05-01

    and it was also in contrast to systems where federated or isolated sensors, acting as single sources and providing information for a single purpose...formal logic is used, humans often use more of the inductive process (called the method of discovery) or infer from the specific to the general ( Searles ...unusual cases where ambiguity is very high. If a situation does not appear to make sense or fit an established pattern, it very well may be some act of

  20. Food choice and intake: the human factor.

    PubMed

    Mela, D J

    1999-08-01

    Human perceptions and selection of food are derived from the prevailing and momentary food, agro-economic and cultural environment, cognitive and biological characteristics of individuals, and the real and perceived intrinsic and extrinsic attributes of foods themselves. The range of items typically chosen and consumed within a given population is largely determined by interaction of the external environmental context with guiding sets of implicit and explicit social and psychobiological 'rules'. Within the rather broad limits of biology, individual food choices and intake behaviours relate to and reflect aspects of food availability, existing habitual behaviours, learning mechanisms, and individual beliefs and expectations. Many of the relevant features of these variables are uniquely human, together determining what is 'food', when, how, by and with whom it is chosen and eaten, and in what quantities. They also provide the opportunities for individuals to establish and maintain a relatively stable set of culturally and biologically determined affective responses ('likes') and intake behaviours. Understanding of the potential contribution of these influences under different conditions can serve to explain many of the observed characteristics of human eating, and highlight potential avenues for intervention.

  1. Synthesis, processing, and secretion of recombinant human factor VIII expressed in mammalian cells

    SciTech Connect

    Kaufman, R.J.; Wasley, L.C.; Dorner, A.J.

    1988-05-05

    The synthesis, processing, and secretion of factor VIII expressed from heterologous genes introduced into Chinese hamster ovary cells has been studied. The results show factor VIII to be synthesized as a primary translation product of approximately 230 kDa that can be detected in the lumen of the endoplasmic reticulum. In this compartment, the majority of the factor VIII is in a complex with a resident protein of the endoplasmic reticulum, binding protein, and may never appear in the medium. Some factor VIII transits the endoplasmic reticulum to the Golgi apparatus, where it is cleaved to generate the mature heavy and light chains. In the absence of von Willebrand factor in the medium, the secreted heavy and light chains are unassociated and subsequently degraded. In the presence of von Willebrand factor in the medium, the heavy and light chains are secreted as a stable complex and activity accumulates linearly with time. The utilization and complexity of asparagine-linked carbohydrate present on the secreted recombinant-derived factor VIII and human plasma-derived factor VIII were compared and found to be very similar. In both cases, the asparagine-linked carbohydrate moieties on the heavy chain are primarily of the hybrid or complex-type. In contrast, the factor VIII from both sources contains a high-mannose type of asparagine-linked carbohydrate on the light chain.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. The effects of humic acid-arsenate complexes on human red blood cells.

    PubMed

    Hseu, You-Cheng; Yang, Hsin-Ling

    2002-06-01

    Humic acid (HA) has been proposed as factor in the cause of Blackfoot disease (BFD) among individuals who live along the southwest coast of Taiwan. In this study, the interaction of the synthetic humic acid, made from catechol, with sodium arsenate (As(V)) was investigated and assessed with respect to damage to human red blood cells. HA is characterized as phenolic and phenolic carboxylic polymer structures containing both -COOH and -OH as their main functional groups. HA and As(V) alone are able to hemolyze 60-100 and 5-20% human red blood cells at concentrations of 50-300 microg/ml and 5-100 mM, respectively, after 6 h. HA is shown to be relatively ineffective in causing ATP depletion of red blood cells. For organometallic complexes composed of HA-As(V) the inhibition effect of EDTA was completely abolished and the use of the triple complex HA-As(V)-EDTA resulted in an enhancement of hemolysis. HA caused lipid peroxidation in a concentration- and time-dependent manner. However, HA-As(V) and As(V) decreased lipid peroxidation. These results indicated that HA initiates oxidative stress on red blood cells and this results in their dysfunction. HA-chelated high-concentration metal complexes inhibited the structures containing the main functional groups involved in decreasing hemolysis, and, thus, HA may be a significant factor in the etiology of BFD.

  7. 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.

  8. 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.

  9. Human factors issues in qualitative and quantitative safety analyses

    SciTech Connect

    Hahn, H.A.

    1993-10-01

    Humans are a critical and integral part of any operational system, be it a nuclear reactor, a facility for assembly or disassembling hazardous components, or a transportation network. In our concern over the safety of these systems, we often focus our attention on the hardware engineering components of such systems. However, experience has repeatedly demonstrated that it is often the human component that is the primary determinant of overall system safety. Both the nuclear reactor accidents at Chernobyl and Three Mile Island and shipping disasters such as the Exxon Valdez and the Herald of Free Enterprise accidents are attributable to human error. Concern over human contributions to system safety prompts us to include reviews of human factors issues in our safety analyses. In the conduct of Probabilistic Risk Assessments (PRAs), human factors issues are addressed using a quantitative method called Human Reliability Analysis (HRA). HRAs typically begin with the identification of potential sources of human error in accident sequences of interest. Human error analysis often employs plant and/or procedures walk-downs in which the analyst considers the ``goodness`` of procedures, training, and human-machine interfaces concerning their potential contribution to human error. Interviews with expert task performers may also be conducted. In the application of HRA, once candidate sources of human error have been identified, error probabilities are developed.

  10. Targeting androgen receptor/Src complex impairs the aggressive phenotype of human fibrosarcoma cells.

    PubMed

    Castoria, Gabriella; Giovannelli, Pia; Di Donato, Marzia; Hayashi, Ryo; Arra, Claudio; Appella, Ettore; Auricchio, Ferdinando; Migliaccio, Antimo

    2013-01-01

    Hormones and growth factors influence the proliferation and invasiveness of human mesenchymal tumors. The highly aggressive human fibrosarcoma HT1080 cell line harbors classical androgen receptor (AR) that responds to androgens triggering cell migration in the absence of significant mitogenesis. As occurs in many human cancer cells, HT1080 cells also express epidermal growth factor receptor (EGFR). We report that the pure anti-androgen Casodex inhibits the growth of HT1080 cell xenografts in immune-depressed mice, revealing a novel role of AR in fibrosarcoma progression. In HT1080 cultured cells EGF, but not androgens, robustly increases DNA synthesis. Casodex abolishes the EGF mitogenic effect, implying a crosstalk between EGFR and AR. The mechanism underlying this crosstalk has been analyzed using an AR-derived small peptide, S1, which prevents AR/Src tyrosine kinase association and androgen-dependent Src activation. Present findings show that in HT1080 cells EGF induces AR/Src Association, and the S1 peptide abolishes both the assembly of this complex and Src activation. The S1 peptide inhibits EGF-stimulated DNA synthesis, cell matrix metalloproteinase-9 (MMP-9) secretion and invasiveness of HT1080 cells. Both Casodex and S1 peptide also prevent DNA synthesis and migration triggered by EGF in various human cancer-derived cells (prostate, breast, colon and pancreas) that express AR. This study shows that targeting the AR domain involved in AR/Src association impairs EGF signaling in human fibrosarcoma HT1080 cells. The EGF-elicited processes inhibited by the peptide (DNA synthesis, MMP-9 secretion and invasiveness) cooperate in increasing the aggressive phenotype of HT1080 cells. Therefore, AR represents a new potential therapeutic target in human fibrosarcoma, as supported by Casodex inhibition of HT1080 cell xenografts. The extension of these findings in various human cancer-derived cell lines highlights the conservation of this process across divergent cancer

  11. 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

  12. [Therapeutic complexes of physical factors in mild arterial hypertension].

    PubMed

    Kniazeva, T A; Nikiforova, T I

    2001-01-01

    Three therapeutic complexes were compared clinically in patients with mild arterial hypertension. Complex 1 consisted of dry air--radon baths, bicycle exercise and exposure of the renal projection area to decimetric electromagnetic field. Its efficacy was 90%, mechanism of the hypotensive action is reduction of enhanced activity of the sympathico-adrenal and renin-angiotensin-aldosterone systems, improvement of water-mineral metabolism and lipid peroxidation. Complex 2 consisted of dry effervescent baths, anaprilin electrophoresis with sinusoidal modulated currents and exposure of the renal projection area to low-frequency alternating magnetic field. Its efficacy was 80%. It affects renin-angiotensin-aldosterone system, water-mineral metabolism and lipid peroxidation. Complex 3 consisted of electric sleep, laser therapy and general sodium chloride baths. Its efficacy was 63%. The effect was due to inhibition of high sympathico-adrenal system.

  13. 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.

  14. Human Factors Design Issues for Spectral Exploitation Tools

    DTIC Science & Technology

    2000-02-01

    widely accepted or utilized in the operational community. This is primarily due to sensor collection limitations, dynamic time constraints, lack of user ... experience , and limited availability of validated exploitation tools and techniques. This effort implements human factors and cognitive engineering

  15. 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.

  16. The first recombinant human coagulation factor VIII of human origin: human cell line and manufacturing characteristics.

    PubMed

    Casademunt, Elisabeth; Martinelle, Kristina; Jernberg, Mats; Winge, Stefan; Tiemeyer, Maya; Biesert, Lothar; Knaub, Sigurd; Walter, Olaf; Schröder, Carola

    2012-08-01

    Since the early 1990s, recombinant human clotting factor VIII (rhFVIII) produced in hamster cells has been available for haemophilia A treatment. However, the post-translational modifications of these proteins are not identical to those of native human FVIII, which may lead to immunogenic reactions and the development of inhibitors against rhFVIII. For the first time, rhFVIII produced in a human host cell line is available. We describe here the establishment of the first human production cell line for rhFVIII and the manufacturing process of this novel product. A human cell line expressing rhFVIII was derived from human embryonic kidney (HEK) 293 F cells transfected with an FVIII expression plasmid. No virus or virus-like particles could be detected following extensive testing. The stringently controlled production process is completely free from added materials of animal or human origin. Multistep purification employing a combination of filtration and chromatography steps ensures the efficient removal of impurities. Solvent/detergent treatment and a 20 nm pore size nanofiltration step, used for the first time in rhFVIII manufacturing, efficiently eliminate any hypothetically present viruses. In contrast to hamster cell-derived products, this rhFVIII product does not contain hamster-like epitopes, which might be expected to be immunogenic. HEK 293 F cells, whose parental cell line HEK 293 has been used by researchers for decades, are a suitable production cell line for rhFVIII and will help avoid immunogenic epitopes. A modern manufacturing process has been developed to ensure the highest level of purity and pathogen safety. © 2012 John Wiley & Sons A/S.

  17. 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.

  18. Human factor roles in design of teleoperator systems

    NASA Technical Reports Server (NTRS)

    Janow, C.; Malone, T. B.

    1973-01-01

    Teleoperator systems are considered, giving attention to types of teleoperators, a manned space vehicle attached manipulator, a free-flying teleoperator, a surface exploration roving vehicle, the human factors role in total system design, the manipulator system, the sensor system, the communication system, the control system, and the mobility system. The role of human factors in the development of teleoperator systems is also discussed, taking into account visual systems, an operator control station, and the manipulators.

  19. 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.

  20. 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

  1. Regulation of immunoglobulin secretion by factor H of human complement.

    PubMed Central

    Tsokos, G C; Inghirami, G; Tsoukas, C D; Balow, J E; Lambris, J D

    1985-01-01

    As human B lymphocytes and macrophages carry surface receptors for Factor H (B1H), we investigated the possibility that this complement component regulates their function. Factor H inhibits immunoglobulin secretion by peripheral mononuclear cells (MNC) stimulated with pokeweed mitogen if present at the initiation of the cultures and at concentrations greater than 50 micrograms/ml. Factor H also inhibited stimulation and differentiation of purified B cells into immunoglobulin-secreting cells by Epstein-Barr virus (EBV). The inhibitory effect of Factor H was abrogated if anti-Factor H antibody was present in the cultures. EBV-transformed B-cell lines secreted less immunoglobulin if Factor H was present in the culture for at least 4 days. Culture of MNC with Factor H did not lead to the generation of suppressor T cells or macrophages. In contrast, Factor H did not cause proliferation of human peripheral total MNC or enriched T-cell or B-cell subpopulations. Also, Factor H did not inhibit the proliferation of MNC in response to several mitogens and antigens. Our results strongly indicate that Factor H is able to block human B-cell differentiation in vitro without blocking the proliferative ability of the cells. Factor H seems to act directly on the B cells through its receptor on their surface, since it inhibited T-dependent and T-independent B-cell differentiation but generated no suppressor cells. Images Figure 1 PMID:2991125

  2. Regulation of immunoglobulin secretion by factor H of human complement.

    PubMed

    Tsokos, G C; Inghirami, G; Tsoukas, C D; Balow, J E; Lambris, J D

    1985-07-01

    As human B lymphocytes and macrophages carry surface receptors for Factor H (B1H), we investigated the possibility that this complement component regulates their function. Factor H inhibits immunoglobulin secretion by peripheral mononuclear cells (MNC) stimulated with pokeweed mitogen if present at the initiation of the cultures and at concentrations greater than 50 micrograms/ml. Factor H also inhibited stimulation and differentiation of purified B cells into immunoglobulin-secreting cells by Epstein-Barr virus (EBV). The inhibitory effect of Factor H was abrogated if anti-Factor H antibody was present in the cultures. EBV-transformed B-cell lines secreted less immunoglobulin if Factor H was present in the culture for at least 4 days. Culture of MNC with Factor H did not lead to the generation of suppressor T cells or macrophages. In contrast, Factor H did not cause proliferation of human peripheral total MNC or enriched T-cell or B-cell subpopulations. Also, Factor H did not inhibit the proliferation of MNC in response to several mitogens and antigens. Our results strongly indicate that Factor H is able to block human B-cell differentiation in vitro without blocking the proliferative ability of the cells. Factor H seems to act directly on the B cells through its receptor on their surface, since it inhibited T-dependent and T-independent B-cell differentiation but generated no suppressor cells.

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

    PubMed Central

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

    2014-01-01

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

  4. 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.

  5. Human Factors in Financial Trading: An Analysis of Trading Incidents.

    PubMed

    Leaver, Meghan; Reader, Tom W

    2016-09-01

    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. 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. 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. 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. 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. This research provides data crucial for ameliorating risk within financial trading organizations, with implications for regulation and policy. © 2016, Human Factors and Ergonomics Society.

  6. 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

  7. 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)

  8. 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)

  9. 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.

  10. 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.

  11. 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.

  12. Human Factors Issues for Interaction with Bio-Inspired Swarms

    DTIC Science & Technology

    2012-10-01

    subtle leaders of fish schools. Pheromone trails also suggest a way to support human interaction as has been explored to a limited extent... Human Factors issues for Interaction with Bio-Inspired Swarms Michael Lewis*, Michael Goodrich**, Katia Sycara+, Mark Steinberg++ * School of...Enabling a human to control such bio-inspired systems is a considerable challenge due to the limitations of each individual robot and the sheer

  13. 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.

  14. 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

  15. 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

  16. Genetic and environmental factors in human osteoporosis.

    PubMed

    Özbaş, Halil; Tutgun Onrat, Serap; Özdamar, Kazım

    2012-12-01

    Osteoporosis is a common disorder, with prolongation of the average life span it has become a major public health problem. On the formation of osteoporosis genetic factors and environmental influences could play a role then it is considered as multi-factorial. Because a variety of functions to affect susceptibility to the formation of osteoporosis VDR-F, VDR-B, COL1A1, ESR1X, ESR1P and CTR are thought to be candidate genes. In this study, the aim is to investigate the relationship between these genes polymorphism and bone mineral density (BMD) values of lumbar vertebra and femoral neck in 188 Turkish people. Lumbar spine and femoral neck BMD of the individuals included in the study were measured by the dual X-ray absorptiometry method. The genotyped polymorphisms by simultaneous amplification of five regions of the genome, containing six SNPs of interest and detecting the amplified product, using the kit MetaBone Clinical Arrays(®). Statistical analyses indicated that; VDR-B gene polymorphisms major (P = 0.013), VDR-F polymorphisms have minor (P = 0.082) effect on femur BMD. None of the other genes has any significant effect on spinal BMD. Patient age, body mass index and diet has significant effect on femoral and spinal BMD. Osteoporosis is a multi-factorial disease and many genetic and non-genetic risk factors contribute to the development of osteoporosis. Early detection of a genetic predisposition to osteoporosis should allow delay and/or limit unfavorable changes in the bone tissue.

  17. 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

  18. Recombinant human factor IX produced from transgenic porcine milk.

    PubMed

    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.

  19. 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.

  20. 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.