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Sample records for human intrinsic factor

  1. Human intrinsic factor expressed in the plant Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Fedosov, Sergey N; Laursen, Niels B; Nexø, Ebba

    2003-01-01

    Intrinsic factor (IF) is the gastric protein that promotes the intestinal uptake of vitamin B12. Gastric IF from animal sources is used in diagnostic tests and in vitamin pills. However, administration of animal IF to humans becomes disadvantageous because of possible pathogenic transmission...

  2. Evidence from intrinsic activity that asymmetry of the human brain is controlled by multiple factors.

    Science.gov (United States)

    Liu, Hesheng; Stufflebeam, Steven M; Sepulcre, Jorge; Hedden, Trey; Buckner, Randy L

    2009-12-01

    Cerebral lateralization is a fundamental property of the human brain and a marker of successful development. Here we provide evidence that multiple mechanisms control asymmetry for distinct brain systems. Using intrinsic activity to measure asymmetry in 300 adults, we mapped the most strongly lateralized brain regions. Both men and women showed strong asymmetries with a significant, but small, group difference. Factor analysis on the asymmetric regions revealed 4 separate factors that each accounted for significant variation across subjects. The factors were associated with brain systems involved in vision, internal thought (the default network), attention, and language. An independent sample of right- and left-handed individuals showed that hand dominance affects brain asymmetry but differentially across the 4 factors supporting their independence. These findings show the feasibility of measuring brain asymmetry using intrinsic activity fluctuations and suggest that multiple genetic or environmental mechanisms control cerebral lateralization.

  3. Intrinsic Patterns of Human Activity

    Science.gov (United States)

    Hu, Kun; Ivanov, Plamen Ch.; Chen, Zhi; Hilton, Michael; Stanley, H. Eugene; Shea, Steven

    2003-03-01

    Activity is one of the defining features of life. Control of human activity is complex, being influenced by many factors both extrinsic and intrinsic to the body. The most obvious extrinsic factors that affect activity are the daily schedule of planned events, such as work and recreation, as well as reactions to unforeseen or random events. These extrinsic factors may account for the apparently random fluctuations in human motion observed over short time scales. The most obvious intrinsic factors are the body clocks including the circadian pacemaker that influences our sleep/wake cycle and ultradian oscillators with shorter time scales [2, 3]. These intrinsic rhythms may account for the underlying regularity in average activity level over longer periods of up to 24 h. Here we ask if the known extrinsic and intrinsic factors fully account for all complex features observed in recordings of human activity. To this end, we measure activity over two weeks from forearm motion in subjects undergoing their regular daily routine. Utilizing concepts from statistical physics, we demonstrate that during wakefulness human activity possesses previously unrecognized complex dynamic patterns. These patterns of activity are characterized by robust fractal and nonlinear dynamics including a universal probability distribution and long-range power-law correlations that are stable over a wide range of time scales (from minutes to hours). Surprisingly, we find that these dynamic patterns are unaffected by changes in the average activity level that occur within individual subjects throughout the day and on different days of the week, and between subjects. Moreover, we find that these patterns persist when the same subjects undergo time-isolation laboratory experiments designed to account for the phase of the circadian pacemaker, and control the known extrinsic factors by restricting behaviors and manipulating scheduled events including the sleep/wake cycle. We attribute these newly

  4. Intrinsic-extrinsic factors in sport motivation.

    Science.gov (United States)

    Pedersen, Darhl M

    2002-10-01

    Participants were 83 students (36 men and 47 women). 10 intrinsic-extrinsic factors involved in sport motivation were obtained. The factors were generated from items obtained from the participants rather than items from the experimenter. This was done to avoid the possible influence of preconceptions on the part of the experimenter regarding what the final dimensions may be. Obtained motivational factors were Social Reinforcement, Fringe Benefits, Fame and Fortune, External Forces, Proving Oneself, Social Benefits, Mental Enrichment, Expression of Self, Sense of Accomplishment, and Self-enhancement. Each factor was referred to an intrinsic-extrinsic dimension to describe its relative position on that dimension. The order of the factors as listed indicates increasing intrinsic motivation. i.e., the first four factors were rated in the extrinsic range, whereas the remaining six were rated to be in the intrinsic range. Next, the participants rated the extent to which each of the various factors was involved in their decision to participate in sport activities. The pattern of use of the motivational factors was the same for both sexes except that men indicated greater use of the Fringe Benefits factor. Overall, the more intrinsic a sport motivation factor was rated, the more likely it was to be rated as a factor in actual sport participation.

  5. Intrinsic Risk Factors of Falls in Elderly

    Directory of Open Access Journals (Sweden)

    Yasmin Amatullah

    2016-09-01

    Full Text Available Background: Falls are common geriatric problems. The risk factors of falls are the intrinsic and extrinsic risk factors. Studies on falls are scarcely conducted in Indonesia, especially in Bandung. Therefore, this study was conducted to identify the intrinsic risk factors of falls among elderly. Methods: A descriptive study was carried out from August to October 2013 at the Geriatric Clinic of Dr. Hasan Sadikin General Hospital Bandung. Fifty three participants were selected according to the inclusion and exclusion criteria using consecutive sampling. The determined variables in this study were classification of the risk of falls, demographic profile, history of falls, disease, and medications. After the selection, the participants were tested by Timed up-and-go test (TUGT. Moreover, an interview and analysis of medical records were carried out to discover the risk factors of falls. The collected data were analyzed and presented in the form of percentages shown in tables. Results: From 53 patients, women (35.66% were considered to have higher risk of fall than men (18.34%. The majority of patients (66% with the risk of fall were from the age group 60–74 years. The major diseases suffered by patients were hypertension, osteoarthritis and diabetes mellitus. Drugs that were widely used were antihypertensive drugs; analgesic and antipyretic drugs and antidiabetic drugs. Conclusions: There are various intrinsic risk factors of falls in elderly and each of the elderly has more than one intrinsic risk factor of falls.

  6. Utility of intersystem extrapolation factors in early reaction phenotyping and the quantitative extrapolation of human liver microsomal intrinsic clearance using recombinant cytochromes P450.

    Science.gov (United States)

    Chen, Yuan; Liu, Liling; Nguyen, Khanh; Fretland, Adrian J

    2011-03-01

    Reaction phenotyping using recombinant human cytochromes P450 (P450) has great utility in early discovery. However, to fully realize the advantages of using recombinant expressed P450s, the extrapolation of data from recombinant systems to human liver microsomes (HLM) is required. In this study, intersystem extrapolation factors (ISEFs) were established for CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 using 11 probe substrates, based on substrate depletion and/or metabolite formation kinetics. The ISEF values for CYP2C9, CYP2D6, and CYP3A4 determined using multiple substrates were similar across substrates. When enzyme kinetics of metabolite formation for CYP1A2, 2C9, 2D6, and 3A4 were used, the ISEFs determined were generally within 2-fold of that determined on the basis of substrate depletion. Validation of ISEFs was conducted using 10 marketed drugs by comparing the extrapolated data with published data. The major isoforms responsible for the metabolism were identified, and the contribution of the predominant P450s was similar to that of previously reported data. In addition, phenotyping data from internal compounds, extrapolated using the rhP450-ISEF method, were comparable to those obtained using an HLM-based inhibition assay approach. Moreover, the intrinsic clearance (CL(int)) calculated from extrapolated rhP450 data correlated well with measured HLM CL(int). The ISEF method established in our laboratory provides a convenient tool in early reaction phenotyping for situations in which the HLM-based inhibition approach is limited by low turnover and/or unavailable metabolite formation. Furthermore, this method allows for quantitative extrapolation of HLM intrinsic clearance from rhP450 phenotyping data simultaneously to obtaining the participating metabolizing enzymes.

  7. Human dignity: intrinsic or relative value?

    Science.gov (United States)

    Thiel, Marie-Jo

    2010-09-01

    Is human dignity an intrinsic value? Or is it a relative value, depending on the perception or assessment of quality of life? History had delineated some of its key features, but the advent of human rights and the Holocaust put special emphasis on this notion, particularly in the field of bioethics. But if modern medicine regards human dignity as crucial, it tends to support this notion while assessing and measuring it. The quality of life becomes the gauge for measuring human dignity, starting from a distinction between a viable and a non-viable existence, which may eventually lead to assisted death, or to letting die. This article argues that the concept of quality of life is of great relevant for medical practice, but on the condition of not being used as a standard to measure the dignity of the individual. Rather, the quality of life should be regarded as an imperative posed by human dignity, which is necessarily intrinsic. If the quality of life measures dignity, humankind is divided into two categories: lives worthy of living, and lives unworthy of living, and society becomes a jungle. Raising the quality of life as a requirement of the inherent human dignity does not solve automatically all problems and does not eliminate a feeling of unworthiness. But it ensures its 'human' value: the equal respect for every human being.

  8. What keeps a body moving? The brain-derived neurotrophic factor val66met polymorphism and intrinsic motivation to exercise in humans.

    Science.gov (United States)

    Caldwell Hooper, Ann E; Bryan, Angela D; Hagger, Martin S

    2014-12-01

    Individuals who are intrinsically motivated to exercise are more likely to do so consistently. In previous research, those with at least one copy of the methionine (met) allele in the brain-derived neurotrophic factor gene (BDNF; rs6265) had greater increases in positive mood and lower perceived exertion during exercise. This study examined whether genotype for BDNF is also related to intrinsic motivation, measured by self-report during a treadmill exercise session and a free-choice behavioral measure (continuing to exercise given the option to stop) among 89 regular exercisers (age M = 23.58, SD = 3.95). Those with at least one copy of the met allele reported greater increases in intrinsic motivation during exercise and were more likely to continue exercising when given the option to stop (55 vs. 33%). Results suggest that underlying genetic factors may partially influence perceptions of inherent rewards associated with exercise and might inform the development of individually targeted interventions.

  9. The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region

    DEFF Research Database (Denmark)

    Kozyraki, R; Kristiansen, M; Silahtaroglu, A

    1998-01-01

    Uptake of vitamin B12 (cyanocobalamin) is facilitated by the cobalamin-binder gastric intrinsic factor (IF), which recognizes a 460-kD receptor, cubilin, present in the epithelium of intestine and kidney. Surface plasmon resonance analysis of ligand-affinity-purified human cubilin demonstrated...

  10. Kinetics of the Attachment of Intrinsic Factor-Bound Cobamides to Ileal Receptors

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    Mathan, V. I.; Babior, Bernard M.; Donaldson, Robert M.

    1974-01-01

    To determine whether the molecular configuration of vitamin B12 influences the attachment of intrinsic factor-vitamin B12 complex to ileal microvillous membrane receptor sites, we have examined the kinetics of uptake of intrinsic factor-bound cyanocobalamin by brush borders and microvillous membranes isolated from guinea pig ileum, and have compared this uptake with that of intrinsic factor alone and with that of intrinsic factor complexed with various analogs of cyanocobalamin. We first studied the kinetics of binding of cyanocobalamin and other cobamides to human gastric intrinsic factor. The binding of cyanocobalamin showed saturation kinetics and, at relatively high concentrations of cyanocobalamin, a Scatchard plot of binding was linear. The dissociation constant for the intrinsic factor-cyanocobalamin complex was 0.066 nM. When the binding of various vitamin B12 analogs to intrinsic factor was determined by competition experiments, the analogs could be separated into two categories: those with affinities similar to that of cyanocobalamin and those with affinities much lower than that of cyanocobalamin. The affinity of cyanocobalamin for intrinsic factor was not altered by various substitutions at the -CN position, while removal of a single amido group on the corrin ring of substitution of the dimethylbenzimidazole base greatly reduced affinity. Removal of the base totally abolished binding. These findings, confirming those reported by others, are consistent with the concept that the cyanocobalamin molecule fits into a “pocket” in the intrinsic factor molecule, with the nucleotide base facing inward and the -CN side of the planar corrin ring facing outward. We then investigated the attachment of intrinsic factor-bound cyanocobalamin to ileal receptor. Attachment to microvillous membranes showed saturation kinetics with a dissociation constant of 0.25 nM. Attachment was rapid and was 70% complete within 5 min; the second-order rate constant for attachment

  11. Intrinsic and extrinsic factors influencing large African herbivore movements

    NARCIS (Netherlands)

    Venter, J.A.; Prins, H.H.T.; Mashanova, A.; Boer, de W.F.; Slotow, R.

    2015-01-01

    Understanding environmental as well as anthropogenic factors that influence large herbivore ecological patterns and processes should underpin their conservation and management. We assessed the influence of intrinsic, extrinsic environmental and extrinsic anthropogenic factors on movement behaviour o

  12. Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H

    DEFF Research Database (Denmark)

    Larsen, Steen; Díez-Sánchez, Carmen; Rabøl, Rasmus

    2014-01-01

    It has been suggested that human mitochondrial variants influence maximal oxygen uptake (VO2max). Whether mitochondrial respiratory capacity per mitochondrion (intrinsic activity) in human skeletal muscle is affected by differences in mitochondrial variants is not known. We recruited 54 males...... and determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30......% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present....

  13. Role of human TRIM5α in intrinsic immunity

    Directory of Open Access Journals (Sweden)

    Emi E. Nakayama

    2012-03-01

    Full Text Available Human immunodeficiency virus (HIV has a very narrow host range. HIV type 1 (HIV-1 does not infect Old World monkeys, such as the rhesus monkey (Rh. Rh TRIM5α was identified as a factor that confers resistance, intrinsic immunity, to HIV-1 infection. Unfortunately, human TRIM5α is almost powerless to restrict HIV-1. However, human TRIM5α potently restricts N-tropic murine leukemia viruses (MLV but not B-tropic MLV, indicating that human TRIM5α represents the restriction factor previously designated as Ref1. African green monkey TRIM5α represents another restriction factor previously designated as Lv1, which restricts both HIV-1 and simian immunodeficiency virus isolated from macaque (SIVmac infection.TRIM5 is a member of the tripartite motif family containing RING, B-box2, and coiled-coil domains. The RING domain is frequently found in E3 ubiquitin ligase, and TRIM5α is thought to degrade viral core via ubiquitin proteasome-dependent and -independent pathways. The alpha isoform of TRIM5 has an additional C-terminal PRYSPRY domain, which is a determinant of species-specific retrovirus restriction by TRIM5α. On the other hand, the target regions of viral capsid protein (CA are scattered on the surface of core. A single amino acid difference in the surface exposed loop between α-helices 6 and 7 (L6/7 of HIV type 2 (HIV-2 CA affects viral sensitivity to human TRIM5α and was also shown to be associated with viral load in West African HIV-2 patients, indicating that human TRIM5α is a critical modulator of HIV-2 replication in vivo. Interestingly, L6/7 of CA corresponds to the MLV determinant of sensitivity to mouse factor Fv1, which potently restricts N-tropic MLV. In addition, human genetic polymorphisms also affect antiviral activity of human TRIM5α. Recently, human TRIM5α was shown to activate signaling pathways that lead to activation of NF-κB and AP-1 by interacting with TAK1 complex. TRIM5α is thus involved in control of viral

  14. Human phoneme recognition depending on speech-intrinsic variability.

    Science.gov (United States)

    Meyer, Bernd T; Jürgens, Tim; Wesker, Thorsten; Brand, Thomas; Kollmeier, Birger

    2010-11-01

    The influence of different sources of speech-intrinsic variation (speaking rate, effort, style and dialect or accent) on human speech perception was investigated. In listening experiments with 16 listeners, confusions of consonant-vowel-consonant (CVC) and vowel-consonant-vowel (VCV) sounds in speech-weighted noise were analyzed. Experiments were based on the OLLO logatome speech database, which was designed for a man-machine comparison. It contains utterances spoken by 50 speakers from five dialect/accent regions and covers several intrinsic variations. By comparing results depending on intrinsic and extrinsic variations (i.e., different levels of masking noise), the degradation induced by variabilities can be expressed in terms of the SNR. The spectral level distance between the respective speech segment and the long-term spectrum of the masking noise was found to be a good predictor for recognition rates, while phoneme confusions were influenced by the distance to spectrally close phonemes. An analysis based on transmitted information of articulatory features showed that voicing and manner of articulation are comparatively robust cues in the presence of intrinsic variations, whereas the coding of place is more degraded. The database and detailed results have been made available for comparisons between human speech recognition (HSR) and automatic speech recognizers (ASR).

  15. Vitamin B12 Phosphate Conjugation and Its Effect on Binding to the Human B12 -Binding Proteins Intrinsic Factor and Haptocorrin

    DEFF Research Database (Denmark)

    Ó Proinsias, Keith; Ociepa, Michał; Pluta, Katarzyna

    2016-01-01

    The binding of vitamin B12 derivatives to human B12 transporter proteins is strongly influenced by the type and site of modification of the cobalamin original structure. We have prepared the first cobalamin derivative modified at the phosphate moiety. The reaction conditions were fully optimized...... and its limitations examined. The resulting derivatives, particularly those bearing terminal alkyne and azide groups, were isolated and used in copper-catalyzed alkyne-azide cycloaddition reactions (CuAAC). Their sensitivity towards light revealed their potential as photocleavable molecules. The binding...

  16. An intrinsically safe mechanism for physically coupling humans with robots.

    Science.gov (United States)

    O'Neill, Gerald; Patel, Harshil; Artemiadis, Panagiotis

    2013-06-01

    Robots are increasingly used in tasks that include physical interaction with humans. Examples can be found in the area of rehabilitation robotics, power augmentation robots, as well as assistive and orthotic devices. However, current methods of physically coupling humans with robots fail to provide intrinsic safety, adaptation and efficiency, which limit the application of wearable robotics only to laboratory and controlled environments. In this paper we present the design and verification of a novel mechanism for physically coupling humans and robots. The device is intrinsically safe, since it is based on passive, non-electric features that are not prone to malfunctions. The device is capable of transmitting forces and torques in all directions between the human user and the robot. Moreover, its re-configurable nature allows for easy and consistent adjustment of the decoupling force. The latter makes the mechanism applicable to a wide range of human-robot coupling applications, ranging from low-force rehabilitation-therapy scenarios to high-force augmentation cases.

  17. Transcriptional profiling of intrinsic PNS factors in the postnatal mouse.

    Science.gov (United States)

    Smith, Robin P; Lerch-Haner, Jessica K; Pardinas, Jose R; Buchser, William J; Bixby, John L; Lemmon, Vance P

    2011-01-01

    Neurons in the peripheral nervous system (PNS) display a higher capacity to regenerate after injury than those in the central nervous system, suggesting cell specific transcriptional modules underlying axon growth and inhibition. We report a systems biology based search for PNS specific transcription factors (TFs). Messenger RNAs enriched in dorsal root ganglion (DRG) neurons compared to cerebellar granule neurons (CGNs) were identified using subtractive hybridization and DNA microarray approaches. Network and transcription factor binding site enrichment analyses were used to further identify TFs that may be differentially active. Combining these techniques, we identified 32 TFs likely to be enriched and/or active in the PNS. Twenty-five of these TFs were then tested for an ability to promote CNS neurite outgrowth in an overexpression screen. Real-time PCR and immunohistochemical studies confirmed that one representative TF, STAT3, is intrinsic to PNS neurons, and that constitutively active STAT3 is sufficient to promote CGN neurite outgrowth.

  18. INNATE, ADAPTIVE AND INTRINSIC IMMUNITY IN HUMAN IMMUNODEFICIENCY VIRUS INFECTION

    Directory of Open Access Journals (Sweden)

    Suneth S. Perera

    2012-01-01

    Full Text Available The first line of defence of the innate immune system functions by recognizing highly conserved sets of molecular structures specific to the microbes, termed pathogen-associated molecular patterns, or PAMPs via the germ line-encoded receptors Pattern-Recognition Receptors (PRRs. In addition to the innate immune system, the vertebrates have also evolved a second line of defence termed adaptive immune system, which uses a diverse set of somatically rearranged receptors T-Cell Receptors (TCRs and B Cell Receptors (BCRs, which have the inherent ability to effectively recognise diverse antigens. The innate and adaptive immune systems are functionally tied in with the intrinsic immunity, which comprises of endogenous antiviral factors. Thus, this effective response to diverse microbial infections, including HIV, requires a coordinated interaction at several functional levels between innate, adaptive and intrinsic immune systems. This review provides a snapshot of roles played by the innate, adaptive and the intrinsic immune systems during HIV-infection, along with discussing recent developments highlighting the genomic basis of these responses and their regulation by micro-RNA (miRNAs.

  19. The balance between 4-hydroxynonenal and intrinsic glutathione/glutathione S-transferase A4 system may be critical for the epidermal growth factor receptor phosphorylation of human esophageal squamous cell carcinomas.

    Science.gov (United States)

    Uno, Kaname; Kato, Katsuaki; Kusaka, Gen; Asano, Naoki; Iijima, Katsunori; Shimosegawa, Tooru

    2011-10-01

    Oxidative stress might participate in the carcinogenesis of human esophageal squamous cell carcinomas (hESCC). 4-Hydroxynonenal (HNE) is a major product of membrane lipid peroxidation with short life. It might act as an important mediator through the generation of adducts and activate epidermal growth factor receptor (EGFR) signaling. It is mainly trapped with glutathione (GSH) and catalyzed by glutathione S-transferases (GSTs). This study aimed to elucidate the possible participation of HNE, GSH/GST system, and EGFR signaling in hESCC development. Immunohistochemistry of HNE adducts, EGFR, and phosphorylated EGFR (pEGFR) was performed with hESCC specimens. The effect of HNE on the phosphorylation of EGFR and its downstream PhospholipaseCγ1 (PLCγ1) was investigated with KYSE30 cell-line. Pretreatment with GSH inducer N-acetylcysteine (NAC) or GSH inhibitor Buthionine sulfoximine (BSO) and mandatory transfection of hGSTA4 gene in KYSE30 were conducted to investigate the relationship between HNE and GSH/GST system. Immunoreactants of HNE adducts, EGFR, and pEGFR were increased in hESCC compared to non-cancerous epithelium with positive correlations. The treatment of HNE ligand-independently induced the phosphorylation of EGFR and PLCγ1 accompanying the diminishment of intracellular GSH level. NAC increased GSH contents but BSO decreased in dose-dependent manners. Reflecting changes in GSH, HNE-induced EGFR phosphorylation was suppressed by NAC, whereas it was promoted by BSO. Mandatory expression of hGSTA4 suppressed HNE-induced events. We first demonstrated that the ligand-independent activation of EGFR by the balance between the stimulation of HNE and the prevention of intrinsic GSH/GST system might participate in the development of hESCC.

  20. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity.

    Science.gov (United States)

    Carrasco-Benso, Maria P; Rivero-Gutierrez, Belen; Lopez-Minguez, Jesus; Anzola, Andrea; Diez-Noguera, Antoni; Madrid, Juan A; Lujan, Juan A; Martínez-Augustin, Olga; Scheer, Frank A J L; Garaulet, Marta

    2016-09-01

    In humans, insulin sensitivity varies according to time of day, with decreased values in the evening and at night. Mechanisms responsible for the diurnal variation in insulin sensitivity are unclear. We investigated whether human adipose tissue (AT) expresses intrinsic circadian rhythms in insulin sensitivity that could contribute to this phenomenon. Subcutaneous and visceral AT biopsies were obtained from extremely obese participants (body mass index, 41.8 ± 6.3 kg/m(2); 46 ± 11 y) during gastric-bypass surgery. To assess the rhythm in insulin signaling, AKT phosphorylation was determined every 4 h over 24 h in vitro in response to different insulin concentrations (0, 1, 10, and 100 nM). Data revealed that subcutaneous AT exhibited robust circadian rhythms in insulin signaling (P Insulin sensitivity reached its maximum (acrophase) around noon, being 54% higher than during midnight (P = 0.009). The amplitude of the rhythm was positively correlated with in vivo sleep duration (r = 0.53; P = 0.023) and negatively correlated with in vivo bedtime (r = -0.54; P = 0.020). No circadian rhythms were detected in visceral AT (P = 0.643). Here, we demonstrate the relevance of the time of the day for how sensitive AT is to the effects of insulin. Subcutaneous AT shows an endogenous circadian rhythm in insulin sensitivity that could provide an underlying mechanism for the daily rhythm in systemic insulin sensitivity.-Carrasco-Benso, M. P., Rivero-Gutierrez, B., Lopez-Minguez, J., Anzola, A., Diez-Noguera, A., Madrid, J. A., Lujan, J. A., Martínez-Augustin, O., Scheer, F. A. J. L., Garaulet, M. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity. © FASEB.

  1. ISS Payload Human Factors

    Science.gov (United States)

    Ellenberger, Richard; Duvall, Laura; Dory, Jonathan

    2016-01-01

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

  2. Intrinsic Motivation and Environmental Factors Affecting Research of Social Work Faculty on Aging

    Science.gov (United States)

    Wells, Janice G.; Short, Glenda F. Lester

    2010-01-01

    Within the context of Self-determination Theory, this research identifies intrinsic motivation and environmental factors that support social-work-faculty research in aging. Intrinsic factors include faculty's interest in gerontology as a field of practice, the desire to advance knowledge in the field of gerontology, including producing…

  3. Intrinsically restless: Unifying science, writing, and the human condition

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    Sissom, Matthew

    The field of physics has always fascinated me, but I never possessed the mathematical skills necessary to extend that interest past the point of curiosity. This thesis was set up to explore how I and other writers, specifically Walt Whitman, use(d) the skills we do have to ask and attempt to answer the same cosmic questions normally reserved for scientists overseeing particle collider experiments. In Tao of Physics, Fritjof Capra attempted to blend the principles of Eastern philosophy with the movements associated with modern physics. In doing so, he offers up a few insights into the human desire to "divide the world into separate objects and events" (117), which I believe, when it comes to fiction, greatly influences the audience's interpretive framework. Capra suggests, "To believe that our abstract concepts of separate `things' and `vents' are realities of nature is an illusion" (117). Humans use this division to cope with our everyday environment, yet it is not a fundamental feature of reality but, rather, an abstraction devised by our discriminating and categorizing intellect. It is a coping mechanism, as Capra refers to it, that pins writers in a corner, encouraging them to forms and styles set by their predecessors to better satisfy the "discriminating and categorizing intellect" of their audience. Writers often struggle to achieve a balance between accurately presenting the human condition that, like Capra's description of subatomic particles as "intrinsically restless" (117), changes based on myriad variables and properly structuring their writing to fit a predetermined model. Whitman, a fan of popular science, drew from the scientific world, using his understanding of the interpretive framework, to better craft his poems' metaphors. In "Song of Myself," Whitman suggests that the celebration of one's own existence cannot be separated from the celebration of the universe, "For every atom belonging to me as good belongs to you" (1-3). Whitman's writing

  4. Interplay between Human Cytomegalovirus and Intrinsic/Innate Host Responses: A Complex Bidirectional Relationship

    Directory of Open Access Journals (Sweden)

    Giada Rossini

    2012-01-01

    Full Text Available The interaction between human cytomegalovirus (HCMV and its host is a complex process that begins with viral attachment and entry into host cells, culminating in the development of a specific adaptive response that clears the acute infection but fails to eradicate HCMV. We review the viral and cellular partners that mediate early host responses to HCMV with regard to the interaction between structural components of virions (viral glycoproteins and cellular receptors (attachment/entry receptors, toll-like receptors, and other nucleic acid sensors or intrinsic factors (PML, hDaxx, Sp100, viperin, interferon inducible protein 16, the reactions of innate immune cells (antigen presenting cells and natural killer cells, the numerous mechanisms of viral immunoevasion, and the potential exploitation of events that are associated with early phases of virus-host interplay as a therapeutic strategy.

  5. Human Factors Laboratory

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    Federal Laboratory Consortium — Purpose: The purpose of the Human Factors Laboratory is to further the understanding of highway user needs so that those needs can be incorporated in roadway design,...

  6. Introduction to human factors

    Energy Technology Data Exchange (ETDEWEB)

    Winters, J.M.

    1988-03-01

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

  7. Dividing of Q factor of viscous and intrinsic attenuation in poroelastic media

    Science.gov (United States)

    Ishikura, K.; Mikada, H.; Goto, T.; Takekawa, J.

    2013-12-01

    Sonic logging has been widely used for many years to understand physical properties of hydrocarbon reservoirs. When gaseous phase exists in the formation fluid, the compressional waves traveling through the formation could be strongly attenuated due to low bulk modulus of gas in the fluid, while the shear waves are not. For acquiring physical properties of fluid in the formation, Biot physics or poroelastic analysis could be the best method. Among the available technologies, quality factors based on the Biot's equation could be used. Although the Biot's theory considers the viscous attenuation induced at the interface between rocks and pore fluids, the intrinsic attenuation caused by the internal friction in the matrix is ignored. In the present study, we investigate how large are the effects of the intrinsic attenuation of compressional waves through the evaluation of the reservoir properties based on the quality factor. We employ a 2D finite-difference scheme to simulate seismic wave propagation in a poroelasic medium. The intrinsic attenuation is included in our model by using the filter of frequency-independent quality factor (constant-Q). We then compare the results compressional waves and shear waves with the intrinsic attenuation in our numerical simulations. Our results clearly show that on compressional and shear waves, the amplitude and phase of the waveforms are strongly affected by the intrinsic attenuation, and we could get only the viscous attenuation by the results of quality factor of compressional wave and shear wave. We conclude that the evaluations of hydrocarbon reservoir require the consideration of the intrinsic attenuation as well as the viscous attenuation predicted by the Biot's theory and also we could get what kind of fluid is contained in the reservoir. The profile of Q factor

  8. Assessing the Factors Deemed to Support Individual Student Intrinsic Motivation in Technology Supported Online and Face-to-Face Discussions

    Science.gov (United States)

    Shroff, Ronnie H.; Vogel, Douglas R.

    2009-01-01

    Research has established that intrinsic motivation has a positive effect on learning and academic achievement. In order to investigate the phenomenon of intrinsic motivation in technology-supported learning environments, this paper investigates the factors deemed to support individual student intrinsic motivation in online discussions. A research…

  9. Let's stay together? Intrinsic and extrinsic factors involved in pair bond dissolution in a recolonizing wolf population.

    Science.gov (United States)

    Milleret, Cyril; Wabakken, Petter; Liberg, Olof; Åkesson, Mikael; Flagstad, Øystein; Andreassen, Harry Peter; Sand, Håkan

    2017-01-01

    For socially monogamous species, breeder bond dissolution has important consequences for population dynamics, but the extent to which extrinsic or intrinsic population factors causes pair dissolution remain poorly understood, especially among carnivores. Using an extensive life-history data set, a survival analysis and competing risks framework, we examined the fate of 153 different wolf (Canis lupus) pairs in the recolonizing Scandinavian wolf population, during 14 winters of snow tracking and DNA monitoring. Wolf pair dissolution was generally linked to a mortality event and was strongly affected by extrinsic (i.e. anthropogenic) causes. No divorce was observed, and among the pair dissolution where causes have been identified, death of one or both wolves was always involved. Median time from pair formation to pair dissolution was three consecutive winters (i.e. approximately 2 years). Pair dissolution was mostly human-related, primarily caused by legal control actions (36·7%), verified poaching (9·2%) and traffic-related causes (2·1%). Intrinsic factors, such as disease and age, accounted for only 7·7% of pair dissolutions. The remaining 44·3% of dissolution events were from unknown causes, but we argue that a large portion could be explained by an additional source of human-caused mortality, cryptic poaching. Extrinsic population factors, such as variables describing the geographical location of the pair, had a stronger effect on risk of pair dissolution compared to anthropogenic landscape characteristics. Population intrinsic factors, such as the inbreeding coefficient of the male pair member, had a negative effect on pair bond duration. The mechanism behind this result remains unknown, but might be explained by lower survival of inbred males or more complex inbreeding effects mediated by behaviour. Our study provides quantitative estimates of breeder bond duration in a social carnivore and highlights the effect of extrinsic (i.e. anthropogenic) and

  10. Social Cognitive and Demographic Factors Related to Adolescents' Intrinsic Satisfaction with School

    Science.gov (United States)

    Briones, Elena; Tabernero, Carmen

    2012-01-01

    Based on social cognitive theory, the purpose of this study is to examine certain social cognitive and demographic factors involved in intrinsic satisfaction amongst secondary school students of different cultural backgrounds in a new migrant-receiving country. Given the role of schools in youth acculturation and adaptation, it is important to…

  11. A Quantitative Analysis of the Extrinsic and Intrinsic Turnover Factors of Relational Database Support Professionals

    Science.gov (United States)

    Takusi, Gabriel Samuto

    2010-01-01

    This quantitative analysis explored the intrinsic and extrinsic turnover factors of relational database support specialists. Two hundred and nine relational database support specialists were surveyed for this research. The research was conducted based on Hackman and Oldham's (1980) Job Diagnostic Survey. Regression analysis and a univariate ANOVA…

  12. Social Cognitive and Demographic Factors Related to Adolescents' Intrinsic Satisfaction with School

    Science.gov (United States)

    Briones, Elena; Tabernero, Carmen

    2012-01-01

    Based on social cognitive theory, the purpose of this study is to examine certain social cognitive and demographic factors involved in intrinsic satisfaction amongst secondary school students of different cultural backgrounds in a new migrant-receiving country. Given the role of schools in youth acculturation and adaptation, it is important to…

  13. Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes

    DEFF Research Database (Denmark)

    Andersen, Christian Brix Folsted; Madsen, Mette; Storm, Tina;

    2010-01-01

    Cobalamin (Cbl, vitamin B(12)) is a bacterial organic compound and an essential coenzyme in mammals, which take it up from the diet. This occurs by the combined action of the gastric intrinsic factor (IF) and the ileal endocytic cubam receptor formed by the 460-kilodalton (kDa) protein cubilin...

  14. Intrinsic and Extrinsic Factors That Influence Black Males to Attend Institutions of Higher Education

    Science.gov (United States)

    Etheridge, Robert

    2013-01-01

    The purpose of this qualitative, narrative study was to explore the intrinsic and extrinsic factors that motivated Black males to attend institutions of higher education. The Self-determination theory and the Integrated Model for Educational Choice formed the theoretical framework for this study. Eight Black males who were between the ages of 18…

  15. Human Factors Review Plan

    Energy Technology Data Exchange (ETDEWEB)

    Paramore, B.; Peterson, L.R. (eds.)

    1985-12-01

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

  16. Helicopter human factors

    Science.gov (United States)

    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.

  17. Deciphering the cause of evolutionary variance within intrinsically disordered regions in human proteins.

    Science.gov (United States)

    Banerjee, Sanghita; Chakraborty, Sandip; De, Rajat K

    2017-02-01

    Why the intrinsically disordered regions evolve within human proteome has became an interesting question for a decade. Till date, it remains an unsolved yet an intriguing issue to investigate why some of the disordered regions evolve rapidly while the rest are highly conserved across mammalian species. Identifying the key biological factors, responsible for the variation in the conservation rate of different disordered regions within the human proteome, may revisit the above issue. We emphasized that among the other biological features (multifunctionality, gene essentiality, protein connectivity, number of unique domains, gene expression level and expression breadth) considered in our study, the number of unique protein domains acts as a strong determinant that negatively influences the conservation of disordered regions. In this context, we justified that proteins having a fewer types of domains preferably need to conserve their disordered regions to enhance their structural flexibility which in turn will facilitate their molecular interactions. In contrast, the selection pressure acting on the stretches of disordered regions is not so strong in the case of multi-domains proteins. Therefore, we reasoned that the presence of conserved disordered stretches may compensate the functions of multiple domains within a single domain protein. Interestingly, we noticed that the influence of the unique domain number and expression level acts differently on the evolution of disordered regions from that of well-structured ones.

  18. Evidence for an intrinsic factor promoting landscape divergence in Madagascan leaf-litter frogs

    Directory of Open Access Journals (Sweden)

    Katharina C. Wollenberg Valero

    2015-05-01

    Full Text Available The endemic Malagasy frog radiations are an ideal model system to study patterns and processes of speciation in amphibians. Large-scale diversity patterns of these frogs, together with other endemic animal radiations, led to the postulation of new and the application of known hypotheses of species diversification causing diversity patterns in this biodiversity hotspot. Both extrinsic and intrinsic factors have been studied in a comparative framework, with extrinsic factors usually being related to the physical environment (landscape, climate, river catchments, mountain chains, and intrinsic factors being clade-specific traits or constraints (reproduction, ecology, morphology, physiology. Despite some general patterns emerging from such large-scale comparative analyses, it became clear that the mechanism of diversification in Madagascar may vary among clades, and may be a multifactorial process. In this contribution, I test for intrinsic factors promoting population-level divergence within a clade of terrestrial, diurnal leaf-litter frogs (genus Gephyromantis that has previously been shown to diversify according to extrinsic factors. Landscape genetic analyses of the microendemic species G. enki and its widely distributed, larger sister species G. boulengeri over a rugged landscape in the Ranomafana area shows that genetic variance of the smaller species cannot be explained by landscape resistance alone. Both topographic and riverine barriers are found to be important in generating this divergence. This case study yields additional evidence for the probable importance of body size in lineage diversification.

  19. Evidence for an intrinsic factor promoting landscape genetic divergence in Madagascan leaf-litter frogs.

    Science.gov (United States)

    Wollenberg Valero, Katharina C

    2015-01-01

    The endemic Malagasy frog radiations are an ideal model system to study patterns and processes of speciation in amphibians. Large-scale diversity patterns of these frogs, together with other endemic animal radiations, led to the postulation of new and the application of known hypotheses of species diversification causing diversity patterns in this biodiversity hotspot. Both extrinsic and intrinsic factors have been studied in a comparative framework, with extrinsic factors usually being related to the physical environment (landscape, climate, river catchments, mountain chains), and intrinsic factors being clade-specific traits or constraints (reproduction, ecology, morphology, physiology). Despite some general patterns emerging from such large-scale comparative analyses, it became clear that the mechanism of diversification in Madagascar may vary among clades, and may be a multifactorial process. In this contribution, I test for intrinsic factors promoting population-level divergence within a clade of terrestrial, diurnal leaf-litter frogs (genus Gephyromantis) that has previously been shown to diversify according to extrinsic factors. Landscape genetic analyses of the microendemic species Gephyromantis enki and its widely distributed, larger sister species Gephyromantis boulengeri over a rugged landscape in the Ranomafana area shows that genetic variance of the smaller species cannot be explained by landscape resistance alone. Both topographic and riverine barriers are found to be important in generating this divergence. This case study yields additional evidence for the probable importance of body size in lineage diversification.

  20. Intrinsically motivated oculomotor exploration guided by uncertainty reduction and conditioned reinforcement in non-human primates.

    Science.gov (United States)

    Daddaoua, Nabil; Lopes, Manuel; Gottlieb, Jacqueline

    2016-02-03

    Intelligent animals have a high degree of curiosity--the intrinsic desire to know--but the mechanisms of curiosity are poorly understood. A key open question pertains to the internal valuation systems that drive curiosity. What are the cognitive and emotional factors that motivate animals to seek information when this is not reinforced by instrumental rewards? Using a novel oculomotor paradigm, combined with reinforcement learning (RL) simulations, we show that monkeys are intrinsically motivated to search for and look at reward-predictive cues, and that their intrinsic motivation is shaped by a desire to reduce uncertainty, a desire to obtain conditioned reinforcement from positive cues, and individual variations in decision strategy and the cognitive costs of acquiring information. The results suggest that free-viewing oculomotor behavior reveals cognitive and emotional factors underlying the curiosity driven sampling of information.

  1. Human Factors Model

    Science.gov (United States)

    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.

  2. The impact of intrinsic and extrinsic factors on the job satisfaction of dentists.

    Science.gov (United States)

    Goetz, K; Campbell, S M; Broge, B; Dörfer, C E; Brodowski, M; Szecsenyi, J

    2012-10-01

    The Two-Factor Theory of job satisfaction distinguishes between intrinsic-motivation (i.e. recognition, responsibility) and extrinsic-hygiene (i.e. job security, salary, working conditions) factors. The presence of intrinsic-motivation facilitates higher satisfaction and performance, whereas the absences of extrinsic factors help mitigate against dissatisfaction. The consideration of these factors and their impact on dentists' job satisfaction is essential for the recruitment and retention of dentists. The objective of the study is to assess the level of job satisfaction of German dentists and the factors that are associated with it. This cross-sectional study was based on a job satisfaction survey. Data were collected from 147 dentists working in 106 dental practices. Job satisfaction was measured with the 10-item Warr-Cook-Wall job satisfaction scale. Organizational characteristics were measured with two items. Linear regression analyses were performed in which each of the nine items of the job satisfaction scale (excluding overall satisfaction) were handled as dependent variables. A stepwise linear regression analysis was performed with overall job satisfaction as the dependent outcome variable, the nine items of job satisfaction and the two items of organizational characteristics controlled for age and gender as predictors. The response rate was 95.0%. Dentists were satisfied with 'freedom of working method' and mostly dissatisfied with their 'income'. Both variables are extrinsic factors. The regression analyses identified five items that were significantly associated with each item of the job satisfaction scale: 'age', 'mean weekly working time', 'period in the practice', 'number of dentist's assistant' and 'working atmosphere'. Within the stepwise linear regression analysis the intrinsic factor 'opportunity to use abilities' (β = 0.687) showed the highest score of explained variance (R(2) = 0.468) regarding overall job satisfaction. With respect to the Two-Factor

  3. Human factors in network security

    OpenAIRE

    Jones, Francis B.

    1991-01-01

    Human factors, such as ethics and education, are important factors in network information security. This thesis determines which human factors have significant influence on network security. Those factors are examined in relation to current security devices and procedures. Methods are introduced to evaluate security effectiveness by incorporating the appropriate human factors into network security controls

  4. HSF transcription factor family, heat shock response, and protein intrinsic disorder.

    Science.gov (United States)

    Westerheide, Sandy D; Raynes, Rachel; Powell, Chase; Xue, Bin; Uversky, Vladimir N

    2012-02-01

    Intrinsically disordered proteins are highly abundant in all kingdoms of life, and several protein functional classes, such as transcription factors, transcriptional regulators, hub and scaffold proteins, signaling proteins, and chaperones are especially enriched in intrinsic disorder. One of the unique cellular reactions to protein damaging stress is the so-called heat shock response that results in the upregulation of heat shock proteins including molecular chaperones. This molecular protective mechanism is conserved from prokaryotes to eukaryotes and allows an organism to respond to various proteotoxic stressors, such as heat shock, oxidative stress, exposure to heavy metals, and drugs. The heat shock response- related proteins can be expressed during normal conditions (e.g., during the cell growth and development) or can be induced by various pathological conditions, such as infection, inflammation, and protein conformation diseases. The initiation of the heat shock response is manifested by the activation of the heat shock transcription factors HSF 1, part of a family of related HSF transcription factors. This review analyzes the abundance and functional roles of intrinsic disorder in various heat shock transcription factors and clearly shows that the heat shock response requires HSF flexibility to be more efficient. © 2012 Bentham Science Publishers

  5. Genetic evidence of an accessory activity required specifically for cubilin brush-border expression and intrinsic factor-cobalamin absorption.

    Science.gov (United States)

    Xu, D; Kozyraki, R; Newman, T C; Fyfe, J C

    1999-11-15

    Cubilin is a high molecular weight multiligand receptor that mediates intestinal absorption of intrinsic factor-cobalamin and selective protein reabsorption in renal tubules. The genetic basis of selective intestinal cobalamin malabsorption with proteinuria was investigated in a canine model closely resembling human Imerslund-Gräsbeck syndrome caused by cubilin mutations. Canine CUBN cDNA was cloned and sequenced, showing high identity with human and rat CUBN cDNAs. An intragenic CUBN marker was identified in the canine family and used to test the hypothesis of genetic linkage of the disease and CUBN loci. Linkage was rejected, indicating that the canine disorder resembling Imerslund-Gräsbeck syndrome is caused by defect of a gene product other than cubilin. These results imply that there may be locus heterogeneity among human kindreds with selective intestinal cobalamin malabsorption and proteinuria and that normal brush-border expression of cubilin requires the activity of an accessory protein.

  6. Expression, fermentation and purification of a predicted intrinsically disordered region of the transcription factor, NFAT5.

    Science.gov (United States)

    DuMond, Jenna F; He, Yi; Burg, Maurice B; Ferraris, Joan D

    2015-11-01

    Hypertonicity stimulates Nuclear Factor of Activated T-cells 5 (NFAT5) nuclear localization and transactivating activity. Many transcription factors are known to contain intrinsically disordered regions (IDRs) which become more structured with local environmental changes such as osmolality, temperature and tonicity. The transactivating domain of NFAT5 is predicted to be intrinsically disordered under normal tonicity, and under high NaCl, the activity of this domain is increased. To study the binding of co-regulatory proteins at IDRs a cDNA construct expressing the NFAT5 TAD was created and transformed into Escherichia coli cells. Transformed E. coli cells were mass produced by fermentation and extracted by cell lysis to release the NFAT5 TAD. The NFAT5 TAD was subsequently purified using a His-tag column, cation exchange chromatography as well as hydrophobic interaction chromatography and then characterized by mass spectrometry (MS). Published by Elsevier Inc.

  7. Intrinsic factors associated with return to sport after anterior cruciate ligament reconstruction: A systematic review

    Directory of Open Access Journals (Sweden)

    Cheryl A. Ross

    2015-04-01

    Full Text Available Objectives: The anterior cruciate ligament is the most commonly injured ligament in the knee, with an average of only 64% of affected athletes returning to their pre-injury level of sport. Intrinsic factors associated with an increased likelihood of return to sport may be addressed during rehabilitation to improve the outcome of the reconstruction. The objectives of this review were to systematically appraise publications from six electronic databases describing intrinsic factors that may be associated with return to sport after anterior cruciate ligament reconstruction.Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines were followed. Methodological quality appraisal was performed according to the Critical Appraisal Skills Programme for cohort studies. We performed a descriptive synthesis of the findings that associated intrinsic factors with return to sport.Results: Ten studies were included in the review. The findings show that fear of re-injury is a common reason for not returning to participation in sport. Younger patients may be more likely to return to sport, but findings regarding gender were equivocal, with male competitive athletes appearing to be more likely to return to sport than their female counterparts. Good knee function is not always associated with a higher likelihood to return to sport.Conclusion: Fear of re-injury and age should be considered in the management of sports participants after anterior cruciate ligament reconstruction.

  8. Helicopter Human Factors

    Science.gov (United States)

    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

  9. Helicopter Human Factors

    Science.gov (United States)

    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

  10. The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region

    DEFF Research Database (Denmark)

    Kozyraki, R; Kristiansen, M; Silahtaroglu, A

    1998-01-01

    -5445 on the short arm of chromosome 10. This is within the autosomal recessive megaloblastic anemia (MGA1) 6-cM region harboring the unknown recessive-gene locus of juvenile megaloblastic anemia caused by intestinal malabsorption of cobalamin (Imerslund-Gräsbeck's disease). In conclusion, the present...... molecular and genetic information on human cubilin now provides circumstantial evidence that an impaired synthesis, processing, or ligand binding of cubilin is the molecular background of this hereditary form of megaloblastic anemia. Udgivelsesdato: 1998-May-15...

  11. Intrinsic factors influencing help-seeking behaviour in an acute stroke situation.

    Science.gov (United States)

    Zock, Elles; Kerkhoff, Henk; Kleyweg, Ruud Peter; van de Beek, Diederik

    2016-09-01

    The proportion of stroke patients eligible for intravenous or intra-arterial treatment is still limited because many patients do not seek medical help immediately after stroke onset. The aim of our study was to explore which intrinsic factors and considerations influence help-seeking behaviour of relatively healthy participants, confronted with stroke situations. Semi-structured interviews were conducted with 25 non-stroke participants aged 50 years or older. We presented 5 clinical stroke situations as if experienced by the participants themselves. Recognition and interpretation of symptoms were evaluated and various factors influencing help-seeking behaviour were explored in-depth. We used the thematic synthesis method for data analysis. Five themes influencing help-seeking behaviour in a stroke situation were identified: influence of knowledge, views about seriousness, ideas about illness and health, attitudes towards others and beliefs about the emergency medical system. A correct recognition of stroke symptoms or a correct interpretation of the stroke situations did not automatically result in seeking medical help. Interestingly, similar factors could lead to different types of actions between participants. Many intrinsic, as well as social and environmental factors are of influence on help-seeking behaviour in an acute stroke situation. All these factors seem to play a complex role in help-seeking behaviour with considerable inter-individual variations. Accomplishing more patients eligible for acute stroke treatment, future research should focus on better understanding of all factors at various levels grounded in a theory of help-seeking behaviour.

  12. Plasticity of the intrinsic period of the human circadian timing system.

    Directory of Open Access Journals (Sweden)

    Frank A J L Scheer

    Full Text Available Human expeditions to Mars will require adaptation to the 24.65-h Martian solar day-night cycle (sol, which is outside the range of entrainment of the human circadian pacemaker under lighting intensities to which astronauts are typically exposed. Failure to entrain the circadian time-keeping system to the desired rest-activity cycle disturbs sleep and impairs cognitive function. Furthermore, differences between the intrinsic circadian period and Earth's 24-h light-dark cycle underlie human circadian rhythm sleep disorders, such as advanced sleep phase disorder and non-24-hour sleep-wake disorders. Therefore, first, we tested whether exposure to a model-based lighting regimen would entrain the human circadian pacemaker at a normal phase angle to the 24.65-h Martian sol and to the 23.5-h day length often required of astronauts during short duration space exploration. Second, we tested here whether such prior entrainment to non-24-h light-dark cycles would lead to subsequent modification of the intrinsic period of the human circadian timing system. Here we show that exposure to moderately bright light ( approximately 450 lux; approximately 1.2 W/m(2 for the second or first half of the scheduled wake episode is effective for entraining individuals to the 24.65-h Martian sol and a 23.5-h day length, respectively. Estimations of the circadian periods of plasma melatonin, plasma cortisol, and core body temperature rhythms collected under forced desynchrony protocols revealed that the intrinsic circadian period of the human circadian pacemaker was significantly longer following entrainment to the Martian sol as compared to following entrainment to the 23.5-h day. The latter finding of after-effects of entrainment reveals for the first time plasticity of the period of the human circadian timing system. Both findings have important implications for the treatment of circadian rhythm sleep disorders and human space exploration.

  13. Text Summarization Evaluation: Correlating Human Performance on an Extrinsic Task with Automatic Intrinsic Metrics

    Science.gov (United States)

    2006-05-01

    computed the Pearson r and Spearman ρ (Siegel and Castellan , 1988) correlation values for the comparison of the human judgments and the ROUGE scores, and...average performance of a system for all topics. Table 4.15 and Table 4.16 show the rank correlations— using Pearson r (Siegel and Castellan , 1988...Intrinsic and Extrinsic Scores Grouped by System (including Full Text) and also Spearman ρ (Siegel and Castellan , 1988) is introduced in this

  14. Intrinsic factors of Peltigera lichens influence the structure of the associated soil bacterial microbiota.

    Science.gov (United States)

    Leiva, Diego; Clavero-León, Claudia; Carú, Margarita; Orlando, Julieta

    2016-11-01

    Definition of lichens has evolved from bi(tri)partite associations to multi-species symbioses, where bacteria would play essential roles. Besides, although soil bacterial communities are known to be affected by edaphic factors, when lichens grow upon them these could become less preponderant. We hypothesized that the structure of both the lichen microbiota and the microbiota in the soil underneath lichens is shaped by lichen intrinsic and extrinsic factors. In this work, intrinsic factors corresponded to mycobiont and cyanobiont identities of Peltigera lichens, metabolite diversity and phenoloxidase activity and extrinsic factors involved the site of the forest where lichens grow. Likewise, the genetic and metabolic structure of the lichen and soil bacterial communities were analyzed by fingerprinting. Among the results, metabolite diversity was inversely related to the genetic structure of bacterial communities of lichens and soils, highlighting the far-reaching effect of these substances; while phenoloxidase activity was inversely related to the metabolic structure only of the lichen bacterial microbiota, presuming a more limited effect of the products of these enzymes. Soil bacterial microbiota was different depending on the site and, strikingly, according to the cyanobiont present in the lichen over them, which could indicate an influence of the photobiont metabolism on the availability of soil nutrients. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. The Use of Fluorescence Microscopy to Study the Association Between Herpesviruses and Intrinsic Resistance Factors

    Directory of Open Access Journals (Sweden)

    Roger D. Everett

    2011-12-01

    Full Text Available Intrinsic antiviral resistance is a branch of antiviral defence that involves constitutively expressed cellular proteins that act within individual infected cells. In recent years it has been discovered that components of cellular nuclear structures known as ND10 or PML nuclear bodies contribute to intrinsic resistance against a variety of viruses, notably of the herpesvirus family. Several ND10 components are rapidly recruited to sites that are closely associated with herpes simplex virus type 1 (HSV-1 genomes during the earliest stages of infection, and this property correlates with the efficiency of ND10 mediated restriction of HSV-1 replication. Similar but distinct recruitment of certain DNA damage response proteins also occurs during infection. These recruitment events are inhibited in a normal wild type HSV-1 infection by the viral regulatory protein ICP0. HSV‑1 mutants that do not express ICP0 are highly susceptible to repression through intrinsic resistance factors, but they replicate more efficiently in cells depleted of certain ND10 proteins or in which ND10 component recruitment is inefficient. This article presents the background to this recruitment phenomenon and summaries how it is conveniently studied by fluorescence microscopy.

  16. Effect of speech-intrinsic variations on human and automatic recognition of spoken phonemes.

    Science.gov (United States)

    Meyer, Bernd T; Brand, Thomas; Kollmeier, Birger

    2011-01-01

    The aim of this study is to quantify the gap between the recognition performance of human listeners and an automatic speech recognition (ASR) system with special focus on intrinsic variations of speech, such as speaking rate and effort, altered pitch, and the presence of dialect and accent. Second, it is investigated if the most common ASR features contain all information required to recognize speech in noisy environments by using resynthesized ASR features in listening experiments. For the phoneme recognition task, the ASR system achieved the human performance level only when the signal-to-noise ratio (SNR) was increased by 15 dB, which is an estimate for the human-machine gap in terms of the SNR. The major part of this gap is attributed to the feature extraction stage, since human listeners achieve comparable recognition scores when the SNR difference between unaltered and resynthesized utterances is 10 dB. Intrinsic variabilities result in strong increases of error rates, both in human speech recognition (HSR) and ASR (with a relative increase of up to 120%). An analysis of phoneme duration and recognition rates indicates that human listeners are better able to identify temporal cues than the machine at low SNRs, which suggests incorporating information about the temporal dynamics of speech into ASR systems.

  17. Discovering intrinsic properties of human observers' visual search and mathematical observers' scanning.

    Science.gov (United States)

    He, Xin; Samuelson, Frank; Zeng, Rongping; Sahiner, Berkman

    2014-11-01

    There is a lack of consensus in measuring observer performance in search tasks. To pursue a consensus, we set our goal to obtain metrics that are practical, meaningful, and predictive. We consider a metric practical if it can be implemented to measure human and computer observers' performance. To be meaningful, we propose to discover intrinsic properties of search observers and formulate the metrics to characterize these properties. If the discovered properties allow verifiable predictions, we consider them predictive. We propose a theory and a conjecture toward two intrinsic properties of search observers: rationality in classification as measured by the location-known-exactly (LKE) receiver operating characteristic (ROC) curve and location uncertainty as measured by the effective set size (M*). These two properties are used to develop search models in both single-response and free-response search tasks. To confirm whether these properties are "intrinsic," we investigate their ability in predicting search performance of both human and scanning channelized Hotelling observers. In particular, for each observer, we designed experiments to measure the LKE-ROC curve and M*, which were then used to predict the same observer's performance in other search tasks. The predictions were then compared to the experimentally measured observer performance. Our results indicate that modeling the search performance using the LKE-ROC curve and M* leads to successful predictions in most cases.

  18. Intrinsic motivation factors based on the self-determinant theory for regular breast cancer screening.

    Science.gov (United States)

    Jung, Su Mi; Jo, Heui-Sug

    2014-01-01

    The purpose of this study was to identify factors of intrinsic motivation that affect regular breast cancer screening and contribute to development of a program for strategies to improve effective breast cancer screening. Subjects were residing in South Korea Gangwon-Province and were female over 40 and under 69 years of age. For the investigation, the Intrinsic Motivation Inventory (IMI) was modified to the situation of cancer screening and was used to survey 905 inhabitants. Multinominal logistic regression analyses were conducted for regular breast cancer screening (RS), one-time breast cancer screening (OS) and non-breast cancer screening (NS). For statistical analysis, IBM SPSS 20.0 was utilized. The determinant factors between RS and NS were "perceived effort and choice" and "stress and strain" - internal motivations related to regular breast cancer screening. Also, determinant factors between RS and OS are "age" and "perceived effort and choice" for internal motivation related to cancer screening. To increase regular screening, strategies that address individual perceived effort and choice are recommended.

  19. Selective Malabsorption of Vitamin B12 and Vitamin B12-Intrinsic Factor With Megaloblastic Anemia in an Adult

    Science.gov (United States)

    Chisholm, Joseph C.

    1985-01-01

    The first case of megaloblastic anemia due to selective malabsorption of vitamin B12 and vitamin B12-intrinsic factor is described in an otherwise normal female adult, in whom pernicious anemia had previously been diagnosed. PMID:4057272

  20. Intrinsic regulation of hemangioma involution by platelet-derived growth factor

    Science.gov (United States)

    Roach, E E; Chakrabarti, R; Park, N I; Keats, E C; Yip, J; Chan, N G; Khan, Z A

    2012-01-01

    Infantile hemangioma is a vascular tumor that exhibits a unique natural cycle of rapid growth followed by involution. Previously, we have shown that hemangiomas arise from CD133+ stem cells that differentiate into endothelial cells when implanted in immunodeficient mice. The same clonally expanded stem cells also produced adipocytes, thus recapitulating the involuting phase of hemangioma. In the present study, we have elucidated the intrinsic mechanisms of adipocyte differentiation using hemangioma-derived stem cells (hemSCs). We found that platelet-derived growth factor (PDGF) is elevated during the proliferating phase and may inhibit adipocyte differentiation. hemSCs expressed high levels of PDGF-B and showed sustained tyrosine phosphorylation of PDGF receptors under basal (unstimulated) conditions. Inhibition of PDGF receptor signaling caused enhanced adipogenesis in hemSCs. Furthermore, exposure of hemSCs to exogenous PDGF-BB reduced the fat content and the expression of adipocyte-specific transcription factors. We also show that these autogenous inhibitory effects are mediated by PDGF receptor-β signaling. In summary, this study identifies PDGF signaling as an intrinsic negative regulator of hemangioma involution and highlights the therapeutic potential of disrupting PDGF signaling for the treatment of hemangiomas. PMID:22717583

  1. Human Factors in Training

    Science.gov (United States)

    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.

  2. Human Factors in Marine Casualties

    Directory of Open Access Journals (Sweden)

    Jelenko Švetak

    2002-05-01

    Full Text Available Human factors play an important role in the origin of accidents,and it is commonly claimed that between seventy andninety-five percent of industrial and transport accidents involvehuman factors, see Figure 1.Some authorities, however, claim that ultimately, all accidentsinvolve human factors.

  3. Assessing Individual-Level Factors Supporting Student Intrinsic Motivation in Online Discussions: A Qualitative Study

    Science.gov (United States)

    Shroff, Ronnie H.; Vogel, Douglas R.; Coombes, John

    2008-01-01

    Research has established that intrinsic motivation has a positive effect on learning and academic achievement. However, little is known about the impact of different technology-supported learning activities on student intrinsic motivation or whether such learning activities significantly enhance student intrinsic motivation compared to traditional…

  4. Predicting permeability from the characteristic relaxation time and intrinsic formation factor of complex conductivity spectra

    Science.gov (United States)

    Revil, A.; Binley, A.; Mejus, L.; Kessouri, P.

    2015-08-01

    Low-frequency quadrature conductivity spectra of siliclastic materials exhibit typically a characteristic relaxation time, which either corresponds to the peak frequency of the phase or the quadrature conductivity or a typical corner frequency, at which the quadrature conductivity starts to decrease rapidly toward lower frequencies. This characteristic relaxation time can be combined with the (intrinsic) formation factor and a diffusion coefficient to predict the permeability to flow of porous materials at saturation. The intrinsic formation factor can either be determined at several salinities using an electrical conductivity model or at a single salinity using a relationship between the surface and quadrature conductivities. The diffusion coefficient entering into the relationship between the permeability, the characteristic relaxation time, and the formation factor takes only two distinct values for isothermal conditions. For pure silica, the diffusion coefficient of cations, like sodium or potassium, in the Stern layer is equal to the diffusion coefficient of these ions in the bulk pore water, indicating weak sorption of these couterions. For clayey materials and clean sands and sandstones whose surface have been exposed to alumina (possibly iron), the diffusion coefficient of the cations in the Stern layer appears to be 350 times smaller than the diffusion coefficient of the same cations in the pore water. These values are consistent with the values of the ionic mobilities used to determine the amplitude of the low and high-frequency quadrature conductivities and surface conductivity. The database used to test the model comprises a total of 202 samples. Our analysis reveals that permeability prediction with the proposed model is usually within an order of magnitude from the measured value above 0.1 mD. We also discuss the relationship between the different time constants that have been considered in previous works as characteristic relaxation time, including

  5. Intrinsic activation of human motoneurons: possible contribution to motor unit excitation.

    Science.gov (United States)

    Gorassini, Monica; Yang, Jaynie F; Siu, Merek; Bennett, David J

    2002-04-01

    The main purpose of this study was to estimate the contribution of intrinsic activation of human motoneurons (e.g., by plateau potentials) during voluntary and reflexive muscle contractions. Pairs of motor units were recorded from either the tibialis anterior or soleus muscle during three different conditions: 1) during a brief muscle vibration followed by a slow relaxation of a steady isometric contraction; 2) during a triangular isometric torque contraction; and 3) during passive sinusoidal muscle stretch superimposed on a steady isometric contraction. In each case, the firing rate of a tonically firing control motor unit was used as a measure of the effective synaptic excitation (i.e., synaptic drive) to a slightly higher-threshold test motor unit that was recruited and de-recruited during a contraction trial. The firing rate of the control unit was compared at recruitment and de-recruitment of the test unit. This was done to determine whether the estimated synaptic drive needed to recruit a motor unit was less than the amount needed to sustain firing as a result of an added depolarization produced from intrinsic sources. After test unit recruitment, the firing rate of the control unit could be decreased significantly (on average by 3.6 Hz from an initial recruitment rate of 9.8 Hz) before the test unit was de-recruited during a descending synaptic drive. Similar decreases in control unit rate occurred in all three experimental conditions. This represents a possible 40% reduction in the estimated synaptic drive needed to maintain firing of a motor unit compared with the estimated amount needed to recruit the unit initially. The firing rates of both the control and test units were modulated together in a highly parallel fashion, suggesting that the unit pairs were driven by common synaptic inputs. This tight correlation further validated the use of the control unit firing rate as a monitor of synaptic drive to the test motor unit. The estimates of intrinsically

  6. Intrinsic $g_{K}$ factors of odd-mass 167−179Lu isotopes

    Indian Academy of Sciences (India)

    H Yakut; A A Kuliev; E Guliyev; Z Yildirim

    2009-11-01

    In this paper, $g_{K}$-factors of the intrinsic magnetic moments and effective spin gyromagnetic factors ($g_{s}^{\\text{eff}}$) of the 167−179Lu isotopes have been studied within the Tamm–Dancoff approximation (TDA) (Kuliev et al, Sov. J. Nucl. Phys. 9, 185 (1969)) by using a realistic potential such as Woods–Saxon potential for the first time. The effects of the spin–spin and spin–isospin interactions on magnetic moments were investigated. The results of the theoretical calculations are compared with the experimental data for related nuclei. The experimental values of $g_{K}$ and $g_{s}^{\\text{eff}}$ were computed from the observed magnetic moments (Georg et al, Eur. Phys. J. A3, 225 (1998)) using the spin matrix elements. The theoretical predictions for the g K factors exhibit good agreement with the experimental $g_{K}$ factors with increasing mass number A of the lutetium isotopes. The strongest influence of the neutron–proton spin interaction occurs at = −1. Sufficient agreement between the calculated and the experimental values of $g_{K}$ is obtained for $κ = (45/A)$ MeV and = −1.

  7. NASA Space Human Factors Program

    Science.gov (United States)

    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.

  8. Tai Chi Chuan Optimizes the Functional Organization of the Intrinsic Human Brain Architecture in Older Adults

    Directory of Open Access Journals (Sweden)

    Gao-Xia eWei

    2014-04-01

    Full Text Available Whether Tai Chi Chuan (TCC can influence the intrinsic functional architecture of the human brain remains unclear. To examine TCC-associated changes in functional connectomes, resting-state functional magnetic resonance images were acquired from 40 older individuals including 22 experienced TCC practitioners (experts and 18 demographically matched TCC-naïve healthy controls, and their local functional homogeneities across the cortical mantle were compared. Compared to the controls, the TCC experts had significantly greater and more experience-dependent functional homogeneity in the right postcentral gyrus (PosCG and less functional homogeneity in the left anterior cingulate cortex (ACC and the right dorsal lateral prefrontal cortex (DLPFC. Increased functional homogeneity in the PosCG was correlated with TCC experience. Intriguingly, decreases in functional homogeneity (improved functional specialization in the left ACC and increases in functional homogeneity (improved functional integration in the right PosCG both predicted performance gains on attention network behavior tests. These findings provide evidence for the functional plasticity of the brain’s intrinsic architecture toward optimizing locally functional organization, with great implications for understanding the effects of TCC on cognition, behavior and health in aging population.

  9. Monosynaptic Ia projections from intrinsic hand muscles to forearm motoneurones in humans

    Science.gov (United States)

    Marchand-Pauvert, V; Nicolas, G; Pierrot-Deseilligny, E

    2000-01-01

    Heteronymous Ia excitatory projections from intrinsic hand muscles to human forearm motoneurones (MNs) were investigated. Changes in firing probability of single motor units (MUs) in the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), extensor carpi radialis (ECR), extensor carpi ulnaris (ECU) and extensor digitorum communis (EDC) were studied after electrical stimuli were applied to the median and ulnar nerve at wrist level and to the corresponding homonymous nerve at elbow level.Homonymous facilitation, occurring at the same latency as the H reflex, and therefore attributed to monosynaptic Ia EPSPs, was found in all the sampled units. In many MUs an early facilitation was also evoked by heteronymous low-threshold afferents from intrinsic hand muscles. The low threshold (between 0.5 and 0.6 times motor threshold (MT)) and the inability of a pure cutaneous stimulation to reproduce this effect indicate that it is due to stimulation of group I muscle afferents.Evidence for a similar central delay (monosynaptic) in heteronymous as in homonymous pathways was accepted when the difference in latencies of the homonymous and heteronymous peaks did not differ from the estimated supplementary afferent conduction time from wrist to elbow level by more than 0.5 ms (conduction velocity in the fastest Ia afferents between wrist and elbow levels being equal to 69 m s−1).A statistically significant heteronymous monosynaptic Ia excitation from intrinsic hand muscles supplied by both median and ulnar nerves was found in MUs belonging to all forearm motor nuclei tested (although not in ECU MUs after ulnar stimulation). It was, however, more often found in flexors than in extensors, in wrist than in finger muscles and in muscles operating in the radial than in the ulnar side.It is argued that the connections of Ia afferents from intrinsic hand muscles to forearm MNs, which are stronger and more widely distributed than in the cat, might

  10. Multiple intrinsic factors act in concert with Lhx2 to direct retinal gliogenesis

    Science.gov (United States)

    de Melo, Jimmy; Clark, Brian S.; Blackshaw, Seth

    2016-09-01

    Müller glia (MG) are the principal glial cell type in the vertebrate retina. Recent work has identified the LIM homeodomain factor encoding gene Lhx2 as necessary for both Notch signaling and MG differentiation in late-stage retinal progenitor cells (RPCs). However, the extent to which Lhx2 interacts with other intrinsic regulators of MG differentiation is unclear. We investigated this question by investigating the effects of overexpression of multiple transcriptional regulators that are either known or hypothesized to control MG formation, in both wildtype and Lhx2-deficient RPCs. We observe that constitutively elevated Notch signaling, induced by N1ICD electroporation, inhibited gliogenesis in wildtype animals, but rescued MG development in Lhx2-deficient retinas. Electroporation of Nfia promoted the formation of cells with MG-like radial morphology, but did not drive expression of MG molecular markers. Plagl1 and Sox9 did not induce gliogenesis in wildtype animals, but nonetheless activated expression of the Müller marker P27Kip1 in Lhx2-deficient cells. Finally, Sox2, Sox8, and Sox9 promoted amacrine cell formation in Lhx2-deficient cells, but not in wildtype retinas. These findings demonstrate that overexpression of individual gliogenic factors typically regulates only a subset of characteristic MG markers, and that these effects are differentially modulated by Lhx2.

  11. Intrinsic hand muscles and digit independence on the preferred and non-preferred hands of humans.

    Science.gov (United States)

    Reilly, Karen T; Hammond, Geoffrey R

    2006-09-01

    Although the superior dexterity of one hand is an almost ubiquitous human experience, it is unclear which characteristics of the motor system controlling the preferred hand produce this superior dexterity. Between-species studies show that greater dexterity is associated with a motor system that permits more independent movements of the digits. If between-hand dexterity differences are mediated by the same mechanism as between-species dexterity differences, then there should be asymmetries within the corticospinal tracts of humans that would result in between-hand independence differences. The evidence for asymmetries in the corticospinal tracts is sparse, and if an asymmetry does exist, it appears to be limited to the control of intrinsic hand muscles. We wondered, therefore, whether there might be a difference in the degree of independent control on the two hands during performance of a task that primarily uses intrinsic hand muscles. We examined digit individuation when subjects produced abduction or adduction forces with a single digit in isolation. Consistent with previous studies in which forces or movements in single digits were generated primarily by extrinsic hand muscles, we found no difference between the individuation of the digits on the preferred and non-preferred hands. We suggest that whereas independence differences underlie large dexterity differences between species, they do not underlie the more subtle dexterity differences between the preferred and non-preferred hands. Instead, the neural substrate for handedness might be asymmetrical connectivity within M1, with more profuse connections within the dominant than non-dominant M1 imparting a greater potential for excitatory and inhibitory interactions between movement representations which might then result in the more efficient coordination of hand and arm movements of the preferred hand.

  12. Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study

    Directory of Open Access Journals (Sweden)

    Weinans Harrie

    2007-02-01

    Full Text Available Abstract Background Tendinosis lesions show an increase of glycosaminoglycan amount, calcifications, and lipid accumulation. Therefore, altered cellular differentiation might play a role in the etiology of tendinosis. This study investigates whether adolescent human tendon tissue contains a population of cells with intrinsic differentiation potential. Methods Cells derived from adolescent non-degenerative hamstring tendons were characterized by immunohistochemistry and FACS-analysis. Cells were cultured for 21 days in osteogenic, adipogenic, and chondrogenic medium and phenotypical evaluation was carried out by immunohistochemical and qPCR analysis. The results were compared with the results of similar experiments on adult bone marrow-derived stromal cells (BMSCs. Results Tendon-derived cells stained D7-FIB (fibroblast-marker positive, but α-SMA (marker for smooth muscle cells and pericytes negative. Tendon-derived cells were 99% negative for CD34 (endothelial cell marker, and 73% positive for CD105 (mesenchymal progenitor-cell marker. In adipogenic medium, intracellular lipid vacuoles were visible and tendon-derived fibroblasts showed upregulation of adipogenic markers FABP4 (fatty-acid binding protein 4 and PPARG (peroxisome proliferative activated receptor γ. In chondrogenic medium, some cells stained positive for collagen 2 and tendon-derived fibroblasts showed upregulation of collagen 2 and collagen 10. In osteogenic medium Von Kossa staining showed calcium deposition although osteogenic markers remained unaltered. Tendon-derived cells and BMCSs behaved largely comparable, although some distinct differences were present between the two cell populations. Conclusion This study suggests that our population of explanted human tendon cells has an intrinsic differentiation potential. These results support the hypothesis that there might be a role for altered tendon-cell differentiation in the pathophysiology of tendinosis.

  13. Human Factors Evaluation Mentor Project

    Data.gov (United States)

    National Aeronautics and Space Administration — To obtain valid and reliable data, Human Factors Engineering (HFE) evaluations are currently conducted by people with specialized training and experience in HF. HFE...

  14. Predicting the effect of extrinsic and intrinsic job satisfaction factors on recruitment and retention of rehabilitation professionals.

    Science.gov (United States)

    Randolph, Diane Smith

    2005-01-01

    The purpose of this study was to ascertain which extrinsic and intrinsic job satisfaction areas are most predictive of rehabilitation professionals' career satisfaction and desire to stay on the job. This article discusses the results of a survey conducted on practicing occupational therapists, physical therapists, and speech-language pathologists regarding factors that contribute to career satisfaction and desire to stay on the job. Five hundred surveys were mailed to each profession; 463 were returned, of which 328 were able to be analyzed. Results from regression analysis showed that intrinsic factors such as professional growth and having a work environment in line with personal values are more significant in predicting career satisfaction than are extrinsic factors such as pay and continuing education. These same intrinsic factors are also significant in predicting the rehabilitation professional's desire to stay on the job. These findings are significant to healthcare managers desiring to recruit and retain qualified occupational therapists, physical therapists, and speech-language pathologists. In addition to extrinsic benefits such as pay, healthcare managers need to focus on provision of intrinsic factors such as opportunities for professional growth, recognition of accomplishments, and opportunities for departmental input to motivate rehabilitation professionals.

  15. STAT3 is a critical cell-intrinsic regulator of human unconventional T cell numbers and function.

    Science.gov (United States)

    Wilson, Robert P; Ives, Megan L; Rao, Geetha; Lau, Anthony; Payne, Kathryn; Kobayashi, Masao; Arkwright, Peter D; Peake, Jane; Wong, Melanie; Adelstein, Stephen; Smart, Joanne M; French, Martyn A; Fulcher, David A; Picard, Capucine; Bustamante, Jacinta; Boisson-Dupuis, Stephanie; Gray, Paul; Stepensky, Polina; Warnatz, Klaus; Freeman, Alexandra F; Rossjohn, Jamie; McCluskey, James; Holland, Steven M; Casanova, Jean-Laurent; Uzel, Gulbu; Ma, Cindy S; Tangye, Stuart G; Deenick, Elissa K

    2015-06-01

    Unconventional T cells such as γδ T cells, natural killer T cells (NKT cells) and mucosal-associated invariant T cells (MAIT cells) are a major component of the immune system; however, the cytokine signaling pathways that control their development and function in humans are unknown. Primary immunodeficiencies caused by single gene mutations provide a unique opportunity to investigate the role of specific molecules in regulating human lymphocyte development and function. We found that individuals with loss-of-function mutations in STAT3 had reduced numbers of peripheral blood MAIT and NKT but not γδ T cells. Analysis of STAT3 mosaic individuals revealed that this effect was cell intrinsic. Surprisingly, the residual STAT3-deficient MAIT cells expressed normal levels of the transcription factor RORγt. Despite this, they displayed a deficiency in secretion of IL-17A and IL-17F, but were able to secrete normal levels of cytokines such as IFNγ and TNF. The deficiency in MAIT and NKT cells in STAT3-deficient patients was mirrored by loss-of-function mutations in IL12RB1 and IL21R, respectively. Thus, these results reveal for the first time the essential role of STAT3 signaling downstream of IL-23R and IL-21R in controlling human MAIT and NKT cell numbers. © 2015 Wilson et al.

  16. STAT3 is a critical cell-intrinsic regulator of human unconventional T cell numbers and function

    Science.gov (United States)

    Wilson, Robert P.; Ives, Megan L.; Rao, Geetha; Lau, Anthony; Payne, Kathryn; Kobayashi, Masao; Arkwright, Peter D.; Peake, Jane; Wong, Melanie; Adelstein, Stephen; Smart, Joanne M.; French, Martyn A.; Fulcher, David A.; Picard, Capucine; Bustamante, Jacinta; Boisson-Dupuis, Stephanie; Gray, Paul; Stepensky, Polina; Warnatz, Klaus; Freeman, Alexandra F.; Rossjohn, Jamie; McCluskey, James; Holland, Steven M.; Casanova, Jean-Laurent; Uzel, Gulbu; Ma, Cindy S.

    2015-01-01

    Unconventional T cells such as γδ T cells, natural killer T cells (NKT cells) and mucosal-associated invariant T cells (MAIT cells) are a major component of the immune system; however, the cytokine signaling pathways that control their development and function in humans are unknown. Primary immunodeficiencies caused by single gene mutations provide a unique opportunity to investigate the role of specific molecules in regulating human lymphocyte development and function. We found that individuals with loss-of-function mutations in STAT3 had reduced numbers of peripheral blood MAIT and NKT but not γδ T cells. Analysis of STAT3 mosaic individuals revealed that this effect was cell intrinsic. Surprisingly, the residual STAT3-deficient MAIT cells expressed normal levels of the transcription factor RORγt. Despite this, they displayed a deficiency in secretion of IL-17A and IL-17F, but were able to secrete normal levels of cytokines such as IFNγ and TNF. The deficiency in MAIT and NKT cells in STAT3-deficient patients was mirrored by loss-of-function mutations in IL12RB1 and IL21R, respectively. Thus, these results reveal for the first time the essential role of STAT3 signaling downstream of IL-23R and IL-21R in controlling human MAIT and NKT cell numbers. PMID:25941256

  17. Human factors in resuscitation teaching.

    Science.gov (United States)

    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.

  18. Looking at the carcinogenicity of human insulin analogues via the intrinsic disorder prism.

    Science.gov (United States)

    Redwan, Elrashdy M; Linjawi, Moustafa H; Uversky, Vladimir N

    2016-03-17

    Therapeutic insulin, in its native and biosynthetic forms as well as several currently available insulin analogues, continues to be the protein of most interest to researchers. From the time of its discovery to the development of modern insulin analogues, this important therapeutic protein has passed through several stages and product generations. Beside the well-known link between diabetes and cancer risk, the currently used therapeutic insulin analogues raised serious concerns due to their potential roles in cancer initiation and/or progression. It is possible that structural variations in some of the insulin analogues are responsible for the appearance of new oncogenic species with high binding affinity to the insulin-like growth factor 1 (IGF1) receptor. The question we are trying to answer in this work is: are there any specific features of the distribution of intrinsic disorder propensity within the amino acid sequences of insulin analogues that may provide an explanation for the carcinogenicity of the altered insulin protein?

  19. Tombusvirus-yeast interactions identify conserved cell-intrinsic viral restriction factors

    Directory of Open Access Journals (Sweden)

    Zsuzsanna eSasvari

    2014-08-01

    Full Text Available To combat viral infections, plants possess innate and adaptive immune pathways, such as RNA silencing, R gene and recessive gene-mediated resistance mechanisms. However, it is likely that additional cell-intrinsic restriction factors (CIRF are also involved in limiting plant virus replication. This review discusses novel CIRFs with antiviral functions, many of them RNA-binding proteins or affecting the RNA binding activities of viral replication proteins. The CIRFs against tombusviruses have been identified in yeast (Saccharomyces cerevisiae, which is developed as an advanced model organism. Grouping of the identified CIRFs based on their known cellular functions and subcellular localization in yeast reveals that TBSV replication is limited by a wide variety of host gene functions. Yeast proteins with the highest connectivity in the network map include the well-characterized Xrn1p 5’-3’ exoribonuclease, Act1p actin protein and Cse4p centromere protein. The protein network map also reveals an important interplay between the pro-viral Hsp70 cellular chaperone and the antiviral co-chaperones, and possibly key roles for the ribosomal or ribosome-associated factors. We discuss the antiviral functions of selected CIRFs, such as the RNA binding nucleolin, ribonucleases, WW-domain proteins, single- and multi-domain cyclophilins, TPR-domain co-chaperones and cellular ion pumps. These restriction factors frequently target the RNA-binding region in the viral replication proteins, thus interfering with the recruitment of the viral RNA for replication and the assembly of the membrane-bound viral replicase. Although many of the characterized CIRFs act directly against TBSV, we propose that the TPR-domain co-chaperones function as guardians of the cellular Hsp70 chaperone system, which is subverted efficiently by TBSV for viral replicase assembly in the absence of the TPR-domain co-chaperones.

  20. A Subtype of Inhibitory Interneuron with Intrinsic Persistent Activity in Human and Monkey Neocortex

    Directory of Open Access Journals (Sweden)

    Bo Wang

    2015-03-01

    Full Text Available A critical step in understanding the neural basis of human cognitive functions is to identify neuronal types in the neocortex. In this study, we performed whole-cell recording from human cortical slices and found a distinct subpopulation of neurons with intrinsic persistent activity that could be triggered by single action potentials (APs but terminated by bursts of APs. This persistent activity was associated with a depolarizing plateau potential induced by the activation of a persistent Na+ current. Single-cell RT-PCR revealed that these neurons were inhibitory interneurons. This type of neuron was found in different cortical regions, including temporal, frontal, occipital, and parietal cortices in human and also in frontal and temporal lobes of nonhuman primate but not in rat cortical tissues, suggesting that it could be unique to primates. The characteristic persistent activity in these inhibitory interneurons may contribute to the regulation of pyramidal cell activity and participate in cortical processing.

  1. Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene.

    Science.gov (United States)

    Tanner, Stephan M; Li, Zhongyuan; Perko, James D; Oner, Cihan; Cetin, Mualla; Altay, Cigdem; Yurtsever, Zekiye; David, Karen L; Faivre, Laurence; Ismail, Essam A; Gräsbeck, Ralph; de la Chapelle, Albert

    2005-03-15

    Hereditary juvenile megaloblastic anemia due to vitamin B12 (cobalamin) deficiency is caused by intestinal malabsorption of cobalamin. In Imerslund-Grasbeck syndrome (IGS), cobalamin absorption is completely abolished and not corrected by the administration of intrinsic factor (IF); if untreated, the disease is fatal. Biallelic mutations either in the cubilin (CUBN) or amnionless (AMN) gene cause IGS. In a series of families clinically diagnosed with likely IGS, at least six displayed no evidence of mutations in CUBN or AMN. A genome-wide search for linkage followed by mutational analysis of candidate genes was performed in five of these families. A region in chromosome 11 showed evidence of linkage in four families. The gastric IF (GIF) gene located in this region harbored homozygous nonsense and missense mutations in these four families and in three additional families. The disease in these cases therefore should be classified as hereditary IF deficiency. Clinically, these patients resembled those with typical IGS; radiocobalamin absorption tests had been inconclusive regarding the nature of the defect. In the diagnosis of juvenile cobalamin deficiency, mutational analysis of the CUBN, AMN, and GIF genes provides a molecular characterization of the underlying defect and may be the diagnostic method of choice.

  2. Composite organization of the cobalamin binding and cubilin recognition sites of intrinsic factor.

    Science.gov (United States)

    Fedosov, Sergey N; Fedosova, Natalya U; Berglund, Lars; Moestrup, Søren K; Nexø, Ebba; Petersen, Torben E

    2005-03-08

    Intrinsic factor (IF(50)) is a cobalamin (Cbl)-transporting protein of 50 kDa, which can be cleaved into two fragments: the 30 kDa N-terminal peptide IF(30) and the 20 kDa C-terminal glycopeptide IF(20). Experiments on binding of Cbl to IF(30), IF(20), and IF(50) revealed comparable association rate constants (k(+)(Cbl) = 4 x 10(6), 14 x 10(6), and 26 x 10(6) M(-1) s(-1), respectively), but the equilibrium dissociation constants were essentially different (K(Cbl) = 200 microM, 0.2 microM, and cubilin in the presence or absence of Cbl. Neither apo nor holo forms of IF(20) and IF(30) were recognized by the receptor. When two fragments were mixed and incubated with Cbl, they associated into a stable complex, IF(30+20).Cbl, which bound to cubilin as well as the noncleaved IF(50).Cbl complex. We suggest that formation of the cubilin recognition site on IF is caused by assembly of two distant domains, which allows the saturated protein to be recognized by the receptor. The obtained parameters for ligand and receptor binding indicate that both full-length IF(50) and the fragments may be involved in Cbl assimilation.

  3. Infection Susceptibility in Gastric Intrinsic Factor (Vitamin B12-Defective Mice Is Subject to Maternal Influences

    Directory of Open Access Journals (Sweden)

    Lynda Mottram

    2016-06-01

    Full Text Available Mice harboring a mutation in the gene encoding gastric intrinsic factor (Gif, a protein essential for the absorption of vitamin B12/cobalamin (Cbl, have potential as a model to explore the role of vitamins in infection. The levels of Cbl in the blood of Giftm1a/tm1a mutant mice were influenced by the maternal genotype, with offspring born to heterozygous (high Cbl, F1 mothers exhibiting a significantly higher serum Cbl level than those born to homozygous (low Cbl, F2 equivalents. Low Cbl levels correlated with susceptibility to an infectious challenge with Salmonella enterica serovar Typhimurium or Citrobacter rodentium, and this susceptibility phenotype was moderated by Cbl administration. Transcriptional and metabolic profiling revealed that Cbl deficient mice exhibited a bioenergetic shift similar to a metabolic phenomenon commonly found in cancerous cells under hypoxic conditions known as the Warburg effect, with this metabolic effect being exacerbated further by infection. Our findings demonstrate a role for Cbl in bacterial infection, with potential general relevance to dietary deficiency and infection susceptibility.

  4. Gender and Middle School Science: An Examination of Intrinsic and Extrinsic Factors Affecting Achievement

    Science.gov (United States)

    Austin, Jennifer

    Gender differences in middle school science were examined utilizing a mixed-methods approach. The intrinsic and extrinsic experiences of male and female non-gifted high-achieving students were investigated through the administration of the CAIMI, student interviews, teacher questionnaires, observations, and document examination. Male and female students were selected from a rural Northeast Georgia school district based on their high performance and high growth during middle school science. Eighty-three percent of the student participants were white and 17% were Hispanic. Half of the male participants and one third of the female participants were eligible for free and reduced meals. Findings revealed that male participants were highly motivated, whereas female participants exhibited varying levels of motivation in science. Both male and female students identified similar instructional strategies as external factors that were beneficial to their success. Due to their selection by both genders, these instructional strategies were considered to be gender-neutral and thereby useful for inclusion within coeducational middle school science classrooms.

  5. A geometric network model of intrinsic grey-matter connectivity of the human brain

    Science.gov (United States)

    Lo, Yi-Ping; O'Dea, Reuben; Crofts, Jonathan J.; Han, Cheol E.; Kaiser, Marcus

    2015-10-01

    Network science provides a general framework for analysing the large-scale brain networks that naturally arise from modern neuroimaging studies, and a key goal in theoretical neuroscience is to understand the extent to which these neural architectures influence the dynamical processes they sustain. To date, brain network modelling has largely been conducted at the macroscale level (i.e. white-matter tracts), despite growing evidence of the role that local grey matter architecture plays in a variety of brain disorders. Here, we present a new model of intrinsic grey matter connectivity of the human connectome. Importantly, the new model incorporates detailed information on cortical geometry to construct ‘shortcuts’ through the thickness of the cortex, thus enabling spatially distant brain regions, as measured along the cortical surface, to communicate. Our study indicates that structures based on human brain surface information differ significantly, both in terms of their topological network characteristics and activity propagation properties, when compared against a variety of alternative geometries and generative algorithms. In particular, this might help explain histological patterns of grey matter connectivity, highlighting that observed connection distances may have arisen to maximise information processing ability, and that such gains are consistent with (and enhanced by) the presence of short-cut connections.

  6. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells

    Science.gov (United States)

    Ramirez-Tagle, Rodrigo; Escobar, Carlos A.; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4′-trimethoxy-2′-hydroxy-chalcone (CH1) and 3′-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas. PMID:26907262

  7. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Ramirez-Tagle, Rodrigo; Escobar, Carlos A; Romero, Valentina; Montorfano, Ignacio; Armisén, Ricardo; Borgna, Vincenzo; Jeldes, Emanuel; Pizarro, Luis; Simon, Felipe; Echeverria, Cesar

    2016-02-22

    Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4'-trimethoxy-2'-hydroxy-chalcone (CH1) and 3'-bromo-3,4-dimethoxy-chalcone (CH2), over human hepatoma cells (HepG2 and Huh-7) and cultured mouse hepatocytes (HepM). Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS) accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i) a caspase-dependent intrinsic pathway; and (ii) by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

  8. Chalcone-Induced Apoptosis through Caspase-Dependent Intrinsic Pathways in Human Hepatocellular Carcinoma Cells

    Directory of Open Access Journals (Sweden)

    Rodrigo Ramirez-Tagle

    2016-02-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most commonly diagnosed cancers worldwide. Chemoprevention of HCC can be achieved through the use of natural or synthetic compounds that reverse, suppress or prevent the development of cancer progression. In this study, we investigated the antiproliferative effects and the mechanism of action of two compounds, 2,3,4′-trimethoxy-2′-hydroxy-chalcone (CH1 and 3′-bromo-3,4-dimethoxy-chalcone (CH2, over human hepatoma cells (HepG2 and Huh-7 and cultured mouse hepatocytes (HepM. Cytotoxic effects were observed over the HepG2 and Huh-7, and no effects were observed over the HepM. For HepG2 cells, treated separately with each chalcone, typical apoptotic laddering and nuclear condensation were observed. Additionally, the caspases and Bcl-2 family proteins activation by using Western blotting and immunocytochemistry were studied. Caspase-8 was not activated, but caspase-3 and -9 were both activated by chalcones in HepG2 cells. Chalcones also induced reactive oxygen species (ROS accumulation after 4, 8 and 24 h of treatment in HepG2 cells. These results suggest that apoptosis in HepG2 was induced through: (i a caspase-dependent intrinsic pathway; and (ii by alterations in the cellular levels of Bcl-2 family proteins, and also, that the chalcone moiety could be a potent candidate as novel anticancer agents acting on human hepatomas.

  9. Thermal compaction of the intrinsically disordered protein tau: entropic, structural, and hydrophobic factors.

    Science.gov (United States)

    Battisti, Anna; Ciasca, Gabriele; Grottesi, Alessandro; Tenenbaum, Alexander

    2017-03-28

    Globular denatured proteins have structural properties similar to those of random coils. Experiments on denatured proteins have shown that when the temperature is increased thermal compaction may take place, resulting in a reduction of their radius of gyration Rg to range between 5% and 35% of its initial value. This phenomenon has been attributed to various causes, namely entropic, hydrophobic, and structural factors. The intrinsically disordered protein tau, which helps in nucleating and stabilizing microtubules in the axons of the neurons, also undergoes a relevant compaction process: when its temperature is increased from 293 K to 333 K its gyration radius decreases by 18%. We have performed an atomistic simulation of this molecule, at the lowest and highest temperatures of the mentioned interval, using both standard molecular dynamics and metadynamics, in parallel with small-angle X-ray scattering experiments. Using the fit of the experimental data and a genetic algorithm to select the most probable configurations among those produced in both atomistic simulations (standard MD and metadynamics), we were able to compute relevant changes, related to the temperature increase, in the average angles between residues, in the transient secondary structures, in the solvent accessible surface area, and in the number of intramolecular H-bonds. The analysis of the data showed how to decompose the compaction phenomenon into three contributions. An estimate of the entropic contribution to the compaction was obtained using the changes in the mean values of the angles between contiguous residues. The computation of the solvent accessible surface at the two temperatures allowed an estimation of the second factor contributing to the compaction, namely the increase in the hydrophobic interaction. We also measured the change in the average number of residues temporarily being in α-helices, 3-helices, PP II helices, β-sheets and β-turns. Those changes in the secondary

  10. Mechanistic insights from comparing intrinsic clearance values between human liver microsomes and hepatocytes to guide drug design.

    Science.gov (United States)

    Di, Li; Keefer, Christopher; Scott, Dennis O; Strelevitz, Timothy J; Chang, George; Bi, Yi-An; Lai, Yurong; Duckworth, Jonathon; Fenner, Katherine; Troutman, Matthew D; Obach, R Scott

    2012-11-01

    Metabolic stability of drug candidates are often determined in both liver microsome and hepatocyte assays. Comparison of intrinsic clearance values between the two assays provides additional information to guide drug design. Intrinsic clearance values from human liver microsomes and hepatocytes were compared for a set of commercial drugs with known metabolic pathways and transporter characteristics. The results showed that for compounds that were predominately metabolized by CYP mediated mechanisms, the intrinsic clearance values from the two assays were comparable. For compounds with non-CYP pathways, such as UGT and AO, intrinsic clearance was faster in hepatocytes than in microsomes. Substrates of uptake or efflux transporters in this study did not have significant differences of intrinsic clearance between microsomes and hepatocytes, when uptake into the hepatocytes was not the rate-limiting step. When hepatic uptake was rate limiting, intrinsic clearance in microsomes was faster than that in hepatocytes, which was more prevalent for compounds with rapid metabolism. Low passive permeability can limit the exposure to drug molecules to the metabolizing enzymes in the hepatocytes in relationship to the rate of metabolism. The faster the rate of metabolism, the higher permeability is needed for molecule to enter the cells and not becoming rate-limiting. The findings are very useful for drug discovery programs to gain additional insights on mechanistic information to help drug design without added experiments. Follow-up studies can then be designed to address specific questions.

  11. Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1.

    Science.gov (United States)

    Aminoff, M; Carter, J E; Chadwick, R B; Johnson, C; Gräsbeck, R; Abdelaal, M A; Broch, H; Jenner, L B; Verroust, P J; Moestrup, S K; de la Chapelle, A; Krahe, R

    1999-03-01

    Megaloblastic anaemia 1 (MGA1, OMIM 261100) is a rare, autosomal recessive disorder characterized by juvenile megaloblastic anaemia, as well as neurological symptoms that may be the only manifestations. At the cellular level, MGA1 is characterized by selective intestinal vitamin B12 (B12, cobalamin) malabsorption. MGA1 occurs worldwide, but its prevalence is higher in several Middle Eastern countries and Norway, and highest in Finland (0.8/100,000). We previously mapped the MGA1 locus by linkage analysis in Finnish and Norwegian families to a 6-cM region on chromosome 10p12.1 (ref. 8). A functional candidate gene encoding the intrinsic factor (IF)-B12 receptor, cubilin, was recently cloned; the human homologue, CUBN, was mapped to the same region. We have now refined the MGA1 region by linkage disequilibrium (LD) mapping, fine-mapped CUBN and identified two independent disease-specific CUBN mutations in 17 Finnish MGA1 families. Our genetic and molecular data indicate that mutations in CUBN cause MGA1.

  12. Foraging strategy of a neotropical primate: how intrinsic and extrinsic factors influence destination and residence time.

    Science.gov (United States)

    Plante, Sabrina; Colchero, Fernando; Calmé, Sophie

    2014-01-01

    Most animals need to actively search for food to meet energetic requirements and live in heterogeneous environments where food resources have complex spatio-temporal patterns of availability. Consequently, foraging animals need to find a balance between effort and resource allocation while accounting for intrinsic and extrinsic factors, which are often overlooked when modelling foraging behaviour. We identified the decision rules for foraging in black howler monkeys (Alouatta pigra), according to food preferences, locations of high-quality patches and previously eaten trees, phenology of food resources and hunger state. We depicted foraging in two stages: (i) the choice of the immediate next tree and (ii) the time spent on this tree. We used a recently developed model for inference of movement processes, incorporating resource selection functions into a Markov chain framework. We found that monkeys tend to move to preferred tree species at each step. However, we did not find conclusively that, at each step, monkeys direct their movements to reach high-quality patches. In fact, they were using these patches intensively, thus limiting the possibility to move towards other high-quality patches. Time spent on a tree was positively and strongly affected by the presence of preferred food items, but not by its species. We also showed that time spent on trees increased as a function of satiation state. We suggest that the strategy adopted by black howlers tends to be efficient because choosing preferred trees at each step and spending spend more time where preferred resources are available should favour energy intake and restrain movement costs. This study showcases a modelling framework that can be widely used in ecology to describe movements as a combination of multiple attraction and repulsion sources, such as mates and competitors. © 2013 The Authors. Journal of Animal Ecology © 2013 British Ecological Society.

  13. Prevalence of gastric parietal cell antibodies and intrinsic factor antibodies in primary biliary cirrhosis.

    Science.gov (United States)

    Liaskos, Christos; Norman, Gary L; Moulas, Anargyros; Garagounis, Athanasios; Goulis, Ioannis; Rigopoulou, Eirini I; Dalekos, George N

    2010-03-01

    We investigated the prevalence of antibodies against gastric parietal cells (GPA), intrinsic factor antibodies (IFA) and the presence of pernicious anemia in a large cohort of primary biliary cirrhosis (PBC) patients as similar data is missing. 157 PBC patients and 357 controls (73 with autoimmune hepatitis (AIH), 35 primary sclerosing cholangitis (PSC), 45 HBV, 37 HCV, 36 alcoholic liver disease (ALD), 35 non-alcoholic fatty liver disease (NAFLD) and 96 healthy) were investigated for IgG-isotype-specific GPA and IFA by ELISAs and vitamin-B(12) levels by a microparticle enzyme immunoassay. The detection of IgG-GPA was significantly higher in PBC (31.8%) compared to AIH (10.9%; p=0.001), PSC (0%; p=0.000), HCV (13.5%; p=0.01), HBV (13.3%; p=0.006), ALD (8.3%; p=0.004), NAFLD (11.4%; p=0.003) and healthy (10.4%; p=0.001). IgG-IFA were detected in 12% of GPA-positive PBC patients and in none of the other liver diseases or in healthy (p=0.001). This reactivity was significantly associated with lower vitamin-B(12) levels compared to those with an IFA-negative test (p=0.025). A significant proportion of PBC patients had IgG-GPA and IFA compared to controls. IgG-IFA were detected only in GPA-positive PBC patients and associated with lower vitamin-B(12) levels compared to those with an IFA-negative test. Copyright 2009 Elsevier B.V. All rights reserved.

  14. Tumor-intrinsic and tumor-extrinsic factors impacting hsp90- targeted therapy.

    Science.gov (United States)

    Alarcon, S V; Mollapour, M; Lee, M-J; Tsutsumi, S; Lee, S; Kim, Y S; Prince, T; Apolo, A B; Giaccone, G; Xu, W; Neckers, L M; Trepel, J B

    2012-11-01

    In 1994 the first heat shock protein 90 (Hsp90) inhibitor was identified and Hsp90 was reported to be a target for anticancer therapeutics. In the past 18 years there have been 17 distinct Hsp90 inhibitors entered into clinical trial, and the small molecule Hsp90 inhibitors have been highly valuable as probes of the role of Hsp90 and its client proteins in cancer. Although no Hsp90 inhibitor has achieved regulatory approval, recently there has been significant progress in Hsp90 inhibitor clinical development, and in the past year RECIST responses have been documented in HER2-positive breast cancer and EML4-ALK-positive non-small cell lung cancer. All of the clinical Hsp90 inhibitors studied to date are specific in their target, i.e. they bind exclusively to Hsp90 and two related heat shock proteins. However, Hsp90 inhibitors are markedly pleiotropic, causing degradation of over 200 client proteins and impacting critical multiprotein complexes. Furthermore, it has only recently been appreciated that Hsp90 inhibitors can, paradoxically, cause transient activation of the protein kinase clients they are chaperoning, resulting in initiation of signal transduction and significant physiological events in both tumor and tumor microenvironment. An additional area of recent progress in Hsp90 research is in studies of the posttranslational modifications of Hsp90 itself and Hsp90 co-chaperone proteins. Together, a picture is emerging in which the impact of Hsp90 inhibitors is shaped by the tumor intracellular and extracellular milieu, and in which Hsp90 inhibitors impact tumor and host on a microenvironmental and systems level. Here we review the tumor intrinsic and extrinsic factors that impact the efficacy of small molecules engaging the Hsp90 chaperone machine.

  15. Antioxidant micronutrients improve intrinsic and UV-induced apoptosis of human lymphocytes particularly in elderly people

    NARCIS (Netherlands)

    Ma, A.G.; Ge, S.; Zhang, M.; Shi, X.X.; Schouten, E.G.; Kok, F.J.; Sun, Y.Y.; Han, X.X.

    2011-01-01

    Objective: Aging and oxidative stress may lead to enhanced cellular damage and programmed cell death. to study the association of intrinsic apoptosis with age and the effect of antioxidant supplementation on intrinsic and UV-induced apoptosis in children, young and elderly people. Methods: The study

  16. Gastric intrinsic factor deficiency with combined GIF heterozygous mutations and FUT2 secretor variant.

    Science.gov (United States)

    Chery, Celine; Hehn, Alain; Mrabet, Nadir; Oussalah, Abderrahim; Jeannesson, Elise; Besseau, Cyril; Alberto, Jean-Marc; Gross, Isabelle; Josse, Thomas; Gérard, Philippe; Guéant-Rodriguez, Rosa Maria; Freund, Jean-Noel; Devignes, Jean; Bourgaud, Frédérique; Peyrin-Biroulet, Laurent; Feillet, François; Guéant, Jean-Louis

    2013-05-01

    Several genome-wide association studies (GWAS) have identified a strong association between serum vitamin B12 and fucosyltransferase 2 (FUT2), a gene associated with susceptibility to Helicobacter pylori infection. Hazra et al. conducted a meta-analysis of three GWAS and found three additional loci in MUT, CUBN and TCN1. Other GWAS conducted in Italy and China confirmed the association for FUT2 gene. Alpha-2-fucosyltransferase (FUT2) catalyzes fucose addition to form H-type antigens in exocrine secretions. FUT2 non-secretor variant produces no secretion of H-type antigens and is associated with high-plasma vitamin B12 levels. This association was explained by the influence of FUT2 on H. pylori, which is a risk factor of gastritis, a main cause of vitamin B12 impaired absorption. However, we recently showed that H. pylori serology had no influence on FUT2 association with vitamin B12, in a large sample population, suggesting the involvement of an alternative mechanism. GIF is another gene associated with plasma levels of vitamin B12 and gastric intrinsic factor (GIF) is a fucosylated protein needed for B12 absorption. Inherited GIF deficiency produces B12 deficiency unrelated with gastritis. We report 2 families with heterozygous GIF mutation, 290T>C, M97T, with decreased binding affinity of GIF for vitamin B12 and one family with heterozygous GIF mutation 435_437delGAA, K145_N146delinsN and no B12 binding activity of mutated GIF. All cases with vitamin B12 deficit carried the FUT2 rs601338 secretor variant. Ulex europeus binding to GIF was influenced by FUT2 genotypes and GIF concentration was lower, in gastric juice from control subjects with the secretor genotype. GIF290C allele was reported in 5 European cases and no Africans among 1282 ambulatory subjects and was associated with low plasma vitamin B12 and anaemia in the single case bearing the FUT2 secretor variant. We concluded that FUT2 secretor variant worsens B12 status in cases with heterozygous GIF

  17. Apigenin induces both intrinsic and extrinsic pathways of apoptosis in human colon carcinoma HCT-116 cells.

    Science.gov (United States)

    Wang, Bo; Zhao, Xin-Huai

    2017-02-01

    Apigenin is one of the plant-originated flavones with anticancer activities. In this study, apigenin was assessed for its in vitro effects on a human colon carcinoma line (HCT‑116 cells) in terms of anti-proliferation, cell cycle progression arrest, apoptosis and intracellular reactive oxygen species (ROS) generation, and then outlined its possible apoptotic mechanism for the cells. Apigenin exerted cytotoxic effect on the cells via inhibiting cell growth in a dose-time-dependent manner and causing morphological changes, arrested cell cycle progression at G0/G1 phase, and decreased mitochondrial membrane potential of the treated cells. Apigenin increased respective ROS generation and Ca2+ release and thereby, caused ER stress in the treated cells. Apigenin shows apoptosis induction towards the cells, resulting in enhanced portion of apoptotic cells. A mechanism involved ROS generation and endoplasmic reticulum stress was outlined for the apigenin-mediated apoptosis via both intrinsic mitochondrial and extrinsic pathways, based on the assayed mRNA and protein expression levels in the cells. With this mechanism, apigenin resulted in the HCT-116 cells with enhanced intracellular ROS generation and Ca2+ release together with damaged mitochondrial membrane, and upregulated protein expression of CHOP, DR5, cleaved BID, Bax, cytochrome c, cleaved caspase-3, cleaved caspase-8 and cleaved caspase-9, which triggered apoptosis of the cells.

  18. Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington's Disease T Lymphocytes.

    Science.gov (United States)

    Miller, James R C; Träger, Ulrike; Andre, Ralph; Tabrizi, Sarah J

    2015-01-01

    Huntington's disease is a fatal neurodegenerative condition caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system is dysregulated in Huntington's disease and may contribute to its pathogenesis. However, it is not clear whether or to what extent the adaptive immune system is also involved. Here, we carry out the first comprehensive investigation of human ex vivo T lymphocytes in Huntington's disease, focusing on the frequency of a range of T lymphocyte subsets, as well as analysis of proliferation, cytokine production and gene transcription. In contrast to the innate immune system, the intrinsic phenotype of T lymphocytes does not appear to be affected by the presence of mutant huntingtin, with Huntington's disease T lymphocytes exhibiting no significant functional differences compared to control cells. The transcriptional profile of T lymphocytes also does not appear to be significantly affected, suggesting that peripheral immune dysfunction in Huntington's disease is likely to be mediated primarily by the innate rather than the adaptive immune system. This study increases our understanding of the effects of Huntington's disease on peripheral tissues, while further demonstrating the differential effects of the mutant protein on different but related cell types. Finally, this study suggests that the potential use of novel therapeutics aimed at modulating the Huntington's disease innate immune system should not be extended to include the adaptive immune system.

  19. Mutant Huntingtin Does Not Affect the Intrinsic Phenotype of Human Huntington's Disease T Lymphocytes.

    Directory of Open Access Journals (Sweden)

    James R C Miller

    Full Text Available Huntington's disease is a fatal neurodegenerative condition caused by a CAG repeat expansion in the huntingtin gene. The peripheral innate immune system is dysregulated in Huntington's disease and may contribute to its pathogenesis. However, it is not clear whether or to what extent the adaptive immune system is also involved. Here, we carry out the first comprehensive investigation of human ex vivo T lymphocytes in Huntington's disease, focusing on the frequency of a range of T lymphocyte subsets, as well as analysis of proliferation, cytokine production and gene transcription. In contrast to the innate immune system, the intrinsic phenotype of T lymphocytes does not appear to be affected by the presence of mutant huntingtin, with Huntington's disease T lymphocytes exhibiting no significant functional differences compared to control cells. The transcriptional profile of T lymphocytes also does not appear to be significantly affected, suggesting that peripheral immune dysfunction in Huntington's disease is likely to be mediated primarily by the innate rather than the adaptive immune system. This study increases our understanding of the effects of Huntington's disease on peripheral tissues, while further demonstrating the differential effects of the mutant protein on different but related cell types. Finally, this study suggests that the potential use of novel therapeutics aimed at modulating the Huntington's disease innate immune system should not be extended to include the adaptive immune system.

  20. Intrinsic and task-evoked network architectures of the human brain

    Science.gov (United States)

    Cole, Michael W.; Bassett, Danielle S.; Power, Jonathan D.; Braver, Todd S.; Petersen, Steven E.

    2014-01-01

    Summary Many functional network properties of the human brain have been identified during rest and task states, yet it remains unclear how the two relate. We identified a whole-brain network architecture present across dozens of task states that was highly similar to the resting-state network architecture. The most frequent functional connectivity strengths across tasks closely matched the strengths observed at rest, suggesting this is an “intrinsic”, standard architecture of functional brain organization. Further, a set of small but consistent changes common across tasks suggests the existence of a task-general network architecture distinguishing task states from rest. These results indicate the brain’s functional network architecture during task performance is shaped primarily by an intrinsic network architecture that is also present during rest, and secondarily by evoked task-general and task-specific network changes. This establishes a strong relationship between resting-state functional connectivity and task-evoked functional connectivity – areas of neuroscientific inquiry typically considered separately. PMID:24991964

  1. Inositol Hexakisphosphate Mediates Apoptosis in Human Breast Adenocarcinoma MCF-7 Cell Line via Intrinsic Pathway

    Science.gov (United States)

    Agarwal, Rakhee; Ali, Nawab

    2010-04-01

    Inositol polyphosphates (InsPs) are naturally occurring compounds ubiquitously present in plants and animals. Inositol hexakisphosphate (InsP6) is the most abundant among all InsPs and constitutes the major portion of dietary fiber in most cereals, legumes and nuts. Certain derivatives of InsPs also regulate cellular signaling mechanisms. InsPs have also been shown to reduce tumor formation and induce apoptosis in cancerous cells. Therefore, in this study, the effects of InsPs on apoptosis were studied in an attempt to investigate their potential anti-cancer therapeutic application and understand their mechanism of action. Acridine orange and ethidium bromide staining suggested that InsP6 dose dependently induced apoptosis in human breast adenocarcinoma MCF-7 cells. Among InsPs tested (InsP3, InsP4, InsP5, and InsP6), InsP6 was found to be the most effective in inducing apoptosis. Furthermore, effects of InsP6 were found most potent inducing apoptosis. Etoposide, the drug known to induce apoptosis in both in vivo and in vitro, was used as a positive control. Western blotting experiments using specific antibodies against known apoptotic markers suggested that InsP6 induced apoptotic changes were mediated via an intrinsic apoptotic pathway.

  2. Human Factors in Financial Trading

    Science.gov (United States)

    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

  3. HUMAN PROSTATE CANCER RISK FACTORS

    Science.gov (United States)

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

  4. Intrinsic functional brain architecture derived from graph theoretical analysis in the human fetus.

    Directory of Open Access Journals (Sweden)

    Moriah E Thomason

    Full Text Available The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA, our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA <31 weeks and older (GA≥31 weeks fetuses demonstrate that brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed.

  5. Intrinsic functional brain architecture derived from graph theoretical analysis in the human fetus.

    Science.gov (United States)

    Thomason, Moriah E; Brown, Jesse A; Dassanayake, Maya T; Shastri, Rupal; Marusak, Hilary A; Hernandez-Andrade, Edgar; Yeo, Lami; Mody, Swati; Berman, Susan; Hassan, Sonia S; Romero, Roberto

    2014-01-01

    The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI) data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA), our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed.

  6. Human Factors in Space Exploration

    Science.gov (United States)

    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.

  7. Combined low doses of PPARgamma and RXR ligands trigger an intrinsic apoptotic pathway in human breast cancer cells.

    Science.gov (United States)

    Bonofiglio, Daniela; Cione, Erika; Qi, Hongyan; Pingitore, Attilio; Perri, Mariarita; Catalano, Stefania; Vizza, Donatella; Panno, Maria Luisa; Genchi, Giuseppe; Fuqua, Suzanne A W; Andò, Sebastiano

    2009-09-01

    Ligand activation of peroxisome proliferator-activated receptor (PPAR)gamma and retinoid X receptor (RXR) induces antitumor effects in cancer. We evaluated the ability of combined treatment with nanomolar levels of the PPARgamma ligand rosiglitazone (BRL) and the RXR ligand 9-cis-retinoic acid (9RA) to promote antiproliferative effects in breast cancer cells. BRL and 9RA in combination strongly inhibit of cell viability in MCF-7, MCF-7TR1, SKBR-3, and T-47D breast cancer cells, whereas MCF-10 normal breast epithelial cells are unaffected. In MCF-7 cells, combined treatment with BRL and 9RA up-regulated mRNA and protein levels of both the tumor suppressor p53 and its effector p21(WAF1/Cip1). Functional experiments indicate that the nuclear factor-kappaB site in the p53 promoter is required for the transcriptional response to BRL plus 9RA. We observed that the intrinsic apoptotic pathway in MCF-7 cells displays an ordinated sequence of events, including disruption of mitochondrial membrane potential, release of cytochrome c, strong caspase 9 activation, and, finally, DNA fragmentation. An expression vector for p53 antisense abrogated the biological effect of both ligands, which implicates involvement of p53 in PPARgamma/RXR-dependent activity in all of the human breast malignant cell lines tested. Taken together, our results suggest that multidrug regimens including a combination of PPARgamma and RXR ligands may provide a therapeutic advantage in breast cancer treatment.

  8. A five-primary photostimulator suitable for studying intrinsically photosensitive retinal ganglion cell functions in humans.

    Science.gov (United States)

    Cao, Dingcai; Nicandro, Nathaniel; Barrionuevo, Pablo A

    2015-01-26

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) can respond to light directly through self-contained photopigment, melanopsin. IpRGCs also receive synaptic inputs from rods and cones. Thus, studying ipRGC functions requires a novel photostimulating method that can account for all of the photoreceptor inputs. Here, we introduced an inexpensive LED-based five-primary photostimulator that can control the excitations of rods, S-, M-, L-cones, and melanopsin-containing ipRGCs in humans at constant background photoreceptor excitation levels, a critical requirement for studying the adaptation behavior of ipRGCs with rod, cone, or melanopsin input. We described the theory and technical aspects (including optics, electronics, software, and calibration) of the five-primary photostimulator. Then we presented two preliminary studies using the photostimulator we have implemented to measure melanopsin-mediated pupil responses and temporal contrast sensitivity function (TCSF). The results showed that the S-cone input to pupil responses was antagonistic to the L-, M- or melanopsin inputs, consistent with an S-OFF and (L + M)-ON response property of primate ipRGCs (Dacey et al., 2005). In addition, the melanopsin-mediated TCSF had a distinctive pattern compared with L + M or S-cone mediated TCSF. Other than controlling individual photoreceptor excitation independently, the five-primary photostimulator has the flexibility in presenting stimuli modulating any combination of photoreceptor excitations, which allows researchers to study the mechanisms by which ipRGCs combine various photoreceptor inputs. © 2015 ARVO.

  9. Chimeric HIV-1 envelope glycoproteins with potent intrinsic granulocyte-macrophage colony-stimulating factor (GM-CSF activity.

    Directory of Open Access Journals (Sweden)

    Gözde Isik

    Full Text Available HIV-1 acquisition can be prevented by broadly neutralizing antibodies (BrNAbs that target the envelope glycoprotein complex (Env. An ideal vaccine should therefore be able to induce BrNAbs that can provide immunity over a prolonged period of time, but the low intrinsic immunogenicity of HIV-1 Env makes the elicitation of such BrNAbs challenging. Co-stimulatory molecules can increase the immunogenicity of Env and we have engineered a soluble chimeric Env trimer with an embedded granulocyte-macrophage colony-stimulating factor (GM-CSF domain. This chimeric molecule induced enhanced B and helper T cell responses in mice compared to Env without GM-CSF. We studied whether we could optimize the activity of the embedded GM-CSF as well as the antigenic structure of the Env component of the chimeric molecule. We assessed the effect of truncating GM-CSF, removing glycosylation-sites in GM-CSF, and adjusting the linker length between GM-CSF and Env. One of our designed Env(GM-CSF chimeras improved GM-CSF-dependent cell proliferation by 6-fold, reaching the same activity as soluble recombinant GM-CSF. In addition, we incorporated GM-CSF into a cleavable Env trimer and found that insertion of GM-CSF did not compromise Env cleavage, while Env cleavage did not compromise GM-CSF activity. Importantly, these optimized Env(GM-CSF proteins were able to differentiate human monocytes into cells with a macrophage-like phenotype. Chimeric Env(GM-CSF should be useful for improving humoral immunity against HIV-1 and these studies should inform the design of other chimeric proteins.

  10. Modulation of the multistate folding of designed TPR proteins through intrinsic and extrinsic factors.

    Science.gov (United States)

    Phillips, J J; Javadi, Y; Millership, C; Main, E R G

    2012-03-01

    Tetratricopeptide repeats (TPRs) are a class of all alpha-helical repeat proteins that are comprised of 34-aa helix-turn-helix motifs. These stack together to form nonglobular structures that are stabilized by short-range interactions from residues close in primary sequence. Unlike globular proteins, they have few, if any, long-range nonlocal stabilizing interactions. Several studies on designed TPR proteins have shown that this modular structure is reflected in their folding, that is, modular multistate folding is observed as opposed to two-state folding. Here we show that TPR multistate folding can be suppressed to approximate two-state folding through modulation of intrinsic stability or extrinsic environmental variables. This modulation was investigated by comparing the thermodynamic unfolding under differing buffer regimes of two distinct series of consensus-designed TPR proteins, which possess different intrinsic stabilities. A total of nine proteins of differing sizes and differing consensus TPR motifs were each thermally and chemically denatured and their unfolding monitored using differential scanning calorimetry (DSC) and CD/fluorescence, respectively. Analyses of both the DSC and chemical denaturation data show that reducing the total stability of each protein and repeat units leads to observable two-state unfolding. These data highlight the intimate link between global and intrinsic repeat stability that governs whether folding proceeds by an observably two-state mechanism, or whether partial unfolding yields stable intermediate structures which retain sufficient stability to be populated at equilibrium.

  11. Human Factors Analysis in Software Engineering

    Institute of Scientific and Technical Information of China (English)

    Xu Ren-zuo; Ma Ruo-feng; Liu Li-na; Xiong Zhong-wei

    2004-01-01

    The general human factors analysis analyzes human functions, effects and influence in a system. But in a narrow sense, it analyzes human influence upon the reliability of a system, it includes traditional human reliability analysis, human error analysis, man-machine interface analysis, human character analysis, and others. A software development project in software engineering is successful or not to be completely determined by human factors. In this paper, we discuss the human factors intensions, declare the importance of human factors analysis for software engineering by listed some instances. At last, we probe preliminarily into the mentality that a practitioner in software engineering should possess.

  12. Sex determination. foxl3 is a germ cell-intrinsic factor involved in sperm-egg fate decision in medaka.

    Science.gov (United States)

    Nishimura, Toshiya; Sato, Tetsuya; Yamamoto, Yasuhiro; Watakabe, Ikuko; Ohkawa, Yasuyuki; Suyama, Mikita; Kobayashi, Satoru; Tanaka, Minoru

    2015-07-17

    Sex determination is an essential step in the commitment of a germ cell to a sperm or egg. However, the intrinsic factors that determine the sexual fate of vertebrate germ cells are unknown. Here, we show that foxl3, which is expressed in germ cells but not somatic cells in the gonad, is involved in sperm-egg fate decision in medaka fish. Adult XX medaka with disrupted foxl3 developed functional sperm in the expanded germinal epithelium of a histologically functional ovary. In chimeric medaka, mutant germ cells initiated spermatogenesis in female wild-type gonad. These results indicate that a germ cell-intrinsic cue for the sperm-egg fate decision is present in medaka and that spermatogenesis can proceed in a female gonadal environment.

  13. Characterization of Skin Aging-Associated Secreted Proteins (SAASP) Produced by Dermal Fibroblasts Isolated from Intrinsically Aged Human Skin.

    Science.gov (United States)

    Waldera Lupa, Daniel M; Kalfalah, Faiza; Safferling, Kai; Boukamp, Petra; Poschmann, Gereon; Volpi, Elena; Götz-Rösch, Christine; Bernerd, Francoise; Haag, Laura; Huebenthal, Ulrike; Fritsche, Ellen; Boege, Fritz; Grabe, Niels; Tigges, Julia; Stühler, Kai; Krutmann, Jean

    2015-08-01

    Most molecular hallmarks of cellular senescence have been identified in studies of cells aged in vitro by driving them into replicative or stress-induced senescence. Comparatively, less is known about the characteristic features of cells that have aged in vivo. Here we provide a systematic molecular analysis of normal human dermal fibroblasts (NHDFs) that were isolated from intrinsically aged human skin of young versus middle aged versus old donors. Intrinsically aged NHDFs in culture exhibited more frequently nuclear foci positive for p53 binding protein 1 and promyelocytic leukemia protein reminiscent of 'DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS)'. Formation of such foci was neither accompanied by increased DNA double strand breaks, nor decreased cell viability, nor telomere shortening. However, it was associated with the development of a secretory phenotype, indicating incipient cell senescence. By quantitative analysis of the entire secretome present in conditioned cell culture supernatant, combined with a multiplex cytokine determination, we identified 998 proteins secreted by intrinsically aged NHDFs in culture. Seventy of these proteins exhibited an age-dependent secretion pattern and were accordingly denoted 'skin aging-associated secreted proteins (SAASP)'. Systematic comparison of SAASP with the classical senescence-associated secretory phenotype (SASP) revealed that matrix degradation as well as proinflammatory processes are common aspects of both conditions. However, secretion of 27 proteins involved in the biological processes of 'metabolism' and 'adherens junction interactions' was unique for NHDFs isolated from intrinsically aged skin. In conclusion, fibroblasts isolated from intrinsically aged skin exhibit some, but not all, molecular hallmarks of cellular senescence. Most importantly, they secrete a unique pattern of proteins that is distinct from the canonical SASP and might reflect specific processes of skin aging.

  14. Human Factors Considerations in System Design

    Science.gov (United States)

    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.

  15. An international survey to identify the intrinsic and extrinsic factors of research studies most likely to change orthopaedic practice.

    Science.gov (United States)

    Thornley, P; de Sa, D; Evaniew, N; Farrokhyar, F; Bhandari, M; Ghert, M

    2016-04-01

    Evidence -based medicine (EBM) is designed to inform clinical decision-making within all medical specialties, including orthopaedic surgery. We recently published a pilot survey of the Canadian Orthopaedic Association (COA) membership and demonstrated that the adoption of EBM principles is variable among Canadian orthopaedic surgeons. The objective of this study was to conduct a broader international survey of orthopaedic surgeons to identify characteristics of research studies perceived as being most influential in informing clinical decision-making. A 29-question electronic survey was distributed to the readership of an established orthopaedic journal with international readership. The survey aimed to analyse the influence of both extrinsic (journal quality, investigator profiles, etc.) and intrinsic characteristics (study design, sample size, etc.) of research studies in relation to their influence on practice patterns. A total of 353 surgeons completed the survey. Surgeons achieved consensus on the 'importance' of three key designs on their practices: randomised controlled trials (94%), meta-analyses (75%) and systematic reviews (66%). The vast majority of respondents support the use of current evidence over historical clinical training; however subjective factors such as journal reputation (72%) and investigator profile (68%) continue to influence clinical decision-making strongly. Although intrinsic factors such as study design and sample size have some influence on clinical decision-making, surgeon respondents are equally influenced by extrinsic factors such as investigator reputation and perceived journal quality.Cite this article: Dr M. Ghert. An international survey to identify the intrinsic and extrinsic factors of research studies most likely to change orthopaedic practice. Bone Joint Res 2016;5:130-136. DOI: 10.1302/2046-3758.54.2000578. © 2016 Ghert et al.

  16. Trefoil factors in human milk

    DEFF Research Database (Denmark)

    Vestergaard, Else Marie; Nexø, Ebba; Wendt, A

    2008-01-01

    We measured concentrations of the gastrointestinal protective peptides Trefoil factors in human milk. By the use of in-house ELISA we detected high amounts of TFF3, less TFF1 and virtually no TFF2 in human breast milk obtained from 46 mothers with infants born extremely preterm (24-27 wk gestation......), preterm (28-37 wk gestation), and full term (38-42 wk gestation). Samples were collected during the first, second, third to fourth weeks and more than 4 wks postpartum. Median (range) TFF1 [TFF3] concentrations in human milk were 320 (30-34000) [1500 (150-27,000)] pmol/L in wk 1, 120 (30-720) [310 (50......-7100)] pmol/L in wk 2, 70 (20-670) [120 (20-650)] pmol/L in wks 3 to 4, and 60 (30-2500) [80 (20-540)] pmol/L in > 4 wks after delivery. The lowest concentrations of TFF1 and TFF3 were found later than 2 wks after birth. In conclusion, TFF was present in term and preterm human milk with rapidly declining...

  17. Intrinsic motivations drive learning of eye movements: an experiment with human adults.

    Science.gov (United States)

    Caligiore, Daniele; Mustile, Magda; Cipriani, Daniele; Redgrave, Peter; Triesch, Jochen; De Marsico, Maria; Baldassarre, Gianluca

    2015-01-01

    Intrinsic motivations drive the acquisition of knowledge and skills on the basis of novel or surprising stimuli or the pleasure to learn new skills. In so doing, they are different from extrinsic motivations that are mainly linked to drives that promote survival and reproduction. Intrinsic motivations have been implicitly exploited in several psychological experiments but, due to the lack of proper paradigms, they are rarely a direct subject of investigation. This article investigates how different intrinsic motivation mechanisms can support the learning of visual skills, such as "foveate a particular object in space", using a gaze contingency paradigm. In the experiment participants could freely foveate objects shown in a computer screen. Foveating each of two "button" pictures caused different effects: one caused the appearance of a simple image (blue rectangle) in unexpected positions, while the other evoked the appearance of an always-novel picture (objects or animals). The experiment studied how two possible intrinsic motivation mechanisms might guide learning to foveate one or the other button picture. One mechanism is based on the sudden, surprising appearance of a familiar image at unpredicted locations, and a second one is based on the content novelty of the images. The results show the comparative effectiveness of the mechanism based on image novelty, whereas they do not support the operation of the mechanism based on the surprising location of the image appearance. Interestingly, these results were also obtained with participants that, according to a post experiment questionnaire, had not understood the functions of the different buttons suggesting that novelty-based intrinsic motivation mechanisms might operate even at an unconscious level.

  18. Expression of atrophy-related transcription factors in the process of intrinsic laryngeal muscle atrophy after denervation.

    Science.gov (United States)

    Sei, Hirofumi; Taguchi, Aki; Nishida, Naoya; Hato, Naohito; Gyo, Kiyofumi

    2015-01-01

    We examined changes in the expressions of three atrophy-related transcription factors (FOXO3a, P-FOXO3a, and PGC-1α) in the process of intrinsic laryngeal muscle atrophy after denervation. In total, 51 Wistar rats were used. After transection of the unilateral recurrent laryngeal nerve, the thyroarytenoid (TA) muscle and the posterior cricoarytenoid (PCA) muscle were excised and subjected to histological and Western blot studies. Relationships between the expressions of transcription factors during atrophy of the intrinsic laryngeal muscles were investigated by comparing the results of the treated side (T) with those of the untreated side (U), and sequential changes in the T/U ratio after denervation were assessed. Loss of wet muscle weight, together with a decrease in muscle fiber cross-sectional area and increase in the number of muscle fibers/mm(2), occurred more quickly in TA muscle than in PCA muscle. Muscle atrophy progressed rapidly between 7 and 28 days after denervation, while expression of FOXO3a was maximal on day 7, in both TA and PCA muscles. By contrast, P-FOXO3a expression decreased gradually after denervation. Expression of PGC-1α increased slowly until day 7, and then it declined. Denervation-induced atrophy of the intrinsic laryngeal muscles was closely linked with the expression of FOXO3a and PGC-1α, suggesting that atrophy of these muscles may involve the actions of these transcription factors. In addition, muscle atrophy progressed faster in TA muscle than in PCA muscle, due mainly to differences in muscle fiber composition.

  19. Human Immunodeficiency Virus-Type 1 LTR DNA contains an intrinsic gene producing antisense RNA and protein products

    Directory of Open Access Journals (Sweden)

    Hsiao Chiu-Bin

    2006-11-01

    Full Text Available Abstract Background While viruses have long been shown to capitalize on their limited genomic size by utilizing both strands of DNA or complementary DNA/RNA intermediates to code for viral proteins, it has been assumed that human retroviruses have all their major proteins translated only from the plus or sense strand of RNA, despite their requirement for a dsDNA proviral intermediate. Several studies, however, have suggested the presence of antisense transcription for both HIV-1 and HTLV-1. More recently an antisense transcript responsible for the HTLV-1 bZIP factor (HBZ protein has been described. In this study we investigated the possibility of an antisense gene contained within the human immunodeficiency virus type 1 (HIV-1 long terminal repeat (LTR. Results Inspection of published sequences revealed a potential transcription initiator element (INR situated downstream of, and in reverse orientation to, the usual HIV-1 promoter and transcription start site. This antisense initiator (HIVaINR suggested the possibility of an antisense gene responsible for RNA and protein production. We show that antisense transcripts are generated, in vitro and in vivo, originating from the TAR DNA of the HIV-1 LTR. To test the possibility that protein(s could be translated from this novel HIV-1 antisense RNA, recombinant HIV antisense gene-FLAG vectors were designed. Recombinant protein(s were produced and isolated utilizing carboxy-terminal FLAG epitope (DYKDDDDK sequences. In addition, affinity-purified antisera to an internal peptide derived from the HIV antisense protein (HAP sequences identified HAPs from HIV+ human peripheral blood lymphocytes. Conclusion HIV-1 contains an antisense gene in the U3-R regions of the LTR responsible for both an antisense RNA transcript and proteins. This antisense transcript has tremendous potential for intrinsic RNA regulation because of its overlap with the beginning of all HIV-1 sense RNA transcripts by 25 nucleotides. The

  20. Factors influencing diversification in angiosperms: at the crossroads of intrinsic and extrinsic traits.

    Science.gov (United States)

    Vamosi, Jana C; Vamosi, Steven M

    2011-03-01

    Recent studies indicate that both key innovations and available area influence species richness in angiosperms. Available area has been observed to have the greatest effect, however, and appears to alter the "carrying capacity" of a lineage rather than alter diversification rates. Here, we review and weigh the evidence of predictors of angiosperm diversification and further dissect how area can place ecological limits on diversification of angiosperms, specifically addressing the following: (1) theoretical mechanisms by which particular intrinsic and extrinsic traits may affect diversification in angiosperm families; (2) evidence that the amount of available area determines the ecological limits on lineages; and (3) geographical distribution of diversification hotspots in angiosperms, concentrating on the effects of zygomorphy, noncontiguous area, and latitude. While we found that dispersal to numerous noncontiguous areas is most important in spurring diversification, diversification of tropical and zygomorphic families appears to be elevated by the generation of more species per given area.

  1. Cellular intrinsic factors involved in the resistance of squamous cell carcinoma to photodynamic therapy.

    Science.gov (United States)

    Gilaberte, Yolanda; Milla, Laura; Salazar, Nerea; Vera-Alvarez, Jesús; Kourani, Omar; Damian, Alejandra; Rivarola, Viviana; Roca, Maria José; Espada, Jesús; González, Salvador; Juarranz, Angeles

    2014-09-01

    Photodynamic therapy (PDT) is widely used to treat non-melanoma skin cancer. However, some patients affected with squamous cell carcinoma (SCC) do not respond adequately to PDT with methyl-δ-aminolevulinic acid (MAL-PDT) and the tumors acquire an infiltrative phenotype and became histologically more aggressive, less differentiated, and more fibroblastic. To search for potential factors implicated in SCC resistance to PDT, we have used the SCC-13 cell line (parental) and resistant SCC-13 cells obtained by repeated MAL-PDT treatments (5th and 10th PDT-resistant generations). Xenografts assays in immunodeficient mice showed that the tumors generated by resistant cells were bigger than those induced by parental cells. Comparative genomic hybridization array (aCGH) showed that the three cell types presented amplicons in 3p12.1 CADM2, 7p11.2 EFGR, and 11q13.3 CCND1 genes. The 5th and 10th PDT-resistant cells showed an amplicon in 5q11.2 MAP3K1, which was not present in parental cells. The changes detected by aCGH on CCND1, EFGR, and MAP3K1 were confirmed in extracts of SCC-13 cells by reverse-transcriptase PCR and by western blot, and by immunohistochemistry in human biopsies from persistent tumors after MAL-PDT. Our data suggest that genomic imbalances related to CCND1, EFGR, and particularly MAP3K1 seem to be involved in the development of the resistance of SCC to PDT.

  2. Characterizing Facial Skin Ageing in Humans: Disentangling Extrinsic from Intrinsic Biological Phenomena

    Directory of Open Access Journals (Sweden)

    Carina Trojahn

    2015-01-01

    Full Text Available Facial skin ageing is caused by intrinsic and extrinsic mechanisms. Intrinsic ageing is highly related to chronological age. Age related skin changes can be measured using clinical and biophysical methods. The aim of this study was to evaluate whether and how clinical characteristics and biophysical parameters are associated with each other with and without adjustment for chronological age. Twenty-four female subjects of three age groups were enrolled. Clinical assessments (global facial skin ageing, wrinkling, and sagging, and biophysical measurements (roughness, colour, skin elasticity, and barrier function were conducted at both upper cheeks. Pearson’s correlations and linear regression models adjusted for age were calculated. Most of the measured parameters were correlated with chronological age (e.g., association with wrinkle score, r=0.901 and with each other (e.g., residual skin deformation and wrinkle score, r=0.606. After statistical adjustment for age, only few associations remained (e.g., mean roughness (Rz and luminance (L*,  β=-0.507, R2=0.377. Chronological age as surrogate marker for intrinsic ageing has the most important influence on most facial skin ageing signs. Changes in skin elasticity, wrinkling, sagging, and yellowness seem to be caused by additional extrinsic ageing.

  3. Role of Intrinsic (Graft) Versus Extrinsic (Host) Factors in the Growth of Transplanted Organs Following Allogeneic and Xenogeneic Transplantation.

    Science.gov (United States)

    Tanabe, T; Watanabe, H; Shah, J A; Sahara, H; Shimizu, A; Nomura, S; Asfour, A; Danton, M; Boyd, L; Dardenne Meyers, A; Ekanayake-Alper, D K; Sachs, D H; Yamada, K

    2017-01-24

    In our studies of life-supporting α-1,3-galactocyltransferase knockout (GalT-KO) pig-to-baboon kidneys, we found that some recipients developed increased serum creatinine with growth of the grafts, without histological or immunological evidence of rejection. We hypothesized that the rapid growth of orthotopic pig grafts in smaller baboon recipients may have led to deterioration of organ function. To test this hypothesis for both kidneys and lungs, we assessed whether the growth of outbred (Yorkshire) organ transplants in miniature swine was regulated by intrinsic (graft) or extrinsic (host environment) factors. Yorkshire kidneys exhibited persistent growth in miniature swine, reaching 3.7 times their initial volume over 3 mo versus 1.2 times for miniature swine kidneys over the same time period. Similar rapid early growth of lung allografts was observed and, in this case, led to organ dysfunction. For xenograft kidneys, a review of our results suggests that there is a threshold for kidney graft volume of 25 cm(3) /kg of recipient body weight at which cortical ischemia is induced in transplanted GalT-KO kidneys in baboons. These results suggest that intrinsic factors are responsible, at least in part, for growth of donor organs and that this property should be taken into consideration for growth-curve-mismatched transplants, especially for life-supporting organs transplanted into a limited recipient space.

  4. Development of an Integrated Human Factors Toolkit

    Science.gov (United States)

    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.

  5. Direct measurement of human ankle stiffness during quiet standing: the intrinsic mechanical stiffness is insufficient for stability.

    Science.gov (United States)

    Loram, Ian D; Lakie, Martin

    2002-12-15

    During quiet standing the human "inverted pendulum" sways irregularly. In previous work where subjects balanced a real inverted pendulum, we investigated what contribution the intrinsic mechanical ankle stiffness makes to achieve stability. Using the results of a plausible model, we suggested that intrinsic ankle stiffness is inadequate for providing stability. Here, using a piezo-electric translator we applied small, unobtrusive mechanical perturbations to the foot while the subject was standing freely. These short duration perturbations had a similar size and velocity to movements which occur naturally during quiet standing, and they produced no evidence of any stretch reflex response in soleus, or gastrocnemius. Direct measurement confirms our earlier conclusion; intrinsic ankle stiffness is not quite sufficient to stabilise the body or pendulum. On average the directly determined intrinsic stiffness is 91 +/- 23 % (mean +/- S.D.) of that necessary to provide minimal stabilisation. The stiffness was substantially constant, increasing only slightly with ankle torque. This stiffness cannot be neurally regulated in quiet standing. Thus we attribute this stiffness to the foot, Achilles' tendon and aponeurosis rather than the activated calf muscle fibres. Our measurements suggest that the triceps surae muscles maintain balance via a spring-like element which is itself too compliant to guarantee stability. The implication is that the brain cannot set ankle stiffness and then ignore the control task because additional modulation of torque is required to maintain balance. We suggest that the triceps surae muscles maintain balance by predictively controlling the proximal offset of the spring-like element in a ballistic-like manner.

  6. Intrinsic Motivating Factors for Academic Success of Young At-Risk Students

    Science.gov (United States)

    Rowan, Tanyia Perry

    2012-01-01

    Motivation as a factor in academic success is well documented in the literature and an important construct in educational planning. The purpose of this qualitative case study was to explore motivating factors for at-risk students who successfully graduated from high school. The framework for this study was based on Maslow's hierarchy of needs…

  7. Intrinsic factors, adrenal gland morphology, and disease burden in captive cheetahs (Acinonyx jubatus) in South Africa.

    Science.gov (United States)

    Gillis-Germitsch, Nina; Vybiral, Pamela-Rose; Codron, Daryl; Clauss, Marcus; Kotze, Antoinette; Mitchell, Emily P

    2017-01-01

    Adrenal gland weight (AW) and corticomedullary ratio (ACMR) are used as indicators of stress in animals. Captive cheetahs (Acinonyx jubatus) have higher ACMRs than free-ranging ones and stress has been linked to gastritis, amyloidosis, glomerulosclerosis, and myocardial fibrosis. We reviewed age, sex, body weight (BW), kidney weight (KW), and left AW and ACMR with necropsy findings in 51 South African captive cheetahs. Eleven common histopathologic lesions were counted for each animal as measure of its disease burden. Adrenal corticomedullary hyperplasia was significantly correlated with left AW and ACMR. Males had significantly higher AWs than females; other parameters showed no difference between the sexes. Disease burden, gastritis, and myocardial fibrosis were moderately correlated with adrenal morphology supporting prior evidence that gastritis and myocardial fibrosis are linked to stress. Glomerulosclerosis was not correlated with adrenal morphology and neither kidney nor liver amyloidosis contributed significantly to variation in AW or ACMR on multivariate analyses. Interstitial nephritis showed much stronger correlations with kidney and liver amyloidosis than gastritis. All three adrenal parameters were correlated with age; age was the only significant variable affecting ACMR on the multivariate analyses; and disease burden as well as systemic amyloidosis and kidney disease (except for fibrosis) showed moderate correlations with age. Age may, therefore, be important in the pathogenesis of disease in captive cheetahs, particularly of amyloidosis and kidney disease. None of the intrinsic measurements or adrenal parameters were sufficiently closely linked to disease to be used as ante-mortem proxies for disease burden or specific diseases. Zoo Biol. 36:40-49, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Intrinsic and extrinsic factors affecting patient engagement in diabetes self-management: perspectives of a certified diabetes educator.

    Science.gov (United States)

    Rodriguez, Kellie M

    2013-02-01

    Patients with diabetes are responsible for the vast majority of management requirements of their condition. However, their ability and motivation to engage in required self-management behaviors may be mitigated by multiple intrinsic and extrinsic factors. Intrinsic barriers include attitudes and health beliefs, limited diabetes knowledge and technical skill, reduced functional health literacy, and inadequate self-efficacy to promote positive behavior change. Extrinsic barriers include financial considerations, inadequate family and community support systems, ineffective clinical relationships, and limited access to effective diabetes health care delivery. Diabetes providers have opportunities for enhancing patient engagement with clinical recommendations and diabetes self-management through effective communication, including efforts to contextually assess patients' perceptions of diabetes and how the condition fits within the context of their changing lives. This article provides a conceptual framework for establishing and building an effective clinical alliance with patients with the goal of empowering them to take more control of their diabetes and reduce their risks for poor diabetes outcomes. Copyright © 2013 Elsevier HS Journals, Inc. All rights reserved.

  9. Human factors in agile manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. Induction of intrinsic and extrinsic apoptosis pathways in the human leukemic MOLT-4 cell line by terpinen-4-ol.

    Science.gov (United States)

    Khaw-on, Patompong; Banjerdpongchai, Ratana

    2012-01-01

    Terpinen-4-ol is a terpene found in the rhizome of Plai (Zingiber montanum (Koenig) Link ex Dietr.). In this study apoptogenic activity and mechanisms of cell death induced by terpinen-4-ol were investigated in the human leukemic MOLT-4 cell line. Terpinen-4-ol exhibited cytotoxicity in MOLT-4 cells, with characteristic morphological features of apoptosis by Wright's staining. The mode of cell death was confirmed to be apoptosis by flow cytometric analysis after staining with annexin V-FITC and propidium iodide. A sub-G1 peak in DNA histograms of cell cycle assays was observed. Terpinen-4-ol induced-MOLT-4 cell apoptosis mediated through an intrinsic pathway involving the loss of mitochondrial transmembrane potential (MTP) and release of cytochrome c into the cytosol. In addition, terpinen-4-ol also induced apoptosis via an extrinsic pathway by caspase-8 activation resulting in the cleavage of cytosolic Bid. Truncated-Bid (tBid) translocated to mitochondria and activated the mitochondrial pathway in conjunction with down-regulation of Bcl-2 protein expression. Caspase-3 activity also increased. In conclusion, terpinen-4-ol can induce human leukemic MOLT-4 cell apoptosis via both intrinsic and extrinsic pathways.

  11. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Boomsma, Wouter Krogh; Nielsen, Sofie Vincents; Lindorff-Larsen, Kresten

    2016-01-01

    The ubiquitin-proteasome system targets misfolded proteins for degradation. Since the accumulation of such proteins is potentially harmful for the cell, their prompt removal is important. E3 ubiquitin-protein ligases mediate substrate ubiquitination by bringing together the substrate with an E2...... ubiquitin-conjugating enzyme, which transfers ubiquitin to the substrate. For misfolded proteins, substrate recognition is generally delegated to molecular chaperones that subsequently interact with specific E3 ligases. An important exception is San1, a yeast E3 ligase. San1 harbors extensive regions...... of intrinsic disorder, which provide both conformational flexibility and sites for direct recognition of misfolded targets of vastly different conformations. So far, no mammalian ortholog of San1 is known, nor is it clear whether other E3 ligases utilize disordered regions for substrate recognition. Here, we...

  12. [SOME CONSIDERATIONS ABOUT THE INTRINSIC VALUE OF THE IMPACT FACTOR OF SCIENTIFIC JOURNALS].

    Science.gov (United States)

    Franco-López, Ángeles; González-Gallego, Javier; Sanz-Valero, Javier; Tuñón, María Jesús; García-De-Lorenzo, Abelardo; Culebras, Jesús M

    2015-12-01

    The reason of higher number of citations of some articles is discussed. Some considerations about the journals' impact factor, its merits and its pitfalls are also made. Scientific journals' impact factor, popularized by the Institute for Scientific Information, has become an objective parameter for authors' evaluation and also for institutions and other related circumstances. There is no reason for the impact factor's gap between some English journals and those written in other languages. English journals probably benefit of the "Mathew's effect", according to which eminent scientists are more rewarded by similar contributions than others less known. It is paradoxical that most of the major achievements of our age do not appear among the 100 most cited articles. There is no homogeneity among all the articles appearing in each scientific journal: half of the articles are cited ten times more than the other half. However, those articles cited 0 times are credited like the better ones. Each article should be evaluated by its own citations, which would be its impact factor; the authors should be evaluated by their H index.

  13. The intrinsic mechanical loss factor of hydroxy-catalysis bonds for use in the mirror suspensions of gravitational wave detectors

    Energy Technology Data Exchange (ETDEWEB)

    Sneddon, P H [Institute for Gravitational Research, Department of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Bull, S [School of Chemical Engineering and Advanced Materials, University of Newcastle, Newcastle NE1 7RU (United Kingdom); Cagnoli, G [Institute for Gravitational Research, Department of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Crooks, D R M [Institute for Gravitational Research, Department of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Elliffe, E J [Institute for Gravitational Research, Department of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Faller, J E [JILA, NIST and University of Colorado, Boulder, CO 80309 (United States); Fejer, M M [Edward L Ginzton Laboratory, Stanford University, Stanford, CA 94305-4088 (United States); Hough, J [Institute for Gravitational Research, Department of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom); Rowan, S [Institute for Gravitational Research, Department of Physics and Astronomy, University of Glasgow, Glasgow G12 8QQ (United Kingdom)

    2003-12-07

    This paper describes investigations into the mechanical losses of bonds created by hydroxy-catalysis bonding. Evaluation of the magnitude of such losses is important for determining thermal noise levels in bonded suspensions for gravitational wave detectors. Three samples were investigated with bonds of varying geometries and surface areas. In two cases, the bonds were between two pieces of fused silica, whilst in the third a fused silica piece was attached to a sapphire substrate. In each case sodium silicate solution was used as the bonding agent. The thickness and Young's modulus of the bond material were evaluated enabling values for the intrinsic mechanical loss factor of the bonding material to be obtained.

  14. Vitamin B12 deficiency with intrinsic factor antibodies in an infant with poor growth and developmental delay.

    Science.gov (United States)

    McNeil, Kathleen; Chowdhury, Dhiman; Penney, Lynette; Rashid, Mohsin

    2014-02-01

    Vitamin B12 deficiency is very rare in infants and may lead to serious hematological and neurodevelopmental abnormalities. The present article describes a case involving a seven-month-old boy with severe vitamin B12 deficiency, likely caused by juvenile pernicious anemia, an entity rarely described. The child presented with feeding intolerance, poor growth and developmental delay. He was noted to have macrocytic anemia, a markedly low serum vitamin B12 level, and elevated homocysteine and methylmalonic acid levels. Antibodies to intrinsic factor were positive. The mother was healthy, with normal vitamin B12 status. Therapy with vitamin B12 supplements led to excellent recovery of symptoms. Vitamin B12 deficiency should be considered in children presenting with failure to thrive, especially when compounded with neurological symptoms. Early diagnosis and adequate treatment is essential to avoid serious complications.

  15. A Cell Line Producing Recombinant Nerve Growth Factor Evokes Growth Responses in Intrinsic and Grafted Central Cholinergic Neurons

    Science.gov (United States)

    Ernfors, Patrik; Ebendal, Ted; Olson, Lars; Mouton, Peter; Stromberg, Ingrid; Persson, Hakan

    1989-06-01

    The rat β nerve growth factor (NGF) gene was inserted into a mammalian expression vector and cotransfected with a plasmid conferring resistance to neomycin into mouse 3T3 fibroblasts. From this transfection a stable cell line was selected that contains several hundred copies of the rat NGF gene and produces excess levels of recombinant NGF. Such genetically modified cells were implanted into the rat brain as a probe for in vivo effects of NGF on central nervous system neurons. In a model of the cortical cholinergic deficits in Alzheimer disease, we demonstrate a marked increase in the survival of, and fiber outgrowth from, grafts of fetal basal forebrain cholinergic neurons, as well as stimulation of fiber formation by intact adult intrinsic cholinergic circuits in the cerebral cortex. Adult cholinergic interneurons in intact striatum also sprout vigorously toward implanted fibroblasts. Our results suggest that this model has implications for future treatment of neurodegenerative diseases.

  16. Cubilin, the endocytic receptor for intrinsic factor-vitamin B(12) complex, mediates high-density lipoprotein holoparticle endocytosis.

    Science.gov (United States)

    Hammad, S M; Stefansson, S; Twal, W O; Drake, C J; Fleming, P; Remaley, A; Brewer, H B; Argraves, W S

    1999-08-31

    Receptors that endocytose high-density lipoproteins (HDL) have been elusive. Here yolk-sac endoderm-like cells were used to identify an endocytic receptor for HDL. The receptor was isolated by HDL affinity chromatography and identified as cubilin, the recently described endocytic receptor for intrinsic factor-vitamin B(12). Cubilin antibodies inhibit HDL endocytosis by the endoderm-like cells and in mouse embryo yolk-sac endoderm, a prominent site of cubilin expression. Cubilin-mediated HDL endocytosis is inhibitable by HDL(2), HDL(3), apolipoprotein (apo)A-I, apoA-II, apoE, and RAP, but not by low-density lipoprotein (LDL), oxidized LDL, VLDL, apoC-I, apoC-III, or heparin. These findings, coupled with the fact that cubilin is expressed in kidney proximal tubules, suggest a role for this receptor in embryonic acquisition of maternal HDL and renal catabolism of filterable forms of HDL.

  17. INTRINSIC FACTORS AND FIRM FINANCIAL ANALYSIS WITH TRIPPLE BOTTOM LINES AS INTERVENING VARIABLE AGAINST FIRM VALUE Empirical Studies on Property and Real Estate Companies Year 2010-2013

    Directory of Open Access Journals (Sweden)

    Mia Andika Sari

    2016-09-01

    Full Text Available This research conducted to examine the influence of intrinsic factors which being peroxided with Capital Structure, Firm Size, Firm Age and Financial factors that being peroxided with liquidity, profitability also with another activities using triple bottom lines as Intervening Variable against Firm Value of Property Industries. The data that being used in this study were obtained from published financial statements during the period 2010 to 2013, as well as annual reports that can be accessed through the IDX website. Data analysis technique used in this study is a regression with panel data and path analysis. The results of this research showed that intrinsic factors and financial variables have a significant influence on the firm value, as well as intrinsic factors and financial variables have a significant influence on the triple bottom lines. From the results of path analysis demonstrated that the indirect effect using the triple bottom lines as a intervening variable was greater than the direct effect.

  18. Human Factors Plan for Maritime Safety

    Science.gov (United States)

    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

  19. NASA information sciences and human factors program

    Science.gov (United States)

    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.

  20. Poor Prognosis Associated With Human Papillomavirus α7 Genotypes in Cervical Carcinoma Cannot Be Explained by Intrinsic Radiosensitivity

    Energy Technology Data Exchange (ETDEWEB)

    Hall, John S.; Iype, Rohan; Armenoult, Lucile S.C. [Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester (United Kingdom); Taylor, Janet [Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester (United Kingdom); Applied Computational Biology and Bioinformatics Group, Paterson Institute for Cancer Research, Manchester (United Kingdom); Miller, Crispin J. [Applied Computational Biology and Bioinformatics Group, Paterson Institute for Cancer Research, Manchester (United Kingdom); Davidson, Susan [Christie National Health Service Foundation Trust, Manchester (United Kingdom); Sanjose, Silvia de; Bosch, Xavier [Cancer Epidemiology Research Program, Catalan Institute of Oncology, L' Hospitalet de Llobregat (Spain); Stern, Peter L. [Immunology Group, Paterson Institute for Cancer Research, Manchester (United Kingdom); West, Catharine M.L., E-mail: Catharine.West@manchester.ac.uk [Translational Radiobiology Group, Institute of Cancer Sciences, Manchester Academic Health Science Centre, University of Manchester, Manchester (United Kingdom)

    2013-04-01

    Purpose: To investigate the relationship between human papillomavirus (HPV) genotype and outcome after radiation therapy and intrinsic radiosensitivity. Methods and Materials: HPV genotyping was performed on cervix biopsies by polymerase chain reaction using SPF-10 broad-spectrum primers, followed by deoxyribonucleic acid enzyme immunoassay and genotyping by reverse hybridization line probe assay (LiPA{sub 25}) (version 1) (n=202). PapilloCheck and quantitative reverse transcription-polymerase chain reaction were used to genotype cervix cancer cell lines (n=16). Local progression-free survival after radiation therapy alone was assessed using log-rank and Cox proportionate hazard analyses. Intrinsic radiosensitivity was measured as surviving fraction at 2 Gy (SF2) using clonogenic assays. Results: Of the 202 tumors, 107 (53.0%) were positive for HPV16, 29 (14.4%) for HPV18, 9 (4.5%) for HPV45, 23 (11.4%) for other HPV genotypes, and 22 (10.9%) were negative; 11 (5.5%) contained multiple genotypes, and 1 tumor was HPV X (0.5%). In 148 patients with outcome data, those with HPVα9-positive tumors had better local progression-free survival compared with α7 patients in univariate (P<.004) and multivariate (hazard ratio 1.54, 95% confidence interval 1.11-1.76, P=.021) analyses. There was no difference in the median SF2 of α9 and α7 cervical tumors (n=63). In the cell lines, 9 were α7 and 4 α9 positive and 3 negative. There was no difference in SF2 between α9 and α7 cell lines (n=14). Conclusion: The reduced radioresponsiveness of α7 cervical tumors is not related to intrinsic radiosensitivity.

  1. DETECTION OF INTRINSIC VANCOMYCIN RESISTANT ENTEROCOCCI IN ANIMAL AND HUMAN FECES

    Science.gov (United States)

    A survey was conducted to determine the occurrence of vancomycin resistant enterococci (VRE) in animal and human fecal samples. Fecal samples from 14 animal species and humans were analyzed by quantitative culture for enterococci and VRE. Over 800 VRE isolates were characterize...

  2. Molecular dissection of the intrinsic factor-vitamin B12 receptor, cubilin, discloses regions important for membrane association and ligand binding

    DEFF Research Database (Denmark)

    Kristiansen, M; Kozyraki, R; Jacobsen, Christian

    1999-01-01

    Cubilin, the receptor for intrinsic factor-vitamin B12, is a novel type of high molecular weight receptor consisting of a 27 CUB (complement components C1r/C1s, Uegf, and bone morphogenic protein-1) domain cluster preceded by 8 epidermal growth factor repeats and a short N-terminal sequence. In a...

  3. Dynamic Correlations between Intrinsic Connectivity and Extrinsic Connectivity of the Auditory Cortex in Humans

    Directory of Open Access Journals (Sweden)

    Zhuang Cui

    2017-08-01

    Full Text Available The arrival of sound signals in the auditory cortex (AC triggers both local and inter-regional signal propagations over time up to hundreds of milliseconds and builds up both intrinsic functional connectivity (iFC and extrinsic functional connectivity (eFC of the AC. However, interactions between iFC and eFC are largely unknown. Using intracranial stereo-electroencephalographic recordings in people with drug-refractory epilepsy, this study mainly investigated the temporal dynamic of the relationships between iFC and eFC of the AC. The results showed that a Gaussian wideband-noise burst markedly elicited potentials in both the AC and numerous higher-order cortical regions outside the AC (non-auditory cortices. Granger causality analyses revealed that in the earlier time window, iFC of the AC was positively correlated with both eFC from the AC to the inferior temporal gyrus and that to the inferior parietal lobule. While in later periods, the iFC of the AC was positively correlated with eFC from the precentral gyrus to the AC and that from the insula to the AC. In conclusion, dual-directional interactions occur between iFC and eFC of the AC at different time windows following the sound stimulation and may form the foundation underlying various central auditory processes, including auditory sensory memory, object formation, integrations between sensory, perceptional, attentional, motor, emotional, and executive processes.

  4. Magnesium absorption in human subjects from leafy vegetables, intrinsically labeled with stable /sup 26/Mg

    Energy Technology Data Exchange (ETDEWEB)

    Schwartz, R.; Spencer, H.; Welsh, J.J.

    1984-04-01

    Collards, turnip greens, leaf lettuce, and spinach, grown in nutrient solution so that their Mg content was 80 to 90% /sup 26/Mg, were tested in ambulant male volunteers stabilized on a constant metabolic diet. The freeze-dried vegetables were incorporated in bran muffins in which the vegetables replaced part of the bran. Bran muffins without vegetables were consumed for breakfast each day. They were also used as a standard test meal to which the vegetable muffins were compared. All subjects participated in three consecutive isotope absorption tests: one of the standard test meal and two of the vegetables. The standard test was carried out after at least 30 days on the controlled diet. Subsequent tests of vegetables followed at 4-wk intervals. Each test meal contained 30 microCi /sup 28/MgCl2 and 50 mg stable /sup 26/Mg, the latter either as the intrinsic label of a test vegetable or as /sup 26/MgCl/sub 2/ in solution taken with the standard bran muffins. Net absorption of both isotopes was measured to establish exchangeability and to determine relative Mg absorption from the vegetables. Exchangeability was 90% or higher from all meals tested. Relative Mg absorption was highest from collards and least from the standard test meal. Net absorption values ranged from 40 to 60%.

  5. Analysis of intrinsic and extrinsic factors influencing the dynamics of bovine Eimeria spp. from central-eastern Poland.

    Science.gov (United States)

    Tomczuk, Krzysztof; Grzybek, Maciej; Szczepaniak, Klaudiusz; Studzińska, Maria; Demkowska-Kutrzepa, Marta; Roczeń-Karczmarz, Monika; Klockiewicz, Maciej

    2015-11-30

    Eimeria infections are common in cattle worldwide, however, little is known about the invasion dynamics of this unicellular parasite. Therefore, the aim of this study was to analyze intrinsic (host age) and extrinsic (herd size and management system) factors influencing the dynamics of Eimeria spp. found in calves from CE Poland. Fecal samples were collected from 356 calves from different types of management systems and from different herd sizes. Flotation and McMaster method were used for parasitological investigation. Oocysts were differentiated on the basis of morphological criteria. Eight Eimeria species were identified and mean species richness (MSR) was significantly affected by host age. The highest MSR was noted for middle age animals. There was an association between species, with a highly significant co-occurrence of Eimeria bovis with Eimeria zuernii. The presence of E. bovis significantly increased the percentage of individuals carrying E. zuernii. The presence of E. bovis significantly increased the percentage of individuals carrying Eimeria canadensis. The overall prevalence of Eimeria spp. reached 52.8% and was significantly affected by the age of cows, with the highest prevalence in animals between 5-10 months old. The most prevalent species were E. bovis (37.4%), E. zuernii (19.9%) and E. canadensis (12.1%). The prevalence of E. bovis was affected by host age (the highest prevalence in age class 2 animals) and management type (the highest prevalence in individuals raised in groups). The prevalence of E. zuernii was affected by age (the lowest prevalence was noted in the oldest individuals) and herd size (individuals infected were present only in the middle and large size herds), whereas the prevalence of E. canadensis was affected by all three factors. Overall, mean OPG of the combined Eimeria spp. was 458.84 (37.93) and differed significantly between age classes. Mean OPGs were generally low for young and mature animals but high for middle age

  6. Hemispheric asymmetry of visual scene processing in the human brain: evidence from repetition priming and intrinsic activity.

    Science.gov (United States)

    Stevens, W Dale; Kahn, Itamar; Wig, Gagan S; Schacter, Daniel L

    2012-08-01

    Asymmetrical specialization of cognitive processes across the cerebral hemispheres is a hallmark of healthy brain development and an important evolutionary trait underlying higher cognition in humans. While previous research, including studies of priming, divided visual field presentation, and split-brain patients, demonstrates a general pattern of right/left asymmetry of form-specific versus form-abstract visual processing, little is known about brain organization underlying this dissociation. Here, using repetition priming of complex visual scenes and high-resolution functional magnetic resonance imaging (MRI), we demonstrate asymmetrical form specificity of visual processing between the right and left hemispheres within a region known to be critical for processing of visual spatial scenes (parahippocampal place area [PPA]). Next, we use resting-state functional connectivity MRI analyses to demonstrate that this functional asymmetry is associated with differential intrinsic activity correlations of the right versus left PPA with regions critically involved in perceptual versus conceptual processing, respectively. Our results demonstrate that the PPA comprises lateralized subregions across the cerebral hemispheres that are engaged in functionally dissociable yet complementary components of visual scene analysis. Furthermore, this functional asymmetry is associated with differential intrinsic functional connectivity of the PPA with distinct brain areas known to mediate dissociable cognitive processes.

  7. Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity

    National Research Council Canada - National Science Library

    Dolinska, Monika B; Kovaleva, Elena; Backlund, Peter; Wingfield, Paul T; Brooks, Brian P; Sergeev, Yuri V

    2014-01-01

    .... The intra-melanosomal domain of human tyrosinase (residues 19-469) and two OCA1B related temperature-sensitive mutants, R422Q and R422W were expressed in insect cells and produced in T. ni larvae...

  8. Albinism-Causing Mutations in Recombinant Human Tyrosinase Alter Intrinsic Enzymatic Activity: e84494

    National Research Council Canada - National Science Library

    Monika B Dolinska; Elena Kovaleva; Peter Backlund; Paul T Wingfield; Brian P Brooks; Yuri V Sergeev

    2014-01-01

    .... Methodology/Principal Findings The intra-melanosomal domain of human tyrosinase (residues 19-469) and two OCA1B related temperature-sensitive mutants, R422Q and R422W were expressed in insect cells and produced...

  9. Intrinsic differentiation potential of adolescent human tendon tissue: an in-vitro cell differentiation study

    NARCIS (Netherlands)

    M. de Mos (Marieke); J.L.M. Koevoet (Wendy); H. Jahr (Holger); M.M.A. Verstegen (Monique); M.P. Heijboer (Rien); N. Kops (Nicole); J.P.T.M. van Leeuwen (Hans); H.H. Weinans (Harrie); G.J.V.M. van Osch (Gerjo); J.A.N. Verhaar (Jan)

    2007-01-01

    textabstractTendinosis lesions show an increase of glycosaminoglycan amount, calcifications, and lipid accumulation. Therefore, altered cellular differentiation might play a role in the etiology of tendinosis. This study investigates whether adolescent human tendon tissue contains a population of

  10. Hypoxia in human colorectal adenocarcinoma: comparison between extrinsic and potential intrinsic hypoxia markers.

    NARCIS (Netherlands)

    Goethals, L.; Debucquoy, A.; Perneel, C.; Geboes, K.; Ectors, N.; Schutter, H. De; Penninckx, F.; McBride, W.H.; Begg, A.C.; Haustermans, K.

    2006-01-01

    PURPOSE: To detect and quantify hypoxia in colorectal adenocarcinomas by use of pimonidazole and iododeoxyuridine (IdUrd) as extrinsic markers and carbonic anhydrase IX (CA IX), microvessel density (MVD), epidermal growth-factor receptor (EGFR), and vascular endothelial growth factor (VEGF) as intri

  11. Summary of intrinsic and extrinsic factors affecting detection probability of marsh birds

    Science.gov (United States)

    Conway, C.J.; Gibbs, J.P.

    2011-01-01

    Many species of marsh birds (rails, bitterns, grebes, etc.) rely exclusively on emergent marsh vegetation for all phases of their life cycle, and many organizations have become concerned about the status and persistence of this group of birds. Yet, marsh birds are notoriously difficult to monitor due to their secretive habits. We synthesized the published and unpublished literature and summarized the factors that influence detection probability of secretive marsh birds in North America. Marsh birds are more likely to respond to conspecific than heterospecific calls, and seasonal peak in vocalization probability varies among co-existing species. The effectiveness of morning versus evening surveys varies among species and locations. Vocalization probability appears to be positively correlated with density in breeding Virginia Rails (Rallus limicola), Soras (Porzana carolina), and Clapper Rails (Rallus longirostris). Movement of birds toward the broadcast source creates biases when using count data from callbroadcast surveys to estimate population density. Ambient temperature, wind speed, cloud cover, and moon phase affected detection probability in some, but not all, studies. Better estimates of detection probability are needed. We provide recommendations that would help improve future marsh bird survey efforts and a list of 14 priority information and research needs that represent gaps in our current knowledge where future resources are best directed. ?? Society of Wetland Scientists 2011.

  12. Dissection of the interaction between the intrinsically disordered YAP protein and the transcription factor TEAD.

    Science.gov (United States)

    Mesrouze, Yannick; Bokhovchuk, Fedir; Meyerhofer, Marco; Fontana, Patrizia; Zimmermann, Catherine; Martin, Typhaine; Delaunay, Clara; Erdmann, Dirk; Schmelzle, Tobias; Chène, Patrick

    2017-04-21

    TEAD (TEA/ATTS domain) transcription factors are the most distal effectors of the Hippo pathway. YAP (Yes-associated protein) is a coactivator protein which, upon binding to TEAD proteins, stimulates their transcriptional activity. Since the Hippo pathway is deregulated in various cancers, designing inhibitors of the YAP:TEAD interaction is an attractive therapeutic strategy for oncology. Understanding the molecular events that take place at the YAP:TEAD interface is therefore important not only to devise drug discovery approaches, but also to gain knowledge on TEAD regulation. In this report, combining single site-directed mutagenesis and double mutant analyses, we conduct a detailed analysis on the role of several residues located at the YAP:TEAD interface. Our results provide quantitative understanding of the interactions taking place at the YAP:TEAD interface and give insights into the formation of the YAP:TEAD complex and more particularly on the interaction between TEAD and the Ω-loop found in YAP.

  13. Human Factors Research and Nuclear Safety.

    Science.gov (United States)

    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…

  14. Human Factors Simulation in Construction Management Education

    Science.gov (United States)

    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…

  15. Strong negative self regulation of prokaryotic transcription factors increases the intrinsic noise of protein expression.

    Science.gov (United States)

    Stekel, Dov J; Jenkins, Dafyd J

    2008-01-18

    Many prokaryotic transcription factors repress their own transcription. It is often asserted that such regulation enables a cell to homeostatically maintain protein abundance. We explore the role of negative self regulation of transcription in regulating the variability of protein abundance using a variety of stochastic modeling techniques. We undertake a novel analysis of a classic model for negative self regulation. We demonstrate that, with standard approximations, protein variance relative to its mean should be independent of repressor strength in a physiological range. Consequently, in that range, the coefficient of variation would increase with repressor strength. However, stochastic computer simulations demonstrate that there is a greater increase in noise associated with strong repressors than predicted by theory. The discrepancies between the mathematical analysis and computer simulations arise because with strong repressors the approximation that leads to Michaelis-Menten-like hyperbolic repression terms ceases to be valid. Because we observe that strong negative feedback increases variability and so is unlikely to be a mechanism for noise control, we suggest instead that negative feedback is evolutionarily favoured because it allows the cell to minimize mRNA usage. To test this, we used in silico evolution to demonstrate that while negative feedback can achieve only a modest improvement in protein noise reduction compared with the unregulated system, it can achieve good improvement in protein response times and very substantial improvement in reducing mRNA levels. Strong negative self regulation of transcription may not always be a mechanism for homeostatic control of protein abundance, but instead might be evolutionarily favoured as a mechanism to limit the use of mRNA. The use of hyperbolic terms derived from quasi-steady-state approximation should also be avoided in the analysis of stochastic models with strong repressors.

  16. Strong negative self regulation of Prokaryotic transcription factors increases the intrinsic noise of protein expression

    Directory of Open Access Journals (Sweden)

    Jenkins Dafyd J

    2008-01-01

    Full Text Available Abstract Background Many prokaryotic transcription factors repress their own transcription. It is often asserted that such regulation enables a cell to homeostatically maintain protein abundance. We explore the role of negative self regulation of transcription in regulating the variability of protein abundance using a variety of stochastic modeling techniques. Results We undertake a novel analysis of a classic model for negative self regulation. We demonstrate that, with standard approximations, protein variance relative to its mean should be independent of repressor strength in a physiological range. Consequently, in that range, the coefficient of variation would increase with repressor strength. However, stochastic computer simulations demonstrate that there is a greater increase in noise associated with strong repressors than predicted by theory. The discrepancies between the mathematical analysis and computer simulations arise because with strong repressors the approximation that leads to Michaelis-Menten-like hyperbolic repression terms ceases to be valid. Because we observe that strong negative feedback increases variability and so is unlikely to be a mechanism for noise control, we suggest instead that negative feedback is evolutionarily favoured because it allows the cell to minimize mRNA usage. To test this, we used in silico evolution to demonstrate that while negative feedback can achieve only a modest improvement in protein noise reduction compared with the unregulated system, it can achieve good improvement in protein response times and very substantial improvement in reducing mRNA levels. Conclusion Strong negative self regulation of transcription may not always be a mechanism for homeostatic control of protein abundance, but instead might be evolutionarily favoured as a mechanism to limit the use of mRNA. The use of hyperbolic terms derived from quasi-steady-state approximation should also be avoided in the analysis of stochastic

  17. Human factors in healthcare level one

    CERN Document Server

    Rosenorn-Lanng, Debbie

    2014-01-01

    The majority of errors, litigation, and complaints in the health service are due to 'human factors', yet the term is still not widely understood and is sometimes used interchangeably to refer to team training or communication skills. Although including these, the subject of 'human factors' goes far beyond this to look at systems, environmental influences, and interactions with equipment, in addition to self-awareness and human interaction. All of these aspects are captured inHuman Factors in Healthcare and are built into a new framework: the SHEEP model, which breaks down into five key areas:

  18. The Human Cytomegalovirus Major Immediate-Early Proteins as Antagonists of Intrinsic and Innate Antiviral Host Responses

    Directory of Open Access Journals (Sweden)

    Michael Nevels

    2009-11-01

    Full Text Available The major immediate-early (IE gene of human cytomegalovirus (CMV is believed to have a decisive role in acute infection and its activity is an important indicator of viral reactivation from latency. Although a variety of gene products are expressed from this region, the 72-kDa IE1 and the 86-kDa IE2 nuclear phosphoproteins are the most abundant and important. Both proteins have long been recognized as promiscuous transcriptional regulators. More recently, a critical role of the IE1 and IE2 proteins in counteracting nonadaptive host cell defense mechanisms has been revealed. In this review we will briefly summarize the available literature on IE1- and IE2-dependent mechanisms contributing to CMV evasion from intrinsic and innate immune responses.

  19. Implementing human factors in clinical practice

    Science.gov (United States)

    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

  20. The intrinsic factor-vitamin B12 receptor, cubilin, is assembled into trimers via a coiled-coil alpha-helix.

    Science.gov (United States)

    Lindblom, A; Quadt, N; Marsh, T; Aeschlimann, D; Mörgelin, M; Mann, K; Maurer, P; Paulsson, M

    1999-03-05

    A large protein was purified from bovine kidney, using selective extraction with EDTA to solubilize proteins anchored by divalent cation-dependent interactions. An antiserum raised against the purified protein labeled the apical cell surface of the epithelial cells in proximal tubules and the luminal surface of small intestine. Ten peptide sequences, derived from the protein, all matched the recently published sequences for rat (Moestrup, S. K., Kozyraki, R., Kristiansen, M., Kaysen, J. H., Holm Rasmussen, H., Brault, D., Pontillon, F., Goda, F. O., Christensen, E. I., Hammond, T. G., and Verroust, P. J. (1998) J. Biol. Chem. 273, 5235-5242) and human cubilin, a receptor for intrinsic factor-vitamin B12 complexes, identifying the protein as bovine cubilin. In electron microscopy, a three-armed structure was seen, indicating an oligomerization of three identical subunits. This model was supported by the Mr values of about 1,500,000 for the intact protein and 440,000 for its subunits obtained by analytical ultracentrifugation. In a search for a potential assembly domain, we identified a region of heptad repeats in the N-terminal part of the cubilin sequence. Computer-assisted analysis supported the presence of a coiled-coil alpha-helix between amino acids 103 and 132 of the human cubilin sequence and predicted the formation of a triple coiled-coil. We therefore conclude that cubilin forms a noncovalent trimer of identical subunits connected by an N-terminal coiled-coil alpha-helix.

  1. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Boomsma, Wouter Krogh; Nielsen, Sofie Vincents; Lindorff-Larsen, Kresten;

    2016-01-01

    conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology...

  2. Albinism-causing mutations in recombinant human tyrosinase alter intrinsic enzymatic activity.

    Directory of Open Access Journals (Sweden)

    Monika B Dolinska

    Full Text Available BACKGROUND: Tyrosinase (TYR catalyzes the rate-limiting, first step in melanin production and its gene (TYR is mutated in many cases of oculocutaneous albinism (OCA1, an autosomal recessive cause of childhood blindness. Patients with reduced TYR activity are classified as OCA1B; some OCA1B mutations are temperature-sensitive. Therapeutic research for OCA1 has been hampered, in part, by the absence of purified, active, recombinant wild-type and mutant human enzymes. METHODOLOGY/PRINCIPAL FINDINGS: The intra-melanosomal domain of human tyrosinase (residues 19-469 and two OCA1B related temperature-sensitive mutants, R422Q and R422W were expressed in insect cells and produced in T. ni larvae. The short trans-membrane fragment was deleted to avoid potential protein insolubility, while preserving all other functional features of the enzymes. Purified tyrosinase was obtained with a yield of >1 mg per 10 g of larval biomass. The protein was a monomeric glycoenzyme with maximum enzyme activity at 37°C and neutral pH. The two purified mutants when compared to the wild-type protein were less active and temperature sensitive. These differences are associated with conformational perturbations in secondary structure. CONCLUSIONS/SIGNIFICANCE: The intramelanosomal domains of recombinant wild-type and mutant human tyrosinases are soluble monomeric glycoproteins with activities which mirror their in vivo function. This advance allows for the structure - function analyses of different mutant TYR proteins and correlation with their corresponding human phenotypes; it also provides an important tool to discover drugs that may improve tyrosinase activity and treat OCA1.

  3. Intrinsically motivated oculomotor exploration guided by uncertainty reduction and conditioned reinforcement in non-human primates

    National Research Council Canada - National Science Library

    Daddaoua, Nabil; Lopes, Manuel; Gottlieb, Jacqueline

    2016-01-01

    ..., a desire to obtain conditioned reinforcement from positive cues, and individual variations in decision strategy and the cognitive costs of acquiring information. The results suggest that free-viewing oculomotor behavior reveals cognitive and emotional factors underlying the curiosity driven sampling of information.

  4. [Extrinsic and intrinsic factors associated with mycotoxigenic fungi populations of maize grains (Zea mays L.) stored in silobags in Argentina].

    Science.gov (United States)

    Castellari, Claudia C; Cendoya, María G; Marcos Valle, Facundo J; Barrera, Viviana; Pacin, Ana M

    2015-01-01

    In order to determine the behavior of mycotoxin-producing fungal populations linked with silobags stored corn grains with a moisture content greater at the recommended as safe, 270 samples taken in three times (beginning, 90 days, final) over a five month period of storage were evaluated. The fungal biota was quantified and identified and the contamination with fumonisin and aflatoxin was determined. Extrinsic factors (environment), intrinsic factors (grains) and technological factors (location of the grains in the profile of silobag) were taken into account to evaluate the presence and quantity of total and mycotoxigenic fungal populations. The pH of grains and O2 levels were significantly reduced after five months, while CO2 concentration increased in the same period. The total counts of mycobiota were significantly higher in grains located in the top layer of silobag. Mycotoxigenic species of Fusarium, Aspergillus, Penicillium and Eurotium were identified. The frequency of isolation of Fusarium verticillioides decreased at the end of storage and Aspergillus flavus was isolated only at the beginning of storage. The counts of the Penicillium spp. and Eurotium spp. were increased at the end of storage. Fumonisin contamination was found in all the samples (100%) with maximum levels of 5.707mg/kg whereas aflatoxin contaminated only 40% with maximum levels of 0.0008mg/kg. The environmental and substrate conditions generated during the storage limited the development of mycotoxigenic fungi and mycotoxin production. Copyright © 2015 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Multidrug Intrinsic Resistance Factors in Staphylococcus aureus Identified by Profiling Fitness within High-Diversity Transposon Libraries

    Directory of Open Access Journals (Sweden)

    Mithila Rajagopal

    2016-08-01

    Full Text Available Staphylococcus aureus is a leading cause of life-threatening infections worldwide. The MIC of an antibiotic against S. aureus, as well as other microbes, is determined by the affinity of the antibiotic for its target in addition to a complex interplay of many other cellular factors. Identifying nontarget factors impacting resistance to multiple antibiotics could inform the design of new compounds and lead to more-effective antimicrobial strategies. We examined large collections of transposon insertion mutants in S. aureus using transposon sequencing (Tn-Seq to detect transposon mutants with reduced fitness in the presence of six clinically important antibiotics—ciprofloxacin, daptomycin, gentamicin, linezolid, oxacillin, and vancomycin. This approach allowed us to assess the relative fitness of many mutants simultaneously within these libraries. We identified pathways/genes previously known to be involved in resistance to individual antibiotics, including graRS and vraFG (graRS/vraFG, mprF, and fmtA, validating the approach, and found several to be important across multiple classes of antibiotics. We also identified two new, previously uncharacterized genes, SAOUHSC_01025 and SAOUHSC_01050, encoding polytopic membrane proteins, as important in limiting the effectiveness of multiple antibiotics. Machine learning identified similarities in the fitness profiles of graXRS/vraFG, SAOUHSC_01025, and SAOUHSC_01050 mutants upon antibiotic treatment, connecting these genes of unknown function to modulation of crucial cell envelope properties. Therapeutic strategies that combine a known antibiotic with a compound that targets these or other intrinsic resistance factors may be of value for enhancing the activity of existing antibiotics for treating otherwise-resistant S. aureus strains.

  6. Human factors in safety and business management.

    Science.gov (United States)

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

    2010-02-01

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

  7. Human factors and simulation in emergency medicine.

    Science.gov (United States)

    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.

  8. Fundamentals of systems ergonomics/human factors.

    Science.gov (United States)

    Wilson, John R

    2014-01-01

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

  9. Handbook of Human Factors in Web Design

    CERN Document Server

    Vu, Kim-Phuong L

    2011-01-01

    The Handbook of Human Factors in Web Design covers basic human factors issues relating to screen design, input devices, and information organization and processing, as well as addresses newer features which will become prominent in the next generation of Web technologies. These include multimodal interfaces, wireless capabilities, and agents that can improve convenience and usability. Written by leading researchers and/or practitioners in the field, this volume reflects the varied backgrounds and interests of individuals involved in all aspects of human factors and Web design and includes chap

  10. Selecting measures for human factors research.

    Science.gov (United States)

    Kantowitz, B H

    1992-08-01

    Selecting measures is a necessary component of human factors research. Proper selection must take into account the representation problem (how is the assignment of numbers to objects or phenomena justified?) and the uniqueness problem (to what degree is this assignment unique?). Other key human factors measurement issues include subject representativeness, variable representativeness, and setting representativeness. It is difficult to create a single measure that captures essential characteristics of complex systems. Several examples illustrate how theory can guide measurement selection in such diverse human factors research as vigilance, turning off warning alarms, information requirements for military command centers, subjective workload, heart-rate signal analysis, and heat stress in nuclear power plants.

  11. Study on Angiogenesis Factor of Human Osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Angiogenesis factor of human osteosarcoma was partially purified and its biological features were studied. The active peptide with 8000 to 10 000 u molecular weight in the conditioned medium obtained from the cultivation of human osteosarcoma cells were partially purified by ultrafiltration, chromatography and dialysis. The angiogenic effects of the fractions were assessed by proliferation assay of human umbilical vein and pig aorta thoracic endothelial cells. The results showed that the chromatography fractions of 4 to 6 could significantly promote the proliferation of the endothelial cells. It was suggested that the human osteosarcoma cells could synthesize and secrete angiogenesis factor with a molecular weight of 8000 to 10 000 u.

  12. Role of intrinsic DNA binding specificity in defining target genes of the mammalian transcription factor PDX1

    Science.gov (United States)

    Liberzon, Arthur; Ridner, Gabriela; Walker, Michael D.

    2004-01-01

    PDX1 is a homeodomain transcription factor essential for pancreatic development and mature beta cell function. Homeodomain proteins typically recognize short TAAT DNA motifs in vitro: this binding displays paradoxically low specificity and affinity, given the extremely high specificity of action of these proteins in vivo. To better understand how PDX1 selects target genes in vivo, we have examined the interaction of PDX1 with natural and artificial binding sites. Comparison of PDX1 binding sites in several target promoters revealed an evolutionarily conserved pattern of nucleotides flanking the TAAT core. Using competitive in vitro DNA binding assays, we defined three groups of binding sites displaying high, intermediate and low affinity. Transfection experiments revealed a striking correlation between the ability of each sequence to activate transcription in cultured beta cells, and its ability to bind PDX1 in vitro. Site selection from a pool of oligonucleotides (sequence NNNTAATNNN) revealed a non-random preference for particular nucleotides at the flanking locations, resembling natural PDX1 binding sites. Taken together, the data indicate that the intrinsic DNA binding specificity of PDX1, in particular the bases adjacent to TAAT, plays an important role in determining the spectrum of target genes. PMID:14704343

  13. Enhanced Peptide Stability Against Protease Digestion Induced by Intrinsic Factor Binding of a Vitamin B12 Conjugate of Exendin-4.

    Science.gov (United States)

    Bonaccorso, Ron L; Chepurny, Oleg G; Becker-Pauly, Christoph; Holz, George G; Doyle, Robert P

    2015-09-08

    Peptide digestion from proteases is a significant limitation in peptide therapeutic development. It has been hypothesized that the dietary pathway of vitamin B12 (B12) may be exploited in this area, but an open question is whether B12-peptide conjugates bound to the B12 gastric uptake protein intrinsic factor (IF) can provide any stability against proteases. Herein, we describe a new conjugate of B12 with the incretin peptide exendin 4 that demonstrates picomolar agonism of the glugacon-like peptide-1 receptor (GLP1-R). Stability studies reveal that Ex-4 is digested by pancreatic proteases trypsin and chymotrypsin and by the kidney endopeptidase meprin β. Prebinding the B12 conjugate to IF, however, resulted in up to a 4-fold greater activity of the B12-Ex-4 conjugate relative to Ex-4, when the IF-B12-Ex-4 complex was exposed to 22 μg/mL of trypsin, 2.3-fold greater activity when exposed to 1.25 μg/mL of chymotrypsin, and there was no decrease in function at up to 5 μg/mL of meprin β.

  14. The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless.

    Science.gov (United States)

    Fyfe, John C; Madsen, Mette; Højrup, Peter; Christensen, Erik I; Tanner, Stephan M; de la Chapelle, Albert; He, Qianchuan; Moestrup, Søren K

    2004-03-01

    Imerslund-Gräsbeck syndrome (I-GS, megaloblastic anemia 1) is an autosomal recessive disorder characterized by intestinal cobalamin (vitamin B(12)) malabsorption and proteinuria. I-GS-causing mutations are found in either of 2 genes encoding the epithelial proteins: cubilin and amnionless (AMN). Cubilin recognizes intrinsic factor (IF)-cobalamin and various other proteins to be endocytosed in the intestine and kidney, respectively, whereas the function of AMN is unknown. Here we show that cubilin and AMN colocalize in the endocytic apparatus of polarized epithelial cells and copurify as a tight complex during IF-cobalamin affinity and nondenaturing gel filtration chromatography. In transfected cells expressing either AMN or a truncated IF-cobalamin-binding cubilin construct, neither protein alone conferred ligand endocytosis. In cubilin transfectants, cubilin accumulated in early biosynthetic compartments. However, in cells cotransfected with AMN and the cubilin construct, cubilin trafficked to the cell surface and endosomes, and the cells exhibited IF-cobalamin endocytosis and lysosomal degradation of IF. These data indicate that cubilin and AMN are subunits of a novel cubilin/AMN (cubam) complex, where AMN binds to the amino-terminal third of cubilin and directs subcellular localization and endocytosis of cubilin with its ligand. Therefore, mutations affecting either of the 2 proteins may abrogate function of the cubam complex and cause IG-S.

  15. Intrinsic architecture underlying the relations among the default, dorsal attention, and frontoparietal control networks of the human brain.

    Science.gov (United States)

    Spreng, R Nathan; Sepulcre, Jorge; Turner, Gary R; Stevens, W Dale; Schacter, Daniel L

    2013-01-01

    Human cognition is increasingly characterized as an emergent property of interactions among distributed, functionally specialized brain networks. We recently demonstrated that the antagonistic "default" and "dorsal attention" networks--subserving internally and externally directed cognition, respectively--are modulated by a third "frontoparietal control" network that flexibly couples with either network depending on task domain. However, little is known about the intrinsic functional architecture underlying this relationship. We used graph theory to analyze network properties of intrinsic functional connectivity within and between these three large-scale networks. Task-based activation from three independent studies were used to identify reliable brain regions ("nodes") of each network. We then examined pairwise connections ("edges") between nodes, as defined by resting-state functional connectivity MRI. Importantly, we used a novel bootstrap resampling procedure to determine the reliability of graph edges. Furthermore, we examined both full and partial correlations. As predicted, there was a higher degree of integration within each network than between networks. Critically, whereas the default and dorsal attention networks shared little positive connectivity with one another, the frontoparietal control network showed a high degree of between-network interconnectivity with each of these networks. Furthermore, we identified nodes within the frontoparietal control network of three different types--default-aligned, dorsal attention-aligned, and dual-aligned--that we propose play dissociable roles in mediating internetwork communication. The results provide evidence consistent with the idea that the frontoparietal control network plays a pivotal gate-keeping role in goal-directed cognition, mediating the dynamic balance between default and dorsal attention networks.

  16. Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition.

    Science.gov (United States)

    Cherkassky, Leonid; Morello, Aurore; Villena-Vargas, Jonathan; Feng, Yang; Dimitrov, Dimiter S; Jones, David R; Sadelain, Michel; Adusumilli, Prasad S

    2016-08-01

    Following immune attack, solid tumors upregulate coinhibitory ligands that bind to inhibitory receptors on T cells. This adaptive resistance compromises the efficacy of chimeric antigen receptor (CAR) T cell therapies, which redirect T cells to solid tumors. Here, we investigated whether programmed death-1-mediated (PD-1-mediated) T cell exhaustion affects mesothelin-targeted CAR T cells and explored cell-intrinsic strategies to overcome inhibition of CAR T cells. Using an orthotopic mouse model of pleural mesothelioma, we determined that relatively high doses of both CD28- and 4-1BB-based second-generation CAR T cells achieved tumor eradication. CAR-mediated CD28 and 4-1BB costimulation resulted in similar levels of T cell persistence in animals treated with low T cell doses; however, PD-1 upregulation within the tumor microenvironment inhibited T cell function. At lower doses, 4-1BB CAR T cells retained their cytotoxic and cytokine secretion functions longer than CD28 CAR T cells. The prolonged function of 4-1BB CAR T cells correlated with improved survival. PD-1/PD-1 ligand [PD-L1] pathway interference, through PD-1 antibody checkpoint blockade, cell-intrinsic PD-1 shRNA blockade, or a PD-1 dominant negative receptor, restored the effector function of CD28 CAR T cells. These findings provide mechanistic insights into human CAR T cell exhaustion in solid tumors and suggest that PD-1/PD-L1 blockade may be an effective strategy for improving the potency of CAR T cell therapies.

  17. A Proposed Framework to Understand the Intrinsic Motivation Factors on University Students' Behavioral Intention to Use a Mobile Application for Learning

    Science.gov (United States)

    Shroff, Ronnie H.; Keyes, Christopher J.

    2017-01-01

    Aim/Purpose: By integrating a motivational perspective into the Technology Acceptance Model, the goal of this study is to empirically test the causal relationship of intrinsic motivational factors on students' behavioral intention to use (BIU) a mobile application for learning. Background: Although the Technology Acceptance Model is a significant…

  18. A Minimal Regulatory Network of Extrinsic and Intrinsic Factors Recovers Observed Patterns of CD4+ T Cell Differentiation and Plasticity.

    Directory of Open Access Journals (Sweden)

    Mariana Esther Martinez-Sanchez

    2015-06-01

    Full Text Available CD4+ T cells orchestrate the adaptive immune response in vertebrates. While both experimental and modeling work has been conducted to understand the molecular genetic mechanisms involved in CD4+ T cell responses and fate attainment, the dynamic role of intrinsic (produced by CD4+ T lymphocytes versus extrinsic (produced by other cells components remains unclear, and the mechanistic and dynamic understanding of the plastic responses of these cells remains incomplete. In this work, we studied a regulatory network for the core transcription factors involved in CD4+ T cell-fate attainment. We first show that this core is not sufficient to recover common CD4+ T phenotypes. We thus postulate a minimal Boolean regulatory network model derived from a larger and more comprehensive network that is based on experimental data. The minimal network integrates transcriptional regulation, signaling pathways and the micro-environment. This network model recovers reported configurations of most of the characterized cell types (Th0, Th1, Th2, Th17, Tfh, Th9, iTreg, and Foxp3-independent T regulatory cells. This transcriptional-signaling regulatory network is robust and recovers mutant configurations that have been reported experimentally. Additionally, this model recovers many of the plasticity patterns documented for different T CD4+ cell types, as summarized in a cell-fate map. We tested the effects of various micro-environments and transient perturbations on such transitions among CD4+ T cell types. Interestingly, most cell-fate transitions were induced by transient activations, with the opposite behavior associated with transient inhibitions. Finally, we used a novel methodology was used to establish that T-bet, TGF-β and suppressors of cytokine signaling proteins are keys to recovering observed CD4+ T cell plastic responses. In conclusion, the observed CD4+ T cell-types and transition patterns emerge from the feedback between the intrinsic or intracellular

  19. A Minimal Regulatory Network of Extrinsic and Intrinsic Factors Recovers Observed Patterns of CD4+ T Cell Differentiation and Plasticity

    Science.gov (United States)

    Martinez-Sanchez, Mariana Esther; Mendoza, Luis; Villarreal, Carlos; Alvarez-Buylla, Elena R.

    2015-01-01

    CD4+ T cells orchestrate the adaptive immune response in vertebrates. While both experimental and modeling work has been conducted to understand the molecular genetic mechanisms involved in CD4+ T cell responses and fate attainment, the dynamic role of intrinsic (produced by CD4+ T lymphocytes) versus extrinsic (produced by other cells) components remains unclear, and the mechanistic and dynamic understanding of the plastic responses of these cells remains incomplete. In this work, we studied a regulatory network for the core transcription factors involved in CD4+ T cell-fate attainment. We first show that this core is not sufficient to recover common CD4+ T phenotypes. We thus postulate a minimal Boolean regulatory network model derived from a larger and more comprehensive network that is based on experimental data. The minimal network integrates transcriptional regulation, signaling pathways and the micro-environment. This network model recovers reported configurations of most of the characterized cell types (Th0, Th1, Th2, Th17, Tfh, Th9, iTreg, and Foxp3-independent T regulatory cells). This transcriptional-signaling regulatory network is robust and recovers mutant configurations that have been reported experimentally. Additionally, this model recovers many of the plasticity patterns documented for different T CD4+ cell types, as summarized in a cell-fate map. We tested the effects of various micro-environments and transient perturbations on such transitions among CD4+ T cell types. Interestingly, most cell-fate transitions were induced by transient activations, with the opposite behavior associated with transient inhibitions. Finally, we used a novel methodology was used to establish that T-bet, TGF-β and suppressors of cytokine signaling proteins are keys to recovering observed CD4+ T cell plastic responses. In conclusion, the observed CD4+ T cell-types and transition patterns emerge from the feedback between the intrinsic or intracellular regulatory core

  20. The organization of the human cerebellum estimated by intrinsic functional connectivity

    Science.gov (United States)

    Krienen, Fenna M.; Castellanos, Angela; Diaz, Julio C.; Yeo, B. T. Thomas

    2011-01-01

    The cerebral cortex communicates with the cerebellum via polysynaptic circuits. Separate regions of the cerebellum are connected to distinct cerebral areas, forming a complex topography. In this study we explored the organization of cerebrocerebellar circuits in the human using resting-state functional connectivity MRI (fcMRI). Data from 1,000 subjects were registered using nonlinear deformation of the cerebellum in combination with surface-based alignment of the cerebral cortex. The foot, hand, and tongue representations were localized in subjects performing movements. fcMRI maps derived from seed regions placed in different parts of the motor body representation yielded the expected inverted map of somatomotor topography in the anterior lobe and the upright map in the posterior lobe. Next, we mapped the complete topography of the cerebellum by estimating the principal cerebral target for each point in the cerebellum in a discovery sample of 500 subjects and replicated the topography in 500 independent subjects. The majority of the human cerebellum maps to association areas. Quantitative analysis of 17 distinct cerebral networks revealed that the extent of the cerebellum dedicated to each network is proportional to the network's extent in the cerebrum with a few exceptions, including primary visual cortex, which is not represented in the cerebellum. Like somatomotor representations, cerebellar regions linked to association cortex have separate anterior and posterior representations that are oriented as mirror images of one another. The orderly topography of the representations suggests that the cerebellum possesses at least two large, homotopic maps of the full cerebrum and possibly a smaller third map. PMID:21795627

  1. A novel triazole derivative of betulinic acid induces extrinsic and intrinsic apoptosis in human leukemia HL-60 cells.

    Science.gov (United States)

    Khan, Imran; Guru, Santosh K; Rath, Santosh K; Chinthakindi, Praveen K; Singh, Buddh; Koul, Surrinder; Bhushan, Shashi; Sangwan, Payare L

    2016-01-27

    In an attempt to arrive at more potent cytotoxic agent than the bioactive natural product betulinic acid, influence of small structural modifications of its 1, 2, 3 triazole derivatives tethered at C-28 and both C3, C-28 using click chemistry approach has been studied. The chemically characterized triazoles have been screened for in vitro cytotoxicity against four human cancer cell lines HL-60, MiaPaCa-2, PC-3 and A549 which has allowed to identify triazole derivative 28{1N (4-fluoro phenyl)-1H-1, 2, 3-triazol-4-yl} methyloxy betulinic ester having better potency profile than the parent compound with IC50 values in the range of 5-7 μM. It caused disruption of mitochondrial membrane potential, rendered Bcl-2 cleavage, Bax translocation and decrease Bcl-2/Bax ratio. These events are accompanied by activation of caspases -9, -3, which cleave the PARP-1. It also induces caspase-8, which is involved in extrinsic apoptotic pathway. Therefore, it induces apoptosis through both intrinsic and extrinsic pathways in human leukemia HL-60 cells.

  2. Human factors and information transfer

    Science.gov (United States)

    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.

  3. Human factors issues for interstellar spacecraft

    Science.gov (United States)

    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.

  4. Evaluating Human Factors in Augmented Reality Systems

    Science.gov (United States)

    2005-12-01

    user’s location and then per- forming the (cognitive) task of Mark A. Livingston Naval Research Laboratory Evaluating Human Factors in Augmented Reality ...00-00-2005 4. TITLE AND SUBTITLE Evaluating Human Factors in Augmented Reality Systems 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...the basis for situation awareness or—in combina- tion with visual cues—a navigation task. Tactile tasks. Via haptic devices, we can apply vir- tual

  5. Development of human factors design review guidelines

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea)

    1997-10-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: 25. Human Factors Engineering Program Review Model and 26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation, which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents of NUREG-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994. (author). 12 refs., 5 figs., 2 tabs.

  6. Space Human Factors: Research to Application

    Science.gov (United States)

    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.

  7. Research on disaster prevention by human factor

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Bok Youn; Kang, Chang Hee; Kang, Sun Duck; Jo, Young Do [Korea Institute of Geology Mining and Materials, Taejon (Korea)

    1998-12-01

    Mining, by its very nature, requires workers and technology to function in an unpredictable environment that can not easily be engineered to accommodate human factors. Miners' physical and cognitive capabilities are sometimes stretched to the point that 'human error' in performance result. Mine safety researchers estimate that 50-85% of all mining injuries are due, in large part, to human error. Further research suggests that the primary causes of these errors in performance lie outside the individual and can be minimized by improvements in equipment design, work environments, work procedures and training. The human factors research is providing the science needed to determine which aspects of the mining environment can be made more worker-friendly and how miners can work more safely in environments that can not be improved. Underground mines have long been recognized as an innately hazardous and physically demanding work environment. Recently, mining is becoming a more complicated process as more sophisticated technologies are introduced. The more complicated or difficult the tasks to be performed, the more critical it is to have a systematic understanding of the humans, the technology, the environments, and how they interact. Human factors is a key component in solving most of today's mine safety and health problems. Human factors research primarily centered around solving problems in the following four areas: 1) How mining methods and equipment affect safety, 2) Evaluating the fit between miner's physical capabilities and the demands of their job, 3) Improving miner's ability to perceive and react to hazards, 4) Understanding how organizational and managerial variables influence safety. Human factor research was begun during the World war II. National Coal Board (British Coal) of Great Britain commenced ergonomics in 1969, and Bureau of Mine of United States started human factor researches in same year. Japan has very short history

  8. Sanguinarine induces apoptosis of human osteosarcoma cells through the extrinsic and intrinsic pathways

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hyunjin; Bergeron, Eric; Senta, Helena; Guillemette, Kim [Cell-Biomaterial Biohybrid Systems, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada); Beauvais, Sabrina [Cell-Biomaterial Biohybrid Systems, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada); Development of Bioprocess, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada); Blouin, Richard [Universite de Sherbrooke, Department of Biology, Canada J1K 2R1 (Canada); Sirois, Joel [Development of Bioprocess, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada); Faucheux, Nathalie, E-mail: Nathalie.Faucheux@Usherbrooke.ca [Cell-Biomaterial Biohybrid Systems, Universite de Sherbrooke, Department of Chemical Engineering and Biotechnological Engineering, Canada J1K 2R1 (Canada)

    2010-08-27

    Research highlights: {yields} We show for the first time the effect of sanguinarine (SA) on MG63 and SaOS-2 cells. {yields} SA altered osteosarcoma cell viability in a concentration and time dependent manner. {yields} SA induced osteosarcoma cell apoptosis and increased caspase-8 and -9 activities. {yields} SA decreased dose dependently the Bcl-2 protein level only in MG63 cells. {yields} SaOS-2 which are osteoblast-derived, seemed more resistant to SA than MG63. -- Abstract: The quaternary benzo[c]phenanthridine alkaloid sanguinarine inhibits the proliferation of cancerous cells from different origins, including lung, breast, pancreatic and colon, but nothing is known of its effects on osteosarcoma, a primary malignant bone tumour. We have found that sanguinarine alters the morphology and reduces the viability of MG-63 and SaOS-2 human osteosarcoma cell lines in concentration- and time-dependent manner. Incubation with 1 {mu}mol/L sanguinarine for 4 and 24 h killed more efficiently MG-63 cells than SaOS-2 cells, while incubation with 5 {mu}mol/L sanguinarine killed almost 100% of both cell populations within 24 h. This treatment also changed the mitochondrial membrane potential in both MG-63 and SaOS-2 cells within 1 h, caused chromatin condensation and the formation of apoptotic bodies. It activated multicaspases, and increased the activities of caspase-8 and caspase-9 in both MG-63 and SaOS-2 cells. These data highlight sanguinarine as a novel potential agent for bone cancer therapy.

  9. INTRINSIC FACTORS AND FIRM FINANCIAL ANALYSIS WITH TRIPPLE BOTTOM LINES AS INTERVENING VARIABLE AGAINST FIRM VALUE Empirical Studies on Property and Real Estate Companies Year 2010-2013

    OpenAIRE

    Sari, Mia Andika; Wiralaga, Harya Kuncara; Warokka, Ari

    2016-01-01

    This research conducted to examine the influence of intrinsic factors which being proxied with Capital Structure, Firm Size, Firm Age and Financial factors that being proxied with liquidity, profitability also with another activities using tripple bottom lines as Intervening Variable against Firm Value of Property Industries. The data that being used in this study were obtained from published financial statements during the period 2010 to 2013, as well as annual reports that can be accessed t...

  10. Physics of Intrinsic and Extrinsic Factors that Cause the Onset of the Deadliest Illness of Mankind and are Important for Diagnostics and Treatment

    Science.gov (United States)

    Saxena, Arjun

    One of the most important topic of research in the field of Physics of Behavior is the deadliest illness of mankind which is the group of illnesses called mental illnesses. They are getting attention increasingly worldwide by the medical communities and their respective governments, because of the following fact. It is now well established that these illnesses cause more loss of human lives, destruction of families, businesses and overall economy than all the other illnesses combined. The purpose of this paper is to identify and provide solutions to two fundamental issues of such illnesses which still remain as problems. One is the stigma associated with them because of their name ``mental''. The patients are regarded as less than normal because their illness is only ``mental'' in origin. The second is that it is still not widely recognized that they are caused by medical problems in their ``brain'' which afflict their ``mind''. This paper explains this and gives an improved 3-D model using the physics of intrinsic and extrinsic factors of both ``brain'' and ``mind''. It leads to an important new name, ``BAMI'' (Brain and Mind Illness), which eliminates the stigma and gives quantitative parameters to diagnose the illness and monitor medicines to treat such illnesses.

  11. γ-Tocotrienol induces apoptosis in human T cell lymphoma through activation of both intrinsic and extrinsic pathways.

    Science.gov (United States)

    Wilankar, Chandan; Khan, Nazir M; Checker, Rahul; Sharma, Deepak; Patwardhan, Raghavendra; Gota, Vikram; Sandur, Santosh Kumar; Devasagayam, T P A

    2011-01-01

    Tocotrienols are members of vitamin E family and possess broad biological activities including antioxidant, anti-inflammatory and antitumor effects. In the present study, we examine the potential of α-tocotrienol (AT) and γ-tocotrienol (GT) in inhibiting the proliferation of human T cell lymphoma Jurkat cells and elucidate the pathways involved in anti tumor effects of GT. GT but not AT inhibited proliferation and induced apoptosis in Jurkat cells in a dose dependent manner. GT treatment resulted in elevated mitochondrial ROS production, activation of JNK and suppression of ERK and p38 MAPK. GT also induced calcium release, loss of mitochondrial membrane potential and cytochrome c release from the mitochondria. These changes were accompanied by increase in Bax expression with a concomitant decrease in Bcl-xl expression suggesting activation of mitochondrial apoptotic pathway. GT induced increase in mitochondrial ROS was abrogated by catalase. Besides, GT also up-regulated surface expression of Fas and FasL on Jurkat cells. Further, caspase activation and PARP degradation were also seen in cells treated with GT. Inhibitors of caspase-8 and caspase-9 significantly abrogated GT mediated apoptosis. In contrast GT was not toxic to normal human peripheral blood mononuclear cells suggesting differential cytotoxicity towards normal lymphocytes and transformed lymphoma cells. Cellular uptake studies with tocotrienols showed higher intracellular accumulation of GT as compared to AT which may be responsible for its better antitumor activity. Our results show antitumor effects of GT in human lymphoma cells via increased mitochondrial ROS generation and activation of both intrinsic and extrinsic apoptotic pathways.

  12. The inactivating factor of glutamine synthetase IF17 is an intrinsically disordered protein, which folds upon binding to its target.

    Science.gov (United States)

    Saelices, Lorena; Galmozzi, Carla V; Florencio, Francisco J; Muro-Pastor, M Isabel; Neira, José L

    2011-11-15

    In cyanobacteria, ammonium is incorporated into carbon skeletons by the sequential action of glutamine synthetase and glutamate synthase (GOGAT). The activity of Synechocystis sp. PCC 6803 glutamine synthetase type I (GS) is controlled by a post-transcriptional process involving protein-protein interactions with two inactivating factors: the 65-residue-long protein (IF7) and the 149-residue-long one (IF17). The sequence of the C terminus of IF17 is similar to IF7; IF7 is an intrinsically disordered protein (IDP). In this work, we study the structural propensities and affinity for GS of IF17 and a chimera protein, IF17N/IF7 (constructed by fusing the first 82 residues of IF17 with the whole IF7) by fluorescence, CD, and NMR. IF17 and IF17N/IF7 are IDPs with residual non-hydrogen-bonded structure, probably formed by α-helical, turn-like, and PPII conformations; several theoretical predictions support these experimental findings. IF17 seems to fold upon binding to GS, as suggested by CD thermal denaturations and steady-state far-UV spectra. The apparent affinity of IF17 for GS, as measured by fluorescence, is slightly smaller (K(D) ~1 μM) than that measured for IF7 (~0.3 μM). The K(D)s determined by CD are similar to those measured by fluorescence, but slightly larger, suggesting possible conformational rearrangements in the IFs and/or GS upon binding. Further, the results with IFN17/IF7 suggest that (i) binding of IF17 to the GS is modulated not only by its C-terminal region but also by its N-terminus and (ii) there are weakly structured (that is, "fuzzy") complexes in the ternary GS-IF system.

  13. Human factors and safety in emergency medicine

    Science.gov (United States)

    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.

  14. The Human Cytomegalovirus IE1 Protein Antagonizes PML Nuclear Body-Mediated Intrinsic Immunity via the Inhibition of PML De Novo SUMOylation.

    Science.gov (United States)

    Schilling, Eva-Maria; Scherer, Myriam; Reuter, Nina; Schweininger, Johannes; Muller, Yves A; Stamminger, Thomas

    2017-02-15

    PML nuclear bodies (NBs) are accumulations of cellular proteins embedded in a scaffold-like structure built by SUMO-modified PML/TRIM19. PML and other NB proteins act as cellular restriction factors against human cytomegalovirus (HCMV); however, this intrinsic defense is counteracted by the immediate early protein 1 (IE1) of HCMV. IE1 directly interacts with the PML coiled-coil domain via its globular core region and disrupts NB foci by inducing a loss of PML SUMOylation. Here, we demonstrate that IE1 acts via abrogating the de novo SUMOylation of PML. In order to overcome reversible SUMOylation dynamics, we made use of a cell-based assay that combines inducible IE1 expression with a SUMO mutant resistant to SUMO proteases. Interestingly, we observed that IE1 expression did not affect preSUMOylated PML; however, it clearly prevented de novo SUMO conjugation. Consistent results were obtained by in vitro SUMOylation assays, demonstrating that IE1 alone is sufficient for this effect. Furthermore, IE1 acts in a selective manner, since K160 was identified as the main target lysine. This is strengthened by the fact that IE1 also prevents As2O3-mediated hyperSUMOylation of K160, thereby blocking PML degradation. Since IE1 did not interfere with coiled-coil-mediated PML dimerization, we propose that IE1 affects PML autoSUMOylation either by directly abrogating PML E3 ligase function or by preventing access to SUMO sites. Thus, our data suggest a novel mechanism for how a viral protein counteracts a cellular restriction factor by selectively preventing the de novo SUMOylation at specific lysine residues without affecting global protein SUMOylation. The human cytomegalovirus IE1 protein acts as an important antagonist of a cellular restriction mechanism that is mediated by subnuclear structures termed PML nuclear bodies. This function of IE1 is required for efficient viral replication and thus constitutes a potential target for antiviral strategies. In this paper, we further

  15. Intrinsic factors determining the physical behaviour and durability ofthe Miocene sandstones used to build the Zaghouan-Carthage aqueduct (Tunis

    Directory of Open Access Journals (Sweden)

    Zoghlami, K.

    2004-12-01

    Full Text Available The present paper addresses the relationship between the intrinsic factors, physical behaviour and durability of Miocene Age sandstone used to build Tunisian Heritage Monuments, and more specifically the Zaghouan-Carthage aqueduct. A petrography study (optical microscopy and mercury intrusion porosi metry was conducted to characterize the porous system of the rock. Stone hydric behaviour was also determined by finding vacuum saturation, desorption, capillary and water vapor transmission. Finally, mechanical strength (compressive strength, abrasion resistance and durability (via accelerated sodium sulfate crystallization ageing were also found. The results obtained were indicative of good hydric performance due to the macroporous nature of the stone and the connectivity of its porous system. This rock was also found to have very low mechanical strength due to its scant lithification, making it particularly susceptible to salt weathering. It was also observed to be highly resistant to chemical alteration, given the absence of chemically unstable minerals in its composition. The durability of the material was consequently found to depend directly on the presence or absence of salts in the monument.

    En este trabajo se estudia la relación entre los factores intrínsecos, el comportamiento físico y la alterabilidad de la arenisca miocénica utilizada en el Patrimonio Monumental de Túnez, en concreto, en el acueducto romano de Zaghouan-Cartago. A partir del estudio petrográfico detallado de la roca se ha caracterizado el sistema poroso mediante microscopía y porosimetría de mercurio. También se ha caracterizado su comportamiento hídrico (absorción al vacío, desorción, capilaridad, permeabilidad al vapor de agua, se ha determinado su comportamiento mecánico (resistencia a compresión, resistencia al desgaste por rozamiento y su durabilidad mediante ensayos acelerados de cristalización de sales (sulfato de sodio. Los resultados

  16. Intrinsic and extrinsic factors act at different spatial and temporal scales to shape population structure, distribution and speciation in Italian Barbus (Osteichthyes: Cyprinidae).

    Science.gov (United States)

    Buonerba, Luca; Zaccara, Serena; Delmastro, Giovanni B; Lorenzoni, Massimo; Salzburger, Walter; Gante, Hugo F

    2015-08-01

    Previous studies have given substantial attention to external factors that affect the distribution and diversification of freshwater fish in Europe and North America, in particular Pleistocene and Holocene glacial cycles. In the present paper we examine sequence variation at one mitochondrial and four nuclear loci (over 3 kbp) from populations sampled across several drainages of all species of Barbus known to inhabit Italian freshwaters (introduced B. barbus and native B. balcanicus, B. caninus, B. plebejus and B. tyberinus). By comparing species with distinct ecological preferences (rheophilic and fluvio-lacustrine) and using a fossil-calibrated phylogeny we gained considerable insight about the intrinsic and extrinsic processes shaping barbel distribution, population structure and speciation. We found that timescales of Italian barbel diversification are older than previously thought, starting in the Early Miocene, and involving local and regional tectonism and basin paleo-evolution rather than Pleistocene glacial cycles. Conversely, more recent environmental factors associated with glaciation-deglaciation cycles have influenced species distributions. These events had a more marked impact on fluvio-lacustrine than on rheophilic species by means of river confluence at low sea levels. We show that genetic structure is influenced by species ecology: populations of small rheophilic species inhabiting upper river stretches of large basins are less connected and more differentiated than large fluvio-lacustrine species that inhabit lower river courses. We report the existence of both natural and human-induced interspecific gene flow, which could have great impacts on the evolution and persistence of species involved. In addition, we provide evidence that B. tyberinus is genetically distinguishable from all other Italian taxa and that its morphological similarity to B. plebejus and intermediacy with B. caninus are best explained by recent common ancestry and similar

  17. Siamese crocodile bile induces apoptosis in NCI-H1299 human non-small cell lung cancer cells via a mitochondria-mediated intrinsic pathway and inhibits tumorigenesis.

    Science.gov (United States)

    Tian, Ling; Deng, Yi-Tao; Dong, Xin; Fan, Jia-Yi; Li, Hua-Liang; Ding, Yu-Mei; Peng, Wei-Xi; Chen, Qing-Xi; Shen, Dong-Yan

    2017-04-01

    Non-small-cell lung cancer (NSCLC) is a widespread and particularly aggressive form of cancer. Patients with NSCLC and early metastases typically have poor prognosis, highlighting the critical need for additional drugs to improve disease outcome following surgical resection. The present study aimed to determine if Siamese crocodile bile (SCB) had an anti‑cancer effect on NCI‑H1299 human NSCLC cells. The inhibitory mechanism of SCB was examined in cell culture and nude mice. In vitro experimental results revealed that SCB inhibited the proliferation and colony‑forming ability of NCI‑H1299 cells by arresting cell cycle and inducing apoptosis. The loss of the mitochondrial membrane potential and the release of cytochrome c indicated that SCB treatment may lead to mitochondrial dysfunction in NCI‑H1299 cells. At the molecular level, SCB altered the ratio of protein expression of Bax/Bcl‑2 and activated associated caspases, suggesting that intrinsic pathway involvement in the SCB‑induced apoptosis of NCI‑H1299 cells. In the in vivo experiments, intraperitoneal injection of SCB for 4 weeks inhibited xenograft tumor growth by 46.8% without observable toxicity in nude mice. Immunohistochemistry analysis of proliferating cell nuclear antigen and vascular endothelial growth factor also revealed that SCB inhibited cell proliferation and metastasis in NSCLC xenograft tumors. Overall, SCB exerted an anti-cancer effect on NCI‑H1299 human NSCLC cells in vitro and in vivo and may have therapeutic potential for the treatment of human NSCLC.

  18. Human Factors and IT Competitive Value

    Directory of Open Access Journals (Sweden)

    Alfonso Vargas

    2004-04-01

    Full Text Available This study analyzes the system of relationships that may explain the impact of information technology (IT on competitive advantage. In this social and economic system, the study focuses on the human factors that play a key role in IT effectiveness. This is a first step to empirically specifying which human resources can complement the effect of IT on organizations. The paper revisits the main theoretical frameworks that can explain the research issue and proposes an empirical model to test the hypotheses. The results, obtained from a Data Envelopment Analysis, show that there are some human factors that positively affect the influence of IT utilization on competitive advantage. Nevertheless, other structural, industrial and internal factors may play an important role in the relationship.

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

    Science.gov (United States)

    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.

  20. Information sciences and human factors overview

    Science.gov (United States)

    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.

  1. Annotated bibliography of human factors applications literature

    Energy Technology Data Exchange (ETDEWEB)

    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.

  2. Human genetic factors in tuberculosis: an update.

    Science.gov (United States)

    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.

  3. Change of Water—Soluble—Protein,Urea—Soluble—Protein and Membrane Intrinsic Protein in Human Senile Cataract

    Institute of Scientific and Technical Information of China (English)

    HuirenZhao; JianhuaYang

    1995-01-01

    Purpose:To analyze the change of water-soluble-protein(WSP),urea-soluble-protein(USP)and membrane intrinsic protein(MIP)in human senile catarct.Methods:The water-soluble-fractions(WSF)were prepared basically according to the method of Kibbelear,et al.But in this study,5mmol/LB-mercaptoethanol was added to the buffer solution.The urea-soluble-fractions(USF)were pre-pared basically according to the method of Kibbelear,et al.Lens fiber cell mem-branes were purified basically according to the method of Russell,et al.SDS-PAGE were performed according to the procedure of Laemmili,et al.using re-solving gel13%and3%stacking gel.Results:The WSPwas fractionated intoHM+α-,β1-3-andγ-crystallin compo-nents.In nuclear cataractous lenses HM+α-and B-crystallin increase,while r-crystallin decrease.The USP from clear lenses contains mainlyαβchains of22KD,whereas in cataractous lenses,especially in nuclear cataractous lenses,the relative amount of the 28-and23KDpolypeptide(the components of β-crys-tallin)increased markedly.Lens fiber cell MIP,clear lens and cataract lens con-tained the main polypeptide of 27KD(MIP)and23KD(MP23).Conclusion:The water-insolube protein,whether in quantity or in quality,plays an important role in cataract formation.Eye Science 1995,11:124-127.

  4. Runway Incursion: Human Factors In Runway Incursions

    Science.gov (United States)

    2007-11-02

    R. S., & Harbeson, M. M. (1981). Effects of Extended Practice on Dual-Task Tracking Performance. Human Factors, 23(5), 627- 631. David , H. (1997...investigated, and test results obtained from the installation at Long Beach airport. Edwards, V., Daskalakis, A. C., Oswald, L. J., Brading , J

  5. Ethanolic extract of Thevetia peruviana flowers enhances TNF-α and TRAIL-induced apoptosis of human cervical cancer cells via intrinsic and extrinsic pathways.

    Science.gov (United States)

    Managit, Chittima; Sakurai, Hiroaki; Saiki, Ikuo

    2017-04-01

    Tumor necrosis factor-α (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) are promising candidates for cancer treatment due to their ability to induce apoptosis through death receptor stimulation. However, their usage may be limited due to the resistance of cancer cells to TNF-α- and TRAIL-induced apoptosis. Currently, there is interest in screening for natural products that can sensitize cancer cells to TNF-α- and TRAIL-induced apoptosis for their use in combination with TNF-α or TRAIL. It was previously reported that the bark extract of Thevetia peruviana showed a reversal effect on TRAIL-resistance in human gastric adenocarcinoma cell lines. In the present study, the effects of the ethanolic extract of T. peruviana flowers on TNF-α- and TRAIL-induced apoptosis of human cervical cancer HeLa cells were investigated in vitro by determining cell viability and apoptosis using a WST-1 cell proliferation assay and immunoblot analysis, respectively. The ethanolic extract of T. peruviana flowers promoted TNF-α and TRAIL-mediated cell death through the activation of the caspase cascade, poly(ADP-ribose) polymerase and BH3-interacting domain death agonist cleavage. Combined treatment using the extract plus TNF-α resulted in downregulation of anti-apoptotic protein, including myeloid cell leukemia sequence-1, B-cell lymphoma-extra large (Bcl-XL), X-linked inhibitor of apoptosis protein and survivin, while the combined treatment with TRAIL downregulated Bcl-XL. Thus, the ethanolic extract of T. peruviana flowers has potential in sensitizing the TNF-α- and TRAIL-induced apoptosis of HeLa cells via the intrinsic and extrinsic pathways.

  6. Predicting Intrinsic Motivation

    Science.gov (United States)

    Martens, Rob; Kirschner, Paul A.

    2004-01-01

    Intrinsic motivation can be predicted from participants' perceptions of the social environment and the task environment (Ryan & Deci, 2000)in terms of control, relatedness and competence. To determine the degree of independence of these factors 251 students in higher vocational education (physiotherapy and hotel management) indicated the extent to…

  7. Analyzing the microfoundations of human violence in the DRC - intrinsic and extrinsic rewards and the prediction of appetitive aggression.

    Science.gov (United States)

    Haer, Roos; Banholzer, Lilli; Elbert, Thomas; Weierstall, Roland

    2013-05-17

    Civil wars are characterized by intense forms of violence, such as torture, maiming and rape. Political scientists suggest that this form of political violence is fostered through the provision of particular intrinsic and extrinsic rewards to combatants. In the field of psychology, the perpetration of this kind of cruelty is observed to be positively linked to appetitive aggression. Over time, combatants start to enjoy the fights and even the perpetration of atrocities. In this study, we examine how receiving rewards (intrinsic versus extrinsic) influence the level of appetitive aggression exhibited by former combatants. We surveyed 95 former combatants in the eastern provinces of the Democratic Republic of the Congo. Linear regression analyses reveal that intrinsic as well as extrinsic rewards are linked to the former combatants' Appetitive Aggression score. However, this relationship is partly determined by the way in which combatants are recruited: While abducted combatants seem to react more strongly to extrinsic rewards, the score of those that joined voluntarily is primarily determined by intrinsic rewards. We conclude that receiving rewards influence the level of appetitive aggression. However, which type of rewards (intrinsic versus extrinsic) is of most importance is determined by the way combatants are recruited.

  8. Human Factors Principles in Information Dashboard Design

    Energy Technology Data Exchange (ETDEWEB)

    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. N-Acetyl Cysteine Depletes Reactive Oxygen Species and Prevents Dental Monomer-Induced Intrinsic Mitochondrial Apoptosis In Vitro in Human Dental Pulp Cells.

    Directory of Open Access Journals (Sweden)

    Yang Jiao

    Full Text Available To investigate the involvement of intrinsic mitochondrial apoptosis in dental monomer-induced cytotoxicity and the influences of N-acetyl cysteine (NAC on this process.Human dental pulp cells (hDPCs were exposed to several dental monomers in the absence or presence of NAC, and cell viability, intracellular redox balance, morphology and function of mitochondria and key indicators of intrinsic mitochondrial apoptosis were evaluated using various commercial kits.Dental monomers exerted dose-dependent cytotoxic effects on hDPCs. Concomitant to the over-production of reactive oxygen species (ROS and depletion of glutathione (GSH, differential changes in activities of superoxide dismutase, glutathione peroxidase, and catalase were detected. Apoptosis, as indicated by positive Annexin V/propidium iodide (PI staining and activation of caspase-3, was observed after dental monomer treatment. Dental monomers impaired the morphology and function of mitochondria, and induced intrinsic mitochondrial apoptosis in hDPCs via up-regulation of p53, Bax and cleaved caspase-3, and down-regulation of Bcl-2. NAC restored cell viability, relieved oxidative stress and blocked the apoptotic effects of dental monomers.Dental monomers induced oxidative stress and mitochondrial intrinsic apoptosis in hDPCs. NAC could reduce the oxidative stress and thus protect hDPCs against dental monomer-induced apoptosis.

  10. The development of human factors technologies -The development of human factors experimental evaluation techniques-

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Bong Sik; Oh, In Suk; Cha, Kyung Hoh; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-07-01

    In this year, we studied the followings: (1) Development of operator mental workload evaluation techniques, (2) Development of a prototype for preliminary human factors experiment, (3) Suitability test of information display on a large scale display panel, (4) Development of guidelines for VDU-based control room design, (5) Development of integrated test facility (ITF). (6) Establishment of an eye tracking system, and we got the following results: (1) Mental workload evaluation techniques for MMI evaluation, (2) PROTOPEX (PROTOtype for preliminary human factors experiment) for preliminary human factors experiments, (3) Usage methods of APTEA (Analysis-Prototyping-Training-Experiment-Analysis) experiment design, (4) Design guidelines for human factors verification, (5) Detail design requirements and development plan of ITF, (6) Eye movement measurement system. 38 figs, 20 tabs, 54 refs. (Author).

  11. MARINE ACCIDENTS RESEARCHED THROUGH HUMAN FACTOR PRISMA

    Directory of Open Access Journals (Sweden)

    Branislav M Ćorović

    2013-07-01

    Full Text Available We are aware of a large number of marine accidents that result in numerous casualties and even deaths and substantial negative environmental effects. The objective of this paper is to indicate factors that contribute to human errors which is identified as the most frequent cause to marine accidents. Despite rapid technological development and safety legislation, this paper identifies the human factor as the waekest link in maritime safety system. This analysis could lead to decrease of vessel accidents. In addition, starting from the European Maritime Safety Agency data and by linear regression model application, we have obtained the trend of number of ships involved in marine accidents as well as the trend of lives lost in marine accidents  in and around European Union waters.

  12. Human factors in aircraft maintenance and inspection

    Science.gov (United States)

    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.

  13. Canadian Ranger Rifle: Human Factors Requirements Validation

    Science.gov (United States)

    2010-08-01

    nation building through programs such as the Junior Canadian Rangers ( JCR )6. Other tasks of the CR include providing local expertise, guidance, and...Requirements FN Fabrique Nationale HF Human Factors HSI Humansystems® Incorporated JCR Junior Canadian Rangers MOTS Military off the Shelf NATO...support the Junior Canadian Rangers ( JCR ) Program, which helps to achieve national and territorial goals through nation building. DEFICIENCY

  14. HSE management excellence: a Human Factors approach

    Directory of Open Access Journals (Sweden)

    Roberto Theobald

    2007-04-01

    Full Text Available Present work discusses the integration of Human Factors in Health, Safety and Enviroment(HSE Management System allowing it as a way of checking the progress obtained, therebyminimizing the efforts and maximizing the result. A bibliographical research was carried outon the theoretical elements of the theme. As a result of this work, a proposal “conceptualstructure” for the integration of “Humais Factors” with the HSE management system ofAssociation of Oil & Gas Produces was presented.

  15. Human Factors Engineering Program Review Model

    Science.gov (United States)

    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

  16. Human factors by descent energy management

    Science.gov (United States)

    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

  17. Addressing Human Factors Gaps in Cyber Defense

    Science.gov (United States)

    2016-09-23

    network attack graphs. Paper presented at the IEEE Workshop on Visualization for Computer Security , Minneapolis, MN. Roberts, J.C. (2007). State of...Cyber security is a high-ranking national priority that is only likely to grow as we become more dependent on cyber systems. From a research perspective...Cyber security , cyber operations, human factors 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT: SAR 18. NUMBER OF PAGES 5 19a

  18. Human factors for a sustainable future.

    Science.gov (United States)

    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.

  19. Space Station crew safety - Human factors model

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    Carpenter, G; Cohen, S

    1976-06-01

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

  1. Activated human neutrophils release hepatocyte growth factor/scatter factor.

    LENUS (Irish Health Repository)

    McCourt, M

    2012-02-03

    BACKGROUND: Hepatocyte growth factor or scatter factor (HGF\\/SF) is a pleiotropic cytokine that has potent angiogenic properties. We have previously demonstrated that neutrophils (PMN) are directly angiogenic by releasing vascular endothelial growth factor (VEGF). We hypothesized that the acute inflammatory response can stimulate PMN to release HGF. AIMS: To examine the effects of inflammatory mediators on PMN HGF release and the effect of recombinant human HGF (rhHGF) on PMN adhesion receptor expression and PMN VEGF release. METHODS: In the first experiment, PMN were isolated from healthy volunteers and stimulated with tumour necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), interleukin-8 (IL-8), and formyl methionyl-leucyl-phenylalanine (fMLP). Culture supernatants were assayed for HGF using ELISA. In the second experiment, PMN were lysed to measure total HGF release and HGF expression in the PMN was detected by Western immunoblotting. Finally, PMN were stimulated with rhHGF. PMN CD 11a, CD 11b, and CD 18 receptor expression and VEGF release was measured using flow cytometry and ELISA respectively. RESULTS: TNF-alpha, LPS and fMLP stimulation resulted in significantly increased release of PMN HGF (755+\\/-216, 484+\\/-221 and 565+\\/-278 pg\\/ml, respectively) compared to controls (118+\\/-42 pg\\/ml). IL-8 had no effect. Total HGF release following cell lysis and Western blot suggests that HGF is released from intracellular stores. Recombinant human HGF did not alter PMN adhesion receptor expression and had no effect on PMN VEGF release. CONCLUSIONS: This study demonstrates that pro-inflammatory mediators can stimulate HGF release from a PMN intracellular store and that activated PMN in addition to secreting VEGF have further angiogenic potential by releasing HGF.

  2. Human reliability, error, and human factors in power generation

    CERN Document Server

    Dhillon, B S

    2014-01-01

    Human reliability, error, and human factors in the area of power generation have been receiving increasing attention in recent years. Each year billions of dollars are spent in the area of power generation to design, construct/manufacture, operate, and maintain various types of power systems around the globe, and such systems often fail due to human error. This book compiles various recent results and data into one volume, and eliminates the need to consult many diverse sources to obtain vital information.  It enables potential readers to delve deeper into a specific area, providing the source of most of the material presented in references at the end of each chapter. Examples along with solutions are also provided at appropriate places, and there are numerous problems for testing the reader’s comprehension.  Chapters cover a broad range of topics, including general methods for performing human reliability and error analysis in power plants, specific human reliability analysis methods for nuclear power pl...

  3. Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin

    DEFF Research Database (Denmark)

    Kristiansen, M; Aminoff, M; Jacobsen, Christian

    2000-01-01

    Megaloblastic anemia 1 (MGA1) is an autosomal recessive disorder caused by the selective intestinal malabsorption of intrinsic factor (IF) and vitamin B(12)/cobalamin (Cbl) in complex. Most Finnish patients with MGA1 carry the disease-specific P1297L mutation (FM1) in the IF-B(12) receptor, cubilin......-IF-Cbl in cubilin-expressing epithelial cells. In conclusion, the data presented show a substantial loss in affinity of the FM1 mutant form of the IF-Cbl binding region of cubilin. This now explains the malabsorption of Cbl and Cbl-dependent anemia in MGA1 patients with the FM1 mutation. (Blood. 2000...

  4. Molecular dissection of the intrinsic factor-vitamin B12 receptor, cubilin, discloses regions important for membrane association and ligand binding.

    Science.gov (United States)

    Kristiansen, M; Kozyraki, R; Jacobsen, C; Nexø, E; Verroust, P J; Moestrup, S K

    1999-07-16

    Cubilin, the receptor for intrinsic factor-vitamin B12, is a novel type of high molecular weight receptor consisting of a 27 CUB (complement components C1r/C1s, Uegf, and bone morphogenic protein-1) domain cluster preceded by 8 epidermal growth factor repeats and a short N-terminal sequence. In addition to binding the vitamin B12-carrier complex, cubilin also binds receptor-associated protein. To delineate the structures for membrane association and ligand binding we established a panel of stable transfected Chinese hamster ovary cells expressing overlapping segments of rat cubilin. Analysis of conditioned media and cell extracts of transfected cells revealed that the N-terminal cubilin region conveys membrane association. Helical plotting of this region demonstrated a conserved amphipathic helix pattern (Lys74-Glu109) as a candidate site for hydrophobic interactions. Ligand affinity chromatography and surface plasmon resonance analysis of the secreted cubilin fragments showed ligand binding in the CUB domain region. Further dissection of binding-active fragments localized the binding site for intrinsic factor-vitamin B12 to CUB domains 5-8 and a receptor-associated protein-binding site to CUB domains 13-14. In conclusion, the N-terminal cubilin region seems crucial for membrane association, whereas the CUB domain cluster harbors distinct sites for ligand binding.

  5. Effect of browned and unbrowned corn products intrinsically labeled with 65Zn on absorption of /sup 65/Zn in humans

    Energy Technology Data Exchange (ETDEWEB)

    Lykken, G.I.; Mahalko, J.; Johnson, P.E.; Milne, D.; Sandstead, H.H.; Garcia, W.J.; Dintzis, F.R.; Inglett, G.E.

    1986-05-01

    Experimental browned and unbrowned corn products were formulated and processed from unenriched, degermed yellow corngrits. The browned product (cornflakes) contained more insoluble dietary fiber and bound more zinc (in vitro) than the unbrowned product (corngrits). During processing some of the cornflakes and corngrits were combined with a small amount of yellow corn endospermhull intrinsically labeled with /sup 65/Zn. The intrinsically labeled corn products were fed, in a crossover design, as components of two breakfasts to six normal, unconfined volunteers. Each volunteer absorbed more /sup 65/Zn from the corngrits than from the cornflakes. The reduced /sup 65/Zn absorption from cornflakes was attributed to heating and toasting reaction products, possibly Maillard, which bound zinc and consequently made the zinc less available for absorption.

  6. Inhibition of the intrinsic factor X activating complex by protein S: evidence for a specific binding of protein S to factor VIII

    NARCIS (Netherlands)

    Koppelman, S.J.

    1995-01-01

    Protein S is a vitamin K-dependent nonenzymatic anticoagulant protein that acts as a cofactor to activated protein C. Recently it was shown that protein S inhibits the prothrombinase reaction independent of activated protein C. In this study, we show that protein S can also inhibit the intrinsic

  7. Inhibition of the intrinsic factor X activating complex by protein S: evidence for a specific binding of protein S to factor VIII

    NARCIS (Netherlands)

    Koppelman, S.J.

    1995-01-01

    Protein S is a vitamin K-dependent nonenzymatic anticoagulant protein that acts as a cofactor to activated protein C. Recently it was shown that protein S inhibits the prothrombinase reaction independent of activated protein C. In this study, we show that protein S can also inhibit the intrinsic fac

  8. Levels of intrinsic coagulation factors and the risk of myocardial infarction among men: opposite and synergistic effects of factors XI and XII

    NARCIS (Netherlands)

    Doggen, Catharina Jacoba Maria; Rosendaal, Frits R.; Meijers, Joost C.M.

    2006-01-01

    The role of the intrinsic coagulation system on the risk of myocardial infarction is unclear. In the Study of Myocardial Infarctions Leiden (SMILE) that included 560 men younger than age 70 with a first myocardial infarction and 646 control subjects, we investigated the risk of myocardial infarction

  9. Sasang Medical Perspectives on Viral Immunity: A Discussion of Intrinsic, Constitutionally Related Factors in Disease Onset and Resistance

    Directory of Open Access Journals (Sweden)

    Gary Wagman

    2017-02-01

    Full Text Available There remain more questions than answers regarding the manifestation of certain diseases, such as Ebola, in some otherwise healthy individuals but not in others. Sasang medicine offers a possible clue to solving this mystery by introducing a constitutionally based, intrinsic approach to determining disease susceptibility. The Sasang constitution is identified by a detailed examination of inherent physiological and psychological traits that are likely, but not yet, to be associated with specific genetic patterns. Hence, it is anticipated that after further examination, the Sasang model will contribute to the advancement of medical research and treatment by establishing genetically traceable psychological and physiological traits that contribute to, or offer protection against, various diseases. To progress along this journey, additional research involving Sasang-based organ-associated emotions and inherent emotional/physiological inclinations is warranted. This study presents an argument in favor of additionally examining constitutionally specific disease components related to viral epidemiology.

  10. Analyzing the microfoundations of human violence in the DRC - intrinsic and extrinsic rewards and the prediction of appetitive aggression

    OpenAIRE

    Haer, Roos; Banholzer, Lilli; Elbert, Thomas; Weierstall, Roland

    2013-01-01

    BackgroundCivil wars are characterized by intense forms of violence, such as torture, maiming and rape. Political scientists suggest that this form of political violence is fostered through the provision of particular intrinsic and extrinsic rewards to combatants. In the field of psychology, the perpetration of this kind of cruelty is observed to be positively linked to appetitive aggression. Over time, combatants start to enjoy the fights and even the perpetration of atrocities. In this stud...

  11. Analyzing the microfoundations of human violence in the DRC : intrinsic and extrinsic rewards and the prediction of appetitive aggression

    OpenAIRE

    Haer, Roos; Banholzer, Lilli; Elbert, Thomas; Weierstall, Roland

    2013-01-01

    BackgroundCivil wars are characterized by intense forms of violence, such as torture, maiming and rape. Political scientists suggest that this form of political violence is fostered through the provision of particular intrinsic and extrinsic rewards to combatants. In the field of psychology, the perpetration of this kind of cruelty is observed to be positively linked to appetitive aggression. Over time, combatants start to enjoy the fights and even the perpetration of atrocities. In this stud...

  12. Human factors engineering program review model

    Energy Technology Data Exchange (ETDEWEB)

    1994-07-01

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

  13. Architecture of human translation initiation factor 3.

    Science.gov (United States)

    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.

  14. Extrinsic and intrinsic factors impacting on the retention of older rural healthcare workers in the north Victorian public sector: a qualitative study.

    Science.gov (United States)

    Warburton, Jeni; Moore, Melissa L; Clune, Samantha J; Hodgkin, Suzanne P

    2014-01-01

    Workforce shortages in Australia's healthcare system, particularly across rural areas, are well documented. Future projections suggest that as the healthcare workforce ages and retires, there is an urgent need for strategies to retain older skilled employees. Very few qualitative studies, with theoretical underpinning, have focused on the retention of older rural nurses and allied healthcare workers. This study aimed to address these gaps in research knowledge. This qualitative study is phase 2 of a large mixed-methods study to determine the factors that impact on the retention of older rural healthcare workers across northern Victoria, Australia. The initial phase, drawing on the effort-reward imbalance model found high levels of imbalance across a large sample of this population. The present study builds on these findings to explore in more depth the organisational (extrinsic) and individual/social (intrinsic) factors associated with retention. A purposeful stratified sample was drawn from participants at the survey phase (phase 1) and invited to take part in a semistructured telephone interview. A diverse group of 17 rural healthcare workers (nurses and allied health) aged 55 years or more, employed in the north Victorian public sector, were interviewed. The data were transcribed and later analysed thematically and inductively. Data were categorised into extrinsic and intrinsic factors that influenced their decisions to remain in their roles or leave employment. The main extrinsic factors included feeling valued by the organisation, workload pressures, feeling valued by clients, collegial support, work flexibility, and a lack of options. The main intrinsic factors included intention to retire, family influences, work enjoyment, financial influences, health, sense of self, and social input. Given the noted imbalance between (high) effort and (low) reward among participants overall, strategies were identified for improving this balance, and in turn, the retention

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

    Science.gov (United States)

    Hirata, Y; Orth, D N

    1979-04-01

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

  16. Humanism as a common factor in psychotherapy.

    Science.gov (United States)

    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.

  17. Review of EPRI Nuclear Human Factors Program

    Energy Technology Data Exchange (ETDEWEB)

    Hanes, L.F.; O`Brien, J.F. [Electric Power Research Institute, Palo Alto, CA (United States)

    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.

  18. New evidence for intrinsic blood coagulation in chickens.

    Science.gov (United States)

    Doerr, J A; Hamilton, P B

    1981-01-01

    Coagulation of blood in chickens is considered the result of an extrinsic clotting system initiated, as in mammals, by tissue thromboplastin released from injured tissues. Blood coagulation in mammals depends principally on an intrinsic mechanism in which thromboplastin is generated from blood itself. Only a negligible role, if any, has been ascribed to an intrinsic system in chickens. A reevaluation of intrinsic coagulation in chickens was undertaken in this study. Whole blood of chickens was found to clot over 30% faster when contacted by suitable surface activators such as kaolin or glass than when such contact was omitted. Plasma recalcification times were significantly (P less than .02) shortened by contact activators. Clotting functions were measurable both by partial thromboplastin time and activated partial thromboplastin time, tests that bypass extrinsic factors. Intrinsic thromboplastin could be generated from dilute whole chicken blood although at a slower rate than that reported for human blood. Modification of whole blood thromboplastin generation techniques permitted measurement of activities that seem analogous to human intrinsic factors VIII and IX but not XI or XII. These data provide evidence of a functioning intrinsic clotting mechanism in chickens. A complete description and role for this mechanism remains to be defined.

  19. Human factors quantification via boundary identification of flight performance margin

    Directory of Open Access Journals (Sweden)

    Yang Changpeng

    2014-08-01

    Full Text Available A systematic methodology including a computational pilot model and a pattern recognition method is presented to identify the boundary of the flight performance margin for quantifying the human factors. The pilot model is proposed to correlate a set of quantitative human factors which represent the attributes and characteristics of a group of pilots. Three information processing components which are influenced by human factors are modeled: information perception, decision making, and action execution. By treating the human factors as stochastic variables that follow appropriate probability density functions, the effects of human factors on flight performance can be investigated through Monte Carlo (MC simulation. Kernel density estimation algorithm is selected to find and rank the influential human factors. Subsequently, human factors are quantified through identifying the boundary of the flight performance margin by the k-nearest neighbor (k-NN classifier. Simulation-based analysis shows that flight performance can be dramatically improved with the quantitative human factors.

  20. Sasang Medical Perspectives on Viral Immunity: A Discussion of Intrinsic, Constitutionally Related Factors in Disease Onset and Resistance.

    Science.gov (United States)

    Wagman, Gary

    2017-01-01

    There remain more questions than answers regarding the manifestation of certain diseases, such as Ebola, in some otherwise healthy individuals but not in others. Sasang medicine offers a possible clue to solving this mystery by introducing a constitutionally based, intrinsic approach to determining disease susceptibility. The Sasang constitution is identified by a detailed examination of inherent physiological and psychological traits that are likely, but not yet, to be associated with specific genetic patterns. Hence, it is anticipated that after further examination, the Sasang model will contribute to the advancement of medical research and treatment by establishing genetically traceable psychological and physiological traits that contribute to, or offer protection against, various diseases. To progress along this journey, additional research involving Sasang-based organ-associated emotions and inherent emotional/physiological inclinations is warranted. This study presents an argument in favor of additionally examining constitutionally specific disease components related to viral epidemiology. Copyright © 2016 Medical Association of Pharmacopuncture Institute. Published by Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

    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…

  3. Human factors and ergonomics for primary care.

    Science.gov (United States)

    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.

  4. Organizational crisis management: the human factor.

    Science.gov (United States)

    Lewis, Gerald

    2005-01-01

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

  5. Angelica polymorpha Maxim Induces Apoptosis of Human SH-SY5Y Neuroblastoma Cells by Regulating an Intrinsic Caspase Pathway.

    Science.gov (United States)

    Rahman, Md Ataur; Bishayee, Kausik; Huh, Sung-Oh

    2016-02-01

    Angelica polymorpha Maxim root extract (APRE) is a popular herbal medicine used for treating stomachache, abdominal pain, stomach ulcers, and rheumatism; however the effect of APRE on cancer cells has not yet been explored. Here, we examined APRE cytotoxicity seen on target neuroblastoma cells (NB) using cell viability assays, DAPI visualization of fragmented DNA, and Western blotting analysis of candidate signaling pathways involved in proliferation and apoptosis. We demonstrated that APRE reduced cell viability in NB to a greater extent than in fibroblast cells. In addition, we found that APRE could inhibit the three classes of MAPK proteins and could also down-regulate the PI3K/AKT/GSK-3β activity all being relevant for proliferation and survival. APRE could also up-regulate Bax expression and down-regulate Bcl-2 and Mcl-1. With APRE treatment, depolarization of mitochondria membrane potential and activation of caspase-3 was demonstrated in the SH-SY5Y cells. We could not found increased activity of death receptor and caspase-8 as markers of the extrinsic apoptosis pathway for the APRE treated cells. In presence of a caspase-3 siRNA and a pan-caspase inhibitor, APRE could not reduce the viability of NB cells to a significant degree. So we predicted that with APRE, the intrinsic pathway was solely responsible for inducing apoptosis as we also showed that the non-caspase autophagy pathway or ER stress-ROS mediated pathways were not involved. These findings demonstrate that an intrinsic mitochondria-mediated apoptosis pathway mediates the apoptotic effects of APRE on SH-SY5Y cells, and that APRE shows promise as a novel agent for neuroblastoma therapy.

  6. Reorganizing the intrinsic functional architecture of the human primary motor cortex during rest with non-invasive cortical stimulation.

    Directory of Open Access Journals (Sweden)

    Rafael Polanía

    Full Text Available The primary motor cortex (M1 is the main effector structure implicated in the generation of voluntary movements and is directly involved in motor learning. The intrinsic horizontal neuronal connections of M1 exhibit short-term and long-term plasticity, which is a strong substrate for learning-related map reorganization. Transcranial direct current stimulation (tDCS applied for few minutes over M1 has been shown to induce relatively long-lasting plastic alterations and to modulate motor performance. Here we test the hypothesis that the relatively long-lasting synaptic modification induced by tDCS over M1 results in the alteration of associations among populations of M1 neurons which may be reflected in changes of its functional architecture. fMRI resting-state datasets were acquired immediately before and after 10 minutes of tDCS during rest, with the anode/cathode placed over the left M1. For each functional dataset, grey-matter voxels belonging to Brodmann area 4 (BA4 were labelled and afterwards BA4 voxel-based synchronization matrices were calculated and thresholded to construct undirected graphs. Nodal network parameters which characterize the architecture of functional networks (connectivity degree, clustering coefficient and characteristic path-length were computed, transformed to volume maps and compared before and after stimulation. At the dorsolateral-BA4 region cathodal tDCS boosted local connectedness, while anodal-tDCS enhanced long distance functional communication within M1. Additionally, the more efficient the functional architecture of M1 was at baseline, the more efficient the tDCS-induced functional modulations were. In summary, we show here that it is possible to non-invasively reorganize the intrinsic functional architecture of M1, and to image such alterations.

  7. Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics--Fluoroquinolones.

    Science.gov (United States)

    Li, Qiming; Xie, Longxiang; Long, Quanxin; Mao, Jinxiao; Li, Hui; Zhou, Mingliang; Xie, Jianping

    2015-07-03

    Antibiotics resistance poses catastrophic threat to global public health. Novel insights into the underlying mechanisms of action will inspire better measures to control drug resistance. Fluoroquinolones are potent and widely prescribed broad-spectrum antibiotics. Bacterial protein degradation pathways represent novel druggable target for the development of new classes of antibiotics. Mycobacteria proteasome accessory factor C (pafC), a component of bacterial proteasome, is involved in fluoroquinolones resistance. PafC deletion mutants are hypersensitive to fluoroquinolones, including moxifloxacin, norfloxacin, ofloxacin, ciprofloxacin, but not to other antibiotics such as isoniazid, rifampicin, spectinomycin, chloramphenicol, capreomycin. This phenotype can be restored by complementation. The pafC mutant is hypersensitive to H2O2 exposure. The iron chelator (bipyridyl) and a hydroxyl radical scavenger (thiourea) can abolish the difference. The finding that pafC is a novel intrinsic selective resistance gene provided new evidence for the bacterial protein degradation pathway as druggable target for the development of new class of antibiotics.

  8. Physiological factors affecting intrinsic water use efficiency of potato clones within a dihaploid mapping population under well-watered and drought-stressed conditions

    DEFF Research Database (Denmark)

    Topbjerg, Henrik Bak; Kaminski, Kacper Piotr; Markussen, Bo

    2014-01-01

    Optimizing crops water use is essential for ensuring food production under future climate scenarios. Therefore, new cultivars that are capable of maintaining production under limited water resource are needed. This study screened for clonal differences in intrinsic water use efficiency (WUEi...... isotope composition (δ15N) in the leaf biomass, but did not relate to stomatal conductance (gs) and carbon isotope composition (δ13C) in the leaf biomass. An was found to correlate significantly with leaf nitrogen concentration ([N]leaf) and chlorophyll content index (CCI) under WW. Leaf abscisic acid...... concentration did not correspond to the changes in gs, indicating that other factors might have been involved in controlling gs among the different clones. Collectively, the clonal differences in WUEi were attributed mainly to the variation in An, which in turn was influenced by plant N metabolism. Clones...

  9. The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein.

    Science.gov (United States)

    Kozyraki, R; Fyfe, J; Kristiansen, M; Gerdes, C; Jacobsen, C; Cui, S; Christensen, E I; Aminoff, M; de la Chapelle, A; Krahe, R; Verroust, P J; Moestrup, S K

    1999-06-01

    Cubilin is the intestinal receptor for the endocytosis of intrinsic factor-vitamin B12. However, several lines of evidence, including a high expression in kidney and yolk sac, indicate it may have additional functions. We isolated apolipoprotein A-I (apoA-I), the main protein of high-density lipoprotein (HDL), using cubilin affinity chromatography. Surface plasmon resonance analysis demonstrated a high-affinity binding of apoA-I and HDL to cubilin, and cubilin-expressing yolk sac cells showed efficient 125I-HDL endocytosis that could be inhibited by IgG antibodies against apoA-I and cubilin. The physiological relevance of the cubilin-apoA-I interaction was further emphasized by urinary apoA-I loss in some known cases of functional cubilin deficiency. Therefore, cubilin is a receptor in epithelial apoA-I/HDL metabolism.

  10. Rapid Prototyping and the Human Factors Engineering Process

    Science.gov (United States)

    2016-08-29

    Rapid prototyping and the human factors • • engineering process David Beevis* and Gaetan St Denist *Senior Human Factors Engineer , Defence and...factors engineering analyses. Therefore, an investigation of the use of the V APS virtual prototyping system was carried out in five organizations. The...factors engineering (HFE) process re- commended for the development of human-machine systems is based on a series of increasin¥ly detailed analyses of

  11. Constitutively active signaling by the G protein βγ-subunit mediates intrinsically increased phosphodiesterase-4 activity in human asthmatic airway smooth muscle cells.

    Directory of Open Access Journals (Sweden)

    Aihua Hu

    Full Text Available Signaling by the Gβγ subunit of Gi protein, leading to downstream c-Src-induced activation of the Ras/c-Raf1/MEK-ERK1/2 signaling pathway and its upregulation of phosphodiesterase-4 (PDE4 activity, was recently shown to mediate the heightened contractility in proasthmatic sensitized isolated airway smooth muscle (ASM, as well as allergen-induced airway hyperresponsiveness and inflammation in an in vivo animal model of allergic asthma. This study investigated whether cultured human ASM (HASM cells derived from asthmatic donor lungs exhibit constitutively increased PDE activity that is attributed to intrinsically upregulated Gβγ signaling coupled to c-Src activation of the Ras/MEK/ERK1/2 cascade. We show that, relative to normal cells, asthmatic HASM cells constitutively exhibit markedly increased intrinsic PDE4 activity coupled to heightened Gβγ-regulated phosphorylation of c-Src and ERK1/2, and direct co-localization of the latter with the PDE4D isoform. These signaling events and their induction of heightened PDE activity are acutely suppressed by treating asthmatic HASM cells with a Gβγ inhibitor. Importantly, along with increased Gβγ activation, asthmatic HASM cells also exhibit constitutively increased direct binding of the small Rap1 GTPase-activating protein, Rap1GAP, to the α-subunit of Gi protein, which serves to cooperatively facilitate Ras activation and, thereby, enable enhanced Gβγ-regulated ERK1/2-stimulated PDE activity. Collectively, these data are the first to identify that intrinsically increased signaling via the Gβγ subunit, facilitated by Rap1GAP recruitment to the α-subunit, mediates the constitutively increased PDE4 activity detected in asthmatic HASM cells. These new findings support the notion that interventions targeted at suppressing Gβγ signaling may lead to novel approaches to treat asthma.

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

    Science.gov (United States)

    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…

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

    Science.gov (United States)

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

    2010-01-01

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

  14. In vitro platinum drug chemosensitivity of human cervical squamous cell carcinoma cell lines with intrinsic and acquired resistance to cisplatin.

    OpenAIRE

    Mellish, K. J.; Kelland, L R; Harrap, K. R.

    1993-01-01

    The platinum drug chemosensitivity of five human cervical squamous cell carcinoma cell lines (HX/151, HX/155, HX/156, HX/160 and HX/171) derived from previously untreated patients has been determined. Compared to our data obtained previously using human ovarian carcinoma cell lines, all five lines were relatively resistant to cisplatin, carboplatin, iproplatin and tetraplatin. One of the lines (HX/156) was exceptionally sensitive to the novel platinum (IV) ammine/amine dicarboxylates JM216 [b...

  15. Inhalation devices and patient interface: human factors.

    Science.gov (United States)

    Leiner, Stefan; Parkins, David; Lastow, Orest

    2015-03-01

    The development of any inhalation product that does not consider the patient needs will fail. The needs of the patients must be identified and aligned with engineering options and physical laws to achieve a robust and intuitive-to-use inhaler. A close interaction between development disciplines and real-use evaluations in clinical studies or in human factor studies is suggested. The same holds true when a marketed product needs to be changed. Caution is warranted if an inhaler change leads to a change in the way the patient handles the device. Finally, the article points out potential problems if many inhaler designs are available. Do they confuse the patients? Can patients recall the correct handling of each inhaler they use? How large is the risk that different inhaler designs pose to the public health? The presentations were given at the Orlando Inhalation Conference: Approaches in International Regulation co-organised by the University of Florida and the International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS) in March 2014.

  16. Human Factors Aspects of Operating Small Reactors

    Energy Technology Data Exchange (ETDEWEB)

    OHara, J.M.; Higgins, J.; Deem, R. (BNL); Xing, J.; DAgostino, A. (NRC)

    2010-11-07

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

  17. Standardized Kaempferia parviflora Extract Inhibits Intrinsic Aging Process in Human Dermal Fibroblasts and Hairless Mice by Inhibiting Cellular Senescence and Mitochondrial Dysfunction

    Directory of Open Access Journals (Sweden)

    Ji-Eun Park

    2017-01-01

    Full Text Available Intrinsic skin aging is a complex biological phenomenon mainly caused by cellular senescence and mitochondrial dysfunction. This study evaluated the inhibitory effect of Kaempferia parviflora Wall ex. Baker ethanol extract (KPE on H2O2-stimulated cellular senescence and mitochondrial dysfunction both in vitro and in vivo. KPE significantly increased cell growth and suppressed senescence-associated β-galactosidase activation. KPE inhibited the expression of cell-cycle inhibitors (p53, p21, p16, and pRb and stimulated the expression of cell-cycle activators (E2F1 and E2F2. H2O2-induced hyperactivation of the phosphatidylinositol 3-kinase/protein kinase B (AKT signaling pathway was suppressed by KPE through regulated expression of forkhead box O3a (FoxO3a and mammalian target of rapamycin (mTOR. KPE attenuated inflammatory mediators (interleukin-6 (IL-6, IL-8, nuclear factor kappa B (NF-κB, and cyclooxygenase-2 (COX-2 and increased the mRNA expression of PGC-1α, ERRα, NRF1, and Tfam, which modulate mitochondrial biogenesis and function. Consequently, reduced ATP levels and increased ROS level were also reversed by KPE treatment. In hairless mice, KPE inhibited wrinkle formation, skin atrophy, and loss of elasticity by increasing the collagen and elastic fibers. The results indicate that KPE prevents intrinsic aging process in hairless mice by inhibiting cellular senescence and mitochondrial dysfunction, suggesting its potential as a natural antiaging agent.

  18. Standardized Kaempferia parviflora Extract Inhibits Intrinsic Aging Process in Human Dermal Fibroblasts and Hairless Mice by Inhibiting Cellular Senescence and Mitochondrial Dysfunction.

    Science.gov (United States)

    Park, Ji-Eun; Woo, Seon Wook; Kim, Mi-Bo; Kim, Changhee; Hwang, Jae-Kwan

    2017-01-01

    Intrinsic skin aging is a complex biological phenomenon mainly caused by cellular senescence and mitochondrial dysfunction. This study evaluated the inhibitory effect of Kaempferia parviflora Wall ex. Baker ethanol extract (KPE) on H2O2-stimulated cellular senescence and mitochondrial dysfunction both in vitro and in vivo. KPE significantly increased cell growth and suppressed senescence-associated β-galactosidase activation. KPE inhibited the expression of cell-cycle inhibitors (p53, p21, p16, and pRb) and stimulated the expression of cell-cycle activators (E2F1 and E2F2). H2O2-induced hyperactivation of the phosphatidylinositol 3-kinase/protein kinase B (AKT) signaling pathway was suppressed by KPE through regulated expression of forkhead box O3a (FoxO3a) and mammalian target of rapamycin (mTOR). KPE attenuated inflammatory mediators (interleukin-6 (IL-6), IL-8, nuclear factor kappa B (NF-κB), and cyclooxygenase-2 (COX-2)) and increased the mRNA expression of PGC-1α, ERRα, NRF1, and Tfam, which modulate mitochondrial biogenesis and function. Consequently, reduced ATP levels and increased ROS level were also reversed by KPE treatment. In hairless mice, KPE inhibited wrinkle formation, skin atrophy, and loss of elasticity by increasing the collagen and elastic fibers. The results indicate that KPE prevents intrinsic aging process in hairless mice by inhibiting cellular senescence and mitochondrial dysfunction, suggesting its potential as a natural antiaging agent.

  19. Differential sensitivity to methylated DNA by ETS-family transcription factors is intrinsically encoded in their DNA-binding domains.

    Science.gov (United States)

    Stephens, Dominique C; Poon, Gregory M K

    2016-10-14

    Transactivation by the ETS family of transcription factors, whose members share structurally conserved DNA-binding domains, is variably sensitive to methylation of their target genes. The mechanism by which DNA methylation controls ETS proteins remains poorly understood. Uncertainly also pervades the effects of hemi-methylated DNA, which occurs following DNA replication and in response to hypomethylating agents, on site recognition by ETS proteins. To address these questions, we measured the affinities of two sequence-divergent ETS homologs, PU.1 and Ets-1, to DNA sites harboring a hemi- and fully methylated CpG dinucleotide. While the two proteins bound unmethylated DNA with indistinguishable affinity, their affinities to methylated DNA are markedly heterogeneous and exhibit major energetic coupling between the two CpG methylcytosines. Analysis of simulated DNA and existing co-crystal structures revealed that hemi-methylation induced non-local backbone and groove geometries that were not conserved in the fully methylated state. Indirect readout of these perturbations was differentially achieved by the two ETS homologs, with the distinctive interfacial hydration in PU.1/DNA binding moderating the inhibitory effects of DNA methylation on binding. This data established a biophysical basis for the pioneering properties associated with PU.1, which robustly bound fully methylated DNA, but not Ets-1, which was substantially inhibited. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  20. The intrinsic abundance ratio and X-factor of CO isotopologues in L1551 shielded from FUV photodissociation

    CERN Document Server

    Lin, Sheng-Jun; Hara, Chihomi; Lai, Shih-Ping; Nakamura, Fumitaka; Sugitani, Koji; Kawabe, Ryohei; Kitamura, Yoshimi; Yoshida, Atsushi; Tatei, Hidefumi; Akashi, Toshiya; Higuchi, Aya E; Tsukagoshi, Takashi

    2016-01-01

    L1551 is chosen because it is relatively isolated in the Taurus molecular cloud shielded from FUV photons, providing an ideal environment for studying the target properties. Our observations cover ~40'x40' with resolution ~30", which are the maps with highest spatial dynamical range to date. We derive the X(13CO)/X(C18O) value on the sub-parsec scales in the range of ~3-27 with a mean value of 8.0+-2.8. Comparing to the visual extinction map derived from the Herschel observations, we found that the abundance ratio reaches its maximum at low Av (i.e., Av ~ 1-4mag), and decreases to the typical solar system value of 5.5 inside L1551 MC. The high X(13CO)/X(C18O) value at the boundary of the cloud is most likely due to the selective FUV photodissociation of C18O. This is in contrast with Orion-A where its internal OB stars keep the abundance ratio at a high level greater than ~10. In addition, we explore the variation of the X-factor, because it is an uncertain but widely used quantity in extragalactic studies. W...

  1. Discussing the Effective Factors on Maintenance of Human Resources

    OpenAIRE

    Bahare Shahriari

    2016-01-01

    In this research, the author has elaborated on detection of effective factors on maintenance and retention of human resources. Since human resources are the most resources for obtaining competitive advantage, it is essential to pay attention to different dimensions of human resources management. One of these dimensions is retention of human resources. Factors such as providing correct and valid information at the time of recruitment, assigning tasks based on competence, existence of a clear c...

  2. Human milk composition: nutrients and bioactive factors.

    Science.gov (United States)

    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.

  3. Pattern of hormone receptors and human epidermal growth factor ...

    African Journals Online (AJOL)

    2015-02-05

    Feb 5, 2015 ... Key words: Breast cancer, human epidermal growth factor receptor 2/neu, immunohistochemistry, ... therapy.[6‑8] Of all these prognostic and predictive factors, ... one of the biggest private medical laboratories in Nigeria.

  4. 1-Benzyl-2-Phenylbenzimidazole (BPB, a Benzimidazole Derivative, Induces Cell Apoptosis in Human Chondrosarcoma through Intrinsic and Extrinsic Pathways

    Directory of Open Access Journals (Sweden)

    Ju-Fang Liu

    2012-12-01

    Full Text Available In this study, we investigated the anticancer effects of a new benzimidazole derivative, 1-benzyl-2-phenyl -benzimidazole (BPB, in human chondrosarcoma cells. BPB-mediated apoptosis was assessed by the MTT assay and flow cytometry analysis. The in vivo efficacy was examined in a JJ012 xenograft model. Here we found that BPB induced apoptosis in human chondrosarcoma cell lines (JJ012 and SW1353 but not in primary chondrocytes. BPB induced upregulation of Bax, Bad and Bak, downregulation of Bcl-2, Bid and Bcl-XL and dysfunction of mitochondria in chondrosarcoma. In addition, BPB also promoted cytosolic releases AIF and Endo G. Furthermore, it triggered extrinsic death receptor-dependent pathway, which was characterized by activating Fas, FADD and caspase-8. Most importantly, animal studies revealed a dramatic 40% reduction in tumor volume after 21 days of treatment. Thus, BPB may be a novel anticancer agent for the treatment of chondrosarcoma.

  5. An improvement of the applicability of human factors guidelines for coping with human factors issues in nuclear power plants

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y. H.; Lee, J. Y. [KAERI, Taejon (Korea, Republic of)

    2003-07-01

    Human factors have been well known as one of the key factors to the system effectiveness as well as the efficiency and safety of nuclear power plants(NPPs). Human factors engineering(HFE) are included in periodic safety review(PSR) on the existing NPPs and the formal safety assessment for the new ones. However, HFE for NPPs is still neither popular in practice nor concrete in methodology. Especially, the human factors guidelines, which are the most frequent form of human factors engineering in practice, reveal the limitations in their applications. We discuss the limitations and their casual factors found in human factors guidelines in order to lesson the workload of HFE practitioners and to improve the applicability of human factors guidelines. According to the purposes and the phases of HFE for NPPs, more selective items and specified criteria should be prepared carefully in the human factors guidelines for the each HFE applications in practice. These finding on the human factors guidelines can be transferred to the other HFE application field, such as military, aviation, telecommunication, HCI, and product safety.

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

    DEFF Research Database (Denmark)

    Hollnagel, Erik

    2014-01-01

    Discussions of the possible future of Human factors/ergonomics (HFE) usually take the past for granted in the sense that the future of HFE is assumed to be more of the same. This paper argues that the nature of work in the early 2010s is so different from the nature of work when HFE was formulated...

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

    Science.gov (United States)

    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.

  8. NAS Human Factors Safety Research Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — This laboratory conducts an integrated program of research on the relationship of factors concerning individuals, work groups, and organizations as employees perform...

  9. Expression of P-gp, MRP, LRP, GST-π and TopoIIα and intrinsic resistance in human lung cancer cell lines.

    Science.gov (United States)

    Wang, Jiarui; Zhang, Jinhui; Zhang, Lichuan; Zhao, Long; Fan, Sufang; Yang, Zhonghai; Gao, Fei; Kong, Ying; Xiao, Gary Guishan; Wang, Qi

    2011-11-01

    This study aimed to determine the relationship between the endogenous levels of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), lung resistance-related protein (LRP), glutathione-s-transferase-π (GST‑π) and topoisomerase IIα (TopoIIα) and intrinsic drug resistance in four human lung cancer cell lines, SK-MES-1, SPCA-1, NCI-H-460 and NCI-H-446, of different histological types. The expression of P-gp, MRP, LRP, GST-π and TopoIIα was measured by immunofluorescence, Western blotting and RT-PCR. Drug resistance to cisplatin, doxorubicin and VP-16 was determined using MTT assays. The correlation between expression of the resistance-related proteins and their roles in the resistance to drugs in these cancer cell lines was analyzed. We found that the endogenous levels of P-gp, MRP, LRP, GST-π and TopoIIα in the four cell lines varied. The level of GST-π in the SK-MES-1 cells was the highest, whereas the level of P-gp in the SPCA-1 cells was the lowest. The chemoresistance to cisplatin, doxorubicin and VP-16 in the four cell lines was different. The SPCA-1 cell line was most resistance to cisplatin; SK-MES-1 was most resistance to VP-16; whereas SK-MES-1 was most sensitive to doxorubicin. There was a positive correlation between GST-π expression and resistance to cisplatin, between TopoIIα expression and resistance to VP-16; and a negative correlation was noted between TopoIIα expression and resistance to doxorubicin. In summary, the endogenous expression of P-gp, MRP, LRP, GST-π and TopoIIα was different in the four human lung cancer cell lines of different histological types, and this variance may be associated with the variation in chemosensitivity to cisplatin, doxorubicin and VP-16. Among the related proteins, GST-π may be useful for the prediction of the intrinsic resistance to cisplatin, whereas TopoIIα may be useful to predict resistance to doxorubicin and VP-16 in human lung cancer cell lines.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  11. Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics - Fluoroquinolones

    Science.gov (United States)

    Li, Qiming; Xie, Longxiang; Long, Quanxin; Mao, Jinxiao; Li, Hui; Zhou, Mingliang; Xie, Jianping

    2015-01-01

    Antibiotics resistance poses catastrophic threat to global public health. Novel insights into the underlying mechanisms of action will inspire better measures to control drug resistance. Fluoroquinolones are potent and widely prescribed broad-spectrum antibiotics. Bacterial protein degradation pathways represent novel druggable target for the development of new classes of antibiotics. Mycobacteria proteasome accessory factor C (pafC), a component of bacterial proteasome, is involved in fluoroquinolones resistance. PafC deletion mutants are hypersensitive to fluoroquinolones, including moxifloxacin, norfloxacin, ofloxacin, ciprofloxacin, but not to other antibiotics such as isoniazid, rifampicin, spectinomycin, chloramphenicol, capreomycin. This phenotype can be restored by complementation. The pafC mutant is hypersensitive to H2O2 exposure. The iron chelator (bipyridyl) and a hydroxyl radical scavenger (thiourea) can abolish the difference. The finding that pafC is a novel intrinsic selective resistance gene provided new evidence for the bacterial protein degradation pathway as druggable target for the development of new class of antibiotics. PMID:26139381

  12. Synergy of aromatic residues and phosphoserines within the intrinsically disordered DNA-binding inhibitory elements of the Ets-1 transcription factor.

    Science.gov (United States)

    Desjardins, Geneviève; Meeker, Charles A; Bhachech, Niraja; Currie, Simon L; Okon, Mark; Graves, Barbara J; McIntosh, Lawrence P

    2014-07-29

    The E26 transformation-specific (Ets-1) transcription factor is autoinhibited by a conformationally disordered serine-rich region (SRR) that transiently interacts with its DNA-binding ETS domain. In response to calcium signaling, autoinhibition is reinforced by calmodulin-dependent kinase II phosphorylation of serines within the SRR. Using mutagenesis and quantitative DNA-binding measurements, we demonstrate that phosphorylation-enhanced autoinhibition requires the presence of phenylalanine or tyrosine (ϕ) residues adjacent to the SRR phosphoacceptor serines. The introduction of additional phosphorylated Ser-ϕ-Asp, but not Ser-Ala-Asp, repeats within the SRR dramatically reinforces autoinhibition. NMR spectroscopic studies of phosphorylated and mutated SRR variants, both within their native context and as separate trans-acting peptides, confirmed that the aromatic residues and phosphoserines contribute to the formation of a dynamic complex with the ETS domain. Complementary NMR studies also identified the SRR-interacting surface of the ETS domain, which encompasses its positively charged DNA-recognition interface and an adjacent region of neutral polar and nonpolar residues. Collectively, these studies highlight the role of aromatic residues and their synergy with phosphoserines in an intrinsically disordered regulatory sequence that integrates cellular signaling and gene expression.

  13. Monitoring Ras Interactions with the Nucleotide Exchange Factor Son of Sevenless (Sos) Using Site-specific NMR Reporter Signals and Intrinsic Fluorescence.

    Science.gov (United States)

    Vo, Uybach; Vajpai, Navratna; Flavell, Liz; Bobby, Romel; Breeze, Alexander L; Embrey, Kevin J; Golovanov, Alexander P

    2016-01-22

    The activity of Ras is controlled by the interconversion between GTP- and GDP-bound forms partly regulated by the binding of the guanine nucleotide exchange factor Son of Sevenless (Sos). The details of Sos binding, leading to nucleotide exchange and subsequent dissociation of the complex, are not completely understood. Here, we used uniformly (15)N-labeled Ras as well as [(13)C]methyl-Met,Ile-labeled Sos for observing site-specific details of Ras-Sos interactions in solution. Binding of various forms of Ras (loaded with GDP and mimics of GTP or nucleotide-free) at the allosteric and catalytic sites of Sos was comprehensively characterized by monitoring signal perturbations in the NMR spectra. The overall affinity of binding between these protein variants as well as their selected functional mutants was also investigated using intrinsic fluorescence. The data support a positive feedback activation of Sos by Ras·GTP with Ras·GTP binding as a substrate for the catalytic site of activated Sos more weakly than Ras·GDP, suggesting that Sos should actively promote unidirectional GDP → GTP exchange on Ras in preference of passive homonucleotide exchange. Ras·GDP weakly binds to the catalytic but not to the allosteric site of Sos. This confirms that Ras·GDP cannot properly activate Sos at the allosteric site. The novel site-specific assay described may be useful for design of drugs aimed at perturbing Ras-Sos interactions.

  14. Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin.

    Science.gov (United States)

    Kristiansen, M; Aminoff, M; Jacobsen, C; de La Chapelle, A; Krahe, R; Verroust, P J; Moestrup, S K

    2000-07-15

    Megaloblastic anemia 1 (MGA1) is an autosomal recessive disorder caused by the selective intestinal malabsorption of intrinsic factor (IF) and vitamin B(12)/cobalamin (Cbl) in complex. Most Finnish patients with MGA1 carry the disease-specific P1297L mutation (FM1) in the IF-B(12) receptor, cubilin. By site-directed mutagenesis, mammalian expression, and functional comparison of the purified wild-type and FM1 mutant forms of the IF-Cbl-binding cubilin region (CUB domains 5-8, amino acid 928-1386), we have investigated the functional implications of the P1297L mutation. Surface plasmon resonance analysis revealed that the P1297L substitution specifically increases the K(d) for IF-Cbl binding several-fold, largely by decreasing the association rate constant. In agreement with the binding data, the wild-type protein, but not the FM1 mutant protein, potently inhibits 37 degrees C uptake of iodine 125-IF-Cbl in cubilin-expressing epithelial cells. In conclusion, the data presented show a substantial loss in affinity of the FM1 mutant form of the IF-Cbl binding region of cubilin. This now explains the malabsorption of Cbl and Cbl-dependent anemia in MGA1 patients with the FM1 mutation. (Blood. 2000;96:405-409)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  16. Investigation of Intrinsic and External Factors Contributing to the Occurrence of Coal Bumps in the Mining Area of Western Beijing, China

    Science.gov (United States)

    Wang, Hongwei; Jiang, Yaodong; Xue, Sheng; Pang, Xufeng; Lin, Zhinan; Deng, Daixin

    2017-04-01

    An investigation has been made to relate the occurrence of coal bumps to specific geological and mining conditions to the mining area of western Beijing. This investigation demonstrates that the high frequency of coal bumps in this area is due to four localized conditions, namely intrinsic coal properties, the presence of overturned strata and thrust faults, high in situ stress and the extraction of coal from island mining faces. Laboratory tests of coal samples indicated that the coals have a short duration of dynamic fracture, high bursting energy and high elastic strain energy, indicating that the coal is intrinsically prone to the occurrence of coal bumps. This investigation has also revealed that there are overturned strata and well-developed large- and medium-scale thrust faults in this area, and the presence of these structures results in plastic flow, severe discontinuities, rapid changes in overburden thickness and dipping of the coal seams. Well-developed secondary fold structures are also present in the axes and limbs of the primary folds. The instability of thrust faults, in combination with large-scale intrusion of igneous rocks, is closely associated with sudden roof breaking and induces sharp variations in electromagnetic radiation (EMR) and micro-seismic signals, which could be used to help predict coal bumps. In situ stress tests in the mining area demonstrate that the maximum and minimum principal stresses are nearly horizontal and that the intermediate principal stress is approximately vertical. The in situ stress level in the area is higher than the average in the Beijing area, North China and mainland China. In addition to the presence of overturned strata and thrust faults and high in situ stress levels, another external factor contributing to the frequency of coal bumps is coal extraction from island mining faces in this area. Island mining faces experience intermittent mining-induced abutment stress when a fault exists at one side of the

  17. Influencing Factors of Rural Human Consumption in China

    Directory of Open Access Journals (Sweden)

    Jun LI

    2014-12-01

    Full Text Available The paper combines the social capital theory, the ordered choice model, and the case study in order to analyze the influence factors of the rural human consumption. The results show the presence of inverted U shape curve relation between human consumption amount and age. Human communication range, income, the highest single human consumption amount and the minimum amount, occupation, family population, the existing of human consumption capacity and the scope of the existing relationships between interpersonal relationship satisfaction and other factors on human consumption level has positive influence on human consumption level. Domestic researches on human behaviour are wide, but most of the studies are focused on the social, human, and psychological disciplines. For the origin of human consumption, scholars focus on four aspects like novelty, human or mutual needs. This research is based on field investigation conducted in Niuxintai village, Liaoning Province, in order to understand the current situation of the rural human consumption in China, and to explain the function and influencing factors of human consumption.

  18. Suggestion: Human Factor Based User Interface Design Tool

    OpenAIRE

    S.Q. Abbas,; Rizwan Beg; Shahnaz Fatima

    2011-01-01

    In this paper, we introduce HFBUIT, Human Factor based user interface tool that enables designers and engineers to create human factor based user interface. This tool will help the designer to utilize the knowledge about the user to configure the interface for different users, i.e. each user may have different skills, level of experience, or cognitive and physical disabilities. The tool makes it easy to knowhuman factors & to reduce the number of usability problems. HFBUIT can be used in real...

  19. The acute effect of bipolar radiofrequency energy thermal chondroplasty on intrinsic biomechanical properties and thickness of chondromalacic human articular cartilage.

    Science.gov (United States)

    Dutcheshen, Nicholas; Maerz, Tristan; Rabban, Patrick; Haut, Roger C; Button, Keith D; Baker, Kevin C; Guettler, Joseph

    2012-08-01

    Radio frequency energy (RFE) thermal chondroplasty has been a widely-utilized method of cartilage debridement in the past. Little is known regarding its effect on tissue mechanics. This study investigated the acute biomechanical effects of bipolar RFE treatment on human chondromalacic cartilage. Articular cartilage specimens were extracted (n = 50) from femoral condyle samples of patients undergoing total knee arthroplasty. Chondromalacia was graded with the Outerbridge classification system. Tissue thicknesses were measured using a needle punch test. Specimens underwent pretreatment load-relaxation testing using a spherical indenter. Bipolar RFE treatment was applied for 45 s and the indentation protocol was repeated. Structural properties were derived from the force-time data. Mechanical properties were derived using a fibril-reinforced biphasic cartilage model. Statistics were performed using repeated measures ANOVA. Cartilage thickness decreased after RFE treatment from a mean of 2.61 mm to 2.20 mm in Grade II, II-III, and III specimens (P resistance to shear and tension could be compromised due to removal of the superficial layer and decreased fibril modulus, RFE treatment increases matrix modulus and decreases tissue permeability which may restore the load- bearing capacity of the cartilage.

  20. Protein intrinsic disorder in Arabidopsis NAC transcription factors: transcriptional activation by ANAC013 and ANAC046 and their interactions with RCD1.

    Science.gov (United States)

    O'Shea, Charlotte; Kryger, Mikael; Stender, Emil G P; Kragelund, Birthe B; Willemoës, Martin; Skriver, Karen

    2015-01-15

    Protein ID (intrinsic disorder) plays a significant, yet relatively unexplored role in transcription factors (TFs). In the present paper, analysis of the transcription regulatory domains (TRDs) of six phylogenetically representative, plant-specific NAC [no apical meristem, ATAF (Arabidopsis transcription activation factor), cup-shaped cotyledon] TFs shows that the domains are present in similar average pre-molten or molten globule-like states, but have different patterns of order/disorder and MoRFs (molecular recognition features). ANAC046 (Arabidopsis NAC 046) was selected for further studies because of its simple MoRF pattern and its ability to interact with RCD1 (radical-induced cell death 1). Experiments in yeast and thermodynamic characterization suggest that its single MoRF region is sufficient for both transcriptional activation and interaction with RCD1. The remainder of the large regulatory domain is unlikely to contribute to the interaction, since the domain and truncations thereof have similar affinities for RCD1, which are also similar for ANAC013-RCD1 interactions. However, different enthalpic and entropic contributions to binding were revealed for ANAC046 and ANAC013, suggestive of differences in binding mechanisms. Although substitution of both hydrophobic and acidic residues of the ANAC046 MoRF region abolished binding, substitution of other residues, even with α-helix-breaking proline, was less disruptive. Together, the biophysical analyses suggest that RCD1-ANAC046 complex formation does not involve folding-upon-binding, but rather fuzziness or an unknown structure in ANAC046. We suggest that the ANAC046 regulatory domain functions as an entropic chain with a terminal hot spot interacting with RCD1. RCD1, a cellular hub, may be able to interact with many different TFs by exploiting their ID-based flexibility, as demonstrated for its interactions with ANAC046 and ANAC013.

  1. Gadolinium chloride elicits apoptosis in human osteosarcoma U-2 OS cells through extrinsic signaling, intrinsic pathway and endoplasmic reticulum stress.

    Science.gov (United States)

    Tsai, Yuh-Feng; Huang, Ching-Wen; Chiang, Jo-Hua; Tsai, Fuu-Jen; Hsu, Yuan-Man; Lu, Chi-Cheng; Hsiao, Chen-Yu; Yang, Jai-Sing

    2016-12-01

    Gadolinium (Gd) compounds are important as magnetic resonance imaging (MRI) contrast agents, and are potential anticancer agents. However, no report has shown the effect of gadolinium chloride (GdCl3) on osteosarcoma in vitro. The present study investigated the apoptotic mechanism of GdCl3 on human osteosarcoma U-2 OS cells. Our results indicated that GdCl3 significantly reduced cell viability of U-2 OS cells in a concentration-dependent manner. GdCl3 led to apoptotic cell shrinkage and DNA fragmentation in U-2 OS cells as revealed by morphologic changes and TUNEL staining. Colorimetric assay analyses also showed that activities of caspase-3, caspase-8, caspase-9 and caspase-4 occurred in GdCl3-treated U-2 OS cells. Pretreatment of cells with pan-caspase inhibitor (Z-VAD-FMK) and specific inhibitors of caspase-3/-8/-9 significantly reduced cell death caused by GdCl3. The increase of cytoplasmic Ca2+ level, ROS production and the decrease of mitochondria membrane potential (ΔΨm) were observed by flow cytometric analysis in U-2 OS cells after GdCl3 exposure. Western blot analyses demonstrated that the levels of Fas, FasL, cytochrome c, Apaf-1, GADD153 and GRP78 were upregulated in GdCl3-treated U-2 OS cells. In conclusion, death receptor, mitochondria-dependent and endoplasmic reticulum (ER) stress pathways contribute to GdCl3-induced apoptosis in U-2 OS cells. GdCl3 might have potential to be used in treatment of osteosarcoma patients.

  2. Actin filament-associated protein 1 (AFAP-1) is a key mediator in inflammatory signaling-induced rapid attenuation of intrinsic P-gp function in human brain capillary endothelial cells.

    Science.gov (United States)

    Hoshi, Yutaro; Uchida, Yasuo; Tachikawa, Masanori; Ohtsuki, Sumio; Terasaki, Tetsuya

    2017-01-23

    The purpose of this study was to identify regulatory molecule(s) involved in the inflammatory signaling-induced decrease in P-glycoprotein (P-gp) efflux function at the blood-brain barrier (BBB) that may occur in brain diseases. We confirmed that in vivo P-gp efflux activity at the BBB was decreased without any change in P-gp protein expression level in a mouse model of acute inflammation induced by 3 mg/kg lipopolysaccharide. In a human BBB model cell line (human brain capillary endothelial cells; hCMEC/D3), 1-h treatment with 10 ng/mL tumor necrosis factor-α (TNF-α; an inflammatory mediator) rapidly reduced P-gp efflux activity, but had no effect on P-gp protein expression level. To clarify the non-transcriptional mechanism that causes the decrease in intrinsic efflux activity of P-gp in acute inflammation, we applied comprehensive quantitative phosphoproteomics to compare hCMEC/D3 cells treated with TNF-α and vehicle (control). Actin filament-associated protein-1 (AFAP-1), MAPK1, and transcription factor AP-1 (AP-1) were significantly phosphorylated in TNF-α-treated cells, and were selected as candidate proteins. In validation experiments, knockdown of AFAP-1 expression blocked the reduction in P-gp efflux activity by TNF-α treatment, whereas inhibition of MAPK function or knockdown of AP-1 expression did not. Quantitative targeted absolute proteomics revealed that the reduction in P-gp activity by TNF-α did not require any change in P-gp protein expression levels in the plasma membrane. Our results demonstrate that AFAP-1 is a key mediator in the inflammatory signaling-induced, translocation-independent rapid attenuation of P-gp efflux activity in human brain capillary endothelial cells.

  3. Assessment factors for human health risk assessment: A discussion paper

    NARCIS (Netherlands)

    Vermeire, T.; Stevenson, H.; Pieters, M.N.; Rennen, M.; Slob, W.; Hakkert, B.C.

    1999-01-01

    The general goal of this discussion paper is to contribute toward the further harmonization of human health risk assessment. It first discusses the development of a formal, harmonized set of assessment factors. The status quo with regard to assessment factors is reviewed, that is, the type of factor

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

    Science.gov (United States)

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

    2014-12-05

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

  5. Use of Computers in Human Factors Engineering

    Science.gov (United States)

    1974-11-01

    SENSES (PHYSIOLOGY), THERMOPLASTIC RESINS, VISUAL ACUITY (U)R RESEARCH CONCERNS DETERMINATION OF THE INFORMATION PRESENTATION REQUIREMENTS OF HUMAN DATA...THE GEOMETRY OF THE wORK STATION, IS CURRENTLY BEING DEVELOPED. IT IS CALLED COMBIMAN, AN ACRONYM FOR COMPUTERIZED BIOMECHANICAL MAN- MODELo COMBIMAN

  6. Factors affecting transmission of mucosal human papillomavirus

    NARCIS (Netherlands)

    N.J. Veldhuijzen; P.J. Snijders; P. Reiss; C.J. Meijer; J.H. van de Wijgert

    2010-01-01

    Human papillomavirus (HPV) is the most common sexually transmitted infection. The effect of HPV on public health is especially related to the burden of anogenital cancers, most notably cervical cancer. Determinants of exposure to HPV are similar to those for most sexually transmitted infections, but

  7. Human Factors in the Management of Production

    DEFF Research Database (Denmark)

    Jensen, Per Langå; Alting, Leo

    2006-01-01

    challenges. Qualitative interviews with Danish stakeholders in the education of engineers (BA & MA) confirm the picture given in international literature. Therefore, the didactics concerning the ‘human factor’ in the curriculum on production management has to reflect these changes. This paper concludes...... with a proposal on essential issues to be addressed in the curriculum qualifying university candidates to production management....

  8. Alternative Control Technologies: Human Factors Issues

    Science.gov (United States)

    1998-10-01

    vertical vibration to the 29,4, 1980, pp 462-466. head and shoulders of seated men", Royal Aircraft Lee, J. M.; Chartier , V. L.; Hartmann, D. P.; Lee, G...Suarez, P. F., Rogers , S., K., Ruck, D. W., for Effective Human-Computer Interaction", 2nd edition, Arndt, C., and Kabrisky, M., "A facial feature

  9. Recent technology products from Space Human Factors research

    Science.gov (United States)

    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.

  10. The Human Factors of Sensor Fusion

    Science.gov (United States)

    2008-05-01

    humans tend to use a combination of deductive and inductive logic, as well as intuition and emotion to reach general conclusions; however, if...into a machine but only resulting in a warning or caution and not as the actual emotion felt by the observer. The element of fear induced by the...extract meaning from text or spoken language which is veiled by semantic features such as sarcasm or formalism that contain a very great amount of

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

    Science.gov (United States)

    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.

  12. Function of IHF in lambda DNA packaging. I. Identification of the strong binding site for integration host factor and the locus for intrinsic bending in cosB.

    Science.gov (United States)

    Xin, W; Feiss, M

    1993-03-20

    Integration host factor (IHF) plays an accessory role in lambda DNA packaging. IHF affects the interaction of the lambda DNA packaging protein, terminase, with cos, the site on lambda DNA at which terminase binds and introduces staggered nicks to generate cohesive ends of mature lambda chromosomes. cos includes cosB, the terminase binding site and cosN, the adjacent nicking site. cosB includes multiple binding sites for gpNu1, the small subunit of terminase, and an IHF binding site, I1. I1 contains two overlapping sequences, called I1A and I1B, that closely match the consensus sequence for IHF binding sites. The I1A sequence was determined to be the site of IHF binding by hydroxyl radical footprinting experiments. Comparison of the pattern of IHF-induced enhancements and diminishments at I1 with published patterns for IHF binding sites at the lambda attachment site identifies I1A as the IHF binding site at I1. The conclusion that I1A is the IHF binding site was confirmed by studies with DNA mutant in I1A. The I1A- mutation, consisting of three adjacent base-pair changes in I1A, abolished IHF binding. In contrast to the I1A- mutation, a mutation in I1B, also consisting of three adjacent base-pair changes, caused a reduction in the affinity of IHF for I1A, and caused a reduction in the magnitude of the net intrinsic bending of cos lambda.

  13. Studying risk factors associated with Human Leptospirosis

    Directory of Open Access Journals (Sweden)

    Ramachandra Kamath

    2014-01-01

    Full Text Available Background: Leptospirosis is one of the most under diagnosed and underreported disease in both developed and developing countries including India. It is established that environmental conditions and occupational habit of the individuals put them at risk of acquiring disease, which varies from community to community. Various seroprevalence studies across the world have documented emerging situation of this neglected tropical disease, but limited have probed to identify the risk factors, especially in India. Objectives: The objective of this study was to identify the environmental and occupational risk factors associated with the disease in Udupi District. Materials and Methods: This population-based case-control study was carried out in Udupi, a District in Southern India from April 2012 until August 2012. Udupi is considered to be endemic for Leptospirosis and reported 116 confirmed cases in the year 2011. Seventy of 116 laboratory confirmed cases and 140 sex matched neighborhood healthy controls participated in the study. A predesigned, semi-structured and validated questionnaire was used for data collection through house to house visit and observations were noted about environmental conditions. Univariate analysis followed by multivariate analysis (back ward conditional logistic regression was performed by using STATA version 9.2 (StataCorp, College Station, TX, USA to identify potential risk factors. Results: Occupational factors such as outdoor activities (matched odds ratio [OR] of 3.95, 95% confidence interval [CI]: 1.19-13.0, presence of cut or wound at body parts during work (matched OR: 4.88, CI: 1.83-13.02 and environmental factors such as contact with rodents through using the food materials ate by rat (matched OR: 4.29, CI: 1.45-12.73 and contact with soil or water contaminated with urine of rat (matched OR: 4.58, CI: 1.43-14.67 were the risk factors identified to be associated with disease. Conclusion: Leptospirosis is still

  14. Tumor Environmental Factors Glucose Deprivation and Lactic Acidosis Induce Mitotic Chromosomal Instability – An Implication in Aneuploid Human Tumors

    Science.gov (United States)

    Zhu, Chunpeng; Hu, Xun

    2013-01-01

    Mitotic chromosomal instability (CIN) plays important roles in tumor progression, but what causes CIN is incompletely understood. In general, tumor CIN arises from abnormal mitosis, which is caused by either intrinsic or extrinsic factors. While intrinsic factors such as mitotic checkpoint genes have been intensively studied, the impact of tumor microenvironmental factors on tumor CIN is largely unknown. We investigate if glucose deprivation and lactic acidosis – two tumor microenvironmental factors – could induce cancer cell CIN. We show that glucose deprivation with lactic acidosis significantly increases CIN in 4T1, MCF-7 and HCT116 scored by micronuclei, or aneuploidy, or abnormal mitosis, potentially via damaging DNA, up-regulating mitotic checkpoint genes, and/or amplifying centrosome. Of note, the feature of CIN induced by glucose deprivation with lactic acidosis is similar to that of aneuploid human tumors. We conclude that tumor environmental factors glucose deprivation and lactic acidosis can induce tumor CIN and propose that they are potentially responsible for human tumor aneuploidy. PMID:23675453

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

    Directory of Open Access Journals (Sweden)

    Hunziker S

    2010-01-01

    Full Text Available 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.

  16. Intrinsic Resistance to 5-Fluorouracil in a Brain Metastatic Variant of Human Breast Cancer Cell Line, MDA-MB-231BR.

    Science.gov (United States)

    Sagara, Atsunobu; Igarashi, Katsuhide; Otsuka, Maky; Karasawa, Takeshi; Gotoh, Noriko; Narita, Michiko; Kuzumaki, Naoko; Narita, Minoru; Kato, Yoshinori

    2016-01-01

    Although drug resistance is often observed in metastatic recurrence of breast cancer, little is known about the intrinsic drug resistance in such metastases. In the present study, we found, for the first time, that MDA-MB-231BR, a brain metastatic variant of a human breast cancer cell line, was refractory to treatment with 5-fluorouracil (5-FU) even without chronic drug exposure, compared to its parent cell line, MDA-MB-231, and a bone metastatic variant, MDA-MB-231SCP2. Both the mRNA and protein levels of COX-2 and BCL2A1 in MDA-MB-231BR were significantly higher than those in MDA-MB-231 or MDA-MB-231SCP2. Neither the COX-2 inhibitor celecoxib nor the NF-κB inhibitor BAY11-7082 could sensitize MDA-MB-231BR to 5-FU, indicating that COX-2 plays little, if any, role in the resistance of MDA-MB-231BR to 5-FU. Although BCL2-family inhibitor ABT-263 failed to sensitize MDA-MB-231BR to 5-FU at a dose at which ABT-263 is considered to bind to BCL2, BCL2-xL, and BCL2-w, but not to BCL2A1, ABT-263 did sensitize MDA-MB-231BR to 5-FU to a level comparable to that in MDA-MB-231 at a dose of 5 μM, at which ABT-263 may disrupt intracellular BCL2A1 protein interactions. More importantly, BCL2A1 siRNA sensitized MDA-MB-231BR to 5-FU, whereas the overexpression of BCL2A1 conferred 5-FU-resistance on MDA-MB-231. These results indicate that BCL2A1 is a key contributor to the intrinsic 5-FU-resistance in MDA-MB-231BR. It is interesting to note that the drug sensitivity of MDA-MB-231BR was distinct from that of MDA-MB-231SCP2 even though they have the same origin (MDA-MB-231). Further investigations pertinent to the present findings may provide valuable insight into the breast cancer brain metastasis.

  17. Human factors survey of advanced instrumentation and controls

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Human Factors Engineering Aspects of Modifications in Control Room Modernization

    Energy Technology Data Exchange (ETDEWEB)

    Hugo, Jacques; Clefton, Gordon; Joe, Jeffrey

    2017-06-01

    This report describes the basic aspects of control room modernization projects in the U.S. nuclear industry and the need for supplementary guidance on the integration of human factors considerations into the licensing and regulatory aspects of digital upgrades. The report pays specific attention to the integration of principles described in NUREG-0711 (Human Factors Engineering Program Review Model) and how supplementary guidance can help to raise general awareness in the industry regarding the complexities of control room modernization projects created by many interdependent regulations, standards and guidelines. The report also describes how human factors engineering principles and methods provided by various resources and international standards can help in navigating through the process of licensing digital upgrades. In particular, the integration of human factors engineering guidance and requirements into the process of licensing digital upgrades can help reduce uncertainty related to development of technical bases for digital upgrades that will avoid the introduction of new failure modes.

  19. Factors likely to enhance mycotoxin introduction into the human diet ...

    African Journals Online (AJOL)

    Factors likely to enhance mycotoxin introduction into the human diet through maize in Kenya. ... African Journal of Food, Agriculture, Nutrition and Development ... are no strict regulations that impose limits on the concentration of mycotoxins in ...

  20. An Integrated Simulation System for Human Factors Study

    CERN Document Server

    Wang, Ying; Bennis, Fouad; Chablat, Damien

    2007-01-01

    It has been reported that virtual reality can be a useful tool for ergonomics study. The proposed integrated simulation system aims at measuring operator's performance in an interactive way for 2D control panel design. By incorporating some sophisticated virtual reality hardware/software, the system allows natural human-system and/or human-human interaction in a simulated virtual environment; enables dynamic objective measurement of human performance; and evaluates the quality of the system design in human factors perspective based on the measurement. It can also be for operation training for some 2D control panels.

  1. Advanced Human Factors Engineering Tool Technologies.

    Science.gov (United States)

    1987-03-20

    the mail and telephone surveys. The authors would also like to extend a special thanks to Mr. David Rose of the Naval Air Development Center for his...ADVANCED NUNAN FACTORS ENGINEERING TOOL TECHNOLOGIES 3/3 (U) CARLON ASSOCIATES INC FAIRFAX Yff S A FLEGER ET AL. UNCLRS 20 NAR B? DARI5-BS-C-NO64 WIL...34" ".--: :’-...2,,. ,..:,.- ,’-"-’:"- "’-::"-,2 ., ..,," ,.- ..’.-.-.’.-,-. : .....v. _ *’--..., ...-- ,,. - -.; , :¢ 4., 5 5 lPeter laines Mr. David M. Ilarrah

  2. Human factors assessment mechanical compression tools

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, C. [BC Research Inc., Vancouver, BC (Canada)

    1999-09-01

    The design and use of mechanical compression tools in electrical distribution functions were examined from the point of view of effects of design and use of tools on human operators. Various alternative tools such as manual compression tools, battery operated tools, wedge pressure tools, hydraulic tools, and insulating piercing connectors were also examined for purposes of comparison. Results of the comparative assessment were summarized and a tool satisfaction ratings table was produced for Burndy MD6, Huskie-Robo (REC 258) and Ampact (small) tools, rating level of effort, fatigue experienced, tool mass, force required to crimp, ease of use, comfort while using the tool, maneuverability, and overall satisfaction. Both the battery operated tool as well as the wedge pressure tool have been found to have ergonomic advantages over the mechanical compression tool.

  3. Development of human factors design review guidelines(II)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea)

    1998-06-01

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: 25. Human Factors Engineering Program Review Model and 26. Review Criteria for Human Factors Aspects of Advanced Controls and Instrumentation, which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents of NUREG-0711. We also computerized the Korean version of NUREG-0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm systems. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994. (author). 11 refs., 2 figs., 2 tabs.

  4. Development of human factors design review guidelines(III)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Oh, In Suk; Suh, Sang Moon; Lee, Hyun Chul [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1999-02-15

    The objective of this study is to develop human factors engineering program review guidelines and alarm system review guidelines in order to resolve the two major technical issues: '25, human factors engineering program review model' and '26, review criteria for human factors aspects of advanced controls and instrumentation', which are related to the development of human factors safety regulation guides being performed by KINS. For the development of human factors program review guidelines, we made a Korean version of NUREG-0711 and added our comments by considering Korean regulatory situation and reviewing the reference documents NUREG--0711, additional comments, and selected portion of the reference documents for the developer of safety regulation guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guides in KINS to see the contents comparatively at a glance and use them easily. For the development of alarm system review guidelines, we made a Korean version of NUREG/CR-6105, which was published by NRC in 1994 as a guideline document for the human factors review of alarm system. Then we will update the guidelines by reviewing the literature related to alarm design published after 1994.

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

    Science.gov (United States)

    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 Factors of Queuing: A Library Circulation Model.

    Science.gov (United States)

    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)

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

    Science.gov (United States)

    1991-01-01

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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  10. A comprehensive resource of interacting protein regions for refining human transcription factor networks.

    Directory of Open Access Journals (Sweden)

    Etsuko Miyamoto-Sato

    Full Text Available Large-scale data sets of protein-protein interactions (PPIs are a valuable resource for mapping and analysis of the topological and dynamic features of interactome networks. The currently available large-scale PPI data sets only contain information on interaction partners. The data presented in this study also include the sequences involved in the interactions (i.e., the interacting regions, IRs suggested to correspond to functional and structural domains. Here we present the first large-scale IR data set obtained using mRNA display for 50 human transcription factors (TFs, including 12 transcription-related proteins. The core data set (966 IRs; 943 PPIs displays a verification rate of 70%. Analysis of the IR data set revealed the existence of IRs that interact with multiple partners. Furthermore, these IRs were preferentially associated with intrinsic disorder. This finding supports the hypothesis that intrinsically disordered regions play a major role in the dynamics and diversity of TF networks through their ability to structurally adapt to and bind with multiple partners. Accordingly, this domain-based interaction resource represents an important step in refining protein interactions and networks at the domain level and in associating network analysis with biological structure and function.

  11. The productivity from a human perspective: Dimensions and factors

    Directory of Open Access Journals (Sweden)

    Mirza Marvel Cequea

    2011-11-01

    Full Text Available Purpose: The purpose of this paper is to review the literature, for both theoretical foundations and empirical research, in order to establish relationships between the variables related to human factors and their impact on productivity.Design/methodology/approach: The strategy employed corresponds to a descriptive non-experimental design, which is the establishment of three criteria for the literature review, in order to narrow down the topic to research works relating productivity with the human factor. This was investigated in databases and journals dealing with related topics, in addition to consulting doctoral theses and published books concerning the influence of human factors on productivity. About 250 papers which were considered the most relevant for the research were selected.Findings:  As a result of this exploration the classification of the factors in two dimensions that are manifested in people when they act in organizations was highlighted: the psychological and the psychosocial dimension. Human factors included in these dimensions are: individual factors (motivation, skills, job satisfaction, identification, commitment and involvement with the organization, group factors (participation, cohesion and management conflict and organizational factors (organizational culture, organizational climate and leadership. All these factors have an impact on the productivity of the organization and are addressed in this research.Originality/value: The selected variables were used to formulate a model that incorporates the human factors identified and considers the phenomenon in a comprehensive manner. It will be addressed through multivariate analysis, with the possible application of structural equations in order to assess the causal relationships that may exist between factors and productivity.

  12. 2014 Space Human Factors Engineering Standing Review Panel

    Science.gov (United States)

    Steinberg, Susan

    2014-01-01

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

  13. Human Factors in Nuclear Power Engineering in Polish Conditions

    Directory of Open Access Journals (Sweden)

    Agnieszka Kaczmarek-Kacprzak

    2014-09-01

    Full Text Available The paper “Human factors in nuclear power engineering in Polish conditions” focuses on analysis of dynamics of preparing Polish society to build fi rst nuclear power plant in XXI century in Poland. Authors compare experience from constructing nuclear power plant Sizewell B (Great Britain and Sizewell C, which is in preparation phase with polish nuclear power program. Paper includes aspects e.g. of creating nuclear safety culture and social opinion about investment. Human factors in nuclear power engineering are as well important as relevant economical and technical factors, but very often negligible. In Poland where history about Czarnobyl is still alive, and social opinion is created on emotions after accident in Fukushima, human factors are crucial and should be under comprehensive consideration.

  14. Design of intrinsically safe power supply

    Institute of Scientific and Technical Information of China (English)

    LI Rui-jin; JIN Lin

    2012-01-01

    Aiming to make a high power direct current supply safely used in coal mine production,this paper made a deep research on characteristics of intrinsically safe power supply,using the mathematical model established according to coal mine intrinsic safety standards.It provides theory support for the application of high power intrinsically safe power supply.The released energy of output short circuit of switch power supply,and the close related factors that influence the biggest output short-circuit spark discharge energy are the theoretical basis of the power supply.It is shown how to make a high power intrinsically safe power supply using the calculated values in the mathematical model,and take values from intrinsically safe requirements parameters scope,then this theoretical calculation value can be developed as the ultimate basis for research of the power supply.It gets the identification method of intrinsically safe from mathematics model of intrinsically safe power supply characteristics study,which solves the problem of theory and application of designing different power intrinsically safe power supply,and designs a kind of high power intrinsically safe power supply through this method.

  15. Effectiveness of human factors simulator; Eficiencia del simulador de factores humanos

    Energy Technology Data Exchange (ETDEWEB)

    Moragas, F.

    2015-07-01

    En 2011, ANAV started the exploitation of the Human Factors Simulator installed in TECNATOM Training Center located in L'Hospital de L'Infant Tarragona. AVAN's Strategic Plan includes the Action Plan for the improvement of human behavior. The plan includes improving the efficiency of the efficiency of the human factors simulator. It is proposed to improve the efficiency into two different terms: winning effectiveness in modeling behaviors, and interweaving the activities in the simulator with the actual strategy of promoting Safety culture and human behaviour. (Author)

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

    Science.gov (United States)

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

    2009-04-23

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

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

    Science.gov (United States)

    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.

  18. 77 FR 3500 - VTECH Communications, Inc., Human Factors Department, Beaverton, OR; Amended Certification...

    Science.gov (United States)

    2012-01-24

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

  19. Human factor engineering applied to nuclear power plant design

    Energy Technology Data Exchange (ETDEWEB)

    Manrique, A. [TECNATOM SA, BWR General Electric Business Manager, Madrid (Spain); Valdivia, J.C. [TECNATOM SA, Operation Engineering Project Manager, Madrid (Spain); Jimenez, A. [TECNATOM SA, Operation Engineering Div. Manager, Madrid (Spain)

    2001-07-01

    For the design and construction of new nuclear power plants as well as for maintenance and operation of the existing ones new man-machine interface designs and modifications are been produced. For these new designs Human Factor Engineering must be applied the same as for any other traditional engineering discipline. Advantages of implementing adequate Human Factor Engineering techniques in the design of nuclear reactors have become not only a fact recognized by the majority of engineers and operators but also an explicit requirement regulated and mandatory for the new designs of the so called advanced reactors. Additionally, the big saving achieved by a nuclear power plant having an operating methodology which significantly decreases the risk of operating errors makes it necessary and almost vital its implementation. The first step for this is preparing a plan to incorporate all the Human Factor Engineering principles and developing an integral design of the Instrumentation and Control and Man-machine interface systems. (author)

  20. Automotive Technology and Human Factors Research: Past, Present, and Future

    Directory of Open Access Journals (Sweden)

    Motoyuki Akamatsu

    2013-01-01

    Full Text Available This paper reviews the history of automotive technology development and human factors research, largely by decade, since the inception of the automobile. The human factors aspects were classified into primary driving task aspects (controls, displays, and visibility, driver workspace (seating and packaging, vibration, comfort, and climate, driver’s condition (fatigue and impairment, crash injury, advanced driver-assistance systems, external communication access, and driving behavior. For each era, the paper describes the SAE and ISO standards developed, the major organizations and conferences established, the major news stories affecting vehicle safety, and the general social context. The paper ends with a discussion of what can be learned from this historical review and the major issues to be addressed. A major contribution of this paper is more than 180 references that represent the foundation of automotive human factors, which should be considered core knowledge and should be familiar to those in the profession.

  1. Human factors engineering plan for reviewing nuclear plant modernization programs

    Energy Technology Data Exchange (ETDEWEB)

    O' Hara, John; Higgins, James [Brookhaven National Laboratory, Upton, NY (United States)

    2004-12-01

    The Swedish Nuclear Power Inspectorate reviews the human factors engineering (HFE) aspects of nuclear power plants (NPPs) involved in the modernization of the plant systems and control rooms. The purpose of a HFE review is to help ensure personnel and public safety by verifying that accepted HFE practices and guidelines are incorporated into the program and nuclear power plant design. Such a review helps to ensure the HFE aspects of an NPP are developed, designed, and evaluated on the basis of a structured top-down system analysis using accepted HFE principles. The review addresses eleven HFE elements: HFE Program Management, Operating Experience Review, Functional Requirements Analysis and Allocation, Task Analysis, Staffing, Human Reliability Analysis, Human-System Interface Design, Procedure Development, Training Program Development, Human Factors Verification and Validation, and Design Implementation.

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

    Energy Technology Data Exchange (ETDEWEB)

    O`Hara, J.; Stubler, W. [Brookhaven National Lab., Upton, NY (United States). Dept. of Advanced Technology; Kramer, J. [Nuclear Regulatory Commission, Washington, DC (United States). Office of Nuclear Regulatory Research

    1998-03-01

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

  3. Intrinsically photosensitive retinal ganglion cell function in relation to age: A pupillometric study in humans with special reference to the age-related optic properties of the lens

    Directory of Open Access Journals (Sweden)

    Herbst Kristina

    2012-04-01

    Full Text Available Abstract Background The activity of melanopsin containing intrinsically photosensitive ganglion retinal cells (ipRGC can be assessed by a means of pupil responses to bright blue (appr.480 nm light. Due to age related factors in the eye, particularly, structural changes of the lens, less light reaches retina. The aim of this study was to examine how age and in vivo measured lens transmission of blue light might affect pupil light responses, in particular, mediated by the ipRGC. Methods Consensual pupil responses were explored in 44 healthy subjects aged between 26 and 68 years. A pupil response was recorded to a continuous 20 s light stimulus of 660 nm (red or 470 nm (blue both at 300 cd/m2 intensity (14.9 and 14.8 log photons/cm2/s, respectively. Additional recordings were performed using four 470 nm stimulus intensities of 3, 30, 100 and 300 cd/m2. The baseline pupil size was measured in darkness and results were adjusted for the baseline pupil and gender. The main outcome parameters were maximal and sustained pupil contraction amplitudes and the postillumination response assessed as area under the curve (AUC over two time-windows: early (0–10 s after light termination and late (10–30 s after light termination. Lens transmission was measured with an ocular fluorometer. Results The sustained pupil contraction and the early poststimulus AUC correlated positively with age (p = 0.02, p = 0.0014, respectively for the blue light stimulus condition only. The maximal pupil contraction amplitude did not correlate to age either for bright blue or red light stimulus conditions. Lens transmission decreased linearly with age (p 2 light (p = 0.02. Conclusions Age did not reduce, but rather enhance pupil responses mediated by ipRGC. The age related decrease of blue light transmission led to similar results, however, the effect of age was greater on these pupil responses than that of the lens transmission. Thus there must

  4. 人凝血因子Ⅸ的研究进展%Research progress in human coagulation factor

    Institute of Scientific and Technical Information of China (English)

    韩静静; 杨忠东

    2013-01-01

    Human coagulation factor Ⅸ (FⅨ) is a zymogen of a vitamin K-dependent serine protease that plays an important role in the intrinsic blood coagulation cascade.Deficiency or dysfunction of FⅨ can result in hemophilia B.This article reviews gene and protein structures of FⅨ as well as research status of FⅨ therapy for hemophilia B.%人凝血因子Ⅸ(human coagulation factor Ⅸ,FⅨ)是一种维生素K依赖性丝氨酸蛋白酶原,在内源性凝血级联反应中起重要作用.FⅨ缺乏或功能异常会导致血友病B.此文综述了FⅨ的基因和蛋白结构,以及FⅨ用于血友病B治疗的研究现状.

  5. Human Factors and Habitability Challenges for Mars Missions

    Science.gov (United States)

    Whitmore, Mihriban

    2015-01-01

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

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    R. L. Boring

    2007-06-01

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

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

    Science.gov (United States)

    Holubec, Keith; Connolly, Janis

    2010-01-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    IMKER, F.W.

    1999-06-30

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Henriksen, K.; Kaye, R.D.; Jones, R. [Hughes Training, Inc., Falls Church, VA (United States); Morisseau, D.S.; Serig, D.L. [Nuclear Regulatory Commission, Washington, DC (United States). Div. of Systems Technology

    1995-07-01

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

  14. Single cycle structure-based humanization of an anti-nerve growth factor therapeutic antibody.

    Directory of Open Access Journals (Sweden)

    Sonia Covaceuszach

    Full Text Available Most forms of chronic pain are inadequately treated by present therapeutic options. Compelling evidence has accumulated, demonstrating that Nerve Growth Factor (NGF is a key modulator of inflammatory and nociceptive responses, and is a promising target for the treatment of human pathologies linked to chronic and inflammatory pain. There is therefore a growing interest in the development of therapeutic molecules antagonising the NGF pathway and its nociceptor sensitization actions, among which function-blocking anti-NGF antibodies are particularly relevant candidates.In this respect, the rat anti-NGF αD11 monoclonal antibody (mAb is a potent antagonist, able to effectively antagonize rodent and human NGF in a variety of in vitro and in vivo systems. Here we show that mAb αD11 displays a significant analgesic effect in two different models of persistent pain in mice, with a remarkable long-lasting activity. In order to advance αD11 mAb towards its clinical application in man, anti-NGF αD11 mAb was humanized by applying a novel single cycle strategy based on the a priori experimental determination of the crystal and molecular structure of the parental Fragment antigen-binding (Fab. The humanized antibody (hum-αD11 was tested in vitro and in vivo, showing that the binding mode and the NGF neutralizing biological activities of the parental antibody are fully preserved, with even a significant affinity improvement. The results firmly establish hum-αD11 as a lead candidate for clinical applications in a therapeutic area with a severe unmet medical need. More generally, the single-cycle structure-based humanization method represents a considerable improvement over the standard humanization methods, which are intrinsically empirical and require several refinement cycles.

  15. Single Cycle Structure-Based Humanization of an Anti-Nerve Growth Factor Therapeutic Antibody

    Science.gov (United States)

    Covaceuszach, Sonia; Marinelli, Sara; Krastanova, Ivet; Ugolini, Gabriele; Pavone, Flaminia; Lamba, Doriano; Cattaneo, Antonino

    2012-01-01

    Most forms of chronic pain are inadequately treated by present therapeutic options. Compelling evidence has accumulated, demonstrating that Nerve Growth Factor (NGF) is a key modulator of inflammatory and nociceptive responses, and is a promising target for the treatment of human pathologies linked to chronic and inflammatory pain. There is therefore a growing interest in the development of therapeutic molecules antagonising the NGF pathway and its nociceptor sensitization actions, among which function-blocking anti-NGF antibodies are particularly relevant candidates. In this respect, the rat anti-NGF αD11 monoclonal antibody (mAb) is a potent antagonist, able to effectively antagonize rodent and human NGF in a variety of in vitro and in vivo systems. Here we show that mAb αD11 displays a significant analgesic effect in two different models of persistent pain in mice, with a remarkable long-lasting activity. In order to advance αD11 mAb towards its clinical application in man, anti-NGF αD11 mAb was humanized by applying a novel single cycle strategy based on the a priori experimental determination of the crystal and molecular structure of the parental Fragment antigen-binding (Fab). The humanized antibody (hum-αD11) was tested in vitro and in vivo, showing that the binding mode and the NGF neutralizing biological activities of the parental antibody are fully preserved, with even a significant affinity improvement. The results firmly establish hum-αD11 as a lead candidate for clinical applications in a therapeutic area with a severe unmet medical need. More generally, the single-cycle structure-based humanization method represents a considerable improvement over the standard humanization methods, which are intrinsically empirical and require several refinement cycles. PMID:22403636

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

    Science.gov (United States)

    Hollnagel, Erik

    2014-01-01

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

  17. Personalizing Sample Databases with Facebook Information to Increase Intrinsic Motivation

    Science.gov (United States)

    Marzo, Asier; Ardaiz, Oscar; Sanz de Acedo, María Teresa; Sanz de Acedo, María Luisa

    2017-01-01

    Motivation is fundamental for students to achieve successful and complete learning. Motivation can be extrinsic, i.e., driven by external rewards, or intrinsic, i.e., driven by internal factors. Intrinsic motivation is the most effective and must be inspired by the task at hand. Here, a novel strategy is presented to increase intrinsic motivation…

  18. Comparative genomics of human stem cell factor (SCF

    Directory of Open Access Journals (Sweden)

    Moein Dehbashi

    2017-03-01

    Full Text Available Stem cell factor (SCF is a critical protein with key roles in the cell such as hematopoiesis, gametogenesis and melanogenesis. In the present study a comparative analysis on nucleotide sequences of SCF was performed in Humanoids using bioinformatics tools including NCBI-BLAST, MEGA6, and JBrowse. Our analysis of nucleotide sequences to find closely evolved organisms with high similarity by NCBI-BLAST tools and MEGA6 showed that human and Chimpanzee (Pan troglodytes were placed into the same cluster. By using JBrowse, we found that SCF in Neanderthal had a single copy number similar to modern human and partly conserved nucleotide sequences. Together, the results approved the gene flow and genetics similarity of SCF among human and P. troglodytes. This may suggest that during evolution, SCF gene transferred partly intact either on the basis of sequence or function from the same ancestors to P. troglodytes, the ancient human like Neanderthal, and then to the modern human.

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

    Science.gov (United States)

    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.

  20. Klotho is a serum factor related to human aging

    Institute of Scientific and Technical Information of China (English)

    肖能明; 张焱明; 郑权; 顾军

    2004-01-01

    Background Does klotho (KL) protein exist in human serum, and is there any correlation between KL protein in serum with human aging? In order to answer those questions, we identified KL protein in human serum and established the correlation between KL protein in human serum and aging.Methods We prepared a polyclonal antibody against human KL protein that was able to recognize the C-terminal of human secreted KL protein. Western blot and enzyme-linked immunosorbent assay (ELISA) were used to identify KL protein in human serum.Results In Western blot, the antibody specifically recognized a 60-kD KL protein in both human and mice serum. The population aged from 0 to 91 years screened by ELISA revealed that the level of serum KL declined while age increased, though each individual level was variable and that the trend of decreasing in serum KL had no difference in sex.Conclusion Our data suggest that KL is a serum factor related to human aging.

  1. Intrinsic-Density Functionals

    CERN Document Server

    Engel, J

    2006-01-01

    The Hohenberg-Kohn theorem and Kohn-Sham procedure are extended to functionals of the localized intrinsic density of a self-bound system such as a nucleus. After defining the intrinsic-density functional, we modify the usual Kohn-Sham procedure slightly to evaluate the mean-field approximation to the functional, and carefully describe the construction of the leading corrections for a system of fermions in one dimension with a spin-degeneracy equal to the number of particles N. Despite the fact that the corrections are complicated and nonlocal, we are able to construct a local Skyrme-like intrinsic-density functional that, while different from the exact functional, shares with it a minimum value equal to the exact ground-state energy at the exact ground-state intrinsic density, to next-to-leading order in 1/N. We briefly discuss implications for real Skyrme functionals.

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

    Science.gov (United States)

    Moore, Dave; Barnard, Tim

    2012-12-01

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

  3. Glycosaminoglycans affect the interaction of human plasma kallikrein with plasminogen, factor XII and inhibitors

    Directory of Open Access Journals (Sweden)

    Gozzo A.J.

    2003-01-01

    Full Text Available Human plasma kallikrein, a serine proteinase, plays a key role in intrinsic blood clotting, in the kallikrein-kinin system, and in fibrinolysis. The proteolytic enzymes involved in these processes are usually controlled by specific inhibitors and may be influenced by several factors including glycosaminoglycans, as recently demonstrated by our group. The aim of the present study was to investigate the effect of glycosaminoglycans (30 to 250 µg/ml on kallikrein activity on plasminogen and factor XII and on the inhibition of kallikrein by the plasma proteins C1-inhibitor and antithrombin. Almost all available glycosaminoglycans (heparin, heparan sulfate, bovine and tuna dermatan sulfate, chondroitin 4- and 6-sulfates reduced (1.2 to 3.0 times the catalytic efficiency of kallikrein (in a nanomolar range on the hydrolysis of plasminogen (0.3 to 1.8 µM and increased (1.9 to 7.7 times the enzyme efficiency in factor XII (0.1 to 10 µM activation. On the other hand, heparin, heparan sulfate, and bovine and tuna dermatan sulfate improved (1.2 to 3.4 times kallikrein inhibition by antithrombin (1.4 µM, while chondroitin 4- and 6-sulfates reduced it (1.3 times. Heparin and heparan sulfate increased (1.4 times the enzyme inhibition by the C1-inhibitor (150 nM.

  4. SafetyNet. Human factors safety training on the Internet

    DEFF Research Database (Denmark)

    Hauland, G.; Pedrali, M.

    2002-01-01

    This report describes user requirements to an Internet based distance learning system of human factors training, i.e. the SafetyNet prototype, within the aviation (pilots and air traffic control), maritime and medical domains. User requirements totraining have been elicited through 19 semi...

  5. Improving human performance: Industry factors influencing the ability to perform

    Directory of Open Access Journals (Sweden)

    Güera Massyn Romo

    2013-03-01

    Full Text Available Learning interventions and new technologies that aim to improve human performance must take cognisance of industry factors inhibiting human performance. The dynamic and fast pace nature of the Information and Communication Technologies (ICT and the engineering industries do not lend themselves to proper skills planning and management. These industries experience real skills gaps, to some of which they contribute by themselves. This study reports on these performance-inhibiting factors such as the underutilisation of available skills, tolerance for individual preferences, and dynamically, and informally refining a role objective while an employee is occupying a certain role. The important professional skills required by individuals to cope with these real life factors are also explored in the skills gaps management context. Moreover, these industries need a profile they refer to as Special Forces, which denotes a high calibre of worker that possesses well-developed professional skills whilst having advanced technical expertise and sufficient experience. This resource profile is required largely due to the poor management of human resource processes in practice and the current reported lack of adequate skills. Furthermore, this study refers to the recent lack of a working definition for these Special Forces leading to the omitted active development of these profiles in industry today, which appears to become a key human performance inhibiting factor.

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

    Energy Technology Data Exchange (ETDEWEB)

    Greitzer, Frank L.; Dauenhauer, Peter M.; Wierks, Tamara G.; Podmore, Robin

    2009-04-01

    This report describes initial human factors evaluation of four visualization tools (Graphical Contingency Analysis, Force Directed Graphs, Phasor State Estimator and Mode Meter/ Mode Shapes) developed by PNNL, and proposed test plans that may be implemented to evaluate their utility in scenario-based experiments.

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

    Science.gov (United States)

    Lane, Kenneth E.; Richardson, Michael D.

    1993-01-01

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

  8. A Virtual Campus Based on Human Factor Engineering

    Science.gov (United States)

    Yang, Yuting; Kang, Houliang

    2014-01-01

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

  9. Neuroscience in ergonomics and human factors research and practice

    NARCIS (Netherlands)

    Erp, J.B.F. van; Brouwer, A.M.

    2013-01-01

    This article explores the possible application of neuroscientific knowledge in human factors research and pratice. Can this knowledge be implemented to improve the design and evaluation of systems and functional environments? Or - to take it one step further - could it bring about the integration of

  10. Human factors in organizational design and management VI

    NARCIS (Netherlands)

    Vink, P.; Koningsveld, E.A.P.; Dhondt, S.

    1998-01-01

    This book contains proceedings of the Sixth International Symposium on Human Factors in Organizational Design and Management held in The Hague, The Netherlands, August 19-22, 1998. The Symposium was sponsored jointly by the International Ergonomics Society, the Dutch Ergonomics Society, NIA TNO and

  11. A Virtual Campus Based on Human Factor Engineering

    Science.gov (United States)

    Yang, Yuting; Kang, Houliang

    2014-01-01

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

  12. Human factors issues of tactice displays for military environments

    NARCIS (Netherlands)

    Erp, J.B.F. van; Self, B.P.

    2008-01-01

    The overall goal of this chapter is to give the reader insights into the human factors issues related to the use of tactile displays. Torso-mounted displays, which are particularly suited for direction and orientation cues, are emphasized. First, perceptual issues relevant to tactile stimulation are

  13. Human factors in organizational design and management VI

    NARCIS (Netherlands)

    Vink, P.; Koningsveld, E.A.P.; Dhondt, S.

    1998-01-01

    This book contains proceedings of the Sixth International Symposium on Human Factors in Organizational Design and Management held in The Hague, The Netherlands, August 19-22, 1998. The Symposium was sponsored jointly by the International Ergonomics Society, the Dutch Ergonomics Society, NIA TNO and

  14. Immunolocalization of transforming growth factor alpha in normal human tissues

    DEFF Research Database (Denmark)

    Christensen, M E; Poulsen, Steen Seier

    1996-01-01

    the distribution of the growth factor in a broad spectrum of normal human tissues. Indirect immunoenzymatic staining methods were used. The polypeptide was detected with a polyclonal as well as a monoclonal antibody. The polyclonal and monoclonal antibodies demonstrated almost identical immunoreactivity. TGF...

  15. Integrating human factors and artificial intelligence in the development of human-machine cooperation

    NARCIS (Netherlands)

    Maanen, P.P. van; Lindenberg, J.; Neericx, M.A.

    2005-01-01

    Increasing machine intelligence leads to a shift from a mere interactive to a much more complex cooperative human-machine relation requiring a multidisciplinary development approach. This paper presents a generic multidisciplinary cognitive engineering method CE+ for the integration of human factors

  16. A Keyword Analysis for Human Resource Management Factors

    Directory of Open Access Journals (Sweden)

    Muhammed Kürşad ÖZLEN

    2014-05-01

    Full Text Available With the constant increasing in technology and education, with development of multinational corporations and frequent changes in economic status and structures, Human Resources become the most crucial, the most reliable and necessary department. Moreover, in many companies, Human Resource Department is the most important department. The main purpose of this research is to mark off top rated factors related with Human Resource Management by analyzing all the abstracts of the published papers of a Human Resource Management journal for the period between the first issue of 2005 and the first issue of 2013. We identified the most frequent categories of the articles during this analyzed period. The literature is reviewed according to the identified factors related to Human Resource Management. If the keywords about Human Resources (35,7 % is not considered, it is observed that the researches, for the selected period, have organizational approach (39,2 % (Management, organizational strategy, organizational performance, organizational culture, contextual issues, technical issues and location and from the individual approach (24,4 % (Individual performance, training and education, employee rights, and behavioral issues. Furthermore, it is also observed that the researchers (a mainly give importance to the practice more than the theory and (b consider the organization more than the individual.

  17. An Illumination Modeling System for Human Factors Analyses

    Science.gov (United States)

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

    2002-01-01

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

  18. Multiscale factors affecting human attitudes toward snow leopards and wolves.

    Science.gov (United States)

    Suryawanshi, Kulbhushansingh R; Bhatia, Saloni; Bhatnagar, Yash Veer; Redpath, Stephen; Mishra, Charudutt

    2014-12-01

    The threat posed by large carnivores to livestock and humans makes peaceful coexistence between them difficult. Effective implementation of conservation laws and policies depends on the attitudes of local residents toward the target species. There are many known correlates of human attitudes toward carnivores, but they have only been assessed at the scale of the individual. Because human societies are organized hierarchically, attitudes are presumably influenced by different factors at different scales of social organization, but this scale dependence has not been examined. We used structured interview surveys to quantitatively assess the attitudes of a Buddhist pastoral community toward snow leopards (Panthera uncia) and wolves (Canis lupus). We interviewed 381 individuals from 24 villages within 6 study sites across the high-elevation Spiti Valley in the Indian Trans-Himalaya. We gathered information on key explanatory variables that together captured variation in individual and village-level socioeconomic factors. We used hierarchical linear models to examine how the effect of these factors on human attitudes changed with the scale of analysis from the individual to the community. Factors significant at the individual level were gender, education, and age of the respondent (for wolves and snow leopards), number of income sources in the family (wolves), agricultural production, and large-bodied livestock holdings (snow leopards). At the community level, the significant factors included the number of smaller-bodied herded livestock killed by wolves and mean agricultural production (wolves) and village size and large livestock holdings (snow leopards). Our results show that scaling up from the individual to higher levels of social organization can highlight important factors that influence attitudes of people toward wildlife and toward formal conservation efforts in general. Such scale-specific information can help managers apply conservation measures at

  19. Human and organizational factors in nuclear safety; Factores humanos y organizativos en la seguridad nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Garcia, A.; Barrientos, M.; Gil, B.

    2015-07-01

    Nuclear installations are socio technical systems where human and organizational factors, in both utilities and regulators, have a significant impact on safety. Three Mile Island (TMI) accident, original of several initiatives in the human factors field, nevertheless became a lost opportunity to timely acquire lessons related to the upper tiers of the system. Nowadays, Spanish nuclear installations have integrated in their processes specialists and activities in human and organizational factors, promoted by the licensees After many years of hard work, Spanish installations have achieved a better position to face new challenges, such as those posed by Fukushima. With this experience, only technology-centered action plan would not be acceptable, turning this accident in yet another lost opportunity. (Author)

  20. The development of human factors experimental evaluation techniques

    Energy Technology Data Exchange (ETDEWEB)

    Sim, Bong Shick; Oh, In Suk; Cha, Kyung Ho; Lee, Hyun Chul; Park, Geun Ok; Cheon, Se Woo; Suh, Sang Moon

    1997-07-01

    New human factors issues, such as evaluation of information navigation, the consideration of operator characteristics, and operator performance assessment, related to the HMI design based on VDUs are being risen. Thus, in order to solve these human factors issues, this project aims to establish the experimental technologies including the techniques for experimental design, experimental measurement, data collection and analysis, and to develop ITF (Integrated Test Facility) suitable for the experiment of HMI design evaluation. For the establish of the experimental data analysis and evaluation methodologies, we developed as the following: (1) a paradigm for human factors experimentation including experimental designs, procedures, and data analysis. (2) the methods for the assessment of operator`s mental workload (3) DAEXESS (data analysis and experiment evaluation supporting system). Also, we have established a experiment execution technologies through the preliminary experiments, such as the suitability evaluation of information display on a LSDP, the evaluation of information display on a LSDP, the evaluation of computerized operation procedure and an experiment of advanced alarm system (ADIOS). Finally, we developed the ITF including human machine simulator, telemetry system, an eye tracking system, an audio/video data measurement system, and three dimensional micro behaviour analysis system. (author). 81 refs., 68 tabs., 73 figs.

  1. Human Factors Issues For Multi-Modular Reactor Units

    Energy Technology Data Exchange (ETDEWEB)

    Tuan Q Tran; Humberto E. Garcia; Ronald L. Boring; Jeffrey C. Joe; Bruce P. Hallbert

    2007-08-01

    Smaller and multi-modular reactor (MMR) will be highly technologically-advanced systems allowing more system flexibility to reactors configurations (e.g., addition/deletion of reactor units). While the technical and financial advantages of systems may be numerous, MMR presents many human factors challenges that may pose vulnerability to plant safety. An important human factors challenge in MMR operation and performance is the monitoring of data from multiple plants from centralized control rooms where human operators are responsible for interpreting, assessing, and responding to different system’s states and failures (e.g., simultaneously monitoring refueling at one plant while keeping an eye on another plant’s normal operating state). Furthermore, the operational, safety, and performance requirements for MMR can seriously change current staffing models and roles, the mode in which information is displayed, procedures and training to support and guide operators, and risk analysis. For these reasons, addressing human factors concerns in MMR are essential in reducing plant risk.

  2. Human factors engineering checklists for application in the SAR process

    Energy Technology Data Exchange (ETDEWEB)

    Overlin, T.K.; Romero, H.A.; Ryan, T.G.

    1995-03-01

    This technical report was produced to assist the preparers and reviewers of the human factors portions of the SAR in completing their assigned tasks regarding analysis and/or review of completed analyses. The checklists, which are the main body of the report, and the subsequent tables, were developed to assist analysts in generating the needed analysis data to complete the human engineering analysis for the SAR. The technical report provides a series of 19 human factors engineering (HFE) checklists which support the safety analyses of the US Department of Energy`s (DOE) reactor and nonreactor facilities and activities. The results generated using these checklists and in the preparation of the concluding analyses provide the technical basis for preparing the human factors chapter, and subsequent inputs to other chapters, required by DOE as a part of the safety analysis reports (SARs). This document is divided into four main sections. The first part explains the origin of the checklists, the sources utilized, and other information pertaining to the purpose and scope of the report. The second part, subdivided into 19 sections, is the checklists themselves. The third section is the glossary which defines terms that could either be unfamiliar or have specific meanings within the context of these checklists. The final section is the subject index in which the glossary terms are referenced back to the specific checklist and page the term is encountered.

  3. Human factors for the Moon: the gap in anthropometric data.

    Science.gov (United States)

    Lia Schlacht, Irene; Foing, Bernard H.; Rittweger, Joern; Masali, Melchiorre; Stevenin, Hervé

    2016-07-01

    Since the space era began, we learned first to survive and then to live in space. In the state of the art, we know how important human factors research and development is to guarantee maximum safety and performance for human missions. With the extension of the duration of space missions, we also need to learn how habitability and comfort factors are closely related to safety and performance. Humanities disciplines such as design, architecture, anthropometry, and anthropology are now involved in mission design from the start. Actual plans for building a simulated Moon village in order to simulate and test Moon missions are now being carried out using a holistic approach, involving multidisciplinary experts cooperating concurrently with regard to the interactions among humans, technology, and the environment. However, in order to implement such plans, we need basic anthropometrical data, which is still missing. In other words: to optimize performance, we need to create doors and ceilings with dimensions that support a natural human movement in the reduced gravity environment of the Moon, but we are lacking detailed anthropometrical data on human movement on the Moon. In the Apollo missions more than 50 years ago, no anthropometrical studies were carried in hypogravity out as far as we know. The necessity to collect data is very consistent with state-of-the-art research. We still have little knowledge of how people will interact with the Moon environment. Specifically, it is not known exactly which posture, which kind of walking and running motions astronauts will use both inside and outside a Moon station. Considering recent plans for a Moon mission where humans will spend extensive time in reduced gravity conditions, the need for anthropometric, biomechanics and kinematics field data is a priority in order to be able to design the right architecture, infrastructure, and interfaces. Objective of this paper: Bring knowledge on the relevance of anthropometrical and

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

    Energy Technology Data Exchange (ETDEWEB)

    Carnino, A. (International Atomic Energy Agency, Vienna (Austria))

    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.

  5. An expansive human regulatory lexicon encoded in transcription factor footprints.

    Science.gov (United States)

    Neph, Shane; Vierstra, Jeff; Stergachis, Andrew B; Reynolds, Alex P; Haugen, Eric; Vernot, Benjamin; Thurman, Robert E; John, Sam; Sandstrom, Richard; Johnson, Audra K; Maurano, Matthew T; Humbert, Richard; Rynes, Eric; Wang, Hao; Vong, Shinny; Lee, Kristen; Bates, Daniel; Diegel, Morgan; Roach, Vaughn; Dunn, Douglas; Neri, Jun; Schafer, Anthony; Hansen, R Scott; Kutyavin, Tanya; Giste, Erika; Weaver, Molly; Canfield, Theresa; Sabo, Peter; Zhang, Miaohua; Balasundaram, Gayathri; Byron, Rachel; MacCoss, Michael J; Akey, Joshua M; Bender, M A; Groudine, Mark; Kaul, Rajinder; Stamatoyannopoulos, John A

    2012-09-06

    Regulatory factor binding to genomic DNA protects the underlying sequence from cleavage by DNase I, leaving nucleotide-resolution footprints. Using genomic DNase I footprinting across 41 diverse cell and tissue types, we detected 45 million transcription factor occupancy events within regulatory regions, representing differential binding to 8.4 million distinct short sequence elements. Here we show that this small genomic sequence compartment, roughly twice the size of the exome, encodes an expansive repertoire of conserved recognition sequences for DNA-binding proteins that nearly doubles the size of the human cis-regulatory lexicon. We find that genetic variants affecting allelic chromatin states are concentrated in footprints, and that these elements are preferentially sheltered from DNA methylation. High-resolution DNase I cleavage patterns mirror nucleotide-level evolutionary conservation and track the crystallographic topography of protein-DNA interfaces, indicating that transcription factor structure has been evolutionarily imprinted on the human genome sequence. We identify a stereotyped 50-base-pair footprint that precisely defines the site of transcript origination within thousands of human promoters. Finally, we describe a large collection of novel regulatory factor recognition motifs that are highly conserved in both sequence and function, and exhibit cell-selective occupancy patterns that closely parallel major regulators of development, differentiation and pluripotency.

  6. Human cytomegalovirus IE2 protein interacts with transcription activating factors

    Institute of Scientific and Technical Information of China (English)

    XU; Jinping(徐进平); YE; Linbai(叶林柏)

    2002-01-01

    The human cytomegalovirus (HCMV) IE86 Cdna was cloned into Pgex-2T and fusion protein GST-IE86 was expressed in E. Coli. SDS-PAGE and Western blot assay indicated that fusion protein GST-IE86 with molecular weight of 92 ku is soluble in the supernatant of cell lysate. Protein GST and fusion protein GST-IE86 were purified by affinity chromatography. The technology of co-separation and specific affinity chromatography was used to study the interactions of HCMV IE86 protein with some transcriptional regulatory proteins and transcriptional factors. The results indicated that IE86 interacts separately with transcriptional factor TFIIB and promoter DNA binding transcription trans-activating factors SP1, AP1 and AP2 to form a heterogenous protein complex. These transcriptional trans-activating factors, transcriptional factor and IE86 protein were adsorbed and retained in the affinity chromatography simultaneously. But IE86 protein could not interact with NF-Кb, suggesting that the function of IE86 protein that can interact with transcriptional factor and transcriptional trans-activating factors has no relevance to protein glycosylation. IE86 protein probably has two domains responsible for binding transcriptional trans-activating regulatory proteins and transcriptional factors respectively, thus activating the transcription of many genes. The interactions accelerated the assembly of the transcriptional initiation complexes.

  7. Lorentz invariant intrinsic decoherence

    CERN Document Server

    Milburn, G J

    2003-01-01

    Quantum decoherence can arise due to classical fluctuations in the parameters which define the dynamics of the system. In this case decoherence, and complementary noise, is manifest when data from repeated measurement trials are combined. Recently a number of authors have suggested that fluctuations in the space-time metric arising from quantum gravity effects would correspond to a source of intrinsic noise, which would necessarily be accompanied by intrinsic decoherence. This work extends a previous heuristic modification of Schr\\"{o}dinger dynamics based on discrete time intervals with an intrinsic uncertainty. The extension uses unital semigroup representations of space and time translations rather than the more usual unitary representation, and does the least violence to physically important invariance principles. Physical consequences include a modification of the uncertainty principle and a modification of field dispersion relations, in a way consistent with other modifications suggested by quantum grav...

  8. Factors influencing trace element composition in human teeth

    Energy Technology Data Exchange (ETDEWEB)

    Tandon, L. [Los Alamos National Lab., NM (United States); Iyengar, G.V. [Biomineral Sciences International, Inc., Bethesda, MD (United States)

    1997-12-01

    The authors recently compiled and reviewed the literature published in or after 1978 for 45 major, minor, and trace elements in human teeth as a part of an International Atomic Energy Agency (IAEA) study. The purpose of this paper is to discuss the various factors that influence the concentration levels of certain trace elements in human teeth. The sampling practices and analytical techniques that are applicable for trace element analysis are also discussed. It is also our intention to identify reference range of values, where data permit such conclusions. The scrutiny was designed to identify only the healthy permanent teeth, and values from teeth with fillings, caries, or periodontal diseases were eliminated.

  9. Space Flight Human System Standards (SFHSS). Volume 2; Human Factors, Habitability and Environmental Factors" and Human Integration Design Handbook (HIDH)

    Science.gov (United States)

    Davis, Jeffrey R.; Fitts, David J.

    2009-01-01

    This viewgraph presentation reviews the standards for space flight hardware based on human capabilities and limitations. The contents include: 1) Scope; 2) Applicable documents; 3) General; 4) Human Physical Characteristics and Capabilities; 5) Human Performance and Cognition; 6) Natural and Induced Environments; 7) Habitability Functions; 8) Architecture; 9) Hardware and Equipment; 10) Crew Interfaces; 11) Spacesuits; 12) Operatons: Reserved; 13) Ground Maintenance and Assembly: Reserved; 14) Appendix A-Reference Documents; 15) Appendix N-Acronyms and 16) Appendix C-Definition. Volume 2 is supported by the Human Integration Design Handbook (HIDH)s.

  10. Transcription of human respiratory syncytial virus genome RNA in vitro: requirement of cellular factor(s).

    OpenAIRE

    Barik, S

    1992-01-01

    Extracts made from human respiratory syncytial virus (RSV)-infected Hep-2 cells synthesized mRNAs encoded by all known viral genes. In contrast, RSV ribonucleoproteins purified from infected cells failed to transcribe in vitro; transcription was restored by addition of a cytoplasmic extract of uninfected Hep-2 cells, demonstrating that a cellular factor(s) has a role in RSV gene expression. Quantitation of the individual gene mRNAs transcribed in vitro revealed polarity of transcription of th...

  11. Intrinsic Time Quantum Geometrodynamics

    CERN Document Server

    Ita, Eyo Eyo; Yu, Hoi-Lai

    2015-01-01

    Quantum Geometrodynamics with intrinsic time development and momentric variables is presented. An underlying SU(3) group structure at each spatial point regulates the theory. The intrinsic time behavior of the theory is analyzed, together with its ground state and primordial quantum fluctuations. Cotton-York potential dominates at early times when the universe was small; the ground state naturally resolves Penrose's Weyl Curvature Hypothesis, and thermodynamic and gravitational `arrows of time' point in the same direction. Ricci scalar potential corresponding to Einstein's General Relativity emerges as a zero-point energy contribution. A new set of fundamental canonical commutation relations without Planck's constant emerges from the unification of Gravitation and Quantum Mechanics.

  12. Vancouver Experience of Recombinant Human Platelet-Derived Growth Factor.

    Science.gov (United States)

    Younger, Alistair; Penner, Murray; Montijo, Harvey E

    2016-12-01

    Joint arthrodesis utilizing autogenous bone graft remains the gold standard of treatment in fusion procedures of the foot and ankle. Graft harvest, however, has been associated with increased morbidity to patients as well as increased costs. With this in mind, multiple clinical studies have evaluated the efficacy of recombinant human platelet-derived growth factor (rh-PDGF-BB) with beta-tricalcium phosphate (B-TCP) to augment in foot and ankle arthrodesis with favorable results. These factors have led to the increased use of rh-PDGF-BB with B-TCP in Vancouver with good clinical results. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Tissue localization of human trefoil factors 1, 2, and 3

    DEFF Research Database (Denmark)

    Madsen, Jens; Nielsen, Ole; Tornøe, Ida

    2007-01-01

    pattern of the three trefoil factors analyzing mRNA from a panel of 20 human tissues by conventional reverse transcriptase (RT) PCR and, in addition, by real-time PCR. These findings were supported by immunohistochemical analysis of paraffin-embedded human tissues using rabbit polyclonal antibodies raised...... against these factors. TFF1 showed highest expression in the stomach and colon, whereas TFF2 and TFF3 showed highest expression in stomach and colon, respectively. All three TFFs were found in the ducts of pancreas. Whereas TFF2 was found to be restricted to these two tissues, the structurally more...... closely related TFF1 and TFF3 showed a more general tissue distribution and were found to colocalize on an array of mucosal surfaces. This is the first thorough parallel description of the tissue distribution of TFFs in normal tissues, and it provides a baseline for similar analysis in diseased tissues...

  14. The Partial Purification of Angiogenesis Factor of Human Osteosarcoma

    Institute of Scientific and Technical Information of China (English)

    WUHua; DENGZhongduan; 等

    2002-01-01

    Objective To partially purify the angiogenesis factor of human osteosarcoma(HuOs) and study its biological features. Methods The active peptide with a molecular weight of 8000-10000 Da in the conditioned medium obtained from the cultivation of Hu-Os cells(osteoblastic osteosarcoma) was partially purified by ultrafiltration, chromatography and dialysis.The angiogenic effects of the fractions were assessed by proliferation assay of human umbilical vein and pig thoracic aorta endothelial cells. Results The chromatography fractions 4-6 could significantly promote the proliferation of the endothelial cells.Conclusion The HuOs cells could synthesize and secrete angiogenesis factor with a molecular weight of 8000-10000 Da.

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

    Science.gov (United States)

    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.

  16. DNA-binding specificities of human transcription factors.

    Science.gov (United States)

    Jolma, Arttu; Yan, Jian; Whitington, Thomas; Toivonen, Jarkko; Nitta, Kazuhiro R; Rastas, Pasi; Morgunova, Ekaterina; Enge, Martin; Taipale, Mikko; Wei, Gonghong; Palin, Kimmo; Vaquerizas, Juan M; Vincentelli, Renaud; Luscombe, Nicholas M; Hughes, Timothy R; Lemaire, Patrick; Ukkonen, Esko; Kivioja, Teemu; Taipale, Jussi

    2013-01-17

    Although the proteins that read the gene regulatory code, transcription factors (TFs), have been largely identified, it is not well known which sequences TFs can recognize. We have analyzed the sequence-specific binding of human TFs using high-throughput SELEX and ChIP sequencing. A total of 830 binding profiles were obtained, describing 239 distinctly different binding specificities. The models represent the majority of human TFs, approximately doubling the coverage compared to existing systematic studies. Our results reveal additional specificity determinants for a large number of factors for which a partial specificity was known, including a commonly observed A- or T-rich stretch that flanks the core motifs. Global analysis of the data revealed that homodimer orientation and spacing preferences, and base-stacking interactions, have a larger role in TF-DNA binding than previously appreciated. We further describe a binding model incorporating these features that is required to understand binding of TFs to DNA.

  17. Intrinsic contractures of the hand.

    Science.gov (United States)

    Paksima, Nader; Besh, Basil R

    2012-02-01

    Contractures of the intrinsic muscles of the fingers disrupt the delicate and complex balance of intrinsic and extrinsic muscles, which allows the hand to be so versatile and functional. The loss of muscle function primarily affects the interphalangeal joints but also may affect etacarpophalangeal joints. The resulting clinical picture is often termed, intrinsic contracture or intrinsic-plus hand. Disruption of the balance between intrinsic and extrinsic muscles has many causes and may be secondary to changes within the intrinsic musculature or the tendon unit. This article reviews diagnosis, etiology, and treatment algorithms in the management of intrinsic contractures of the fingers. Copyright © 2012 Elsevier Inc. All rights reserved.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Quantifying Risk Factors for Human Brucellosis in Rural Northern Tanzania

    OpenAIRE

    Kunda John; Julie Fitzpatrick; Nigel French; Rudovick Kazwala; Dominic Kambarage; Mfinanga, Godfrey S; Alastair MacMillan; Sarah Cleaveland

    2010-01-01

    BACKGROUND: Brucellosis is a zoonosis of veterinary, public health and economic significance in most developing countries. Human brucellosis is a severely debilitating disease that requires prolonged treatment with a combination of antibiotics. The disease can result in permanent and disabling sequel, and results in considerable medical expenses in addition to loss of income due to loss of working hours. A study was conducted in Northern Tanzania to determine the risk factors for transmission...

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

    Science.gov (United States)

    2000-03-01

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

  1. The challenges for human factors in knowledge work

    DEFF Research Database (Denmark)

    Ipsen, Christine; Møller, Niels; Jensen, Per Langaa

    2011-01-01

    The development towards a service and knowledge intensive economy arise new challenges for ergonomics and human factors. Knowledge on work within mass service production exists, but the challenges within knowledge work have still to be addressed. The focus of this paper is on some of the challeng...... with the demands of the knowledge intensive work when KPI’s are central management tools. Especially handling the balance between high motivation and enthusiasm and burn out will be addressed....

  2. Purification of human platelet-derived growth factor

    Energy Technology Data Exchange (ETDEWEB)

    Raines, E.W.; Ross, R.

    1985-01-01

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

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

    Science.gov (United States)

    2007-11-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Casey, S.M.

    1980-06-01

    The purpose of this document is to provide an overview of the recommended activities and methods to be employed by a team of human factors engineers during the development of a nuclear waste retrieval system. This system, as it is presently conceptualized, is intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository. This document, and the others in this series, have been developed for the purpose of implementing human factors engineering principles during the design and construction of the retrieval system facilities and equipment. The methodology presented has been structured around a basic systems development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Within each of these phases, the recommended activities of the human engineering team have been stated, along with descriptions of the human factors engineering design techniques applicable to the specific design issues. Explicit examples of how the techniques might be used in the analysis of human tasks and equipment required in the removal of spent fuel canisters have been provided. Only those techniques having possible relevance to the design of the waste retrieval system have been reviewed. This document is intended to provide the framework for integrating human engineering with the rest of the system development effort. The activities and methodologies reviewed in this document have been discussed in the general order in which they will occur, although the time frame (the total duration of the development program in years and months) in which they should be performed has not been discussed.

  5. Transforming growth factor (TGF)-. alpha. in human milk

    Energy Technology Data Exchange (ETDEWEB)

    Okada, Masaki; Wakai, Kae; Shizume, Kazuo (Research Institute for Growth Sciences, Tokyo (Japan)); Iwashita, Mitsutoshi (Tokyo Women' s Medical College (Japan)); Ohmura, Eiji; Kamiya, Yoshinobu; Murakami, Hitomi; Onoda, Noritaka; Tsushima, Toshio

    1991-01-01

    Transforming growth factor (TGF)-{alpha} and epidermal growth factor (EGF) were measured in human milk by means of homologous radioimmunoassay. As previously reported, EGF concentration in the colostrum was approximately 200 ng/ml and decreased to 50 ng/ml by day 7 postpartum. The value of immunoreactive (IR)-TGF-{alpha} was 2.2-7.2 ng/ml, much lower than that of EGF. In contrast to EGF, the concentration of IR-TGF-{alpha} was fairly stable during the 7 postpartum days. There was no relationship between the concentrations of IR-TGF-{alpha} and IR-EGF, suggesting that the regulatory mechanism in the release of the two growth factors is different. On gel-chromatography using a Sephadex G-50 column, IR-EGF appeared in the fraction corresponding to that of authentic human EGF, while 70%-80% of the IR-TGF-{alpha} was eluted as a species with a molecular weight greater than that of authentic human TGF-{alpha}. Although the physiological role of TGF-{alpha} in milk is not known, it is possible that it is involved in the development of the mammary gland and/or the growth of newborn infants.

  6. The Influence of Human Factor in Aircraft Maintenance

    Directory of Open Access Journals (Sweden)

    Darko Virovac

    2017-06-01

    during aircraft maintenance. In the EASA approved aircraft maintenance organisation, which includes in its working system the human factor as well, the tendency is to apply the approach by continuous monitoring and analysis of errors in aircraft maintenance. Such approach achieves advance prevention or reduction of the occurrence of harmful events, such as accidents, incidents, injuries and in a wider sense damages related to aircraft operation and maintenance. The research presented in this paper is a result of gathering and systematization of errors caused by human factors over the last five years in one organisation for aircraft maintenance certified according to the European standards. The study encompasses an analysis of 28 (twenty-eight investigations of individual cases and provides insight into the main factors of errors. The results of analyses on the cause of occurrence of human error show similar results like the Boeing study which was carried out for the world fleet.

  7. [Human factors and crisis resource management: improving patient safety].

    Science.gov (United States)

    Rall, M; Oberfrank, S

    2013-10-01

    A continuing high number of patients suffer harm from medical treatment. In 60-70% of the cases the sources of harm can be attributed to the field of human factors (HFs) and teamwork; nevertheless, those topics are still neither part of medical education nor of basic and advanced training even though it has been known for many years and it has meanwhile also been demonstrated for surgical specialties that training in human factors and teamwork considerably reduces surgical mortality.Besides the medical field, the concept of crisis resource management (CRM) has already proven its worth in many other industries by improving teamwork and reducing errors in the domain of human factors. One of the best ways to learn about CRM and HFs is realistic simulation team training with well-trained instructors in CRM and HF. The educational concept of the HOTT (hand over team training) courses for trauma room training offered by the DGU integrates these elements based on the current state of science. It is time to establish such training for all medical teams in emergency medicine and operative care. Accompanying safety measures, such as the development of a positive culture of safety in every department and the use of effective critical incident reporting systems (CIRs) should be pursued.

  8. Transgenic Soybean Production of Bioactive Human Epidermal Growth Factor (EGF.

    Directory of Open Access Journals (Sweden)

    Yonghua He

    Full Text Available Necrotizing enterocolitis (NEC is a devastating condition of premature infants that results from the gut microbiome invading immature intestinal tissues. This results in a life-threatening disease that is frequently treated with the surgical removal of diseased and dead tissues. Epidermal growth factor (EGF, typically found in bodily fluids, such as amniotic fluid, salvia and mother's breast milk, is an intestinotrophic growth factor and may reduce the onset of NEC in premature infants. We have produced human EGF in soybean seeds to levels biologically relevant and demonstrated its comparable activity to commercially available EGF. Transgenic soybean seeds expressing a seed-specific codon optimized gene encoding of the human EGF protein with an added ER signal tag at the N' terminal were produced. Seven independent lines were grown to homozygous and found to accumulate a range of 6.7 +/- 3.1 to 129.0 +/- 36.7 μg EGF/g of dry soybean seed. Proteomic and immunoblot analysis indicates that the inserted EGF is the same as the human EGF protein. Phosphorylation and immunohistochemical assays on the EGF receptor in HeLa cells indicate the EGF protein produced in soybean seed is bioactive and comparable to commercially available human EGF. This work demonstrates the feasibility of using soybean seeds as a biofactory to produce therapeutic agents in a soymilk delivery platform.

  9. Novel factors modulating human β-cell proliferation.

    Science.gov (United States)

    Shirakawa, J; Kulkarni, R N

    2016-09-01

    β-Cell dysfunction in type 1 and type 2 diabetes is accompanied by a progressive loss of β-cells, and an understanding of the cellular mechanism(s) that regulate β-cell mass will enable approaches to enhance hormone secretion. It is becoming increasingly recognized that enhancement of human β-cell proliferation is one potential approach to restore β-cell mass to prevent and/or cure type 1 and type 2 diabetes. While several reports describe the factor(s) that enhance β-cell replication in animal models or cell lines, promoting effective human β-cell proliferation continues to be a challenge in the field. In this review, we discuss recent studies reporting successful human β-cell proliferation including WS6, an IkB kinase and EBP1 inhibitor; harmine and 5-IT, both DYRK1A inhibitors; GNF7156 and GNF4877, GSK-3β and DYRK1A inhibitors; osteoprotegrin and Denosmab, receptor activator of NF-kB (RANK) inhibitors; and SerpinB1, a protease inhibitor. These studies provide important examples of proteins and pathways that may prove useful for designing therapeutic strategies to counter the different forms of human diabetes.

  10. Neural Basis of Intrinsic Motivation: Evidence from Event-Related Potentials

    Directory of Open Access Journals (Sweden)

    Jia Jin

    2015-01-01

    Full Text Available Human intrinsic motivation is of great importance in human behavior. However, although researchers have focused on this topic for decades, its neural basis was still unclear. The current study employed event-related potentials to investigate the neural disparity between an interesting stop-watch (SW task and a boring watch-stop task (WS to understand the neural mechanisms of intrinsic motivation. Our data showed that, in the cue priming stage, the cue of the SW task elicited smaller N2 amplitude than that of the WS task. Furthermore, in the outcome feedback stage, the outcome of the SW task induced smaller FRN amplitude and larger P300 amplitude than that of the WS task. These results suggested that human intrinsic motivation did exist and that it can be detected at the neural level. Furthermore, intrinsic motivation could be quantitatively indexed by the amplitude of ERP components, such as N2, FRN, and P300, in the cue priming stage or feedback stage. Quantitative measurements would also be convenient for intrinsic motivation to be added as a candidate social factor in the construction of a machine learning model.

  11. Neural Basis of Intrinsic Motivation: Evidence from Event-Related Potentials.

    Science.gov (United States)

    Jin, Jia; Yu, Liping; Ma, Qingguo

    2015-01-01

    Human intrinsic motivation is of great importance in human behavior. However, although researchers have focused on this topic for decades, its neural basis was still unclear. The current study employed event-related potentials to investigate the neural disparity between an interesting stop-watch (SW) task and a boring watch-stop task (WS) to understand the neural mechanisms of intrinsic motivation. Our data showed that, in the cue priming stage, the cue of the SW task elicited smaller N2 amplitude than that of the WS task. Furthermore, in the outcome feedback stage, the outcome of the SW task induced smaller FRN amplitude and larger P300 amplitude than that of the WS task. These results suggested that human intrinsic motivation did exist and that it can be detected at the neural level. Furthermore, intrinsic motivation could be quantitatively indexed by the amplitude of ERP components, such as N2, FRN, and P300, in the cue priming stage or feedback stage. Quantitative measurements would also be convenient for intrinsic motivation to be added as a candidate social factor in the construction of a machine learning model.

  12. Review of Significant Incidents and Close Calls in Human Spaceflight from a Human Factors Perspective

    Science.gov (United States)

    Silva-Martinez, Jackelynne; Ellenberger, Richard; Dory, Jonathan

    2017-01-01

    This project aims to identify poor human factors design decisions that led to error-prone systems, or did not facilitate the flight crew making the right choices; and to verify that NASA is effectively preventing similar incidents from occurring again. This analysis was performed by reviewing significant incidents and close calls in human spaceflight identified by the NASA Johnson Space Center Safety and Mission Assurance Flight Safety Office. The review of incidents shows whether the identified human errors were due to the operational phase (flight crew and ground control) or if they initiated at the design phase (includes manufacturing and test). This classification was performed with the aid of the NASA Human Systems Integration domains. This in-depth analysis resulted in a tool that helps with the human factors classification of significant incidents and close calls in human spaceflight, which can be used to identify human errors at the operational level, and how they were or should be minimized. Current governing documents on human systems integration for both government and commercial crew were reviewed to see if current requirements, processes, training, and standard operating procedures protect the crew and ground control against these issues occurring in the future. Based on the findings, recommendations to target those areas are provided.

  13. Human Systems Interface and Plant Modernization Process: Technical Basis and Human Factors Review Guidance

    Science.gov (United States)

    2000-03-01

    NUREG /CR-6637 BNL- NUREG -52567 Human Systems Interface and Plant Modernization Process: Technical Basis and Human Factors Review Guidance Brookhaven...NOTICE Availability of Reference Materials Cited in NRC Publications NRC publications in the NUREG series, NRC regu- <http://www.nrc.gov>lations, and...sources: access NUREG -series publications and other NRCrecords in NRC’s Agencywide Document Access 1. The Superintendent of Documents and Management

  14. Quantitative risk analysis offshore-Human and organizational factors

    Energy Technology Data Exchange (ETDEWEB)

    Espen Skogdalen, Jon, E-mail: jon.espen.skogdalen@gmail.co [Department of Industrial Economics, Risk Management and Planning, University of Stavanger, 4036 Stavanger (Norway); Vinnem, Jan Erik, E-mail: jev@preventor.n [Department of Industrial Economics, Risk Management and Planning, University of Stavanger, 4036 Stavanger (Norway)

    2011-04-15

    Quantitative Risk Analyses (QRAs) are one of the main tools for risk management within the Norwegian and UK oil and gas industry. Much criticism has been given to the limitations related to the QRA-models and that the QRAs do not include human and organizational factors (HOF-factors). Norway and UK offshore legislation and guidelines require that the HOF-factors are included in the QRAs. A study of 15 QRAs shows that the factors are to some extent included, and there are large differences between the QRAs. The QRAs are categorized into four levels according to the findings. Level 1 QRAs do not describe or comment on the HOF-factors at all. Relevant research projects have been conducted to fulfill the requirements of Level 3 analyses. At this level, there is a systematic collection of data related to HOF. The methods are systematic and documented, and the QRAs are adjusted. None of the QRAs fulfill the Level 4 requirements. Level 4 QRAs include the model and describe the HOF-factors as well as explain how the results should be followed up in the overall risk management. Safety audits by regulatory authorities are probably necessary to point out the direction for QRA and speed up the development.

  15. [Factors associated with job satisfaction of human resources in healthcare].

    Science.gov (United States)

    Вежновець, Тетяна А; Парій, Валентин Д; Вишнивецький, Іван І; Москаленко, Максим В

    Healthcare employee satisfaction is an important criterion for the efficiency of human resource management and prognostic impact factor for high turnover of staff. Furthermore, job satisfaction positively affects patient satisfaction, which is an important indicator for quality of care. The goal of our study was to identify factors associated with job satisfaction in healthcare organizations in Ukraine. We conducted sociological and psychological survey of 190 healthcare professionals (81% response rate) in Kherson City Hospital. Job satisfaction and organizational climate was assessed through developed questionnaire, "Test Motype" method of Gerchikov (motivational profile designing) and "Diagnosis Syndrome emotional burnout" method of Boyko. Spearman rank correlation was used for analysis. Job satisfaction positively correlated with personnel age and time record, career prospects, professional development, superior-subordinate, peer-to-peer and patient communications (psatisfaction did not correlate with responsibility of executives, factors for satisfaction of job description, working conditions and range of wages (all p> 0.05). Based on findings we developed dual job satisfaction-dissatisfaction approach specific for healthcare employee in Ukraine. This model includes internal factors such as work experience, career prospects, professional motivation; external factors such as leadership, governance, work environment, customer satisfaction and preventive factors such as staff role, job description, company policies, salary and benefits.

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

    Energy Technology Data Exchange (ETDEWEB)

    Ngo, J.C.; Huang, M.; Roth, D.A.; Furie, B.C.; Furie, B. (Wyeth); (MBL)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    Casey, S. M.

    1980-06-01

    The nuclear waste retrieval system intended to be used for the removal of storage canisters (each canister containing a spent fuel rod assembly) located in an underground salt bed depository is discussed. The implementation of human factors engineering principles during the design and construction of the retrieval system facilities and equipment is reported. The methodology is structured around a basic system development effort involving preliminary development, equipment development, personnel subsystem development, and operational test and evaluation. Examples of application of the techniques in the analysis of human tasks, and equipment required in the removal of spent fuel canisters is provided. The framework for integrating human engineering with the rest of the system development effort is documented.

  19. Workforce scheduling: A new model incorporating human factors

    Directory of Open Access Journals (Sweden)

    Mohammed Othman

    2012-12-01

    Full Text Available Purpose: The majority of a company’s improvement comes when the right workers with the right skills, behaviors and capacities are deployed appropriately throughout a company. This paper considers a workforce scheduling model including human aspects such as skills, training, workers’ personalities, workers’ breaks and workers’ fatigue and recovery levels. This model helps to minimize the hiring, firing, training and overtime costs, minimize the number of fired workers with high performance, minimize the break time and minimize the average worker’s fatigue level.Design/methodology/approach: To achieve this objective, a multi objective mixed integer programming model is developed to determine the amount of hiring, firing, training and overtime for each worker type.Findings: The results indicate that the worker differences should be considered in workforce scheduling to generate realistic plans with minimum costs. This paper also investigates the effects of human fatigue and recovery on the performance of the production systems.Research limitations/implications: In this research, there are some assumptions that might affect the accuracy of the model such as the assumption of certainty of the demand in each period, and the linearity function of Fatigue accumulation and recovery curves. These assumptions can be relaxed in future work.Originality/value: In this research, a new model for integrating workers’ differences with workforce scheduling is proposed. To the authors' knowledge, it is the first time to study the effects of different important human factors such as human personality, skills and fatigue and recovery in the workforce scheduling process. This research shows that considering both technical and human factors together can reduce the costs in manufacturing systems and ensure the safety of the workers.

  20. Human Factors in Training - Space Flight Resource Management Training

    Science.gov (United States)

    Bryne, Vicky; Connell, Erin; Barshi, Immanuel; Arsintescu, L.

    2009-01-01

    . Work on SFRM training has been conducted in collaboration with the Expedition Vehicle Division at the Mission Operations Directorate (MOD) and with United Space Alliance (USA) which provides training to Flight Controllers. The space flight resource management training work is part of the Human Factors in Training Directed Research Project (DRP) of the Space Human Factors Engineering (SHFE) Project under the Space Human Factors and Habitability (SHFH) Element of the Human Research Program (HRP). Human factors researchers at the Ames Research Center have been investigating team work and distributed decision making processes to develop a generic SFRM training framework for flight controllers. The work proposed for FY10 continues to build on this strong collaboration with MOD and the USA Training Group as well as previous research in relevant domains such as aviation. In FY10, the work focuses on documenting and analyzing problem solving strategies and decision making processes used in MCC by experienced FCers.

  1. NYD-SP27,一个新的精子内源性去获能因子%NYD-SP27, a novel intrinsic decapacitation factor in sperm

    Institute of Scientific and Technical Information of China (English)

    Ye Bi; Wen-Ming Xu; Hau Yan Wong; Hui Zhu; Zuo-Min Zhou; Hsiao Chang Chan; Jia-Hao Sha

    2009-01-01

    在受精之前精子必须完成一个被称为"获能"的活化过程,最终发生项体反应.到目前为止,虽然已有研究证实多种来源的去获能因子在这一过程中发挥作用,但对于阻止精子发生过早获能的详细机制还不甚了解.在本文的研究中,我们通过特异性抗体的免疫荧光证实NYD-SP27,磷脂酶C Zeta 1(PLCZl)的一种亚型,定位于小鼠和人精子的顶体部.Western blot和双染的研究表明在精子发生获能和顶体反应的过程中NYD-SP27逐渐从精子上丢失.关键性获能活化因子HCO3的缺乏可以阻止NYD-SP27自精子上的丢失.抗NYD-SP27的抗体也同样能够阻止NYD-SP27自精子上的丢失,减少获能精子的数量,抑制ATP和孕酮诱发的顶体反应以及抑制精子内PLC偶联的Ca2+的动员,而这些均能够由PLC inhibitor u73122所模拟.这些数据有力的表明NYD-SP27是一种生理性的PLC抑制剂,它作为精子内的内源性的去获能因子发挥作用以阻止过早的获能和顶体反应的发生.%Prior to fertilization sperm has to undergo an activation process known as capaciation, leading to the acrosome reaction. Till now, little is known about the mechanism for preventing premature capacitation in sperm although decapacitation factors from various sources have been thought to be involved. In this study, we report that NYD-SP27, an isoform of phospholipase C Zeta 1 (PLCZI), is localized to the sperm acrosome in mouse and human spermatozoa by immunofluorescence using a specific antibody. Westem blot and double staining analyses show NYD-SP27 becomes detached from sperm, as they undergo capacitation and acrosome reaction. The absence of HCO3-, a key factor in activating capacitation, from the capacitation-inducing medium prevents the loss of NYD-SP27 from sperm. The anti-NYD-SP27 antibody also prevents the loss of NYD-SP27 from sperm, reduced the number of capacitated sperm, inhibited the acrosome reaction induced by ATP and

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  3. Human Resource – Potential Factor of Organiztional Crisis

    Directory of Open Access Journals (Sweden)

    Mihail Cristian Negrulescu

    2008-10-01

    Full Text Available At the level of any economic system, the change brings about the modification of the internal operating method of the relations between the actors and of the work habits. In other words, the substance (main, important modifications can be shaped on each of the organizational dominant of the system at a structural, functional or cultural level, in which the main actor, the human resource, intends to be part of this equation of changes. In this context, significant is the role played by the main organization actors, a role which can be materialized either as a factor of innovation, prevention and even progress, or as a conflict promoting factor, which, in time, generates a state of abnormality, of crisis. That is why major importance must be allotted to the human resources at the level of each organisation, considering the progress focused on knowledge, experience, experiments, attitude, behaviour and competences, these implying factors of correction and efficient reaction for the administration of the organizational crises.

  4. Identifying Human Factors Issues in Aircraft Maintenance Operations

    Science.gov (United States)

    Veinott, Elizabeth S.; Kanki, Barbara G.; Shafto, Michael G. (Technical Monitor)

    1995-01-01

    Maintenance operations incidents submitted to the Aviation Safety Reporting System (ASRS) between 1986-1992 were systematically analyzed in order to identify issues relevant to human factors and crew coordination. This exploratory analysis involved 95 ASRS reports which represented a wide range of maintenance incidents. The reports were coded and analyzed according to the type of error (e.g, wrong part, procedural error, non-procedural error), contributing factors (e.g., individual, within-team, cross-team, procedure, tools), result of the error (e.g., aircraft damage or not) as well as the operational impact (e.g., aircraft flown to destination, air return, delay at gate). The main findings indicate that procedural errors were most common (48.4%) and that individual and team actions contributed to the errors in more than 50% of the cases. As for operational results, most errors were either corrected after landing at the destination (51.6%) or required the flight crew to stop enroute (29.5%). Interactions among these variables are also discussed. This analysis is a first step toward developing a taxonomy of crew coordination problems in maintenance. By understanding what variables are important and how they are interrelated, we may develop intervention strategies that are better tailored to the human factor issues involved.

  5. New polymorphic variants of human blood clotting factor IX

    Energy Technology Data Exchange (ETDEWEB)

    Surin, V.L.; Luk`yanenko, A.V.; Tagiev, A.F.; Smirnova, O.V. [Hematological Research Center, Moscow (Russian Federation); Plutalov, O.V.; Berlin, Yu.A. [Shemyakin Institute of Bioorganic Chemistry, Moscow (Russian Federation)

    1995-04-01

    The polymorphism of Alu-repeats, which are located in the introns of the human factor IX gene (copies 1-3), was studied. To identify polymorphic variants, direct sequencing of PCR products that contained appropriate repeats was used. In each case, 20 unrelated X chromosomes were studied. A polymorphic Dra I site was found near the 3{prime}-end of Alu copy 3 within the region of the polyA tract. A PCR-based testing system with internal control of restriction hydrolysis was suggested. Testing 81 unrelated X chromosomes revealed that the frequency of the polymorphic Dra I site is 0.23. Taq I polymorphism, which was revealed in Alu copy 4 of factor IX gene in our previous work, was found to be closely linked to Dra I polymorphism. Studies in linkage between different types of polymorphisms of the factor IX gene revealed the presence of a rare polymorphism in intron a that was located within the same minisatellite region as the known polymorphic insertion 50 bp/Dde I. However, the size of the insertion in our case was 26 bp. Only one polymorphic variant was found among over 150 unrelated X chromosomes derived from humans from Moscow and its vicinity. 10 refs., 4 figs., 1 tab.

  6. Quantifying risk factors for human brucellosis in rural northern Tanzania.

    Directory of Open Access Journals (Sweden)

    Kunda John

    Full Text Available BACKGROUND: Brucellosis is a zoonosis of veterinary, public health and economic significance in most developing countries. Human brucellosis is a severely debilitating disease that requires prolonged treatment with a combination of antibiotics. The disease can result in permanent and disabling sequel, and results in considerable medical expenses in addition to loss of income due to loss of working hours. A study was conducted in Northern Tanzania to determine the risk factors for transmission of brucellosis to humans in Tanzania. METHODS: This was a matched case-control study. Any patient with a positive result by a competitive ELISA (c-ELISA test for brucellosis, and presenting to selected hospitals with at least two clinical features suggestive of brucellosis such as headache, recurrent or continuous fever, sweating, joint pain, joint swelling, general body malaise or backache, was defined as a case. For every case in a district, a corresponding control was traced and matched by sex using multistage cluster sampling. Other criteria for inclusion as a control included a negative c-ELISA test result and that the matched individual would present to hospital if falls sick. RESULTS: Multivariable analysis showed that brucellosis was associated with assisted parturition during abortion in cattle, sheep or goat. It was shown that individuals living in close proximity to other households had a higher risk of brucellosis. People who were of Christian religion were found to have a higher risk of brucellosis compared to other religions. The study concludes that assisting an aborting animal, proximity to neighborhoods, and Christianity were associated with brucellosis infection. There was no association between human brucellosis and Human Immunodeficiency Virus (HIV serostatus. Protecting humans against contact with fluids and tissues during assisted parturition of livestock may be an important means of reducing the risk of transferring brucellosis from

  7. Human Factors Considerations in New Nuclear Power Plants: Detailed Analysis.

    Energy Technology Data Exchange (ETDEWEB)

    OHara,J.; Higgins, J.; Brown, W.; Fink, R.

    2008-02-14

    This Nuclear Regulatory Commission (NRC) sponsored study has identified human-performance issues in new and advanced nuclear power plants. To identify the issues, current industry developments and trends were evaluated in the areas of reactor technology, instrumentation and control technology, human-system integration technology, and human factors engineering (HFE) methods and tools. The issues were organized into seven high-level HFE topic areas: Role of Personnel and Automation, Staffing and Training, Normal Operations Management, Disturbance and Emergency Management, Maintenance and Change Management, Plant Design and Construction, and HFE Methods and Tools. The issues where then prioritized into four categories using a 'Phenomena Identification and Ranking Table' methodology based on evaluations provided by 14 independent subject matter experts. The subject matter experts were knowledgeable in a variety of disciplines. Vendors, utilities, research organizations and regulators all participated. Twenty issues were categorized into the top priority category. This Brookhaven National Laboratory (BNL) technical report provides the detailed methodology, issue analysis, and results. A summary of the results of this study can be found in NUREG/CR-6947. The research performed for this project has identified a large number of human-performance issues for new control stations and new nuclear power plant designs. The information gathered in this project can serve as input to the development of a long-term strategy and plan for addressing human performance in these areas through regulatory research. Addressing human-performance issues will provide the technical basis from which regulatory review guidance can be developed to meet these challenges. The availability of this review guidance will help set clear expectations for how the NRC staff will evaluate new designs, reduce regulatory uncertainty, and provide a well-defined path to new nuclear power plant

  8. Human factors evaluation of teletherapy: Human-system interfaces and procedures. Volume 3

    Energy Technology Data Exchange (ETDEWEB)

    Kaye, R.D.; Henriksen, K.; Jones, R. [Hughes Training, Inc., Falls Church, VA (United States); Morisseau, D.S.; Serig, D.I. [Nuclear Regulatory Commission, Washington, DC (United States). Div. of Systems Technology

    1995-07-01

    A series of human factors evaluations was undertaken to better understand the contributing factors to human error in the teletherapy environment. Teletherapy is a multidisciplinary methodology for treating cancerous tissue through selective exposure to an external beam of ionizing radiation. The principal sources of radiation are a radioactive isotope, typically cobalt60 (Co-60), or a linear accelerator device capable of producing very high energy x-ray and electron beams. A team of human factors specialists conducted site visits to radiation oncology departments at community hospitals, university centers, and free-standing clinics. In addition, a panel of radiation oncologists, medical physicists, and radiation technologists served as subject matter experts. A function and task analysis was initially performed to guide subsequent evaluations in the areas of user-system interfaces, procedures, training and qualifications, and organizational policies and practices. The present report focuses on an evaluation of the human-system interfaces in relation to the treatment machines and supporting equipment (e.g., simulators, treatment planning computers, control consoles, patient charts) found in the teletherapy environment. The report also evaluates operating, maintenance and emergency procedures and practices involved in teletherapy. The evaluations are based on the function and task analysis and established human engineering guidelines, where applicable.

  9. Preparation and characterization of conjugates of (modified) human serum albumin and liposomes : Drug carriers with an intrinsic anti-HIV activity

    NARCIS (Netherlands)

    Kamps, JAAM; Swart, PJ; Morselt, HWM; Pauwels, R; DeBethune, MP; DeClercq, E; Meijer, DKF; Scherphof, GL

    1996-01-01

    Human serum albumin (HSA) derivatized with cis-aconitic anhydride (Aco-HSA) that was earlier shown to inhibit replication of human immunodeficiency virus type 1 (HIV-1), was covalently coupled to conventional liposomes, consisting of phosphatidylcholine, cholesterol and

  10. An integrated approach to rotorcraft human factors research

    Science.gov (United States)

    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.

  11. [Surgeons can learn from pilots: human factors in surgery].

    Science.gov (United States)

    Sockeel, P; Chatelain, E; Massoure, M-P; David, P; Chapellier, X; Buffat, S

    2009-06-01

    Human factors (HF) study is mandatory to get air transport pilot licences. In aviation, crew resource management (CRM) and declaration of adverse events (feedback) result in improving of air safety. Air missions and surgical procedures have similarities. Bridging the gap is tempting, despite severe warnings against simplistic adaptation. Putting HF theory into surgical practice: how to? Educational principles derived from CRM improve professional attitudes of a team. We propose to translate concepts of CRM to clinical teams. CRM training applying in surgery could allow the work environment to be restructured to reduce human error. Feedback: in aviation, the Bureau of Flight Safety deals with investigations for air events. Pilots, air traffic controllers can anonymously declare nuisance, resulting in a feedback for the whole air force. Adverse events are analysed. Usually, multilevel problems are found, rather than the only responsibility of the last operator. Understanding the mechanisms of human failure finally improves safety. In surgery, CRM and feedback would probably be helpful. Anyway, it requires time; people have to change their mind. Nevertheless people such as fighter pilots, who were very unwilling at the beginning, now consider HF as a cornerstone for security. But it is difficult to estimate the extent of HF-related morbidity and mortality. We propose as a first step to consider CRM and feedback in surgical procedure. HF deals with the mechanisms of human errors and the ways to improve safety and probably improve the surgical team's efficacy.

  12. Cloning the human gene for macrophage migration inhibitory factor (MIF)

    Energy Technology Data Exchange (ETDEWEB)

    Paralkar, V.; Wistow, G. (National Institutes of Health, Bethesda, MD (United States))

    1994-01-01

    Macrophage migration inhibitory factor (MIF) was originally identified as a lymphokine. However, recent work strongly suggests a wider role for MIF beyond the immune system. It is expressed specifically in the differentiating cells of the immunologically privileged eye lens and brain, is a delayed early response gene in fibroblasts, and is expressed in many tissues. Here, the authors report the structure of the remarkably small gene for human MIF that has three exons separated by introns of only 189 and 95 bp and covers less than 1 kb. The cloned sequence also includes 1 kb of 5[prime] flanking region. Primer extension and 5[prime] rapid amplification of cDNA ends (RACE) of human brain RNA both indicate the presence of a single transcription start site in a TATA-less promoter. Northern blot analysis shows a single size of MIF mRNA (about 800 nt) in all human tissues examined. In contrast to previous reports, they find no evidence for multiple genes for MIF in the human genome. 20 refs., 3 figs.

  13. Humanized cobra venom factor decreases myocardial ischemia-reperfusion injury.

    Science.gov (United States)

    Gorsuch, W Brian; Guikema, Benjamin J; Fritzinger, David C; Vogel, Carl-Wilhelm; Stahl, Gregory L

    2009-12-01

    Cobra venom factor (CVF) is a complement activating protein in cobra venom, which functionally resembles C3b, and has been used for decades for decomplementation of serum to investigate the role of complement in many model systems of disease. The use of CVF for clinical practice is considered impractical because of immunogenicity issues. Humanization of CVF was recently demonstrated to yield a potent CVF-like molecule. In the present study, we demonstrate that mice treated with recombinant humanized CVF (HC3-1496) are protected from myocardial ischemia-reperfusion (MI/R) injuries with resultant preservation of cardiac function. Also, C3 deposition in the myocardium following MI/R was not observed following treatment with HC3-1496. HC3-1496 led to complement activation and depletion of C3, but preserved C5 titers. These data suggest, unlike CVF, HC3-1496 does not form a C5 convertase in the mouse, similar to recent studies in human sera/plasma. These results suggest that humanized CVF (HC3-1496) protects the ischemic myocardium from reperfusion injuries induced by complement activation and represents a novel anti-complement therapy for potential clinical use.

  14. 2015 Space Human Factors Engineering Standing Review Panel

    Science.gov (United States)

    Steinberg, Susan

    2015-01-01

    The 2015 Space Human Factors Engineering (SHFE) Standing Review Panel (from here on referred to as the SRP) met for a site visit in Houston, TX on December 2 - 3, 2015. The SRP reviewed the updated research plans for the Risk of Inadequate Design of Human and Automation/Robotic Integration (HARI Risk), the Risk of Inadequate Human-Computer Interaction (HCI Risk), and the Risk of Inadequate Mission, Process and Task Design (MPTask Risk). The SRP also received a status update on the Risk of Incompatible Vehicle/Habitat Design (Hab Risk) and the Risk of Performance Errors Due to Training Deficiencies (Train Risk). The SRP is pleased with the progress and responsiveness of the SHFE team. The presentations were much improved this year. The SRP is also pleased with the human-centered design approach. Below are some of the more extensive comments from the SRP. We have also made comments in each section concerning gaps/tasks in each. The comments below reflect more significant changes that impact more than just one particular section.

  15. SNPs altering ammonium transport activity of human Rhesus factors characterized by a yeast-based functional assay.

    Directory of Open Access Journals (Sweden)

    Aude Deschuyteneer

    Full Text Available Proteins of the conserved Mep-Amt-Rh family, including mammalian Rhesus factors, mediate transmembrane ammonium transport. Ammonium is an important nitrogen source for the biosynthesis of amino acids but is also a metabolic waste product. Its disposal in urine plays a critical role in the regulation of the acid/base homeostasis, especially with an acid diet, a trait of Western countries. Ammonium accumulation above a certain concentration is however pathologic, the cytotoxicity causing fatal cerebral paralysis in acute cases. Alteration in ammonium transport via human Rh proteins could have clinical outcomes. We used a yeast-based expression assay to characterize human Rh variants resulting from non synonymous single nucleotide polymorphisms (nsSNPs with known or unknown clinical phenotypes and assessed their ammonium transport efficiency, protein level, localization and potential trans-dominant impact. The HsRhAG variants (I61R, F65S associated to overhydrated hereditary stomatocytosis (OHSt, a disease affecting erythrocytes, proved affected in intrinsic bidirectional ammonium transport. Moreover, this study reveals that the R202C variant of HsRhCG, the orthologue of mouse MmRhcg required for optimal urinary ammonium excretion and blood pH control, shows an impaired inherent ammonium transport activity. Urinary ammonium excretion was RHcg gene-dose dependent in mouse, highlighting MmRhcg as a limiting factor. HsRhCG(R202C may confer susceptibility to disorders leading to metabolic acidosis for instance. Finally, the analogous R211C mutation in the yeast ScMep2 homologue also impaired intrinsic activity consistent with a conserved functional role of the preserved arginine residue. The yeast expression assay used here constitutes an inexpensive, fast and easy tool to screen nsSNPs reported by high throughput sequencing or individual cases for functional alterations in Rh factors revealing potential causal variants.

  16. SNPs altering ammonium transport activity of human Rhesus factors characterized by a yeast-based functional assay.

    Science.gov (United States)

    Deschuyteneer, Aude; Boeckstaens, Mélanie; De Mees, Christelle; Van Vooren, Pascale; Wintjens, René; Marini, Anna Maria

    2013-01-01

    Proteins of the conserved Mep-Amt-Rh family, including mammalian Rhesus factors, mediate transmembrane ammonium transport. Ammonium is an important nitrogen source for the biosynthesis of amino acids but is also a metabolic waste product. Its disposal in urine plays a critical role in the regulation of the acid/base homeostasis, especially with an acid diet, a trait of Western countries. Ammonium accumulation above a certain concentration is however pathologic, the cytotoxicity causing fatal cerebral paralysis in acute cases. Alteration in ammonium transport via human Rh proteins could have clinical outcomes. We used a yeast-based expression assay to characterize human Rh variants resulting from non synonymous single nucleotide polymorphisms (nsSNPs) with known or unknown clinical phenotypes and assessed their ammonium transport efficiency, protein level, localization and potential trans-dominant impact. The HsRhAG variants (I61R, F65S) associated to overhydrated hereditary stomatocytosis (OHSt), a disease affecting erythrocytes, proved affected in intrinsic bidirectional ammonium transport. Moreover, this study reveals that the R202C variant of HsRhCG, the orthologue of mouse MmRhcg required for optimal urinary ammonium excretion and blood pH control, shows an impaired inherent ammonium transport activity. Urinary ammonium excretion was RHcg gene-dose dependent in mouse, highlighting MmRhcg as a limiting factor. HsRhCG(R202C) may confer susceptibility to disorders leading to metabolic acidosis for instance. Finally, the analogous R211C mutation in the yeast ScMep2 homologue also impaired intrinsic activity consistent with a conserved functional role of the preserved arginine residue. The yeast expression assay used here constitutes an inexpensive, fast and easy tool to screen nsSNPs reported by high throughput sequencing or individual cases for functional alterations in Rh factors revealing potential causal variants.

  17. The development of human factors technologies -The development of human behaviour analysis techniques-

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Lee, Yong Heui; Park, Keun Ok; Chun, Se Woo; Suh, Sang Moon; Park, Jae Chang [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of)

    1995-07-01

    In order to contribute to human error reduction through the studies on human-machine interaction in nuclear power plants, this project has objectives to develop SACOM(Simulation Analyzer with a Cognitive Operator Model) and techniques for human error analysis and application. In this year, we studied the followings: (1) Site investigation of operator tasks, (2) Development of operator task micro structure and revision of micro structure, (3) Development of knowledge representation software and SACOM prototype, (4) Development of performance assessment methodologies in task simulation and analysis of the effects of performance shaping factors. human error analysis and application techniques> (1) Classification of error shaping factors(ESFs) and development of software for ESF evaluation, (2) Analysis of human error occurrences and revision of analysis procedure, (3) Experiment for human error data collection using a compact nuclear simulator, (4) Development of a prototype data base system of the analyzed information on trip cases. 55 figs, 23 tabs, 33 refs. (Author).

  18. Risk management with regard to the effect of human factors

    Directory of Open Access Journals (Sweden)

    I. A. Kiseleva

    2016-01-01

    Full Text Available One of the most important components in today's market is a party decision-making under risk and uncertainty. The first step in making such decisions - to adequately process the information for estimating the future value of assets and the interests of investors probabilities of each particular scenario. The next step is to choose the alternative that has the greatest utility for the investor. Each of these steps is associated with numerous difficulties, the roots of which stem from the specificity of human psychology. The article notes that an integral part of professional risk management is to identify the nature of the object of management in the sphere of economy. Since the domestic theory of risk management is being formed-tion, the problem of a clear comprehensive definition of “risk” becomes now particularly relevant-ness. The article deals with along with economic forecasts of the risks and the human factor in decision-tions solutions. Along with economic forecasts, the report focuses on psychological problems and attempts to take into account the human factor in decision-making at the forecast of risks arising in the company. The important parameters are the status and position of the person in the society, as well as its social well-being. Analysis Meto-ing risk assessment concluded that the need to develop new models and methods of risk management, taking into account the four-lovecheskogo factor. Economic psychology and its applications have developed into a special branch of economic knowledge - the so-called behavioral economics, which surely develops a wide range of economic issues - from the actual theory of individual behavior to the problems of public choice and the financial economy. The most interesting item is the fact that the concept of “risk” is considered from different points of view - as the economist-mathematician with the position, and a psychologist.

  19. Advances in human factors and ergonomics in healthcare

    CERN Document Server

    Duffy, Vincent G

    2010-01-01

    Based on recent research, this book discusses how to improve quality, safety, efficiency, and effectiveness in patient care through the application of human factors and ergonomics principles. It provides guidance for those involved with the design and application of systems and devices for effective and safe healthcare delivery from both a patient and staff perspective. Its huge range of chapters covers everything from the proper design of bed rails to the most efficient design of operating rooms, from the development of quality products to the rating of staff patient interaction. It considers

  20. Recombinant Human Factor IX Produced from Transgenic Porcine Milk

    OpenAIRE

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

    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 precipitat...

  1. Immunoassays of human trefoil factors 1 and 2

    DEFF Research Database (Denmark)

    Vestergaard, E M; Brynskov, J; Ejskjaer, K;

    2004-01-01

    The trefoil factors (TFF1-3) are cysteine-rich peptides expressed in the gastrointestinal tract where they play a critical role in mucosal protection and repair. The expression is up-regulated at sites of ulceration in various chronic inflammatory diseases. Recently, we presented an ELISA method ...... for measurement of TFF3. The aims of the present study were to develop and evaluate ELISAs for the other two known human trefoil peptides, TFF1 and TFF2, and to carry out a cross-sectional study on serum TFF levels in patients with inflammatory bowel disease (IBD)....

  2. Risk factors for human brucellosis in northern Jordan.

    Science.gov (United States)

    Abo-Shehada, M N; Abu-Halaweh, M

    2013-02-01

    Little is known about the risk factors of human brucellosis in Jordan. A case-control study was conducted involving 56 Jordanians who had been treated for brucellosis and at least 3 matched controls for each case (n = 247). Matching was for sex, age, locality (the same village) and socioeconomic standard. Univariate and multivariate logistic regression analyses were used. In all, 17 risk factors were examined related to: contact with various livestock, milk and milk product consumption, drinking-water treatment and disease awareness. Most variables were associated with brucellosis in the univariate analysis but the final logistic model included only 4: milking sheep and goats (OR 3.5), consumption of raw feta cheese made from sheep and goat milk (OR 2.8) and consumption of cows' milk (OR 0.4) and boiled feta cheese (OR 0.4). Small ruminant farmers need to be trained in safer milking practices and feta cheese making procedures.

  3. Mechanisms of drug sensitization to TRA-8, an agonistic death receptor 5 antibody, involve modulation of the intrinsic apoptotic pathway in human breast cancer cells.

    Science.gov (United States)

    Amm, Hope M; Zhou, Tong; Steg, Adam D; Kuo, Huichien; Li, Yufeng; Buchsbaum, Donald J

    2011-04-01

    TRA-8, a monoclonal antibody to death receptor 5 induces apoptosis in various cancer cells; however, the degree of sensitivity varies from highly sensitive to resistant. We have previously shown that resistance to TRA-8 can be reversed by using chemotherapeutic agents, but the mechanism underlying this sensitization was not fully understood. Here, we examined the combination of TRA-8 with doxorubicin or bortezomib in breast cancer cells. In TRA-8-resistant BT-474 and T47D cells, both chemotherapy agents synergistically sensitized cells to TRA-8 cytotoxicity with enhanced activation of apoptosis shown by cleavage of caspases and PARP, reduced Bid, increased proapoptotic Bcl-2 proteins, and increased mitochondrial membrane depolarization. Doxorubicin or bortezomib combined with TRA-8 also reduced Bcl-XL and X-linked inhibitors of apoptosis (XIAP) in treated cells. Furthermore, targeting these proteins with pharmacologic modulators, AT-101, BH3I-2' and AT-406, produced sensitization to TRA-8. TRA-8 combined with AT-101 or BH3I-2', inhibitors of antiapoptotic Bcl-2 proteins, produced synergistic cytotoxicity against ZR-75-1, BT-474, and T47D cells. The IAP-targeting compound, AT-406, was synergistic with TRA-8 in BT-474 cells, and to a lesser extent T47D cells. Activation of the intrinsic apoptotic pathway was a common mechanism associated with sensitization of TRA-8-resistant breast cancer cell lines. Collectively, these studies show that the Bcl-2 and IAP families of proteins are involved in TRA-8 and chemotherapy resistance via their modulation of the intrinsic apoptotic pathway. Targeting these proteins with novel agents sensitized TRA-8-resistant breast cancer cells, suggesting this approach may represent a potent therapeutic strategy in the treatment of breast cancer. ©2011 AACR.

  4. Factors Involved in Extracellular Matrix Turnover in Human Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Gregori Casals

    2013-11-01

    Full Text Available Background: The molecular mechanisms by which myocardial ischemia translates into ventricular remodeling remain unclear. Methods: We investigated whether hypoxia and proinflammatory cytokines are specific inducers of remodeling signals in an in vitro model of cultured adult human ventricular myocytes (AC16 cells. Results:Hypoxia modified the ratio of matrix remodeling factors by increasing the aminoterminal propeptide of type III procollagen (PIIINP and reducing tissue inhibitor of matrix metalloproteinase type 1 (TIMP-1 secretion in AC16 cells. These effects, however, were not associated with either modifications in expression of matrix metalloproteinase type 2, collagen-I or metalloproteinase activity. Hypoxia does, actually increase the production of the cardiac antifibrogenic growth factors, Apelin and VEGF, through an Hypoxia Inducible Factor type 1-dependent mechanism. Concerning proinflammatory signaling pathways, IL1β emerged as a powerful inducer of matrix turnover, since it significantly enhanced PIIINP, TIMP-1 and hyaluronic acid production and increased metalloproteinase activity. In contrast, TNFα did not modify matrix turnover but markedly induced the production of Apelin and VEGF. Conclusion: Hypoxia and increased TNFα activity likely exert cardioprotective actions by activating the cardiac antifibrogenic factors Apelin and VEGF. In contrast, IL1β is a strong promoter of interstitial collagen remodeling that may contribute to ventricular dilation and heart failure in the ischemic myocardium.

  5. [Transfer factor effectiveness patients with persistent genital human papillomavirus infection].

    Science.gov (United States)

    Morfin-Maciel, Blanca María; Sotelo-Ortiz, Julieta Margarita

    2012-01-01

    Human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. Most HPV infections are cleared within two years by the immune system. Only in 5% to 10% of infected women the infection persists determining a high risk of developing cervical intraepithelial neoplasia. The transfer factor (TF) or dialyzable leukocyte extract is an immunomodulator that has been successfully used as an adjuvant in the treatment of intracelular infections such as recurrent herpes virus diseases. One daily dose of transfer factor was given for five days and subsequently each week for five weeks to a group of women with persistent genital papillomavirus infection. We included 13 patients, aged 19 to 45 years, with first intercourse between the ages of 14 to 23, and a mean of three sexual partners in their lifetime. All of them had persistent HPV that had been treated before with local and ablative therapeutic options, including cervical freezing, cervical conization, cauterizing loop, imiquimod and podophyllin. Transfer factor was administered daily for 5 days, and subsequently at 7-day intervals for 5 weeks. We found a clinical significant improvement in the gynaecological evaluation of cervical, vaginal, vulvar and perineal lesions. No recurrences have developed for at least 1 year of follow-up. The use of transfer factor in women with HPV showed resolution of genital lesions, without recurrences for at least one year after the treatment was ended.

  6. Contribution of thermal and nonthermal factors to the regulation of body temperature in humans

    National Research Council Canada - National Science Library

    Igor B. Mekjavic; Ola Eiken

    2006-01-01

    .... This reciprocal inhibition theory, presumably reflecting the manner in which thermal factors contribute to homeothermy in humans, does not incorporate the effect of nonthermal factors on temperature regulation...

  7. SCN5A variant that blocks fibroblast growth factor homologous factor regulation causes human arrhythmia

    Science.gov (United States)

    Musa, Hassan; Kline, Crystal F.; Sturm, Amy C.; Murphy, Nathaniel; Adelman, Sara; Wang, Chaojian; Yan, Haidun; Johnson, Benjamin L.; Csepe, Thomas A.; Kilic, Ahmet; Higgins, Robert S. D.; Janssen, Paul M. L.; Fedorov, Vadim V.; Weiss, Raul; Salazar, Christina; Hund, Thomas J.; Pitt, Geoffrey S.; Mohler, Peter J.

    2015-01-01

    Nav channels are essential for metazoan membrane depolarization, and Nav channel dysfunction is directly linked with epilepsy, ataxia, pain, arrhythmia, myotonia, and irritable bowel syndrome. Human Nav channelopathies are primarily caused by variants that directly affect Nav channel permeability or gating. However, a new class of human Nav channelopathies has emerged based on channel variants that alter regulation by intracellular signaling or cytoskeletal proteins. Fibroblast growth factor homologous factors (FHFs) are a family of intracellular signaling proteins linked with Nav channel regulation in neurons and myocytes. However, to date, there is surprisingly little evidence linking Nav channel gene variants with FHFs and human disease. Here, we provide, to our knowledge, the first evidence that mutations in SCN5A (encodes primary cardiac Nav channel Nav1.5) that alter FHF binding result in human cardiovascular disease. We describe a five*generation kindred with a history of atrial and ventricular arrhythmias, cardiac arrest, and sudden cardiac death. Affected family members harbor a novel SCN5A variant resulting in p.H1849R. p.H1849R is localized in the central binding core on Nav1.5 for FHFs. Consistent with these data, Nav1.5 p.H1849R affected interaction with FHFs. Further, electrophysiological analysis identified Nav1.5 p.H1849R as a gain-of-function for INa by altering steady-state inactivation and slowing the rate of Nav1.5 inactivation. In line with these data and consistent with human cardiac phenotypes, myocytes expressing Nav1.5 p.H1849R displayed prolonged action potential duration and arrhythmogenic afterdepolarizations. Together, these findings identify a previously unexplored mechanism for human Nav channelopathy based on altered Nav1.5 association with FHF proteins. PMID:26392562

  8. Changes in intrinsic subtype of breast cancer during tumor progression in the same patient.

    Science.gov (United States)

    Kim, Chungyeul; Lee, Jungjoo; Lee, Wonyoung; Kim, Aeree

    2015-01-01

    Hormone receptor (HR), human epidermal growth factor receptor 2 (HER2) and Ki67 are important prognostic factors and key variables in classification of the intrinsic subtype, which is essential for choice of adjuvant therapy in breast cancer management. There has been earlier reports that instability of hormonal and HER2 status during progression of tumor. However, breast cancer treatment guidelines recently recommended using the intrinsic subtype that is determined by four immunohistochemical (IHC) assays, estrogen receptor (ER), progesterone receptor (PR), HER2 and Ki67. The purpose of study was to investigate whether the intrinsic subtype changes during the tumor progression from ductal carcinoma in situ (DCIS) to lymph node metastasis. The study included 90 patients with breast cancer in Korea University Guro Hospital, between 1992 and 2008. All individuals had DCIS, invasive carcinoma and lymph node metastasis lesion. IHC staining for ER, PR, HER2 and Ki67 as well as SISH assay for HER2 gene amplification was done with following standard method. Overall 25% of breast cancer changed their intrinsic phenotype during progression. Study demonstrated that a subset of breast cancers can change their intrinsic subtype during cancer progression. These changes have an impact on patient prognosis and management, because each breast cancer subtype has their own differently optimized treatment options according to St. Gallen and NCCN guideline.

  9. Human factors/ergonomics implications of big data analytics: Chartered Institute of Ergonomics and Human Factors annual lecture.

    Science.gov (United States)

    Drury, Colin G

    2015-01-01

    In recent years, advances in sensor technology, connectedness and computational power have come together to produce huge data-sets. The treatment and analysis of these data-sets is known as big data analytics (BDA), and the somewhat related term data mining. Fields allied to human factors/ergonomics (HFE), e.g. statistics, have developed computational methods to derive meaningful, actionable conclusions from these data bases. This paper examines BDA, often characterised by volume, velocity and variety, giving examples of successful BDA use. This examination provides context by considering examples of using BDA on human data, using BDA in HFE studies, and studies of how people perform BDA. Significant issues for HFE are the reliance of BDA on correlation rather than hypotheses and theory, the ethics of BDA and the use of HFE in data visualisation.

  10. Connective Tissue Growth Factor Expression in Human Bronchial Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    Amrita DOSANJH

    2006-01-01

    Connective tissue growth factor (CTGF) is a cysteine-rich protein that promotes extracellular matrix deposition. CTGF is selectively induced by transforming growth factor β and des-Arg kallidin in lung fibroblasts and increases steady-state mRNA levels of α type I collagen, 5α-integrin and fibronectin in fibroblasts. Bronchial epithelial cells have been proposed to functionally interact with lung fibroblasts. We therefore investigated if bronchial epithelial cells are able to synthesize CTGF. Human bronchial epithelial cells were grown to subconfluence in standard growth media. Proliferating cells grown in small airway growth media were harvested following starvation for up to 24 h. Expression of CTGF transcripts was measured by PCR. Immunocytochemistry was also completed using a commercially available antibody.The cells expressed readily detectable CTGF transcripts. Starvation of these cells resulted in a quantitative decline of CTGF transcripts. Direct sequencing of the PCR product identified human CTGF. Immunocytochemistry confirmed intracellular CTGF in the cells and none in negative control cells. We conclude that bronchial epithelial cells could be a novel source of CTGF. Bronchial epithelial cell-derived CTGF could thus directly influence the deposition of collagen in certain fibrotic lung diseases.

  11. Human factors and error prevention in emergency medicine.

    Science.gov (United States)

    Bleetman, Anthony; Sanusi, Seliat; Dale, Trevor; Brace, Samantha

    2012-05-01

    Emergency departments are one of the highest risk areas in health care. Emergency physicians have to assemble and manage unrehearsed multidisciplinary teams with little notice and manage critically ill patients. With greater emphasis on management and leadership skills, there is an increasing awareness of the importance of human factors in making changes to improve patient safety. Non-clinical skills are required to achieve this in an information-poor environment and to minimise the risk of errors. Training in these non-clinical skills is a mandatory component in other high-risk industries, such as aviation and, needs to be part of an emergency physician's skill set. Therefore, there remains an educational gap that we need to fill before an emergency physician is equipped to function as a team leader and manager. This review will examine the lessons from aviation and how these are applicable to emergency medicine. Solutions to averting errors are discussed and the need for formal human factors training in emergency medicine.

  12. Mutations and binding sites of human transcription factors

    KAUST Repository

    Kamanu, Frederick Kinyua

    2012-06-01

    Mutations in any genome may lead to phenotype characteristics that determine ability of an individual to cope with adaptation to environmental challenges. In studies of human biology, among the most interesting ones are phenotype characteristics that determine responses to drug treatments, response to infections, or predisposition to specific inherited diseases. Most of the research in this field has been focused on the studies of mutation effects on the final gene products, peptides, and their alterations. Considerably less attention was given to the mutations that may affect regulatory mechanism(s) of gene expression, although these may also affect the phenotype characteristics. In this study we make a pilot analysis of mutations observed in the regulatory regions of 24,667 human RefSeq genes. Our study reveals that out of eight studied mutation types, insertions are the only one that in a statistically significant manner alters predicted transcription factor binding sites (TFBSs). We also find that 25 families of TFBSs have been altered by mutations in a statistically significant manner in the promoter regions we considered. Moreover, we find that the related transcription factors are, for example, prominent in processes related to intracellular signaling; cell fate; morphogenesis of organs and epithelium; development of urogenital system, epithelium, and tube; neuron fate commitment. Our study highlights the significance of studying mutations within the genes regulatory regions and opens way for further detailed investigations on this topic, particularly on the downstream affected pathways. 2012 Kamanu, Medvedeva, Schaefer, Jankovic, Archer and Bajic.

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

    Science.gov (United States)

    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.

  14. The challenges for human factors in knowledge work

    DEFF Research Database (Denmark)

    Ipsen, Christine; Møller, Niels; Jensen, Per Langaa

    2011-01-01

    The development towards a service and knowledge intensive economy arise new challenges for ergonomics and human factors. Knowledge on work within mass service production exists, but the challenges within knowledge work have still to be addressed. The focus of this paper is on some of the challeng...... with the demands of the knowledge intensive work when KPI’s are central management tools. Especially handling the balance between high motivation and enthusiasm and burn out will be addressed.......The development towards a service and knowledge intensive economy arise new challenges for ergonomics and human factors. Knowledge on work within mass service production exists, but the challenges within knowledge work have still to be addressed. The focus of this paper is on some of the challenges...... in knowledge intensive work to establish productive and satisfying jobs by a case study of our own place of work: a university department. Testimonials from a young associate professor, a first line manager and the department manager lead us to identify some of the major challenges for ergonomics to comply...

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

    Science.gov (United States)

    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.

  16. Stem cell factor and c-Kit in human primordial germ cells and fetal ovaries

    DEFF Research Database (Denmark)

    Høyer, Poul Erik; Byskov, Anne Grete; Møllgård, Kjeld

    2005-01-01

    Prenatal ovary (human), Primordial germ cells, Folliculogenesis, c-Kit, Stem cell factor, immunohistochemistry......Prenatal ovary (human), Primordial germ cells, Folliculogenesis, c-Kit, Stem cell factor, immunohistochemistry...

  17. Verification and validation of human factors issues in control room design and upgrades

    Energy Technology Data Exchange (ETDEWEB)

    Green, M.; Collier, S. [Inst. for Energiteknikk, Halden (Norway). OECD Halden Reactor Project

    1999-12-01

    Systems, facilities and equipment are periodically updated during a power plant's lifetime. This has human factors implications, especially if the central control room is involved. Human factors work may therefore be required. There is an extensive literature on human factors itself, but not so much on how it is verified and validated. Therefore, HRP and the Swedish Nuclear Power Inspectorate commissioned a study. The objective was to review the literature and establish a knowledge base on verification and validation (V and V) of human factors issues. The report first discusses verification and validation as applied to human factors work. It describes a design process and the typical human factors topics involved. It then presents a generic method for V and V of human factors. This is built on a review of standards, guidelines and other references given in an annotated bibliography. The method is illustrated by application to some human factors topics.

  18. Kinetic studies on the activation of human factor X. The role of metal ions on the reaction catalyzed by the venom coagulant protein of Viper russelli.

    Science.gov (United States)

    Morris, S; Robey, F A; Kosow, D P

    1978-07-10

    The effect of Ca2+, Mg2+, and Mn2+ on the initial rate of activation of human Factor X by the venom coagulant protein of Vipera russelli has been investigated. Neither Mg2+ nor Mn2+ alone support the reaction. Ca2+ is an essential activator and exhibits cooperative kinetics. Both Mg2+ and Mn2+ enhance the reaction cooperatively when Ca2+ is present at suboptimal concentrations. Similarly, Ca2+ quenches the intrinsic fluorescence of human Factor X in a cooperative manner. While neither Mg2+ nor Mn2+ by themselves affect the fluorescence of human Factor X, they decrease the cooperativity of the Ca2+ binding to the protein as judged by Hill plots of the Ca2+ -induced fluoresence quenching. EPR measurements indicate that there are three high affinity Mn2+ binding sites on human Factor X which can also bind Ca2+. Positive cooperativity was not observed for Mn2+ binding. These data indicate that Ca2+ can cause a conformational change of the Factor X molecule which allows the activation reaction to proceed. We propose that Mn2+ does not support the activation of human Factor X because it cannot induce a necessary conformational change in the absence of Ca2+.

  19. Cooperative research for human factors review of advanced control rooms

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Park, Jae Chang; Lee, Yong Hee; Oh, In Seok; Lee, Hyun Chul

    2000-12-01

    This project has been performed as cooperative research between KAERI and USNRC. Human factors issues related to soft controls, which is one of key features of advanced HSI, are identified in this project. The issues are analyzed for the evaluation approaches in either experimental or analytical ways. Also, issues requiring additional researches for the evaluation of advanced HSI are identified in the areas of advanced information systems design, computer-based procedure systems, soft controls, human systems interface and plant modernization process, and maintainability of digital systems. The issues are analyzed to discriminate the urgency of researches on it to high, medium, and low levels in consideration of advanced HSI development status in Korea, and some of the issues that can be handled by experimental researches are identified. Additionally, an experimental study is performed to compare operator's performance on human error detection in advanced control rooms vs. in conventional control rooms. It is found that advanced control rooms have several design characteristics hindering operator's error detection performance compared to conventional control rooms.

  20. Expression of epidermal growth factor receptors in human brain tumors.

    Science.gov (United States)

    Libermann, T A; Razon, N; Bartal, A D; Yarden, Y; Schlessinger, J; Soreq, H

    1984-02-01

    The expression of receptors for epidermal growth factor (EGF-R) was determined in 29 samples of brain tumors from 22 patients. Primary gliogenous tumors, of various degrees of cancer, five meningiomas, and two neuroblastomas were examined. Tissue samples were frozen in liquid nitrogen immediately after the operation and stored at -70 degrees until use. Cerebral tissue samples from 11 patients who died from diseases not related to the central nervous system served as controls. Immunoprecipitation of functional EGF-R-kinase complexes revealed high levels of EGF-R in all of the brain tumors of nonneuronal origin that were examined. The level of EGF-R varied between tumors from different patients and also between specimens prelevated from different areas of the same tumor. In contrast, the levels of EGF-R from control specimens were invariably low. The biochemical properties of EGF-R in brain tumor specimens were found to be indistinguishable from those of the well-characterized EGF-R from the A-431 cell line, derived from human epidermoid carcinomas. Human brain EGF-R displays a molecular weight of 170,000 by polyacrylamide-sodium dodecyl sulfate gel electrophoresis. It is phosphorylated mainly in tyrosine residues and shows a 2-dimensional phosphopeptide map similar to that obtained with the phosphorylated EGF-R from membranes of A-431 cells. Our observations suggest that induction of EGF-R expression may accompany the malignant transformation of human brain cells of nonneuronal origin.

  1. Tissue factor: A potent stimulator of Von Willebrand factor synthesis by human umbilical vein endothelial cells

    Science.gov (United States)

    Meiring, Muriel; Allers, W.; Le Roux, E.

    2016-01-01

    Inflammation and dysfunction of endothelial cells are thought to be triggers for the secretion of Von Willebrand factor. The aim of this study was to examine the effects of the inflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF-α) and the coagulation factors, tissue factor and thrombin on the release and cleavage potential of ultra-large von Willebrand factor (ULVWF) and its cleavage protease by cultured human umbilical vein endothelial cells (HUVEC). HUVEC were treated with IL-6, IL-8, and TNF-α, tissue factor (TF) and thrombin, and combinations thereof for 24 hours under static conditions. The cells were then exposed to shear stress after which the VWF-propeptide levels and the VWF cleavage protease, ADAMTS13 content were measured. All treatments and their combinations, excluding IL-6, significantly stimulated the secretion of VWF from HUVEC. The VWF secretion from the HUVEC was stimulated most by the combination of TF with TNF-α. Slightly lower levels of ADAMTS13 secretion were found with all treatments. This may explain the thrombogenicity of patients with inflammation where extremely high VWF levels and slightly lower ADAMTS13 levels are present.

  2. Helicopter flights with night-vision goggles: Human factors aspects

    Science.gov (United States)

    Brickner, Michael S.

    1989-01-01

    Night-vision goggles (NVGs) and, in particular, the advanced, helmet-mounted Aviators Night-Vision-Imaging System (ANVIS) allows helicopter pilots to perform low-level flight at night. It consists of light intensifier tubes which amplify low-intensity ambient illumination (star and moon light) and an optical system which together produce a bright image of the scene. However, these NVGs do not turn night into day, and, while they may often provide significant advantages over unaided night flight, they may also result in visual fatigue, high workload, and safety hazards. These problems reflect both system limitations and human-factors issues. A brief description of the technical characteristics of NVGs and of human night-vision capabilities is followed by a description and analysis of specific perceptual problems which occur with the use of NVGs in flight. Some of the issues addressed include: limitations imposed by a restricted field of view; problems related to binocular rivalry; the consequences of inappropriate focusing of the eye; the effects of ambient illumination levels and of various types of terrain on image quality; difficulties in distance and slope estimation; effects of dazzling; and visual fatigue and superimposed symbology. These issues are described and analyzed in terms of their possible consequences on helicopter pilot performance. The additional influence of individual differences among pilots is emphasized. Thermal imaging systems (forward looking infrared (FLIR)) are described briefly and compared to light intensifier systems (NVGs). Many of the phenomena which are described are not readily understood. More research is required to better understand the human-factors problems created by the use of NVGs and other night-vision aids, to enhance system design, and to improve training methods and simulation techniques.

  3. Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo

    DEFF Research Database (Denmark)

    He, Qianchuan; Madsen, Mette; Kilkenney, Adam;

    2005-01-01

    Amnionless (AMN) and cubilin gene products appear to be essential functional subunits of an endocytic receptor called cubam. Mutation of either gene causes autosomal recessive Imerslund-Gräsbeck syndrome (I-GS, OMIM no. 261100) in humans, a disorder characterized by selective intestinal malabsorp......Amnionless (AMN) and cubilin gene products appear to be essential functional subunits of an endocytic receptor called cubam. Mutation of either gene causes autosomal recessive Imerslund-Gräsbeck syndrome (I-GS, OMIM no. 261100) in humans, a disorder characterized by selective intestinal...... malabsorption of cobalamin (vitamin B12) and urinary loss of several specific low-molecular-weight proteins. Vital insight into the molecular pathology of I-GS has been obtained from studies of dogs with a similar syndrome. In this work, we show that I-GS segregates in a large canine kindred due to an in...

  4. Measurement of foot intrinsic muscle morphology and its relationship with human body static balance stability%足部内在肌形态的测量和与人体静态平衡稳定性的关系

    Institute of Scientific and Technical Information of China (English)

    许正勇; 张先熠

    2016-01-01

    为探究采用超声波技术测量足部内在肌形态的可重复性,并通过对足部内在肌形态与闭眼单腿站立时间的相关性分析探讨足部内在肌对维持人体稳定性的影响。对15名健康青年受试者采用B型超声波技术重复测量趾短屈肌、拇短屈肌、拇展肌及小趾展肌等4个足部内在肌的纵向图像以及横截面图像,用ImageJ图像处理软件测量肌肉厚度及横截面积,用SPSS数据处理软件对两次测量数据进行组内相关系数(ICC)分析,以检测该测试方式的可重复性;同时还测量了闭眼单腿站立时间用以评价平衡稳定性,并对其与4个足部内在肌的形态进行Pearson相关系数分析,探讨内在肌形态对静态平衡能力的影响。结果发现:采用超声波技术对足部内在肌厚度与横截面积的两次测量值的ICC值大部分大于0.9,表明该测试方法的可重复性良好;拇展肌厚度、趾短屈肌及小趾展肌的横截面积与闭眼单腿站立时间成显著性相关,而拇展肌横截面积与其成非常显著相关;足部内在肌横截面积越大,闭眼单腿站立时间越久。结果说明:采用B型超声波技术测量足部内在肌形态的可靠性良好;足部内在肌的形态会影响人体静态平衡控制,对足部核心区稳定性的作用不可忽视。%In order to probe into the repeatability of measuring foot intrinsic muscle morphology by using ultrasonic technology, and to study the effects of foot intrinsic muscles on maintaining human body stability by analyzing the correlation between foot intrinsic muscle morphology and eyes closed single leg standing time, the authors repeat-edly measured the longitudinal and cross-sectional images of such 4 foot intrinsic muscles as flexor digitorum bre-vis, flexor hallucis brevis, abductor hallucis and abductor digiti minimi of 15 healthy young testees by using type B ultrasonic technology, measured muscle thicknesses

  5. Intrinsic Depletion or Not

    DEFF Research Database (Denmark)

    Klösgen, Beate; Bruun, Sara; Hansen, Søren;

    with an AFM (2).    The intuitive explanation for the depletion based on "hydrophobic mismatch" between the obviously hydrophilic bulk phase of water next to the hydrophobic polymer. It would thus be an intrinsic property of all interfaces between non-matching materials. The detailed physical interaction path......  The presence of a depletion layer of water along extended hydrophobic interfaces, and a possibly related formation of nanobubbles, is an ongoing discussion. The phenomenon was initially reported when we, years ago, chose thick films (~300-400Å) of polystyrene as cushions between a crystalline...

  6. Human Factors Engineering and Ergonomics in Systems Engineering

    Science.gov (United States)

    Whitmore, Mihriban

    2017-01-01

    The study, discovery, and application of information about human abilities, human limitations, and other human characteristics to the design of tools, devices, machines, systems, job tasks and environments for effective human performance.

  7. 75 FR 69912 - Pipeline Safety: Control Room Management/Human Factors

    Science.gov (United States)

    2010-11-16

    ... Safety: Control Room Management/Human Factors AGENCY: Pipeline and Hazardous Materials Safety..., 2010, PHMSA published a Control Room Management/Human Factors notice of proposed rulemaking (NPRM... to expedite the program implementation deadlines of the Control Room Management/Human Factors rule...

  8. 75 FR 5536 - Pipeline Safety: Control Room Management/Human Factors, Correction

    Science.gov (United States)

    2010-02-03

    ... Safety: Control Room Management/Human Factors, Correction AGENCY: Pipeline and Hazardous Materials Safety... Regulations to address human factors and other aspects of control room management for pipelines where... 63310) entitled ``Pipeline Safety: Control Room Management/Human Factors.'' This final rule...

  9. THE INFLUENCE OF INFORMATION TECHNOLOGIES ON THE HUMAN FACTOR WITHIN AN ORGNANIZATION

    OpenAIRE

    Sarkiunaite, Ingrida

    2005-01-01

    The article discusses a number of important changes of influence of information technologies on human factor within the organization. The focus of the article is on human factor and IT using problem. According to the theoretical and empirical material of IT influence on human factor, aspects of information technology are analyzed.

  10. Design for human factors (DfHF): a grounded theory for integrating human factors into production design processes.

    Science.gov (United States)

    Village, Judy; Searcy, Cory; Salustri, Filipo; Patrick Neumann, W

    2015-01-01

    The 'design for human factors' grounded theory explains 'how' human factors (HF) went from a reactive, after-injury programme in safety, to being proactively integrated into each step of the production design process. In this longitudinal case study collaboration with engineers and HF Specialists in a large electronics manufacturer, qualitative data (e.g. meetings, interviews, observations and reflections) were analysed using a grounded theory methodology. The central tenet in the theory is that when HF Specialists acclimated to the engineering process, language and tools, and strategically aligned HF to the design and business goals of the organisation, HF became a means to improve business performance. This led to engineers 'pulling' HF Specialists onto their team. HF targets were adopted into engineering tools to communicate HF concerns quantitatively, drive continuous improvement, visibly demonstrate change and lead to benchmarking. Senior management held engineers accountable for HF as a key performance indicator, thus integrating HF into the production design process. Practitioner Summary: Research and practice lack explanations about how HF can be integrated early in design of production systems. This three-year case study and the theory derived demonstrate how ergonomists changed their focus to align with design and business goals to integrate HF into the design process.

  11. Age-related changes in the intrinsic functional connectivity of the human ventral vs. dorsal striatum from childhood to middle age

    Directory of Open Access Journals (Sweden)

    James N. Porter

    2015-02-01

    Full Text Available The striatum codes motivated behavior. Delineating age-related differences within striatal circuitry can provide insights into neural mechanisms underlying ontogenic behavioral changes and vulnerabilities to mental disorders. To this end, a dual ventral/dorsal model of striatal function was examined using resting state intrinsic functional connectivity (iFC imaging in 106 healthy individuals, ages 9–44. Broadly, the dorsal striatum (DS is connected to prefrontal and parietal cortices and contributes to cognitive processes; the ventral striatum (VS is connected to medial orbitofrontal and anterior cingulate cortices, and contributes to affective valuation and motivation. Findings revealed patterns of age-related changes that differed between VS and DS iFCs. We found an age-related increase in DS iFC with posterior cingulate cortex (pCC that stabilized after the mid-twenties, but a decrease in VS iFC with anterior insula (aIns and dorsal anterior cingulate cortex (dACC that persisted into mid-adulthood. These distinct developmental trajectories of VS vs. DS iFC might underlie adolescents’ unique behavioral patterns and vulnerabilities to psychopathology, and also speaks to changes in motivational networks that extend well past 25 years old.

  12. Age-related changes in the intrinsic functional connectivity of the human ventral vs. dorsal striatum from childhood to middle age.

    Science.gov (United States)

    Porter, James N; Roy, Amy K; Benson, Brenda; Carlisi, Christina; Collins, Paul F; Leibenluft, Ellen; Pine, Daniel S; Luciana, Monica; Ernst, Monique

    2015-02-01

    The striatum codes motivated behavior. Delineating age-related differences within striatal circuitry can provide insights into neural mechanisms underlying ontogenic behavioral changes and vulnerabilities to mental disorders. To this end, a dual ventral/dorsal model of striatal function was examined using resting state intrinsic functional connectivity (iFC) imaging in 106 healthy individuals, ages 9-44. Broadly, the dorsal striatum (DS) is connected to prefrontal and parietal cortices and contributes to cognitive processes; the ventral striatum (VS) is connected to medial orbitofrontal and anterior cingulate cortices, and contributes to affective valuation and motivation. Findings revealed patterns of age-related changes that differed between VS and DS iFCs. We found an age-related increase in DS iFC with posterior cingulate cortex (pCC) that stabilized after the mid-twenties, but a decrease in VS iFC with anterior insula (aIns) and dorsal anterior cingulate cortex (dACC) that persisted into mid-adulthood. These distinct developmental trajectories of VS vs. DS iFC might underlie adolescents' unique behavioral patterns and vulnerabilities to psychopathology, and also speaks to changes in motivational networks that extend well past 25 years old.

  13. Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics - Fluoroquinolones

    OpenAIRE

    Qiming Li; Longxiang Xie; Quanxin Long; Jinxiao Mao; Hui Li; Mingliang Zhou; Jianping Xie

    2015-01-01

    Antibiotics resistance poses catastrophic threat to global public health. Novel insights into the underlying mechanisms of action will inspire better measures to control drug resistance. Fluoroquinolones are potent and widely prescribed broad-spectrum antibiotics. Bacterial protein degradation pathways represent novel druggable target for the development of new classes of antibiotics. Mycobacteria proteasome accessory factor C (pafC), a component of bacterial proteasome, is involved in fluoro...

  14. Intrinsically Disordered Energy Landscapes

    Science.gov (United States)

    Chebaro, Yassmine; Ballard, Andrew J.; Chakraborty, Debayan; Wales, David J.

    2015-05-01

    Analysis of an intrinsically disordered protein (IDP) reveals an underlying multifunnel structure for the energy landscape. We suggest that such ‘intrinsically disordered’ landscapes, with a number of very different competing low-energy structures, are likely to characterise IDPs, and provide a useful way to address their properties. In particular, IDPs are present in many cellular protein interaction networks, and several questions arise regarding how they bind to partners. Are conformations resembling the bound structure selected for binding, or does further folding occur on binding the partner in a induced-fit fashion? We focus on the p53 upregulated modulator of apoptosis (PUMA) protein, which adopts an -helical conformation when bound to its partner, and is involved in the activation of apoptosis. Recent experimental evidence shows that folding is not necessary for binding, and supports an induced-fit mechanism. Using a variety of computational approaches we deduce the molecular mechanism behind the instability of the PUMA peptide as a helix in isolation. We find significant barriers between partially folded states and the helix. Our results show that the favoured conformations are molten-globule like, stabilised by charged and hydrophobic contacts, with structures resembling the bound state relatively unpopulated in equilibrium.

  15. Human Factors, Habitability and Environmental Health and the Human Integration Design Handbook. Volume 2

    Science.gov (United States)

    Houbec, Keith; Tillman, Barry; Connolly, Janis

    2010-01-01

    For decades, Space Life Sciences and NASA as an Agency have considered NASA-STD-3000, Man-Systems Integration Standards, a significant contribution to human spaceflight programs and to human-systems integration in general. The document has been referenced in numerous design standards both within NASA and by organizations throughout the world. With research program and project results being realized, advances in technology and new information in a variety of topic areas now available, the time arrived to update this extensive suite of requirements and design information. During the past several years, a multi-NASA center effort has been underway to write the update to NASA-STD-3000 with standards and design guidance that would be applicable to all future human spaceflight programs. NASA-STD-3001 - Volumes 1 and 2 - and the Human Integration Design Handbook (HIDH) were created. Volume 1, Crew Health, establishes NASA s spaceflight crew health standards for the pre-flight, in-flight, and post-flight phases of human spaceflight. Volume 2, Human Factors, Habitability and Environmental Health, focuses on the requirements of human-system integration and how the human crew interacts with other systems, and how the human and the system function together to accomplish the tasks for mission success. The HIDH is a compendium of human spaceflight history and knowledge, and provides useful background information and research findings. And as the HIDH is a stand-alone companion to the Standards, the maintenance of the document has been streamlined. This unique and flexible approach ensures that the content is current and addresses the fundamental advances of human performance and human capabilities and constraints research. Current work focuses on the development of new sections of Volume 2 and collecting updates to the HIDH. The new sections in development expand the scope of the standard and address mission operations and support operations. This effort is again collaboration

  16. Effect of Human Cytomegalovirus Infection on Nerve Growth Factor Expression in Human Glioma U251 Cells

    Institute of Scientific and Technical Information of China (English)

    HAI-TAO WANG; BIN WANG; ZHI-JUN LIU; ZHI-QIANG BAI; LING LI; HAI-YAN LIU; DONG-MENG QIAN; ZHI-YONG YAN; XU-XIA SONG

    2009-01-01

    Objectives To explore the change of endogenic nerve growth factor (NGF) expression in human glioma cells infected with human cytomegalovirus (HCMV). Methods U251 cells were cultured in RPMI 1640 culture medium and infected with HCMV AD169 strain in vitro to establish a cell model of viral infection. Morphologic changes of U251 cells were observed under inverted microscope before and after infection with HCMV. Expression of NGF gene and protein of cells was detected by RT-PCR and Western blotting before and after infection with HCMV. Results The cytopathic effects of HCMV-infected cells appeared on day 5 after infection. However, differential NGF expression was evident on day 7. NGF expression was decreased significantly in U251 cells on day 7 after infection in comparison with control group (P<0.05). Conclusion HCMV can down-regulate endogenous NGF levels in human glioma cell line U251.

  17. Amnionless function is required for cubilin brush-border expression and intrinsic factor-cobalamin (vitamin B12) absorption in vivo.

    Science.gov (United States)

    He, Qianchuan; Madsen, Mette; Kilkenney, Adam; Gregory, Brittany; Christensen, Erik I; Vorum, Henrik; Højrup, Peter; Schäffer, Alejandro A; Kirkness, Ewen F; Tanner, Stephan M; de la Chapelle, Albert; Giger, Urs; Moestrup, Søren K; Fyfe, John C

    2005-08-15

    Amnionless (AMN) and cubilin gene products appear to be essential functional subunits of an endocytic receptor called cubam. Mutation of either gene causes autosomal recessive Imerslund-Gräsbeck syndrome (I-GS, OMIM no. 261100) in humans, a disorder characterized by selective intestinal malabsorption of cobalamin (vitamin B12) and urinary loss of several specific low-molecular-weight proteins. Vital insight into the molecular pathology of I-GS has been obtained from studies of dogs with a similar syndrome. In this work, we show that I-GS segregates in a large canine kindred due to an in-frame deletion of 33 nucleotides in exon 10 of AMN. In a second, unrelated I-GS kindred, affected dogs exhibit a homozygous substitution in the AMN translation initiation codon. Studies in vivo demonstrated that both mutations abrogate AMN expression and block cubilin processing and targeting to the apical membrane. The essential features of AMN dysfunction observed in vivo are recapitulated in a heterologous cell-transfection system, thus validating the system for analysis of AMN-cubilin interactions. Characterization of canine AMN mutations that cause I-GS establishes the canine model as an ortholog of the human disorder well suited to studies of AMN function and coevolution with cubilin.

  18. Human roughness perception and possible factors effecting roughness sensation.

    Science.gov (United States)

    Aktar, Tugba; Chen, Jianshe; Ettelaie, Rammile; Holmes, Melvin; Henson, Brian

    2017-06-01

    Surface texture sensation is significant for business success, in particular for solid surfaces for most of the materials; including foods. Mechanisms of roughness perception are still unknown, especially under different conditions such as lubricants with varying viscosities, different temperatures, or under different force loads during the observation of the surface. This work aims to determine the effect of those unknown factors, with applied sensory tests on 62 healthy participants. Roughness sensation of fingertip was tested under different lubricants including water and diluted syrup solutions at room temperature (25C) and body temperature (37C) by using simple pair-wise comparison to observe the just noticeable difference threshold and perception levels. Additionally, in this research applied force load during roughness observation was tested with pair-wise ranking method to illustrate its possible effect on human sensation. Obtained results showed that human's capability of roughness discrimination reduces with increased viscosity of the lubricant, where the influence of the temperature was not found to be significant. Moreover, the increase in the applied force load showed an increase in the sensitivity of roughness discrimination. Observed effects of the applied factors were also used for estimating the oral sensation of texture during eating. These findings are significant for our fundamental understanding to texture perception, and for the development of new food products with controlled textural features. Texture discrimination ability, more specifically roughness discrimination capability, is a significant factor for preference and appreciation for a wide range of materials, including food, furniture, or fabric. To explore the mechanism of sensation capability through tactile senses, it is necessary to identify the relevant factors and define characteristics that dominate the process involved. The results that will be obtained under these principles

  19. Impact of In Vitro System, Chemical Mistures, and Stereochemistry on the Intrinsic Clearance of 1,2,4-Triazole Fungicides in Human and Rat

    Science.gov (United States)

    The exposure of humans and ecologically important species to environmental chemicals typically occurs at unknown concentrations and for uncertain durations. Exposure becomes an internal dose when the chemical crosses the body barrier. Characterizing internal dose is important for...

  20. Expression of epidermal growth factor receptors in human endometrial carcinoma

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Ottesen, B

    1993-01-01

    Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous...... hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent....../inactive endometria and seven of 13 (54%) endometria with adenomatous hyperplasia were EGF-R positive, with an immunostaining pattern rather similar to that of the carcinomas....

  1. Human factors assessments of innovative technologies: Robotics sector

    Energy Technology Data Exchange (ETDEWEB)

    Moran, J.B. [Operating Engineers National Hazmat Program, Beaver, WV (United States)

    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.

  2. Human factors regulation in response to advanced reactor design trends

    Energy Technology Data Exchange (ETDEWEB)

    Innes, L.; Harrison, F. (Atomic Energy Control Board, Ottawa, Ontario (Canada)); Rhodes, W. (Rhodes Associates Inc., Willowdale, Ontario (Canada))

    1993-01-01

    This paper presents the direction being taken in the Canadian regulatory program to guide the incorporation of human factors principles, knowledge, information, and methods in activities such as those that address the design and implementation of the advanced control room (ACR) in nuclear power plants. Within the current activity in the international nuclear industry aimed at the development of ACR concepts, the steps that are being taken to develop design review guidelines for ACRs, such as the work sponsored by the U.S. Nuclear Regulatory Commission are filling an identified important need. The salient feature of most ACR projects is the increased use of digital technology for the analysis, synthesis, management, and display of information. The greatly increased functionality of the devices that can be introduced during such projects allows changes to be made at the design and implementation stages that are not necessarily based on prior function allocation or task analyses.

  3. Integrated Human Factors Design Guidelines for Sound Interface

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jung Woon; Lee, Yong Hee; Oh, In Seok; Lee, Hyun Chul [KAERI, Daejeon (Korea, Republic of); Cha, Woo Chang [Kumoh National Univ. of Technology, Gumi (Korea, Republic of)

    2004-05-15

    Digital MMI, such as CRT, LCD etc., has been used increasingly in the design of main control room of the Korean standard nuclear power plants following the YGN units 3 and 4. The utilization of digital MMI may introduce various kind of sound interface into the control room design. In this project, for five top-level guideline items, including Sound Formats, Alarms, Sound Controls, Communications, and Environments, a total of 147 detail guidelines were developed and a database system for these guidelines was developed. The integrated human factors design guidelines for sound interface and the database system developed in this project will be useful for the design of sound interface of digital MMI in Korean NPPs.

  4. Human Factors in Fire Safety Management and Prevention

    Directory of Open Access Journals (Sweden)

    M.A. Othuman Mydin

    2014-07-01

    Full Text Available Fire protection is the study and practice of mitigating the unwanted effects of potentially destructive fires. It involves the study of the behavior, compartmentalization, and investigation of fire and its related emergencies, as well as the research and development, production, testing and application of mitigating systems. Problems still occurred despite of the adequate fire safety systems installed. For most people in high-risk buildings, not all accidents were caused by them. They were more likely to be the victims of a fire that occurred. Besides damaging their properties and belongings, some people were burned to death for not knowing what to do if fire happens in their place. This paper will present the human factors in fire safety management and prevention system.

  5. [Human factors caused the third plague epidemic in Harbin].

    Science.gov (United States)

    Jin, Dong-Ying; Li, Zhi-Ping

    2011-03-01

    The third plague epidemic in Harbin broke out in 1946 and ended in 1954. Different from the first two plague epidemics (imported), the third prevalence was both imported and idiopathic infectious disease which was caused by human factors. Japanese troops set forbidden zones to build a biological weapon center, which destroyed the natural environment and offered a good growth condition for Citellus Undulatus. In 1945, on the eve of surrender, the Japanese blew up the Unit 731 germ factory located in a bungalow district, which caused diffusion of infected plague fleas. Mice of the district were infected and a man-made plague focus was created. During the prevalence of the third plague, prevention departments at all levels took a series of actions and with people's efforts, the plague was effectively controlled.

  6. Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3).

    Science.gov (United States)

    Senthilkumar, Kalimuthu; Elumalai, Perumal; Arunkumar, Ramachandran; Banudevi, Sivanantham; Gunadharini, Nandagopal Dharmalingam; Sharmila, Govindaraj; Selvakumar, Kandaswamy; Arunakaran, Jagadeesan

    2010-11-01

    Progression of prostate cancer is facilitated by growth factors that activate critical signaling cascades thereby promote prostate cancer cell growth, survival, and migration. To investigate the effect of quercetin on insulin-like growth factor signaling and apoptosis in androgen independent prostate cancer cells (PC-3), IGF-IR, PI-3K, p-Akt, Akt, cyclin D1, Bad, cytochrome c, PARP, caspases-9 and 10 protein levels were assessed by western blot analysis. Mitochondrial membrane potency was detected by rhodamine-123 staining. Quercetin induced caspase-3 activity assay was performed for activation of apoptosis. Further, RT-PCR was also performed for Bad, IGF-I, II, IR, and IGFBP-3 mRNA expression. Quercetin significantly increases the proapoptotic mRNA levels of Bad, IGFBP-3 and protein levels of Bad, cytochrome C, cleaved caspase-9, caspase-10, cleaved PARP and caspase-3 activity in PC-3 cells. IGF-IRβ, PI3K, p-Akt, and cyclin D1 protein expression and mRNA levels of IGF-I, II and IGF-IR were decreased significantly. Further, treatment with PI3K inhibitor (LY294002) and quercetin showed decreased p-Akt levels. Apoptosis is confirmed by loss of mitochondrial membrane potential in quercetin treated PC-3 cells. This study suggests that quercetin decreases the survival of androgen independent prostate cancer cells by modulating the expression of insulin-like growth factors (IGF) system components, signaling molecules and induces apoptosis, which could be very useful for the androgen independent prostate cancer treatment.

  7. Stomagenesis versus myogenesis: Parallels in intrinsic and extrinsic regulation of transcription factor mediated specialized cell-type differentiation in plants and animals.

    Science.gov (United States)

    Putarjunan, Aarthi; Torii, Keiko U

    2016-05-01

    Although the last common unicellular ancestor of plants and animals diverged several billion years ago, and while having developed unique developmental programs that facilitate differentiation and proliferation specific to plant and animal systems, there still exists a high degree of conservation in the logic regulating these developmental processes within these two seemingly diverse kingdoms. Stomatal differentiation in plants involves a series of orchestrated cell division events mediated by a family of closely related bHLH transcription factors (TFs) to create a pair of mature guard cells. These TFs are in turn regulated by a number of upstream signaling components that ultimately function to achieve lineage specific differentiation and organized tissue patterning on the plant epidermis. The logic involved in the specification of the myogenic differentiation program in animals is intriguingly similar to stomatal differentiation in plants: Closely-related myogenic bHLHs, known as MRFs (Myogenic Regulatory Factors) provide lineage specificity essential for cell-fate determination. These MRFs, similar to the bHLHs in plants, are regulated by several upstream signaling cascades that succinctly regulate each differentiation step, leading to the production of mature muscle fibers. This review aims at providing a perspective on the emerging parallels in the logic employed by key bHLH transcription factors and their upstream signaling components that function to precisely regulate key cell-state transition events in the stomatal as well as myogenic cell lineages. © 2016 The Authors. Development, Growth & Differentiation published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Developmental Biologists.

  8. Procoagulant tissue factor-exposing vesicles in human seminal fluid.

    Science.gov (United States)

    Franz, C; Böing, A N; Hau, C M; Montag, M; Strowitzki, T; Nieuwland, R; Toth, B

    2013-06-01

    Recent studies indicate that various types of vesicles, like microparticles (MP) and exosomes, are present in blood, saliva, bone marrow, urine and synovial fluid. These vesicles, which are released upon activation or shear stress, are thought to play a role in coagulation, neovascularisation, inflammation and intercellular signalling. Seminal fluid is a cell-, sperm- and protein-rich suspension. Although seminal fluid is known to contain vesicles like prostasomes, MP and exosomes have never been characterised. Therefore, the aim of our study was to analyse and characterise vesicles in seminal fluid in male partners of patients undergoing controlled ovarian stimulation for IVF/ICSI. MP from seminal fluid of patients during routine IVF/ICSI procedures were detected and analysed with flow cytometry (FACS) and transmission electron microscopy (TEM), using antibodies against tissue factor (TF), CD10, CD13, CD26 and annexin V. The coagulant properties of vesicles were studied using a fibrin generation test. MP were detected in human seminal fluid by both flow cytometry and TEM. Seminal fluid-derived MP expressed CD10, CD13, CD26 and TF, which was highly procoagulant and a powerful trigger of the extrinsic pathway of coagulation. The extent to which the procoagulant activity of MP in seminal fluid contributes to the implantation process itself and therefore affects human reproduction needs to be further elucidated.

  9. Pluripotent stem cell transcription factors during human odontogenesis.

    Science.gov (United States)

    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.

  10. Psychobiological Factors Affecting Cortisol Variability in Human-Dog Dyads

    Science.gov (United States)

    Schöberl, Iris; Wedl, Manuela; Beetz, Andrea; Kotrschal, Kurt

    2017-01-01

    Stress responses within dyads are modulated by interactions such as mutual emotional support and conflict. We investigated dyadic psychobiological factors influencing intra-individual cortisol variability in response to different challenging situations by testing 132 owners and their dogs in a laboratory setting. Salivary cortisol was measured and questionnaires were used to assess owner and dog personality as well as owners' social attitudes towards the dog and towards other humans. We calculated the individual coefficient of variance of cortisol (iCV = sd/mean*100) over the different test situations as a parameter representing individual variability of cortisol concentration. We hypothesized that high cortisol variability indicates efficient and adaptive coping and a balanced individual and dyadic social performance. Female owners of male dogs had lower iCV than all other owner gender-dog sex combinations (F = 14.194, pNeuroticism (NEO-FFI) and of owners who were insecure-ambivalently attached to their dogs (FERT), had low iCV (F = 4.290, p = 0.041 and F = 5.948, p = 0.016), as had dogs of owners with human-directed separation anxiety (RSQ) or dogs of owners with a strong desire of independence (RSQ) (F = 7.661, p = 0.007 and F = 9.192, p = 0.003). We suggest that both owner and dog social characteristics influence dyadic cortisol variability, with the human partner being more influential than the dog. Our results support systemic approaches (i.e. considering the social context) in science and in counselling. PMID:28178272

  11. Selection and characterization of a human neutralizing antibody to human fibroblast growth factor-2

    Energy Technology Data Exchange (ETDEWEB)

    Tao, Jun [Department of Immunology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515 (China); Xiang, Jun-Jian, E-mail: txjj@jnu.edu.cn [Laboratory of Antibody Engineering, College of Life Sciences and Technologies, Jinan University, Guangzhou 510632 (China); Department of Immunology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515 (China); Li, Dan [Department of Immunology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515 (China); Deng, Ning; Wang, Hong; Gong, Yi-Ping [Laboratory of Antibody Engineering, College of Life Sciences and Technologies, Jinan University, Guangzhou 510632 (China)

    2010-04-09

    Compelling evidences suggest that fibroblast growth factor-2 (FGF-2) plays important roles in tumor growth, angiogenesis and metastasis. Molecules blocking the FGF-2 signaling have been proposed as anticancer agents. Through screening of a human scFv phage display library, we have isolated several human single-chain Fv fragments (scFvs) that bind to human FGF-2. After expression and purification in bacteria, one scFv, named 1A2, binds to FGF-2 with a high affinity and specificity, and completes with FGF-2 binding to its receptor. This 1A2 scFv was then cloned into the pIgG1 vector and expressed in 293T cells. The purified hIgG1-1A2 antibody showed a high binding affinity of 8 x 10{sup -9} M to rhFGF-2. In a set of vitro assays, it inhibited various biological activities of FGF-2 such as the proliferation, migration and tube formation of human umbilical vein endothelial cells. More importantly, hIgG1-1A2 antibody also efficiently blocked the growth while inducing apoptosis of glioma cells. For the first time, we generated a human anti-FGF-2 antibody with proven in vitro anti-tumor activity. It may therefore present a new therapeutic candidate for the treatment of cancers that are dependent on FGF-2 signaling for growth and survival.

  12. Humanized versus murine anti-human epidermal growth factor receptor monoclonal antibodies for immunoscintigraphic studies

    Energy Technology Data Exchange (ETDEWEB)

    Morales, Alejo A. Morales; Duconge, Jorge; Alvarez-Ruiz, Daniel; Becquer-Viart, Maria de Los Angeles; Nunez-Gandolff, Gilda; Fernandez, Eduardo; Caballero-Torres, Idania; Iznaga-Escobar, Normando

    2000-02-01

    The anti-human epidermal growth factor receptor (EGF-R) humanized antibody h-R3 (IgG{sub 1}), which binds to an extracellular domain of EGF-R, was used to evaluate the biodistribution on nude mice xenografted with A431 epidermoid carcinoma cell line. Results are compared with its murine version ior egf/r3 monoclonal antibody (mAb). Twenty-one athymic female 4NMRI nu/nu mice were injected intravenously with 10 {mu}g/100 {mu}Ci of {sup 99m}Tc-labeled mAbs. The mAb ior C5 that recognizes an antigen expressed preferentially on the surface of malignant and cytoplasm of normal colorectal cells was used as negative control. Immunoreactivity of {sup 99m}Tc-labeled mAbs was measured by enzyme linked immunosorbent assay on A431 cell line and the immunoreactive fractions determined by Lindmo method. Among all organs significant accumulation was found in tumor (6.14{+-}2.50 %ID/g, 5.06{+-}2.61 %ID/g for murine and humanized mAbs, respectively) 4 h after injection. The immunoreactive fractions were found to be 0.88 and 0.81 for murine and humanized mAb, respectively. Thus, we expect better results using the humanized mAb h-R3 for diagnostic immunoscintigraphy.

  13. The human factors of quality and QA in R D environments

    Energy Technology Data Exchange (ETDEWEB)

    Hill, S.G.

    1990-01-01

    Achieving quality is a human activity. It is therefore important to consider the human in the design, development and evaluation of work processes and environments in an effort to enhance human performance and minimize error. It is also important to allow for individual differences when considering human factors issues. Human Factors is the field of study which can provide information on integrating the human into the system. Human factors and quality are related for the customer of R D work, R D personnel who perform the work, and the quality professional who overviews the process of quality in the work. 18 refs., 1 fig.

  14. Basic Fibroblast Growth Factor and Fibroblast Growth Factor Receptor-1in Human Meningiomas

    Institute of Scientific and Technical Information of China (English)

    YI Wei; CHEN Jian; Filimon H. Golwa; XUE Delin

    2005-01-01

    The expression of basic fibroblast growth factor (bFGF) and fibroblast growth factor receptor-1 (FGFR-1) in human meningiomas and the relationships between their expression and the tumors' histological features and angiogenesis were investigated by means of immunohistochemical technique. The expression of bFGF and FGFR-1 was detected by antibody of bFGF or FGFR-1.The tumors' angiogenesis was evaluated by microvascular density (MVD) and, which was observed by use of CD34-antibody immunohistochemically. The results showed that there were varied degrees of the expression of bFGF and FGFR-1 proteins in meningiomas. The expression was correlated with the tumors' histological characters and angiogenesis. It was concluded that bFGF and FGFR-1 might play important roles in meningiomas' angiogenesis and proliferation. The expression positive rate of bFGF and FGFR-1 may provide an indication of evaluating the histological and malignant degree of the tumor.

  15. Motivating crowding theory - opening the black box of intrinsic motivation

    DEFF Research Database (Denmark)

    Jacobsen, Christian Bøtcher

    2010-01-01

    employees. Motivation crowding theory claims that this may be at the expense of intrinsic motivation, if the extrinsic motivation factor is perceived to be controlling. On the other hand, intrinsic motivation will be enhanced (crowded in), if the extrinsic motivation factor is perceived to be supportive......Public employees work for many other reasons than because they are paid for it. In other words, intrinsic motivation is an important determinant for their performance. Nonetheless, public sector organizations increasingly rely on extrinsic motivation factors such as monetary incentives to motivate....... Studies have found support for the motivation crowding claim, but have neglected intrinsic motivation. This study opens the black box of intrinsic motivation and finds a meaningful distinction between task motivation and public service motivation. Among 2,772 physiotherapists in the Danish public sector...

  16. Motivating crowding theory - opening the black box of intrinsic motivation

    DEFF Research Database (Denmark)

    Jacobsen, Christian Bøtcher

    2010-01-01

    Public employees work for many other reasons than because they are paid for it. In other words, intrinsic motivation is an important determinant for their performance. Nonetheless, public sector organizations increasingly rely on extrinsic motivation factors such as monetary incentives to motivate...... employees. Motivation crowding theory claims that this may be at the expense of intrinsic motivation, if the extrinsic motivation factor is perceived to be controlling. On the other hand, intrinsic motivation will be enhanced (crowded in), if the extrinsic motivation factor is perceived to be supportive....... Studies have found support for the motivation crowding claim, but have neglected intrinsic motivation. This study opens the black box of intrinsic motivation and finds a meaningful distinction between task motivation and public service motivation. Among 2,772 physiotherapists in the Danish public sector...

  17. A HUMAN FACTORS ENGINEERING PROCESS TO SUPPORT HUMAN-SYSTEM INTERFACE DESIGN IN CONTROL ROOM MODERNIZATION

    Energy Technology Data Exchange (ETDEWEB)

    Kovesdi, C.; Joe, J.; Boring, R.

    2017-05-01

    The primary objective of the United States (U.S.) Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) program is to sustain operation of the existing commercial nuclear power plants (NPPs) through a multi-pathway approach in conducting research and development (R&D). The Advanced Instrumentation, Information, and Control (II&C) System Technologies pathway conducts targeted R&D to address aging and reliability concerns with legacy instrumentation and control (I&C) and other information systems in existing U.S. NPPs. Control room modernization is an important part following this pathway, and human factors experts at Idaho National Laboratory (INL) have been involved in conducting R&D to support migration of new digital main control room (MCR) technologies from legacy analog and legacy digital I&C. This paper describes a human factors engineering (HFE) process that supports human-system interface (HSI) design in MCR modernization activities, particularly with migration of old digital to new digital I&C. The process described in this work is an expansion from the LWRS Report INL/EXT-16-38576, and is a requirements-driven approach that aligns with NUREG-0711 requirements. The work described builds upon the existing literature by adding more detail around key tasks and decisions to make when transitioning from HSI Design into Verification and Validation (V&V). The overall objective of this process is to inform HSI design and elicit specific, measurable, and achievable human factors criteria for new digital technologies. Upon following this process, utilities should have greater confidence with transitioning from HSI design into V&V.

  18. Análise de fatores extrínsecos e intrínsecos que predispõem a quedas em idosos Analysis of extrinsic and intrinsic factors that predispose elderly individuals to fall

    Directory of Open Access Journals (Sweden)

    Sionara Tamanini de Almeida

    2012-08-01

    Full Text Available OBJETIVO: Analisar, em uma amostra de idosos de Porto Alegre, RS, os fatores intrínsecos e extrínsecos que predispõem ao risco de queda e fraturas. MÉTODOS: O estudo contou com uma amostra aleatória de 267 idosos, aos quais foram aplicados dois testes de equilíbrio: o Teste do Alcance Funcional (TAF e o Timed Up and Go Test (TUG. Os idosos também responderam a um questionário (13 questões divididas em quatro categorias sobre fatores sociodemográficos e sobre a saúde. RESULTADOS: Participaram idosos de ambos os sexos (76,8% mulheres com idades entre 60 e 90 anos (média = 70,22 anos; DP = ± 7,30 anos. Foram encontradas relações estatisticamente significativas (p OBJECTIVE: In a sample of elderly individuals from Porto Alegre - RS, Brazil, to analyze the intrinsic and extrinsic factors that predispose them to the risk of falls and fractures. METHODS: The study included a random sample of 267 elderly individuals, to whom two balance tests were applied: the Functional Reach Test (FRT and the Timed Up and Go Test (TUG. The elderly also answered a questionnaire (13 questions divided into four categories on sociodemographic and health factors. RESULTS: Elderly individuals from both genders (76.8% women, aged between 60 and 90 years (mean = 70.22 years, SD = ± 7.30 years participated in the study. A statistically significant association (p < 0.05 was found between age, self-perception of eyesight, type of dwelling, last monthly income, and the FRT; the same was found between age range, self-rated health (p < 0.001 and the TUG. CONCLUSION: It was identified that, in the sample of elderly individuals living in Porto Alegre - RS, Brazil, the intrinsic factors that predispose to the risk of falls and fractures are older age, poor self-perception of eyesight, and poor selfrated health; the extrinsic factors are type of dwelling (living in a house and a monthly income < one minimum wage.

  19. Production of human intestinal trefoil factor in Pichia pastoris

    Institute of Scientific and Technical Information of China (English)

    SUN Yong; PENG Xi; Lü Shang-jun; ZHANG Yong; WANG Shi-liang

    2006-01-01

    Objective:To construct a Pichia pastoris (P. Pastoris) expression vector of human intestinal trefoil factor (hITF) and study its expression and purification procedures. Methods:hITF gene encoding mature peptide was modified with a polyhistidine tag sequence at the N-terminal, and then inserted into the P. Pastoris expression vector pGAPZαA at the ownstream of the α-mating factor signal. After gene sequencing, the recombinant pGAPZαA-hITF was transformed into the P. Pastoris strain X-33 with lithium chloride. rhITF was induced to constitutively express in shake flask, and then analyzed with Tricine SDS-PAGE and Western blotting. The obtained rhITF was isolated from the cultured supernatants y ammonium sulfate precipitation, Ni-NTA affinity chromatography, and ultrafiltration. Results:The correctness and integrity of rhITF were identified by restriction digestion and gene sequencing. rhITF was successfully expressed to 50 mg/L as a secretive protein. After purification, the purity was above 95%.Tricine SDS-PAGE and Western-blot analysis howed that rhITF presented as a single band with a molecular weight of 10 kDa, a little larger than 7 879 Da as assayed by mass spectrometry analysis. Conclusion:hITF P. Pastoris expression vector is successfully constructed and rhITF is expressed in P. Pastoris at commercially relevant level. This research lays foundation for the further functional tudying of hITF.

  20. Coconut oil consumption and cardiovascular risk factors in humans.

    Science.gov (United States)

    Eyres, Laurence; Eyres, Michael F; Chisholm, Alexandra; Brown, Rachel C

    2016-04-01

    Coconut oil is being heavily promoted as a healthy oil, with benefits that include support of heart health. To assess the merits of this claim, the literature on the effect of coconut consumption on cardiovascular risk factors and outcomes in humans was reviewed. Twenty-one research papers were identified for inclusion in the review: 8 clinical trials and 13 observational studies. The majority examined the effect of coconut oil or coconut products on serum lipid profiles. Coconut oil generally raised total and low-density lipoprotein cholesterol to a greater extent than cis unsaturated plant oils, but to a lesser extent than butter. The effect of coconut consumption on the ratio of total cholesterol to high-density lipoprotein cholesterol was often not examined. Observational evidence suggests that consumption of coconut flesh or squeezed coconut in the context of traditional dietary patterns does not lead to adverse cardiovascular outcomes. However, due to large differences in dietary and lifestyle patterns, these findings cannot be applied to a typical Western diet. Overall, the weight of the evidence from intervention studies to date suggests that replacing coconut oil with cis unsaturated fats would alter blood lipid profiles in a manner consistent with a reduction in risk factors for cardiovascular disease.

  1. 影响本安电源可靠性的因素及解决方法%The influence factors for the reliability of the intrinsically safe power

    Institute of Scientific and Technical Information of China (English)

    王小波

    2013-01-01

    According to explosion-proof principle and requirement of safety certification mark, this paper analyzes the problem which possibly appears during the production checking and intrinsic safety explosion test. By resolv-ing the circuit consisting of low-dropout regulator, the technical factors influencing the stability of intrinsically safe circuit have been presented. The paper also suggested corresponding solution based on analysis of the discreteness of low dropout regulator, the temperature-drift characteristics of limiting current, differential pressure distribution, max output capacity, heat dissipation, and related electrical specification. In the end, the paper lists all the notice during the design of intrinsically safe circuit, safe explosion-proof test, and manufacturing process.%  矿用本安型仪器需按照安全标志国家中心的要求进行防爆检验。针对由于设计或防爆检验时本安参数测量存在的不合理问题,从防爆原理、安全标志认证要求入手,对本安电路在防爆检验和生产检验过程中可能出现的问题进行了分析;通过对基于低压差稳压器组成的电路进行实例解析,找出了影响本质安全型电路可靠性的技术因素。在分析低压差稳压器的离散性、极限电流温漂特性、压差分配、最大输出能力、散热等电气特性的基础上,提出相应的解决办法。给出了本质安全型电路在设计、防爆检验以及生产中的注意事项。

  2. Congenic mice provide in vivo evidence for a genetic locus that modulates intrinsic transforming growth factor β1-mediated signaling and bone acquisition.

    Science.gov (United States)

    Mukherjee, Aditi; Larson, Emily A; Carlos, Amy S; Belknap, John K; Rotwein, Peter; Klein, Robert F

    2012-06-01

    Osteoporosis, the most common skeletal disorder, is characterized by low bone mineral density (BMD) and an increased risk of fragility fractures. BMD is the best clinical predictor of future osteoporotic fracture risk, but is a complex trait controlled by multiple environmental and genetic determinants with individually modest effects. Quantitative trait locus (QTL) mapping is a powerful method for identifying chromosomal regions encompassing genes involved in shaping complex phenotypes, such as BMD. Here we have applied QTL analysis to male and female genetically-heterogeneous F(2) mice derived from a cross between C57BL/6 and DBA/2 strains, and have identified 11 loci contributing to femoral BMD. Further analysis of a QTL on mouse chromosome 7 following the generation of reciprocal congenic strains has allowed us to determine that the high BMD trait, which tracks with the DBA/2 chromosome and exerts equivalent effects on male and female mice, is manifested by enhanced osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro and by increased growth of metatarsal bones in short-term primary culture. An insertion/deletion DNA polymorphism in Ltbp4 exon 12 that causes the in-frame removal of 12 codons in the DBA/2-derived gene maps within 0.6 Mb of the marker most tightly linked to the QTL. LTBP4, one of four paralogous mouse proteins that modify the bioavailability of the transforming growth factor β (TGF-β) family of growth factors, is expressed in differentiating MSC-derived osteoblasts and in long bones, and reduced responsiveness to TGF-β1 is observed in MSCs of mice homozygous for the DBA/2 chromosome 7. Taken together, our results identify a potential genetic and biochemical relationship between decreased TGF-β1-mediated signaling and enhanced femoral BMD that may be regulated by a variant LTBP4 molecule. Copyright © 2012 American Society for Bone and Mineral Research.

  3. Gaussian Intrinsic Entanglement

    Science.gov (United States)

    Mišta, Ladislav; Tatham, Richard

    2016-12-01

    We introduce a cryptographically motivated quantifier of entanglement in bipartite Gaussian systems called Gaussian intrinsic entanglement (GIE). The GIE is defined as the optimized mutual information of a Gaussian distribution of outcomes of measurements on parts of a system, conditioned on the outcomes of a measurement on a purifying subsystem. We show that GIE vanishes only on separable states and exhibits monotonicity under Gaussian local trace-preserving operations and classical communication. In the two-mode case, we compute GIE for all pure states as well as for several important classes of symmetric and asymmetric mixed states. Surprisingly, in all of these cases, GIE is equal to Gaussian Rényi-2 entanglement. As GIE is operationally associated with the secret-key agreement protocol and can be computed for several important classes of states, it offers a compromise between computable and physically meaningful entanglement quantifiers.

  4. Intrinsic Time Quantum Gravity

    CERN Document Server

    Yu, Hoi Lai

    2016-01-01

    Correct identification of the true gauge symmetry of General Relativity being 3d spatial diffeomorphism invariant(3dDI) (not the conventional infinite tensor product group with principle fibre bundle structure), together with intrinsic time extracted from clean decomposition of the canonical structure yields a self-consistent theory of quantum gravity. A new set of fundamental commutation relations is also presented. The basic variables are the eight components of the unimodular part of the spatial dreibein and eight SU(3) generators which correspond to Klauder's momentric variables that characterize a free theory of quantum gravity. The commutation relations are not canonical, but have well defined group theoretical meanings. All fundamental entities are dimensionless; and the quantum wave functionals are preferentially in the dreibein representation. The successful quantum theory of gravity involves only broad spectrum of knowledge and deep insights but no exotic idea.

  5. The Intrinsic Analysis In Nicholas Sparks’ Novel Message In A Bottle

    OpenAIRE

    Hotden

    2011-01-01

    Literature is a kind of imaginative writing. It reflects a problem of life done by human being. Novel is one of literary work that has intrinsic elements. Studying intrinsic elements in a novel, it means to study life experience of group human being through a novel. The writer analyzes the intrinsic elements in novel Message in a Bottle by Nicholas Sparks. Therefore, this paper is entitled become: THE INTRINSIC ANALYSIS IN NICHOLAS SPARKS’ NOVEL MESSAGE IN A BOTTLE. The writer is interested i...

  6. Creativity as Mediator for Intrinsic Motivation and Sales Performance

    Science.gov (United States)

    Bodla, Mahmood A.; Naeem, Basharat

    2014-01-01

    Substantial theoretical and empirical literature indicates inconsistent performance implications of intrinsic motivation, suggesting the possibility of some explanatory mechanisms. However, little is known about the factors that might explain intrinsic motivation and sales force performance relation, particularly in highly competitive and…

  7. In vivo measurement of actinides in the human lung. [Calibration and comparison of Phoswich, large-area proportional counter, and intrinsic germanium planar array detector systems

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, A.L.; Campbell, G.W.; Griffith, R.V.

    1979-11-06

    The problems associated with the in vivo detection and measurement of actinides in the human lung are discussed together with various measurement systems currently in use. In particular, the methods and calibration procedures employed at the Lawrence Livermore Laboratory, namely, the use of twin Phoswich detectors and a new, more realistic, tissue-equivalent phantom, are described. Methods for the measurement of chest-wall thickness, fat content, and normal human background counts are also discussed. Detection-efficiency values and minimum detectable activity estimates are given for three common actinides, /sup 238/Pu, /sup 239/Pu, and /sup 241/Am.

  8. Factors governing risk of cougar attacks on humans

    Science.gov (United States)

    Mattson, David; Logan, Kenneth; Sweanor, Linda

    2011-01-01

    Since the 1980s wildlife managers in the United States and Canada have expressed increasing concern about the physical threat posed by cougars (Puma concolor) to humans. We developed a conceptual framework and analyzed 386 human–cougar encounters (29 fatal attacks, 171 instances of nonfatal contact, and 186 close-threatening encounters) to provide information relevant to public safety. We conceived of human injury and death as the outcome of 4 transitions affected by different suites of factors: (1) a human encountering a cougar: (2) given an encounter, odds that the cougar would be aggressive; (3) given aggression, odds that the cougar would attack; and (4) given an attack, odds that the human would die. We developed multivariable logistic regression models to explain variation in odds at transitions three and four using variables pertaining to characteristics of involved people and cougars. Young (≤ 2.5 years) or unhealthy (by weight, condition, or disease) cougars were more likely than any others to be involved in close (typically females were more likely than males to attack, and of attacking animals, adults were more likely than juveniles to kill the victim (32% versus 9% fatality, respectively). During close encounters, victims who used a weapon killed the involved cougar in 82% of cases. Other mitigating behaviors (e.g., yelling, backing away, throwing objects, increasing stature) also substantially lessened odds of attack. People who were moving quickly or erratically when an encounter happened (running, playing, skiing, snowshoeing, biking, ATV-riding) were more likely to be attacked and killed compared to people who were less active (25% versus 8% fatality). Children (≤ 10 years) were more likely than single adults to be attacked, but intervention by people of any age reduced odds of a child’s death by 4.6×. Overall, cougar attacks on people in Canada and the United States were rare (currently 4 to 6/year) compared to attacks by large felids and

  9. B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans

    NARCIS (Netherlands)

    Avery, Danielle T.; Deenick, Elissa K.; Ma, Cindy S.; Suryani, Santi; Simpson, Nicholas; Chew, Gary Y.; Chan, Tyani D.; Palendira, Umamainthan; Bustamante, Jacinta; Boisson-Dupuis, Stephanie; Choo, Sharon; Bleasel, Karl E.; Peake, Jane; King, Cecile; French, Martyn A.; Engelhard, Dan; Al-Hajjar, Sami; Al-Muhsen, Saleh; Magdorf, Klaus; Roesler, Joachim; Arkwright, Peter D.; Hissaria, Pravin; Riminton, D. Sean; Wong, Melanie; Brink, Robert; Fulcher, David A.; Casanova, Jean-Laurent; Cook, Matthew C.; Tangye, Stuart G.

    2010-01-01

    Engagement of cytokine receptors by specific ligands activate Janus kinase-signal transducer and activator of transcription (STAT) signaling pathways. The exact roles of STATs in human lymphocyte behavior remain incompletely defined. Interleukin (IL)-21 activates STAT1 and STAT3 and has emerged as a

  10. Intrinsic antecedents of academic research productivity of a large ...

    African Journals Online (AJOL)

    Intrinsic antecedents of academic research productivity of a large South African university. ... are made for how academics might increase their research productivity. ... South Africa, research productivity, human resources management ...

  11. A development of the Human Factors Assessment Guide for the Study of Erroneous Human Behaviors in Nuclear Power Plants

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Yeon Ju; Lee, Yong Hee; Jang, Tong Il; Kim, Sa Kil [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-08-15

    The aim of this paper is to describe a human factors assessment guide for the study of the erroneous characteristic of operators in nuclear power plants (NPPs). We think there are still remaining the human factors issues such as an uneasy emotion, fatigue and stress, varying mental workload situation by digital environment, and various new type of unsafe response to digital interface for better decisions, although introducing an advanced main control room. These human factors issues may not be resolved through the current human reliability assessment which evaluates the total probability of a human error occurring throughout the completion of a specific task. This paper provides an assessment guide for the human factors issues a set of experimental methodology, and presents an assessment case of measurement and analysis especially from neuro physiology approach. It would be the most objective psycho-physiological research technique on human performance for a qualitative analysis considering the safety aspects. This paper can be trial to experimental assessment of erroneous behaviors and their influencing factors, and it can be used as an index for recognition and a method to apply human factors engineering V and V, which is required as a mandatory element of human factor engineering program plan for a NPP design.

  12. Hemoglobin is a co-factor of human trypanosome lytic factor.

    Directory of Open Access Journals (Sweden)

    Justin Widener

    2007-09-01

    Full Text Available 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.

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

    Science.gov (United States)

    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.

  14. Characterization of golimumab, a human monoclonal antibody specific for human tumor necrosis factor α.

    Science.gov (United States)

    Shealy, David J; Cai, Ann; Staquet, Kim; Baker, Audrey; Lacy, Eilyn R; Johns, Laura; Vafa, Omid; Gunn, George; Tam, Susan; Sague, Sarah; Wang, Dana; Brigham-Burke, Mike; Dalmonte, Paul; Emmell, Eva; Pikounis, Bill; Bugelski, Peter J; Zhou, Honghui; Scallon, Bernard J; Giles-Komar, Jill

    2010-01-01

    We prepared and characterized golimumab (CNTO148), a human IgG1 tumor necrosis factor alpha (TNFα) antagonist monoclonal antibody chosen for clinical development based on its molecular properties. Golimumab was compared with infliximab, adalimumab and etanercept for affinity and in vitro TNFα neutralization. The affinity of golimumab for soluble human TNFα, as determined by surface plasmon resonance, was similar to that of etanercept (18 pM versus 11 pM), greater than that of infliximab (44 pM) and significantly greater than that of adalimumab (127 pM, p=0.018).  The concentration of golimumab necessary to neutralize TNFα-induced E-selectin expression on human endothelial cells by 50% was significantly less than those for infliximab (3.2 fold; p=0.017) and adalimumab (3.3-fold; p=0.008) and comparable to that for etanercept. The conformational stability of golimumab was greater than that of infliximab (primary melting temperature [Tm] 74.8 °C vs. 69.5 °C) as assessed by differential scanning calorimetry.  In addition, golimumab showed minimal aggregation over the intended shelf life when formulated as a high concentration liquid product (100 mg/mL) for subcutaneous administration.  In vivo, golimumab at doses of 1 and 10 mg/kg significantly delayed disease progression in a mouse model of human TNFα-induced arthritis when compared with untreated mice, while infliximab was effective only at 10 mg/kg. Golimumab also significantly reduced histological scores for arthritis severity and cartilage damage, as well as serum levels of pro-inflammatory cytokines and chemokines associated with arthritis. Thus, we have demonstrated that golimumab is a highly stable human monoclonal antibody with high affinity and capacity to neutralize human TNFα in vitro and in vivo.

  15. Human Factors for Situation Assessment in Grid Operations

    Energy Technology Data Exchange (ETDEWEB)

    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

  16. Experiences in the application of human factors engineering to human-system interface modernization

    Energy Technology Data Exchange (ETDEWEB)

    Trueba Alonso, Pedro; Fernandez Illobre, Luis; Ortega Pascual, Fernando [Tecnatom S.A., San Sebastian de los Reyes (Spain). Simulation and Control Rooms Div.

    2015-07-15

    Almost all the existing Nuclear Power Plants (NPPs) include plans to modernize their existing Instrumentation and Control (I and C) systems and associated Human System Interfaces (HSIs), due to obsolescence problems. Tecnatom, S.A. has been participating in modernization programs in NPPs to help them to plan, specify, design and implement the modernization of control rooms and associated I and C and HSIs. The application of Human Factors Engineering (HFE) in modernization programs is nowadays unavoidable. This is because is becoming a regulatory requirement, and also because it is needed to ensure that any plant modification, involving the modernization of I and C and HSI, is well designed to improve overall plant operations, reliability, and safety. This paper shows some experiences obtained during the application of HFE to the modernization of these HSIs. The experience applying HFE in modernizations and design modifications show a positive effect, improving the associated HSIs, with the acceptability of the final user.

  17. Muscle Carnosine Is Associated with Cardiometabolic Risk Factors in Humans.

    Directory of Open Access Journals (Sweden)

    Barbora de Courten

    Full Text Available Carnosine is a naturally present dipeptide abundant in skeletal muscle and an over-the counter food additive. Animal data suggest a role of carnosine supplementation in the prevention and treatment of obesity, insulin resistance, type 2 diabetes and cardiovascular disease but only limited human data exists.Samples of vastus lateralis muscle were obtained by needle biopsy. We measured muscle carnosine levels (high-performance liquid chromatography, % body fat (bioimpedance, abdominal subcutaneous and visceral adiposity (magnetic resonance imaging, insulin sensitivity (euglycaemic hyperinsulinemic clamp, resting energy expenditure (REE, indirect calorimetry, free-living ambulatory physical activity (accelerometers and lipid profile in 36 sedentary non-vegetarian middle aged men (45±7 years with varying degrees of adiposity and glucose tolerance. Muscle carnosine content was positively related to % body fat (r = 0.35, p = 0.04 and subcutaneous (r = 0.38, p = 0.02 but not visceral fat (r = 0.17, p = 0.33. Muscle carnosine content was inversely associated with insulin sensitivity (r = -0.44, p = 0.008, REE (r = -0.58, p<0.001 and HDL-cholesterol levels (r = -0.34, p = 0.048. Insulin sensitivity and physical activity were the best predictors of muscle carnosine content after adjustment for adiposity.Our data shows that higher carnosine content in human skeletal muscle is positively associated with insulin resistance and fasting metabolic preference for glucose. Moreover, it is negatively associated with HDL-cholesterol and basal energy expenditure. Intervention studies targeting insulin resistance, metabolic and cardiovascular disease risk factors are necessary to evaluate its putative role in the prevention and management of type 2 diabetes and cardiovascular disease.

  18. Applying Human Factors during the SIS Life Cycle

    Energy Technology Data Exchange (ETDEWEB)

    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.

  19. Homologous radioimmunoassay for human epidermal growth factor (urogastrone)

    Energy Technology Data Exchange (ETDEWEB)

    Dailey, G.E.; Kraus, J.W.; Orth, D.N.

    1978-06-01

    Epidermal growth factor (EGF), a polypeptide hormone originally discovered in the mouse submaxillary gland, stimulates growth in a variety of tissues in several species. This hormone has recently been identified in human urine. A homologous RIA for human EGF (RIA-hEGF) has been developed. In general, levels were similar to those recently reported using a heterologous RIA system. Twenty-four-hour urinary excretion of RIA-hEGF by normal adult males and females was 63.0 +- 3.0 and 52.0 +- 3.5 (mean +- SE) ..mu..g/total vol, or 29.7 +- 1.1 and 39.8 +- 1.7 ..mu..g/g creatinine, respectively. Excretion by females taking oral contraceptives was significantly greater (60.1 +- 2.7 ..mu..g/g creatinine; P < 0.01) than that by females who were not. Recent evidence suggests the probable identity of hEGF and ..beta..-urogastrone, a potent inhibitor of gastric acid secretion. Adult males with active peptic ulcer disease appeared to have lower urinary RIA-hEGF excretion (22.9 +- 2.6 ..mu..g/g creatinine) than normal men, but this was not significant (P > 0.05). Several of those with very low values had histories of alcohol abuse. Excretion by patients with Cushing's syndrome was normal. Patients with psoriasis or recovering from major burns excreted both abnormally high and abnormally low levels of RIA-hEGF, with no obvious correlation to their clinical condition. There was no apparent diurnal or postprandial variation in urinary RIA-hEGF excretion by normal subjects. An excellent linear correlation was observed between RIA-hEGF and creatinine concentrations in each urine sample for each subject, suggesting that RIA-hEGF concentration in a random urine sample provides a valid index of 24-h RIA-hEGF excretion.

  20. Comparative view on risk factor of human death

    Energy Technology Data Exchange (ETDEWEB)

    Takeda, Atsuhiko; Sugahara, Tsutomu [Health Research Foundation, Kyoto (Japan)

    1999-09-01

    Human being, namely. 'living' get involved in risk factor. Even if risk is limited to lethal danger, human history is coresponding with numberless risks from ancient up to today. For example, there is increase in risk of death by car-crash owing to get high efficiency in transfer. In Japan, the death toll by car-accident is about ten thousands per year constantly. State of deaths by car-accident not only include driver itself but cyclist and pedestrian. Death rate of both the cyclist and pedestrian amounts to 40% of all. In the age, rate of fracture as result of fall-down while walking is very high. It shows that the aged who give up driving and get out of danger car-crush are attacked the another accident as walkers. On type of danger, the decrease in risk of one-side come to increase in risk of other side. That is 'risk trade-off'. Examples of risk trade-off as above are numerous in environment. Acceptable death rate of various causes is about 10{sup -4} per year in generally. Flight accident happens on rare occasions (10{sup -7} per year in Japan, usually). Spite of insignificant probability, people fear by both reasons that the possibility of rescue is very few and the size of accident is enormous. In the cases of flight and nuclear power plant, estimated accidents is sever, but its probability is very small. Therefore, risk of annual deaths by accident must be considered as multiplication of size of risk (deaths per year) by probability (frequency per year). Obtained result by such analysis shall conduct to right risk perception and stable 'risk acceptance'. (author)