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Sample records for affect human safety

  1. How does human error affect safety in anesthesia?

    PubMed

    Gravenstein, J S

    2000-01-01

    Anesthesia morbidity and mortality, while acceptable, are not zero. Most mishaps have a multifactorial cause in which human error plays a significant part. Good design of anesthesia machines, ventilators, and monitors can prevent some, but not all, human error. Attention to the system in which the errors occur is important. Modern training with simulators is designed to reduce the frequency of human errors and to teach anesthesiologists how to deal with the consequences of such errors. PMID:10601526

  2. 76 FR 65734 - Guidance for Industry on Evaluating the Safety of Flood-Affected Food Crops for Human Consumption...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-24

    ... HUMAN SERVICES Food and Drug Administration Guidance for Industry on Evaluating the Safety of Flood-Affected Food Crops for Human Consumption; Availability AGENCY: Food and Drug Administration, HHS. ACTION... entitled ``Guidance for Industry: Evaluating the Safety of Flood-Affected Food Crops for Human...

  3. Head-up displays and their automotive application: an overview of human factors issues affecting safety.

    PubMed

    Ward, N J; Parkes, A

    1994-12-01

    In response to the recent innovations to use head-up displays (HUDs) in vehicles, this paper discusses the relevant human factors issues arising from this display format and the potential safety implications. A review is made of the relevant HUD literature, primarily from the aviation field. The primary issues for automotive HUDs relevant to system performance and safety in the driving task involve interference from background scene complexity, system novelty, user perceptual style, cognitive disruption, and perceptual tunnelling. Basic research is necessary to investigate the extent of these issues as well as to resolve fundamental design specifications (e.g. HUD size, shape, placement, information content). It is suggested that the introduction of HUDs into vehicles be carefully considered. This will necessitate not only the reconsideration what constitutes an in-vehicle display, but also what constitutes the information to be conveyed. PMID:7857487

  4. Food Affects Human Behavior.

    ERIC Educational Resources Information Center

    Kolata, Gina

    1982-01-01

    A conference on whether food and nutrients affect human behavior was held on November 9, 1982 at the Massachusetts Institute of Technology. Various research studies on this topic are reviewed, including the effects of food on brain biochemistry (particularly sleep) and effects of tryptophane as a pain reducer. (JN)

  5. Roundtable on public policy affecting patient safety.

    PubMed

    Crane, Robert M; Raymond, Brian

    2011-03-01

    On April 15, 2010, patient safety experts were assembled to discuss the adequacy of the public policy response to the Institute of Medicine report "To Err is Human" 10 years after its publication. The experts concluded that additional government actions should be considered. Actions that deserve consideration include the development of an educational campaign to improve public and provider understanding of the issue as a means to support change similar to successful public health campaigns, support the evolution of payment reform away from fee for service, create a clearer aim or goal for patient safety activities, support the development and use of better safety measures to judge status and improvement, and support for additional learning of what works particularly on implementation issues. Participants included: Moderator Robert Crane, senior advisor, Kaiser Permanente Participants Doug Bonacum, vice president, Safety Management, Kaiser Permanente Janet Corrigan, PhD, president and CEO, National Quality Forum Helen Darling, MA, president and CEO, National Business Group on Health Susan Edgman-Levitan, PA, executive director, John D. Stoeckle Center for Primary Care Innovation, Massachusetts General Hospital David M. Lawrence, MD, MPH, chairman and CEO (Retired), Kaiser Foundation Health Plan and Hospitals, Inc Lucian Leape, MD, adjunct professor of Health Policy, Harvard School of Public Health Diane C. Pinakiewicz, president, National Patient Safety Foundation Robert M. Wachter, MD, professor and associate chairman, Department of Medicine, University of California, San Francisco. PMID:22026014

  6. Radar: Human Safety Net

    ERIC Educational Resources Information Center

    Ritz, John M.

    2016-01-01

    Radar is a technology that can be used to detect distant objects not visible to the human eye. A predecessor of radar, called the telemobiloscope, was first used to detect ships in the fog in 1904 off the German coast. Many scientists have worked on the development and refinement of radar (Hertz with electromagnetic waves; Popov with determining…

  7. BAY 81-8973, a full-length recombinant factor VIII: Human heat shock protein 70 improves the manufacturing process without affecting clinical safety.

    PubMed

    Maas Enriquez, Monika; Thrift, John; Garger, Stephen; Katterle, Yvonne

    2016-11-01

    BAY 81-8973 is a full-length, unmodified recombinant human factor VIII (FVIII) approved for the treatment of hemophilia A. BAY 81-8973 has the same amino acid sequence as the currently marketed sucrose-formulated recombinant FVIII (rFVIII-FS) product and is produced using additional advanced manufacturing technologies. One of the key manufacturing advances for BAY 81-8973 is introduction of the gene for human heat shock protein 70 (HSP70) into the rFVIII-FS cell line. HSP70 facilitates proper folding of proteins, enhances cell survival by inhibiting apoptosis, and potentially impacts rFVIII glycosylation. HSP70 expression in the BAY 81-8973 cell line along with other manufacturing advances resulted in a higher-producing cell line and improvements in the pharmacokinetics of the final product as determined in clinical studies. HSP70 protein is not detected in the harvest or in the final BAY 81-8973 product. However, because this is a new process, clinical trial safety assessments included monitoring for anti-HSP70 antibodies. Most patients, across all age groups, had low levels of anti-HSP70 antibodies before exposure to the investigational product. During BAY 81-8973 treatment, 5% of patients had sporadic increases in anti-HSP70 antibody levels above a predefined threshold (cutoff value, 239 ng/mL). No clinical symptoms related to anti-HSP70 antibody development occurred. In conclusion, addition of HSP70 to the BAY 81-8973 cell line is an innovative technology for manufacturing rFVIII aimed at improving protein folding and expression. Improved pharmacokinetics and no effect on safety of BAY 81-8973 were observed in clinical trials in patients with hemophilia A. PMID:27436242

  8. [Reactor safety and human failure].

    PubMed

    Smidt, D

    1979-12-01

    Reactor safety is given by the reliable solution of 3 tasks: on-time shutdown, continuous decay-heat removal, safe containment. After describing the general strategy of their solution even under upset conditions the most important engineered safeguards of pressurized water reactors are summarized. The important problem of human failure is discussed in some more detail. For the example Harrisburg some difficulties, but also some technical countermeasures are illustrated. PMID:537639

  9. Safety and the Human Factor.

    ERIC Educational Resources Information Center

    Smith, Ann

    1982-01-01

    Discusses four elements of safety programs: (1) safety training; (2) safety inspections; (3) accident investigations; and (4) protective safety equipment. Also discusses safety considerations in water/wastewater treatment facilities focusing on falls, drowning hazards, trickling filters, confined space entry, collection/distribution system safety,…

  10. Mobility Techniques that Affect Travel Safety.

    ERIC Educational Resources Information Center

    Newman, M.

    1998-01-01

    Discusses the benefits of individuals with visual impairments using a ball-bearing, rolling-tipped cane for traveling. Major benefits include reduced fatigue, increased durability and sensitivity, more stability, better sound cues, and greater safety. A method for assessing cane congruence is also discussed. (CR)

  11. Human aspects of mission safety

    NASA Technical Reports Server (NTRS)

    Connors, Mary M.

    1989-01-01

    Recent discussions of psychology's involvement in spaceflight have emphasized its role in enhancing space living conditions and incresing crew productivity. While these goals are central to space missions, behavioral scientists should not lose sight of a more basic flight requirement - that of crew safety. This paper examines some of the processes employed in the American space program in support of crew safety and suggests that behavioral scientists could contribute to flight safety, both through these formal processes and through less formal methods. Various safety areas of relevance to behavioral scientists are discussed.

  12. Arthropods affecting the human eye.

    PubMed

    Panadero-Fontán, Rosario; Otranto, Domenico

    2015-02-28

    Ocular infestations by arthropods consist in the parasitization of the human eye, either directly (e.g., some insect larvae causing ophthalmomyiasis) or via arthropods feeding on lachrymal/conjunctival secretions (e.g., some eye-seeking insects, which also act as vectors of eye pathogens). In addition, demodicosis and phthiriasis may also cause eye discomfort in humans. Ophthalmomyiasis by larvae of the families Oestridae, Calliphoridae and Sarcophagidae, are frequent causative agents of human ocular infestations. Over the last decades, the extensive use of macrocyclic lactones in cattle has reduced the frequency of infestations by Hypoderma bovis and Hypoderma lineatum (family Oestridae), and consequently, human infestations by these species. A prompt diagnosis of ocular myiasis (e.g., by serological tests) is pivotal for positive prognoses, particularly when the larvae are not detectable during the ophthalmologic examination. Molecular diagnoses may also assist physicians and parasitologists in achieving time-efficient diagnoses of infestations by Oestridae causing myiasis. Finally, due to widespread international travel to exotic destinations, cases of myiasis are increasing in non-endemic areas, therefore requiring physicians to acquire a profound knowledge of the clinical symptoms linked to these infestations to prevent costly, inappropriate treatments or severe complications. PMID:25620292

  13. Improving Safety through Human Factors Engineering.

    PubMed

    Siewert, Bettina; Hochman, Mary G

    2015-10-01

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

  14. Human cerebral response to animal affective vocalizations

    PubMed Central

    Belin, Pascal; Fecteau, Shirley; Charest, Ian; Nicastro, Nicholas; Hauser, Marc D; Armony, Jorge L

    2007-01-01

    It is presently unknown whether our response to affective vocalizations is specific to those generated by humans or more universal, triggered by emotionally matched vocalizations generated by other species. Here, we used functional magnetic resonance imaging in normal participants to measure cerebral activity during auditory stimulation with affectively valenced animal vocalizations, some familiar (cats) and others not (rhesus monkeys). Positively versus negatively valenced vocalizations from cats and monkeys elicited different cerebral responses despite the participants' inability to differentiate the valence of these animal vocalizations by overt behavioural responses. Moreover, the comparison with human non-speech affective vocalizations revealed a common response to the valence in orbitofrontal cortex, a key component on the limbic system. These findings suggest that the neural mechanisms involved in processing human affective vocalizations may be recruited by heterospecific affective vocalizations at an unconscious level, supporting claims of shared emotional systems across species. PMID:18077254

  15. How do humans affect wildlife nematodes?

    USGS Publications Warehouse

    Weinstein, Sara B.; Lafferty, Kevin D.

    2015-01-01

    Human actions can affect wildlife and their nematode parasites. Species introductions and human-facilitated range expansions can create new host–parasite interactions. Novel hosts can introduce parasites and have the potential to both amplify and dilute nematode transmission. Furthermore, humans can alter existing nematode dynamics by changing host densities and the abiotic conditions that affect larval parasite survival. Human impacts on wildlife might impair parasites by reducing the abundance of their hosts; however, domestic animal production and complex life cycles can maintain transmission even when wildlife becomes rare. Although wildlife nematodes have many possible responses to human actions, understanding host and parasite natural history, and the mechanisms behind the changing disease dynamics might improve disease control in the few cases where nematode parasitism impacts wildlife.

  16. How do humans affect wildlife nematodes?

    PubMed

    Weinstein, Sara B; Lafferty, Kevin D

    2015-05-01

    Human actions can affect wildlife and their nematode parasites. Species introductions and human-facilitated range expansions can create new host-parasite interactions. Novel hosts can introduce parasites and have the potential to both amplify and dilute nematode transmission. Furthermore, humans can alter existing nematode dynamics by changing host densities and the abiotic conditions that affect larval parasite survival. Human impacts on wildlife might impair parasites by reducing the abundance of their hosts; however, domestic animal production and complex life cycles can maintain transmission even when wildlife becomes rare. Although wildlife nematodes have many possible responses to human actions, understanding host and parasite natural history, and the mechanisms behind the changing disease dynamics might improve disease control in the few cases where nematode parasitism impacts wildlife. PMID:25680855

  17. Human factors in safety and business management.

    PubMed

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

    2010-02-01

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

  18. Humans Process Dog and Human Facial Affect in Similar Ways

    PubMed Central

    Schirmer, Annett; Seow, Cui Shan; Penney, Trevor B.

    2013-01-01

    Humans share aspects of their facial affect with other species such as dogs. Here we asked whether untrained human observers with and without dog experience are sensitive to these aspects and recognize dog affect with better-than-chance accuracy. Additionally, we explored similarities in the way observers process dog and human expressions. The stimulus material comprised naturalistic facial expressions of pet dogs and human infants obtained through positive (i.e., play) and negative (i.e., social isolation) provocation. Affect recognition was assessed explicitly in a rating task using full face images and images cropped to reveal the eye region only. Additionally, affect recognition was assessed implicitly in a lexical decision task using full faces as primes and emotional words and pseudowords as targets. We found that untrained human observers rated full face dog expressions from the positive and negative condition more accurately than would be expected by chance. Although dog experience was unnecessary for this effect, it significantly facilitated performance. Additionally, we observed a range of similarities between human and dog face processing. First, the facial expressions of both species facilitated lexical decisions to affectively congruous target words suggesting that their processing was equally automatic. Second, both dog and human negative expressions were recognized from both full and cropped faces. Third, female observers were more sensitive to affective information than were male observers and this difference was comparable for dog and human expressions. Together, these results extend existing work on cross-species similarities in facial emotions and provide evidence that these similarities are naturally exploited when humans interact with dogs. PMID:24023954

  19. Human factors and safety in emergency medicine

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

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

  20. Human safety in the lunar environment

    NASA Technical Reports Server (NTRS)

    Lewis, Robert H.

    1992-01-01

    Any attempt to establish a continuously staffed base or permanent settlement on the Moon must safely meet the challenges posed by the Moon's surface environment. This environment is drastically different from the Earth's, and radiation and meteoroids are significant hazards to human safety. These dangers may be mitigated through the use of underground habitats, the piling up of lunar materials as shielding, and the use of teleoperated devices for surface operations. The lunar environment is detailed along with concepts for survival.

  1. Human factors engineering and patient safety.

    PubMed

    Scanlon, Matthew C; Karsh, Ben-Tzion; Densmore, Emily M

    2006-12-01

    The pediatric population has features different from those of adults and that are dynamic during the pediatric age range. Pediatric-specific issues result in potential risks for harm during medical care. Basic and applied human factors research has resulted in improvements in the performance of health adults and those adults who have functional limitations. Future work should focus on systematically understanding the human factors needs of children with the goal of redesigning systems of health care to optimize the safety of children and the performance of their care providers. PMID:17126685

  2. Human factors and ergonomics as a patient safety practice

    PubMed Central

    Carayon, Pascale; Xie, Anping; Kianfar, Sarah

    2014-01-01

    Background Human factors and ergonomics (HFE) approaches to patient safety have addressed five different domains: usability of technology; human error and its role in patient safety; the role of healthcare worker performance in patient safety; system resilience; and HFE systems approaches to patient safety. Methods A review of various HFE approaches to patient safety and studies on HFE interventions was conducted. Results This paper describes specific examples of HFE-based interventions for patient safety. Studies show that HFE can be used in a variety of domains. Conclusions HFE is a core element of patient safety improvement. Therefore, every effort should be made to support HFE applications in patient safety. PMID:23813211

  3. Safety of human papillomavirus vaccines: a review

    PubMed Central

    Stillo, Michela; Carrillo Santisteve, Paloma; Lopalco, Pier Luigi

    2015-01-01

    Introduction: Between 2006 and 2009, two different human papillomavirus virus (HPV) vaccines were licensed for use: a quadrivalent (qHPVv) and a bivalent (bHPVv) vaccine. Since 2008, HPV vaccination programmes have been implemented in the majority of the industrialized countries. Since 2013, HPV vaccination has been part of the national programs of 66 countries including almost all countries in North America and Western Europe. Despite all the efforts made by individual countries, coverage rates are lower than expected. Vaccine safety represents one of the main concerns associated with the lack of acceptance of HPV vaccination both in the European Union/European Economic Area and elsewhere. Areas covered: Safety data published on bivalent and quadrivalent HPV vaccines, both in pre-licensure and post-licensure phase, are reviewed. Expert opinion: Based on the latest scientific evidence, both HPV vaccines seem to be safe. Nevertheless, public concern and rumors about adverse events (AE) represent an important barrier to overcome in order to increase vaccine coverage. Passive surveillance of AEs is an important tool for detecting safety signals, but it should be complemented by activities aimed at assessing the real cause of all suspect AEs. Improved vaccine safety surveillance is the first step for effective communication based on scientific evidence. PMID:25689872

  4. Zoonotic helminths affecting the human eye

    PubMed Central

    2011-01-01

    Nowaday, zoonoses are an important cause of human parasitic diseases worldwide and a major threat to the socio-economic development, mainly in developing countries. Importantly, zoonotic helminths that affect human eyes (HIE) may cause blindness with severe socio-economic consequences to human communities. These infections include nematodes, cestodes and trematodes, which may be transmitted by vectors (dirofilariasis, onchocerciasis, thelaziasis), food consumption (sparganosis, trichinellosis) and those acquired indirectly from the environment (ascariasis, echinococcosis, fascioliasis). Adult and/or larval stages of HIE may localize into human ocular tissues externally (i.e., lachrymal glands, eyelids, conjunctival sacs) or into the ocular globe (i.e., intravitreous retina, anterior and or posterior chamber) causing symptoms due to the parasitic localization in the eyes or to the immune reaction they elicit in the host. Unfortunately, data on HIE are scant and mostly limited to case reports from different countries. The biology and epidemiology of the most frequently reported HIE are discussed as well as clinical description of the diseases, diagnostic considerations and video clips on their presentation and surgical treatment. Homines amplius oculis, quam auribus credunt Seneca Ep 6,5 Men believe their eyes more than their ears PMID:21429191

  5. National plan to enhance aviation safety through human factors improvements

    NASA Technical Reports Server (NTRS)

    Foushee, Clay

    1990-01-01

    The purpose of this section of the plan is to establish a development and implementation strategy plan for improving safety and efficiency in the Air Traffic Control (ATC) system. These improvements will be achieved through the proper applications of human factors considerations to the present and future systems. The program will have four basic goals: (1) prepare for the future system through proper hiring and training; (2) develop a controller work station team concept (managing human errors); (3) understand and address the human factors implications of negative system results; and (4) define the proper division of responsibilities and interactions between the human and the machine in ATC systems. This plan addresses six program elements which together address the overall purpose. The six program elements are: (1) determine principles of human-centered automation that will enhance aviation safety and the efficiency of the air traffic controller; (2) provide new and/or enhanced methods and techniques to measure, assess, and improve human performance in the ATC environment; (3) determine system needs and methods for information transfer between and within controller teams and between controller teams and the cockpit; (4) determine how new controller work station technology can optimally be applied and integrated to enhance safety and efficiency; (5) assess training needs and develop improved techniques and strategies for selection, training, and evaluation of controllers; and (6) develop standards, methods, and procedures for the certification and validation of human engineering in the design, testing, and implementation of any hardware or software system element which affects information flow to or from the human.

  6. Human freezing in response to affective films.

    PubMed

    Hagenaars, Muriel A; Roelofs, Karin; Stins, John F

    2014-01-01

    Human freezing has been objectively assessed using a passive picture viewing paradigm as an analog for threat. These results should be replicated for other stimuli in order to determine their stability and generalizability. Affective films are used frequently to elicit affective responses, but it is unknown whether they also elicit freezing-like defense responses. To test whether this is the case, 50 participants watched neutral, pleasant and unpleasant film fragments while standing on a stabilometric platform and wearing a polar band to assess heart rate. Freezing-like responses (indicated by overall reduced body sway and heart rate deceleration) were observed for the unpleasant film only. The unpleasant film also elicited early reduced body sway (1-2 s after stimulus onset). Heart rate and body sway were correlated during the unpleasant film only. The results suggest that ecologically valid stimuli like films are adequate stimuli in evoking defense responses. The results also underscore the importance of including time courses in human experimental research on defense reactions in order to delineate different stages in the defense response. PMID:23805855

  7. Does Excessive Daytime Sleepiness Affect Children's Pedestrian Safety?

    PubMed Central

    Avis, Kristin T.; Gamble, Karen L.; Schwebel, David C.

    2014-01-01

    Study Objectives: Many cognitive factors contribute to unintentional pedestrian injury, including reaction time, impulsivity, risk-taking, attention, and decision-making. These same factors are negatively influenced by excessive daytime sleepiness (EDS), which may place children with EDS at greater risk for pedestrian injury. Design, Participants, and Methods: Using a case-control design, 33 children age 8 to 16 y with EDS from an established diagnosis of narcolepsy or idiopathic hypersomnia (IHS) engaged in a virtual reality pedestrian environment while unmedicated. Thirty-three healthy children matched by age, race, sex, and household income served as controls. Results: Children with EDS were riskier pedestrians than healthy children. They were twice as likely to be struck by a virtual vehicle in the virtual pedestrian environment than healthy controls. Attentional skills of looking at oncoming traffic were not impaired among children with EDS, but decision-making for when to cross the street safely was significantly impaired. Conclusions: Results suggest excessive daytime sleepiness (EDS) from the clinical sleep disorders known as the hypersomnias of central origin may have significant consequences on children's daytime functioning in a critical domain of personal safety, pedestrian skills. Cognitive processes involved in safe pedestrian crossings may be impaired in children with EDS. In the pedestrian simulation, children with EDS appeared to show a pattern consistent with inattentional blindness, in that they “looked but did not process” information in their pedestrian environment. Results highlight the need for heightened awareness of potentially irreversible consequences of untreated sleep disorders and identify a possible target for pediatric injury prevention. Citation: Avis KT; Gamble KL; Schwebel DC. Does excessive daytime sleepiness affect children's pedestrian safety? SLEEP 2014;37(2):283-287. PMID:24497656

  8. Human factors and safety in emergency medicine.

    PubMed

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

    1994-12-01

    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. PMID:7740192

  9. Issues affecting advanced passive light-water reactor safety analysis

    SciTech Connect

    Beelman, R.J.; Fletcher, C.D.; Modro, S.M.

    1992-08-01

    Next generation commercial reactor designs emphasize enhanced safety through improved safety system reliability and performance by means of system simplification and reliance on immutable natural forces for system operation. Simulating the performance of these safety systems will be central to analytical safety evaluation of advanced passive reactor designs. Yet the characteristically small driving forces of these safety systems pose challenging computational problems to current thermal-hydraulic systems analysis codes. Additionally, the safety systems generally interact closely with one another, requiring accurate, integrated simulation of the nuclear steam supply system, engineered safeguards and containment. Furthermore, numerical safety analysis of these advanced passive reactor designs wig necessitate simulation of long-duration, slowly-developing transients compared with current reactor designs. The composite effects of small computational inaccuracies on induced system interactions and perturbations over long periods may well lead to predicted results which are significantly different than would otherwise be expected or might actually occur. Comparisons between the engineered safety features of competing US advanced light water reactor designs and analogous present day reactor designs are examined relative to the adequacy of existing thermal-hydraulic safety codes in predicting the mechanisms of passive safety. Areas where existing codes might require modification, extension or assessment relative to passive safety designs are identified. Conclusions concerning the applicability of these codes to advanced passive light water reactor safety analysis are presented.

  10. Issues affecting advanced passive light-water reactor safety analysis

    SciTech Connect

    Beelman, R.J.; Fletcher, C.D.; Modro, S.M.

    1992-01-01

    Next generation commercial reactor designs emphasize enhanced safety through improved safety system reliability and performance by means of system simplification and reliance on immutable natural forces for system operation. Simulating the performance of these safety systems will be central to analytical safety evaluation of advanced passive reactor designs. Yet the characteristically small driving forces of these safety systems pose challenging computational problems to current thermal-hydraulic systems analysis codes. Additionally, the safety systems generally interact closely with one another, requiring accurate, integrated simulation of the nuclear steam supply system, engineered safeguards and containment. Furthermore, numerical safety analysis of these advanced passive reactor designs wig necessitate simulation of long-duration, slowly-developing transients compared with current reactor designs. The composite effects of small computational inaccuracies on induced system interactions and perturbations over long periods may well lead to predicted results which are significantly different than would otherwise be expected or might actually occur. Comparisons between the engineered safety features of competing US advanced light water reactor designs and analogous present day reactor designs are examined relative to the adequacy of existing thermal-hydraulic safety codes in predicting the mechanisms of passive safety. Areas where existing codes might require modification, extension or assessment relative to passive safety designs are identified. Conclusions concerning the applicability of these codes to advanced passive light water reactor safety analysis are presented.

  11. [Medical simulation as a professional tool which affect the safety of the patient used in the learning process].

    PubMed

    Czekajlo, Michael; Dąbrowski, Marek; Dąbrowska, Agata; Torres, Kamil; Torres, Anna; Witt, Magdalena; Gąsiorowski, Łukasz; Szukała, Magdalena

    2015-06-01

    Simulation is the methodology of teaching, learning process using educational equipment from simple simulators, designed to study individual tasks, through advanced mannequins called human patient stimulators faithfully mimic the human and its parameters. The medical simulation's main task is education and improvement patients' safety. Advanced human simulators can realistically cough, vomit with artificial chyme and bleed with artificial blood causing a real stress of medical personnel and the need for immediate action. Medical simulation gives the opportunity to prepare medical personnel to the profession more effectively, in less time than traditional education and also clearly affects the patients' safety. PMID:26098659

  12. Neurovestibular Effects of Spaceflight - Considerations for Human Safety and Performance

    NASA Astrophysics Data System (ADS)

    Groen, E.

    2012-01-01

    From orbital spaceflight we know that astronauts may suffer from sensori-motor problems during the first days in weightlessness, and again upon return to Earth. Symptoms include spatial disorientation, motion illusions, postural imbalance, and motion sickness. Symptoms are typically triggered by head movements, indicating a central role of the vestibular system. TNO research has shown that the same symptoms can be elicited by exposing subjects to hyper-gravity in a human centrifuge. This suggests that not weightlessness itself, but the change in G-load causes vestibular adaptation problems. Suborbital spaceflight will expose participants to a sequence of highly variable G-levels. Hence it can be anticipated that this will affect vestibular functioning, with potential consequences for ride comfort (passengers) and flight safety (crew). We therefore propose to invest in research on the physiological responses to G-load profiles specific for suborbital flights with the purpose to establish comfort and safety guidelines for the commercial spaceflight sector.

  13. [Human papillomavirus vaccine. Efficacy and safety].

    PubMed

    Bruni, Laia; Serrano, Beatriz; Bosch, Xavier; Castellsagué, Xavier

    2015-05-01

    Human papillomavirus (HPV) related disease remains a major cause of morbidity and mortality worldwide. Prophylactic vaccines have been recognized as the most effective intervention to control for HPV-related diseases. This article reviews the major phaseii/iii trials of the bivalent (HPVs16/18), quadrivalent (HPVs6/11/16/18), and the recently approved 9-valent vaccine (HPVs6/11/16/18/31/33/45/52/58). Large trials have been conducted showing the safety, immunogenicity and high efficacy of the bivalent and quadrivalent vaccines in the prevention of pre-invasive lesions and infection, especially when administered at young ages before exposure to HPV. Trials of the 9-valent vaccine have also demonstrated the safety, immunogenicity and efficacy of the vaccine in the prevention of infection and disease associated with the vaccine types, and its potential to substantially increase the overall prevention of HPV-related diseases. Post-licensure country reports have shown the recent and early impact of these vaccines at population level after the implementation of established HPV vaccination programs, including decreases in the prevalence of vaccine HPV types, the incidence of genital warts, and the incidence of high-grade cervical abnormalities. If widely implemented, current HPV vaccines may drastically reduce the incidence of cervical cancer and other HPV-related cancers and diseases. PMID:25937455

  14. Parameters affecting of Akkuyu's safety assessment for severe core damages

    NASA Astrophysics Data System (ADS)

    Kavun, Yusuf; Karasulu, Muzaffer

    2015-07-01

    We have looked at all past core meltdowns (Three Mile Island, Chernobyl and Fukushima incidents) and postulated the fourth one might be taking place in the future most probably in a newly built reactors anywhere of the earth in any type of NPP. The probability of this observation is high considering the nature of the machine and human interaction. Operation experience is a very significant parameter as well as the safety culture of the host nation. The concerns is not just a lack of experience with industry with the new comers, but also the infrastructure and established institutions who will be dealing with the Emergencies. Lack of trained and educated Emergency Response Organizations (ERO) is a major concern. The culture on simple fire drills even makes the difference when a severe condition occurs in the industry. The study assumes the fourth event will be taking place at the Akkuyu NGS and works backwards as required by the "what went wrong " scenarios and comes up with interesting results. The differences studied in depth to determine the impact to the severe accidents. The all four design have now core catchers. We have looked at the operator errors'like in TMI); Operator errors combined with design deficiencies(like in Chernobyl) and natural disasters( like in Fukushima) and found operator errors to be more probable event on the Akkuyu's postulated next incident. With respect to experiences of the operators we do not have any data except for long and successful operating history of the Soviet design reactors up until the Chernobyl incident. Since the Akkuyu will be built, own and operated by the Russians we have found no alarming concerns at the moment. At the moment, there is no body be able to operate those units in Turkey. Turkey is planning to build the required manpower during the transition period. The resolution of the observed parameters lies to work and educate, train of the host nation and exercise together.

  15. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  16. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  17. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 26 2012-07-01 2011-07-01 true Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  18. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  19. 40 CFR 230.76 - Actions affecting human use.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Actions affecting human use. 230.76... Minimize Adverse Effects § 230.76 Actions affecting human use. Minimization of adverse effects on human use... aquatic areas; (c) Timing the discharge to avoid the seasons or periods when human recreational...

  20. Human Hallucinogen Research: Guidelines for Safety

    PubMed Central

    Johnson, Matthew W.; Richards, William A.; Griffiths, Roland R.

    2010-01-01

    There has recently been a renewal of human research with classical hallucinogens (psychedelics). This paper first briefly discusses the unique history of human hallucinogen research, and then reviews the risks of hallucinogen administration and safeguards for minimizing these risks. Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence, their administration involves unique psychological risks. The most likely risk is overwhelming distress during drug action (“bad trip”), which could lead to potentially dangerous behavior such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens. Safeguards against these risks include the exclusion of volunteers with personal or family history of psychotic disorders or other severe psychiatric disorders, establishing trust and rapport between session monitors and volunteer before the session, careful volunteer preparation, a safe physical session environment, and interpersonal support from at least two study monitors during the session. Investigators should probe for the relatively rare hallucinogen persisting perception disorder in follow up contact. Persisting adverse reactions are rare when research is conducted along these guidelines. Incautious research may jeopardize participant safety and future research. However, carefully conducted research may inform the treatment of psychiatric disorders, and may lead to advances in basic science. PMID:18593734

  1. 29 CFR 1960.19 - Other Federal agency standards affecting occupational safety and health.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... safety and health. 1960.19 Section 1960.19 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL... EMPLOYEE OCCUPATIONAL SAFETY AND HEALTH PROGRAMS AND RELATED MATTERS Standards § 1960.19 Other Federal agency standards affecting occupational safety and health. (a) Where employees of different...

  2. 29 CFR 1960.19 - Other Federal agency standards affecting occupational safety and health.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... safety and health. 1960.19 Section 1960.19 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL... EMPLOYEE OCCUPATIONAL SAFETY AND HEALTH PROGRAMS AND RELATED MATTERS Standards § 1960.19 Other Federal agency standards affecting occupational safety and health. (a) Where employees of different...

  3. [Affective computing--a mysterious tool to explore human emotions].

    PubMed

    Li, Xin; Li, Honghong; Dou, Yi; Hou, Yongjie; Li, Changwu

    2013-12-01

    Perception, affection and consciousness are basic psychological functions of human being. Affection is the subjective reflection of different kinds of objects. The foundation of human being's thinking is constituted by the three basic functions. Affective computing is an effective tool of revealing the affectiveness of human being in order to understand the world. Our research of affective computing focused on the relation, the generation and the influent factors among different affections. In this paper, the affective mechanism, the basic theory of affective computing, is studied, the method of acquiring and recognition of affective information is discussed, and the application of affective computing is summarized as well, in order to attract more researchers into this working area. PMID:24645628

  4. Affective Learning: Environmental Ethics and Human Ecology

    ERIC Educational Resources Information Center

    Gough, Noel P.

    1977-01-01

    This discussion of home economics as a discipline which should focus on its affective foundations, covers the following areas: Affective context of home economics education, the adequacy of the home economics value complex for coping with environmental problems, and toward an acceptable environmental ethic. (SH)

  5. Does pre-slaughter stress affect pork safety risk?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Salmonella is the top food safety priority for the pork industry. Although contamination of pork occurs along the slaughter and processing line, infected live pigs entering the abattoir constitute the original Salmonella contamination source. However, the extent of carcass contamination is not only ...

  6. Does Pre-Slaughter Stress Affect Pork Safety?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although much of the Salmonella contamination of pork occurs along the slaughter and processing line, infected pigs delivered to the abattoirs are considered as the original source of pork contaminations. Studies of the effects of pre-slaughter stressors on food safety risk in market pigs are scarce...

  7. The Importance of Multilateral Safety Requirements for Human Spaceflight

    NASA Technical Reports Server (NTRS)

    Pido, Kelle

    2005-01-01

    The International Space Station (ISS) Program initially implemented safety requirements in a series of bilateral agreements between NASA and each International Partner. As the program matured and multilateral processes began to be developed, the differences between these bilaterally agreed requirement sets became more significant. Efforts to develop multilateral safety requirements were hampered for many reasons including assessment of national standards used in the bilateral agreements, requirements baselines for existing contracts, and resource limitations to address requirements changes late in the development and operations phases. To avoid similar requirements issues in the future, international safety requirements need to be developed for human spaceflight. This paper will provide the background of the ISS bilateral Safety and Mission Assurance requirements and processes, describe the activities to develop multilateral safety requirements and processes, and give examples of issues that were encountered. Further, the paper will make recommendations regarding the development of international safety requirements for human spaceflight and the safety topics to be addressed.

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

    PubMed Central

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

    2013-01-01

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

  9. Infrasound from Wind Turbines Could Affect Humans

    ERIC Educational Resources Information Center

    Salt, Alec N.; Kaltenbach, James A.

    2011-01-01

    Wind turbines generate low-frequency sounds that affect the ear. The ear is superficially similar to a microphone, converting mechanical sound waves into electrical signals, but does this by complex physiologic processes. Serious misconceptions about low-frequency sound and the ear have resulted from a failure to consider in detail how the ear…

  10. Does Globalization Affect Human Well-Being?

    ERIC Educational Resources Information Center

    Tsai, Ming-Chang

    2007-01-01

    The prevailing theorizing of globalization's influence of human well-being suggests to assess both the favorable and unfavorable outcomes. This study formulates a dialectical model, adopts a comprehensive globalization measure and uses a three-wave panel data during 1980-2000 to empirically test direct and indirect effects of global flows' human…

  11. Produce Surface Characteristics Affect Product Quality and Safety

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The surface characteristics of fresh-cut fruits and vegetables vary largely among produce types, maturities and processing procedure. Studies have shown that the surface topography of produce significantly affected adherence, attachment, and biofilm formation of bacteria, as well as their removal a...

  12. An Empirical Analysis of Human Performance and Nuclear Safety Culture

    SciTech Connect

    Jeffrey Joe; Larry G. Blackwood

    2006-06-01

    The purpose of this analysis, which was conducted for the US Nuclear Regulatory Commission (NRC), was to test whether an empirical connection exists between human performance and nuclear power plant safety culture. This was accomplished through analyzing the relationship between a measure of human performance and a plant’s Safety Conscious Work Environment (SCWE). SCWE is an important component of safety culture the NRC has developed, but it is not synonymous with it. SCWE is an environment in which employees are encouraged to raise safety concerns both to their own management and to the NRC without fear of harassment, intimidation, retaliation, or discrimination. Because the relationship between human performance and allegations is intuitively reciprocal and both relationship directions need exploration, two series of analyses were performed. First, human performance data could be indicative of safety culture, so regression analyses were performed using human performance data to predict SCWE. It also is likely that safety culture contributes to human performance issues at a plant, so a second set of regressions were performed using allegations to predict HFIS results.

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

    PubMed Central

    Carayon, Pascale; Wood, Kenneth E.

    2011-01-01

    Patient safety is a global challenge that requires knowledge and skills in multiple areas, including human factors and systems engineering. In this chapter, numerous conceptual approaches and methods for analyzing, preventing and mitigating medical errors are described. Given the complexity of healthcare work systems and processes, we emphasize the need for increasing partnerships between the health sciences and human factors and systems engineering to improve patient safety. Those partnerships will be able to develop and implement the system redesigns that are necessary to improve healthcare work systems and processes for patient safety. PMID:20543237

  14. Safety assessment of probiotics for human use

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The safety of probiotics is tied to their intended use, which includes consideration of the potential vulnerability of the consumer or patient, dose and duration of consumption, and both the manner and frequency of administration. Unique to probiotics is that they are living organisms when administ...

  15. Safety assessment of probiotics for human use

    PubMed Central

    Akkermans, Louis MA; Haller, Dirk; Hammerman, Cathy; Heimbach, James; Hörmannsperger, Gabriele; Huys, Geert; Levy, Dan D; Lutgendorff, Femke; Mack, David; Phothirath, Phoukham; Solano-Aguilar, Gloria; Vaughan, Elaine

    2010-01-01

    The safety of probiotics is tied to their intended use, which includes consideration of potential vulnerability of the consumer or patient, dose and duration of consumption, and both the manner and frequency of administration. Unique to probiotics is that they are alive when administered, and unlike other food or drug ingredients, possess the potential for infectivity or in situ toxin production. Since numerous types of microbes are used as probiotics, safety is also intricately tied to the nature of the specific microbe being used. The presence of transferable antibiotic resistance genes, which comprises a theoretical risk of transfer to a less innocuous member of the gut microbial community, must also be considered. Genetic stability of the probiotic over time, deleterious metabolic activities, and the potential for pathogenicity or toxicogenicity must be assessed depending on the characteristics of the genus and species of the microbe being used. Immunological effects must be considered, especially in certain vulnerable populations, including infants with undeveloped immune function. A few reports about negative probiotic effects have surfaced, the significance of which would be better understood with more complete understanding of the mechanisms of probiotic interaction with the host and colonizing microbes. Use of readily available and low cost genomic sequencing technologies to assure the absence of genes of concern is advisable for candidate probiotic strains. The field of probiotic safety is characterized by the scarcity of studies specifically designed to assess safety contrasted with the long history of safe use of many of these microbes in foods. PMID:21327023

  16. Fall protection characteristics of safety belts and human impact tolerance.

    PubMed

    Hino, Yasumichi; Ohdo, Katsutoshi; Takahashi, Hiroki

    2014-01-01

    Many fatal accidents due to falls from heights have occurred at construction sites not only in Japan but also in other countries. This study aims to determine the fall prevention performance of two types of safety belts: a body belt, which has been used for more than 40 yr in the Japanese construction industry as a general type of safety equipment for fall accident prevention, and a full harness, which has been used in many other countries. To determine human tolerance for impact trauma, this study discusses features of safety belts with reference to relevant studies in the medical science, automobile crash safety, and aircrew safety. For this purpose, simple drop tests were carried out in a virtual workplace to measure impact load, head acceleration, and posture in the experiments, the Hybrid-III pedestrian model was used as a human dummy. Hybrid-III is typically employed in official automobile crash tests (New Car Assessment Program: NCAP) and is currently recognized as a model that faithfully reproduces dynamic responses. Experimental results shows that safety performance strongly depends on both the variety of safety belts used and the shock absorbers attached onto lanyards. These findings indicate that fall prevention equipment, such as safety belts, lanyards, and shock absorbers, must be improved to reduce impact injuries to the human head and body during falls. PMID:25345426

  17. Fall Protection Characteristics of Safety Belts and Human Impact Tolerance.

    PubMed

    Hino, Yasumichi; Ohdo, Katsutoshi; Takahashi, Hiroki

    2014-08-23

    Many fatal accidents due to falls from heights have occurred at construction sites not only in Japan but also in other countries. This study aims to determine the fall prevention performance of two types of safety belts: a body belt(1)), which has been used for more than 40 yr in the Japanese construction industry as a general type of safety equipment for fall accident prevention, and a full harness(2, 3)), which has been used in many other countries. To determine human tolerance for impact trauma, this study discusses features of safety belts with reference(4-9)) to relevant studies in the medical science, automobile crash safety, and aircrew safety. For this purpose, simple drop tests were carried out in a virtual workplace to measure impact load, head acceleration, and posture in the experiments, the Hybrid-III pedestrian model(10)) was used as a human dummy. Hybrid-III is typically employed in official automobile crash tests (New Car Assessment Program: NCAP) and is currently recognized as a model that faithfully reproduces dynamic responses. Experimental results shows that safety performance strongly depends on both the variety of safety belts used and the shock absorbers attached onto lanyards. These findings indicate that fall prevention equipment, such as safety belts, lanyards, and shock absorbers, must be improved to reduce impact injuries to the human head and body during falls. PMID:25152087

  18. Space station crew safety alternatives study. Volume 3: Safety impact of human factors

    NASA Technical Reports Server (NTRS)

    Rockoff, L. A.; Raasch, R. F.; Peercy, R. L., Jr.

    1985-01-01

    The first 15 years of accumulated space station concepts for Initial Operational Capability (IOC) during the early 1990's was considered. Twenty-five threats to the space station are identified and selected threats addressed as impacting safety criteria, escape and rescue, and human factors safety concerns. Of the 25 threats identified, eight are discussed including strategy options for threat control: fire, biological or toxic contamination, injury/illness, explosion, loss of pressurization, radiation, meteoroid penetration and debris. Of particular interest here is volume three (of five volumes) pertaining to the safety impact of human factors.

  19. Parameters affecting greywater quality and its safety for reuse.

    PubMed

    Maimon, Adi; Friedler, Eran; Gross, Amit

    2014-07-15

    Reusing greywater (GW) for on-site irrigation is becoming a common practice worldwide. Alongside its benefits, GW reuse might pose health and environmental risks. The current study assesses the risks associated with on-site GW reuse and the main factors affecting them. GW from 34 households in Israel was analyzed for physicochemical parameters, Escherichia coli (as an indicator for rotavirus), Pseudomonas aeruginosa and Staphylococcus aureus. Each participating household filled out a questionnaire about their GW sources, treatment and usages. Quantitative microbial risk assessment (QMRA) was performed based on the measured microbial quality, and on exposure scenarios derived from the questionnaires and literature data. The type of treatment was found to have a significant effect on the quality of the treated GW. The average E. coli counts in GW (which exclude kitchen effluent) treated by professionally-designed system resulted in acceptable risk under all exposure scenarios while the risk from inadequately-treated GW was above the accepted level as set by the WHO. In conclusion, safe GW reuse requires a suitable and well-designed treatment system. A risk-assessment approach should be used to adjust the current regulations/guidelines and to assess the performance of GW treatment and reuse systems. PMID:24751591

  20. New Safety Model for the Commercial Human Spaceflight Industry

    NASA Astrophysics Data System (ADS)

    Quinn, A.; Bond, S.; Maropoulos, P.

    2012-01-01

    The aviation and space domains have safety guidelines and recommended practices for Design Organisations (DOs) and Operators alike. In terms of Aerospace DOs there are certification criteria to meet and to demonstrate compliance there are Advisory Circulars or Acceptable Means of Compliance to follow. Additionally there are guidelines such as Aerospace Recommended Practices (ARP), Military Standards (MIL-STD 882 series) and System Safety Handbooks to follow in order to identify and manage failure conditions. In terms of Operators there are FAA guidelines and a useful ARP that details many tools and techniques in understanding Operator Safety Risks. However there is currently no methodology for linking the DO and Operator safety efforts. In the space domain NASA have provided safety standards and guidelines to follow and also within Europe there are European Co-operation of Space Standardization (ECSS) to follow. Within the emerging Commercial Human Spaceflight Industry, the FAA's Office of Commercial Space Transportation has provided hazard analysis guidelines. However all of these space domain safety documents are based on the existing aerospace methodology and once again, there is no link between the DO and Operator's safety effort. This paper addresses the problematic issue and presents a coherent methodology of joining up the System Safety effort of the DOs to the Operator Safety Risk Management such that a 'Total System' approach is adopted. Part of the rationale is that the correct mitigation (control) can be applied within the correct place in the accident sequence. Also this contiguous approach ensures that the Operator is fully aware of the safety risks (at the accident level) and therefore has an appreciation of the Total System Risk. The authors of this paper contend that it is better practice to have a fully integrated safety model as opposed to disparate requirements or guidelines. Our methodology is firstly to review 'best practice' approaches from

  1. Human Factors Research and Nuclear Safety.

    ERIC Educational Resources Information Center

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

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

  2. Plant sterols: factors affecting their efficacy and safety as functional food ingredients

    PubMed Central

    Berger, Alvin; Jones, Peter JH; Abumweis, Suhad S

    2004-01-01

    Plant sterols are naturally occurring molecules that humanity has evolved with. Herein, we have critically evaluated recent literature pertaining to the myriad of factors affecting efficacy and safety of plant sterols in free and esterified forms. We conclude that properly solubilized 4-desmetyl plant sterols, in ester or free form, in reasonable doses (0.8–1.0 g of equivalents per day) and in various vehicles including natural sources, and as part of a healthy diet and lifestyle, are important dietary components for lowering low density lipoprotein (LDL) cholesterol and maintaining good heart health. In addition to their cholesterol lowering properties, plant sterols possess anti-cancer, anti-inflammatory, anti-atherogenicity, and anti-oxidation activities, and should thus be of clinical importance, even for those individuals without elevated LDL cholesterol. The carotenoid lowering effect of plant sterols should be corrected by increasing intake of food that is rich in carotenoids. In pregnant and lactating women and children, further study is needed to verify the dose required to decrease blood cholesterol without affecting fat-soluble vitamins and carotenoid status. PMID:15070410

  3. Task analysis for industrial work process from aspects of human reliability and system safety.

    PubMed

    Yu, F J; Hwang, S L; Huang, Y H

    1999-06-01

    In the design, development, and manufacturing stage of industrial products, engineers usually focus on the problems caused by hardware or software, but pay less attention to problems caused by "human error," which may significantly affect system reliability and safety. Although operating procedures are strictly followed, human error still may occur occasionally. Among the influencing factors, the inappropriate design of standard operation procedure (SOP) or standard assembly procedure (SAP) is an important and latent reason for unexpected results found during human operation. To reduce the error probability and error effects of these unexpected behaviors in the industrial work process, overall evaluation of SOP or SAP quality has become an essential task. The human error criticality analysis (HECA) method was developed to identify the potentially critical problems caused by human error in the human operation system. This method performs task analysis on the basis of operation procedure. For example, SOP, analyzes the human error probability (HEP) for each human operation step, and assesses its error effects to the whole system. The results of the analysis will show the interrelationship that exists between critical human tasks, critical human error modes, and human reliability information of the human operation system. To identify the robustness of the model, a case study of initiator assembly tasks was conducted. Results show that the HECA method is practicable in evaluating the operation procedure, and the information is valuable in identifying the means to upgrade human reliability and system safety for human tasks. PMID:10765413

  4. Toward an Affective Pedagogy of Human Rights Education

    ERIC Educational Resources Information Center

    Hung, Ruyu

    2014-01-01

    This paper explores the notion of Affective Pedagogy of Human Rights Education (APHRE) on a theoretical level and suggests a concept of curricular framework. APHRE highlights the significance of affectivity and body in the process of learning, factors usually neglected in the mainstream intellectualistic approach to learning, especially in areas…

  5. A Safety-Case Regime for Commercial Human Spaceflight

    NASA Astrophysics Data System (ADS)

    Sgobba, T.; Trujillo, M.

    2012-01-01

    Currently the commercial human spaceflight community seems to be embracing the obsolete design principles of "fly-fix-fly", and betting on public acceptance of risks comparable to those of the early times of aviation industry. The nascent space tourism industry maintains that early safety regulations (apart public safety) would kill industry and that such regulations could be developed only later when substantial operational experience is gained. Truly, most of current commercial aviation safety regulations are based on prescriptive requirements (i.e. explicitly required design solution for an implicit goal), which have been incrementally developed over more than a half century of mass transportation by air, and cannot be in general directly applied to innovative systems. However modern complex safety-critical systems cannot risk catastrophic failures while their operational experience is being accumulated, for such reason they are developed through the so called safety-case regime. ESA is currently drafting a safety standard for its future human rated transportation systems that is based on such regime. Such standard can be easily tailored with few modifications and applied to the development of a sub-orbital commercial space vehicle. In any case, because the safety-case regime makes extensive use of generically formulated requirements, the support of skilled safety engineers fully integrated into the design team is required since the very beginning. Furthermore the safety certification team needs also to be experienced in the review of safety-case based designs. Finally a quantitative safety target needs to be included and verified as the ultimate "prove of goodness" of system design.

  6. Targeting of blood safety measures to affected areas with ongoing local transmission of malaria.

    PubMed

    Domanović, D; Kitchen, A; Politis, C; Panagiotopoulos, T; Bluemel, J; Van Bortel, W; Overbosch, D; Lieshout-Krikke, R; Fabra, C; Facco, G; Zeller, H

    2016-06-01

    An outbreak of locally acquired Plasmodium vivax malaria in Greece started in 2009 and peaked in 2011. Targeting of blood safety measures to affected areas with ongoing transmission of malaria raised questions of how to define spatial boundaries of such an area and when to trigger any specific blood safety measures, including whether and which blood donation screening strategy to apply. To provide scientific advice the European Centre for Disease Prevention and Control (ECDC) organised expert meetings in 2013. The outcomes of these consultations are expert opinions covering spatial targeting of blood safety measures to affected areas with ongoing local transmission of malaria and blood donation screening strategy for evidence of malaria infection in these areas. Opinions could help EU national blood safety authorities in developing a preventive strategy during malaria outbreaks. PMID:27238883

  7. Evaluating Models of Human Performance: Safety-Critical Systems Applications

    NASA Technical Reports Server (NTRS)

    Feary, Michael S.

    2012-01-01

    This presentation is part of panel discussion on Evaluating Models of Human Performance. The purpose of this panel is to discuss the increasing use of models in the world today and specifically focus on how to describe and evaluate models of human performance. My presentation will focus on discussions of generating distributions of performance, and the evaluation of different strategies for humans performing tasks with mixed initiative (Human-Automation) systems. I will also discuss issues with how to provide Human Performance modeling data to support decisions on acceptability and tradeoffs in the design of safety critical systems. I will conclude with challenges for the future.

  8. Electrical Safety for Human Space Flight Payload Hardware

    NASA Astrophysics Data System (ADS)

    Runnells, James A.

    2010-09-01

    Human Space Flight payload hardware designs must address both mission success and safety requirements for flight on the Space Shuttle, International Space Station(ISS), or International Partner(IP) Launch Vehicles. Flight hardware generally can be considered either Government Furnished Equipment(GFE) or Payload hardware, although some Commercial-off-the-shelf(COTS) hardware is also flown. In this case we will use the payload flight hardware system safety perspective, which closely resembles the GFE system safety process with a few exceptions. Why is Human space flight hardware treated differently than ground hardware? The key reason flight hardware is treated more conservatively than ground hardware is the relative impact to crew and vehicle, and the relative inability to provide immediate recovery of a disabled space vehicle or crewmember on-orbit. One aspect of safe payload flight hardware design is Electrical Power Systems(EPS), including the safe design and operations of electrical power systems for payloads.

  9. Food safety. [chemical contaminants and human toxic diseases

    NASA Technical Reports Server (NTRS)

    Pier, S. M.; Valentine, J. L.

    1975-01-01

    Illness induced by unsafe food is a problem of great public health significance. This study relates exclusively to the occurrence of chemical agents which will result in food unsafe for human consumption since the matter of food safety is of paramount importance in the mission and operation of the manned spacecraft program of the National Aeronautics and Space Administration.

  10. Focus on food safety: Human pathogens on plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This article introduces the first Focus Issue of Phytopathology, a dedicated issue of the journal that highlights a topic of significant interest to our readership. This first Focus Issue addresses the topic of food safety and the biology of human pathogens on plants, a relatively new problem in pla...

  11. Consensus and stratification in the affective meaning of human sociality

    PubMed Central

    Ambrasat, Jens; von Scheve, Christian; Conrad, Markus; Schauenburg, Gesche; Schröder, Tobias

    2014-01-01

    We investigate intrasocietal consensus and variation in affective meanings of concepts related to authority and community, two elementary forms of human sociality. Survey participants (n = 2,849) from different socioeconomic status (SES) groups in German society provided ratings of 909 social concepts along three basic dimensions of affective meaning. Results show widespread consensus on these meanings within society and demonstrate that a meaningful structure of socially shared knowledge emerges from organizing concepts according to their affective similarity. The consensus finding is further qualified by evidence for subtle systematic variation along SES differences. In relation to affectively neutral words, high-status individuals evaluate intimacy-related and socially desirable concepts as less positive and powerful than middle- or low-status individuals, while perceiving antisocial concepts as relatively more threatening. This systematic variation across SES groups suggests that the affective meaning of sociality is to some degree a function of social stratification. PMID:24843121

  12. Safety Metrics for Human-Computer Controlled Systems

    NASA Technical Reports Server (NTRS)

    Leveson, Nancy G; Hatanaka, Iwao

    2000-01-01

    The rapid growth of computer technology and innovation has played a significant role in the rise of computer automation of human tasks in modem production systems across all industries. Although the rationale for automation has been to eliminate "human error" or to relieve humans from manual repetitive tasks, various computer-related hazards and accidents have emerged as a direct result of increased system complexity attributed to computer automation. The risk assessment techniques utilized for electromechanical systems are not suitable for today's software-intensive systems or complex human-computer controlled systems.This thesis will propose a new systemic model-based framework for analyzing risk in safety-critical systems where both computers and humans are controlling safety-critical functions. A new systems accident model will be developed based upon modem systems theory and human cognitive processes to better characterize system accidents, the role of human operators, and the influence of software in its direct control of significant system functions Better risk assessments will then be achievable through the application of this new framework to complex human-computer controlled systems.

  13. Elementary Affective Education in Human Relations: Teachers Guide.

    ERIC Educational Resources Information Center

    Florida Univ., Gainesville. P. K. Yonge Lab. School.

    The activities and resources in this teacher's guide have been developed and field tested as part of the research and development mission of the P. K. Yonge Laboratory School of the College of Education of the University of Florida. The Elementary Affective Education for Human Relations Project utilized classroom teachers in a variety of settings…

  14. How Do Volcanoes Affect Human Life? Integrated Unit.

    ERIC Educational Resources Information Center

    Dayton, Rebecca; Edwards, Carrie; Sisler, Michelle

    This packet contains a unit on teaching about volcanoes. The following question is addressed: How do volcanoes affect human life? The unit covers approximately three weeks of instruction and strives to present volcanoes in an holistic form. The five subject areas of art, language arts, mathematics, science, and social studies are integrated into…

  15. The comparative psychopathology of affective disorders in animals and humans.

    PubMed

    Healy, D

    1987-01-01

    Reviews of animal models of affective disorders commonly concentrate on the behavioural features thereof, the supposed neurochemical substrates, the mode of production and the response to treatment of the state in question but ignore questions of psycho pathology. An attempt is made to deal critically with the psychopathology of human and animal affective disorders in the light of current operational criteria for the diagnosis of major depressive disorders. It is argued thatthe psychopathological tradition stemming from Jaspers may be more appropriate to a consideration of animal models of affective disorders than the psychopathological positions implicit in psychoanalysis, behaviourism or current cognitive psychologies and in addition more suited to meet these criteria. The adoption of such a perspective results in a shift of emphasis from abnormalities of psychological content to demonstrable neuropsychological deficits and a definition of affective disorders, whether in animals or humans, as psychosomatic illnesses, possibly involving a pathology of circadian rhythmicity. This perspective also suggests that animal models may be useful in the devel opment of more refined diagnostic criteria for affective disorders in humans. PMID:22158981

  16. Incorporating affective bias in models of human decision making

    NASA Technical Reports Server (NTRS)

    Nygren, Thomas E.

    1991-01-01

    Research on human decision making has traditionally focused on how people actually make decisions, how good their decisions are, and how their decisions can be improved. Recent research suggests that this model is inadequate. Affective as well as cognitive components drive the way information about relevant outcomes and events is perceived, integrated, and used in the decision making process. The affective components include how the individual frames outcomes as good or bad, whether the individual anticipates regret in a decision situation, the affective mood state of the individual, and the psychological stress level anticipated or experienced in the decision situation. A focus of the current work has been to propose empirical studies that will attempt to examine in more detail the relationships between the latter two critical affective influences (mood state and stress) on decision making behavior.

  17. Spacecraft Fire Safety: A Human Space Flight Program Perspective

    NASA Technical Reports Server (NTRS)

    Pedley, Michael D.

    2003-01-01

    This paper presents viewgraphs on the International Space Station's fire safety program from a human space flight perspective. The topics include: 1) Typical Manned Spacecraft Materials; 2) Typical Flammable Hardware Protection; 3) Materials Flammability; 4) Fire Retardants; 5) Nonflammable Foam Cushion Material; 6) Electrical Wire and Cable; 7) Russian Solid-Fuel Oxygen Generator (SFOG); 8) GOX Ignition Mechanisms; 9) Fire Detection; and 10) Fire Suppression.

  18. Direct Human Contact with Siloxanes (Silicones) – Safety or Risk Part 1. Characteristics of Siloxanes (Silicones)

    PubMed Central

    Mojsiewicz-Pieńkowska, Krystyna; Jamrógiewicz, Marzena; Szymkowska, Katarzyna; Krenczkowska, Dominika

    2016-01-01

    Siloxanes are commonly known as silicones. They belong to the organosilicon compounds and are exclusively obtained by synthesis. Their chemical structure determines a range of physicochemical properties which were recognized as unique. Due to the susceptibility to chemical modifications, ability to create short, long or complex polymer particles, siloxanes found an application in many areas of human life. Siloxanes differ in particle size, molecular weight, shape and chemical groups. As a result, this determines the different physico-chemical properties, that directly affect the safety or the risk of their use. The areas that can be a source of danger to human health will be commented in this paper. PMID:27303296

  19. The impact of natural odors on affective states in humans.

    PubMed

    Weber, Sandra T; Heuberger, Eva

    2008-06-01

    Laboratory studies have shown a significant influence of certain fragrances on affective as well as cognitive states in humans. The aim of the current study was to measure the relationship between complex, natural odors and affective states, that is, calmness, alertness, and mood, in the field. In 4 experiments, the emotional impact, intensity, and hedonics of complex, natural plant odors were assessed in 32 healthy human subjects and compared with control conditions involving a similar outdoor environment without the tested fragrant plants. In all experiments, the selected fragrances were evaluated as more intense than the odors in the control conditions but pleasantness ratings differed only in 2 of the 4 experiments. The fragrances improved subjective ratings of calmness, alertness, and mood depending on the sequence of the conditions but independent of visual features of the environment. In contrast, a fifth experiment which tested the influence of natural and artificial pleasant odors and an artificial unpleasant odor on calmness, alertness, and mood in 22 subjects showed that the unpleasant odor impaired these affective states in humans independent of the order of presentation. On the other hand, no effects of the pleasant odors on mood and calmness were observed in this experiment. PMID:18353767

  20. Positive Affect and the Complex Dynamics of Human Flourishing

    PubMed Central

    Fredrickson, Barbara L.; Losada, Marcial F.

    2011-01-01

    Extending B. L. Fredrickson’s (1998) broaden-and-build theory of positive emotions and M. Losada’s (1999) nonlinear dynamics model of team performance, the authors predict that a ratio of positive to negative affect at or above 2.9 will characterize individuals in flourishing mental health. Participants (N = 188) completed an initial survey to identify flourishing mental health and then provided daily reports of experienced positive and negative emotions over 28 days. Results showed that the mean ratio of positive to negative affect was above 2.9 for individuals classified as flourishing and below that threshold for those not flourishing. Together with other evidence, these findings suggest that a set of general mathematical principles may describe the relations between positive affect and human flourishing. PMID:16221001

  1. Positive affect and the complex dynamics of human flourishing.

    PubMed

    Fredrickson, Barbara L; Losada, Marcial F

    2005-10-01

    Extending B. L. Fredrickson's (1998) broaden-and-build theory of positive emotions and M. Losada's (1999) nonlinear dynamics model of team performance, the authors predict that a ratio of positive to negative affect at or above 2.9 will characterize individuals in flourishing mental health. Participants (N=188) completed an initial survey to identify flourishing mental health and then provided daily reports of experienced positive and negative emotions over 28 days. Results showed that the mean ratio of positive to negative affect was above 2.9 for individuals classified as flourishing and below that threshold for those not flourishing. Together with other evidence, these findings suggest that a set of general mathematical principles may describe the relations between positive affect and human flourishing. PMID:16221001

  2. Alaska Humans Factors Safety Study: The Southern Coastal Area

    NASA Technical Reports Server (NTRS)

    Chappell, Sheryl L.; Reynard, William (Technical Monitor)

    1995-01-01

    At the request of the Alaska Air Carriers Association, researchers from the NASA Aviation Safety Reporting System, at NASA Ames Research Center, conducted a study on aspects of safety in Alaskan Part 135 air taxi operations. An interview form on human factors safety issues was created by a representative team from the FAA-Alaska, NTSB-Alaska, NASA-ASRS, and representatives of the Alaska Air Carriers Association which was subsequently used in the interviews of pilots and managers. Because of the climate and operational differences, the study was broken into two geographical areas, the southern coastal areas and the northern portion of the state. This presentation addresses the southern coastal areas, specifically: Anchorage, Dillingham, King Salmon, Kodiak, Cold Bay, Juneau, and Ketchikan. The interview questions dealt with many of the potential pressures on pilots and managers associated with the daily air taxi operations in Alaska. The impact of the environmental factors such as the lack of available communication, navigation and weather information systems was evaluated. The results of this study will be used by government and industry working in Alaska. These findings will contribute important information on specific Alaska safety issues for eventual incorporation into training materials and policies that will help to assure the safe conduct of air taxi flights in Alaska.

  3. Alaska Humans Factors Safety Study: The Northern Area

    NASA Technical Reports Server (NTRS)

    Connell, Linda; Reynard, William (Technical Monitor)

    1995-01-01

    At the request of the Alaska Air Carriers Association, researchers from the NASA Aviation Safety Reporting System, at NASA Ames Research Center, conducted a study on aspects of safety in Alaskan Part 135 air taxi operations. An interview form on human factors safety issues was created by a representative team from the FAA-Alaska, NTSB-Alaska, NASAASRS, and representatives of the Alaska Air Carriers Association which was subsequently used in the interviews of pilots and managers. Because of the climate and operational differences, the study was broken into two geographical areas, the southern coastal areas and the northern portion of the state. This presentation addresses the northern area, specifically: Bethel, Fairbanks, Nome, Kotzebue, and Barrow. The interview questions dealt with many of the potential pressures on pilots and managers associated with the daily air taxi operations in Alaska. The impact of the environmental factors such as the lack of available communication, navigation and weather information systems was evaluated. The results of this study will be used by government and industry working in Alaska. These findings will contribute important information on specific Alaska safety issues for eventual incorporation into training materials and policies that will help to assure the safe conduct of air taxi flights in Alaska.

  4. The effects of physical environments in medical wards on medication communication processes affecting patient safety.

    PubMed

    Liu, Wei; Manias, Elizabeth; Gerdtz, Marie

    2014-03-01

    Physical environments of clinical settings play an important role in health communication processes. Effective medication management requires seamless communication among health professionals of different disciplines. This paper explores how physical environments affect communication processes for managing medications and patient safety in acute care hospital settings. Findings highlighted the impact of environmental interruptions on communication processes about medications. In response to frequent interruptions and limited space within working environments, nurses, doctors and pharmacists developed adaptive practices in the local clinical context. Communication difficulties were associated with the ward physical layout, the controlled drug key and the medication retrieving device. Health professionals should be provided with opportunities to discuss the effects of ward environments on medication communication processes and how this impacts medication safety. Hospital administrators and architects need to consider health professionals' views and experiences when designing hospital spaces. PMID:24486620

  5. Global water resources affected by human interventions and climate change.

    PubMed

    Haddeland, Ingjerd; Heinke, Jens; Biemans, Hester; Eisner, Stephanie; Flörke, Martina; Hanasaki, Naota; Konzmann, Markus; Ludwig, Fulco; Masaki, Yoshimitsu; Schewe, Jacob; Stacke, Tobias; Tessler, Zachary D; Wada, Yoshihide; Wisser, Dominik

    2014-03-01

    Humans directly change the dynamics of the water cycle through dams constructed for water storage, and through water withdrawals for industrial, agricultural, or domestic purposes. Climate change is expected to additionally affect water supply and demand. Here, analyses of climate change and direct human impacts on the terrestrial water cycle are presented and compared using a multimodel approach. Seven global hydrological models have been forced with multiple climate projections, and with and without taking into account impacts of human interventions such as dams and water withdrawals on the hydrological cycle. Model results are analyzed for different levels of global warming, allowing for analyses in line with temperature targets for climate change mitigation. The results indicate that direct human impacts on the water cycle in some regions, e.g., parts of Asia and in the western United States, are of the same order of magnitude, or even exceed impacts to be expected for moderate levels of global warming (+2 K). Despite some spread in model projections, irrigation water consumption is generally projected to increase with higher global mean temperatures. Irrigation water scarcity is particularly large in parts of southern and eastern Asia, and is expected to become even larger in the future. PMID:24344275

  6. Global water resources affected by human interventions and climate change

    PubMed Central

    Haddeland, Ingjerd; Heinke, Jens; Biemans, Hester; Eisner, Stephanie; Flörke, Martina; Hanasaki, Naota; Konzmann, Markus; Ludwig, Fulco; Masaki, Yoshimitsu; Schewe, Jacob; Stacke, Tobias; Tessler, Zachary D.; Wada, Yoshihide; Wisser, Dominik

    2014-01-01

    Humans directly change the dynamics of the water cycle through dams constructed for water storage, and through water withdrawals for industrial, agricultural, or domestic purposes. Climate change is expected to additionally affect water supply and demand. Here, analyses of climate change and direct human impacts on the terrestrial water cycle are presented and compared using a multimodel approach. Seven global hydrological models have been forced with multiple climate projections, and with and without taking into account impacts of human interventions such as dams and water withdrawals on the hydrological cycle. Model results are analyzed for different levels of global warming, allowing for analyses in line with temperature targets for climate change mitigation. The results indicate that direct human impacts on the water cycle in some regions, e.g., parts of Asia and in the western United States, are of the same order of magnitude, or even exceed impacts to be expected for moderate levels of global warming (+2 K). Despite some spread in model projections, irrigation water consumption is generally projected to increase with higher global mean temperatures. Irrigation water scarcity is particularly large in parts of southern and eastern Asia, and is expected to become even larger in the future. PMID:24344275

  7. The safety of human pluripotent stem cells in clinical treatment.

    PubMed

    Simonson, Oscar E; Domogatskaya, Anna; Volchkov, Pavel; Rodin, Sergey

    2015-01-01

    Human pluripotent stem cells (hPSCs) have practically unlimited proliferation potential and a capability to differentiate into any cell type in the human body. Since the first derivation in 1998, they have been an attractive source of cells for regenerative medicine. Numerous ethical, technological, and regulatory complications have been hampering hPSC use in clinical applications. Human embryonic stem cells (ESCs), parthenogenetic human ESCs, human nuclear transfer ESCs, and induced pluripotent stem cells are four types of hPSCs that are different in many clinically relevant features such as propensity to epigenetic abnormalities, generation methods, and ability for development of autologous cell lines. Propensity to genetic mutations and tumorigenicity are common features of all pluripotent cells that complicate hPSC-based therapies. Several recent advances in methods of derivation, culturing, and monitoring of hPSCs have addressed many ethical concerns and technological challenges in development of clinical-grade hPSC lines. Generation of banks of such lines may be useful to minimize immune rejection of hPSC-derived allografts. In this review, we discuss different sources of hPSCs available at the moment, various safety risks associated with them, and possible solutions for successful use of hPSCs in the clinic. We also discuss ongoing clinical trials of hPSC-based treatments. PMID:26140342

  8. Affect is central to patient safety: the horror stories of young anaesthetists.

    PubMed

    Iedema, Rick; Jorm, Christine; Lum, Martin

    2009-12-01

    This paper analyses talk produced by twenty-four newly qualified anaesthetists. Data were collected from round table discussions at the Young Fellows Conference of the Australia and New Zealand College of Anaesthetists 2006. The talk consisted to an important extent of narratives about experiences of horror. The paper isolates three themes: the normalization of horror, the functionalisation of horror for pedagogic purposes, and the problematization of horror. The last theme provides a springboard into our argument that confronting the affect invested in coping with medical-clinical failure is central to enabling young doctors, and clinicians generally, to address and resolve such adverse events. We conclude that the negotiation of affect through shared or 'dialogic' narrative is central to enabling doctors to deal with adverse events on a personal level, and to enabling them at a collective level to become attentive to threats to patients' safety. PMID:19846244

  9. The Safety of Cruciferous Plants in Humans: A Systematic Review

    PubMed Central

    Scott, Ori; Galicia-Connolly, Elaine; Adams, Denise; Surette, Soleil; Vohra, Sunita; Yager, Jerome Y.

    2012-01-01

    Some cruciferous plants may serve as preventive treatments for several medical conditions; our objective was to systematically investigate their safety in humans. Four electronic databases were searched, and, of 10,831 references identified, 50 were included. Data were extracted by two independent reviewers, whereafter the association between interventions and adverse events was assessed. Adverse events in 53 subjects were identified through clinical trials; of these, altered drug metabolism was rated as certainly/likely caused by cruciferous plants. Adverse events in 1247 subjects were identified through observational studies, of which none received high causality ratings. Adverse events in 35 subjects were identified through case reports, of which allergies and warfarin resistance were rated as certainly/likely caused by cruciferous plants. We conclude that cruciferous plants are safe in humans, with the exception of allergies. Individuals treated with warfarin should consult their physician. Further investigation of uses of cruciferous plants in preventative medicine is warranted. PMID:22500092

  10. Perinatal Oxidative Stress May Affect Fetal Ghrelin Levels in Humans

    PubMed Central

    Luo, Zhong-Cheng; Bilodeau, Jean-François; Monique Nuyt, Anne; Fraser, William D.; Julien, Pierre; Audibert, Francois; Xiao, Lin; Garofalo, Carole; Levy, Emile

    2015-01-01

    In vitro cell model studies have shown that oxidative stress may affect beta-cell function. It is unknown whether oxidative stress may affect metabolic health in human fetuses/newborns. In a singleton pregnancy cohort (n = 248), we studied maternal (24–28 weeks gestation) and cord plasma biomarkers of oxidative stress [malondialdehyde (MDA), F2-isoprostanes] in relation to fetal metabolic health biomarkers including cord plasma glucose-to-insulin ratio (an indicator of insulin sensitivity), proinsulin-to-insulin ratio (an indicator of beta-cell function), insulin, IGF-I, IGF-II, leptin, adiponectin and ghrelin concentrations. Strong positive correlations were observed between maternal and cord plasma biomarkers of oxidative stress (r = 0.33 for MDA, r = 0.74 for total F2-isoprostanes, all p < 0.0001). Adjusting for gestational age at blood sampling, cord plasma ghrelin concentrations were consistently negatively correlated to oxidative stress biomarkers in maternal (r = −0.32, p < 0.0001 for MDA; r = −0.31, p < 0.0001 for F2-isoprostanes) or cord plasma (r = −0.13, p = 0.04 for MDA; r = −0.32, p < 0.0001 for F2-isoprostanes). Other fetal metabolic health biomarkers were not correlated to oxidative stress. Adjusting for maternal and pregnancy characteristics, similar associations were observed. Our study provides the first preliminary evidence suggesting that oxidative stress may affect fetal ghrelin levels in humans. The implications in developmental “programming” the vulnerability to metabolic syndrome related disorders remain to be elucidated. PMID:26643495

  11. Efficacy and Safety of Human Retinal Progenitor Cells

    PubMed Central

    Semo, Ma'ayan; Haamedi, Nasrin; Stevanato, Lara; Carter, David; Brooke, Gary; Young, Michael; Coffey, Peter; Sinden, John; Patel, Sara; Vugler, Anthony

    2016-01-01

    Purpose We assessed the long-term efficacy and safety of human retinal progenitor cells (hRPC) using established rodent models. Methods Efficacy of hRPC was tested initially in Royal College of Surgeons (RCS) dystrophic rats immunosuppressed with cyclosporine/dexamethasone. Due to adverse effects of dexamethasone, this drug was omitted from a subsequent dose-ranging study, where different hRPC doses were tested for their ability to preserve visual function (measured by optokinetic head tracking) and retinal structure in RCS rats at 3 to 6 months after grafting. Safety of hRPC was assessed by subretinal transplantation into wild type (WT) rats and NIH-III nude mice, with analysis at 3 to 6 and 9 months after grafting, respectively. Results The optimal dose of hRPC for preserving visual function/retinal structure in dystrophic rats was 50,000 to 100,000 cells. Human retinal progenitor cells integrated/survived in dystrophic and WT rat retina up to 6 months after grafting and expressed nestin, vimentin, GFAP, and βIII tubulin. Vision and retinal structure remained normal in WT rats injected with hRPC and there was no evidence of tumors. A comparison between dexamethasone-treated and untreated dystrophic rats at 3 months after grafting revealed an unexpected reduction in the baseline visual acuity of dexamethasone-treated animals. Conclusions Human retinal progenitor cells appear safe and efficacious in the preclinical models used here. Translational Relevance Human retinal progenitor cells could be deployed during early stages of retinal degeneration or in regions of intact retina, without adverse effects on visual function. The ability of dexamethasone to reduce baseline visual acuity in RCS dystrophic rats has important implications for the interpretation of preclinical and clinical cell transplant studies. PMID:27486556

  12. Investigational new drug safety reporting requirements for human drug and biological products and safety reporting requirements for bioavailability and bioequivalence studies in humans. Final rule.

    PubMed

    2010-09-29

    The Food and Drug Administration (FDA) is amending its regulations governing safety reporting requirements for human drug and biological products subject to an investigational new drug application (IND). The final rule codifies the agency's expectations for timely review, evaluation, and submission of relevant and useful safety information and implements internationally harmonized definitions and reporting standards. The revisions will improve the utility of IND safety reports, reduce the number of reports that do not contribute in a meaningful way to the developing safety profile of the drug, expedite FDA's review of critical safety information, better protect human subjects enrolled in clinical trials, subject bioavailability and bioequivalence studies to safety reporting requirements, promote a consistent approach to safety reporting internationally, and enable the agency to better protect and promote public health. PMID:20879180

  13. Does acute exposure to mobile phones affect human attention?

    PubMed

    Russo, Riccardo; Fox, Elaine; Cinel, Caterina; Boldini, Angela; Defeyter, Margaret A; Mirshekar-Syahkal, Dariush; Mehta, Amit

    2006-04-01

    Recent studies have indicated that acute exposure to low level radiofrequency (RF) electromagnetic fields generated by mobile phones affects human cognition. However, the relatively small samples used, in addition to methodological problems, make the outcomes of these studies difficult to interpret. In our study we tested a large sample of volunteers (168) using a series of cognitive tasks apparently sensitive to RF exposure (a simple reaction task, a vigilance task, and a subtraction task). Participants performed those tasks twice, in two different sessions. In one session they were exposed to RFs, with half of subjects exposed to GSM signals and the other half exposed to CW signals, while in the other session they were exposed to sham signals. No significant effects of RF exposure on performance for either GSM or CW were found, independent of whether the phone was positioned on the left or on the right side. PMID:16304701

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

    PubMed

    Slone, Edward; Burles, Ford; Iaria, Giuseppe

    2016-05-01

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

  15. [Development of human embryonic stem cell platforms for human health-safety evaluation].

    PubMed

    Yu, Guang-yan; Cao, Tong; Zou, Xiao-hui; Zhang, Xue-hui; Fu, Xin; Peng, Shuang-qing; Deng, Xu-liang; Li, Sheng-lin; Liu, He; Xiao, Ran; Ouyang, Hong-wei; Peng, Hui; Chen, Xiao; Zhao, Zeng-ming; Wang, Xiao-ying; Fang, Hai-qin; Lu, Lu; Ren, Yu-lan; Xu, Ming-ming

    2016-02-18

    The human embryonic stem cells (hESCs) serve as a self-renewable, genetically-healthy, pluripotent and single source of all body cells, tissues and organs. Therefore, it is considered as the good standard for all human stem cells by US, Europe and international authorities. In this study, the standard and healthy human mesenchymal progenitors, ligament tissues, cardiomyocytes, keratinocytes, primary neurons, fibroblasts, and salivary serous cells were differentiated from hESCs. The human cellular health-safety of NaF, retinoic acid, 5-fluorouracil, dexamethasone, penicillin G, adriamycin, lead acetate PbAc, bisphenol A-biglycidyl methacrylate (Bis-GMA) were evaluated selectively on the standardized platforms of hESCs, hESCs-derived cardiomyocytes, keratinocytes, primary neurons, and fibroblasts. The evaluations were compared with those on the currently most adopted cellular platforms. Particularly, the sensitivity difference of PM2.5 toxicity on standardized and healthy hESCs derived fibroblasts, currently adopted immortalized human bronchial epithelial cells Beas-2B and human umbilical vein endothelial cells (HUVECs) were evaluated. The RESULTS showed that the standardized hESCs cellular platforms provided more sensitivity and accuracy for human cellular health-safety evaluation. PMID:26885900

  16. Human Factors And Safety Considerations Of Night Vision Systems Flight

    NASA Astrophysics Data System (ADS)

    Verona, Robert W.; Rash, Clarence E.

    1989-03-01

    Military aviation night vision systems greatly enhance the capability to operate during periods of low illumination. After flying with night vision devices, most aviators are apprehensive about returning to unaided night flight. Current night vision imaging devices allow aviators to fly during ambient light conditions which would be extremely dangerous, if not impossible, with unaided vision. However, the visual input afforded with these devices does not approach that experienced using the unencumbered, unaided eye during periods of daylight illumination. Many visual parameters, e,g., acuity, field-of-view, depth perception, etc., are compromised when night vision devices are used. The inherent characteristics of image intensification based sensors introduce new problems associated with the interpretation of visual information based on different spatial and spectral content from that of unaided vision. In addition, the mounting of these devices onto the helmet is accompanied by concerns of fatigue resulting from increased head supported weight and shift in center-of-gravity. All of these concerns have produced numerous human factors and safety issues relating to thb use of night vision systems. These issues are identified and discussed in terms of their possible effects on user performance and safety.

  17. Cross-Species Affective Neuroscience Decoding of the Primal Affective Experiences of Humans and Related Animals

    PubMed Central

    Panksepp, Jaak

    2011-01-01

    Background The issue of whether other animals have internally felt experiences has vexed animal behavioral science since its inception. Although most investigators remain agnostic on such contentious issues, there is now abundant experimental evidence indicating that all mammals have negatively and positively-valenced emotional networks concentrated in homologous brain regions that mediate affective experiences when animals are emotionally aroused. That is what the neuroscientific evidence indicates. Principal Findings The relevant lines of evidence are as follows: 1) It is easy to elicit powerful unconditioned emotional responses using localized electrical stimulation of the brain (ESB); these effects are concentrated in ancient subcortical brain regions. Seven types of emotional arousals have been described; using a special capitalized nomenclature for such primary process emotional systems, they are SEEKING, RAGE, FEAR, LUST, CARE, PANIC/GRIEF and PLAY. 2) These brain circuits are situated in homologous subcortical brain regions in all vertebrates tested. Thus, if one activates FEAR arousal circuits in rats, cats or primates, all exhibit similar fear responses. 3) All primary-process emotional-instinctual urges, even ones as complex as social PLAY, remain intact after radical neo-decortication early in life; thus, the neocortex is not essential for the generation of primary-process emotionality. 4) Using diverse measures, one can demonstrate that animals like and dislike ESB of brain regions that evoke unconditioned instinctual emotional behaviors: Such ESBs can serve as ‘rewards’ and ‘punishments’ in diverse approach and escape/avoidance learning tasks. 5) Comparable ESB of human brains yield comparable affective experiences. Thus, robust evidence indicates that raw primary-process (i.e., instinctual, unconditioned) emotional behaviors and feelings emanate from homologous brain functions in all mammals (see Appendix S1), which are regulated by higher

  18. The Development of Dynamic Human Reliability Analysis Simulations for Inclusion in Risk Informed Safety Margin Characterization Frameworks

    SciTech Connect

    Jeffrey C. Joe; Diego Mandelli; Ronald L. Boring; Curtis L. Smith; Rachel B. Shirley

    2015-07-01

    The United States Department of Energy is sponsoring the Light Water Reactor Sustainability program, which has the overall objective of supporting the near-term and the extended operation of commercial nuclear power plants. One key research and development (R&D) area in this program is the Risk-Informed Safety Margin Characterization pathway, which combines probabilistic risk simulation with thermohydraulic simulation codes to define and manage safety margins. The R&D efforts to date, however, have not included robust simulations of human operators, and how the reliability of human performance or lack thereof (i.e., human errors) can affect risk-margins and plant performance. This paper describes current and planned research efforts to address the absence of robust human reliability simulations and thereby increase the fidelity of simulated accident scenarios.

  19. Common problems in the elicitation and analysis of expert opinion affecting probabilistic safety assessments

    SciTech Connect

    Meyer, M.A.; Booker, J.M.

    1990-01-01

    Expert opinion is frequently used in probabilistic safety assessment (PSA), particularly in estimating low probability events. In this paper, we discuss some of the common problems encountered in eliciting and analyzing expert opinion data and offer solutions or recommendations. The problems are: that experts are not naturally Bayesian. People fail to update their existing information to account for new information as it becomes available, as would be predicted by the Bayesian philosophy; that experts cannot be fully calibrated. To calibrate experts, the feedback from the known quantities must be immediate, frequent, and specific to the task; that experts are limited in the number of things that they can mentally juggle at a time to 7 {plus minus} 2; that data gatherers and analysts can introduce bias by unintentionally causing an altering of the expert's thinking or answers; that the level of detail the data, or granularity, can affect the analyses; and the conditioning effect poses difficulties in gathering and analyzing of the expert data. The data that the expert gives can be conditioned on a variety of factors that can affect the analysis and the interpretation of the results. 31 refs.

  20. Temperature Affects Human Sweet Taste via At Least Two Mechanisms

    PubMed Central

    Nachtigal, Danielle

    2015-01-01

    The reported effects of temperature on sweet taste in humans have generally been small and inconsistent. Here, we describe 3 experiments that follow up a recent finding that cooling from 37 to 21 °C does not reduce the initial sweetness of sucrose but increases sweet taste adaptation. In experiment 1, subjects rated the sweetness of sucrose, glucose, and fructose solutions at 5–41 °C by dipping the tongue tip into the solutions after 0-, 3-, or 10-s pre-exposures to the same solutions or to H2O; experiment 2 compared the effects of temperature on the sweetness of 3 artificial sweeteners (sucralose, aspartame, and saccharin); and experiment 3 employed a flow-controlled gustometer to rule out the possibility the effects of temperature in the preceding experiments were unique to dipping the tongue into a still taste solution. The results (i) confirmed that mild cooling does not attenuate sweetness but can increase sweet taste adaptation; (ii) demonstrated that cooling to 5–12 °C can directly reduce sweetness intensity; and (iii) showed that both effects vary across stimuli. These findings have implications for the TRPM5 hypothesis of thermal effects on sweet taste and raise the possibility that temperature also affects an earlier step in the T1R2–T1R3 transduction cascade. PMID:25963040

  1. Affective Man-Machine Interface: Unveiling Human Emotions through Biosignals

    NASA Astrophysics Data System (ADS)

    van den Broek, Egon L.; Lisý, Viliam; Janssen, Joris H.; Westerink, Joyce H. D. M.; Schut, Marleen H.; Tuinenbreijer, Kees

    As is known for centuries, humans exhibit an electrical profile. This profile is altered through various psychological and physiological proce-sses, which can be measured through biosignals; e.g., electromyography (EMG) and electrodermal activity (EDA). These biosignals can reveal our emotions and, as such, can serve as an advanced man-machine interface (MMI) for empathic consumer products. However, such a MMI requires the correct classification of biosignals to emotion classes. This chapter starts with an introduction on biosignals for emotion detection. Next, a state-of-the-art review is presented on automatic emotion classification. Moreover, guidelines are presented for affective MMI. Subsequently, a research is presented that explores the use of EDA and three facial EMG signals to determine neutral, positive, negative, and mixed emotions, using recordings of 21 people. A range of techniques is tested, which resulted in a generic framework for automated emotion classification with up to 61.31% correct classification of the four emotion classes, without the need of personal profiles. Among various other directives for future research, the results emphasize the need for parallel processing of multiple biosignals.

  2. Temperature Affects Human Sweet Taste via At Least Two Mechanisms.

    PubMed

    Green, Barry G; Nachtigal, Danielle

    2015-07-01

    The reported effects of temperature on sweet taste in humans have generally been small and inconsistent. Here, we describe 3 experiments that follow up a recent finding that cooling from 37 to 21 °C does not reduce the initial sweetness of sucrose but increases sweet taste adaptation. In experiment 1, subjects rated the sweetness of sucrose, glucose, and fructose solutions at 5-41 °C by dipping the tongue tip into the solutions after 0-, 3-, or 10-s pre-exposures to the same solutions or to H2O; experiment 2 compared the effects of temperature on the sweetness of 3 artificial sweeteners (sucralose, aspartame, and saccharin); and experiment 3 employed a flow-controlled gustometer to rule out the possibility the effects of temperature in the preceding experiments were unique to dipping the tongue into a still taste solution. The results (i) confirmed that mild cooling does not attenuate sweetness but can increase sweet taste adaptation; (ii) demonstrated that cooling to 5-12 °C can directly reduce sweetness intensity; and (iii) showed that both effects vary across stimuli. These findings have implications for the TRPM5 hypothesis of thermal effects on sweet taste and raise the possibility that temperature also affects an earlier step in the T1R2-T1R3 transduction cascade. PMID:25963040

  3. Bayesian Safety Risk Modeling of Human-Flightdeck Automation Interaction

    NASA Technical Reports Server (NTRS)

    Ancel, Ersin; Shih, Ann T.

    2015-01-01

    Usage of automatic systems in airliners has increased fuel efficiency, added extra capabilities, enhanced safety and reliability, as well as provide improved passenger comfort since its introduction in the late 80's. However, original automation benefits, including reduced flight crew workload, human errors or training requirements, were not achieved as originally expected. Instead, automation introduced new failure modes, redistributed, and sometimes increased workload, brought in new cognitive and attention demands, and increased training requirements. Modern airliners have numerous flight modes, providing more flexibility (and inherently more complexity) to the flight crew. However, the price to pay for the increased flexibility is the need for increased mode awareness, as well as the need to supervise, understand, and predict automated system behavior. Also, over-reliance on automation is linked to manual flight skill degradation and complacency in commercial pilots. As a result, recent accidents involving human errors are often caused by the interactions between humans and the automated systems (e.g., the breakdown in man-machine coordination), deteriorated manual flying skills, and/or loss of situational awareness due to heavy dependence on automated systems. This paper describes the development of the increased complexity and reliance on automation baseline model, named FLAP for FLightdeck Automation Problems. The model development process starts with a comprehensive literature review followed by the construction of a framework comprised of high-level causal factors leading to an automation-related flight anomaly. The framework was then converted into a Bayesian Belief Network (BBN) using the Hugin Software v7.8. The effects of automation on flight crew are incorporated into the model, including flight skill degradation, increased cognitive demand and training requirements along with their interactions. Besides flight crew deficiencies, automation system

  4. Human health and safety risks management in underground coal mines using fuzzy TOPSIS.

    PubMed

    Mahdevari, Satar; Shahriar, Kourosh; Esfahanipour, Akbar

    2014-08-01

    The scrutiny of health and safety of personnel working in underground coal mines is heightened because of fatalities and disasters that occur every year worldwide. A methodology based on fuzzy TOPSIS was proposed to assess the risks associated with human health in order to manage control measures and support decision-making, which could provide the right balance between different concerns, such as safety and costs. For this purpose, information collected from three hazardous coal mines namely Hashouni, Hojedk and Babnizu located at the Kerman coal deposit, Iran, were used to manage the risks affecting the health and safety of their miners. Altogether 86 hazards were identified and classified under eight categories: geomechanical, geochemical, electrical, mechanical, chemical, environmental, personal, and social, cultural and managerial risks. Overcoming the uncertainty of qualitative data, the ranking process is accomplished by fuzzy TOPSIS. After running the model, twelve groups with different risks were obtained. Located in the first group, the most important risks with the highest negative effects are: materials falling, catastrophic failure, instability of coalface and immediate roof, firedamp explosion, gas emission, misfire, stopping of ventilation system, wagon separation at inclines, asphyxiation, inadequate training and poor site management system. According to the results, the proposed methodology can be a reliable technique for management of the minatory hazards and coping with uncertainties affecting the health and safety of miners when performance ratings are imprecise. The proposed model can be primarily designed to identify potential hazards and help in taking appropriate measures to minimize or remove the risks before accidents can occur. PMID:24815558

  5. Long-term efficacy and safety of human papillomavirus vaccination

    PubMed Central

    De Vincenzo, Rosa; Conte, Carmine; Ricci, Caterina; Scambia, Giovanni; Capelli, Giovanni

    2014-01-01

    In this paper, we review the published evidence about the long-term efficacy of the available human papillomavirus (HPV) vaccines and their safety profile. Two prophylactic HPV vaccines – bivalent (bHPV) and quadrivalent (qHPV) – are now available, and vaccination programs are being widely implemented, primarily targeting adolescent girls. Efficacy has been widely demonstrated for both vaccines. Since the risk of HPV exposure potentially persists throughout a woman’s sexual life, vaccine duration of protection is critical to overall effectiveness. Interpreting the results of long-term efficacy studies for the two HPV vaccines can be puzzling, due to the heterogeneity of studies, different methods used in the assessment of immunogenicity, histopathological and virological end points, and statistical power issues. Moreover, an immunologic correlate of protection has not yet been established, and it is unknown whether higher antibody levels will really result in a longer duration of protection. Disease prevention remains the most important measure of long-term duration of vaccine efficacy. To date, the longest follow-up of an HPV vaccine has been 9.4 years for the bHPV vaccine. Long-term follow-up for qHPV vaccine goes up to 8 years. The vaccine continues to be immunogenic and well tolerated up to 9 years following vaccination. All randomized controlled clinical trials of the bHPV and the qHPV vaccines provide evidence of an excellent safety profile. The most common complaint reported is pain in the injection site, which is self-limiting and spontaneously resolved. The incidence of systemic adverse events (AEs), serious AEs, and discontinuations due to a serious AE reported in clinical studies are similar between the two vaccines and their control groups. In particular, no increased risk of autoimmune disease has been shown among HPV-vaccinated subjects in long-term observation studies. As these are crucial topics in HPV vaccination, it is important to establish

  6. 75 FR 5536 - Pipeline Safety: Control Room Management/Human Factors, Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-03

    ... . SUPPLEMENTARY INFORMATION: On December 3, 2009, PHMSA published a final rule in the Federal Register (74 FR... 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...

  7. Person-centered work environments, psychological safety, and positive affect in healthcare: a theoretical framework.

    PubMed

    Rathert, Cheryl; May, Douglas R

    2008-01-01

    We propose that in order to systematically improve healthcare quality, healthcare organizations (HCOs) need work environments that are person-centered: environments that support the careprovider as well as the patient. We further argue that HCOs have a moral imperative to provide a workplace where professional care standards can be achieved. We draw upon a large body of research from several disciplines to propose and articulate a theoretical framework that explains how the work environment should be related to the well-being of patients and careproviders, that is, the potential mediating mechanisms. Person-centered work environments include: 1. Climates for patient-centered care. 2. Climates for quality improvement. 3. Benevolent ethical climates. Such a work environment should support the provision of patient-centered care, and should lead to positive psychological states for careproviders, including psychological safety and positive affect. The model contributes to theory by specifying relationships between important organizational variables. The model can potentially contribute to practice by linking specific work environment attributes to outcomes for careproviders and patients. PMID:18839753

  8. Transposable element insertions have strongly affected human evolution

    PubMed Central

    Britten, Roy J.

    2010-01-01

    Comparison of a full collection of the transposable element (TE) sequences of vertebrates with genome sequences shows that the human genome makes 655 perfect full-length matches. The cause is that the human genome contains many active TEs that have caused TE inserts in relatively recent times. These TE inserts in the human genome are several types of young Alus (AluYa5, AluYb8, AluYc1, etc.). Work in many laboratories has shown that such inserts have many effects including changes in gene expression, increases in recombination, and unequal crossover. The time of these very effective changes in the human lineage genome extends back about 4 million years according to these data and very likely much earlier. Rapid human lineage-specific evolution, including brain size is known to have also occurred in the last few million years. Alu insertions likely underlie rapid human lineage evolution. They are known to have many effects. Examples are listed in which TE sequences have influenced human-specific genes. The proposed model is that the many TE insertions created many potentially effective changes and those selected were responsible for a part of the striking human lineage evolution. The combination of the results of these events that were selected during human lineage evolution was apparently effective in producing a successful and rapidly evolving species. PMID:21041622

  9. Games that ''Work'': Using Computer Games to Teach Alcohol-Affected Children about Fire and Street Safety

    ERIC Educational Resources Information Center

    Coles, Claire D.; Strickland, Dorothy C.; Padgett, Lynne; Bellmoff, Lynnae

    2007-01-01

    Unintentional injuries are a leading cause of death and disability for children. Those with developmental disabilities, including children affected by prenatal alcohol exposure, are at highest risk for injuries. Although teaching safety skills is recommended to prevent injury, cognitive limitations and behavioral problems characteristic of…

  10. Immunogenicity and Safety of the Quadrivalent Human Papillomavirus Vaccine in HIV-1–Infected Women

    PubMed Central

    Kojic, Erna Milunka; Kang, Minhee; Cespedes, Michelle S.; Umbleja, Triin; Godfrey, Catherine; Allen, Reena T.; Firnhaber, Cynthia; Grinsztejn, Beatriz; Palefsky, Joel M.; Webster-Cyriaque, Jennifer Y.; Saah, Alfred; Aberg, Judith A.; Cu-Uvin, Susan

    2014-01-01

    Background. Women infected with human immunodeficiency virus (HIV) are disproportionately affected by human papillomavirus (HPV)–related anogenital disease, particularly with increased immunosuppression. AIDS Clinical Trials Group protocol A5240 was a trial of 319 HIV-infected women in the United States, Brazil, and South Africa to determine immunogenicity and safety of the quadrivalent HPV vaccine in 3 strata based on screening CD4 count: >350 (stratum A), 201–350 (stratum B), and ≤200 cells/µL (stratum C). Methods. Safety and serostatus of HPV types 6, 11, 16, and 18 were examined. HPV serological testing was performed using competitive Luminex immunoassay (HPV-4 cLIA). HPV type-specific seroconversion analysis was done for participants who were seronegative for the given type at baseline. Results. Median age of patients was 36 years; 11% were white, 56% black, and 31% Hispanic. Median CD4 count was 310 cells/µL, and 40% had undetectable HIV-1 load. No safety issues were identified. Seroconversion proportions among women at week 28 for HPV types 6, 11,16, and 18 were 96%, 98%, 99%, and 91%, respectively, for stratum A; 100%, 98%, 98%, and 85%, respectively, for stratum B, and 84%, 92%, 93%, and 75%, respectively, for stratum C. Conclusions. The quadrivalent HPV vaccine targeted at types 6, 11, 16, and 18 was safe and immunogenic in HIV-infected women aged 13–45 years. Women with HIV RNA load >10 000 copies/mL and/or CD4 count <200 cells/µL had lower rates of seroconversion rates. Clinical Trials Registration. NCT00604175. PMID:24723284

  11. Formaldehyde Crosses the Human Placenta and Affects Human Trophoblast Differentiation and Hormonal Functions

    PubMed Central

    Pidoux, Guillaume; Gerbaud, Pascale; Guibourdenche, Jean; Thérond, Patrice; Ferreira, Fatima; Simasotchi, Christelle; Evain-Brion, Danièle; Gil, Sophie

    2015-01-01

    The chorionic villus of the human placenta is the source of specific endocrine functions and nutrient exchanges. These activities are ensured by the syncytiotrophobast (ST), which bathes in maternal blood. The ST arises and regenerates throughout pregnancy by fusion of underlying cytotrophoblasts (CT). Any anomaly of ST formation or regeneration can affect pregnancy outcome and fetal growth. Because of its direct interaction with maternal blood, the ST is sensitive to drugs, pollutants and xenohormones. Ex vivo assays of perfused cotyledon show that formaldehyde, a common pollutant present in furniture, paint and plastics, can accumulate in the human placenta and cross to the fetal compartment. By means of RT-qPCR, immunoblot and immunocytochemistry experiments, we demonstrate in vitro that formaldehyde exerts endocrine toxicity on human trophoblasts, including a decrease in the production of protein hormones of pregnancy. In addition, formaldehyde exposure triggered human trophoblast fusion by upregulating syncitin-1 receptor expression (ASC-type amino-acid transporter 2: ASCT2). Moreover, we show that formaldehyde-exposed trophoblasts present an altered redox status associated with oxidative stress, and an increase in ASCT2 expression intended to compensate for this stress. Finally, we demonstrate that the adverse effects of formaldehyde on trophoblast differentiation and fusion are reversed by N-acetyl-L-cysteine (Nac), an antioxidant. PMID:26186596

  12. ANALYSIS OF DISCRIMINATING FACTORS IN HUMAN ACTIVITIES THAT AFFECT EXPOSURE

    EPA Science Inventory

    Accurately modeling exposure to particulate matter (PM) and other pollutants ultimately involves the utilization of human location-activity databases to assist in understanding the potential variability of microenvironmental exposures. This paper critically considers and stati...

  13. Safety Characteristics in System Application Software for Human Rated Exploration

    NASA Technical Reports Server (NTRS)

    Mango, E. J.

    2016-01-01

    NASA and its industry and international partners are embarking on a bold and inspiring development effort to design and build an exploration class space system. The space system is made up of the Orion system, the Space Launch System (SLS) and the Ground Systems Development and Operations (GSDO) system. All are highly coupled together and dependent on each other for the combined safety of the space system. A key area of system safety focus needs to be in the ground and flight application software system (GFAS). In the development, certification and operations of GFAS, there are a series of safety characteristics that define the approach to ensure mission success. This paper will explore and examine the safety characteristics of the GFAS development.

  14. AGRICULTURAL CHEMICAL SAFETY ASSESSMENT: A MULTISECTOR APPROACH TO THE MODERNIZATION OF HUMAN SAFETY REQUIREMENTS.

    EPA Science Inventory

    Better understanding of toxicological mechanisms, enhanced testing capabilities, and demands for more sophisticated data for safety and health risk assessment have generated international interest in improving the current testing paradigm for agricultural chemicals. To address th...

  15. Positive Affect and the Complex Dynamics of Human Flourishing

    ERIC Educational Resources Information Center

    Fredrickson, Barbara L.; Losada, Marcial F.

    2005-01-01

    Extending B. L. Fredrickson's (1998) broaden-and-build theory of positive emotions and M. Losada's (1999) nonlinear dynamics model of team performance, the authors predict that a ratio of positive to negative affect at or above 2.9 will characterize individuals in flourishing mental health. Participants (N=188) completed an initial survey to…

  16. Hemispheric Asymmetries in Children's Perception of Nonlinguistic Human Affective Sounds

    ERIC Educational Resources Information Center

    Pollak, Seth D.; Holt, Lori L.; Fries, Alison B. Wismer

    2004-01-01

    In the present work, we developed a database of nonlinguistic sounds that mirror prosodic characteristics typical of language and thus carry affective information, but do not convey linguistic information. In a dichotic-listening task, we used these novel stimuli as a means of disambiguating the relative contributions of linguistic and affective…

  17. Affective neuroscience of pleasure: reward in humans and animals

    PubMed Central

    2010-01-01

    Introduction Pleasure and reward are generated by brain circuits that are largely shared between humans and other animals. Discussion Here, we survey some fundamental topics regarding pleasure mechanisms and explicitly compare humans and animals. Conclusion Topics surveyed include liking, wanting, and learning components of reward; brain coding versus brain causing of reward; subjective pleasure versus objective hedonic reactions; roles of orbitofrontal cortex and related cortex regions; subcortical hedonic hotspots for pleasure generation; reappraisals of dopamine and pleasure-electrode controversies; and the relation of pleasure to happiness. PMID:18311558

  18. Human error risk management methodology for safety audit of a large railway organisation.

    PubMed

    Cacciabue, P C

    2005-11-01

    This paper considers the application of the human error risk management for engineering systems (HERMES) methodology for safety assessment studies. The application concerns the recurrent safety audits (RSA) of a large organisation in the domain of railway transportation systems. The objective of the study was the identification of the most relevant areas of intervention for improving safety and reliability of the service. The methodology has been applied to the whole organisation and its working processes. Specific attention was paid to train drivers. A number of critical indicators of safety and recurrent safety audit matrices were identified, which enabled the assessment of the safety level of the organisation and the generation of safety recommendations. The application of HERMES to this case study shows that the methodology is applicable in practice and can give valuable and significant results. PMID:16122693

  19. Mevalonate availability affects human and rat resistance vessel function.

    PubMed Central

    Roullet, J B; Xue, H; Roullet, C M; Fletcher, W S; Cipolla, M J; Harker, C T; McCarron, D A

    1995-01-01

    Previous data in rat conductance vessels indicated that cellular mevalonate contributes to vascular tone and systemic blood pressure control. Using exogenous mevalonate (M) or lovastatin, a 3-hydroxy-3-methyl-glutaryl CoA (HMG-CoA) reductase inhibitor (L), we characterized the role of mevalonate availability in resistance artery function, both in experimental animals and humans. Rat mesenteric artery resistance vessels (MARV, n = 9) were incubated for 48 h with either L, M, L + M, or vehicle (V) and tested for reactivity to NE, serotonin, acetylcholine, atrial natriuretic peptide, and sodium nitroprusside (SNP). Lovastatin increased sensitivity to NE (P < 0.03) and serotonin (P < 0.003), and significantly impaired the response to all three vasodilators. These effects were reversed by co-incubation with mevalonate. Mevalonate alone had no effect. In separate experiments, intravascular free Ca2+ concentration (ivfCa2+) was determined in fura-2AM loaded MARV. Basal ivfCa2+ was increased after a 48-h exposure to L (52.7 +/- 4.6 nM, L, vs. 29.7 +/- 2.4 nM, V, n = 12, P < 0.003), as were ivfCa2+ levels following stimulation with low (100 nM) NE concentrations. Similar ivfCa2+ concentrations were achieved during maximum contraction with NE (10 mM) in both groups. Human resistance arteries of human adipose tissue were also studied. Lovastatin increased the sensitivity to NE (ED50 = 372 +/- 56 nM, V, and 99 +/- 33 nM, L, P < 0.001) and significantly decreased the relaxation to acetylcholine and SNP of human vessels. We conclude that mevalonate availability directly contribute to resistance vessel function and vascular signal transduction systems in both experimental animals and humans. The study calls for the identification of non-sterol, mevalonate-derived vasoactive metabolites, and suggests that disorders of the mevalonate pathway can alter vascular tone and cause hypertension. PMID:7615793

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

    PubMed

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

    2014-12-01

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

  1. Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape.

    PubMed

    Moreira-Arce, Dario; Vergara, Pablo M; Boutin, Stan

    2015-01-01

    Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250 m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250 m scale negatively affected the diurnal occurrence of Darwin´s fox, whereas at 500 m scale roads had a stronger negative effect on the diurnal occurrence of Darwin´s foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in native forest remnants

  2. Diurnal Human Activity and Introduced Species Affect Occurrence of Carnivores in a Human-Dominated Landscape

    PubMed Central

    Moreira-Arce, Dario; Vergara, Pablo M.; Boutin, Stan

    2015-01-01

    Diurnal human activity and domestic dogs in agro-forestry mosaics should theoretically modify the diurnal habitat use patterns of native carnivores, with these effects being scale-dependent. We combined intensive camera trapping data with Bayesian occurrence probability models to evaluate both diurnal and nocturnal patterns of space use by carnivores in a mosaic of land-use types in southern Chile. A total of eight carnivores species were recorded, including human-introduced dogs. During the day the most frequently detected species were the culpeo fox and the cougar. Conversely, during the night, the kodkod and chilla fox were the most detected species. The best supported models showed that native carnivores responded differently to landscape attributes and dogs depending on both the time of day as well as the spatial scale of landscape attributes. The positive effect of native forest cover at 250m and 500 m radius buffers was stronger during the night for the Darwin's fox and cougar. Road density at 250m scale negatively affected the diurnal occurrence of Darwin´s fox, whereas at 500m scale roads had a stronger negative effect on the diurnal occurrence of Darwin´s foxes and cougars. A positive effect of road density on dog occurrence was evidenced during both night and day. Patch size had a positive effect on cougar occurrence during night whereas it affected negatively the occurrence of culpeo foxes and skunks during day. Dog occurrence had a negative effect on Darwin's fox occurrence during day-time and night-time, whereas its negative effect on the occurrence of cougar was evidenced only during day-time. Carnivore occurrences were not influenced by the proximity to a conservation area. Our results provided support for the hypothesis that diurnal changes to carnivore occurrence were associated with human and dog activity. Landscape planning in our study area should be focused in reducing both the levels of diurnal human activity in native forest remnants and

  3. Human performance cognitive-behavioral modeling: a benefit for occupational safety

    NASA Technical Reports Server (NTRS)

    Gore, Brian F.

    2002-01-01

    Human Performance Modeling (HPM) is a computer-aided job analysis software methodology used to generate predictions of complex human-automation integration and system flow patterns with the goal of improving operator and system safety. The use of HPM tools has recently been increasing due to reductions in computational cost, augmentations in the tools' fidelity, and usefulness in the generated output. An examination of an Air Man-machine Integration Design and Analysis System (Air MIDAS) model evaluating complex human-automation integration currently underway at NASA Ames Research Center will highlight the importance to occupational safety of considering both cognitive and physical aspects of performance when researching human error.

  4. Human performance cognitive-behavioral modeling: a benefit for occupational safety.

    PubMed

    Gore, Brian F

    2002-01-01

    Human Performance Modeling (HPM) is a computer-aided job analysis software methodology used to generate predictions of complex human-automation integration and system flow patterns with the goal of improving operator and system safety. The use of HPM tools has recently been increasing due to reductions in computational cost, augmentations in the tools' fidelity, and usefulness in the generated output. An examination of an Air Man-machine Integration Design and Analysis System (Air MIDAS) model evaluating complex human-automation integration currently underway at NASA Ames Research Center will highlight the importance to occupational safety of considering both cognitive and physical aspects of performance when researching human error. PMID:12189105

  5. The village/commune safety policy and HIV prevention efforts among key affected populations in Cambodia: finding a balance

    PubMed Central

    2012-01-01

    The Village/Commune Safety Policy was launched by the Ministry of Interior of the Kingdom of Cambodia in 2010 and, due to a priority focus on “cleaning the streets”, has created difficulties for HIV prevention programs attempting to implement programs that work with key affected populations including female sex workers and people who inject drugs. The implementation of the policy has forced HIV program implementers, the UN and various government counterparts to explore and develop collaborative ways of delivering HIV prevention services within this difficult environment. The following case study explores some of these efforts and highlights the promising development of a Police Community Partnership Initiative that it is hoped will find a meaningful balance between the Village/Commune Safety Policy and HIV prevention efforts with key affected populations in Cambodia. PMID:22770267

  6. The village/commune safety policy and HIV prevention efforts among key affected populations in Cambodia: finding a balance.

    PubMed

    Thomson, Nick; Leang, Supheap; Chheng, Kannarath; Weissman, Amy; Shaw, Graham; Crofts, Nick

    2012-01-01

    The Village/Commune Safety Policy was launched by the Ministry of Interior of the Kingdom of Cambodia in 2010 and, due to a priority focus on "cleaning the streets", has created difficulties for HIV prevention programs attempting to implement programs that work with key affected populations including female sex workers and people who inject drugs. The implementation of the policy has forced HIV program implementers, the UN and various government counterparts to explore and develop collaborative ways of delivering HIV prevention services within this difficult environment. The following case study explores some of these efforts and highlights the promising development of a Police Community Partnership Initiative that it is hoped will find a meaningful balance between the Village/Commune Safety Policy and HIV prevention efforts with key affected populations in Cambodia. PMID:22770267

  7. Skin Blood Perfusion and Oxygenation Colour Affect Perceived Human Health

    PubMed Central

    Stephen, Ian D.; Coetzee, Vinet; Law Smith, Miriam; Perrett, David I.

    2009-01-01

    Skin blood perfusion and oxygenation depends upon cardiovascular, hormonal and circulatory health in humans and provides socio-sexual signals of underlying physiology, dominance and reproductive status in some primates. We allowed participants to manipulate colour calibrated facial photographs along empirically-measured oxygenated and deoxygenated blood colour axes both separately and simultaneously, to optimise healthy appearance. Participants increased skin blood colour, particularly oxygenated, above basal levels to optimise healthy appearance. We show, therefore, that skin blood perfusion and oxygenation influence perceived health in a way that may be important to mate choice. PMID:19337378

  8. Disturbances of electrodynamic activity affect abortion in human

    NASA Astrophysics Data System (ADS)

    Jandová, A.; Nedbalová, M.; Kobilková, J.; Čoček, A.; Dohnalová, A.; Cifra, M.; Pokorný, J.

    2011-12-01

    Biochemical research of biological systems is highly developed, and it has disclosed a spectrum of chemical reactions, genetic processes, and the pathological development of various diseases. The fundamental hypothesis of physical processes in biological systems, in particular of coherent electrically polar vibrations and electromagnetic activity, was formulated by H. Fröhlich he assumed connection of cancer process with degradation of coherent electromagnetic activity. But the questions of cellular structures capable of the coherent electrical polar oscillation, mechanisms of energy supply, and the specific role of the endogenous electromagnetic fields in transport, organisation, interactions, and information transfer remained open. The nature of physical disturbances caused by some diseases (including the recurrent abortion in humans and the cancer) was unknown. We have studied the reasons of recurrent abortions in humans by means of the cell mediated immunity (using immunologic active RNA prepared from blood of inbred laboratory mice strain C3H/H2K, infected with the lactate dehydrogenase elevating virus-LD V) and the cytogenetic examination from karyotype pictures. The recurrent abortion group contained women with dg. spontaneous abortion (n = 24) and the control group was composed of 30 healthy pregnant women. Our hypothesis was related to quality of endometrium in relation to nidation of the blastocyst. The energetic insufficiency (ATP) inhibits normal development of fetus and placenta. We hope that these ideas might have impact on further research, which could provide background for effective interdisciplinary cooperation of malignant and non-malignant diseases.

  9. Safety Aspects in a Human-Robot Interaction Scenario: A Human Worker Is Co-operating with an Industrial Robot

    NASA Astrophysics Data System (ADS)

    Zaeh, Michael; Roesel, Wolfgang

    This paper presents a concept of a smart working environment designed to allow true joint actions of humans and industrial robots. The proposed system perceives its environment with multiple sensor modalities and acts in it with an industrial robot manipulator to assemble workpieces in combination with a human worker. In combination with the reactive behavior of the robot, safe collaboration between the human and the robot is possible. Generally, the application scenario is situated in a factory, where a human worker is supported by a robot to accomplish a given hybrid assembly scenario, that covers manual and automated assembly steps. For an effective human-robot collaboration, new safety methods have to be developed and proven. Human workers as well as objects in the environment have to be detected and a collision avoidance algorithm has to ensure the safety for persons and equipment.

  10. Functional TLR5 genetic variants affect human colorectal cancer survival.

    PubMed

    Klimosch, Sascha N; Försti, Asta; Eckert, Jana; Knezevic, Jelena; Bevier, Melanie; von Schönfels, Witigo; Heits, Nils; Walter, Jessica; Hinz, Sebastian; Lascorz, Jesus; Hampe, Jochen; Hartl, Dominik; Frick, Julia-Stefanie; Hemminki, Kari; Schafmayer, Clemens; Weber, Alexander N R

    2013-12-15

    Toll-like receptors (TLR) are overexpressed on many types of cancer cells, including colorectal cancer cells, but little is known about the functional relevance of these immune regulatory molecules in malignant settings. Here, we report frequent single-nucleotide polymorphisms (SNP) in the flagellin receptor TLR5 and the TLR downstream effector molecules MyD88 and TIRAP that are associated with altered survival in a large cohort of Caucasian patients with colorectal cancer (n = 613). MYD88 rs4988453, a SNP that maps to a promoter region shared with the acetyl coenzyme-A acyl-transferase-1 (ACAA1), was associated with decreased survival of patients with colorectal cancer and altered transcriptional activity of the proximal genes. In the TLR5 gene, rs5744174/F616L was associated with increased survival, whereas rs2072493/N592S was associated with decreased survival. Both rs2072493/N592S and rs5744174/F616L modulated TLR5 signaling in response to flagellin or to different commensal and pathogenic intestinal bacteria. Notably, we observed a reduction in flagellin-induced p38 phosphorylation, CD62L shedding, and elevated expression of interleukin (IL)-6 and IL-1β mRNA in human primary immune cells from TLR5 616LL homozygote carriers, as compared with 616FF carriers. This finding suggested that the well-documented effect of cytokines like IL-6 on colorectal cancer progression might be mediated by TLR5 genotype-dependent flagellin sensing. Our results establish an important link between TLR signaling and human colorectal cancer with relevance for biomarker and therapy development. PMID:24154872

  11. Components That Affect the Personal Motivation to Implement Campus Safety Protocols

    ERIC Educational Resources Information Center

    Burt, Ernest, III

    2013-01-01

    This study examined components that have an effect on crisis response team members' personal motivation to perform campus safety protocols. The research method for this study was a quantitative design. The variables measured were compensation, experience, training, and communication. The motivation sources for this study included instrumental…

  12. Pregnancy does not affect human olfactory detection thresholds.

    PubMed

    Cameron, E Leslie

    2014-02-01

    Hyperosmia is suspected in pregnancy; however, no empirical study using validated measures of olfactory function has clearly confirmed the anecdotal reports of this phenomenon. The goal of the current study is to compare the olfactory sensitivity of pregnant women to that of nonpregnant women and men. All participants rated their sense of smell and pregnant women listed the odors to which they were most sensitive. Detection thresholds were measured using a well-validated protocol. A group of pregnant and nonpregnant women was studied longitudinally using a signal detection procedure designed to detect small differences in sensitivity. Pregnant women, particularly in the 1st trimester, rated their sense of smell to be higher than nonpregnant women and men and indicated many (primarily unpleasant) odors to which they were more sensitive. Women rated their sense of smell higher than men. However, there was no sex difference in thresholds and neither thresholds nor signal detection measures of sensitivity were significantly affected by either sex or pregnancy status. The implications of the lack of relationship between self-report and measures of olfactory sensitivity, particularly in pregnancy, are discussed. PMID:24302690

  13. Noisy human neighbours affect where urban monkeys live

    PubMed Central

    Duarte, Marina H. L.; Vecci, Marco A.; Hirsch, André; Young, Robert J.

    2011-01-01

    Urban areas and many natural habitats are being dominated by a new selection pressure: anthropogenic noise. The ongoing expansion of urban areas, roads and airports throughout the world makes the noise almost omnipresent. Urbanization and the increase of noise levels form a major threat to living conditions in and around cities. Insight into the behavioural strategies of urban survivors may explain the sensitivity of other species to urban selection pressures. Here, we show that urban black-tufted marmosets (Callithrix penicillata) living in noisy urban areas may select their home-range based primarily on ambient noise level. We have tested the hypothesis that the noise from vehicular traffic and visitors in an urban park in Brazil influences the use of home-range (space) by urban marmosets. Marmosets even avoided noisy areas with high food availability. In addition, they systematically preferred the quieter areas even with dynamic changes in the acoustic landscape of the park between weekdays and Sundays (no observations were made on Saturdays). These data provide evidence that the use of home-range by wild animals can be affected by a potential aversive stimulus such as noise pollution. PMID:21715396

  14. Noisy human neighbours affect where urban monkeys live.

    PubMed

    Duarte, Marina H L; Vecci, Marco A; Hirsch, André; Young, Robert J

    2011-12-23

    Urban areas and many natural habitats are being dominated by a new selection pressure: anthropogenic noise. The ongoing expansion of urban areas, roads and airports throughout the world makes the noise almost omnipresent. Urbanization and the increase of noise levels form a major threat to living conditions in and around cities. Insight into the behavioural strategies of urban survivors may explain the sensitivity of other species to urban selection pressures. Here, we show that urban black-tufted marmosets (Callithrix penicillata) living in noisy urban areas may select their home-range based primarily on ambient noise level. We have tested the hypothesis that the noise from vehicular traffic and visitors in an urban park in Brazil influences the use of home-range (space) by urban marmosets. Marmosets even avoided noisy areas with high food availability. In addition, they systematically preferred the quieter areas even with dynamic changes in the acoustic landscape of the park between weekdays and Sundays (no observations were made on Saturdays). These data provide evidence that the use of home-range by wild animals can be affected by a potential aversive stimulus such as noise pollution. PMID:21715396

  15. MISR Satellite Observations of Aerosol Types Affecting Human Health

    NASA Astrophysics Data System (ADS)

    Kalashnikova, O. V.; Franklin, M.; Garay, M. J.; Diner, D. J.

    2015-12-01

    Ground-based observations of pollutants and concentrations of particulate matter (PM), that includes small particles designated PM2.5 and dust-dominated PM10, are the gold standard in studies of environmental impacts on human health. However, because monitoring stations are costly, they typically provide only limited spatial coverage, especially in rural and remote areas. We will demonstrate how data from the Multi-angle Imaging SpectroRadiometer (MISR) instrument that has been flying on NASA's Terra Earth Observing System satellite since early 2000 can be used to provide estimates of surface PM types. The current MISR operational aerosol retrieval uses a combination of multi-spectral and multi-angle data to retrieve aerosol optical depth (AOD) and particle property information (including dust AOD) globally at 17.6 km spatial resolution. Using the same algorithm with data collected in all 36-channels at 275 m resolution (Local Mode), which is available over greater Los Angeles area, and also was activated during 2013 DISCOVER-AQ California field campaign, high-resolution 4.4 km aerosol retrievals were performed in addition to the standard 17.6 km retrievals. The 4.4 km spatial resolution of the PM information data is fine enough to be able to resolve local differences in PM loading that may be important for understanding regional health effects of pollution in the region. In particular, we demonstrate that MISR high-resolution AOD retrievals are in better agreement with ground-based aerosol observations and reveal more details about the aerosol spatial variability compared to the MISR standard 17.6 km product. Then we will discuss techniques and show examples of the application of high-resolution MISR data to provide estimates of surface PM for the greater Los Angeles area in 2008 and for California San Joaquin Valley during the 2013 DISCOVER-AQ field campaign. Finally, we will discuss future NASA instruments that will provide new information allowing for better

  16. Aging affects the cardiovascular responses to cold stress in humans

    PubMed Central

    Hess, Kari L.; Wilson, Thad E.; Sauder, Charity L.; Gao, Zhaohui; Ray, Chester A.

    2009-01-01

    Cardiovascular-related mortality peaks during cold winter months, particularly in older adults. Acute physiological responses, such as increases in blood pressure, in response to cold exposure may contribute to these associations. To determine whether the blood pressure-raising effect (pressor response) of non-internal body temperature-reducing cold stress is greater with age, we measured physiological responses to 20 min of superficial skin cooling, via water-perfused suit, in 12 younger [25 ± 1 (SE) yr old] and 12 older (65 ± 2 yr old) adults. We found that superficial skin cooling elicited an increase in blood pressure from resting levels (pressor response; P < 0.05) in younger and older adults. However, the magnitude of this pressor response (systolic and mean blood pressure) was more than twofold higher in older adults (P < 0.05 vs. younger adults). The magnitude of the pressor response was similar at peripheral (brachial) and central (estimated in the aorta) measurement sites. Regression analysis revealed that aortic pulse wave velocity, a measure of central arterial stiffness obtained before cooling, was the best predictor of the increased pressor response to superficial skin cooling in older adults, explaining ∼63% of its variability. These results indicate that there is a greater pressor response to non-internal body temperature-reducing cold stress with age in humans that may be mediated by increased levels of central arterial stiffness. PMID:19679742

  17. Mimicry profiles are affected by human-induced habitat changes.

    PubMed Central

    Azmeh, S; Owen, J; Sørensen, K; Grewcock, D; Gilbert, F

    1998-01-01

    Mimicry theory predicts that mimics in a Batesian mimicry complex evolve to resemble models closely, and that there is a limit on the numbers of mimics relative to models. For hoverflies (Diptera: Syrphidae), supposed mimics of social wasps (Hymenoptera: Vespidae, neither of these is true; many mimics are imperfect and in the UK and Europe they outnumber their models manifold. We hypothesized that the high abundance of mimics relative to models in the UK may be the result not just of mimic model dynamics, but of habitat changes caused by humans. Most of the larvae of poor mimics are aphidophagous, and changes from ancient forest to agricultural and/or urban habitats may have vastly augmented aphid numbers. Using new and literature data, we compared mimicry profiles of habitats differing in their degree of habitat disturbance. In both cases more highly disturbed habitats had proportionally more poor mimics and fewer high-fidelity mimics than less disturbed habitats. This supports the hypothesis that habitat change has an effect on model to mimic ratios. PMID:9881474

  18. Family Poverty Affects the Rate of Human Infant Brain Growth

    PubMed Central

    Hanson, Jamie L.; Hair, Nicole; Shen, Dinggang G.; Shi, Feng; Gilmore, John H.; Wolfe, Barbara L.; Pollak, Seth D.

    2013-01-01

    Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems. PMID:24349025

  19. Family poverty affects the rate of human infant brain growth.

    PubMed

    Hanson, Jamie L; Hair, Nicole; Shen, Dinggang G; Shi, Feng; Gilmore, John H; Wolfe, Barbara L; Pollak, Seth D

    2013-01-01

    Living in poverty places children at very high risk for problems across a variety of domains, including schooling, behavioral regulation, and health. Aspects of cognitive functioning, such as information processing, may underlie these kinds of problems. How might poverty affect the brain functions underlying these cognitive processes? Here, we address this question by observing and analyzing repeated measures of brain development of young children between five months and four years of age from economically diverse backgrounds (n = 77). In doing so, we have the opportunity to observe changes in brain growth as children begin to experience the effects of poverty. These children underwent MRI scanning, with subjects completing between 1 and 7 scans longitudinally. Two hundred and three MRI scans were divided into different tissue types using a novel image processing algorithm specifically designed to analyze brain data from young infants. Total gray, white, and cerebral (summation of total gray and white matter) volumes were examined along with volumes of the frontal, parietal, temporal, and occipital lobes. Infants from low-income families had lower volumes of gray matter, tissue critical for processing of information and execution of actions. These differences were found for both the frontal and parietal lobes. No differences were detected in white matter, temporal lobe volumes, or occipital lobe volumes. In addition, differences in brain growth were found to vary with socioeconomic status (SES), with children from lower-income households having slower trajectories of growth during infancy and early childhood. Volumetric differences were associated with the emergence of disruptive behavioral problems. PMID:24349025

  20. Glycolytic pathway affects differentiation of human monocytes to regulatory macrophages.

    PubMed

    Suzuki, Hiroaki; Hisamatsu, Tadakazu; Chiba, Sayako; Mori, Kiyoto; Kitazume, Mina T; Shimamura, Katsuyoshi; Nakamoto, Nobuhiro; Matsuoka, Katsuyoshi; Ebinuma, Hirotoshi; Naganuma, Makoto; Kanai, Takanori

    2016-08-01

    Cellular metabolic state and individual metabolites have been reported to regulate the functional phenotype of immune cells. Cytokine production by regulatory and inflammatory macrophages is thought to mainly involve fatty acid oxidation and glycolysis, respectively, which fuel mitochondrial oxidative phosphorylation. However, the association between metabolic pathways and the acquisition of specific macrophage phenotypes remains unclear. This study assessed the relationship between glycolysis and the differentiation of regulatory macrophages. Human monocytes derived from peripheral blood were cultured in vitro in the presence of macrophage colony-stimulating factor to yield regulatory macrophages (M-Mϕs). M-Mϕs had a regulatory macrophage phenotype and produced substantial IL-10 following stimulation with lipopolysaccharide. To analyze the role of glycolysis, glycolysis inhibitors (2-deoxy-d-glucose or dichloroacetate) were added during M-Mϕ differentiation. These cells cultured with glycolysis inhibitors produced significantly lower amounts of IL-10, but produced significantly higher amounts of IL-6 compared to M-Mϕs differentiated without glycolysis inhibitors. Such phenotypic change of M-Mϕs differentiated with glycolysis inhibitors was associated with the alteration of the gene expression pattern related to macrophage differentiation, such as CSF1, MMP9 and VEGFA. M-Mϕs differentiated with glycolysis inhibitors seemed to retain plasticity to become IL-10 producing cells. Furthermore, increased level of pyruvate in culture medium was found to partially reverse the effects of glycolysis inhibitors on cytokine production of M-Mϕs. These results indicate the importance of glycolytic pathway in macrophage differentiation to a regulatory phenotype, and pyruvate may be one of the key metabolites in this process. PMID:27208804

  1. Safety of protein hydrolysates, fractions thereof and bioactive peptides in human nutrition.

    PubMed

    Schaafsma, G

    2009-10-01

    This paper evaluates the safety for humans with regard to consumption of protein hydrolysates and fractions thereof, including bioactive peptides. The available literature on the safety of protein, protein hydrolysates, fractions thereof and free amino acids on relevant food legislation is reviewed and evaluated. A new concept for the safety assessment of protein hydrolysates and fractions thereof is developed. Benchmarks for the evaluation are safety of total protein intake, safety of free amino acid intake, documented history of safe use, outcome of questionnaires in efficacy studies and safety studies. Similar to the intake of intact proteins with a history of safe use, the intake of hydrolysates made from them, does not raise concern about safety, provided the applied proteolytic enzymes are food grade and thus of suitable quality. The safety of hydrolysates and of fractions thereof, including the so-called bioactive peptides, should always be assessed by the company before market introduction (company safety assessment). Only when a novel protein source is used or a novel production process is applied, which results in significant changes in nutritional value, metabolic effect or increased level of undesirable substances, that products might fall under novel food regulations. This means that company safety assessment should be reviewed and approved by external independent experts (external safety evaluation) and the novel protein hydrolysate (fraction) is authorized by competent authorities before market introduction. It is argued that good judgement on the safety of hydrolysates and the fractions thereof can be obtained by comparing the anticipated intake of amino acids by these products with those levels to be reasonably expected to be ingested under normal conditions of consumption of a balanced and varied diet. The paper shows a decision tree that can be used for safety assessment. PMID:19623200

  2. A systematic process for assessing human spacecraft conceptual designs in terms of relative safety and operational characteristics

    NASA Astrophysics Data System (ADS)

    Higdon, Kevin Paul

    The research efforts in this dissertation are focused on reducing uncertainty in the conceptual design phase through a process of establishing a minimum functionality baseline before trading Safety and Operability in proposed spacecraft configurations. The challenge in human spacecraft development is how to combine the parts into a working design that complies with many requirements for top level mission objectives, safety, and mission success. The design methodologies presented here provides designers and decision makers with additional methods that provide an overall view of candidate design concepts. This work establishes a definition for a minimum functional design and is the first to group the fundamental mass parameters of a human spacecraft in the categories of Physics, Physiology, Safety, and Operability. The minimum functional baseline configuration described in this work is different from previous approaches because it eliminates the bias toward a minimum set of requirements. The amount of Safety in the spacecraft is the mass dedicated to safety through similar or dissimilar redundancy, safety components, margins, and dispersions. The amount of Operability in the spacecraft is the mass used to perform mission objectives and make functions easier or efficient. Because human spacecraft are highly coupled systems, the introduction of mass in one subsystem has downstream effects on other subsystems that are not easily recognized by designers and the use of rapidly reconfigurable prototypes allows designers and multidisciplinary teams to utilize Boundary Objects as a means of communication for maturing designs. The mass addition process coupled with the minimum functionality approach creates a tradespace of spacecraft configurations and provides designers with an overall view of how various levels of Safety or Operability will affect the overall spacecraft mass. The decisions made in the conceptual design phase are critical to the success of the program and

  3. Analysis of the safety and pharmacodynamics of human fibrinogen concentrate in animals

    SciTech Connect

    Beyerle, Andrea; Nolte, Marc W.; Solomon, Cristina; Herzog, Eva; Dickneite, Gerhard

    2014-10-01

    Fibrinogen, a soluble 340 kDa plasma glycoprotein, is critical in achieving and maintaining hemostasis. Reduced fibrinogen levels are associated with an increased risk of bleeding and recent research has investigated the efficacy of fibrinogen concentrate for controlling perioperative bleeding. European guidelines on the management of perioperative bleeding recommend the use of fibrinogen concentrate if significant bleeding is accompanied by plasma fibrinogen levels less than 1.5–2.0 g/l. Plasma-derived human fibrinogen concentrate has been available for therapeutic use since 1956. The overall aim of the comprehensive series of non-clinical investigations presented was to evaluate i) the pharmacodynamic and pharmacokinetic characteristics and ii) the safety and tolerability profile of human fibrinogen concentrate Haemocomplettan P® (RiaSTAP®). Pharmacodynamic characteristics were assessed in rabbits, pharmacokinetic parameters were determined in rabbits and rats and a safety pharmacology study was performed in beagle dogs. Additional toxicology tests included: single-dose toxicity tests in mice and rats; local tolerance tests in rabbits; and neoantigenicity tests in rabbits and guinea pigs following the introduction of pasteurization in the manufacturing process. Human fibrinogen concentrate was shown to be pharmacodynamically active in rabbits and dogs and well tolerated, with no adverse events and no influence on circulation, respiration or hematological parameters in rabbits, mice, rats and dogs. In these non-clinical investigations, human fibrinogen concentrate showed a good safety profile. This data adds to the safety information available to date, strengthening the current body of knowledge regarding this hemostatic agent. - Highlights: • A comprehensive series of pre-clinical investigations of human fibrinogen concentrate. • Human fibrinogen concentrate was shown to be pharmacodynamically active. • Human fibrinogen concentrate was well tolerated

  4. Antidepressants and Suicide Risk: How Did Specific Information in FDA Safety Warnings Affect Treatment Patterns?

    PubMed Central

    Busch, Susan H.; Frank, Richard G.; Leslie, Doug; Martin, Andres; Martin, Erika; Rosenheck, Robert; Barry, Colleen L.

    2009-01-01

    Objective From June 2003 through October 2004, the Food and Drug Administration (FDA) released five safety warnings related to antidepressant use and increased suicide risk in children. While researchers have documented a decline in antidepressant use in children over this time period, less is known about whether specific safety information conveyed in individual warnings was reflected in treatment patterns. Methods Thomson Marketscan claims data (2001–2005) for a national sample of privately insured children were used to construct treatment episodes (N=23,529). For each new episode of major depressive disorder, it was determined whether children’s treatment followed specific recommendations included in warnings released by the FDA. Treatment recommendations pertained to the use of the antidepressants paroxetine and fluoxetine and to patient monitoring. Treatment patterns were expected to change as the nature of risk information conveyed by the FDA changed over time. Results The timing of FDA recommendations was associated with trends in the use of paroxetine and fluoxetine by children with major depressive disorder newly initiating antidepressant treatment. However, no evidence of increases in outpatient visits (i.e., monitoring) among depressed children initiating antidepressants was found. Conclusions Release of specific risk and benefit information by the FDA was associated with changes in prescribing, but not outpatient follow-up. These results suggest the FDA plays an important role in communicating information to the public and providers, but while public health safety warnings were associated with changes in some practice patterns, not all recommendations conveyed in warnings were followed. PMID:20044412

  5. How the choice of safety performance function affects the identification of important crash prediction variables.

    PubMed

    Wang, Ketong; Simandl, Jenna K; Porter, Michael D; Graettinger, Andrew J; Smith, Randy K

    2016-03-01

    Across the nation, researchers and transportation engineers are developing safety performance functions (SPFs) to predict crash rates and develop crash modification factors to improve traffic safety at roadway segments and intersections. Generalized linear models (GLMs), such as Poisson or negative binomial regression, are most commonly used to develop SPFs with annual average daily traffic as the primary roadway characteristic to predict crashes. However, while more complex to interpret, data mining models such as boosted regression trees have improved upon GLMs crash prediction performance due to their ability to handle more data characteristics, accommodate non-linearities, and include interaction effects between the characteristics. An intersection data inventory of 36 safety relevant parameters for three- and four-legged non-signalized intersections along state routes in Alabama was used to study the importance of intersection characteristics on crash rate and the interaction effects between key characteristics. Four different SPFs were investigated and compared: Poisson regression, negative binomial regression, regularized generalized linear model, and boosted regression trees. The models did not agree on which intersection characteristics were most related to the crash rate. The boosted regression tree model significantly outperformed the other models and identified several intersection characteristics as having strong interaction effects. PMID:26710265

  6. Safety.

    ERIC Educational Resources Information Center

    Education in Science, 1996

    1996-01-01

    Discusses safety issues in science, including: allergic reactions to peanuts used in experiments; explosions in lead/acid batteries; and inspection of pressure vessels, such as pressure cookers or model steam engines. (MKR)

  7. The Child in the Process: Affecting His Human Potential through LIFE.

    ERIC Educational Resources Information Center

    Sheridan, Vivian A.; Spidal, David A.

    Language materials of the Language Improvement to Facilitate Education (LIFE) Project are described as carefully sequenced curriculum materials which use visuals to educate deaf children in the affective domain. The affective domain is defined as the area of human experiences related to interest, appreciation, attitudes, adjustments and values;…

  8. Capturing Safety Requirements to Enable Effective Task Allocation Between Humans and Automaton in Increasingly Autonomous Systems

    NASA Technical Reports Server (NTRS)

    Neogi, Natasha A.

    2016-01-01

    There is a current drive towards enabling the deployment of increasingly autonomous systems in the National Airspace System (NAS). However, shifting the traditional roles and responsibilities between humans and automation for safety critical tasks must be managed carefully, otherwise the current emergent safety properties of the NAS may be disrupted. In this paper, a verification activity to assess the emergent safety properties of a clearly defined, safety critical, operational scenario that possesses tasks that can be fluidly allocated between human and automated agents is conducted. Task allocation role sets were proposed for a human-automation team performing a contingency maneuver in a reduced crew context. A safety critical contingency procedure (engine out on takeoff) was modeled in the Soar cognitive architecture, then translated into the Hybrid Input Output formalism. Verification activities were then performed to determine whether or not the safety properties held over the increasingly autonomous system. The verification activities lead to the development of several key insights regarding the implicit assumptions on agent capability. It subsequently illustrated the usefulness of task annotations associated with specialized requirements (e.g., communication, timing etc.), and demonstrated the feasibility of this approach.

  9. The efficacy and safety of human oocyte vitrification.

    PubMed

    Nagy, Zsolt Peter; Chang, Ching-Chien; Shapiro, Daniel B; Bernal, Diana Patricia; Kort, Hilton I; Vajta, Gábor

    2009-11-01

    Vitrification is now a widely applied and highly successful approach for cryopreservation in reproductive biology. Rapidly increasing data prove that it is also a highly efficient technique for low-temperature storage of human oocytes. The latest approaches with appropriately selected cryoprotectants, tools and techniques, and properly adjusted parameters allow close to 100% morphological survival rates, and in vitro embryo development, as well pregnancy and implantation rates, comparable with those achieved with fresh oocytes. With standardization of the technique and elimination of biosafety problems by preserving all the positive features, vitrification may become a common part of the everyday routine in a human embryo laboratory, and it may offer a solution for various medical and social situations as well as for simple logistic problems commonly occurring in assisted reproduction. PMID:19806513

  10. Higher-order Multivariable Polynomial Regression to Estimate Human Affective States

    NASA Astrophysics Data System (ADS)

    Wei, Jie; Chen, Tong; Liu, Guangyuan; Yang, Jiemin

    2016-03-01

    From direct observations, facial, vocal, gestural, physiological, and central nervous signals, estimating human affective states through computational models such as multivariate linear-regression analysis, support vector regression, and artificial neural network, have been proposed in the past decade. In these models, linear models are generally lack of precision because of ignoring intrinsic nonlinearities of complex psychophysiological processes; and nonlinear models commonly adopt complicated algorithms. To improve accuracy and simplify model, we introduce a new computational modeling method named as higher-order multivariable polynomial regression to estimate human affective states. The study employs standardized pictures in the International Affective Picture System to induce thirty subjects’ affective states, and obtains pure affective patterns of skin conductance as input variables to the higher-order multivariable polynomial model for predicting affective valence and arousal. Experimental results show that our method is able to obtain efficient correlation coefficients of 0.98 and 0.96 for estimation of affective valence and arousal, respectively. Moreover, the method may provide certain indirect evidences that valence and arousal have their brain’s motivational circuit origins. Thus, the proposed method can serve as a novel one for efficiently estimating human affective states.

  11. Higher-order Multivariable Polynomial Regression to Estimate Human Affective States.

    PubMed

    Wei, Jie; Chen, Tong; Liu, Guangyuan; Yang, Jiemin

    2016-01-01

    From direct observations, facial, vocal, gestural, physiological, and central nervous signals, estimating human affective states through computational models such as multivariate linear-regression analysis, support vector regression, and artificial neural network, have been proposed in the past decade. In these models, linear models are generally lack of precision because of ignoring intrinsic nonlinearities of complex psychophysiological processes; and nonlinear models commonly adopt complicated algorithms. To improve accuracy and simplify model, we introduce a new computational modeling method named as higher-order multivariable polynomial regression to estimate human affective states. The study employs standardized pictures in the International Affective Picture System to induce thirty subjects' affective states, and obtains pure affective patterns of skin conductance as input variables to the higher-order multivariable polynomial model for predicting affective valence and arousal. Experimental results show that our method is able to obtain efficient correlation coefficients of 0.98 and 0.96 for estimation of affective valence and arousal, respectively. Moreover, the method may provide certain indirect evidences that valence and arousal have their brain's motivational circuit origins. Thus, the proposed method can serve as a novel one for efficiently estimating human affective states. PMID:26996254

  12. Higher-order Multivariable Polynomial Regression to Estimate Human Affective States

    PubMed Central

    Wei, Jie; Chen, Tong; Liu, Guangyuan; Yang, Jiemin

    2016-01-01

    From direct observations, facial, vocal, gestural, physiological, and central nervous signals, estimating human affective states through computational models such as multivariate linear-regression analysis, support vector regression, and artificial neural network, have been proposed in the past decade. In these models, linear models are generally lack of precision because of ignoring intrinsic nonlinearities of complex psychophysiological processes; and nonlinear models commonly adopt complicated algorithms. To improve accuracy and simplify model, we introduce a new computational modeling method named as higher-order multivariable polynomial regression to estimate human affective states. The study employs standardized pictures in the International Affective Picture System to induce thirty subjects’ affective states, and obtains pure affective patterns of skin conductance as input variables to the higher-order multivariable polynomial model for predicting affective valence and arousal. Experimental results show that our method is able to obtain efficient correlation coefficients of 0.98 and 0.96 for estimation of affective valence and arousal, respectively. Moreover, the method may provide certain indirect evidences that valence and arousal have their brain’s motivational circuit origins. Thus, the proposed method can serve as a novel one for efficiently estimating human affective states. PMID:26996254

  13. Nonclinical safety of mavrilimumab, an anti-GMCSF receptor alpha monoclonal antibody, in cynomolgus monkeys: Relevance for human safety

    SciTech Connect

    Ryan, Patricia C.; Sleeman, Matthew A.; Rebelatto, Marlon; Wang, Bing; Lu, Hong; Chen, Xiaomin; Wu, Chi-Yuan; Hinrichs, Mary Jane; Roskos, Lorin; Towers, Heidi; McKeever, Kathleen; Dixit, Rakesh

    2014-09-01

    Mavrilimumab (CAM-3001) is an investigational human IgG4 monoclonal antibody (MAb) targeting GM-CSF receptor alpha which is currently being developed for the treatment of RA. GM-CSF plays a central role in the pathogenesis of rheumatoid arthritis (RA) through the activation, differentiation, and survival of macrophages and neutrophils. To support clinical development, the nonclinical safety of mavrilimumab was evaluated in several studies with cynomolgus monkeys as the pharmacologically relevant species. Comprehensive toxicity parameters were assessed in each study, and treatment duration ranged from 4 to 26 weeks. Mavrilimumab has an acceptable safety profile in monkeys with no changes in any parameters other than microscopic findings in lung. In several studies, minimal accumulation of foamy alveolar macrophages was observed. This finding was only seen in studies of at least 11 weeks duration, was reversible following a dose-free recovery period and was considered non-adverse. At higher dose levels (≥ 30 mg/kg/week), in a 26-week repeat-IV dose study, the presence of lung foreign material, cholesterol clefts, and granulomatous inflammation was also observed in a few animals and was considered adverse. The dose- and time-related accumulation of foamy macrophages in lung following exposure to mavrilimumab observed in several NHP studies was expected based upon the known role of GM-CSFRα signaling in the function of alveolar macrophages. Overall, a clean no-observed-adverse-effect-level (NOAEL) without any effects in lung was established and provided adequate clinical safety margins. In clinical studies in RA patients, mavrilimumab has demonstrated good clinical activity with adequate safety to support further clinical development. A Phase 2b study of mavrilimumab in subjects with RA is in progress. - Highlights: • Mavrilimumab is a MAB targeting GM-CSFRα being developed for RA therapy. • Mavrilimumab has an acceptable safety profile in cynomolgus monkeys.

  14. Is it the real deal? Perception of virtual characters versus humans: an affective cognitive neuroscience perspective

    PubMed Central

    de Borst, Aline W.; de Gelder, Beatrice

    2015-01-01

    Recent developments in neuroimaging research support the increased use of naturalistic stimulus material such as film, avatars, or androids. These stimuli allow for a better understanding of how the brain processes information in complex situations while maintaining experimental control. While avatars and androids are well suited to study human cognition, they should not be equated to human stimuli. For example, the uncanny valley hypothesis theorizes that artificial agents with high human-likeness may evoke feelings of eeriness in the human observer. Here we review if, when, and how the perception of human-like avatars and androids differs from the perception of humans and consider how this influences their utilization as stimulus material in social and affective neuroimaging studies. First, we discuss how the appearance of virtual characters affects perception. When stimuli are morphed across categories from non-human to human, the most ambiguous stimuli, rather than the most human-like stimuli, show prolonged classification times and increased eeriness. Human-like to human stimuli show a positive linear relationship with familiarity. Secondly, we show that expressions of emotions in human-like avatars can be perceived similarly to human emotions, with corresponding behavioral, physiological and neuronal activations, with exception of physical dissimilarities. Subsequently, we consider if and when one perceives differences in action representation by artificial agents versus humans. Motor resonance and predictive coding models may account for empirical findings, such as an interference effect on action for observed human-like, natural moving characters. However, the expansion of these models to explain more complex behavior, such as empathy, still needs to be investigated in more detail. Finally, we broaden our outlook to social interaction, where virtual reality stimuli can be utilized to imitate complex social situations. PMID:26029133

  15. In vitro test of nicotine's permeability through human skin. Risk evaluation and safety aspects.

    PubMed

    Zorin, S; Kuylenstierna, F; Thulin, H

    1999-08-01

    Permeability tests with Franz' diffusion cells and an in vitro test model were made to evaluate the importance of dermal absorption of nicotine as a pathway for intoxication. Studies were carried out to ensure that safety procedures, when spilling nicotine on skin, are sufficient to prevent poisoning. Pure nicotine and nicotine in various concentrations in water or ethanol were applied on human skin or gloves in Franz' cells. Washing was simulated by removing nicotine from skin after 3 or 5 min. Permeation rate (flux) and lag time were calculated and estimated for human skin. Different glove materials were tested for their nicotine breakthrough time. Flux depended on concentration in a non-linear way when nicotine-water solutions were tested. Highest flux was found in 50% w/w nicotine dissolved in water. Solutions with low concentration of nicotine (1% w/w) dissolved in water had a similar permeation rate to 100% nicotine. Flux was found to be low when using ethanol as a vehicle; flux was also pH-dependent. The nicotine-water solution containing acetic acid had the lowest flux. The tests where nicotine was washed away revealed that skin served as a possible nicotine depot, because nicotine concentration in the receptor compartment continued to increase after removing the nicotine from the surface. The length of contact time affected the amount of substance passing the skin, resulting in great difference between 3 and 5 min contact time, 5 min giving higher nicotine concentration and 3 min lower. This emphasizes the importance of washing away nicotine spilled on skin rapidly. Two glove types were tested and they were found to be appropriate in their use with nicotine if changed regularly. PMID:10518466

  16. [Safety value of contaminant in water pollution accident based on human health risk].

    PubMed

    Zheng, Bing-Hui; Luo, Jin-Hong; Fu, Qing; Qin, Yan-Wen; Hu, Lin-Lin

    2012-02-01

    The acute human health risk assessment of contaminant in water pollution accident is a new study field of environmental sciences. This study established a model for calculating acute safety value of contaminant in water pollutant. The acute safety value of contaminant in mainly water pollution during 2000-2010 was calculated by this model. The safety value of sodium cyanide, cadmium, formaldehyde, ammonia, toluene, nitrobenzene, microcystin-LR were 0.1, 0.6, 8, 20, 6, 0.07, 0.004 mg x L(-1), respectively. The differences of safety value calculate methods between acute and chronic exposure were compared from the following aspects, the toxicology exposure end-point, allocation of intake, exposure sensitive subpopulation. PMID:22509564

  17. Preclinical safety studies on autologous cultured human skin fibroblast transplantation.

    PubMed

    Zeng, Wei; Zhang, Shuying; Liu, Dai; Chai, Mi; Wang, Jiaqi; Zhao, Yuming

    2014-01-01

    Recently, FDA approved the clinical use of autologous fibroblasts (LAVIV™) for the improvement of nasolabial fold wrinkles in adults. The use of autologous fibroblasts for the augmentation of dermal and subcutaneous defects represents a potentially exciting natural alternative to the use of other filler materials for its long-term corrective ability and absence of allergic adverse effects proved by clinical application. However, compared to the clinical evidence, preclinical studies are far from enough. In this study, human skin-derived fibroblasts were cultured and expanded for both in vitro and in vivo observations. In vitro, the subcultured fibroblasts were divided into two groups. One set of cells underwent cell cycle and karyotype analysis at passages 5 and 10. The second group of cells was cocultured in medium with different concentrations of human skin extract D for the measurement of collagen concentration and cell count. In vivo, the subcultured fibroblasts were injected into nude mice subcutaneously. Biopsies were taken for morphology observation and specific collagen staining at 1, 2, and 3 months after injection. The results in vitro showed no significant differences in cell cycle distribution between passages 5 and 10. Cell proliferation and secretion were inhibited as the concentration of extract D increased. In vivo, the fibroblasts were remarkably denser on the experimental side with no dysplastic cells. Mitotic cells were easily observed at the end of the first month but were rare at the end of the third month. Type III collagen was detected at the end of the first month, while collagen type I was positive at the end of the second month. The content of both collagens increased as time passed. The above results indicated that the use of the autologous fibroblasts was safe, providing a basic support for clinical use of fibroblasts. PMID:23211390

  18. Two approaches for assessing human safety of disperse blue 1.

    PubMed

    Haws, L C; Jackson, B A; Turnbull, D; Dressler, W E

    1994-02-01

    /kg/day, respectively. The safe level of Disperse Blue 1 derived using the threshold approach is approximately 20 times greater than the maximum average daily applied dose of 2.7 micrograms/kg/day associated with its use in semipermanent hair color formulations, while the exposure associated with the 10(-5) risk level using the linearized multistage model in the conventional approach was determined to be 1.5 times greater. Because oral absorption is substantially more than dermal absorption, the actual margin of safety is most likely much greater than either of these comparisons suggests.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:8159817

  19. A severe human ESD (electrostatic discharge) model for safety and high reliability system qualification testing

    SciTech Connect

    Fisher, R J

    1989-01-01

    A severe human electrostatic discharge (ESD) equivalent source model has been developed for use in qualification testing of systems that have stringent safety or very high reliability requirements. The model produces the now-acknowledged worst-case waveform, and the values of the constituent components have been selected from measured human body electrical parameters to maximize the peak amplitude and rate of rise of the short-circuit discharge current and energy transfer to the victim system. 18 refs., 5 figs.

  20. Preclinical Studies on the Pharmacokinetics, Safety and Toxicology of Oxfendazole: Toward First in Human Studies

    PubMed Central

    Codd, Ellen E.; Ng, Hanna H.; McFarlane, Claire; Riccio, Edward S.; Doppalapudi, Rupa; Mirsalis, Jon C.; Horton, R. John; Gonzalez, Armando E.; Garcia, H. Hugo; Gilman, Robert H.

    2015-01-01

    A two-week study in rats identified target organs of oxfendazole toxicity to be bone marrow, epididymis, liver, spleen, testis, and thymus. Female rats had greater oxfendazole exposure and exhibited toxicities at lower doses than did males. Decreased WBC levels, a class effect of benzimidazole anthelminthics, returned to normal during the recovery period. The NOAEL was determined to be >5 but < 25 mg/kg/d and the MTD 100 mg/kg/d. The highest dose, 200 mg/kg/d resulted in significant toxicity and mortality, leading to euthanization of the main study animals in this group after seven days. Oxfendazole did not exhibit genetic toxicology signals in standard Ames bacterial, mouse lymphoma or rat micronucleus assays, nor did it provoke safety concerns when evaluated for behavioral effects in rats or cardiovascular safety effects in dogs. These results support the transition of oxfendazole to First in Human safety studies preliminary to its evaluation in human helminth diseases. PMID:25701764

  1. 75 FR 69912 - Pipeline Safety: Control Room Management/Human Factors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-16

    ....gov . SUPPLEMENTARY INFORMATION: On September 17, 2010 (75 FR 56972), PHMSA published a NPRM proposing... Houston, Texas (75 FR 67450, November 2, 2010) prior to submitting comments. PHMSA planned this workshop... Safety: Control Room Management/Human Factors AGENCY: Pipeline and Hazardous Materials...

  2. Practical Applications of Cosmic Ray Science: Spacecraft, Aircraft, Ground Based Computation and Control Systems and Human Health and Safety

    NASA Technical Reports Server (NTRS)

    Atwell, William; Koontz, Steve; Normand, Eugene

    2012-01-01

    In this paper we review the discovery of cosmic ray effects on the performance and reliability of microelectronic systems as well as on human health and safety, as well as the development of the engineering and health science tools used to evaluate and mitigate cosmic ray effects in earth surface, atmospheric flight, and space flight environments. Three twentieth century technological developments, 1) high altitude commercial and military aircraft; 2) manned and unmanned spacecraft; and 3) increasingly complex and sensitive solid state micro-electronics systems, have driven an ongoing evolution of basic cosmic ray science into a set of practical engineering tools (e.g. ground based test methods as well as high energy particle transport and reaction codes) needed to design, test, and verify the safety and reliability of modern complex electronic systems as well as effects on human health and safety. The effects of primary cosmic ray particles, and secondary particle showers produced by nuclear reactions with spacecraft materials, can determine the design and verification processes (as well as the total dollar cost) for manned and unmanned spacecraft avionics systems. Similar considerations apply to commercial and military aircraft operating at high latitudes and altitudes near the atmospheric Pfotzer maximum. Even ground based computational and controls systems can be negatively affected by secondary particle showers at the Earth's surface, especially if the net target area of the sensitive electronic system components is large. Accumulation of both primary cosmic ray and secondary cosmic ray induced particle shower radiation dose is an important health and safety consideration for commercial or military air crews operating at high altitude/latitude and is also one of the most important factors presently limiting manned space flight operations beyond low-Earth orbit (LEO).

  3. Human and nature-caused hazards: the affect heuristic causes biased decisions.

    PubMed

    Siegrist, Michael; Sütterlin, Bernadette

    2014-08-01

    People are more concerned about the negative consequences of human hazards compared with natural hazards. Results of four experiments show that the same negative outcome (e.g., number of birds killed by an oil spill) was more negatively evaluated when caused by humans than when caused by nature. Results further show that when identical risk information was provided, participants evaluated nuclear power more negatively compared with solar power. The affect associated with the hazard per se influenced the interpretation of the new information. Furthermore, the affect experienced in the situation fully mediated the evaluation of the negative outcomes of a hazard. People's reliance on the affect heuristic is a challenge for acceptance of cost-benefit analyses because equally negative outcomes are differently evaluated depending on the cause. Symbolically significant information and the affect evoked by this information may result in biased and riskier decisions. PMID:24576178

  4. Examining dog-human play: the characteristics, affect, and vocalizations of a unique interspecific interaction.

    PubMed

    Horowitz, Alexandra; Hecht, Julie

    2016-07-01

    Despite the growing interest in research on the interaction between humans and dogs, only a very few research projects focus on the routines between dogs and their owners. In this study, we investigated one such routine: dog-human play. Dyadic interspecific play is known to be a common interaction between owner and charge, but the details of what counts as play have not been thoroughly researched. Similarly, though people represent that "play" is pleasurable, no study has yet undertaken to determine whether different forms of play are associated with different affective states. Thus, we aimed to generate an inventory of the forms of dyadic play, the vocalizations within play, and to investigate the relationship of affect to elements of play. Via a global citizen science project, we solicited videotapes of dog-human play sessions from dog owners. We coded 187 play bouts via frame-by-frame video playback. We then assessed the relationship between various intra-bout variables and owner affect (positive or neutral) during play (dog affect was overwhelmingly positive). Amount of physical contact ("touch"), level of activity of owner ("movement"), and physical closeness of dog-owner dyad ("proximity") were highly correlated with positive affect. Owner vocalizations were found to contain different elements in positive- and neutral-affect play. One novel category of play, "tease", was found. We conclude that not all play is created equal: the experience of play to the owner participant is strongly related to a few identifiable characteristics of the interaction. PMID:27003698

  5. Factors affecting yield and safety of protein production from cassava by Cephalosporium eichhorniae

    SciTech Connect

    Mikami, Y.; Gregory, K.F.; Levadoux, W.L.; Balagopalan, C.; Whitwill, S.T.

    1982-01-01

    The properties of C. eichhorniae 152 (ATCC 38255) affecting protein production from cassava carbohydrate, for use as an animal feed, were studied. This strain is a true thermophile, showing optimum growth at 45-47 degrees, maximum protein yield at 45 degrees, and no growth at 25 degrees. It has an optimum pH of approximately 3.8 and is obligately acidophilic, being unable to sustain growth at pH of more than or equal to 6.0 in a liquid medium, or pH of more than or equal to 7.0 on solid media. The optimum growth conditions of pH 3.8 and 45 degrees were strongly inhibitive to potential contaminants. It rapidly hydrolyzed cassava starch. It did not utilize sucrose, but approximately 16% of the small sucrose component of cassava was chemically hydrolyzed during the process. Growth with cassava meal (50 g/l) was complete in approximately 20 h, yielding 22.5 g/l (dry biomass), containing 41% crude protein (48-50% crude protein in the mycelium) and 31% true protein (7.0 g/l). Resting and germinating spores (10 to the power of 6 - 10 to the power of 8 per animal) injected by various routes into normal and gamma-irradiated 6-week-old mice and 7-day-old chickens failed to initiate infections.

  6. An Evaluation of the Effects of Human Factors and Ergonomics on Health Care and Patient Safety Practices: A Systematic Review

    PubMed Central

    Zhang, Longhao; Zhao, Pujing; Chen, Ying; Zhang, Mingming

    2015-01-01

    Background From the viewpoint of human factors and ergonomics (HFE), errors often occur because of the mismatch between the system, technique and characteristics of the human body. HFE is a scientific discipline concerned with understanding interactions between human behavior, system design and safety. Objective To evaluate the effectiveness of HFE interventions in improving health care workers’ outcomes and patient safety and to assess the quality of the available evidence. Methods We searched databases, including MEDLINE, EMBASE, BIOSIS Previews and the CBM (Chinese BioMedical Literature Database), for articles published from 1996 to Mar.2015. The quality assessment tool was based on the risk of bias criteria developed by the Cochrane Effective Practice and Organization of Care (EPOC) Group. The interventions of the included studies were categorized into four relevant domains, as defined by the International Ergonomics Association. Results For this descriptive study, we identified 8, 949 studies based on our initial search. Finally, 28 studies with 3,227 participants were included. Among the 28 included studies, 20 studies were controlled studies, two of which were randomized controlled trials. The other eight studies were before/after surveys, without controls. Most of the studies were of moderate or low quality. Five broad categories of outcomes were identified in this study: 1) medical errors or patient safety, 2) health care workers’ quality of working life (e.g. reduced fatigue, discomfort, workload, pain and injury), 3) user performance (e.g., efficiency or accuracy), 4) health care workers’ attitudes towards the interventions(e.g., satisfaction and preference), and 5) economic evaluations. Conclusion The results showed that the interventions positively affected the outcomes of health care workers. Few studies considered the financial merits of these interventions. Most of the included studies were of moderate quality. This review highlights the need

  7. A customized vision system for tracking humans wearing reflective safety clothing from industrial vehicles and machinery.

    PubMed

    Mosberger, Rafael; Andreasson, Henrik; Lilienthal, Achim J

    2014-01-01

    This article presents a novel approach for vision-based detection and tracking of humans wearing high-visibility clothing with retro-reflective markers. Addressing industrial applications where heavy vehicles operate in the vicinity of humans, we deploy a customized stereo camera setup with active illumination that allows for efficient detection of the reflective patterns created by the worker's safety garments. After segmenting reflective objects from the image background, the interest regions are described with local image feature descriptors and classified in order to discriminate safety garments from other reflective objects in the scene. In a final step, the trajectories of the detected humans are estimated in 3D space relative to the camera. We evaluate our tracking system in two industrial real-world work environments on several challenging video sequences. The experimental results indicate accurate tracking performance and good robustness towards partial occlusions, body pose variation, and a wide range of different illumination conditions. PMID:25264956

  8. A Customized Vision System for Tracking Humans Wearing Reflective Safety Clothing from Industrial Vehicles and Machinery

    PubMed Central

    Mosberger, Rafael; Andreasson, Henrik; Lilienthal, Achim J.

    2014-01-01

    This article presents a novel approach for vision-based detection and tracking of humans wearing high-visibility clothing with retro-reflective markers. Addressing industrial applications where heavy vehicles operate in the vicinity of humans, we deploy a customized stereo camera setup with active illumination that allows for efficient detection of the reflective patterns created by the worker's safety garments. After segmenting reflective objects from the image background, the interest regions are described with local image feature descriptors and classified in order to discriminate safety garments from other reflective objects in the scene. In a final step, the trajectories of the detected humans are estimated in 3D space relative to the camera. We evaluate our tracking system in two industrial real-world work environments on several challenging video sequences. The experimental results indicate accurate tracking performance and good robustness towards partial occlusions, body pose variation, and a wide range of different illumination conditions. PMID:25264956

  9. Some Challenges in the Design of Human-Automation Interaction for Safety-Critical Systems

    NASA Technical Reports Server (NTRS)

    Feary, Michael S.; Roth, Emilie

    2014-01-01

    Increasing amounts of automation are being introduced to safety-critical domains. While the introduction of automation has led to an overall increase in reliability and improved safety, it has also introduced a class of failure modes, and new challenges in risk assessment for the new systems, particularly in the assessment of rare events resulting from complex inter-related factors. Designing successful human-automation systems is challenging, and the challenges go beyond good interface development (e.g., Roth, Malin, & Schreckenghost 1997; Christoffersen & Woods, 2002). Human-automation design is particularly challenging when the underlying automation technology generates behavior that is difficult for the user to anticipate or understand. These challenges have been recognized in several safety-critical domains, and have resulted in increased efforts to develop training, procedures, regulations and guidance material (CAST, 2008, IAEA, 2001, FAA, 2013, ICAO, 2012). This paper points to the continuing need for new methods to describe and characterize the operational environment within which new automation concepts are being presented. We will describe challenges to the successful development and evaluation of human-automation systems in safety-critical domains, and describe some approaches that could be used to address these challenges. We will draw from experience with the aviation, spaceflight and nuclear power domains.

  10. Incident reporting: Its role in aviation safety and the acquisition of human error data

    NASA Technical Reports Server (NTRS)

    Reynard, W. D.

    1983-01-01

    The rationale for aviation incident reporting systems is presented and contrasted to some of the shortcomings of accident investigation procedures. The history of the United State's Aviation Safety Reporting System (ASRS) is outlined and the program's character explained. The planning elements that resulted in the ASRS program's voluntary, confidential, and non-punitive design are discussed. Immunity, from enforcement action and misuse of the volunteered data, is explained and evaluated. Report generation techniques and the ASRS data analysis process are described; in addition, examples of the ASRS program's output and accomplishments are detailed. Finally, the value of incident reporting for the acquisition of safety information, particularly human error data, is explored.

  11. Affective Education: A Teacher's Manual to Promote Student Self-Actualization and Human Relations Skills.

    ERIC Educational Resources Information Center

    Snyder, Thomas R.

    This teacher's manual presents affective education as a program to promote student self-actualization and human relations skills. Abraham Maslow's hierarchy of needs and Erik Erikson's life stages of psychosocial development form the conceptual base for this program. The goals and objectives of this manual are concerned with problem-solving…

  12. Definition and Measurement in the Affective Domain: Appreciation of Human Accomplishments.

    ERIC Educational Resources Information Center

    Campbell, Paul B.; Beers, Joan S.

    The first three levels of the taxonomy in the affective domain guided the development of two inventories--the Pennsylvania Inventory of Cultural Appreciations (PICA) for 11th graders and Things People Do (TPD) for 5th graders--to measure appreciation of human accomplishments in seven areas: politics, sciences, sports, literature, visual arts,…

  13. Human-Computer Interaction: A Review of the Research on Its Affective and Social Aspects.

    ERIC Educational Resources Information Center

    Deaudelin, Colette; Dussault, Marc; Brodeur, Monique

    2003-01-01

    Discusses a review of 34 qualitative and non-qualitative studies related to affective and social aspects of student-computer interactions. Highlights include the nature of the human-computer interaction (HCI); the interface, comparing graphic and text types; and the relation between variables linked to HCI, mainly trust, locus of control,…

  14. Absence of venous thromboembolism risk following quadrivalent human papillomavirus vaccination, Vaccine Safety Datalink, 2008–2011

    PubMed Central

    Naleway, Allison L.; Crane, Brad; Smith, Ning; Daley, Matthew F.; Donahue, James; Gee, Julianne; Greene, Sharon K.; Harrington, Theresa; Jackson, Lisa A.; Klein, Nicola P.; Tseng, Hung Fu; Vellozzi, Claudia; Weintraub, Eric S.

    2016-01-01

    Background To investigate concerns about a potential association between quadrivalent human papillomavirus vaccination (HPV4) and venous thromboembolism (VTE), we conducted a self-controlled case series study in adolescents and young adults 9–26 years of age in the Vaccine Safety Datalink. Methods We identified potential VTE cases diagnosed in 2008 through 2011 who had also received at least one HPV4 dose during that period. We confirmed each presumptive diagnosis by medical record review. We calculated incidence rate ratios (IRRs) and 95% confidence intervals (CI) to estimate the risk in the 1–60 day period following HPV4 exposure and in subsets of that period. IRRs were stratified by age, gender, hormonal contraceptive use, and recent surgery or trauma. Results We identified 313 potential cases of VTE among HPV4 vaccinees, and 291 (93%) had sufficient medical records for review. Of these, we confirmed 156 (54%) cases. VTE was uncommon among males (n = 3) and 9–12 year olds (n = 4). Nearly all confirmed cases (97%) had at least one known risk factor for VTE, including hormonal contraceptive use, obesity, and hypercoagulability. Sixteen (10%) confirmed cases occurred in the 1–60 days following HPV4 exposure. The risk of VTE varied from 1.47 (95% CI: 0.47–4.64) in the 1–7 days following HPV4 exposure to 0.92 (95% CI: 0.54–1.57) in the 1–60 days following vaccination. It was not possible to calculate a stratified IRR for males due to small sample size; the other risk factors evaluated did not significantly affect the risk of VTE after HPV4 exposure. Conclusion The risk of developing VTE among 9- to 26-year-olds was not elevated following HPV4 exposure. Sample size limited our ability to rigorously evaluate potential effect modifiers, such as gender, through stratified analysis. PMID:26549361

  15. Immunogenicity and safety of the human papillomavirus vaccine in patients with autoimmune diseases: A systematic review.

    PubMed

    Pellegrino, Paolo; Radice, Sonia; Clementi, Emilio

    2015-07-01

    Whereas safety and efficacy of HPV vaccines in healthy women have been shown in several randomised controlled clinical trials and in post marketing analyses, only few data exist in patients affected by autoimmune diseases. These issues are significant as autoimmune conditions are recognised as a risk factor for the persistence of HPV infection. Herein we review and systematise the existing literature to assess immunogenicity and safety of HPV vaccination in patients with autoimmune diseases, including systemic lupus erythematosus and juvenile idiopathic arthritis. The results of our literature revision suggest that the HPV vaccines are efficacious and safe in most of the patients affected by autoimmune diseases. Yet, some points of concern remain to be tackled, including the effects of concomitant therapies, the risk of disease exacerbation and the cost-effectiveness of such immunisation programmes in these populations. PMID:26036945

  16. Cigarette smoke affects posttranslational modifications and inhibits capacitation-induced changes in human sperm proteins.

    PubMed

    Shrivastava, Vibha; Marmor, Hannah; Chernyak, Sholom; Goldstein, Marc; Feliciano, Miriam; Vigodner, Margarita

    2014-01-01

    Sperm are highly dependent on posttranslational modifications of proteins. Massive phosphorylation on tyrosine residue is required for sperm capacitation. Sumoylation has also been recently implicated in spermatogenesis and sperm functions. Cigarette smoke is known to cause oxidative stress in different tissues, and several studies suggest that it causes oxidative stress in sperm. Whether tobacco affects posttranslational modifications in human sperm is currently unknown. In this study, we show that a short exposure of human sperm to physiological concentrations of cigarette smoke extract (CSE) causes the partial de-sumoylation of many sperm proteins. Furthermore, the presence of a low concentration of CSE in the human tubal fluid during an induction of in vitro capacitation inhibits the capacitation-associated increase in protein phosphorylation. Collectively, changes in posttranslational modifications may be one of the mechanisms through which exposure to tobacco can negatively affect sperm functions and cause fertility problems. PMID:24345728

  17. How does enhancing cognition affect human values? How does this translate into social responsibility?

    PubMed

    Cabrera, Laura Y

    2015-01-01

    The past decade has seen a rise in the use of different technologies aimed at enhancing cognition of normal healthy individuals. While values have been acknowledged to be an important aspect of cognitive enhancement practices, the discussion has predominantly focused on just a few values, such as safety, peer pressure, and authenticity. How are values, in a broader sense, affected by enhancing cognitive abilities? Is this dependent on the type of technology or intervention used to attain the enhancement, or does the cognitive domain targeted play a bigger role in how values are affected? Values are not only likely to be affected by cognitive enhancement practices; they also play a crucial role in defining the type of interventions that are likely to be undertaken. This paper explores the way values affect and are affected by enhancing cognitive abilities. Furthermore, it argues that knowledge of the interplay between values and cognitive enhancement makes a strong case for social responsibility around cognitive enhancement practices. PMID:25048389

  18. Safety-Information-Driven Human Mobility Patterns with Metapopulation Epidemic Dynamics

    NASA Astrophysics Data System (ADS)

    Wang, Bing; Cao, Lang; Suzuki, Hideyuki; Aihara, Kazuyuki

    2012-11-01

    With the help of mass media, people receive information concerning the status of an infectious disease to guide their mobility. Herein, we develop a theoretical framework to investigate the safety-information-driven human mobility with metapopulation epidemic dynamics. Individuals respond to the safety information of a city by taking safe moves (passing cities with a more number of healthy individuals) or unsafe moves (passing cities with a less number of healthy individuals). Our findings show that the critical threshold depends on mobility in such a way that personal execution of safe moves unexpectedly promotes the global spread of a disease, while unsafe moves counterintuitively cause a locally, relatively small outbreak size. Our analysis underlines the role of safety consideration in the spatial spread of an infectious disease with clear implications for the model of mobility driven by individuals' benefit.

  19. Safety-Information-Driven Human Mobility Patterns with Metapopulation Epidemic Dynamics

    PubMed Central

    Wang, Bing; Cao, Lang; Suzuki, Hideyuki; Aihara, Kazuyuki

    2012-01-01

    With the help of mass media, people receive information concerning the status of an infectious disease to guide their mobility. Herein, we develop a theoretical framework to investigate the safety-information-driven human mobility with metapopulation epidemic dynamics. Individuals respond to the safety information of a city by taking safe moves (passing cities with a more number of healthy individuals) or unsafe moves (passing cities with a less number of healthy individuals). Our findings show that the critical threshold depends on mobility in such a way that personal execution of safe moves unexpectedly promotes the global spread of a disease, while unsafe moves counterintuitively cause a locally, relatively small outbreak size. Our analysis underlines the role of safety consideration in the spatial spread of an infectious disease with clear implications for the model of mobility driven by individuals' benefit. PMID:23189237

  20. The Human Bathtub: Safety and Risk Predictions Including the Dynamic Probability of Operator Errors

    SciTech Connect

    Duffey, Romney B.; Saull, John W.

    2006-07-01

    Reactor safety and risk are dominated by the potential and major contribution for human error in the design, operation, control, management, regulation and maintenance of the plant, and hence to all accidents. Given the possibility of accidents and errors, now we need to determine the outcome (error) probability, or the chance of failure. Conventionally, reliability engineering is associated with the failure rate of components, or systems, or mechanisms, not of human beings in and interacting with a technological system. The probability of failure requires a prior knowledge of the total number of outcomes, which for any predictive purposes we do not know or have. Analysis of failure rates due to human error and the rate of learning allow a new determination of the dynamic human error rate in technological systems, consistent with and derived from the available world data. The basis for the analysis is the 'learning hypothesis' that humans learn from experience, and consequently the accumulated experience defines the failure rate. A new 'best' equation has been derived for the human error, outcome or failure rate, which allows for calculation and prediction of the probability of human error. We also provide comparisons to the empirical Weibull parameter fitting used in and by conventional reliability engineering and probabilistic safety analysis methods. These new analyses show that arbitrary Weibull fitting parameters and typical empirical hazard function techniques cannot be used to predict the dynamics of human errors and outcomes in the presence of learning. Comparisons of these new insights show agreement with human error data from the world's commercial airlines, the two shuttle failures, and from nuclear plant operator actions and transient control behavior observed in transients in both plants and simulators. The results demonstrate that the human error probability (HEP) is dynamic, and that it may be predicted using the learning hypothesis and the minimum

  1. Industry Initiated Core Safety Attributes for Human Spaceflight for the 7th IAASS Conference

    NASA Technical Reports Server (NTRS)

    Mango, Edward J.

    2014-01-01

    Now that the NASA Commercial Crew Program (CCP) is beginning its full certification contract for crew transportation to the International Space Station (ISS), is it time for industry to embrace a minimum set of core safety attributes? Those attributes can then be evolved into an industry-led set of basic safety standards and requirements. After 50 years of human space travel sponsored by governments, there are two basic conditions that now exist within the international space industry. The first, there is enough of a space-faring history to encourage the space industry to design, develop and operate human spaceflight systems without government contracts for anything other than services. Second, industry is capable of defining and enforcing a set of industry-based safety attributes and standards for human spaceflight to low-Earth orbit (LEO). This paper will explore both of these basic conditions with a focus on the safety attributes and standards. In the United States, the Federal Aviation Administration (FAA) is now starting to dialogue with industry about the basic safety principles and attributes needed for potential future regulatory oversight. This process is not yet formalized and will take a number of years once approval is given to move forward. Therefore, throughout the next few years, it is an excellent time and opportunity for industry to collaborate together and develop the core set of attributes and standards. As industry engages and embraces a common set of safety attributes, then government agencies, like the FAA and NASA can use that industry-based product to strengthen their efforts on a safe commercial spaceflight foundation for the future. As the commercial space industry takes the lead role in establishing core safety attributes, and then enforcing those attributes, the entire planet can move away from governmental control of design and development and let industry expand safe and successful space operations in LEO. At that point the

  2. Analysis of human factors effects on the safety of transporting radioactive waste materials: Technical report

    SciTech Connect

    Abkowitz, M.D.; Abkowitz, S.B.; Lepofsky, M.

    1989-04-01

    This report examines the extent of human factors effects on the safety of transporting radioactive waste materials. It is seen principally as a scoping effort, to establish whether there is a need for DOE to undertake a more formal approach to studying human factors in radioactive waste transport, and if so, logical directions for that program to follow. Human factors effects are evaluated on driving and loading/transfer operations only. Particular emphasis is placed on the driving function, examining the relationship between human error and safety as it relates to the impairment of driver performance. Although multi-modal in focus, the widespread availability of data and previous literature on truck operations resulted in a primary study focus on the trucking mode from the standpoint of policy development. In addition to the analysis of human factors accident statistics, the report provides relevant background material on several policies that have been instituted or are under consideration, directed at improving human reliability in the transport sector. On the basis of reported findings, preliminary policy areas are identified. 71 refs., 26 figs., 5 tabs.

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

    NASA Technical Reports Server (NTRS)

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

    2013-01-01

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

  4. Sex differences in the brain response to affective scenes with or without humans.

    PubMed

    Proverbio, Alice Mado; Adorni, Roberta; Zani, Alberto; Trestianu, Laura

    2009-10-01

    Recent findings have demonstrated that women might be more reactive than men to viewing painful stimuli (vicarious response to pain), and therefore more empathic [Han, S., Fan, Y., & Mao, L. (2008). Gender difference in empathy for pain: An electrophysiological investigation. Brain Research, 1196, 85-93]. We investigated whether the two sexes differed in their cerebral responses to affective pictures portraying humans in different positive or negative contexts compared to natural or urban scenarios. 440 IAPS slides were presented to 24 Italian students (12 women and 12 men). Half the pictures displayed humans while the remaining scenes lacked visible persons. ERPs were recorded from 128 electrodes and swLORETA (standardized weighted Low-Resolution Electromagnetic Tomography) source reconstruction was performed. Occipital P115 was greater in response to persons than to scenes and was affected by the emotional valence of the human pictures. This suggests that processing of biologically relevant stimuli is prioritized. Orbitofrontal N2 was greater in response to positive than negative human pictures in women but not in men, and not to scenes. A late positivity (LP) to suffering humans far exceeded the response to negative scenes in women but not in men. In both sexes, the contrast suffering-minus-happy humans revealed a difference in the activation of the occipito/temporal, right occipital (BA19), bilateral parahippocampal, left dorsal prefrontal cortex (DPFC) and left amygdala. However, increased right amygdala and right frontal area activities were observed only in women. The humans-minus-scenes contrast revealed a difference in the activation of the middle occipital gyrus (MOG) in men, and of the left inferior parietal (BA40), left superior temporal gyrus (STG, BA38) and right cingulate (BA31) in women (270-290 ms). These data indicate a sex-related difference in the brain response to humans, possibly supporting human empathy. PMID:19061906

  5. Biosafety Test for Plant Growth-Promoting Bacteria: Proposed Environmental and Human Safety Index (EHSI) Protocol

    PubMed Central

    Vílchez, Juan I.; Navas, Alfonso; González-López, Jesús; Arcos, Susana C.; Manzanera, Maximino

    2016-01-01

    Plant growth-promoting bacteria (PGPB) colonize plants and enhance their growth by different mechanisms. Some of these microorganisms may represent a potential threat to human, animal or plant health; however, their use might be approved in parts of Europe if they have been recommended as plant growth enhancers. The current regulatory framework has resulted in a fragmented, contradictory system, and there is an urgent need to establish harmonized protocols for the predictability, efficiency, consistency and especially the safety of PGPB for human and animal health and for the environment. In response to current efforts to update biosafety policies and provide alternative methods to replace the use of vertebrate animals, we propose a panel of tests and an evaluation system to reliably determine the biosafety of bacterial strains used as PGPB. Based on the results of different tests, we propose a scoring system to evaluate the safety of candidates for PGPB within the limitations of the assays used. PMID:26779168

  6. Human T-lymphotropic virus and transfusion safety: does one size fit all?

    PubMed

    Marano, Giuseppe; Vaglio, Stefania; Pupella, Simonetta; Facco, Giuseppina; Catalano, Liviana; Piccinini, Vanessa; Liumbruno, Giancarlo Maria; Grazzini, Giuliano

    2016-01-01

    Human T-cell leukemia viruses (HTLV-1 and HTLV-2) are associated with a variety of human diseases, including some severe ones. Transfusion transmission of HTLV through cellular blood components is undeniable. HTLV screening of blood donations became mandatory in different countries to improve the safety of blood supplies. In Japan and Europe, most HTLV-infected donors are HTLV-1 positive, whereas in the United States a higher prevalence of HTLV-2 is reported. Many industrialized countries have also introduced universal leukoreduction of blood components, and pathogen inactivation technologies might be another effective preventive strategy, especially if and when generalized to all blood cellular products. Considering all measures available to minimize HTLV blood transmission, the question is what would be the most suitable and cost-effective strategy to ensure a high level of blood safety regarding these viruses, considering that there is no solution that can be deemed optimal for all countries. PMID:26388300

  7. Proteome Analysis of Human Sebaceous Follicle Infundibula Extracted from Healthy and Acne-Affected Skin

    PubMed Central

    Bek-Thomsen, Malene; Lomholt, Hans B.; Scavenius, Carsten; Enghild, Jan J.; Brüggemann, Holger

    2014-01-01

    Acne vulgaris is a very common disease of the pilosebaceous unit of the human skin. The pathological processes of acne are not fully understood. To gain further insight sebaceous follicular casts were extracted from 18 healthy and 20 acne-affected individuals by cyanoacrylate-gel biopsies and further processed for mass spectrometry analysis, aiming at a proteomic analysis of the sebaceous follicular casts. Human as well as bacterial proteins were identified. Human proteins enriched in acne and normal samples were detected, respectively. Normal follicular casts are enriched in proteins such as prohibitins and peroxiredoxins which are involved in the protection from various stresses, including reactive oxygen species. By contrast, follicular casts extracted from acne-affected skin contained proteins involved in inflammation, wound healing and tissue remodeling. Among the most distinguishing proteins were myeloperoxidase, lactotransferrin, neutrophil elastase inhibitor and surprisingly, vimentin. The most significant biological process among all acne-enriched proteins was ‘response to a bacterium’. Identified bacterial proteins were exclusively from Propionibacterium acnes. The most abundant P. acnes proteins were surface-exposed dermatan sulphate adhesins, CAMP factors, and a so far uncharacterized lipase in follicular casts extracted from normal as well as acne-affected skin. This is a first proteomic study that identified human proteins together with proteins of the skin microbiota in sebaceous follicular casts. PMID:25238151

  8. Human infant faces provoke implicit positive affective responses in parents and non-parents alike.

    PubMed

    Senese, Vincenzo Paolo; De Falco, Simona; Bornstein, Marc H; Caria, Andrea; Buffolino, Simona; Venuti, Paola

    2013-01-01

    Human infants' complete dependence on adult caregiving suggests that mechanisms associated with adult responsiveness to infant cues might be deeply embedded in the brain. Behavioural and neuroimaging research has produced converging evidence for adults' positive disposition to infant cues, but these studies have not investigated directly the valence of adults' reactions, how they are moderated by biological and social factors, and if they relate to child caregiving. This study examines implicit affective responses of 90 adults toward faces of human and non-human (cats and dogs) infants and adults. Implicit reactions were assessed with Single Category Implicit Association Tests, and reports of childrearing behaviours were assessed by the Parental Style Questionnaire. The results showed that human infant faces represent highly biologically relevant stimuli that capture attention and are implicitly associated with positive emotions. This reaction holds independent of gender and parenthood status and is associated with ideal parenting behaviors. PMID:24282537

  9. Human Infant Faces Provoke Implicit Positive Affective Responses in Parents and Non-Parents Alike

    PubMed Central

    Senese, Vincenzo Paolo; De Falco, Simona; Bornstein, Marc H.; Caria, Andrea; Buffolino, Simona; Venuti, Paola

    2013-01-01

    Human infants' complete dependence on adult caregiving suggests that mechanisms associated with adult responsiveness to infant cues might be deeply embedded in the brain. Behavioural and neuroimaging research has produced converging evidence for adults' positive disposition to infant cues, but these studies have not investigated directly the valence of adults' reactions, how they are moderated by biological and social factors, and if they relate to child caregiving. This study examines implicit affective responses of 90 adults toward faces of human and non-human (cats and dogs) infants and adults. Implicit reactions were assessed with Single Category Implicit Association Tests, and reports of childrearing behaviours were assessed by the Parental Style Questionnaire. The results showed that human infant faces represent highly biologically relevant stimuli that capture attention and are implicitly associated with positive emotions. This reaction holds independent of gender and parenthood status and is associated with ideal parenting behaviors. PMID:24282537

  10. Whose fault is it anyway? A practical illustration of human factors in process safety.

    PubMed

    Hughes, Gareth; Kornowa-Weichel, Megan

    2004-11-11

    Major process accidents have typically occurred not through a single failure, but through a combination of events, some of which had contributors from past actions and failures (latent or unrevealed failures). People are integral and key features of business systems; therefore systems, tools, and equipment should be designed with the potential capabilities and limitations of people in mind. This paper demonstrates the benefits of using human factors approaches to improve system safety and reliability. Practical examples from past experience are quoted and a framework for human error prediction is described. Guidance is given on the practicalities of deriving recommendations from these types of studies. PMID:15518974

  11. Human-System Safety Methods for Development of Advanced Air Traffic Management Systems

    SciTech Connect

    Nelson, W.R.

    1999-05-24

    The Idaho National Engineering and Environmental Laboratory (INEEL) is supporting the National Aeronautics and Space Administration in the development of advanced air traffic management (ATM) systems as part of the Advanced Air Transportation Technologies program. As part of this program INEEL conducted a survey of human-system safety methods that have been applied to complex technical systems, to identify lessons learned from these applications and provide recommendations for the development of advanced ATM systems. The domains that were surveyed included offshore oil and gas, commercial nuclear power, commercial aviation, and military. The survey showed that widely different approaches are used in these industries, and that the methods used range from very high-level, qualitative approaches to very detailed quantitative methods such as human reliability analysis (HRA) and probabilistic safety assessment (PSA). In addition, the industries varied widely in how effectively they incorporate human-system safety assessment in the design, development, and testing of complex technical systems. In spite of the lack of uniformity in the approaches and methods used, it was found that methods are available that can be combined and adapted to support the development of advanced air traffic management systems.

  12. How Malaria Has Affected the Human Genome and What Human Genetics Can Teach Us about Malaria

    PubMed Central

    Kwiatkowski, Dominic P.

    2005-01-01

    Malaria is a major killer of children worldwide and the strongest known force for evolutionary selection in the recent history of the human genome. The past decade has seen growing evidence of ethnic differences in susceptibility to malaria and of the diverse genetic adaptations to malaria that have arisen in different populations: epidemiological confirmation of the hypotheses that G6PD deficiency, α+ thalassemia, and hemoglobin C protect against malaria mortality; the application of novel haplotype-based techniques demonstrating that malaria-protective genes have been subject to recent positive selection; the first genetic linkage maps of resistance to malaria in experimental murine models; and a growing number of reported associations with resistance and susceptibility to human malaria, particularly in genes involved in immunity, inflammation, and cell adhesion. The challenge for the next decade is to build the global epidemiological infrastructure required for statistically robust genomewide association analysis, as a way of discovering novel mechanisms of protective immunity that can be used in the development of an effective malaria vaccine. PMID:16001361

  13. A humanized version of Foxp2 does not affect ultrasonic vocalization in adult mice.

    PubMed

    Hammerschmidt, K; Schreiweis, C; Minge, C; Pääbo, S; Fischer, J; Enard, W

    2015-11-01

    The transcription factor FOXP2 has been linked to severe speech and language impairments in humans. An analysis of the evolution of the FOXP2 gene has identified two amino acid substitutions that became fixed after the split of the human and chimpanzee lineages. Studying the functional consequences of these two substitutions in the endogenous Foxp2 gene of mice showed alterations in dopamine levels, striatal synaptic plasticity, neuronal morphology and cortico-striatal-dependent learning. In addition, ultrasonic vocalizations (USVs) of pups had a significantly lower average pitch than control littermates. To which degree adult USVs would be affected in mice carrying the 'humanized' Foxp2 variant remained unclear. In this study, we analyzed USVs of 68 adult male mice uttered during repeated courtship encounters with different females. Mice carrying the Foxp2(hum/hum) allele did not differ significantly in the number of call elements, their element structure or in their element composition from control littermates. We conclude that neither the structure nor the usage of USVs in adult mice is affected by the two amino acid substitutions that occurred in FOXP2 during human evolution. The reported effect for pup vocalization thus appears to be transient. These results are in line with accumulating evidence that mouse USVs are hardly influenced by vocal learning. Hence, the function and evolution of genes that are necessary, but not sufficient for vocal learning in humans, must be either studied at a different phenotypic level in mice or in other organisms. PMID:26250064

  14. Effects of Virtual Human Appearance Fidelity on Emotion Contagion in Affective Inter-Personal Simulations.

    PubMed

    Volante, Matias; Babu, Sabarish V; Chaturvedi, Himanshu; Newsome, Nathan; Ebrahimi, Elham; Roy, Tania; Daily, Shaundra B; Fasolino, Tracy

    2016-04-01

    Realistic versus stylized depictions of virtual humans in simulated inter-personal situations and their ability to elicit emotional responses in users has been an open question for artists and researchers alike. We empirically evaluated the effects of near visually realistic vs. non-realistic stylized appearance of virtual humans on the emotional response of participants in a medical virtual reality system that was designed to educate users in recognizing the signs and symptoms of patient deterioration. In a between-subjects experiment protocol, participants interacted with one of three different appearances of a virtual patient, namely visually realistic, cartoon-shaded and charcoal-sketch like conditions in a mixed reality simulation. Emotional impact were measured via a combination of quantitative objective measures were gathered using skin Electrodermal Activity (EDA) sensors, and quantitative subjective measures such as the Differential Emotion Survey (DES IV), Positive and Negative Affect Schedule (PANAS), and Social Presence questionnaire. The emotional states of the participants were analyzed across four distinct time steps during which the medical condition of the virtual patient deteriorated (an emotionally stressful interaction), and were contrasted to a baseline affective state. Objective EDA results showed that in all three conditions, male participants exhibited greater levels of arousal as compared to female participants. We found that negative affect levels were significantly lower in the visually realistic condition, as compared to the stylized appearance conditions. Furthermore, in emotional dimensions of interest-excitement, surprise, anger, fear and guilt participants in all conditions responded similarly. However, in social emotional constructs of shyness, presence, perceived personality, and enjoyment-joy, we found that participants responded differently in the visually realistic condition as compared to the cartoon and sketch conditions. Our

  15. Physical characteristics of indigestible solids affect emptying from the fasting human stomach.

    PubMed Central

    Meyer, B; Beglinger, C; Neumayer, M; Stalder, G A

    1989-01-01

    Gastric emptying of indigestible solids depends on their size. It is not clear whether physical characteristics other than particle size affect emptying of indigestible solids from the fasting human stomach. We studied gastric emptying of three differently shaped particles, (cubes, spheres, rods) of either hard or soft consistency during the fasting state in human volunteers. The shape of indigestible particles did not affect their emptying. The area under the gastric emptying curve (AUC: particles x hour) was for hard cubes 24.7 (2.2), for hard spheres 27.9 (1.6), for hard rods 26.9 (2.7). All soft particles emptied faster than their identically shaped hard counterparts, but there was no difference among the three shapes (AUC for soft cubes: 29.2 (3.0), for soft spheres 32.0 (1.8), for soft rods 34.1 (1.2). If gastric emptying of hard and soft particles was compared independently of their shape, soft particles emptied significantly faster than hard ones: AUC 31.8 (1.2) v 26.5 (1.3) (p less than 0.01). In conclusion, the consistency but not the shape significantly affects gastric emptying. Specific physical characteristics other than size and shape may affect gastric emptying of indigestible particles which may be of importance in the design of drugs. PMID:2599438

  16. The Design of Transportation Equipment in Terms of Human Capabilities. The Role of Engineering Psychology in Transport Safety.

    ERIC Educational Resources Information Center

    McFarland, Ross A.

    Human factors engineering is considered with regard to the design of safety factors for aviation and highway transportation equipment. Current trends and problem areas are identified for jet air transportation and for highway transportation. Suggested solutions to transportation safety problems are developed by applying the techniques of human…

  17. Chronic Electromagnetic Exposure at Occupational Safety Level Does Not Affect the Metabolic Profile nor Cornea Healing after LASIK Surgery

    PubMed Central

    Dabouis, Vincent; Gentilhomme, Edgar; Vignal, Rodolphe; Bourbon, Fréderic; Fauvelle, Florence; Debouzy, Jean-Claude

    2014-01-01

    LASIK eye surgery has become a very common practice for myopic people, especially those in the military. Sometimes undertaken by people who need to keep a specific medical aptitude, this surgery could be performed in secret from the hierarchy and from the institute medical staff. However, even though the eyes have been previously described as one of the most sensitive organs to electromagnetic fields in the human body, no data exist on the potential deleterious effects of electromagnetic fields on the healing eye. The consequences of chronic long-lasting radar exposures at power density, in accordance with the occupational safety standards (9.71 GHz, 50 W/m2), were investigated on cornea healing. The metabolic and clinical statuses after experimental LASIK keratotomy were assessed on the different eye segments in a New Zealand rabbit model. The analysis methods were performed after 5 months of exposure (1 hour/day, 3 times/week). Neither clinical or histological examinations, nor experimental data, such as light scattering, 1H-NMR HRMAS metabolomics, 13C-NMR spectra of lipidic extracts, and antioxidant status, evidenced significant modifications. It was concluded that withdrawing the medical aptitude of people working in electromagnetic field environments (i.e., radar operators in the navy) after eye surgery was not justified. PMID:24757560

  18. Low-frequency sound affects active micromechanics in the human inner ear.

    PubMed

    Kugler, Kathrin; Wiegrebe, Lutz; Grothe, Benedikt; Kössl, Manfred; Gürkov, Robert; Krause, Eike; Drexl, Markus

    2014-10-01

    Noise-induced hearing loss is one of the most common auditory pathologies, resulting from overstimulation of the human cochlea, an exquisitely sensitive micromechanical device. At very low frequencies (less than 250 Hz), however, the sensitivity of human hearing, and therefore the perceived loudness is poor. The perceived loudness is mediated by the inner hair cells of the cochlea which are driven very inadequately at low frequencies. To assess the impact of low-frequency (LF) sound, we exploited a by-product of the active amplification of sound outer hair cells (OHCs) perform, so-called spontaneous otoacoustic emissions. These are faint sounds produced by the inner ear that can be used to detect changes of cochlear physiology. We show that a short exposure to perceptually unobtrusive, LF sounds significantly affects OHCs: a 90 s, 80 dB(A) LF sound induced slow, concordant and positively correlated frequency and level oscillations of spontaneous otoacoustic emissions that lasted for about 2 min after LF sound offset. LF sounds, contrary to their unobtrusive perception, strongly stimulate the human cochlea and affect amplification processes in the most sensitive and important frequency range of human hearing. PMID:26064536

  19. Low-frequency sound affects active micromechanics in the human inner ear

    PubMed Central

    Kugler, Kathrin; Wiegrebe, Lutz; Grothe, Benedikt; Kössl, Manfred; Gürkov, Robert; Krause, Eike; Drexl, Markus

    2014-01-01

    Noise-induced hearing loss is one of the most common auditory pathologies, resulting from overstimulation of the human cochlea, an exquisitely sensitive micromechanical device. At very low frequencies (less than 250 Hz), however, the sensitivity of human hearing, and therefore the perceived loudness is poor. The perceived loudness is mediated by the inner hair cells of the cochlea which are driven very inadequately at low frequencies. To assess the impact of low-frequency (LF) sound, we exploited a by-product of the active amplification of sound outer hair cells (OHCs) perform, so-called spontaneous otoacoustic emissions. These are faint sounds produced by the inner ear that can be used to detect changes of cochlear physiology. We show that a short exposure to perceptually unobtrusive, LF sounds significantly affects OHCs: a 90 s, 80 dB(A) LF sound induced slow, concordant and positively correlated frequency and level oscillations of spontaneous otoacoustic emissions that lasted for about 2 min after LF sound offset. LF sounds, contrary to their unobtrusive perception, strongly stimulate the human cochlea and affect amplification processes in the most sensitive and important frequency range of human hearing. PMID:26064536

  20. Does Human Migration Affect International Trade? A Complex-Network Perspective

    PubMed Central

    Fagiolo, Giorgio; Mastrorillo, Marina

    2014-01-01

    This paper explores the relationships between international human migration and merchandise trade using a complex-network approach. We firstly compare the topological structure of worldwide networks of human migration and bilateral trade over the period 1960–2000. Next, we ask whether pairs of countries that are more central in the migration network trade more. We show that: (i) the networks of international migration and trade are strongly correlated, and such correlation can be mostly explained by country economic/demographic size and geographical distance; (ii) centrality in the international-migration network boosts bilateral trade; (iii) intensive forms of country centrality are more trade enhancing than their extensive counterparts. Our findings suggest that bilateral trade between any two countries is not only affected by the presence of migrants from either countries, but also by their relative embeddedness in the complex web of corridors making up the network of international human migration. PMID:24828376

  1. Imagination in human social cognition, autism, and psychotic-affective conditions.

    PubMed

    Crespi, Bernard; Leach, Emma; Dinsdale, Natalie; Mokkonen, Mikael; Hurd, Peter

    2016-05-01

    Complex human social cognition has evolved in concert with risks for psychiatric disorders. Recently, autism and psychotic-affective conditions (mainly schizophrenia, bipolar disorder, and depression) have been posited as psychological 'opposites' with regard to social-cognitive phenotypes. Imagination, considered as 'forming new ideas, mental images, or concepts', represents a central facet of human social evolution and cognition. Previous studies have documented reduced imagination in autism, and increased imagination in association with psychotic-affective conditions, yet these sets of findings have yet to be considered together, or evaluated in the context of the diametric model. We first review studies of the components, manifestations, and neural correlates of imagination in autism and psychotic-affective conditions. Next, we use data on dimensional autism in healthy populations to test the hypotheses that: (1) imagination represents the facet of autism that best accounts for its strongly male-biased sex ratio, and (2) higher genetic risk of schizophrenia is associated with higher imagination, in accordance with the predictions of the diametric model. The first hypothesis was supported by a systematic review and meta-analysis showing that Imagination exhibits the strongest male bias of all Autism Quotient (AQ) subscales, in non-clinical populations. The second hypothesis was supported, for males, by associations between schizophrenia genetic risk scores, derived from a set of single-nucleotide polymorphisms, and the AQ Imagination subscale. Considered together, these findings indicate that imagination, especially social imagination as embodied in the default mode human brain network, mediates risk and diametric dimensional phenotypes of autism and psychotic-affective conditions. PMID:26896903

  2. Ecology of conflict: marine food supply affects human-wildlife interactions on land.

    PubMed

    Artelle, Kyle A; Anderson, Sean C; Reynolds, John D; Cooper, Andrew B; Paquet, Paul C; Darimont, Chris T

    2016-01-01

    Human-wildlife conflicts impose considerable costs to people and wildlife worldwide. Most research focuses on proximate causes, offering limited generalizable understanding of ultimate drivers. We tested three competing hypotheses (problem individuals, regional population saturation, limited food supply) that relate to underlying processes of human-grizzly bear (Ursus arctos horribilis) conflict, using data from British Columbia, Canada, between 1960-2014. We found most support for the limited food supply hypothesis: in bear populations that feed on spawning salmon (Oncorhynchus spp.), the annual number of bears/km(2) killed due to conflicts with humans increased by an average of 20% (6-32% [95% CI]) for each 50% decrease in annual salmon biomass. Furthermore, we found that across all bear populations (with or without access to salmon), 81% of attacks on humans and 82% of conflict kills occurred after the approximate onset of hyperphagia (July 1(st)), a period of intense caloric demand. Contrary to practices by many management agencies, conflict frequency was not reduced by hunting or removal of problem individuals. Our finding that a marine resource affects terrestrial conflict suggests that evidence-based policy for reducing harm to wildlife and humans requires not only insight into ultimate drivers of conflict, but also management that spans ecosystem and jurisdictional boundaries. PMID:27185189

  3. Ecology of conflict: marine food supply affects human-wildlife interactions on land

    PubMed Central

    Artelle, Kyle A.; Anderson, Sean C.; Reynolds, John D.; Cooper, Andrew B.; Paquet, Paul C.; Darimont, Chris T.

    2016-01-01

    Human-wildlife conflicts impose considerable costs to people and wildlife worldwide. Most research focuses on proximate causes, offering limited generalizable understanding of ultimate drivers. We tested three competing hypotheses (problem individuals, regional population saturation, limited food supply) that relate to underlying processes of human-grizzly bear (Ursus arctos horribilis) conflict, using data from British Columbia, Canada, between 1960–2014. We found most support for the limited food supply hypothesis: in bear populations that feed on spawning salmon (Oncorhynchus spp.), the annual number of bears/km2 killed due to conflicts with humans increased by an average of 20% (6–32% [95% CI]) for each 50% decrease in annual salmon biomass. Furthermore, we found that across all bear populations (with or without access to salmon), 81% of attacks on humans and 82% of conflict kills occurred after the approximate onset of hyperphagia (July 1st), a period of intense caloric demand. Contrary to practices by many management agencies, conflict frequency was not reduced by hunting or removal of problem individuals. Our finding that a marine resource affects terrestrial conflict suggests that evidence-based policy for reducing harm to wildlife and humans requires not only insight into ultimate drivers of conflict, but also management that spans ecosystem and jurisdictional boundaries. PMID:27185189

  4. Deliberate Microbial Infection Research Reveals Limitations to Current Safety Protections of Healthy Human Subjects.

    PubMed

    Evers, David L; Fowler, Carol B; Mason, Jeffrey T; Mimnall, Rebecca K

    2015-08-01

    Here we identify approximately 40,000 healthy human volunteers who were intentionally exposed to infectious pathogens in clinical research studies dating from late World War II to the early 2000s. Microbial challenge experiments continue today under contemporary human subject research requirements. In fact, we estimated 4,000 additional volunteers who were experimentally infected between 2010 and the present day. We examine the risks and benefits of these experiments and present areas for improvement in protections of participants with respect to safety. These are the absence of maximum limits to risk and the potential for institutional review boards to include questionable benefits to subjects and society when weighing the risks and benefits of research protocols. The lack of a duty of medical care by physician-investigators to research subjects is likewise of concern. The transparency of microbial challenge experiments and the safety concerns raised in this work may stimulate further dialogue on the risks to participants of human experimentation. PMID:25150847

  5. Updating Human Factors Engineering Guidelines for Conducting Safety Reviews of Nuclear Power Plants

    SciTech Connect

    O, J.M.; Higgins, J.; Stephen Fleger - NRC

    2011-09-19

    The U.S. Nuclear Regulatory Commission (NRC) reviews the human factors engineering (HFE) programs of applicants for nuclear power plant construction permits, operating licenses, standard design certifications, and combined operating licenses. The purpose of these safety reviews is to help ensure that personnel performance and reliability are appropriately supported. Detailed design review procedures and guidance for the evaluations is provided in three key documents: the Standard Review Plan (NUREG-0800), the HFE Program Review Model (NUREG-0711), and the Human-System Interface Design Review Guidelines (NUREG-0700). These documents were last revised in 2007, 2004 and 2002, respectively. The NRC is committed to the periodic update and improvement of the guidance to ensure that it remains a state-of-the-art design evaluation tool. To this end, the NRC is updating its guidance to stay current with recent research on human performance, advances in HFE methods and tools, and new technology being employed in plant and control room design. This paper describes the role of HFE guidelines in the safety review process and the content of the key HFE guidelines used. Then we will present the methodology used to develop HFE guidance and update these documents, and describe the current status of the update program.

  6. The Voice of Emotion across Species: How Do Human Listeners Recognize Animals' Affective States?

    PubMed Central

    Scheumann, Marina; Hasting, Anna S.; Kotz, Sonja A.; Zimmermann, Elke

    2014-01-01

    Voice-induced cross-taxa emotional recognition is the ability to understand the emotional state of another species based on its voice. In the past, induced affective states, experience-dependent higher cognitive processes or cross-taxa universal acoustic coding and processing mechanisms have been discussed to underlie this ability in humans. The present study sets out to distinguish the influence of familiarity and phylogeny on voice-induced cross-taxa emotional perception in humans. For the first time, two perspectives are taken into account: the self- (i.e. emotional valence induced in the listener) versus the others-perspective (i.e. correct recognition of the emotional valence of the recording context). Twenty-eight male participants listened to 192 vocalizations of four different species (human infant, dog, chimpanzee and tree shrew). Stimuli were recorded either in an agonistic (negative emotional valence) or affiliative (positive emotional valence) context. Participants rated the emotional valence of the stimuli adopting self- and others-perspective by using a 5-point version of the Self-Assessment Manikin (SAM). Familiarity was assessed based on subjective rating, objective labelling of the respective stimuli and interaction time with the respective species. Participants reliably recognized the emotional valence of human voices, whereas the results for animal voices were mixed. The correct classification of animal voices depended on the listener's familiarity with the species and the call type/recording context, whereas there was less influence of induced emotional states and phylogeny. Our results provide first evidence that explicit voice-induced cross-taxa emotional recognition in humans is shaped more by experience-dependent cognitive mechanisms than by induced affective states or cross-taxa universal acoustic coding and processing mechanisms. PMID:24621604

  7. Triclosan and bisphenol a affect decidualization of human endometrial stromal cells.

    PubMed

    Forte, Maurizio; Mita, Luigi; Cobellis, Luigi; Merafina, Verdiana; Specchio, Raffaella; Rossi, Sergio; Mita, Damiano Gustavo; Mosca, Lavinia; Castaldi, Maria Antonietta; De Falco, Maria; Laforgia, Vincenza; Crispi, Stefania

    2016-02-15

    In recent years, impaired fertility and endometrium related diseases are increased. Many evidences suggest that environmental pollution might be considered a risk factor for endometrial physiopathology. Among environmental pollutants, endocrine disrupting chemicals (EDCs) act on endocrine system, causing hormonal imbalance which, in turn, leads to female and male reproductive dysfunctions. In this work, we studied the effects of triclosan (TCL) and bisphenol A (BPA), two widespread EDCs, on human endometrial stromal cells (ESCs), derived from endometrial biopsies from woman not affected by endometriosis. Cell proliferation, cell cycle, migration and decidualization mechanisms were investigated. Treatments have been performed with both the EDCs separately or in presence and in absence of progesterone used as decidualization stimulus. Both TCL and BPA did not affect cell proliferation, but they arrested ESCs at G2/M phase of cell cycle enhancing cell migration. TCL and BPA also increased gene expression and protein levels of some decidualization markers, such as insulin growth factor binding protein 1 (IGFBP1) and prolactin (PRL), amplifying the effect of progesterone alone. All together, our data strongly suggest that TCL and BPA might alter human endometrium physiology so affecting fertility and pregnancy outcome. PMID:26604029

  8. Do different degrees of human activity affect the diet of Brazilian silverside Atherinella brasiliensis?

    PubMed

    Alves, V E N; Patrício, J; Dolbeth, M; Pessanha, A; Palma, A R T; Dantas, E W; Vendel, A L

    2016-08-01

    The aim of the present study was to test whether different degrees of human activity affect the diet of the Brazilian silverside Atherinella brasiliensis in two tropical estuaries. Fish were collected along the salinity gradient of two Brazilian estuaries, the heavily impacted Paraiba Estuary and the less impacted Mamanguape Estuary, in the dry and wet seasons. The findings confirm that A. brasiliensis has generalist feeding habits and is able to change its diet under different environmental conditions. The results indicate clear spatial (i.e. along the estuarine gradient) changes in diet composition in both estuaries, but diet was also influenced by the degree of anthropogenic disturbance. During the wet season in the nutrient enriched Paraiba Estuary, when human activity was higher, the diet of A. brasiliensis was poorer and dominated by few dietary items, reflecting the potential impoverishment of prey items in this heavily disturbed system. The specimens collected in the most affected estuary also had a greater frequency of micro-plastics and parasites in their stomachs, reflecting the greater degree of human disturbance in the estuary. The present findings suggest that the diet of A. brasiliensis could be a useful indicator of changes in the ecological quality of these and other tropical estuaries of the western Atlantic Ocean. PMID:27328827

  9. Inference of human affective states from psychophysiological measurements extracted under ecologically valid conditions

    PubMed Central

    Betella, Alberto; Zucca, Riccardo; Cetnarski, Ryszard; Greco, Alberto; Lanatà, Antonio; Mazzei, Daniele; Tognetti, Alessandro; Arsiwalla, Xerxes D.; Omedas, Pedro; De Rossi, Danilo; Verschure, Paul F. M. J.

    2014-01-01

    Compared to standard laboratory protocols, the measurement of psychophysiological signals in real world experiments poses technical and methodological challenges due to external factors that cannot be directly controlled. To address this problem, we propose a hybrid approach based on an immersive and human accessible space called the eXperience Induction Machine (XIM), that incorporates the advantages of a laboratory within a life-like setting. The XIM integrates unobtrusive wearable sensors for the acquisition of psychophysiological signals suitable for ambulatory emotion research. In this paper, we present results from two different studies conducted to validate the XIM as a general-purpose sensing infrastructure for the study of human affective states under ecologically valid conditions. In the first investigation, we recorded and classified signals from subjects exposed to pictorial stimuli corresponding to a range of arousal levels, while they were free to walk and gesticulate. In the second study, we designed an experiment that follows the classical conditioning paradigm, a well-known procedure in the behavioral sciences, with the additional feature that participants were free to move in the physical space, as opposed to similar studies measuring physiological signals in constrained laboratory settings. Our results indicate that, by using our sensing infrastructure, it is indeed possible to infer human event-elicited affective states through measurements of psychophysiological signals under ecological conditions. PMID:25309310

  10. Nonsense mutations in the human. beta. -globin gene affect mRNA metabolism

    SciTech Connect

    Baserga, S.J.; Benz, E.J. Jr. )

    1988-04-01

    A number of premature translation termination mutations (nonsense mutations) have been described in the human {alpha}- and {beta}-globin genes. Studies on mRNA isolated from patients with {beta}{sup 0}-thalassemia have shown that for both the {beta}-17 and the {beta}-39 mutations less than normal levels of {beta}-globin mRNA accumulate in peripheral blood cells. (The codon at which the mutation occurs designates the name of the mutation; there are 146 codons in human {beta}-globin mRNA). In vitro studies using the cloned {beta}-39 gene have reproduced this effect in a heterologous transfection system and have suggested that the defect resides in intranuclear metabolism. The authors have asked if this phenomenon of decreased mRNA accumulation is a general property of nonsense mutations and if the effect depends on the location or the type of mutation. Toward this end, they have studied the effect of five nonsense mutations and two missense mutations on the expression of human {beta}-globin mRNA in a heterologous transfection system. In all cases studied, the presence of a translation termination codon correlates with a decrease in the steady-state level of mRNA. The data suggest that the metabolism of a mammalian mRNA is affected by the presence of a mutation that affects translation.

  11. Human factors and safety considerations of night-vision systems flight using thermal imaging systems

    NASA Astrophysics Data System (ADS)

    Rash, Clarence E.; Verona, Robert W.; Crowley, John S.

    1990-10-01

    Helmet Mounted Systems (HMS) must be lightweight, balanced and compatible with life support and head protection assemblies. This paper discusses the design of one particular HMS, the GEC Ferranti NITE-OP/NIGHTBIRD aviator's Night Vision Goggle (NVG) developed under contracts to the Ministry of Defence for all three services in the United Kingdom (UK) for Rotary Wing and fast jet aircraft. The existing equipment constraints, safety, human factor and optical performance requirements are discussed before the design solution is presented after consideration of these material and manufacturing options.

  12. On Space Exploration and Human Error: A Paper on Reliability and Safety

    NASA Technical Reports Server (NTRS)

    Bell, David G.; Maluf, David A.; Gawdiak, Yuri

    2005-01-01

    NASA space exploration should largely address a problem class in reliability and risk management stemming primarily from human error, system risk and multi-objective trade-off analysis, by conducting research into system complexity, risk characterization and modeling, and system reasoning. In general, in every mission we can distinguish risk in three possible ways: a) known-known, b) known-unknown, and c) unknown-unknown. It is probably almost certain that space exploration will partially experience similar known or unknown risks embedded in the Apollo missions, Shuttle or Station unless something alters how NASA will perceive and manage safety and reliability

  13. Affective Bicultural and Global-Human Identity Scales for Mexican-American adolescents.

    PubMed

    Der-Karabetian, A; Ruiz, Y

    1997-06-01

    Scales were developed to measure affective aspects of Latino, American, and global-human identities among first- and second-generation Mexican-American adolescents. Participants were 84 boys and 93 girls from the Los Angeles high schools. 60 were born in Mexico, and 117 were born in the United States and had at least one parent born in Mexico. The affective Latino and American measures were independent and predictably related to a behaviorally oriented measure of acculturation. They were also used to identify Berry's four modes of acculturation: Separated, Assimilated, Marginalized, and Bicultural. The four acculturation groups rated similarly on self-esteem and academic aspiration. The first and second generations each scored higher on Latino identity than on American identity. PMID:9198403

  14. Cognitive and affective components of mental workload: Understanding the effects of each on human decision making behavior

    NASA Technical Reports Server (NTRS)

    Nygren, Thomas E.

    1992-01-01

    Human factors and ergonomics researchers have recognized for some time the increasing importance of understanding the role of the construct of mental workload in flight research. Current models of mental workload suggest that it is a multidimensional and complex construct, but one that has proved difficult to measure. Because of this difficulty, emphasis has usually been placed on using direct reports through subjective measures such as rating scales to assess levels of mental workload. The NASA Task Load Index (NASA/TLX, Hart and Staveland) has been shown to be a highly reliable and sensitive measure of perceived mental workload. But a problem with measures like TLX is that there is still considerable disagreement as to what it is about mental workload that these subjective measures are actually measuring. The empirical use of subjective workload measures has largely been to provide estimates of the cognitive components of the actual mental workload required for a task. However, my research suggests that these measures may, in fact have greater potential in accurately assessing the affective components of workload. That is, for example, TLX may be more likely to assess the positive and negative feelings associated with varying workload levels, which in turn may potentially influence the decision making behavior that directly bears on performance and safety issues. Pilots, for example, are often called upon to complete many complex tasks that are high in mental workload, stress, and frustration, and that have significant dynamic decision making components -- often ones that involve risk as well.

  15. Health in the hot zone - How could global warming affect humans?

    SciTech Connect

    Monastersky, R.

    1996-04-06

    A soon-to-be-released report from the World Health Organization examines the health effects of global warming, calling climate change one of the largest public health challenges for the upcoming century. The issue extends beyond tropical illness: deaths caused directly by heat, dwindling agricultural yields etc. could all affect human health. This article looks at the following health related effects and gives an overview of the scientific information available on each: temperature and mortality; tropical trouble, including vecorborne diseases and increase in susceptable populations; and waterborne problems such as cholera, harmful algal bloomes, food shortages.

  16. Does correlated color temperature affect the ability of humans to identify veins?

    PubMed

    Argyraki, Aikaterini; Clemmensen, Line Katrine Harder; Petersen, Paul Michael

    2016-01-01

    In the present study we provide empirical evidence and demonstrate statistically that white illumination settings can affect the human ability to identify veins in the inner hand vasculature. A special light-emitting diode lamp with high color rendering index (CRI 84-95) was developed and the effect of correlated color temperature was evaluated, in the range between 2600 and 5700 K at an illuminance of 40±9  lx on the ability of adult humans to identify veins. It is shown that the ability to identify veins can, on average, be increased up to 24% when white illumination settings that do not resemble incandescent light are applied. The illuminance reported together with the effect of white illumination settings on direct visual perception of biosamples are relevant for clinical investigations during the night. PMID:26831595

  17. Dominant factors affecting temperature rise in simulations of human thermoregulation during RF exposure.

    PubMed

    Laakso, Ilkka; Hirata, Akimasa

    2011-12-01

    Numerical models of the human thermoregulatory system can be used together with realistic voxel models of the human anatomy to simulate the body temperature increases caused by the power absorption from radio-frequency electromagnetic fields. In this paper, the Pennes bioheat equation with a thermoregulatory model is used for calculating local peak temperatures as well as the body-core-temperature elevation in a realistic human body model for grounded plane-wave exposures at frequencies 39, 800 and 2400 MHz. The electromagnetic power loss is solved by the finite-difference time-domain (FDTD) method, and the discretized bioheat equation is solved by the geometric multigrid method. Human thermoregulatory models contain numerous thermophysiological and computational parameters--some of which may be subject to considerable uncertainty--that affect the simulated core and local temperature elevations. The goal of this paper is to find how greatly the computed temperature is influenced by changes in various modelling parameters, such as the skin blood flow rate, models for vasodilation and sweating, and clothing and air movement. The results show that the peak temperature rises are most strongly affected by the modelling of tissue blood flow and its temperature dependence, and mostly unaffected by the central control mechanism for vasodilation and sweating. Almost the opposite is true for the body-core-temperature rise, which is however typically greatly lower than the peak temperature rise. It also seems that ignoring the thermoregulation and the blood temperature increase is a good approximation when the local 10 g averaged specific absorption rate is smaller than 10 W kg(-1). PMID:22080753

  18. Dominant factors affecting temperature rise in simulations of human thermoregulation during RF exposure

    NASA Astrophysics Data System (ADS)

    Laakso, Ilkka; Hirata, Akimasa

    2011-12-01

    Numerical models of the human thermoregulatory system can be used together with realistic voxel models of the human anatomy to simulate the body temperature increases caused by the power absorption from radio-frequency electromagnetic fields. In this paper, the Pennes bioheat equation with a thermoregulatory model is used for calculating local peak temperatures as well as the body-core-temperature elevation in a realistic human body model for grounded plane-wave exposures at frequencies 39, 800 and 2400 MHz. The electromagnetic power loss is solved by the finite-difference time-domain (FDTD) method, and the discretized bioheat equation is solved by the geometric multigrid method. Human thermoregulatory models contain numerous thermophysiological and computational parameters—some of which may be subject to considerable uncertainty—that affect the simulated core and local temperature elevations. The goal of this paper is to find how greatly the computed temperature is influenced by changes in various modelling parameters, such as the skin blood flow rate, models for vasodilation and sweating, and clothing and air movement. The results show that the peak temperature rises are most strongly affected by the modelling of tissue blood flow and its temperature dependence, and mostly unaffected by the central control mechanism for vasodilation and sweating. Almost the opposite is true for the body-core-temperature rise, which is however typically greatly lower than the peak temperature rise. It also seems that ignoring the thermoregulation and the blood temperature increase is a good approximation when the local 10 g averaged specific absorption rate is smaller than 10 W kg-1.

  19. Structural Design Requirements and Factors of Safety for Spaceflight Hardware: For Human Spaceflight. Revision A

    NASA Technical Reports Server (NTRS)

    Bernstein, Karen S.; Kujala, Rod; Fogt, Vince; Romine, Paul

    2011-01-01

    This document establishes the structural requirements for human-rated spaceflight hardware including launch vehicles, spacecraft and payloads. These requirements are applicable to Government Furnished Equipment activities as well as all related contractor, subcontractor and commercial efforts. These requirements are not imposed on systems other than human-rated spacecraft, such as ground test articles, but may be tailored for use in specific cases where it is prudent to do so such as for personnel safety or when assets are at risk. The requirements in this document are focused on design rather than verification. Implementation of the requirements is expected to be described in a Structural Verification Plan (SVP), which should describe the verification of each structural item for the applicable requirements. The SVP may also document unique verifications that meet or exceed these requirements with NASA Technical Authority approval.

  20. Human immunodeficiency virus type 1 (HIV-1) derived vectors: safety considerations and controversy over therapeutic applications.

    PubMed

    Romano, Gaetano; Claudio, Pier Paolo; Tonini, Tiziana; Giordano, Antonio

    2003-01-01

    The latest generation of lentiviral vectors based on HIV-1 is one of the most efficient tools for gene transduction of mammalian cells. However, the possible employment of HIV-based vectors in clinical trials is a very controversial issue, mainly due to safety and ethical concerns. HIV-1 is a lethal pathogenic agent, which induces AIDS. Genetic vectors must derive either from viruses that are not pathogenic in humans, or that eventually just cause mild illnesses. Patients exposed to HIV-based vectors will test seropositive to certain components of HIV-1. In addition, there might be other possible adverse effects in patients that cannot be predicted, as many aspects of the pathogenesis of AIDS have not been completely understood yet. On these grounds, it seems necessary to improve the design of other lentiviral vectors, which derive from viruses that are not pathogenic in humans and are distantly related to primate retroviridae. PMID:14693483

  1. The pharmacokinetics of phenylethyl alcohol (PEA): safety evaluation comparisons in rats, rabbits, and humans.

    PubMed

    Politano, Valerie T; Diener, Robert M; Christian, Mildred S; Hawkins, David R; Ritacco, Gretchen; Api, Anne Marie

    2013-01-01

    The present studies were conducted to compare the dermal absorption, plasma pharmacokinetics, and excretion of phenylethyl alcohol (PEA) by pregnant and nonpregnant rats, rabbits, and humans. The PEA is a natural fragrance material that is widely used in perfumes, soaps, and lotions and is a major ingredient of natural rose oil. Following dermal (430, 700, or 1400 mg/kg body weight [bw]), gavage (430 mg/kg bw), or dietary (430 mg/kg bw) administration of PEA to rats, plasma concentrations of PEA were found to be low regardless of the route of administration. The plasma concentrations of phenylacetic acid (PAA, the major metabolite of PEA) greatly exceeded the concentrations of PEA and were highest after gavage, followed by dermal then dietary administration. Absorption, distribution, metabolism, and excretion were compared following topical application of ¹⁴C-labeled PEA to rats, rabbits, and humans (specific activities of dosing solutions: 58-580, 164, and 50 µCi/mL, respectively). In rabbits, the plasma concentration-time profile for PAA was markedly prolonged compared to rats or humans. In humans, only 7.6% of the applied dose of PEA was absorbed, versus 77% in rats and 50% in rabbits. Based on a human dermal systemic exposure of 0.3 mg/kg per day from the use of multiple consumer personal care products containing PEA, a rat dermal no observed adverse effect level of 70 mg/kg per day, and the percentage of dose absorbed in humans, the margin of safety exceeds 2600 concluding that, under normal fragrance use conditions, PEA is not a developmental toxicity hazard for humans. PMID:23385160

  2. Clinical safety of tbo-filgrastim, a short-acting human granulocyte colony-stimulating factor.

    PubMed

    Pettengell, Ruth; Bias, Peter; Mueller, Udo; Lang, Nicole

    2016-06-01

    The recombinant human granulocyte colony-stimulating factor (G-CSF) known as filgrastim (Tevagrastim(®), Ratiograstim(®), Biograstim(®)) in Europe (approved in 2008) and tbo-filgrastim (Granix(®)) in the USA (approved in 2012; Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel) is indicated to reduce the duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. This article presents pooled clinical data for tbo-filgrastim compared with Neupogen(®) (Amgen, Thousand Oaks, CA, USA) as well as tbo-filgrastim post-marketing safety data. The safety and efficacy of tbo-filgrastim were evaluated in three phase III studies in 677 patients receiving myelosuppressive chemotherapy and study drug (348 patients with breast cancer, 237 with lung cancer, 92 with non-Hodgkin lymphoma). In each study, the efficacy of tbo-filgrastim was similar to that of Neupogen. Overall, 633 (93.5 %) patients receiving the study drug experienced 6093 treatment-emergent adverse events (AEs), most of which were related to chemotherapy. Adverse events related to the study drug (tbo-filgrastim or Neupogen) were experienced by 185 (27.3 %) patients; 19 (2.8 %) had severe drug-related AEs, 5 (0.7 %) had drug-related serious AEs, and 6 (0.9 %) discontinued the study due to drug-related AEs. Overall, the most common drug-related AEs were bone pain (7.1 %), myalgia (4.0 %), and asthenia (4.4 %). The post-marketing safety profile of tbo-filgrastim was consistent with that observed during the clinical studies. The availability of tbo-filgrastim, a G-CSF with safety and efficacy comparable to those of Neupogen, provides physicians with an alternative treatment option for supportive care of patients with non-myeloid malignancies receiving myelosuppressive chemotherapy. PMID:26780505

  3. Integrating Safety and Lessons-Learned Data with Human Performance for Successful Management and Oversight

    SciTech Connect

    Prevette, S.S.; Bilson, H.E.

    2008-07-01

    This paper documents the improvements Fluor Hanford, Inc. (Fluor Hanford) is making in analyzing and using safety-related and lessons-learned data in cleaning up the U.S. Department of Energy's (DOE's) site at Hanford in southeastern Washington state. Results of the application of Statistical Process Control (SPC) and Dashboards to support planning and decision making have been shared at past Waste Management conferences. Recently, Fluor Hanford has implemented and refined a process called the 'Data Analysis Working Group' to integrate data from several sources, including opinions from subject-matter experts. The process also includes a risk-ranking tool used to prioritize potential risks and past problems for management and oversight of the Hanford cleanup. Human Performance and Lessons Learned information also is included in this process. Fluor Hanford has applied SPC in a non-traditional (that is non-manufacturing) manner. Dr. Shewhart's 75-year-old control-chart methodologies have been updated to modern data processing, but are still founded on his sound, tried and true principles. These methods are playing a key role in safety and quality at Hanford. The performance-indicator system used by Fluor Hanford has been featured by several professional societies in their publications, primarily the American Society of Safety Engineers and the American Society for Quality. The system also has been featured in past Waste Management conferences. Eleven years ago, Fluor Hanford's statistician produced 300 data files and accompanying charts a month. Today, those numbers exceed 3,000 a month, almost one chart for every employee. This activity also includes entering data for approximately 500 safety inspections each month. The challenge is in effectively analyzing and prioritizing this information and providing it to senior management to make pro-active decisions and policies. That challenge is being met by Fluor's Data Analysis Working Group process. (authors)

  4. A Real-time Evaluation of Human-based Approaches to Safety Testing: What We Can Do Now (TDS)

    EPA Science Inventory

    Despite ever-increasing efforts in early safety assessment in all industries, there are still many chemicals that prove toxic in humans. While greater use of human in vitro test methods may serve to reduce this problem, the formal validation process applied to such tests represen...

  5. Assessment of Human Safety and Thermal Comfort in High-Temperature Environment: CFD and Human Thermoregulation Model

    NASA Astrophysics Data System (ADS)

    Xuefeng, Han; Wenguo, Weng; Shifei, Shen

    2010-05-01

    The safety and the thermal comfort of victims and firefighters are important in the building fires, which are a little dependent on the occupant fatalities. In order to investigate the effects of the dangerous environment on human body in fires, numerical calculation of the heat transfer and human thermoregulation are presented in this paper. The numerical manikins coupled with human thermal models were proved as powerful tools for visualizing thermal comfort. The two-node model by Gagge and multi-code thermoregulation models were investigated, and the Gagge's model was coupled with the CFD for high-temperature environment simulation, with which a numerical manikin was built. During the simulation, temperatures of skin and core compartment of Computer Simulated Person (CPS) were recorded respectively, and the Predicted Mean Vote index values were counted. The thermal load on skin is much higher than neutral cases and the skin can be burnt in minutes if no protection and heat abstraction methods were introduced. Though existing models can predict thermal comfort in general indoor environment, they are not suitable in predicting the thermal comfort with high-temperature cases. It was suggested that more research combining CFD coupling thermoregulation models with thermal manikin experiment are needed.

  6. Practical Applications of Cosmic Ray Science: Spacecraft, Aircraft, Ground-Based Computation and Control Systems, and Human Health and Safety

    NASA Technical Reports Server (NTRS)

    Atwell, William; Koontz, Steve; Normand, Eugene

    2012-01-01

    Three twentieth century technological developments, 1) high altitude commercial and military aircraft; 2) manned and unmanned spacecraft; and 3) increasingly complex and sensitive solid state micro-electronics systems, have driven an ongoing evolution of basic cosmic ray science into a set of practical engineering tools needed to design, test, and verify the safety and reliability of modern complex technological systems. The effects of primary cosmic ray particles and secondary particle showers produced by nuclear reactions with the atmosphere, can determine the design and verification processes (as well as the total dollar cost) for manned and unmanned spacecraft avionics systems. Similar considerations apply to commercial and military aircraft operating at high latitudes and altitudes near the atmospheric Pfotzer maximum. Even ground based computational and controls systems can be negatively affected by secondary particle showers at the Earth s surface, especially if the net target area of the sensitive electronic system components is large. Finally, accumulation of both primary cosmic ray and secondary cosmic ray induced particle shower radiation dose is an important health and safety consideration for commercial or military air crews operating at high altitude/latitude and is also one of the most important factors presently limiting manned space flight operations beyond low-Earth orbit (LEO). In this paper we review the discovery of cosmic ray effects on the performance and reliability of microelectronic systems as well as human health and the development of the engineering and health science tools used to evaluate and mitigate cosmic ray effects in ground-based atmospheric flight, and space flight environments. Ground test methods applied to microelectronic components and systems are used in combinations with radiation transport and reaction codes to predict the performance of microelectronic systems in their operating environments. Similar radiation transport

  7. 1981 NRC/BNL/IEEE standards workshop on human factors and nuclear safety. The man-machine interface and human reliability: an assessment and projection

    SciTech Connect

    Hall, R.E.; Fragola, J.R.; Luckas, W.J. Jr.

    1981-09-01

    The role of the human in the safety of nuclear power plant operations was addressed in a meeting held in Myrtle Beach, SC in August 1981. Presentation were made on Control Room reviews, safety parameter display systems, the integration of human factors in the entire design process, and the use of automated control features. A need was shown for the development of a taxonomy or model to structure future data gathering and the need for models and data to address the issue of cognitive behavior. The primary effect of this behavior on risk was identified. Discussion sessions on the human impact on reliability, and control room design and evaluation were included. (ACR)

  8. Differential Muscle Involvement in Mice and Humans Affected by McArdle Disease.

    PubMed

    Krag, Thomas O; Pinós, Tomàs; Nielsen, Tue L; Brull, Astrid; Andreu, Antoni L; Vissing, John

    2016-05-01

    McArdle disease (muscle glycogenosis type V) is caused by myophosphorylase deficiency, which leads to impaired glycogen breakdown. We investigated how myophosphorylase deficiency affects muscle physiology, morphology, and glucose metabolism in 20-week-old McArdle mice and compared the findings to those in McArdle disease patients. Muscle contractions in the McArdle mice were affected by structural degeneration due to glycogen accumulation, and glycolytic muscles fatigued prematurely, as occurs in the muscles of McArdle disease patients. Homozygous McArdle mice showed muscle fiber disarray, variations in fiber size, vacuoles, and some internal nuclei associated with cytosolic glycogen accumulation and ongoing regeneration; structural damage was seen only in a minority of human patients. Neither liver nor brain isoforms of glycogen phosphorylase were upregulated in muscles, thus providing no substitution for the missing muscle isoform. In the mice, the tibialis anterior (TA) muscles were invariably more damaged than the quadriceps muscles. This may relate to a 7-fold higher level of myophosphorylase in TA compared to quadriceps in wild-type mice and suggests higher glucose turnover in the TA. Thus, despite differences, the mouse model of McArdle disease shares fundamental physiological and clinical features with the human disease and could be used for studies of pathogenesis and development of therapies. PMID:27030740

  9. Factors affecting platinum concentrations in human surgical tumour specimens after cisplatin.

    PubMed Central

    Stewart, D. J.; Molepo, J. M.; Green, R. M.; Montpetit, V. A.; Hugenholtz, H.; Lamothe, A.; Mikhael, N. Z.; Redmond, M. D.; Gadia, M.; Goel, R.

    1995-01-01

    We assessed factors which affect cisplatin concentrations in human surgical tumour specimens. Cisplatin 10 mg m-2 was given i.v. to 45 consenting patients undergoing surgical resection of neoplasms, and platinum was assayed in resected tumour and in deproteinated plasma by flameless atomic absorption spectrophotometry. By multiple stepwise regression analysis of normalised data, patient characteristics that emerged as being most closely associated (P < 0.05) with tumour platinum concentrations (after correcting for associations with other variables) were tumour 'source' [primary brain lymphomas, medulloblastomas and meningiomas ('type LMM') > 'others' > lung cancer > head/neck cancer > gliomas) or tumour 'type' (LMM > brain metastases > extracerebral tumours > gliomas), serum calcium and chloride (positive correlations) and bilirubin (negative). Tumour location (intracranial vs extracranial) did not correlate with platinum concentrations. If values for a single outlier were omitted, high-grade gliomas had significantly higher platinum concentrations (P < 0.003) than low-grade gliomas. For intracranial tumours, the computerised tomographic scan feature that correlated most closely with platinum concentrations in multivariate analysis was the darkness of peritumoral oedema. Tumour source or type is a much more important correlate of human tumour cisplatin concentrations than is intracranial vs extracranial location. Serum calcium, chloride and bilirubin levels may affect tumour cisplatin uptake or retention. CT scan characteristics may help predict cisplatin concentrations in intracranial tumours. PMID:7880744

  10. Overview of Development and Deployment of Codes, Standards and Regulations Affecting Energy Storage System Safety in the United States

    SciTech Connect

    Conover, David R.

    2014-08-22

    This report acquaints stakeholders and interested parties involved in the development and/or deployment of energy storage systems (ESS) with the subject of safety-related codes, standards and regulations (CSRs). It is hoped that users of this document gain a more in depth and uniform understanding of safety-related CSR development and deployment that can foster improved communications among all ESS stakeholders and the collaboration needed to realize more timely acceptance and approval of safe ESS technology through appropriate CSR.

  11. Safety of human papillomavirus 6, 11, 16 and 18 (recombinant): systematic review and meta-analysis

    PubMed Central

    Coelho, Pedro Luiz Spinelli; Calestini, Gustavo Lacerda da Silva; Alvo, Fernando Salgueiro; Freitas, Jefferson Michel de Moura; Castro, Paula Marcela Vilela; Konstantyner, Tulio

    2015-01-01

    Objective: To identify and quantify the adverse effects associated with the recombinant human papillomavirus (types 6, 11, 16 and 18) vaccine in adolescents. Data source: Systematic review of randomized clinical trials from PubMed, SciELO and Lilacs databases. Articles investigating the safety of the vaccine in subjects under 18 years and comparing the recombinant human papillomavirus types 6, 11, 16 and 18 vaccine with a control group were included. Meta-analyses were performed for the outcomes of pain, erythema, swelling and fever, using clinical trials with maximum Jadad score. Data synthesis: Fourteen studies were included. The most common adverse effects related to the human papillomavirus vaccine were effects with no severity (pain, erythema, edema, and fever). Five studies were used for the meta-analyses: pain-risk difference (RD)=11% (p<0.001); edema-RD=8% (p<0.001); erythema-RD=5% (p<0.001); fever-RD=2% (p<0.003). Conclusions: The recombinant human papillomavirus types 6, 11, 16 and 18 vaccine was safe and well tolerated. The main adverse effects related to vaccination were pain, erythema, edema and fever. The low frequency of severe adverse effects encourages the administration of the vaccine in the population at risk. PMID:26376359

  12. An alternative approach to solar system exploration providing safety of human mission to Mars.

    PubMed

    Gitelson, J I; Bartsev, S I; Mezhevikin, V V; Okhonin, V A

    2003-01-01

    For systematic human Mars exploration, meeting crew safety requirements, it seems perspective to assemble into a spacecraft: an electrical rocket, a well-shielded long-term life support system, and a manipulator-robots operating in combined "presence effect" and "master-slave" mode. The electrical spacecraft would carry humans to the orbit of Mars, providing short distance (and low signal time delay) between operator and robot-manipulators, which are landed on the surface of the planet. Long-term hybrid biological and physical/chemical LSS could provide environment supporting human health and well being. Robot-manipulators operating in "presence effect" and "master-slave" mode exclude necessity of human landing on Martian surface decreasing the level of risk for crew. Since crewmen would not have direct contact with the Martian environment then the problem of mutual biological protection is essentially reduced. Lightweight robot-manipulators, without heavy life support systems and without the necessity of returning to the mother vessel, could be sent as scouts to different places on the planet surface, scanning the most interesting for exobiological research site. Some approximate estimations of electric spacecraft, long-term hybrid LSS, radiation protection and mission parameters are conducted and discussed. PMID:12577896

  13. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies.

    PubMed

    Méplan, Catherine; Johnson, Ian T; Polley, Abigael C J; Cockell, Simon; Bradburn, David M; Commane, Daniel M; Arasaradnam, Ramesh P; Mulholland, Francis; Zupanic, Anze; Mathers, John C; Hesketh, John

    2016-08-01

    Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk.-Méplan, C., Johnson, I. T., Polley, A. C. J., Cockell, S., Bradburn, D. M., Commane, D. M., Arasaradnam, R. P., Mulholland, F., Zupanic, A., Mathers, J. C., Hesketh, J. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies. PMID:27103578

  14. Common genetic polymorphisms affect the human requirement for the nutrient choline

    PubMed Central

    da Costa, Kerry-Ann; Kozyreva, Olga G.; Song, Jiannan; Galanko, Joseph A.; Fischer, Leslie M.; Zeisel, Steven H.

    2006-01-01

    Humans eating diets deficient in the essential nutrient choline can develop organ dysfunction. We hypothesized that common single nucleotide polymorphisms (SNPs) in genes involved in choline metabolism influence the dietary requirement of this nutrient. Fifty-seven humans were fed a low choline diet until they developed organ dysfunction or for up to 42 days. We tested DNA SNPs for allelic association with susceptibility to developing organ dysfunction associated with choline deficiency. We identified an SNP in the promoter region of the phosphatidylethanolamine N-methyltransferase gene (PEMT; −744 G→C; rs12325817) for which 18 of 23 carriers of the C allele (78%) developed organ dysfunction when fed a low choline diet (odds ratio 25, P=0.002). The first of two SNPs in the coding region of the choline dehydrogenase gene (CHDH; +318 A→C; rs9001) had a protective effect on susceptibility to choline deficiency, while a second CHDH variant (+432 G→T; rs12676) was associated with increased susceptibility to choline deficiency. A SNP in the PEMT coding region (+5465 G→A; rs7946) and a betaine:homocysteine methyl-transferase (BHMT) SNP (+742 G→A; rs3733890) were not associated with susceptibility to choline deficiency. Identification of common polymorphisms that affect dietary requirements for choline could enable us to identify individuals for whom we need to assure adequate dietary choline intake.—da Costa, K.-A., Kozyreva, O. G., Song, J., Galanko, J. A., Fischer, L. M., Zeisel, S. H. Common genetic polymorphisms affect the human requirement for the nutrient choline. PMID:16816108

  15. Structure-mechanical function relations at nano-scale in heat-affected human dental tissue.

    PubMed

    Sui, Tan; Sandholzer, Michael A; Le Bourhis, Eric; Baimpas, Nikolaos; Landini, Gabriel; Korsunsky, Alexander M

    2014-04-01

    The knowledge of the mechanical properties of dental materials related to their hierarchical structure is essential for understanding and predicting the effect of microstructural alterations on the performance of dental tissues in the context of forensic and archaeological investigation as well as laser irradiation treatment of caries. So far, few studies have focused on the nano-scale structure-mechanical function relations of human teeth altered by chemical or thermal treatment. The response of dental tissues to thermal treatment is thought to be strongly affected by the mineral crystallite size, their spatial arrangement and preferred orientation. In this study, synchrotron-based small and wide angle X-ray scattering (SAXS/WAXS) techniques were used to investigate the micro-structural alterations (mean crystalline thickness, crystal perfection and degree of alignment) of heat-affected dentine and enamel in human dental teeth. Additionally, nanoindentation mapping was applied to detect the spatial and temperature-dependent nano-mechanical properties variation. The SAXS/WAXS results revealed that the mean crystalline thickness distribution in dentine was more uniform compared with that in enamel. Although in general the mean crystalline thickness increased both in dentine and enamel as the temperature increased, the local structural variations gradually reduced. Meanwhile, the hardness and reduced modulus in enamel decreased as the temperature increased, while for dentine, the tendency reversed at high temperature. The analysis of the correlation between the ultrastructure and mechanical properties coupled with the effect of temperature demonstrates the effect of mean thickness and orientation on the local variation of mechanical property. This structural-mechanical property alteration is likely to be due to changes of HAp crystallites, thus dentine and enamel exhibit different responses at different temperatures. Our results enable an improved understanding of

  16. A Whole-Genome RNA Interference Screen for Human Cell Factors Affecting Myxoma Virus Replication

    PubMed Central

    Teferi, Wondimagegnehu M.; Dodd, Kristopher; Maranchuk, Rob; Favis, Nicole

    2013-01-01

    Myxoma virus (MYXV) provides an important model for investigating host-pathogen interactions. Recent studies have also highlighted how mutations in transformed human cells can expand the host range of this rabbit virus. Although virus growth depends upon interactions between virus and host proteins, the nature of these interactions is poorly understood. To address this matter, we performed small interfering RNA (siRNA) screens for genes affecting MYXV growth in human MDA-MB-231 cells. By using siRNAs targeting the whole human genome (21,585 genes), a subset of human phosphatases and kinases (986 genes), and also a custom siRNA library targeting selected statistically significant genes (“hits”) and nonsignificant genes (“nonhits”) of the whole human genome screens (88 genes), we identified 711 siRNA pools that promoted MYXV growth and 333 that were inhibitory. Another 32 siRNA pools (mostly targeting the proteasome) were toxic. The overall overlap in the results was about 25% for the hits and 75% for the nonhits. These pro- and antiviral genes can be clustered into pathways and related groups, including well-established inflammatory and mitogen-activated protein kinase pathways, as well as clusters relating to β-catenin and the Wnt signaling cascade, the cell cycle, and cellular metabolism. The validity of a subset of these hits was independently confirmed. For example, treating cells with siRNAs that might stabilize cells in G1, or inhibit passage into S phase, stimulated MYXV growth, and these effects were reproduced by trapping cells at the G1/S boundary with an inhibitor of cyclin-dependent kinases 4/6. By using 2-deoxy-d-glucose and plasmids carrying the gene for phosphofructokinase, we also confirmed that infection is favored by aerobic glycolytic metabolism. These studies provide insights into how the growth state and structure of cells affect MYXV growth and how these factors might be manipulated to advantage in oncolytic virus therapy. PMID

  17. Recombination affects accumulation of damaging and disease-associated mutations in human populations.

    PubMed

    Hussin, Julie G; Hodgkinson, Alan; Idaghdour, Youssef; Grenier, Jean-Christophe; Goulet, Jean-Philippe; Gbeha, Elias; Hip-Ki, Elodie; Awadalla, Philip

    2015-04-01

    Many decades of theory have demonstrated that, in non-recombining systems, slightly deleterious mutations accumulate non-reversibly, potentially driving the extinction of many asexual species. Non-recombining chromosomes in sexual organisms are thought to have degenerated in a similar fashion; however, it is not clear the extent to which damaging mutations accumulate along chromosomes with highly variable rates of crossing over. Using high-coverage sequencing data from over 1,400 individuals in the 1000 Genomes and CARTaGENE projects, we show that recombination rate modulates the distribution of putatively deleterious variants across the entire human genome. Exons in regions of low recombination are significantly enriched for deleterious and disease-associated variants, a signature varying in strength across worldwide human populations with different demographic histories. Regions with low recombination rates are enriched for highly conserved genes with essential cellular functions and show an excess of mutations with demonstrated effects on health, a phenomenon likely affecting disease susceptibility in humans. PMID:25685891

  18. Foetal bovine serum-derived exosomes affect yield and phenotype of human cardiac progenitor cell culture

    PubMed Central

    Angelini, Francesco; Ionta, Vittoria; Rossi, Fabrizio; Miraldi, Fabio; Messina, Elisa; Giacomello, Alessandro

    2016-01-01

    Introduction: Cardiac progenitor cells (CPCs) represent a powerful tool in cardiac regenerative medicine. Pre-clinical studies suggest that most of the beneficial effects promoted by the injected cells are due to their paracrine activity exerted on endogenous cells and tissue. Exosomes are candidate mediators of this paracrine effects. According to their potential, many researchers have focused on characterizing exosomes derived from specific cell types, but, up until now, only few studies have analyzed the possible in vitro effects of bovine serum-derived exosomes on cell proliferation or differentiation. Methods: The aim of this study was to analyse, from a qualitative and quantitative point of view, the in vitro effects of bovine serum exosomes on human CPCs cultured either as cardiospheres or as monolayers of cardiosphere-forming cells. Results: Effects on proliferation, yield and molecular patterning were detected. We show, for the first time, that exogenous bovine exosomes support the proliferation and migration of human cardiosphere-forming cells, and that their depletion affects cardiospheres formation, in terms of size, yield and extra-cellular matrix production. Conclusion: These results stress the importance of considering differential biological effects of exogenous cell culture supplements on the final phenotype of primary human cell cultures.

  19. Human cytomegalovirus RL13 protein interacts with host NUDT14 protein affecting viral DNA replication.

    PubMed

    Wang, Guili; Ren, Gaowei; Cui, Xin; Lu, Zhitao; Ma, Yanping; Qi, Ying; Huang, Yujing; Liu, Zhongyang; Sun, Zhengrong; Ruan, Qiang

    2016-03-01

    The interaction between the host and human cytomegalovirus (HCMV) is important in determining the outcome of a viral infection. The HCMV RL13 gene product exerts independent, inhibitory effects on viral growth in fibroblasts and epithelial cells. At present, there are few reports on the interactions between the HCMV RL13 protein and human host proteins. The present study provided direct evidence for the specific interaction between HCMV RL13 and host nucleoside diphosphate linked moiety X (nudix)‑type motif 14 (NUDT14), a UDP‑glucose pyrophosphatase, using two‑hybrid screening, an in vitro glutathione S‑transferase pull‑down assay, and co‑immunoprecipitation in human embryonic kidney HEK293 cells. Additionally, the RL13 protein was shown to co‑localize with the NUDT14 protein in the HEK293 cell membrane and cytoplasm, demonstrated using fluorescence confocal microscopy. Decreasing the expression level of NUDT14 via NUDT14‑specific small interfering RNAs increased the number of viral DNA copies in the HCMV‑infected cells. However, the overexpression of NUDT14 in a stably expressing cell line did not affect viral DNA levels significantly in the HCMV infected cells. Based on the known functions of NUDT14, the results of the present study suggested that the interaction between the RL13 protein and NUDT14 protein may be involved in HCMV DNA replication, and that NUDT14 may offer potential in the modulation of viral infection. PMID:26781650

  20. The cross-mammalian neurophenomenology of primal emotional affects: From animal feelings to human therapeutics.

    PubMed

    Panksepp, Jaak

    2016-06-01

    The neural correlates of human emotions are easy to harvest. In contrast, the neural constitution of emotional feelings in humans has resisted systematic scientific analysis. This review summarizes how preclinical affective neuroscience initiatives are making progress in decoding the neural nature of such feelings in animal brains. This has been achieved by studying the rewarding and punishing effects of deep brain stimulation (DBS) of subcortical emotional networks (labeled SEEING, RAGE, FEAR, LUST, CARE, PANIC, and PLAY systems) that evoke distinct emotion action patterns, as well as rewarding and punishing effects in animals. The implications of this knowledge for development of new psychiatric interventions, especially depression, are discussed. Three new antidepressive therapeutics arising from this work are briefly noted: 1) DBS of the medial forebrain bundle (MFB) in humans, 2) reduction of psychological pain that may arise from excessive PANIC arousal, and 3) facilitation of social joy through the study of social play in rats The overall argument is that we may more readily develop new psychiatric interventions through preclinical models if we take animal emotional feelings seriously, as opposed to just behavioral changes, as targets for development of new treatments. PMID:26876723

  1. The Affective Slider: A Digital Self-Assessment Scale for the Measurement of Human Emotions

    PubMed Central

    Betella, Alberto; Verschure, Paul F. M. J.

    2016-01-01

    Self-assessment methods are broadly employed in emotion research for the collection of subjective affective ratings. The Self-Assessment Manikin (SAM), a pictorial scale developed in the eighties for the measurement of pleasure, arousal, and dominance, is still among the most popular self-reporting tools, despite having been conceived upon design principles which are today obsolete. By leveraging on state-of-the-art user interfaces and metacommunicative pictorial representations, we developed the Affective Slider (AS), a digital self-reporting tool composed of two slider controls for the quick assessment of pleasure and arousal. To empirically validate the AS, we conducted a systematic comparison between AS and SAM in a task involving the emotional assessment of a series of images taken from the International Affective Picture System (IAPS), a database composed of pictures representing a wide range of semantic categories often used as a benchmark in psychological studies. Our results show that the AS is equivalent to SAM in the self-assessment of pleasure and arousal, with two added advantages: the AS does not require written instructions and it can be easily reproduced in latest-generation digital devices, including smartphones and tablets. Moreover, we compared new and normative IAPS ratings and found a general drop in reported arousal of pictorial stimuli. Not only do our results demonstrate that legacy scales for the self-report of affect can be replaced with new measurement tools developed in accordance to modern design principles, but also that standardized sets of stimuli which are widely adopted in research on human emotion are not as effective as they were in the past due to a general desensitization towards highly arousing content. PMID:26849361

  2. The Affective Slider: A Digital Self-Assessment Scale for the Measurement of Human Emotions.

    PubMed

    Betella, Alberto; Verschure, Paul F M J

    2016-01-01

    Self-assessment methods are broadly employed in emotion research for the collection of subjective affective ratings. The Self-Assessment Manikin (SAM), a pictorial scale developed in the eighties for the measurement of pleasure, arousal, and dominance, is still among the most popular self-reporting tools, despite having been conceived upon design principles which are today obsolete. By leveraging on state-of-the-art user interfaces and metacommunicative pictorial representations, we developed the Affective Slider (AS), a digital self-reporting tool composed of two slider controls for the quick assessment of pleasure and arousal. To empirically validate the AS, we conducted a systematic comparison between AS and SAM in a task involving the emotional assessment of a series of images taken from the International Affective Picture System (IAPS), a database composed of pictures representing a wide range of semantic categories often used as a benchmark in psychological studies. Our results show that the AS is equivalent to SAM in the self-assessment of pleasure and arousal, with two added advantages: the AS does not require written instructions and it can be easily reproduced in latest-generation digital devices, including smartphones and tablets. Moreover, we compared new and normative IAPS ratings and found a general drop in reported arousal of pictorial stimuli. Not only do our results demonstrate that legacy scales for the self-report of affect can be replaced with new measurement tools developed in accordance to modern design principles, but also that standardized sets of stimuli which are widely adopted in research on human emotion are not as effective as they were in the past due to a general desensitization towards highly arousing content. PMID:26849361

  3. Neural Coding of Cooperative vs. Affective Human Interactions: 150 ms to Code the Action's Purpose

    PubMed Central

    Proverbio, Alice Mado; Riva, Federica; Paganelli, Laura; Cappa, Stefano F.; Canessa, Nicola; Perani, Daniela; Zani, Alberto

    2011-01-01

    The timing and neural processing of the understanding of social interactions was investigated by presenting scenes in which 2 people performed cooperative or affective actions. While the role of the human mirror neuron system (MNS) in understanding actions and intentions is widely accepted, little is known about the time course within which these aspects of visual information are automatically extracted. Event-Related Potentials were recorded in 35 university students perceiving 260 pictures of cooperative (e.g., 2 people dragging a box) or affective (e.g., 2 people smiling and holding hands) interactions. The action's goal was automatically discriminated at about 150–170 ms, as reflected by occipito/temporal N170 response. The swLORETA inverse solution revealed the strongest sources in the right posterior cingulate cortex (CC) for affective actions and in the right pSTS for cooperative actions. It was found a right hemispheric asymmetry that involved the fusiform gyrus (BA37), the posterior CC, and the medial frontal gyrus (BA10/11) for the processing of affective interactions, particularly in the 155–175 ms time window. In a later time window (200–250 ms) the processing of cooperative interactions activated the left post-central gyrus (BA3), the left parahippocampal gyrus, the left superior frontal gyrus (BA10), as well as the right premotor cortex (BA6). Women showed a greater response discriminative of the action's goal compared to men at P300 and anterior negativity level (220–500 ms). These findings might be related to a greater responsiveness of the female vs. male MNS. In addition, the discriminative effect was bilateral in women and was smaller and left-sided in men. Evidence was provided that perceptually similar social interactions are discriminated on the basis of the agents' intentions quite early in neural processing, differentially activating regions devoted to face/body/action coding, the limbic system and the MNS. PMID:21760948

  4. Characterization of human-induced pluripotent stem cell-derived cardiomyocytes: bioenergetics and utilization in safety screening.

    PubMed

    Rana, Payal; Anson, Blake; Engle, Sandra; Will, Yvonne

    2012-11-01

    Cardiotoxicity remains the number one reason for drug withdrawal from the market, and Food and Drug Administration issued black box warnings, thus demonstrating the need for more predictive preclinical safety screening, especially early in the drug discovery process when much chemical substrate is available. Whereas human-ether-a-go-go related gene screening has become routine to mitigate proarrhythmic risk, the development of in vitro assays predicting additional on- and off-target biochemical toxicities will benefit from cellular models exhibiting true cardiomyocyte characteristics such as native tissue-like mitochondrial activity. Human stem cell-derived tissue cells may provide such a model. This hypothesis was tested using a combination of flux analysis, gene and protein expression, and toxicity-profiling techniques to characterize mitochondrial function in induced pluripotent stem cell (iPSC) derived human cardiomyocytes in the presence of differing carbon sources over extended periods in cell culture. Functional analyses demonstrate that iPSC-derived cardiomyocytes are (1) capable of utilizing anaerobic or aerobic respiration depending upon the available carbon substrate and (2) bioenergetically closest to adult heart tissue cells when cultured in galactose or galactose supplemented with fatty acids. We utilized this model to test a variety of kinase inhibitors with known clinical cardiac liabilities for their potential toxicity toward these cells. We found that the kinase inhibitors showed a dose-dependent toxicity to iPSC cardiomyocytes grown in galactose and that oxygen consumption rates were significantly more affected than adenosine triphosphate production. Sorafenib was found to have the most effect, followed by sunitinib, dasatinib, imatinib, lapatinib, and nioltinib. PMID:22843568

  5. Exposure to Phthalates Affects Calcium Handling and Intercellular Connectivity of Human Stem Cell-Derived Cardiomyocytes

    PubMed Central

    Posnack, Nikki Gillum; Idrees, Rabia; Ding, Hao; Jaimes III, Rafael; Stybayeva, Gulnaz; Karabekian, Zaruhi; Laflamme, Michael A.; Sarvazyan, Narine

    2015-01-01

    Background The pervasive nature of plastics has raised concerns about the impact of continuous exposure to plastic additives on human health. Of particular concern is the use of phthalates in the production of flexible polyvinyl chloride (PVC) products. Di-2-ethylhexyl-phthalate (DEHP) is a commonly used phthalate ester plasticizer that imparts flexibility and elasticity to PVC products. Recent epidemiological studies have reported correlations between urinary phthalate concentrations and cardiovascular disease, including an increased risk of high blood pressure and coronary risk. Yet, there is little direct evidence linking phthalate exposure to adverse effects in human cells, including cardiomyocytes. Methods and Results The effect of DEHP on calcium handling was examined using monolayers of gCAMP3 human embryonic stem cell-derived cardiomyocytes, which contain an endogenous calcium sensor. Cardiomyocytes were exposed to DEHP (5 – 50 μg/mL), and calcium transients were recorded using a Zeiss confocal imaging system. DEHP exposure (24 – 72 hr) had a negative chronotropic and inotropic effect on cardiomyocytes, increased the minimum threshold voltage required for external pacing, and modified connexin-43 expression. Application of Wy-14,643 (100 μM), an agonist for the peroxisome proliferator-activated receptor alpha, did not replicate DEHP’s effects on calcium transient morphology or spontaneous beating rate. Conclusions Phthalates can affect the normal physiology of human cardiomyocytes, including DEHP elicited perturbations in cardiac calcium handling and intercellular connectivity. Our findings call for additional studies to clarify the extent by which phthalate exposure can alter cardiac function, particularly in vulnerable patient populations who are at risk for high phthalate exposure. PMID:25799571

  6. Training experience in gestures affects the display of social gaze in baboons' communication with a human.

    PubMed

    Bourjade, Marie; Canteloup, Charlotte; Meguerditchian, Adrien; Vauclair, Jacques; Gaunet, Florence

    2015-01-01

    Gaze behaviour, notably the alternation of gaze between distal objects and social partners that accompanies primates' gestural communication is considered a standard indicator of intentionality. However, the developmental precursors of gaze behaviour in primates' communication are not well understood. Here, we capitalized on the training in gestures dispensed to olive baboons (Papio anubis) as a way of manipulating individual communicative experience with humans. We aimed to delineate the effects of such a training experience on gaze behaviour displayed by the monkeys in relation with gestural requests. Using a food-requesting paradigm, we compared subjects trained in requesting gestures (i.e. trained subjects) to naïve subjects (i.e. control subjects) for their occurrences of (1) gaze behaviour, (2) requesting gestures and (3) temporal combination of gaze alternation with gestures. We found that training did not affect the frequencies of looking at the human's face, looking at food or alternating gaze. Hence, social gaze behaviour occurs independently from the amount of communicative experience with humans. However, trained baboons-gesturing more than control subjects-exhibited most gaze alternation combined with gestures, whereas control baboons did not. By reinforcing the display of gaze alternation along with gestures, we suggest that training may have served to enhance the communicative function of hand gestures. Finally, this study brings the first quantitative report of monkeys producing requesting gestures without explicit training by humans (controls). These results may open a window on the developmental mechanisms (i.e. incidental learning vs. training) underpinning gestural intentional communication in primates. PMID:25138999

  7. Regulatory, biosafety and safety challenges for novel cells as substrates for human vaccines.

    PubMed

    Hess, Ralf D; Weber, Friedemann; Watson, Keith; Schmitt, Siegfried

    2012-04-01

    In the development of novel substrates used for production of human vaccines there has been significant progress made in recent years. Emerging and re-emerging infectious diseases like the recent porcine Influenza A virus (H1N1) pandemic necessitated the availability of unprecedented amounts of vaccines. In addition, the high demand for vaccines in the industrialised countries has also been paralleled by a steep increase in demand in developing countries. The manufacturing capability for viral vaccines produced in embryonated hen eggs and conventional/classical cell substrates, such as chicken embryo fibroblasts, has now reached its capacity limit. This constraint may be overcome by utilising other recognised cell substrates such as Madin Darby Canine Kidney (MDCK) (dog origin), Chinese Hamster Ovary (CHO) (hamster cells) or Vero cells (monkey origin) or as an alternative, introduce new cell substrates of human or avian origin. Using new cell substrates may prove to be a highly replication-proficient way of producing live viral vaccines such as Influenza A viruses. Despite some advantages, cell substrates may pose a small residual risk to humans since some of them are known to be tumourigenic in immunosuppressed animals. However, this residual risk should be considered acceptable by regulators. Safety testing requirements for cell substrates used in the manufacture of vaccines is mandated by published guidance from organisations such as World Health Organization (WHO), United States Food and Drug Administration (FDA), European Medicines Agency (EMA) and International Conferences on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human use (ICH) as well as requirements laid down in compendial monographs (Ph. Eur. and USP). This paper considers the guidance contained in these regulatory documents. In addition, the safety challenges and almost arbitrary risk-based classification of cell substrates used in the production of human

  8. Safety Assessment of Two New Lactobacillus Strains as Probiotic for Human Using a Rat Model

    PubMed Central

    Shokryazdan, Parisa; Faseleh Jahromi, Mohammad; Liang, Juan Boo; Kalavathy, Ramasamy; Sieo, Chin Chin; Ho, Yin Wan

    2016-01-01

    Two previously isolated Lactobacillus strains (L. fermentum HM3 from human milk and L. buchneri FD2 from fermented dates), intended as probiotic for human, were assessed for their safety using acute and subacute oral toxicity tests in rats. In addition, their effects on cecal microflora and harmful bacterial enzymes (β-glucuronidase and β-glucosidase) of the tested animals were also determined. The results showed that L. buchneri FD2, L. fermentum HM3, or a mixture of them were safe up to a level of 1010 CFU/kg BW/day in a 14-day or 28-day treatment period. Both strains were well tolerated and there were no observed adverse effects on growth, feed consumption, cellular blood components and vital organs of the treated animals. The Lactobacillus strains were also able to reduce harmful intestinal bacterial enzymes, and decrease pathogenic bacterial populations while increasing beneficial bacterial populations. These results suggest that the two Lactobacillus strains are safe and could be potential probiotic for human. PMID:27467068

  9. Safety Assessment of Two New Lactobacillus Strains as Probiotic for Human Using a Rat Model.

    PubMed

    Shokryazdan, Parisa; Faseleh Jahromi, Mohammad; Liang, Juan Boo; Kalavathy, Ramasamy; Sieo, Chin Chin; Ho, Yin Wan

    2016-01-01

    Two previously isolated Lactobacillus strains (L. fermentum HM3 from human milk and L. buchneri FD2 from fermented dates), intended as probiotic for human, were assessed for their safety using acute and subacute oral toxicity tests in rats. In addition, their effects on cecal microflora and harmful bacterial enzymes (β-glucuronidase and β-glucosidase) of the tested animals were also determined. The results showed that L. buchneri FD2, L. fermentum HM3, or a mixture of them were safe up to a level of 1010 CFU/kg BW/day in a 14-day or 28-day treatment period. Both strains were well tolerated and there were no observed adverse effects on growth, feed consumption, cellular blood components and vital organs of the treated animals. The Lactobacillus strains were also able to reduce harmful intestinal bacterial enzymes, and decrease pathogenic bacterial populations while increasing beneficial bacterial populations. These results suggest that the two Lactobacillus strains are safe and could be potential probiotic for human. PMID:27467068

  10. Safety pharmacology, toxicology and pharmacokinetic assessment of human Gc globulin (vitamin D binding protein).

    PubMed

    Pihl, Tina Holberg; Jørgensen, Charlotte Svaerke; Santoni-Rugiu, Eric; Leifsson, Páll Skúli; Hansen, Erik Wind; Laursen, Inga; Houen, Gunnar

    2010-11-01

    Gc globulin is an important protein of the plasma actin-scavenger system. As such, it has been shown to bind free actin and prevent hypercoagulation and shock in patients with massive actin release resulting from severe tissue injuries. Treatment of such patients with Gc globulin could therefore potentially be life-saving. This article presents pre-clinical toxicology experiments conducted on purified plasma-derived human Gc globulin. The Gc globulin formulation was shown to be stable for at least 4 years with full retention of actin-binding capacity. In vitro studies did not reveal activation of the kallikrein system or the complement system and cellular studies showed no toxic effects on a variety of human cell lines. In vivo studies showed no acute toxic effects in mice, rats or guinea pigs upon intravenous infusion. A 14-day local tolerance study in rabbits showed no adverse effects, and 14-day toxicity studies in rats and horses did not show any unwanted reactions. In a 14-day toxicology study in beagle dogs, formation of antibodies was seen and in the end of the study period, three out of four dogs showed clinical immunological reactions, which could be ascribed to the formation of antibodies. The half-life, T, for human Gc globulin was 12 hr in rats, 16 hr in horses and 30 hr in dogs. The safety profile of plasma-derived Gc globulin is concluded to be consistent to that required for use in man. PMID:20560927

  11. Factors Affecting the Absorption, Metabolism, and Excretion of Cocoa Flavanols in Humans.

    PubMed

    Cifuentes-Gomez, Tania; Rodriguez-Mateos, Ana; Gonzalez-Salvador, Isidro; Alañon, María Elena; Spencer, Jeremy P E

    2015-09-01

    Cocoa is rich in a subclass of flavonoids known as flavanols, the cardiovascular health benefits of which have been extensively reported. The appearance of flavanol metabolites in the systemic circulation after flavanol-rich food consumption is likely to mediate the physiological effects on the vascular system, and these levels are influenced by numerous factors, including food matrix, processing, intake, age, gender, or genetic polymorphisms, among others. This review will focus on our current understanding of factors affecting the absorption, metabolism, and excretion of cocoa flavanols in humans. Second, it will identify gaps in these contributing factors that need to be addressed to conclusively translate our collective knowledge into the context of public health, dietary guidelines, and evidence-based dietary recommendations. PMID:25711140

  12. Expression in cultured human neuroblastoma cells of epitopes associated with affected neurons in Alzheimer's disease.

    PubMed Central

    Ko, L. W.; Sheu, K. F.; Young, O.; Thaler, H.; Blass, J. P.

    1990-01-01

    Of three human neuroblastoma lines tested, IMR32K (and IMR32 parental line) was the only cell line that, after its exposure to a differentiation medium, consistently developed materials recognized immunocytochemically by a panel of antibodies against paired helical filaments (PHF). Ultrastructurally, these cells accumulated, at their perikarya and neuritic extensions, spatially discrete arrays of fibrils, which occasionally occurred in twisted pairs. When these fibrillar structures appeared as paired helices, they exhibited dimensions and configurations reminiscent of PHF found in affected Alzheimer neurons, although less compact. Immunoelectron microscope examinations of the fibrillar structures in these neuroblastoma cells with one of these anti-PHF immunoprobes revealed that only subsets of fibrillar structures that appeared thickened or aggregated to form bundles were selectively immunolabeled. Cultures of these immortal neuroblastoma lines may provide a convenient model for studying aspects of PHF formation that are hard to examine in Alzheimer brain obtained at autopsy. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:1691594

  13. Controlling a virtual forehand prosthesis using an adaptive and affective Human-Machine Interface.

    PubMed

    Rezazadeh, I Mohammad; Firoozabadi, S M P; Golpayegani, S M R Hashemi; Hu, H

    2011-01-01

    This paper presents the design of an adaptable Human-Machine Interface (HMI) for controlling virtual forearm prosthesis. Direct physical performance measures (obtained score and completion time) for the requested tasks were calculated. Furthermore, bioelectric signals from the forehead were recorded using one pair of electrodes placed on the frontal region of the subject head to extract the mental (affective) measures while performing the tasks. By employing the proposed algorithm and above measures, the proposed HMI can adapt itself to the subject's mental states, thus improving the usability of the interface. The quantitative results from 15 subjects show that the proposed HMI achieved better physical performance measures in comparison to a conventional non-adaptive myoelectric controller (p < 0.001). PMID:22255248

  14. Copper, lead and zinc concentrations of human breast milk as affected by maternal dietary practices

    SciTech Connect

    Umoren, J.; Kies, C.

    1986-03-01

    Maternal dietary practices have been found to affect the concentrations of some nutrients in human breast milk. Lead toxicity is a concern in young children. Lead, copper and zinc are thought to compete for intestinal absorption sites. The objective of the current project was to compare copper, lead and zinc contents of breast milk from practicing lacto-vegetarian and omnivore, lactating women at approximately four months post-partum. Analyses were done by atomic absorption spectrophotometry using a carbon rod attachment. Copper concentrations were higher in milk samples from lacto-ovo-vegetarians. Milk samples from the omnivores had the highest lead and zinc concentrations. Lead and copper concentrations in milk were negatively correlated. The higher zinc concentrations in the milk of the omnivore women may have been related to better utilization of zinc from meat than from plant food sources.

  15. Gangliosides do not affect ABC transporter function in human neuroblastoma cells.

    PubMed

    Dijkhuis, Anne-Jan; Klappe, Karin; Kamps, Willem; Sietsma, Hannie; Kok, Jan Willem

    2006-06-01

    Previous studies have indicated a role for glucosylceramide synthase (GCS) in multidrug resistance (MDR), either related to turnover of ceramide (Cer) or generation of gangliosides, which modulate apoptosis and/or the activity of ABC transporters. This study challenges the hypothesis that gangliosides modulate the activity of ABC transporters and was performed in two human neuroblastoma cell lines, expressing either functional P-glycoprotein (Pgp) or multidrug resistance-related protein 1 (MRP1). Two inhibitors of GCS, D,L-threo-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol (t-PPPP) and N-butyldeoxynojirimycin (NB-dNJ), very efficiently depleted ganglioside content in two human neuroblastoma cell lines. This was established by three different assays: equilibrium radiolabeling, cholera toxin binding, and mass analysis. Fluorescence-activated cell sorting (FACS) analysis showed that ganglioside depletion only slightly and in the opposite direction affected Pgp- and MRP1-mediated efflux activity. Moreover, both effects were marginal compared with those of well-established inhibitors of either MRP1 (i.e., MK571) or Pgp (i.e., GF120918). t-PPPP slightly enhanced cellular sensitivity to vincristine, as determined by 3-[4,5-dimethylthiazol-2-yl]2,5-diphenyl tetrazolium bromide analysis, in both neuroblastoma cell lines, whereas NB-dNJ was without effect. MRP1 expression and its localization in detergent-resistant membranes were not affected by ganglioside depletion. Together, these results show that gangliosides are not relevant to ABC transporter-mediated MDR in neuroblastoma cells. PMID:16547352

  16. Amyloid Precursor Protein (APP) Affects Global Protein Synthesis in Dividing Human Cells

    PubMed Central

    Liang, Shuang; Rambo, Brittany; Skucha, Sylvia; Weber, Megan J.; Alani, Sara; Bocchetta, Maurizio

    2015-01-01

    Hypoxic non-small cell lung cancer (NSCLC) is dependent on Notch-1 signaling for survival. Targeting Notch-1 by means of γ-secretase inhibitors (GSI) proved effective in killing hypoxic NSCLC. Post-mortem analysis of GSI-treated, NSCLC-burdened mice suggested enhanced phosphorylation of 4E-BP1 at threonines 37/46 in hypoxic tumor tissues. In vitro dissection of this phenomenon revealed that Amyloid Precursor Protein (APP) inhibition was responsible for a non-canonical 4E-BP1 phosphorylation pattern rearrangement—a process, in part, mediated by APP regulation of the pseudophosphatase Styx. Upon APP depletion we observed modifications of eIF-4F composition indicating increased recruitment of eIF-4A to the mRNA cap. This phenomenon was supported by the observation that cells with depleted APP were partially resistant to silvestrol, an antibiotic that interferes with eIF-4A assembly into eIF-4F complexes. APP downregulation in dividing human cells increased the rate of global protein synthesis, both cap- and IRES-dependent. Such an increase seemed independent of mTOR inhibition. After administration of Torin-1, APP downregulation and Mechanistic Target of Rapamycin Complex 1 (mTORC-1) inhibition affected 4E-BP1 phosphorylation and global protein synthesis in opposite fashions. Additional investigations indicated that APP operates independently of mTORC-1. Key phenomena described in this study were reversed by overexpression of the APP C-terminal domain. The presented data suggest that APP may be a novel regulator of protein synthesis in dividing human cells, both cancerous and primary. Furthermore, APP appears to affect translation initiation using mechanisms seemingly dissimilar to mTORC-1 regulation of cap-dependent protein synthesis. PMID:25283437

  17. Amyloid precursor protein (APP) affects global protein synthesis in dividing human cells.

    PubMed

    Sobol, Anna; Galluzzo, Paola; Liang, Shuang; Rambo, Brittany; Skucha, Sylvia; Weber, Megan J; Alani, Sara; Bocchetta, Maurizio

    2015-05-01

    Hypoxic non-small cell lung cancer (NSCLC) is dependent on Notch-1 signaling for survival. Targeting Notch-1 by means of γ-secretase inhibitors (GSI) proved effective in killing hypoxic NSCLC. Post-mortem analysis of GSI-treated, NSCLC-burdened mice suggested enhanced phosphorylation of 4E-BP1 at threonines 37/46 in hypoxic tumor tissues. In vitro dissection of this phenomenon revealed that Amyloid Precursor Protein (APP) inhibition was responsible for a non-canonical 4E-BP1 phosphorylation pattern rearrangement-a process, in part, mediated by APP regulation of the pseudophosphatase Styx. Upon APP depletion we observed modifications of eIF-4F composition indicating increased recruitment of eIF-4A to the mRNA cap. This phenomenon was supported by the observation that cells with depleted APP were partially resistant to silvestrol, an antibiotic that interferes with eIF-4A assembly into eIF-4F complexes. APP downregulation in dividing human cells increased the rate of global protein synthesis, both cap- and IRES-dependent. Such an increase seemed independent of mTOR inhibition. After administration of Torin-1, APP downregulation and Mechanistic Target of Rapamycin Complex 1 (mTORC-1) inhibition affected 4E-BP1 phosphorylation and global protein synthesis in opposite fashions. Additional investigations indicated that APP operates independently of mTORC-1. Key phenomena described in this study were reversed by overexpression of the APP C-terminal domain. The presented data suggest that APP may be a novel regulator of protein synthesis in dividing human cells, both cancerous and primary. Furthermore, APP appears to affect translation initiation using mechanisms seemingly dissimilar to mTORC-1 regulation of cap-dependent protein synthesis. PMID:25283437

  18. Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date.

    PubMed

    Sami, Musa Basser; Rabiner, Eugenii A; Bhattacharyya, Sagnik

    2015-08-01

    A significant body of epidemiological evidence has linked psychotic symptoms with both acute and chronic use of cannabis. Precisely how these effects of THC are mediated at the neurochemical level is unclear. While abnormalities in multiple pathways may lead to schizophrenia, an abnormality in dopamine neurotransmission is considered to be the final common abnormality. One would thus expect cannabis use to be associated with dopamine signaling alterations. This is the first systematic review of all studies, both observational as well as experimental, examining the acute as well as chronic effect of cannabis or its main psychoactive ingredient, THC, on the dopamine system in man. We aimed to review all studies conducted in man, with any reported neurochemical outcomes related to the dopamine system after cannabis, cannabinoid or endocannabinoid administration or use. We identified 25 studies reporting outcomes on over 568 participants, of which 244 participants belonged to the cannabis/cannabinoid exposure group. In man, there is as yet little direct evidence to suggest that cannabis use affects acute striatal dopamine release or affects chronic dopamine receptor status in healthy human volunteers. However some work has suggested that acute cannabis exposure increases dopamine release in striatal and pre-frontal areas in those genetically predisposed for, or at clinical high risk of psychosis. Furthermore, recent studies are suggesting that chronic cannabis use blunts dopamine synthesis and dopamine release capacity. Further well-designed studies are required to definitively delineate the effects of cannabis use on the dopaminergic system in man. PMID:26068702

  19. Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain

    PubMed Central

    Richards, Alexander L; Jones, Lesley; Moskvina, Valentina; Kirov, George; Gejman, Pablo V; Levinson, Douglas F; Sanders, Alan R; Purcell, Shaun; Visscher, Peter M; Craddock, Nick; Owen, Michael J; Holmans, Peter; O’Donovan, Michael C

    2016-01-01

    It is widely thought that alleles that influence susceptibility to common diseases, including schizophrenia, will frequently do so through effects on gene expression. Since only a small proportion of the genetic variance for schizophrenia has been attributed to specific loci, this remains an unproven hypothesis. The International Schizophrenia Consortium (ISC) recently reported a substantial polygenic contribution to that disorder, and that schizophrenia risk alleles are enriched among SNPs selected for marginal evidence for association (p<0.5) from genome wide association studies (GWAS). It follows that if schizophrenia susceptibility alleles are enriched for those that affect gene expression, those marginally associated SNPs which are also eQTLs should carry more true association signals compared with SNPs which are not. To test this, we identified marginally associated (p<0.5) SNPs from two of the largest available schizophrenia GWAS datasets. We assigned eQTL status to those SNPs based upon an eQTL dataset derived from adult human brain. Using the polygenic score method of analysis reported by the ISC, we observed and replicated the observation that higher probability cis-eQTLs predicted schizophrenia better than those with a lower probability for being a cis-eQTL. Our data support the hypothesis that alleles conferring risk of schizophrenia are enriched among those that affect gene expression. Moreover, our data show that notwithstanding the likely developmental origin of schizophrenia, studies of adult brain tissue can in principle allow relevant susceptibility eQTLs to be identified. PMID:21339752

  20. Azithromycin differentially affects the IL-13-induced expression profile in human bronchial epithelial cells.

    PubMed

    Mertens, Tinne C J; Hiemstra, Pieter S; Taube, Christian

    2016-08-01

    The T helper 2 (Th2) cytokine interleukin(IL)-13 is a central regulator in goblet cell metaplasia and induces the recently described Th2 gene signature consisting of periostin (POSTN), chloride channel regulator 1 (CLCA1) and serpin B2 (SERPINB2) in airway epithelial cells. This Th2 gene signature has been proposed as a biomarker to classify asthma into Th2-high and Th2-low phenotypes. Clinical studies have shown that the macrolide antibiotic azithromycin reduced clinical symptoms in neutrophilic asthma, but not in the classical Th2-mediated asthma despite the ability of azithromycin to reduce IL-13-induced mucus production. We therefore hypothesize that azithromycin differentially affects the IL-13-induced expression profile. To investigate this, we focus on IL-13-induced mucin and Th2-signature expression in human bronchial epithelial cells and how this combined expression profile is affected by azithromycin treatment. Primary bronchial epithelial cells were differentiated at air liquid interface in presence of IL-13 with or without azithromycin. Azithromycin inhibited IL-13-induced MUC5AC, which was accompanied by inhibition of IL-13-induced CLCA1 and SERPINB2 expression. In contrast, IL-13-induced expression of POSTN was further increased in cells treated with azithromycin. This indicates that azithromycin has a differential effect on the IL-13-induced Th2 gene signature. Furthermore, the ability of azithromycin to decrease IL-13-induced MUC5AC expression may be mediated by a reduction in CLCA1. PMID:27246785

  1. Human resources management and firm performance: The differential role of managerial affective and continuance commitment.

    PubMed

    Gong, Yaping; Law, Kenneth S; Chang, Song; Xin, Katherine R

    2009-01-01

    In this study, the authors developed a dual-concern (i.e., maintenance and performance) model of human resources (HR) management. The authors identified commonly examined HR practices that apply to the middle manager level and classified them into the maintenance- and performance-oriented HR subsystems. The authors found support for the 2-factor model on the basis of responses from 2,148 managers from 463 firms operating in China. Regression results indicate that the performance-oriented HR subsystems had a positive relationship with firm performance and that the relationship was mediated by middle managers' affective commitment to the firm. The maintenance-oriented HR subsystems had a positive relationship with middle managers' continuance commitment but not with their affective commitment and firm performance. This study contributes to the understanding of how HR practices relate to firm performance and offers an improved test of the argument that valuable and firm-specific HR provide a source of competitive advantage. (PsycINFO Database Record (c) 2009 APA, all rights reserved). PMID:19186911

  2. Glyceroglycolipids Affect Uptake of Carotenoids Solubilized in Mixed Micelles by Human Intestinal Caco-2 Cells.

    PubMed

    Kotake-Nara, Eiichi; Yonekura, Lina; Nagao, Akihiko

    2015-09-01

    We previously reported that phospholipids markedly affected the uptake of carotenoids solubilized in mixed micelles by human intestinal Caco-2 cells. In the present study, we found that two classes of dietary glyceroglycolipids and the corresponding lysoglyceroglycolipids affected uptake of β-carotene and lutein by differentiated Caco-2 cells. The levels of carotenoid uptake from micelles containing digalactosyldiacylglycerol or sulfoquinovosyldiacylglycerol were significantly lower than that from control micelles. On the other hand, the uptakes from micelles containing digalactosylmonoacylglycerol or sulfoquinovosylmonoacylglycerol were significantly higher than that from control micelles. In dispersed cells and Caco-2 cells with poor cell-to-cell adhesion, however, the levels of uptake from micelles containing these lyso-lipids were much lower than that from control micelles. The uptake levels from control micelles were markedly decreased depending on the development of cell-to-cell/cell-matrix adhesion in Caco-2 cells, but the uptake levels from the micelles containing these lyso-lipids were not substantially changed, suggesting that the intercellular barrier formed by cell-to-cell/cell-matrix adhesion inhibited the uptake from control micelles, but not from the lyso-lipid-containing micelles. The lyso-lipids appeared to enhance carotenoid uptake by decreasing the intercellular barrier integrity. The results showed that some types of glyceroglycolipids have the potential to modify the intestinal uptake of carotenoids. PMID:26012480

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

    PubMed Central

    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. PMID:26529236

  4. Rewards, aversions and affect in adolescence: Emerging convergences across laboratory animal and human data

    PubMed Central

    Spear, Linda Patia

    2011-01-01

    The adolescent transition is associated with increases in reward- and sensation-seeking, peer-directed social interactions, and risk-taking, with exploratory use of alcohol and other drugs often beginning at this time. These age-related behaviors may have biological roots embedded in the evolutionary past, with similar adolescent-typical characteristics evident across a variety of mammalian species. Drawing across human behavioral and fMRI data and studies conducting in laboratory animals, this review examines processing of rewards, aversions, and affect in adolescence. Evidence for both hyper- and hypo-reactivity during adolescence in the processing of rewards is reviewed, along with possible contributors to these differences. Indications of sometimes heightened reward reactivity during adolescence are contrasted with frequent attenuations in adolescent sensitivity to aversive stimuli. At the same time, adolescents appear particularly prone to becoming emotionally aroused, especially in social contexts. Emerging evidence hints that exaggerated adolescent reactivity in reward and affective systems may be promoted in part by unusual strong cross-reactivity between these systems during adolescence. Such age-related propensities may promote adolescent risk taking, especially in social and exciting contexts, and contribute to adolescent-typical propensities to attach greater benefit and less cost to risky behaviors such as alcohol and drug use than individuals at other ages. PMID:21918675

  5. Human factors and safety issues associated with actinide retrieval from spent light water reactor fuel assemblies

    SciTech Connect

    Spelt, P.F.

    1992-01-01

    A major problem in environmental restoration and waste management is the disposition of used fuel assemblies from the many light water reactors in the United States, which present a radiation hazard to those whose job is to dispose of them, with a similar threat to the general environment associated with long-term storage in fuel repositories around the country. Actinides resident in the fuel pins as a result of their use in reactor cores constitute a significant component of this hazard. Recently, the Department of Energy has initiated an Actinide Recycle Program to study the feasibility of using pyrochemical (molten salt) processes to recover actinides from the spent fuel assemblies of commercial reactors. This project concerns the application of robotics technology to the operation and maintenance functions of a plant whose objective is to recover actinides from spent fuel assemblies, and to dispose of the resulting hardware and chemical components from this process. Such a procedure involves a number of safety and human factors issues. The purpose of the project is to explore the use of robotics and artificial intelligence to facilitate accomplishment of the program goals while maintaining the safety of the humans doing the work and the integrity of the environment. This project will result in a graphic simulation on a Silicon Graphics workstation as a proof of principle demonstration of the feasibility of using robotics along with an intelligent operator interface. A major component of the operator-system interface is a hybrid artificial intelligence system developed at Oak Ridge National Laboratory, which combines artificial neural networks and an expert system into a hybrid, self-improving computer-based system interface. 10 refs.

  6. Human factors and safety issues associated with actinide retrieval from spent light water reactor fuel assemblies

    SciTech Connect

    Spelt, P.F.

    1992-08-01

    A major problem in environmental restoration and waste management is the disposition of used fuel assemblies from the many light water reactors in the United States, which present a radiation hazard to those whose job is to dispose of them, with a similar threat to the general environment associated with long-term storage in fuel repositories around the country. Actinides resident in the fuel pins as a result of their use in reactor cores constitute a significant component of this hazard. Recently, the Department of Energy has initiated an Actinide Recycle Program to study the feasibility of using pyrochemical (molten salt) processes to recover actinides from the spent fuel assemblies of commercial reactors. This project concerns the application of robotics technology to the operation and maintenance functions of a plant whose objective is to recover actinides from spent fuel assemblies, and to dispose of the resulting hardware and chemical components from this process. Such a procedure involves a number of safety and human factors issues. The purpose of the project is to explore the use of robotics and artificial intelligence to facilitate accomplishment of the program goals while maintaining the safety of the humans doing the work and the integrity of the environment. This project will result in a graphic simulation on a Silicon Graphics workstation as a proof of principle demonstration of the feasibility of using robotics along with an intelligent operator interface. A major component of the operator-system interface is a hybrid artificial intelligence system developed at Oak Ridge National Laboratory, which combines artificial neural networks and an expert system into a hybrid, self-improving computer-based system interface. 10 refs.

  7. In silico assessment of drug safety in human heart applied to late sodium current blockers

    PubMed Central

    Trenor, Beatriz; Gomis-Tena, Julio; Cardona, Karen; Romero, Lucia; Rajamani, Sridharan; Belardinelli, Luiz; Giles, Wayne R; Saiz, Javier

    2013-01-01

    Drug-induced action potential (AP) prolongation leading to Torsade de Pointes is a major concern for the development of anti-arrhythmic drugs. Nevertheless the development of improved anti-arrhythmic agents, some of which may block different channels, remains an important opportunity. Partial block of the late sodium current (INaL) has emerged as a novel anti-arrhythmic mechanism. It can be effective in the settings of free radical challenge or hypoxia. In addition, this approach can attenuate pro-arrhythmic effects of blocking the rapid delayed rectifying K+ current (IKr). The main goal of our computational work was to develop an in-silico tool for preclinical anti-arrhythmic drug safety assessment, by illustrating the impact of IKr/INaL ratio of steady-state block of drug candidates on “torsadogenic” biomarkers. The O’Hara et al. AP model for human ventricular myocytes was used. Biomarkers for arrhythmic risk, i.e., AP duration, triangulation, reverse rate-dependence, transmural dispersion of repolarization and electrocardiogram QT intervals, were calculated using single myocyte and one-dimensional strand simulations. Predetermined amounts of block of INaL and IKr were evaluated. “Safety plots” were developed to illustrate the value of the specific biomarker for selected combinations of IC50s for IKr and INaL of potential drugs. The reference biomarkers at baseline changed depending on the “drug” specificity for these two ion channel targets. Ranolazine and GS967 (a novel potent inhibitor of INaL) yielded a biomarker data set that is considered safe by standard regulatory criteria. This novel in-silico approach is useful for evaluating pro-arrhythmic potential of drugs and drug candidates in the human ventricle. PMID:23696033

  8. Quiescence does not affect p53 and stress response by irradiation in human lung fibroblasts

    SciTech Connect

    Dai, Jiawen; Itahana, Koji; Baskar, Rajamanickam

    2015-02-27

    Cells in many organs exist in both proliferating and quiescent states. Proliferating cells are more radio-sensitive, DNA damage pathways including p53 pathway are activated to undergo either G{sub 1}/S or G{sub 2}/M arrest to avoid entering S and M phase with DNA damage. On the other hand, quiescent cells are already arrested in G{sub 0}, therefore there may be fundamental difference of irradiation response between proliferating and quiescent cells, and this difference may affect their radiosensitivity. To understand these differences, proliferating and quiescent human normal lung fibroblasts were exposed to 0.10–1 Gy of γ-radiation. The response of key proteins involved in the cell cycle, cell death, and metabolism as well as histone H2AX phosphorylation were examined. Interestingly, p53 and p53 phosphorylation (Ser-15), as well as the cyclin-dependent kinase inhibitors p21 and p27, were induced similarly in both proliferating and quiescent cells after irradiation. Furthermore, the p53 protein half-life, and expression of cyclin A, cyclin E, proliferating cell nuclear antigen (PCNA), Bax, or cytochrome c expression as well as histone H2AX phosphorylation were comparable after irradiation in both phases of cells. The effect of radioprotection by a glycogen synthase kinase 3β inhibitor on p53 pathway was also similar between proliferating and quiescent cells. Our results showed that quiescence does not affect irradiation response of key proteins involved in stress and DNA damage at least in normal fibroblasts, providing a better understanding of the radiation response in quiescent cells, which is crucial for tissue repair and regeneration. - Highlights: • p53 response by irradiation was similar between proliferating and quiescent cells. • Quiescent cells showed similar profiles of cell cycle proteins after irradiation. • Radioprotection of GSK-3β inhibitor caused similar effects between these cells. • Quiescence did not affect p53 response despite its

  9. Larval food quantity affects the capacity of adult mosquitoes to transmit human malaria.

    PubMed

    Shapiro, Lillian L M; Murdock, Courtney C; Jacobs, Gregory R; Thomas, Rachel J; Thomas, Matthew B

    2016-07-13

    Adult traits of holometabolous insects are shaped by conditions experienced during larval development, which might impact interactions between adult insect hosts and parasites. However, the ecology of larval insects that vector disease remains poorly understood. Here, we used Anopheles stephensi mosquitoes and the human malaria parasite Plasmodium falciparum, to investigate whether larval conditions affect the capacity of adult mosquitoes to transmit malaria. We reared larvae in two groups; one group received a standard laboratory rearing diet, whereas the other received a reduced diet. Emerging adult females were then provided an infectious blood meal. We assessed mosquito longevity, parasite development rate and prevalence of infectious mosquitoes over time. Reduced larval food led to increased adult mortality and caused a delay in parasite development and a slowing in the rate at which parasites invaded the mosquito salivary glands, extending the time it took for mosquitoes to become infectious. Together, these effects increased transmission potential of mosquitoes in the high food regime by 260-330%. Such effects have not, to our knowledge, been shown previously for human malaria and highlight the importance of improving knowledge of larval ecology to better understand vector-borne disease transmission dynamics. PMID:27412284

  10. 50 Hz sinusoidal magnetic fields do not affect human lymphocyte activation and proliferation in vitro

    NASA Astrophysics Data System (ADS)

    Capri, Miriam; Mesirca, Pietro; Remondini, Daniel; Carosella, Simona; Pasi, Sara; Castellani, Gastone; Franceschi, Claudio; Bersani, Ferdinando

    2004-12-01

    In the last 30 years, an increasing public concern about the possible harmful effects of electromagnetic fields generated by power lines and domestic appliances has pushed the scientific community to search for a correct and comprehensive answer to this problem. In this work the effects of exposure to 50 Hz sinusoidal magnetic fields, with a magnetic flux density of 0.05 mT and 2.5 mT (peak values), were studied on human peripheral blood mononuclear cells (PBMCs) collected from healthy young and elderly donors. Cell activation and proliferation were investigated by using flow cytometry techniques and 3H-TdR incorporation assays, respectively. The results obtained indicated that exposure to the fields altered neither DNA synthesis nor the capacity of lymphocytes to enter the activation phase and progress into the cell cycle. Thus, the conclusions are that two important functional phases of human lymphocytes, such as activation and proliferation, are not affected by exposures to 50 Hz magnetic fields similar to those found under power lines.

  11. Larval food quantity affects the capacity of adult mosquitoes to transmit human malaria

    PubMed Central

    Shapiro, Lillian L. M.; Murdock, Courtney C.; Jacobs, Gregory R.; Thomas, Rachel J.; Thomas, Matthew B.

    2016-01-01

    Adult traits of holometabolous insects are shaped by conditions experienced during larval development, which might impact interactions between adult insect hosts and parasites. However, the ecology of larval insects that vector disease remains poorly understood. Here, we used Anopheles stephensi mosquitoes and the human malaria parasite Plasmodium falciparum, to investigate whether larval conditions affect the capacity of adult mosquitoes to transmit malaria. We reared larvae in two groups; one group received a standard laboratory rearing diet, whereas the other received a reduced diet. Emerging adult females were then provided an infectious blood meal. We assessed mosquito longevity, parasite development rate and prevalence of infectious mosquitoes over time. Reduced larval food led to increased adult mortality and caused a delay in parasite development and a slowing in the rate at which parasites invaded the mosquito salivary glands, extending the time it took for mosquitoes to become infectious. Together, these effects increased transmission potential of mosquitoes in the high food regime by 260–330%. Such effects have not, to our knowledge, been shown previously for human malaria and highlight the importance of improving knowledge of larval ecology to better understand vector-borne disease transmission dynamics. PMID:27412284

  12. Lead and cadmium at very low doses affect in vitro immune response of human lymphocytes

    SciTech Connect

    Borella, P.; Giardino, A. )

    1991-08-01

    The effect of lead chloride and cadmium chloride on in vitro immunoglobulin (Ig) production by human lymphocytes was investigated. After 7 days in culture, lead added in the range of human exposure (207-1035 {mu}g/liter) significantly enhanced Ig production either when cells were activated by pokeweed mitogen (PWM) or not. The effect was dose-dependent and was related to the Pb were measured in the extracellular medium and in the cells. Independently of the mitogen addition, about 2% of the Pb added was accumulated in the cells, most being associated with the nuclear fraction. Those findings suggest that the Pb effects could depend on its uptake and distribution in the cells. Cadmium added in the 50-500 nM range exhibited a dose-independent mitogenic activity in unstimulated cells, whereas the Ig secretion was not significantly affected by Cd when cells were PWM-activated. A considerable intraindividual variability, however, was observed when blood donors were separately examined, with both an increase, a decrease, or no variation on Ig production. Furthermore, higher percentages of Cd were accumulated in the nuclear fraction, and lower in the cytosol and precipitate, in PWM-activated compared to resting lymphocytes. Genetic factors could be of importance for the observed variability of the immune response to cadmium, and the authors support the hypothesis that differences in the metallothionein (MT) inducibility could play a role.

  13. Interacting Physical and Biological Processes Affecting Nutrient Transport Through Human Dominated Landscapes

    NASA Astrophysics Data System (ADS)

    Finlay, J. C.

    2015-12-01

    Human activities increasingly dominate biogeochemical cycles of limiting nutrients on Earth. Urban and agricultural landscapes represent the largest sources of excess nutrients that drive water quality degradation. The physical structure of both urban and agricultural watersheds has been extensively modified, and these changes have large impacts on water and nutrient transport. Despite strong physical controls over nutrient transport in human dominated landscapes, biological processes play important roles in determining the fates of both nitrogen and phosphorus. This talk uses examples from research in urban and agricultural watersheds in the Midwestern USA to illustrate interactions of physical and biological controls over nutrient cycles that have shifted nitrogen (N) and phosphorus (P) sources and cycling in unexpected ways in response to management changes. In urban watersheds, efforts to improve water quality have been hindered by legacy sources of phosphorus added to storm water through transport to drainage systems by vegetation. Similarly, reductions in field erosion in agricultural watersheds have not led to major reductions in phosphorus transport, because of continued release of biological sources of P. Where management of phosphorus has been most effective in reducing eutrophication of lakes, decreases in N removal processes have led to long term increases in N concentration and transport. Together, these examples show important roles for biological processes affecting nutrient movement in highly modified landscapes. Consideration of the downstream physical and biological responses of management changes are thus critical toward identification of actions that will most effectively reduce excess nutrients watersheds and coastal zones.

  14. Surface chemical functionalities affect the behavior of human adipose-derived stem cells in vitro

    NASA Astrophysics Data System (ADS)

    Liu, Xujie; Feng, Qingling; Bachhuka, Akash; Vasilev, Krasimir

    2013-04-01

    This study examines the effect of surface chemical functionalities on the behavior of human adipose-derived stem cells (hASCs) in vitro. Plasma polymerized films rich in amine (sbnd NH2), carboxyl (sbnd COOH) and methyl (sbnd CH3), were generated on hydroxyapatite (HAp) substrates. The surface chemical functionalities were characterized by X-ray photoelectron spectroscopy (XPS). The ability of different substrates to absorb proteins was evaluated. The results showed that substrates modified with hydrophilic functional group (sbnd COOH and sbnd NH2) can absorb more proteins than these modified with more hydrophobic functional group (sbnd CH3). The behavior of human adipose-derived stem cells (hASCs) cultured on different substrates was investigated in vitro: cell counting kit-8 (CCK-8) analysis was used to characterize cell proliferation, scanning electronic microscopy (SEM) analysis was used to characterize cell morphology and alkaline phosphatase (ALP) activity analysis was used to account for differentiation. The results of this study demonstrated that the sbnd NH2 modified surfaces encourage osteogenic differentiation; the sbnd COOH modified surfaces promote cell adhesion and spreading and the sbnd CH3 modified surfaces have the lowest ability to induce osteogenic differentiation. These findings confirmed that the surface chemical states of biomaterials can affect the behavior of hASCs in vitro.

  15. Safety and kinetic properties of a humanized antibody to human interleukin-6 receptor in healthy non-human primates.

    PubMed

    Shinkura, H; Imazeki, I; Fukushima, N; Chiba, N; Takahashi, F; Aikawa, H; Kitamura, H; Furuichi, T; Horiba, N; Ohsugi, Y

    1997-10-19

    A monoclonal antibody, hPM-1, was constructed by grafting the complementarity determining regions to human interleukin-6 (IL-6) receptor, raised in mouse, onto a human antibody backbone (humanized antibody). It is expected to be useful as a therapeutic agent for IL-6-related diseases such as multiple myeloma. To investigate the toxicological and kinetic properties of hPM-1 preliminarily, normal cynomolgus monkeys, which showed cross-reactivity with hPM-1, were intravenously administered with hPM-1 at doses of 0 (vehicle), 4 or 40 mg/kg once a week for 13 weeks. Upon toxicological examination, there were no changes in clinical signs, food consumption, body weights, urinalyses, body temperatures, electrocardiograms, hematological and biochemical parameters including blood platelet counts, serum levels of immunoglobulin G and C-reactive protein, and pathological findings. In a kinetic study, serum concentrations of hPM-1 showed a linearity between doses of 4 and 40 mg/kg. The serum concentrations, even at a dose of 4 mg/kg, were maintained at a high enough level to inhibit the IL-6 functions throughout the period of the study. Concentrations of hPM-1 in bone marrow were almost equal to those in serum. The antibodies against hPM-1 were detected only in one of four monkeys receiving hPM-1. This study suggests that blockage of the IL-6 receptor by hPM-1 does not induce any influence on a healthy living body, and hPM-1 is not toxic under the conditions of this investigation. PMID:9328216

  16. Human Apolipoprotein E Isoforms differentially affect Bone Mass and Turnover in vivo

    PubMed Central

    Dieckmann, Marco; Beil, F. Timo; Mueller, Brigitte; Bartelt, Alexander; Marshall, Robert P.; Koehne, Till; Amling, Michael; Ruether, Wolfgang; Cooper, Jackie A.; Humphries, Steve E.; Herz, Joachim; Niemeier, Andreas

    2012-01-01

    The primary role of apolipoprotein E (apoE) is to mediate the cellular uptake of lipoproteins. However, a new role for apoE as a regulator of bone metabolism in mice has recently been established. In contrast to mice, the human APOE gene is characterized by three common isoforms APOE ε2, ε3 and ε4 that result in different metabolic properties of the apoE isoforms, but it remains controversial whether the APOE polymorphism influences bone traits in humans. To clarify this, we investigated bone phenotypes of apoE knock-in mice, which express one human isoform each (apoE2 k.i., apoE3 k.i., apoE4 k.i.) in place of the mouse apoE. Analysis of 12 week-old female knock-in mice revealed increased levels of biochemical bone formation and resorption markers in apoE2 k.i. animals as compared to apoE3 k.i. and apoE4 k.i., with a reduced OPG/RANKL ratio in apoE2 k.i., indicating increased turnover with prevailing resorption in apoE2 k.i.. Accordingly, histomorphometric and μCT analyses demonstrated significantly lower trabecular bone mass in apoE2 than in apoE3 and apoE4 k.i. animals, which was reflected by a significant reduction of lumbar vertebrae maximum force resistance. Unlike trabecular bone, femoral cortical thickness, and stability was not differentially affected by the apoE isoforms. To extend these observations to the human situation, plasma from middle-aged healthy men homozygous for ε2/ε2, ε3/ε3, and ε4/ε4 (n=21, n=80, n=55 respectively) was analyzed with regard to bone turnover markers. In analogy to apoE2 k.i. mice, a lower OPG/RANKL ratio was observed in the serum of ε2/ε2 carriers as compared to ε3/ε3 and ε4/ε4 individuals (p=0.02 for ε2/ε2 vs ε4/ε4). In conclusion, the current data strongly underline the general importance of apoE as a regulator of bone metabolism and identifies the APOE ε2 allele as a potential genetic risk factor for low trabecular bone mass and vertebral fractures in humans. PMID:22991192

  17. Systemic Inflammation Affects Human Osteocyte-Specific Protein and Cytokine Expression.

    PubMed

    Pathak, Janak L; Bakker, Astrid D; Luyten, Frank P; Verschueren, Patrick; Lems, Willem F; Klein-Nulend, Jenneke; Bravenboer, Nathalie

    2016-06-01

    Bone remodeling can be disturbed in active rheumatoid arthritis (RA), possibly as a result of elevated levels of circulating inflammatory cytokines. Osteocyte-specific proteins and cytokines play a vital role in bone remodeling by orchestrating bone formation and/or bone resorption. Therefore, we aimed to investigate the effect of RA-serum or inflammatory cytokines on expression of human osteocyte-specific proteins and cytokines. Human trabecular bone chips were cultured with RA-serum or inflammatory cytokines for 7-days. Live-dead staining was performed to assess cell viability. Gene expression of osteocyte-specific proteins and cytokines was analyzed by qPCR. Immuno-staining was performed for osteocyte-specific markers. Approximately 60 % of the osteocytes on the bone chips were alive at day-7. Cells in or on the bone chips did express the gene for osteocyte markers SOST, FGF23, DMP1, and MEPE, and the cytokines IL-1β, IL-6, and TNFα at day 0 and 7. Active RA-serum treatment enhanced IL-1β, TNFα, SOST, and DKK1 gene expression. IL-1β treatment enhanced IL-1β, TNFα, IL-6, IL-8, FGF23, and SOST gene expression. TNFα treatment enhanced IL-1β, TNFα, IL-6, IL-8, and FGF23 gene expression. IL-8 treatment enhanced TNFα, IL-8, and FGF23 gene expression. A combination of IL-1β, IL-6, and TNFα treatment synergistically upregulated IL-1β, IL-6, and IL-8 gene expression, as well as enhanced TNFα, OPG, SOST, and FGF23, and inhibited DKK1 gene expression. In conclusion, gene expression of human osteocyte-specific proteins and cytokines was affected by RA-serum, and exogenous recombinant cytokines treatment suggesting that osteocytes could provide a new target to prevent systemic inflammation-induced bone loss in RA. PMID:26887974

  18. Anthocyanidins modulate the activity of human DNA topoisomerases I and II and affect cellular DNA integrity.

    PubMed

    Habermeyer, Michael; Fritz, Jessica; Barthelmes, Hans U; Christensen, Morten O; Larsen, Morten K; Boege, Fritz; Marko, Doris

    2005-09-01

    In the present study, we investigated the effect of anthocyanidins on human topoisomerases I and II and its relevance for DNA integrity within human cells. Anthocyanidins bearing vicinal hydroxy groups at the B-ring (delphinidin, DEL; cyanidin, CY) were found to potently inhibit the catalytic activity of human topoisomerases I and II, without discriminating between the IIalpha and the IIbeta isoforms. However, in contrast to topoisomerase poisons, DEL and CY did not stabilize the covalent DNA-topoisomerase intermediates (cleavable complex) of topoisomerase I or II. Using recombinant topoisomerase I, the presence of CY or DEL (> or = 1 microM) effectively prohibited the stabilization of the cleavable complex by the topoisomerase I poison camptothecin. We furthermore investigated whether the potential protective effect vs topoisomerase I poisons is reflected also on the cellular level, affecting the DNA damaging properties of camptothecin. Indeed, in HT29 cells, low micromolar concentrations of DEL (1-10 microM) significantly diminished the DNA strand breaking effect of camptothecin (100 microM). However, at concentrations > or = 50 microM, all anthocyanidins tested (delphinidin, cyanidin, malvidin, pelargonidin, and paeonidin), including those not interfering with topoisomerases, were found to induce DNA strand breaks in the comet assay. All of these analogues were able to compete with ethidium bromide for the intercalation into calf thymus DNA and to replace the minor groove binder Hoechst 33258. These data indicate substantial affinity to double-stranded DNA, which might contribute at least to the DNA strand breaking effect of anthocyanidins at higher concentrations (> or = 50 microM). PMID:16167831

  19. Factors affecting human heterocyclic amine intake and the metabolism of PhIP.

    PubMed

    Knize, Mark G; Kulp, Kristen S; Salmon, Cynthia P; Keating, Garrett A; Felton, James S

    2002-09-30

    We are working to understand possible human health effects from exposure to heterocyclic amines that are formed in meat during cooking. Laboratory-cooked beef, pork, and chicken are capable of producing tens of nanograms of MeIQx, IFP, and PhIP per gram of meat and smaller amounts of other heteroyclic amines. Well-done restaurant-cooked beef, pork, and chicken may contain PhIP and IFP at concentrations as high as tens of nanograms per gram and MeIQx at levels up to 3 ng/g. Although well-done chicken breast prepared in the laboratory may contain large amounts of PhIP, a survey of flame-grilled meat samples cooked in private homes showed PhIP levels in beef steak and chicken breast are not significantly different (P=0.36). The extremely high PhIP levels reported in some studies of grilled chicken are not seen in home-cooked samples.Many studies suggest individuals may have varying susceptibility to carcinogens and that diet may influence metabolism, thus affecting cancer susceptibility. To understand the human metabolism of PhIP, we examined urinary metabolites of PhIP in volunteers following a single well-done meat exposure. Using solid-phase extraction and LC/MS/MS, we quantified four major PhIP metabolites in human urine. In addition to investigating individual variation, we examined the interaction of PhIP with a potentially chemopreventive food. In a preliminary study of the effect of broccoli on PhIP metabolism, we fed chicken to six volunteers before and after eating steamed broccoli daily for 3 days. Preliminary results suggest that broccoli, which contains isothiocyanates shown to induce Phases I and II metabolism in vitro, may affect both the rate of metabolite excretion and the metabolic products of a dietary carcinogen. This newly developed methodology will allow us to assess prevention strategies that reduce the possible risks associated with PhIP exposure. PMID:12351155

  20. 75 FR 51273 - Expanded Human Immunodeficiency Virus (HIV) Testing for Disproportionately Affected Populations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-19

    ... (HIV) Testing for Disproportionately Affected Populations AGENCY: Centers for Disease Control and... Affected Populations''. Additional funding from the Patient Protection and Affordable Care Act has been... (HIV) Testing for Disproportionately Affected Populations'' to make awards to state and county...

  1. Creatine Metabolism and Safety Profiles after Six-Week Oral Guanidinoacetic Acid Administration in Healthy Humans

    PubMed Central

    Ostojic, Sergej M.; Niess, Barbara; Stojanovic, Marko; Obrenovic, Milos

    2013-01-01

    Objectives; Guanidinoacetic acid (GAA) is a natural precursor of creatine, yet the potential use of GAA as a nutritional additive for restoring creatine availability in humans has been limited by unclear efficacy and safety after exogenous GAA administration. The present study evaluated the effects of orally administered GAA on serum and urinary GAA, creatine and creatinine concentration, and on the occurrence of adverse events in healthy humans. Methods and Results; Twenty-four healthy volunteers were randomized in a double-blind design to receive either GAA (2.4 grams daily) or placebo (PLA) by oral administration for 6 weeks. Clinical trial registration: www.clinicaltrials.gov, identification number NCT01133899. Serum creatine and creatinine increased significantly from before to after administration in GAA-supplemented participants (P < 0.05). The proportion of participants who reported minor side effects was 58.3% in the GAA group and 45.5% in the placebo group (P = 0.68). A few participants experienced serum creatine levels above 70 µmol/L. Conclusion; Exogenous GAA is metabolized to creatine, resulting in a significant increase of fasting serum creatine after intervention. GAA had an acceptable side-effects profile with a low incidence of biochemical abnormalities. PMID:23329885

  2. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    PubMed

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. PMID:26890892

  3. Pyoverdine and proteases affect the response of Pseudomonas aeruginosa to gallium in human serum.

    PubMed

    Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco; Visca, Paolo

    2015-09-01

    Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections. PMID:26149986

  4. Quiescence does not affect p53 and stress response by irradiation in human lung fibroblasts.

    PubMed

    Dai, Jiawen; Itahana, Koji; Baskar, Rajamanickam

    2015-02-27

    Cells in many organs exist in both proliferating and quiescent states. Proliferating cells are more radio-sensitive, DNA damage pathways including p53 pathway are activated to undergo either G1/S or G2/M arrest to avoid entering S and M phase with DNA damage. On the other hand, quiescent cells are already arrested in G0, therefore there may be fundamental difference of irradiation response between proliferating and quiescent cells, and this difference may affect their radiosensitivity. To understand these differences, proliferating and quiescent human normal lung fibroblasts were exposed to 0.10-1 Gy of γ-radiation. The response of key proteins involved in the cell cycle, cell death, and metabolism as well as histone H2AX phosphorylation were examined. Interestingly, p53 and p53 phosphorylation (Ser-15), as well as the cyclin-dependent kinase inhibitors p21 and p27, were induced similarly in both proliferating and quiescent cells after irradiation. Furthermore, the p53 protein half-life, and expression of cyclin A, cyclin E, proliferating cell nuclear antigen (PCNA), Bax, or cytochrome c expression as well as histone H2AX phosphorylation were comparable after irradiation in both phases of cells. The effect of radioprotection by a glycogen synthase kinase 3β inhibitor on p53 pathway was also similar between proliferating and quiescent cells. Our results showed that quiescence does not affect irradiation response of key proteins involved in stress and DNA damage at least in normal fibroblasts, providing a better understanding of the radiation response in quiescent cells, which is crucial for tissue repair and regeneration. PMID:25637534

  5. Pyoverdine and Proteases Affect the Response of Pseudomonas aeruginosa to Gallium in Human Serum

    PubMed Central

    Bonchi, Carlo; Frangipani, Emanuela; Imperi, Francesco

    2015-01-01

    Gallium is an iron mimetic which has recently been repurposed as an antibacterial agent due to its capability to disrupt bacterial iron metabolism. In this study, the antibacterial activity of gallium nitrate [Ga(NO3)3] was investigated in complement-free human serum (HS) on 55 Pseudomonas aeruginosa clinical isolates from cystic fibrosis and non-cystic fibrosis patients. The susceptibility of P. aeruginosa to Ga(NO3)3 in HS was dependent on the bacterial ability to acquire iron from serum binding proteins (i.e., transferrin). The extent of serum protein degradation correlated well with P. aeruginosa growth in HS, while pyoverdine production did not. However, pyoverdine-deficient P. aeruginosa strains were unable to grow in HS and overcome iron restriction, albeit capable of releasing proteases. Predigestion of HS with proteinase K promoted the growth of all strains, irrespective of their ability to produce proteases and/or pyoverdine. The MICs of Ga(NO3)3 were higher in HS than in an iron-poor Casamino Acids medium, where proteolysis does not affect iron availability. Coherently, strains displaying high proteolytic activity were less susceptible to Ga(NO3)3 in HS. Our data support a model in which both pyoverdine and proteases affect the response of P. aeruginosa to Ga(NO3)3 in HS. The relatively high Ga(NO3)3 concentration required to inhibit the growth of highly proteolytic P. aeruginosa isolates in HS poses a limitation to the potential of Ga(NO3)3 in the treatment of P. aeruginosa bloodstream infections. PMID:26149986

  6. Local 24-h hyperglycemia does not affect endothelium-dependent or -independent vasoreactivity in humans.

    PubMed

    Houben, A J; Schaper, N C; de Haan, C H; Huvers, F C; Slaaf, D W; de Leeuw, P W; Nieuwenhuijzen Kruseman, C

    1996-06-01

    Hyperglycemia induces regional hemodynamic changes, as suggested by animal studies. These hemodynamic changes may play an initiating role in the pathogenesis of diabetic microangiopathy. The aim of the present study was to evaluate the effects of acute local hyperglycemia for 24 h on basal human forearm muscle and skin blood flow and endothelium-dependent and -independent vasoreactivity. Local hyperglycemia (approximately 15 mM) was induced by infusion of 5% glucose into the brachial artery of the nondominant arm. In control experiments, the same individual amount of glucose was infused intravenously in the dominant arm to correct for possible systemic effects of the infused glucose. Vasoreactivity of the forearm vasculature was evaluated by local infusion of acetylcholine (ACh), sodium nitroprusside (SNP), NG-monomethyl-L-arginine (L-NMMA), and norepinephrine (NE) into the brachial artery. Regional hemodynamic measurements were performed at baseline and after 6, 12, and 24 h of local hyperglycemia. Median (with interquartile range) basal forearm (muscle) blood flow (FBF) was not influenced by the 24-h local hyperglycemia [infused-to-contralateral arm FBF ratio for glucose 1.32 (1.16-1.64) vs. control 1.54 (1.34-1.69)]. Skin microcirculatory blood flow (laser Doppler flowmetry, LDF) was not influenced by the 24-h local hyperglycemia [LDF ratio for glucose 1.00 (0.62-1.56) vs control 0.80 (0.58-1.14)]. In addition, the vasoreactivity of both muscle and skin (not shown) vasculature to ACh [percent change in FBF ratio for glucose 167% (81-263) vs. control 148% (94-211)], SNP [for glucose 486% (178-586) vs. control 293% (196-454)], L-NMMA [for glucose -36% (-56 to -22) vs. control -41% (-51 to -24)], and NE [for glucose -48% (-72 to -41) vs. control -66% (-79 to -33)] was also not affected by the local hyperglycemia. Thus, in contrast to animal studies, our results suggest that a moderate-to-severe hyperglycemia does not affect the regulation of basal blood flow or

  7. Curcumin affects cell survival and cell volume regulation in human renal and intestinal cells

    PubMed Central

    Kössler, Sonja; Nofziger, Charity; Jakab, Martin; Dossena, Silvia; Paulmichl, Markus

    2012-01-01

    Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1E,6E-heptadiene-3,5-dione or diferuloyl methane) is a polyphenol derived from the Curcuma longa plant, commonly known as turmeric. This substance has been used extensively in Ayurvedic medicine for centuries for its anti-oxidant, analgesic, anti-inflammatory and antiseptic activity. More recently curcumin has been found to possess anti-cancer properties linked to its pro-apoptotic and anti-proliferative actions. The underlying mechanisms of these diverse effects are complex, not fully elucidated and subject of intense scientific debate. Despite increasing evidence indicating that different cation channels can be a molecular target for curcumin, very little is known about the effect of curcumin on chloride channels. Since, (i) the molecular structure of curcumin indicates that the substance could potentially interact with chloride channels, (ii) chloride channels play a role during the apoptotic process and regulation of the cell volume, and (iii) apoptosis is a well known effect of curcumin, we set out to investigate whether or not curcumin could (i) exert a modulatory effect (direct or indirect) on the swelling activated chloride current IClswell in a human cell system, therefore (ii) affect cell volume regulation and (iii) ultimately modulate cell survival. The IClswell channels, which are essential for regulating the cell volume after swelling, are also known to be activated under isotonic conditions as an early event in the apoptotic process. Here we show that long-term exposure of a human kidney cell line to extracellular 0.1–10 μM curcumin modulates IClswell in a dose-dependent manner (0.1 μM curcumin is ineffective, 0.5–5.0 μM curcumin increase, while 10 μM curcumin decrease the current), and short-term exposure to micromolar concentrations of curcumin does not affect IClswell neither if applied from the extracellular nor from the intracellular side – therefore, a direct effect of curcumin on

  8. GAD2 Alternative Transcripts in the Human Prefrontal Cortex, and in Schizophrenia and Affective Disorders

    PubMed Central

    Li, Chao; Gao, Yuan; Gondré-Lewis, Marjorie C.; Lipska, Barbara K.; Shin, Joo Heon; Xie, Bin; Ye, Tianzhang; Weinberger, Daniel R.; Kleinman, Joel E.; Hyde, Thomas M.

    2016-01-01

    Genetic variation and early adverse environmental events work together to increase risk for schizophrenia. γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in adult mammalian brain, plays a major role in normal brain development, and has been strongly implicated in the pathobiology of schizophrenia. GABA synthesis is controlled by two glutamic acid decarboxylase (GAD) genes, GAD1 and GAD2, both of which produce a number of alternative transcripts. Genetic variants in the GAD1 gene are associated with increased risk for schizophrenia, and reduced expression of its major transcript in the human dorsolateral prefrontal cortex (DLPFC). No consistent changes in GAD2 expression have been found in brains from patients with schizophrenia. In this work, with the use of RNA sequencing and PCR technologies, we confirmed and tracked the expression of an alternative truncated transcript of GAD2 (ENST00000428517) in human control DLPFC homogenates across lifespan besides the well-known full length transcript of GAD2. In addition, using quantitative RT-PCR, expression of GAD2 full length and truncated transcripts were measured in the DLPFC of patients with schizophrenia, bipolar disorder and major depression. The expression of GAD2 full length transcript is decreased in the DLPFC of schizophrenia and bipolar disorder patients, while GAD2 truncated transcript is increased in bipolar disorder patients but decreased in schizophrenia patients. Moreover, the patients with schizophrenia with completed suicide or positive nicotine exposure showed significantly higher expression of GAD2 full length transcript. Alternative transcripts of GAD2 may be important in the growth and development of GABA-synthesizing neurons as well as abnormal GABA signaling in the DLPFC of patients with schizophrenia and affective disorders. PMID:26848839

  9. Transcriptional modulator ZBED6 affects cell cycle and growth of human colorectal cancer cells

    PubMed Central

    Akhtar Ali, Muhammad; Younis, Shady; Wallerman, Ola; Gupta, Rajesh; Andersson, Leif; Sjöblom, Tobias

    2015-01-01

    The transcription factor ZBED6 (zinc finger, BED-type containing 6) is a repressor of IGF2 whose action impacts development, cell proliferation, and growth in placental mammals. In human colorectal cancers, IGF2 overexpression is mutually exclusive with somatic mutations in PI3K signaling components, providing genetic evidence for a role in the PI3K pathway. To understand the role of ZBED6 in tumorigenesis, we engineered and validated somatic cell ZBED6 knock-outs in the human colorectal cancer cell lines RKO and HCT116. Ablation of ZBED6 affected the cell cycle and led to increased growth rate in RKO cells but reduced growth in HCT116 cells. This striking difference was reflected in the transcriptome analyses, which revealed enrichment of cell-cycle–related processes among differentially expressed genes in both cell lines, but the direction of change often differed between the cell lines. ChIP sequencing analyses displayed enrichment of ZBED6 binding at genes up-regulated in ZBED6-knockout clones, consistent with the view that ZBED6 modulates gene expression primarily by repressing transcription. Ten differentially expressed genes were identified as putative direct gene targets, and their down-regulation by ZBED6 was validated experimentally. Eight of these genes were linked to the Wnt, Hippo, TGF-β, EGF receptor, or PI3K pathways, all involved in colorectal cancer development. The results of this study show that the effect of ZBED6 on tumor development depends on the genetic background and the transcriptional state of its target genes. PMID:26056301

  10. Bioaerosols from a Food Waste Composting Plant Affect Human Airway Epithelial Cell Remodeling Genes

    PubMed Central

    Chang, Ming-Wei; Lee, Chung-Ru; Hung, Hsueh-Fen; Teng, Kuo-Sheng; Huang, Hsin; Chuang, Chun-Yu

    2013-01-01

    The composting procedure in food waste plants generates airborne bioaerosols that have the potential to damage human airway epithelial cells. Persistent inflammation and repair responses induce airway remodeling and damage to the respiratory system. This study elucidated the expression changes of airway remodeling genes in human lung mucoepidermoid NCI-H292 cells exposed to bioaerosols from a composting plant. Different types of microorganisms were detectable in the composting plant, using the agar culture method. Real-time polymerase chain reaction was used to quantify the level of Aspergillus fumigatus and the profile of remodeling genes. The real-time PCR results indicated that the amount of A. fumigatus in the composting hall was less than 102 conidia. The endotoxins in the field bioaerosols were determined using a limulus amebocyte lysate test. The endotoxin levels depended on the type of particulate matter (PM), with coarse particles (2.5–10 μm) having higher endotoxin levels than did fine particles (0.5–2.5 μm). After exposure to the conditioned medium of field bioaerosol samples, NCI-H292 cells showed increased pro-inflammatory interleukin (IL)-6 release and activated epidermal growth factor receptor (EGFR), transforming growth factor (TGF)-β1 and cyclin-dependent kinase inhibitor 1 (p21WAF1/CIP1) gene expression, but not of matrix metallopeptidase (MMP)-9. Airborne endotoxin levels were higher inside the composting hall than they were in other areas, and they were associated with PM. This suggested that airborne bioaerosols in the composting plant contained endotoxins and microorganisms besides A. fumigatus that cause the inflammatory cytokine secretion and augment the expression of remodeling genes in NCI-H292 cells. It is thus necessary to monitor potentially hazardous materials from bioaerosols in food composting plants, which could affect the health of workers. PMID:24368426

  11. CD82 expression alters with human endometrial cycles and affects the uterine endometrial receptivity in vitro.

    PubMed

    Wei, Xiaowei; Liu, Shuai; Wang, Xiaoqi; Yan, Qiu

    2012-03-01

    Embryo implantation is a process that requires both temporal and spatial synchronization of the uterine endometrium and the embryo, and the endometrium becomes receptive to the embryo during the window of implantation. Although the expression patterns of many implantation-related molecules change dynamically during this process, the impact of CD82 on endometrial receptivity has not been elucidated. By immunohistochemical staining, we found that CD82 levels rose from the proliferative phase to the secretory phase in human endometrium. Specifically, the highest level appeared in mid- and late-secretory phases. Consistently, RL95-2 cells, representative of high-receptive endometrial epithelium, expressed higher levels of CD82 than did HEC-1A cells, which are representative of low-receptive endometrial epithelium, as detected by reverse transcription-polymerase chain reaction, Western blot and immunofluorescence. Furthermore, progesterone up-regulated the expression of CD82 in both epithelial cell lines. Down-regulation of CD82 in RL95-2 cells by either CD82 siRNA transfection or treatment with a CD82 antibody significantly decreased the adhesion of human embryonic JAR cells to RL95-2 cell monolayers (P < 0.01) and inhibited the phosphorylation of focal adhesion kinase (FAK). In contrast, up-regulation of CD82 in HEC-1A cells by CD82 cDNA transfection promoted embryonic JAR cell adhesion to HEC-1A monolayers (P < 0.05) and activated the phosphorylation of FAK. In conclusion, the expression of CD82 increases in endometrial tissues during the window of embryo implantation, CD82 expression affects endometrial receptivity of the uterine epithelial cells in vitro, and the FAK signaling pathway may be involved in this phenomenon. The correlation between CD82 and endometrial receptivity suggests that CD82 may serve as a potential marker of endometrial function. PMID:22393164

  12. Dietary Sodium Restriction Decreases Insulin Secretion Without Affecting Insulin Sensitivity in Humans

    PubMed Central

    Byrne, Loretta M.; Yu, Chang; Wang, Thomas J.; Brown, Nancy J.

    2014-01-01

    Context: Interruption of the renin-angiotensin-aldosterone system prevents incident diabetes in high-risk individuals, although the mechanism remains unclear. Objective: To test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system or exogenous aldosterone impairs insulin secretion in humans. Design: We conducted a randomized, blinded crossover study of aldosterone vs vehicle and compared the effects of a low-sodium versus a high-sodium diet. Setting: Academic clinical research center. Participants: Healthy, nondiabetic, normotensive volunteers. Interventions: Infusion of exogenous aldosterone (0.7 μg/kg/h for 12.5 h) or vehicle during low or high sodium intake. Low sodium (20 mmol/d; n = 12) vs high sodium (160 mmol/d; n = 17) intake for 5–7 days. Main Outcome Measures: Change in acute insulin secretory response assessed during hyperglycemic clamps while in sodium balance during a low-sodium vs high-sodium diet during aldosterone vs vehicle. Results: A low-sodium diet increased endogenous aldosterone and plasma renin activity, and acute glucose-stimulated insulin (−16.0 ± 5.6%; P = .007) and C-peptide responses (−21.8 ± 8.4%; P = .014) were decreased, whereas the insulin sensitivity index was unchanged (−1.0 ± 10.7%; P = .98). Aldosterone infusion did not affect the acute insulin response (+1.8 ± 4.8%; P = .72) or insulin sensitivity index (+2.0 ± 8.8%; P = .78). Systolic blood pressure and serum potassium were similar during low and high sodium intake and during aldosterone infusion. Conclusions: Low dietary sodium intake reduces insulin secretion in humans, independent of insulin sensitivity. PMID:25029426

  13. GH safety workshop position paper: A critical appraisal of recombinant human GH therapy in children and adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recombinant human Growth Hormone (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, t...

  14. Accumulation of distinct prelamin A variants in human diploid fibroblasts differentially affects cell homeostasis.

    PubMed

    Candelario, Jose; Borrego, Stacey; Reddy, Sita; Comai, Lucio

    2011-02-01

    Lamin A is a component of the nuclear lamina that plays a major role in the structural organization and function of the nucleus. Lamin A is synthesized as a prelamin A precursor which undergoes four sequential post-translational modifications to generate mature lamin A. Significantly, a large number of point mutations in the LMNA gene cause a range of distinct human disorders collectively known as laminopathies. The mechanisms by which mutations in lamin A affect cell function and cause disease are unclear. Interestingly, recent studies have suggested that alterations in the normal lamin A pathway can contribute to cellular dysfunction. Specifically, we and others have shown, at the cellular level, that in the absence of mutations or altered splicing events, increased expression of wild-type prelamin A results in a growth defective phenotype that resembles that of cells expressing the mutant form of lamin A, termed progerin, associated with Hutchinson-Gilford Progeria syndrome (HGPS). Remarkably, the phenotypes of cells expressing elevated levels of wild-type prelamin A can be reversed by either treatment with farnesyltransferase inhibitors or overexpression of ZMPSTE24, a critical prelamin A processing enzyme, suggesting that minor increases in the steady-state levels of one or more prelamin A intermediates is sufficient to induce cellular toxicity. Here, to investigate the molecular basis of the lamin A pathway toxicity, we characterized the phenotypic changes occurring in cells expressing distinct prelamin A variants mimicking specific prelamin A processing intermediates. This analysis demonstrates that distinct prelamin A variants differentially affect cell growth, nuclear membrane morphology, nuclear distribution of lamin A and the fundamental process of transcription. Expression of prelamin A variants that are constitutively farnesylated induced the formation of lamin A aggregates and dramatic changes in nuclear membrane morphology, which led to reduced

  15. Single Nucleotide Polymorphisms of Human STING Can Affect Innate Immune Response to Cyclic Dinucleotides

    PubMed Central

    Yi, Guanghui; Brendel, Volker P.; Shu, Chang; Li, Pingwei; Palanathan, Satheesh; Cheng Kao, C.

    2013-01-01

    The STING (stimulator of interferon genes) protein can bind cyclic dinucleotides to activate the production of type I interferons and inflammatory cytokines. The cyclic dinucleotides can be bacterial second messengers c-di-GMP and c-di-AMP, 3’5’-3’5’ cyclic GMP-AMP (3’3’ cGAMP) produced by Vibrio cholerae and metazoan second messenger 2’5’-3’5’ Cyclic GMP-AMP (2’3’ cGAMP). Analysis of single nucleotide polymorphism (SNP) data from the 1000 Genome Project revealed that R71H-G230A-R293Q (HAQ) occurs in 20.4%, R232H in 13.7%, G230A-R293Q (AQ) in 5.2%, and R293Q in 1.5% of human population. In the absence of exogenous ligands, the R232H, R293Q and AQ SNPs had only modest effect on the stimulation of IFN-β and NF-κB promoter activities in HEK293T cells, while HAQ had significantly lower intrinsic activity. The decrease was primarily due to the R71H substitution. The SNPs also affected the response to the cyclic dinucleotides. In the presence of c-di-GMP, the R232H variant partially decreased the ability to activate IFN-βsignaling, while it was defective for the response to c-di-AMP and 3’3’ cGAMP. The R293Q dramatically decreased the stimulatory response to all bacterial ligands. Surprisingly, the AQ and HAQ variants maintained partial abilities to activate the IFN-β signaling in the presence of ligands due primarily to the G230A substitution. Biochemical analysis revealed that the recombinant G230A protein could affect the conformation of the C-terminal domain of STING and the binding to c-di-GMP. Comparison of G230A structure with that of WT revealed that the conformation of the lid region that clamps onto the c-di-GMP was significantly altered. These results suggest that hSTING variation can affect innate immune signaling and that the common HAQ haplotype expresses a STING protein with reduced intrinsic signaling activity but retained the ability to response to bacterial cyclic dinucleotides. PMID:24204993

  16. Accumulation of distinct prelamin A variants in human diploid fibroblasts differentially affects cell homeostasis

    SciTech Connect

    Candelario, Jose; Borrego, Stacey; Reddy, Sita; Comai, Lucio

    2011-02-01

    Lamin A is a component of the nuclear lamina that plays a major role in the structural organization and function of the nucleus. Lamin A is synthesized as a prelamin A precursor which undergoes four sequential post-translational modifications to generate mature lamin A. Significantly, a large number of point mutations in the LMNA gene cause a range of distinct human disorders collectively known as laminopathies. The mechanisms by which mutations in lamin A affect cell function and cause disease are unclear. Interestingly, recent studies have suggested that alterations in the normal lamin A pathway can contribute to cellular dysfunction. Specifically, we and others have shown, at the cellular level, that in the absence of mutations or altered splicing events, increased expression of wild-type prelamin A results in a growth defective phenotype that resembles that of cells expressing the mutant form of lamin A, termed progerin, associated with Hutchinson-Gilford Progeria syndrome (HGPS). Remarkably, the phenotypes of cells expressing elevated levels of wild-type prelamin A can be reversed by either treatment with farnesyltransferase inhibitors or overexpression of ZMPSTE24, a critical prelamin A processing enzyme, suggesting that minor increases in the steady-state levels of one or more prelamin A intermediates is sufficient to induce cellular toxicity. Here, to investigate the molecular basis of the lamin A pathway toxicity, we characterized the phenotypic changes occurring in cells expressing distinct prelamin A variants mimicking specific prelamin A processing intermediates. This analysis demonstrates that distinct prelamin A variants differentially affect cell growth, nuclear membrane morphology, nuclear distribution of lamin A and the fundamental process of transcription. Expression of prelamin A variants that are constitutively farnesylated induced the formation of lamin A aggregates and dramatic changes in nuclear membrane morphology, which led to reduced

  17. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    SciTech Connect

    Vuillemenot, Brian R.; Kennedy, Derek; Reed, Randall P.; Boyd, Robert B.; Butt, Mark T.; Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O'Neill, Charles A.

    2014-05-15

    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

  18. Immunosuppressive Drugs Affect High-Mannose/Hybrid N-Glycans on Human Allostimulated Leukocytes

    PubMed Central

    Pocheć, Ewa; Bocian, Katarzyna; Ząbczyńska, Marta; Korczak-Kowalska, Grażyna; Lityńska, Anna

    2015-01-01

    N-glycosylation plays an important role in the majority of physiological and pathological processes occurring in the immune system. Alteration of the type and abundance of glycans is an element of lymphocyte differentiation; it is also common in the development of immune-mediated inflammatory diseases. The N-glycosylation process is very sensitive to different environmental agents, among them the pharmacological environment of immunosuppressive drugs. Some results show that high-mannose oligosaccharides have the ability to suppress different stages of the immune response. We evaluated the effects of cyclosporin A (CsA) and rapamycin (Rapa) on high-mannose/hybrid-type glycosylation in human leukocytes activated in a two-way mixed leukocyte reaction (MLR). CsA significantly reduced the number of leukocytes covered by high-mannose/hybrid N-glycans, and the synergistic action of CsA and Rapa led to an increase of these structures on the remaining leukocytes. This is the first study indicating that β1 and β3 integrins bearing high-mannose/hybrid structures are affected by Rapa and CsA. Rapa taken separately and together with CsA changed the expression of β1 and β3 integrins and, by regulating the protein amount, increased the oligomannose/hybrid-type N-glycosylation on the leukocyte surface. We suggest that the changes in the glycosylation profile of leukocytes may promote the development of tolerance in transplantation. PMID:26339568

  19. Molecular basis of human transcobalamin II deficiency in an affected family

    SciTech Connect

    Li, N.; Seetharam, S.; Seetharam, B.

    1994-09-01

    Transcobalamin II (TC II) deficiency is an autosomal recessive disease leading to cobalamin (Cbl, Vitamin B{sub 12}) deficiency. Patients with this disorder fail to absorb and transport Cbl across cellular membranes and develop Cbl deficiency, symptoms of which include failure to thrive, megaloblastic anemia, impaired immunodefence and neurological disorders. The molecular basis for this disease is not known. By means of Southern blotting and sequence analysis of TC II, cDNA amplified from fibroblasts of an affected child and his parents, we have identified two mutant TC II alleles. The maternally derived allele had a gross deletion, while the paternally derived allele had a 4-nucleotide ({sup 1023}TCTG) deletion which caused a reading frame shift and generation of a premature termination codon, 146 nucleotides downstream from the deletion. Both these deletions caused markedly reduced levels of TC II mRNA and protein. In addition, these two deletions were unique to this family and were not detected in four other unrelated TC II deficient patients who also exhibited the same (TC II protein/mRNA deficiency) phenotypes. Based on this study we suggest, (1) that the molecular defect in the most common form of human TC II deficiency (lack of immunoprecipitable plasma TC II) is heterogeneous and (2) these mutations cause TC II mRNA and protein deficiency leading to defective plasma transport of Cbl and the development of Cbl deficiency.

  20. A dynamic evolution model of human opinion as affected by advertising

    NASA Astrophysics Data System (ADS)

    Luo, Gui-Xun; Liu, Yun; Zeng, Qing-An; Diao, Su-Meng; Xiong, Fei

    2014-11-01

    We propose a new model to investigate the dynamics of human opinion as affected by advertising, based on the main idea of the CODA model and taking into account two practical factors: one is that the marginal influence of an additional friend will decrease with an increasing number of friends; the other is the decline of memory over time. Simulations show several significant conclusions for both advertising agencies and the general public. A small difference of advertising’s influence on individuals or advertising coverage will result in significantly different advertising effectiveness within a certain interval of value. Compared to the value of advertising’s influence on individuals, the advertising coverage plays a more important role due to the exponential decay of memory. Meanwhile, some of the obtained results are in accordance with people’s daily cognition about advertising. The real key factor in determining the success of advertising is the intensity of exchanging opinions, and people’s external actions always follow their internal opinions. Negative opinions also play an important role.

  1. Experimental Evidence for Anomalous Retroactive Influences on Human Cognition and Affect

    NASA Astrophysics Data System (ADS)

    Bem, Daryl J.

    2011-11-01

    Six experiments are described that take well-established psychological effects on human cognition and affect and "time-reverse" them so that the individual's responses are obtained before the putatively causal stimulus events occur. Two of the experiments tested for the retroactive facilitation of recall: It is well known that rehearsing or practicing a set of verbal materials enhances an individual's ability to recall them on a subsequent test. In our experiments, participants were first shown 48 common words one at a time and were then asked to recall as many of those words as they could. They were then given practice exercises on a randomly selected subset of those words. The results show that participants recalled more of the words they later practiced than the control words they did not practice. Two experiments on retroactive priming provide evidence for retroactive influence on an individual's response times when judging the pleasantness or unpleasantness of visual stimuli. Finally, two experiments provide evidence for the retroactive habituation to emotionally arousing visual stimuli. Each of the six experiments yielded statistically significant results, with a combined z = 3.66, p = .0001, and an effect size (d) of 0.25. The six experiments are a subset of nine retroactive influence experiments reported in Bem [1] that yielded a combined z = 6.66, p = 1.34×10-11, and an effect size of 0.22.

  2. African dust carries microbes across the ocean: are they affecting human and ecosystem health?

    USGS Publications Warehouse

    Kellogg, Christina A.; Griffin, Dale W.

    2003-01-01

    Atmospheric transport of dust from northwest Africa to the western Atlantic Ocean region may be responsible for a number of environmental hazards, including the demise of Caribbean corals; red tides; amphibian diseases; increased occurrence of asthma in humans; and oxygen depletion (eutrophication) in estuaries. Studies of satellite images suggest that hundreds of millions of tons of dust are trans-ported annually at relatively low altitudes across the Atlantic Ocean to the Caribbean Sea and southeastern United States. The dust emanates from the expanding Sahara/Sahel desert region in Africa and carries a wide variety of bacteria and fungi. The U.S. Geological Survey, in collaboration with the NASA/Goddard Spaceflight Center, is conducting a study to identify microbes--bacteria, fungi, viruses--transported across the Atlantic in African soil dust. Each year, millions of tons of desert dust blow off the west African coast and ride the trade winds across the ocean, affecting the entire Caribbean basin, as well as the southeastern United States. Of the dust reaching the U.S., Florida receives about 50 percent, while the rest may range as far north as Maine or as far west as Colorado. The dust storms can be tracked by satellite and take about one week to cross the Atlantic.

  3. Characterization of human arterial tissue affected by atherosclerosis using multimodal nonlinear optical microscopy

    NASA Astrophysics Data System (ADS)

    Baria, Enrico; Cicchi, Riccardo; Rotellini, Matteo; Nesi, Gabriella; Massi, Daniela; Pavone, Francesco S.

    2016-03-01

    Atherosclerosis is a widespread cardiovascular disease caused by the deposition of lipids (such as cholesterol and triglycerides) on the inner arterial wall. The rupture of an atherosclerotic plaque, resulting in a thrombus, is one of the leading causes of death in the Western World. Preventive assessment of plaque vulnerability is therefore extremely important and can be performed by studying collagen organization and lipid composition in atherosclerotic arterial tissues. Routinely used diagnostic methods, such as histopathological examination, are limited to morphological analysis of the examined tissues, whereas an exhaustive characterization requires immune-histochemical examination and a morpho-functional approach. Instead, a label-free and non-invasive alternative is provided by nonlinear microscopy. In this study, we combined SHG and FLIM microscopy in order to characterize collagen organization and lipids in human carotid ex vivo tissues affected by atherosclerosis. SHG and TPF images, acquired from different regions within atherosclerotic plaques, were processed through image pattern analysis methods (FFT, GLCM). The resulting information on collagen and cholesterol distribution and anisotropy, combined with collagen and lipids fluorescence lifetime measured from FLIM images, allowed characterization of carotid samples and discrimination of different tissue regions. The presented method can be applied for automated classification of atherosclerotic lesions and plaque vulnerability. Moreover, it lays the foundation for a potential in vivo diagnostic tool to be used in clinical setting.

  4. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health.

    PubMed

    Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

    2016-01-01

    The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies. PMID:27507964

  5. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health

    PubMed Central

    Vernocchi, Pamela; Del Chierico, Federica; Putignani, Lorenza

    2016-01-01

    The gut microbiota is composed of a huge number of different bacteria, that produce a large amount of compounds playing a key role in microbe selection and in the construction of a metabolic signaling network. The microbial activities are affected by environmental stimuli leading to the generation of a wide number of compounds, that influence the host metabolome and human health. Indeed, metabolite profiles related to the gut microbiota can offer deep insights on the impact of lifestyle and dietary factors on chronic and acute diseases. Metagenomics, metaproteomics and metabolomics are some of the meta-omics approaches to study the modulation of the gut microbiota. Metabolomic research applied to biofluids allows to: define the metabolic profile; identify and quantify classes and compounds of interest; characterize small molecules produced by intestinal microbes; and define the biochemical pathways of metabolites. Mass spectrometry and nuclear magnetic resonance spectroscopy are the principal technologies applied to metabolomics in terms of coverage, sensitivity and quantification. Moreover, the use of biostatistics and mathematical approaches coupled with metabolomics play a key role in the extraction of biologically meaningful information from wide datasets. Metabolomic studies in gut microbiota-related research have increased, focusing on the generation of novel biomarkers, which could lead to the development of mechanistic hypotheses potentially applicable to the development of nutritional and personalized therapies. PMID:27507964

  6. Nanotechnology research and regulation: A plan to ensure human and environmental safety

    NASA Astrophysics Data System (ADS)

    Reddy, Anitha

    The influence of nanotechnology spans numerous fields and is increasing rapidly due to the financial and research contributions to the field. The impact of nanotechnologybased products on human health and the environment is far from being understood. Research output related to environmental, health, and safety issues is too slow and far behind developments to address the vast number of types of nanoparticles and new uses being discovered. This thesis summarizes nanotechnology related regulations, applications, and current research related to environmental and human toxicity in order to put into perspective the gaping holes existing in the safe production, use, and disposal of nanotechnology. There were a number of conclusions that were determined following the literature survey of this thesis. There is currently a lack of international cooperation between regulatory agencies and research institutions who are involved with nanotechnology. The only entities that have made regulatory progress include the United States, European Union, and Australia. The toxicological impacts of nanotechnology are not fully understood due to the dearth of research, as well as the absence of testing and measuring infrastructure. Chapter 6 of this thesis proposes an effective and specific research strategy to expedite the creation of enforceable regulations in order to protect the environment, workers, and general public based on the conclusions described in the paragraph above. The strategy outlines the need for the development of an interagency committee, precationary limits, nanomaterial tracer system, nanomaterial data gathering, priority list, funds for toxicity research, and open database to information and materials. The aspects of the outline strategy will ensure the successful and efficient regulation of nanotechnology.

  7. Perceiving Threat In the Face of Safety: Excitation and Inhibition of Conditioned Fear in Human Visual Cortex

    PubMed Central

    2013-01-01

    Previous findings have established that cortical sensory systems exhibit experience-dependent biases toward stimuli consistently associated with threat. It remains unclear whether safety cues also facilitate perceptual engagement or how competition between learned threat and safety cues is resolved within visual cortex. Here, we used classical discrimination conditioning with simple luminance modulated visual stimuli that predicted the presence or absence of an aversive sound to examine visuocortical competition between features signaling threat versus safety. We tracked steady-state visual evoked potentials to label distinct visual cortical responses in humans to conditioned and control stimuli. Trial-by-trial expectancy ratings collected online confirmed that participants discriminated between threat and safety cues. Conditioning was associated with heightened activation of the extended visual cortex in response to the threat, but not the safety, stimulus. Cortical facilitation for the threatening stimulus was selective and not decreased by simultaneously presenting safe and associatively novel cues. Our findings shed light on the sensory brain dynamics associated with experience-dependent acquisition of perceptual biases for danger and safety signals. PMID:23283323

  8. Velocity, safety, or both? How do balance and strength of goal conflicts affect drivers' behaviour, feelings and physiological responses?

    PubMed

    Schmidt-Daffy, Martin; Brandenburg, Stefan; Beliavski, Alina

    2013-06-01

    Motivational models of driving behaviour agree that choice of speed is modulated by drivers' goals. Whilst it is accepted that some goals favour fast driving and others favour safe driving, little is known about the interplay of these conflicting goals. In the present study, two aspects of this interplay are investigated: the balance of conflict and the strength of conflict. Thirty-two participants completed several simulated driving runs in which fast driving was rewarded with a monetary gain if the end of the track was reached. However, unpredictably, some runs ended with the appearance of a deer. In these runs, fast driving was punished with a monetary loss. The ratio between the magnitudes of gains and losses varied in order to manipulate the balance of conflict. The absolute magnitudes of both gains and losses altered the strength of conflict. Participants drove slower, reported an increase in anxiety-related feelings, and showed indications of physiological arousal if there was more money at stake. In contrast, only marginal effects of varying the ratio between gains and losses were observed. Results confirm that the strength of a safety-velocity conflict is an important determinant of drivers' behaviour, feelings, and physiological responses. The lack of evidence for the balance of conflict playing a role suggests that in each condition, participants subjectively weighted the loss higher than the gain (loss aversion). It is concluded that the interplay of the subjective values that drivers attribute to objective incentives for fast and safe driving is a promising field for future research. Incorporating this knowledge into motivational theories of driving behaviour might improve their contribution to the design of adequate road safety measures. PMID:23523895

  9. Conditions for the successful integration of Human and Organizational Factors (HOF) in the nuclear safety analysis.

    PubMed

    Tosello, Michèle; Lévêque, Françoise; Dutillieu, Stéphanie; Hernandez, Guillaume; Vautier, Jean-François

    2012-01-01

    This communication presents some elements which come from the experience feedback at CEA about the conditions for the successful integration of HOF in the nuclear safety analysis. To point out some of these conditions, one of the concepts proposed by Edgar Morin to describe the functioning of "complex" systems: the dialogical principle has been used. The idea is to look for some dialogical pairs. The elements of this kind of pair are both complementary and antagonist to one another. Three dialogical pairs are presented in this communication. The first two pairs are related to the organization of the HOF network and the last one is related to the methods which are used to analyse the working situations. The three pairs are: specialist - non-specialist actors of the network, centralized - distributed human resources in the network and microscopic - macroscopic levels of HOF methods to analyse the working situations. To continuously improve these three dialogical pairs, it is important to keep the differences which exist between the two elements of a pair and to find and maintain a balance between the two elements of the pairs. PMID:22317122

  10. Safety and Efficacy Data on Vaccines and Immunization to Human Papillomavirus

    PubMed Central

    Kash, Natalie; Lee, Michael A.; Kollipara, Ramya; Downing, Christopher; Guidry, Jacqueline; Tyring, Stephen K.

    2015-01-01

    Since the discovery of the causal association between human papillomavirus (HPV) and cervical cancer, efforts to develop an effective prophylactic vaccine to prevent high-risk HPV infections have been at the forefront of modern medical research. HPV causes 530,000 cervical cancer cases worldwide, which is the second most common cause of cancer deaths in women; a worldwide collaboration among epidemiologists, molecular biologists, vaccinologists, virologists, and clinicians helped lead to the development of two highly effective prophylactive HPV vaccines. The first, Gardasil, is a quadrivalent vaccine made up of recombinant HPV L1 capsid proteins from the two high-risk HPV types (16/18) responsible for 70% of cervical cancer cases as well as two low-risk HPV types (6/11) which are the causative agent for genital warts. The second, Cervarix, is a bivalent vaccine that was FDA approved three years after Gardasil and is also composed of L1 capsid proteins from HPV types 16/18. This review article focuses on the safety and efficacy data of both FDA-approved vaccines, as well as highlighting a few advances in future HPV vaccines that show promise in becoming additional treatment options for this worldwide disease. PMID:26239350

  11. A safety-modified SV40 Tag developed for human cancer immunotherapy

    PubMed Central

    Tseng-Rogenski, Stephanie S; Arredouani, Mohamed S; Escara-Wilke, June F; Neeley, Yilin C; Imperiale, Michael J; Sanda, Martin G

    2008-01-01

    Simian virus 40 (SV40)-like DNA sequences have been found in a variety of human tumors, raising the possibility that strategies targeting SV40 may provide a potential avenue for immunotherapy directed against SV40 large T Antigen (Tag)-expressing tumors. We generated a recombinant vaccinia (vac-mTag) expressing mTag and herein assessed the ability of mTag to transform cells and to interact with anti-oncoproteins, as well as screened for the presence of potential HLA-A2.1-restricted epitopes within mTag. We found that transfection of cells with mTag did not lead to their transformation. Also, we demonstrated that mTag protein is degraded rapidly in cells. In addition, our work revealed that mTag did not physically interact with certain anti-oncoproteins. Finally, two potential HLA-A2.1-restricted functional epitopes within mTag sequence were identified. Our results show that mTag lacks the oncogenecity of full-length Tag and harbors potential HLA-A2.1-restricted immunogenic epitopes, hence suggesting the safety of vac-mTag for use in cancer immunotherapy. PMID:19920890

  12. The efficacy and safety of the quadrivalent human papillomavirus 6/11/16/18 vaccine gardasil.

    PubMed

    Haupt, Richard M; Sings, Heather L

    2011-11-01

    Human papillomavirus (HPV) infection causes cervical cancer, a significant portion of anal, genital, and oropharyngeal cancers, genital warts, and recurrent respiratory papillomatosis. In June 2006, a quadrivalent HPV-6/11/16/18 vaccine (Gardasil/Silgard) was licensed in the United States, and subsequently in the European Union (September 2006). It has since been approved in 121 countries, with >74 million doses distributed globally as of March 2011. As the incidence of HPV infection peaks 5-10 years after the onset of sexual activity, preadolescents and adolescents represent an appropriate target group to implement HPV vaccination programs so as to achieve the maximal public health benefit. In this article, we provide an overview of the prophylactic efficacy of the vaccine in young women who were found to be negative to at least one of the four vaccine HPV types, thus approximating sexually naive adolescents. Because adolescents are also at high risk for other infections which are preventable by currently available vaccines, the development of concurrent immunization strategies may lead to better compliance, thereby contributing to the overall goal of protection against preventable diseases. We also summarize concomitant administration studies with meningococcal, diphtheria, tetanus, and pertussis vaccines, which were conducted in adolescents aged 9-15 years. Prophylactic efficacy in other populations (males aged 16-26 years) is also summarized along with long-term safety and efficacy studies. PMID:22018560

  13. Safety of higher dosages of Viscum album L. in animals and humans - systematic review of immune changes and safety parameters

    PubMed Central

    2011-01-01

    Background Viscum album L extracts (VAE, mistletoe) and isolated mistletoe lectins (ML) have immunostimulating properties and a strong dose-dependent cytotoxic activity. They are frequently used in complementary cancer treatment, mainly to improve quality of life, but partly also to influence tumour growth, especially by injecting VAE locally and in high dosage. The question is raised whether these higher dosages can induce any harm or immunosuppressive effects. Methods Systematic review of all experiments and clinical studies investigating higher dosages of VAE in animals and humans (Viscum album > 1 mg in humans corresponding to > 0.02 mg/kg in animals or ML > 1 ng/kg) and assessing immune parameters or infections or adverse drug reactions. Results 69 clinical studies and 48 animal experiments reported application of higher doses of VAE or ML and had assessed immune changes and/or harm. In these studies, Viscum album was applied in dosages up to 1500 mg in humans and 1400 mg/kg in animals, ML was applied up to 6.4 μg/kg in humans and in animals up to 14 μg/kg subcutaneously, 50 μg/kg nasally and 500 μg/kg orally. A variety of immune parameters showed fluctuating or rising outcomes, but no immunosuppressive effect. Side effects consisted mainly of dose-dependent flu-like symptoms (FLS), fever, local reactions at the injection site and various mild unspecific effects. Occasionally, allergic reactions were reported. After application of high doses of recombinant ML, reversible hepatotoxicity was observed in some cases. Conclusions Application of higher dosages of VAE or ML is not accompanied by immunosuppression; altogether VAE seems to exhibit low risk but should be monitored by clinicians when applied in high dosages. PMID:21871125

  14. Replacement of Val3 in Human Thymidylate Synthase Affects Its Kinetic Properties and Intracellular Stability

    SciTech Connect

    Huang, Xiao; Gibson, Lydia M.; Bell, Brittnaie J.; Lovelace, Leslie L.; Pea, Maria Marjorette O.; Berger, Franklin G.; Berger, Sondra H.; Lebioda, Lukasz

    2010-11-03

    Human and other mammalian thymidylate synthase (TS) enzymes have an N-terminal extension of {approx}27 amino acids that is not present in bacterial TSs. The extension, which is disordered in all reported crystal structures of TSs, has been considered to play a primary role in protein turnover but not in catalytic activity. In mammalian cells, the variant V3A has a half-life similar to that of wild-type human TS (wt hTS) while V3T is much more stable; V3L, V3F, and V3Y have half-lives approximately half of that for wt hTS. Catalytic turnover rates for most Val3 mutants are only slightly diminished, as expected. However, two mutants, V3L and V3F, have strongly compromised dUMP binding, with K{sub m,app} values increased by factors of 47 and 58, respectively. For V3L, this observation can be explained by stabilization of the inactive conformation of the loop of residues 181-197, which prevents substrate binding. In the crystal structure of V3L, electron density corresponding to a leucine residue is present in a position that stabilizes the loop of residues 181-197 in the inactive conformation. Since this density is not observed in other mutants and all other leucine residues are ordered in this structure, it is likely that this density represents Leu3. In the crystal structure of a V3F {center_dot} FdUMP binary complex, the nucleotide is bound in an alternative mode to that proposed for the catalytic complex, indicating that the high K{sub m,app} value is caused not by stabilization of the inactive conformer but by substrate binding in a nonproductive, inhibitory site. These observations show that the N-terminal extension affects the conformational state of the hTS catalytic region. Each of the mechanisms leading to the high K{sub m,app} values can be exploited to facilitate design of compounds acting as allosteric inhibitors of hTS.

  15. Genetic factors affecting gene transcription and catalytic activity of UDP-glucuronosyltransferases in human liver

    PubMed Central

    Liu, Wanqing; Ramírez, Jacqueline; Gamazon, Eric R.; Mirkov, Snezana; Chen, Peixian; Wu, Kehua; Sun, Chang; Cox, Nancy J.; Cook, Edwin; Das, Soma; Ratain, Mark J.

    2014-01-01

    The aim of this study was to discover cis- and trans-acting factors significantly affecting mRNA expression and catalytic activity of human hepatic UDP-glucuronosyltransferases (UGTs). Transcription levels of five major hepatic UGT1A (UGT1A1, UGT1A3, UGT1A4, UGT1A6 and UGT1A9) and five UGT2B (UGT2B4, UGT2B7, UGT2B10, UGT2B15 and UGT2B17) genes were quantified in human liver tissue samples (n = 125) using real-time PCR. Glucuronidation activities of 14 substrates were measured in 47 livers. We genotyped 167 tagSNPs (single-nucleotide polymorphisms) in UGT1A (n = 43) and UGT2B (n = 124), as well as the known functional UGT1A1*28 and UGT2B17 CNV (copy number variation) polymorphisms. Transcription levels of 15 transcription factors (TFs) known to regulate these UGTs were quantified. We found that UGT expression and activity were highly variable among the livers (median and range of coefficient of variations: 135%, 74–217% and 52%, 39–105%, respectively). CAR, PXR and ESR1 were found to be the most important trans-regulators of UGT transcription (median and range of correlation coefficients: 46%, 6–58%; 47%, 9–58%; and 52%, 24–75%, respectively). Hepatic UGT activities were mainly determined by UGT gene transcription levels. Twenty-one polymorphisms were significantly (FDR-adjusted P < 0.05) associated with mRNA expression and/or activities of UGT1A1, UGT1A3 and UGT2B17. We found novel SNPs in the UGT2B17 CNV region accounting for variability in UGT2B17 gene transcription and testosterone glucuronidation rate, in addition to that attributable to the UGT2B17 CNV. Our study discovered novel pharmacogenetic markers and provided detailed insight into the genetic network regulating hepatic UGTs. PMID:24879639

  16. Factors affecting antimicrobial activity of MUC7 12-mer, a human salivary mucin-derived peptide

    PubMed Central

    Wei, Guo-Xian; Campagna, Alexander N; Bobek, Libuse A

    2007-01-01

    affect the activity. Conclusion MUC7 12-mer peptide is effective anticandidal agent at physiological concentrations of variety of ions in the oral cavity. These results suggest that, especially in combination with EDTA, it could potentially be applied as an alternative therapeutic agent for the treatment of human oral candidiasis. PMID:17996119

  17. AGE-RELATED FACTORS AFFECTING THE POST-YIELD ENERGY DISSIPATION OF HUMAN CORTICAL BONE

    PubMed Central

    Nyman, Jeffry S.; Roy, Anuradha; Tyler, Jerrod H.; Acuna, Rae L.; Gayle, Heather J.; Wang, Xiaodu

    2007-01-01

    The risk of bone fracture depends in part on the quality of the tissue, not just the size and mass. This study assessed the post-yield energy dissipation of cortical bone in tension as a function of age and composition. Tensile specimens were prepared from tibiae of human cadavers in which male and female donors were divided into two age groups: middle aged (51 to 56 years old, n = 9) and elderly (72 to 90 years old, n = 8). By loading, unloading, and reloading a specimen with rest period inserted in between, tensile properties at incremental strain levels were assessed. In addition, the post-yield toughness was estimated and partitioned as follows: plastic strain energy related to permanent deformation, released elastic strain energy related to stiffness loss, and hysteresis energy related to viscous behavior. Porosity, mineral and collagen content, and collagen crosslinks of each specimen were also measured to determine the micro and ultrastructural properties of the tissue. It was found that age affected all the energy terms plus strength but not elastic stiffness. The post-yield energy terms were correlated with porosity, pentosidine (a marker of non-enzymatic crosslinks), and collagen content, all of which significantly varied with age. General linear models with the highest possible R2 value suggested that the pentosidine concentration and collagen content provided the best explanation of the age-related decrease in the post-yield energy dissipation of bone. Among them, pentosidine concentration had the greatest contribution to plastic strain energy and was the best explanatory variable of damage accumulation. PMID:17266142

  18. E-Cigarette Affects the Metabolome of Primary Normal Human Bronchial Epithelial Cells

    PubMed Central

    Aug, Argo; Altraja, Siiri; Kilk, Kalle; Porosk, Rando; Soomets, Ursel; Altraja, Alan

    2015-01-01

    E-cigarettes are widely believed to be safer than conventional cigarettes and have been even suggested as aids for smoking cessation. However, while reasonable with some regards, this judgment is not yet supported by adequate biomedical research data. Since bronchial epithelial cells are the immediate target of inhaled toxicants, we hypothesized that exposure to e-cigarettes may affect the metabolome of human bronchial epithelial cells (HBEC) and that the changes are, at least in part, induced by oxidant-driven mechanisms. Therefore, we evaluated the effect of e-cigarette liquid (ECL) on the metabolome of HBEC and examined the potency of antioxidants to protect the cells. We assessed the changes of the intracellular metabolome upon treatment with ECL in comparison of the effect of cigarette smoke condensate (CSC) with mass spectrometry and principal component analysis on air-liquid interface model of normal HBEC. Thereafter, we evaluated the capability of the novel antioxidant tetrapeptide O-methyl-l-tyrosinyl-γ-l-glutamyl-l-cysteinylglycine (UPF1) to attenuate the effect of ECL. ECL caused a significant shift in the metabolome that gradually gained its maximum by the 5th hour and receded by the 7th hour. A second alteration followed at the 13th hour. Treatment with CSC caused a significant initial shift already by the 1st hour. ECL, but not CSC, significantly increased the concentrations of arginine, histidine, and xanthine. ECL, in parallel with CSC, increased the content of adenosine diphosphate and decreased that of three lipid species from the phosphatidylcholine family. UPF1 partially counteracted the ECL-induced deviations, UPF1’s maximum effect occurred at the 5th hour. The data support our hypothesis that ECL profoundly alters the metabolome of HBEC in a manner, which is comparable and partially overlapping with the effect of CSC. Hence, our results do not support the concept of harmlessness of e-cigarettes. PMID:26536230

  19. Donor Age of Human Platelet Lysate Affects Proliferation and Differentiation of Mesenchymal Stem Cells

    PubMed Central

    Lohmann, Michael; Walenda, Gudrun; Hemeda, Hatim; Joussen, Sylvia; Drescher, Wolf; Jockenhoevel, Stefan; Hutschenreuter, Gabriele; Zenke, Martin; Wagner, Wolfgang

    2012-01-01

    The regenerative potential declines upon aging. This might be due to cell-intrinsic changes in stem and progenitor cells or to influences by the microenvironment. Mesenchymal stem cells (MSC) raise high hopes in regenerative medicine. They are usually culture expanded in media with fetal calf serum (FCS) or other serum supplements such as human platelet lysate (HPL). In this study, we have analyzed the impact of HPL-donor age on culture expansion. 31 single donor derived HPLs (25 to 57 years old) were simultaneously compared for culture of MSC. Proliferation of MSC did not reveal a clear association with platelet counts of HPL donors or growth factors concentrations (PDGF-AB, TGF-β1, bFGF, or IGF-1), but it was significantly higher with HPLs from younger donors (<35 years) as compared to older donors (>45 years). Furthermore, HPLs from older donors increased activity of senescence-associated beta-galactosidase (SA-βgal). HPL-donor age did not affect the fibroblastoid colony-forming unit (CFU-f) frequency, immunophenotype or induction of adipogenic differentiation, whereas osteogenic differentiation was significantly lower with HPLs from older donors. Concentrations of various growth factors (PDGF-AB, TGF-β1, bFGF, IGF-1) or hormones (estradiol, parathormone, leptin, 1,25 vitamin D3) were not associated with HPL-donor age or MSC growth. Taken together, our data support the notion that aging is associated with systemic feedback mechanisms acting on stem and progenitor cells, and this is also relevant for serum supplements in cell culture: HPLs derived from younger donors facilitate enhanced expansion and more pronounced osteogenic differentiation. PMID:22662236

  20. Review of the toxicology, human exposure and safety assessment for bisphenol A diglycidylether (BADGE).

    PubMed

    Poole, A; van Herwijnen, P; Weideli, H; Thomas, M C; Ransbotyn, G; Vance, C

    2004-09-01

    BADGE (whose chemical names are bisphenol A diglycidylether and 2,2-bis(4-(2,3-epoxypropyl)phenyl)propane) is the lowest molecular weight oligomer in commercial epoxy resins and the major component in commercial liquid epoxy resins. The major application areas for epoxy resins are protective coatings and civil engineering. Additional applications include printed circuit boards, composites, adhesives and tooling, while a relatively small amount of epoxy resins (< 10%) finds use in protective coatings inside food and drink cans. The use of BADGE in food-contact applications was first regulated through EC Directive 2002/16/EC and amended in EC Directive 2004/13/EC with migration levels in food-contact applications being generally well below the regulatory thresholds. The paper discusses the commercial use of BADGE focusing on the current knowledge of human exposure from canned food applications. To assess the safety of this application, the exposure data are compared with no adverse effect levels (NOAEL) from various toxicological investigations with BADGE including reproductive and developmental assays, endocrine toxicity investigations, and sub-chronic and chronic assays. Consumer exposure to BADGE is almost exclusively from migration of BADGE from can coatings into food. Using a worst-case scenario that assumes BADGE migrates at the same level into all types of food, the estimated per capita daily intake for a 60-kg individual is approximately 0.16 microg kg(-1) body weight day(-1). A review of one- and two-generation reproduction studies and developmental investigations found no evidence of reproductive or endocrine toxicity, the upper ranges of dosing being determined by maternal toxicity. The lack of endocrine toxicity in the reproductive and developmental toxicological tests is supported by negative results from both in vivo and in vitro assays designed specifically to detect oestrogenic and androgenic properties of BADGE. An examination of data from sub

  1. A human liver microphysiology platform for investigating physiology, drug safety, and disease models.

    PubMed

    Vernetti, Lawrence A; Senutovitch, Nina; Boltz, Robert; DeBiasio, Richard; Shun, Tong Ying; Gough, Albert; Taylor, D Lansing

    2016-01-01

    This paper describes the development and characterization of a microphysiology platform for drug safety and efficacy in liver models of disease that includes a human, 3D, microfluidic, four-cell, sequentially layered, self-assembly liver model (SQL-SAL); fluorescent protein biosensors for mechanistic readouts; as well as a microphysiology system database (MPS-Db) to manage, analyze, and model data. The goal of our approach is to create the simplest design in terms of cells, matrix materials, and microfluidic device parameters that will support a physiologically relevant liver model that is robust and reproducible for at least 28 days for stand-alone liver studies and microfluidic integration with other organs-on-chips. The current SQL-SAL uses primary human hepatocytes along with human endothelial (EA.hy926), immune (U937) and stellate (LX-2) cells in physiological ratios and is viable for at least 28 days under continuous flow. Approximately, 20% of primary hepatocytes and/or stellate cells contain fluorescent protein biosensors (called sentinel cells) to measure apoptosis, reactive oxygen species (ROS) and/or cell location by high content analysis (HCA). In addition, drugs, drug metabolites, albumin, urea and lactate dehydrogenase (LDH) are monitored in the efflux media. Exposure to 180 μM troglitazone or 210 μM nimesulide produced acute toxicity within 2-4 days, whereas 28 μM troglitazone produced a gradual and much delayed toxic response over 21 days, concordant with known mechanisms of toxicity, while 600 µM caffeine had no effect. Immune-mediated toxicity was demonstrated with trovafloxacin with lipopolysaccharide (LPS), but not levofloxacin with LPS. The SQL-SAL exhibited early fibrotic activation in response to 30 nM methotrexate, indicated by increased stellate cell migration, expression of alpha-smooth muscle actin and collagen, type 1, alpha 2. Data collected from the in vitro model can be integrated into a database with access to related

  2. A human liver microphysiology platform for investigating physiology, drug safety, and disease models

    PubMed Central

    Vernetti, Lawrence A.; Senutovitch, Nina; Boltz, Robert; DeBiasio, Richard; Shun, Tong Ying; Gough, Albert; Taylor, D. Lansing

    2015-01-01

    This paper describes the development and characterization of a microphysiology platform for drug safety and efficacy in liver models of disease that includes a human, 3D, microfluidic, four-cell, sequentially layered, self-assembly liver model (SQL-SAL); fluorescent protein biosensors for mechanistic readouts; as well as a microphysiology system database (MPS-Db) to manage, analyze, and model data. The goal of our approach is to create the simplest design in terms of cells, matrix materials, and microfluidic device parameters that will support a physiologically relevant liver model that is robust and reproducible for at least 28 days for stand-alone liver studies and microfluidic integration with other organs-on-chips. The current SQL-SAL uses primary human hepatocytes along with human endothelial (EA.hy926), immune (U937) and stellate (LX-2) cells in physiological ratios and is viable for at least 28 days under continuous flow. Approximately, 20% of primary hepatocytes and/or stellate cells contain fluorescent protein biosensors (called sentinel cells) to measure apoptosis, reactive oxygen species (ROS) and/or cell location by high content analysis (HCA). In addition, drugs, drug metabolites, albumin, urea and lactate dehydrogenase (LDH) are monitored in the efflux media. Exposure to 180μM troglitazone or 210μM nimesulide produced acute toxicity within 2–4 days, whereas 28μM troglitazone produced a gradual and much delayed toxic response over 21 days, concordant with known mechanisms of toxicity, while 600μM caffeine had no effect. Immune-mediated toxicity was demonstrated with trovafloxacin with lipopolysaccharide (LPS), but not levofloxacin with LPS. The SQL-SAL exhibited early fibrotic activation in response to 30nM methotrexate, indicated by increased stellate cell migration, expression of alpha-smooth muscle actin and collagen, type 1, alpha 2. Data collected from the in vitro model can be integrated into a database with access to related chemical

  3. [Safety concentration of genotoxic carcinogens in water pollution accident based on human health risk].

    PubMed

    Luo, Jin-Hong; Zheng, Bing-Hui; Fu, Qing; Hung, Min-Sheng

    2012-02-01

    It was an urgent problem to determine short-term exposure safety concentration of genetic carcinogens in water pollution accident in China. Based on the hypothesis that the relationship between exposure dosage and carcinogenic risk was linear, the calculation process of genetic carcinogens safety concentration was put forwarded, and the method using life-time exposed safety concentration to calculate short-term exposure safety concentration was set up. Based on the statistical result of water pollution accident occurred in china during 2000-2010, arsenic was a major characteristic contaminate in water pollution accident. According to the method of short-term exposure safety concentration of genotoxic carcinogens, the safety concentration of arsenic was 0.5 mg x L(-1), it showed that the method was feasible in emergence management of water pollution accident. PMID:22509565

  4. Trends Affecting Ohio State University Extension in the 21st Century and the Implications for Human Capital

    ERIC Educational Resources Information Center

    Cochran, Graham R.; Ferrari, Theresa M.; Chen, Claire Yueh-Ti

    2012-01-01

    Research with a diverse array of organizations in the public and private sectors has documented a common set of trends affecting organizations and their human capital in the 21st century. Similar trends have been identified as important for Extension organizations and the Cooperative Extension System. It is important to determine if such trends…

  5. High pressure treatment of human norovirus virus-like particles: factors affecting destruction efficacy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human norovirus (NoV) accounts for more than 90% of nonbacterial gastroenteritis. To date, the efficacy of human NoV inactivation interventions cannot be accurately evaluated because the virus is nonculturable. In this study, we aimed to estimate inactivation of human NoV by high pressure processing...

  6. Genome scan identifies a locus affecting gamma-globin expression in human beta-cluster YAC transgenic mice

    SciTech Connect

    Lin, S.D.; Cooper, P.; Fung, J.; Weier, H.U.G.; Rubin, E.M.

    2000-03-01

    Genetic factors affecting post-natal g-globin expression - a major modifier of the severity of both b-thalassemia and sickle cell anemia, have been difficult to study. This is especially so in mice, an organism lacking a globin gene with an expression pattern equivalent to that of human g-globin. To model the human b-cluster in mice, with the goal of screening for loci affecting human g-globin expression in vivo, we introduced a human b-globin cluster YAC transgene into the genome of FVB mice . The b-cluster contained a Greek hereditary persistence of fetal hemoglobin (HPFH) g allele resulting in postnatal expression of human g-globin in transgenic mice. The level of human g-globin for various F1 hybrids derived from crosses between the FVB transgenics and other inbred mouse strains was assessed. The g-globin level of the C3HeB/FVB transgenic mice was noted to be significantly elevated. To map genes affecting postnatal g-globin expression, a 20 centiMorgan (cM) genome scan of a C3HeB/F VB transgenics [prime] FVB backcross was performed, followed by high-resolution marker analysis of promising loci. From this analysis we mapped a locus within a 2.2 cM interval of mouse chromosome 1 at a LOD score of 4.2 that contributes 10.4% of variation in g-globin expression level. Combining transgenic modeling of the human b-globin gene cluster with quantitative trait analysis, we have identified and mapped a murine locus that impacts on human g-globin expression in vivo.

  7. Issues for resolving adverse effects on the safety culture of human work underload and workload transitions in complex human-machine systems

    SciTech Connect

    Ryan, T.G.

    1996-08-01

    A workshop was conducted whose specific purpose was to build on earlier work of the US National Research Council, US federal government agencies, and the larger human factors community to: (1) clarify human factors issues pertaining to degraded safety 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. The workshop affirmed that: (1) work underload and workload transition are issues that will have to be addressed by designers of advanced human-machine systems, especially those relying on automation, if cost, performance, safety, and operator acceptability are to be optimized, (2) human machine allocation models, standards and guidelines which go beyond simple capability approaches will be needed to preclude or seriously diminish the work underload and workload transition problems, and (3) the 16 workload definition, measurement, situational awareness, and trust issues identified during the workshop, need resolution if these models, standards, and guidelines are to be achieved.

  8. Safety of recombinant human granulocyte-macrophage colony-stimulating factor in healing pediatric severe burns.

    PubMed

    Chi, Y F; Chai, J K; Luo, H M; Zhang, Q X; Feng, R

    2015-01-01

    We explored the safety of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for healing burns in children. Subjects were randomly assigned to two groups: the experimental group received external rhGM-CSF gel, and the control group received rhGM-CSF gel matrix components, applied to the burn surface. Neither group was given any other drugs that promote wound healing. Each day we recorded the pulse, body temperature, and respiration status in the two groups. We detected the blood routine, urine routine, and hepatic and renal function before the patients received drug treatment and after 72 h. The wound scab and healing states in the two groups were recorded every 4 days to evaluate wound healing rate and time taken for complete healing. Adverse reactions and their rate of occurrence were also recorded. The median time of healing was 15 days in the experimental group and 19 days in the control group (log-rank χ(2) = 5.139, P < 0.05). After 10 days, the experimental group healing rate was consistently higher than that of the control group (significantly different using intuitive analysis), suggesting the experimental group method was more effective. There were no obvious adverse reactions. There was no significant difference between the blood routine, urine routine, and liver and kidney function in the two groups before the treatment and after 3 days (P > 0.05). Compared with saline treatment of severe burns, rhGM-CSF can effectively shorten the healing time without significant adverse reactions, and is an effective and safe treatment for burns in children. PMID:25867422

  9. Safety and Efficacy of Human Wharton's Jelly-Derived Mesenchymal Stem Cells Therapy for Retinal Degeneration

    PubMed Central

    Leow, S. N.; Luu, Chi D.; Hairul Nizam, M. H.; Mok, P. L.; Ruhaslizan, R.; Wong, H. S.; Wan Abdul Halim, Wan Haslina; Ng, M. H.; Ruszymah, B. H. I.; Chowdhury, S. R.; Bastion, M. L. C.; Then, K. Y.

    2015-01-01

    Purpose To investigate the safety and efficacy of subretinal injection of human Wharton’s Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats. Methods RCS rats were divided into 2 groups: hWJ-MSCs treated group (n = 8) and placebo control group (n = 8). In the treatment group, hWJ-MSCs from healthy donors were injected into the subretinal space in one eye of each rat at day 21. Control group received saline injection of the same volume. Additional 3 animals were injected with nanogold-labelled stem cells for in vivo tracking of cells localisation using a micro-computed tomography (microCT). Retinal function was assessed by electroretinography (ERG) 3 days before the injection and repeated at days 15, 30 and 70 after the injection. Eyes were collected at day 70 for histology, cellular and molecular studies. Results No retinal tumor formation was detected by histology during the study period. MicroCT scans showed that hWJ-MSCs stayed localised in the eye with no systemic migration. Transmission electron microscopy showed that nanogold-labelled cells were located within the subretinal space. Histology showed preservation of the outer nuclear layer (ONL) in the treated group but not in the control group. However, there were no significant differences in the ERG responses between the groups. Confocal microscopy showed evidence of hWJ-MSCs expressing markers for photoreceptor, Müller cells and bipolar cells. Conclusions Subretinal injection of hWJ-MSCs delay the loss of the ONL in RCS rats. hWJ-MSCs appears to be safe and has potential to differentiate into retinal-like cells. The potential of this cell-based therapy for the treatment of retinal dystrophies warrants further studies. PMID:26107378

  10. Automation of closed environments in space for human comfort and safety

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This report culminates the work accomplished during a three year design project on the automation of an Environmental Control and Life Support System (ECLSS) suitable for space travel and colonization. The system would provide a comfortable living environment in space that is fully functional with limited human supervision. A completely automated ECLSS would increase astronaut productivity while contributing to their safety and comfort. The first section of this report, section 1.0, briefly explains the project, its goals, and the scheduling used by the team in meeting these goals. Section 2.0 presents an in-depth look at each of the component subsystems. Each subsection describes the mathematical modeling and computer simulation used to represent that portion of the system. The individual models have been integrated into a complete computer simulation of the CO2 removal process. In section 3.0, the two simulation control schemes are described. The classical control approach uses traditional methods to control the mechanical equipment. The expert control system uses fuzzy logic and artificial intelligence to control the system. By integrating the two control systems with the mathematical computer simulation, the effectiveness of the two schemes can be compared. The results are then used as proof of concept in considering new control schemes for the entire ECLSS. Section 4.0 covers the results and trends observed when the model was subjected to different test situations. These results provide insight into the operating procedures of the model and the different control schemes. The appendix, section 5.0, contains summaries of lectures presented during the past year, homework assignments, and the completed source code used for the computer simulation and control system.

  11. Initial Assessment of Sulfur-Iodine Process Safety Issues and How They May Affect Pilot Plant Design and Operation

    SciTech Connect

    Robert S. Cherry

    2006-09-01

    The sulfur-iodine process to make hydrogen by the thermochemical splitting of water is under active development as part of a U.S. Department of Energy program. An integrated lab scale system is currently being designed and built. The next planned stage of development is a pilot plant with a thermal input of about 500 kW, equivalent to about 30,000 standard liters per hour of hydrogen production. The sulfur-iodine process contains a variety of hazards, including temperatures up to 850 ºC and hazardous chemical species including SO2, H2SO4, HI, I2, and of course H2. The siting and design of a pilot plant must consider these and other hazards. This report presents an initial analysis of the hazards that might affect pilot plant design and should be considered in the initial planning. The general hazards that have been identified include reactivity, flammability, toxicity, pressure, electrical hazards, and industrial hazards such as lifting and rotating equipment. Personnel exposure to these hazards could occur during normal operations, which includes not only running the process at the design conditions but also initial inventory loading, heatup, startup, shutdown, and system flushing before equipment maintenance. Because of the complexity and severity of the process, these ancillary operations are expected to be performed frequently. In addition, personnel could be exposed to the hazards during various abnormal situations which could include unplanned phase changes of liquids or solids, leaks of process fluids or cooling water into other process streams, unintentional introducion of foreign species into the process, and unexpected side reactions. Design of a pilot plant will also be affected by various codes and regulations such as the International Building Code, the International Fire Code, various National Fire Protection Association Codes, and the Emergency Planning and Community Right-to-Know Act.

  12. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults

    PubMed Central

    Allen, D B; Backeljauw, P; Bidlingmaier, M; Biller, B M K; Boguszewski, M; Burman, P; Butler, G; Chihara, K; Christiansen, J; Cianfarani, S; Clayton, P; Clemmons, D; Cohen, P; Darendeliler, F; Deal, C; Dunger, D; Erfurth, E M; Fuqua, J S; Grimberg, A; Haymond, M; Higham, C; Ho, K; Hoffman, A R; Hokken-Koelega, A; Johannsson, G; Juul, A; Kopchick, J; Lee, P; Pollak, M; Radovick, S; Robison, L; Rosenfeld, R; Ross, R J; Savendahl, L; Saenger, P; Toft Sorensen, H; Stochholm, K; Strasburger, C; Swerdlow, A; Thorner, M

    2015-01-01

    Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that ‘for approved indications, GH is safe’; however, the statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement. PMID:26563978

  13. An Overview of the NASA Aviation Safety Program (AVSP) Systemwide Accident Prevention (SWAP) Human Performance Modeling (HPM) Element

    NASA Technical Reports Server (NTRS)

    Foyle, David C.; Goodman, Allen; Hooley, Becky L.

    2003-01-01

    An overview is provided of the Human Performance Modeling (HPM) element within the NASA Aviation Safety Program (AvSP). Two separate model development tracks for performance modeling of real-world aviation environments are described: the first focuses on the advancement of cognitive modeling tools for system design, while the second centers on a prescriptive engineering model of activity tracking for error detection and analysis. A progressive implementation strategy for both tracks is discussed in which increasingly more complex, safety-relevant applications are undertaken to extend the state-of-the-art, as well as to reveal potential human-system vulnerabilities in the aviation domain. Of particular interest is the ability to predict the precursors to error and to assess potential mitigation strategies associated with the operational use of future flight deck technologies.

  14. Connecting art and science: An interdisciplinary strategy and its impact on the affective domain of community college human anatomy students

    NASA Astrophysics Data System (ADS)

    Petti, Kevin

    Educational objectives are often described within the framework of a three-domain taxonomy: cognitive, affective and psychomotor. While most of the research on educational objectives has focused on the cognitive domain, the research that has been conducted on the affective domain, which speaks to emotions, attitudes, and values, has identified a number of positive outcomes. One approach to enhancing the affective domain is that of interdisciplinary education. Science education research in the realm of interdisciplinary education and affective outcomes is limited; especially research conducted on community college students of human anatomy. This project investigated the relationship between an interdisciplinary teaching strategy and the affective domain in science education by utilizing an interdisciplinary lecture in a human anatomy class. Subjects were anatomy students in a California community college who listened to a one-hour lecture describing the cultural, historical and scientific significance of selected pieces of art depicting human dissection in European medieval and Renaissance universities. The focus was on how these renderings represent the state of anatomy education during their respective eras. After listening to the lecture, subjects were administered a 35-question survey that was composed of 14 demographic questions and 21 Likert-style statements that asked respondents to rate the extent to which the intervention influenced their affective domain. Descriptive statistics were then used to determine which component of the affective domain was most influenced, and multiple regression analysis was used to examine the extent to which individual differences along the affective continuum were explained by select demographic measures such as gender, race/ethnicity, education level, and previous exposure to science courses. Results indicate that the interdisciplinary intervention had a positive impact on every component of the affective domain hierarchy

  15. Safe Thinking and Affect Regulation (STAR): Human Immunodeficiency Virus Prevention in Alternative/Therapeutic Schools

    ERIC Educational Resources Information Center

    Brown, Larry K.; Nugent, Nicole R.; Houck, Christopher D.; Lescano, Celia M.; Whiteley, Laura B.; Barker, David; Viau, Lisa; Zlotnick, Caron

    2011-01-01

    Objective: To evaluate the effectiveness of Safe Thinking and Affect Regulation (STAR), a 14-session HIV-prevention program for adolescents at alternative/therapeutic schools. Because these youth frequently have difficulties with emotions and cognitions, it was designed to improve sexuality-specific affect management and cognitive monitoring, as…

  16. An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions

    PubMed Central

    Pattee, Gary L.; Wymer, James P.; Lomen-Hoerth, Catherine; Appel, Stanley H.; Formella, Andrea E.; Pope, Laura E.

    2014-01-01

    Abstract Background: Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient’s emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. Objective: To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. Methods: Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. Clinical trial registration: #NCT00056524. Results: A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose

  17. Understanding the relationship between safety investment and safety performance of construction projects through agent-based modeling.

    PubMed

    Lu, Miaojia; Cheung, Clara Man; Li, Heng; Hsu, Shu-Chien

    2016-09-01

    The construction industry in Hong Kong increased its safety investment by 300% in the past two decades; however, its accident rate has plateaued to around 50% for one decade. Against this backdrop, researchers have found inconclusive results on the causal relationship between safety investment and safety performance. Using agent-based modeling, this study takes an unconventional bottom-up approach to study safety performance on a construction site as an outcome of a complex system defined by interactions among a worksite, individual construction workers, and different safety investments. Instead of focusing on finding the absolute relationship between safety investment and safety performance, this study contributes to providing a practical framework to investigate how different safety investments interacting with different parameters such as human and environmental factors could affect safety performance. As a result, we could identify cost-effective safety investments under different construction scenarios for delivering optimal safety performance. PMID:27240124

  18. The refinement of uncertainty/safety factors in risk assessment by the incorporation of data on toxicokinetic variability in humans.

    PubMed

    Dorne, J L C M; Renwick, A G

    2005-07-01

    The derivation of safe levels of exposure in humans for compounds that are assumed to cause threshold toxicity has relied on the application of a 100-fold uncertainty factor to a measure for the threshold, such as the no observed adverse effect level (NOAEL) or the benchmark dose (BMD). This 100-fold safety factor consists of the product of two 10-fold factors allowing for human variability and interspecies differences. The International Programme on Chemical Safety has suggested the subdivision of these 10-fold factors to allow for variability in toxicokinetics and toxicodynamics. This subdivision allows the replacement of the default uncertainty factors with a chemical-specific adjustment factor (CSAF) when suitable data are available. This short review describes potential options to refine safety factors used in risk assessment, with particular emphasis on pathway-related uncertainty factors associated with variability in kinetics. These pathway-related factors were derived from a database that quantified interspecies differences and human variability in phase I metabolism, phase II metabolism, and renal excretion. This approach allows metabolism and pharmacokinetic data in healthy adults and subgroups of the population to be incorporated in the risk-assessment process and constitutes an intermediate approach between simple default factors and chemical-specific adjustment factors. PMID:15800035

  19. LD-Aminopterin in the Canine Homologue of Human Atopic Dermatitis: A Randomized, Controlled Trial Reveals Dosing Factors Affecting Optimal Therapy

    PubMed Central

    Zebala, John A.; Mundell, Alan; Messinger, Linda; Griffin, Craig E.; Schuler, Aaron D.; Kahn, Stuart J.

    2014-01-01

    Background Options are limited for patients with atopic dermatitis (AD) who do not respond to topical treatments. Antifolate therapy with systemic methotrexate improves the disease, but is associated with adverse effects. The investigational antifolate LD-aminopterin may offer improved safety. It is not known how antifolate dose and dosing frequency affect efficacy in AD, but a primary mechanism is thought to involve the antifolate-mediated accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). However, recent in vitro studies indicate that AICAR increases then decreases as a function of antifolate concentration. To address this issue and understand how dosing affects antifolate efficacy in AD, we examined the efficacy and safety of different oral doses and schedules of LD-aminopterin in the canine model of AD. Methods and Findings This was a multi-center, double-blind trial involving 75 subjects with canine AD randomized to receive up to 12 weeks of placebo, once-weekly (0.007, 0.014, 0.021 mg/kg) or twice-weekly (0.007 mg/kg) LD-aminopterin. The primary efficacy outcome was the Global Score (GS), a composite of validated measures of disease severity and itch. GS improved in all once-weekly cohorts, with 0.014 mg/kg being optimal and significant (43%, P<0.01). The majority of improvement was seen by 8 weeks. In contrast, GS in the twice-weekly cohort was similar to placebo and worse than all once-weekly cohorts. Adverse events were similar across all treated cohorts and placebo. Conclusions Once-weekly LD-aminopterin was safe and efficacious in canine AD. Twice-weekly dosing negated efficacy despite having the same daily and weekly dose as effective once-weekly regimens. Optimal dosing in this homologue of human AD correlated with the concentration-selective accumulation of AICAR in vitro, consistent with AICAR mediating LD-aminopterin efficacy in AD. PMID:25255447

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

    NASA Technical Reports Server (NTRS)

    Washburn, David A.

    1992-01-01

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

  1. Safety issues of Lactobacillus bulgaricus with respect to human gelatinases in vitro.

    PubMed

    Stamatova, Iva; Meurman, Jukka H; Kari, Kirsti; Tervahartiala, Taina; Sorsa, Timo; Baltadjieva, Maria

    2007-10-01

    In oral medicine and dentistry probiotics have shown promising results in controlling dental diseases and yeast infections. This study was made to investigate the effect of eight strains of Lactobacillus bulgaricus and their effects on human matrix metalloproteinase-9 (MMP-9). The hypothesis was that these bacteria used in yoghurt production for centuries are not proteolytic and thus can be safely used in the development of probiotic preparations. Bacterial cell fractions and supernatant specimens were prepared and studied with gelatinase zymography and MMP-9 activation was assessed by immunoblotting. The effect of synthetic MMP inhibitors and a serine protease inhibitor (Pefabloc) on bacterial proteinases was studied with zymography. The results showed very low gelatinolytic activity. There was a slight difference between the supernatant and cell fractions so that the supernatant specimens produced weak gelatinolytic bands in zymography while hardly anything was seen in the cell fraction series. The tested synthetic MMP inhibitors and Pefabloc did not affect the proteolytic activity of the lactobacilli strains. The lactobacilli did not seem to induce the conversion of proMMP-9 to its active form. Consequently, our study hypothesis was confirmed and the studied Lactobacillus strains are not likely to degrade host tissue components. PMID:17854478

  2. Cross-species affective functions of the medial forebrain bundle-implications for the treatment of affective pain and depression in humans.

    PubMed

    Coenen, Volker A; Schlaepfer, Thomas E; Maedler, Burkhard; Panksepp, Jaak

    2011-10-01

    Major depression (MD) might be conceptualized as pathological under-arousal of positive affective systems as parts of a network of brain regions assessing, reconciling and storing emotional stimuli versus an over-arousal of parts of the same network promoting separation-distress/GRIEF. In this context depression can be explained as an emotional pain state that is the result of a disregulation of several sub-systems that under physiological conditions are concerned with bodily or emotional homeostasis of the human organism in a social context. Physiologically, homeostasis is maintained by influences of the SEEKING system represented - amongst others - by the medial forebrain bundle (MFB). Neuroimaging studies show that the MFB has a proven access to the GRIEF/Sadness system. A functional decoupling of these systems with a dysfunctional GRIEF pathway might result in MD. Therewith GRIEF and SEEKING/PLEASURE systems play important roles as opponents in maintenance of emotional homeostasis. Chronic electrical modulation of the reward SEEKING pathways with deep brain stimulation might show anti-depressive effects in humans suffering from MD by re-initiating an emotional equilibrium (of higher or lower activity) between these opposing systems. PMID:21184778

  3. Using the WTO/TBT enquiry point to monitor tendencies in the regulation of environment, health, and safety issues affecting the chemical industry.

    PubMed

    Pio Borges Menezes, Rodrigo; Maria de Souza Antunes, Adelaide

    2005-04-01

    The growing importance of technical regulation affecting the use and sale of chemical products is a topic of interest not only for the chemical industry, but also for governments, nongovernmental organizations, consumers, and interested communities. The results of such regulation on behalf of the environment, health and safety of individuals, as well as its economic effects on industrial activity, are well understood in the United States and recently in the European Union. In less developed countries, however, the general level of public understanding of these issues is still minimal. It is common knowledge that the so-called "regulatory asymmetry" between countries at different levels of development contributes to the establishment of technical barriers to trade. Such asymmetries, however, also have other impacts: the displacement of polluting industrial sectors to countries which have less demanding regulations, the concentration of unsafe and harmful environmental conditions in certain parts of the globe, and the competitive disadvantage for industries located in countries where control is more rigid. This study analyses information on a wide range of technical regulations issued by World Trade Organization (WTO) members, and focuses on those regulations that affect the chemical industry. This information is available through the WTO Enquiry Points, organizations created in each country to administrate the Technical Barriers to Trade Agreement (TBT). This article consists of an analysis of 4,301 notifications of technical regulations by WTO member states in the 7-year period following the establishment of the WTO in 1995. Starting from this mass of information, 585 notifications that affect the circulation or use of chemical products were isolated. Of this group, 71% refer to only 15 countries. This group of notifications was further classified according to their motivation (the environment, health, safety), by the type of product affected (medications, fuels

  4. Safety Characteristics in System Application of Software for Human Rated Exploration Missions for the 8th IAASS Conference

    NASA Technical Reports Server (NTRS)

    Mango, Edward J.

    2016-01-01

    NASA and its industry and international partners are embarking on a bold and inspiring development effort to design and build an exploration class space system. The space system is made up of the Orion system, the Space Launch System (SLS) and the Ground Systems Development and Operations (GSDO) system. All are highly coupled together and dependent on each other for the combined safety of the space system. A key area of system safety focus needs to be in the ground and flight application software system (GFAS). In the development, certification and operations of GFAS, there are a series of safety characteristics that define the approach to ensure mission success. This paper will explore and examine the safety characteristics of the GFAS development. The GFAS system integrates the flight software packages of the Orion and SLS with the ground systems and launch countdown sequencers through the 'agile' software development process. A unique approach is needed to develop the GFAS project capabilities within this agile process. NASA has defined the software development process through a set of standards. The standards were written during the infancy of the so-called industry 'agile development' movement and must be tailored to adapt to the highly integrated environment of human exploration systems. Safety of the space systems and the eventual crew on board is paramount during the preparation of the exploration flight systems. A series of software safety characteristics have been incorporated into the development and certification efforts to ensure readiness for use and compatibility with the space systems. Three underlining factors in the exploration architecture require the GFAS system to be unique in its approach to ensure safety for the space systems, both the flight as well as the ground systems. The first are the missions themselves, which are exploration in nature, and go far beyond the comfort of low Earth orbit operations. The second is the current exploration

  5. A functional MiR-124 binding-site polymorphism in IQGAP1 affects human cognitive performance.

    PubMed

    Yang, Lixin; Zhang, Rui; Li, Ming; Wu, Xujun; Wang, Jianhong; Huang, Lin; Shi, Xiaodong; Li, Qingwei; Su, Bing

    2014-01-01

    As a product of the unique evolution of the human brain, human cognitive performance is largely a collection of heritable traits. Rather surprisingly, to date there have been no reported cases to highlight genes that underwent adaptive evolution in humans and which carry polymorphisms that have a marked effect on cognitive performance. IQ motif containing GTPase activating protein 1 (IQGAP1), a scaffold protein, affects learning and memory in a dose-dependent manner. Its expression is regulated by miR-124 through the binding sites in the 3'UTR, where a SNP (rs1042538) exists in the core-binding motif. Here we showed that this SNP can influence the miR-target interaction both in vitro and in vivo. Individuals carrying the derived T alleles have higher IQGAP1 expression in the brain as compared to the ancestral A allele carriers. We observed a significant and male-specific association between rs1042538 and tactile performances in two independent cohorts. Males with the derived allele displayed higher tactual performances as compared to those with the ancestral allele. Furthermore, we found a highly diverged allele-frequency distribution of rs1042538 among world human populations, likely caused by natural selection and/or recent population expansion. These results suggest that current human populations still carry sequence variations that affect cognitive performances and that these genetic variants may likely have been subject to comparatively recent natural selection. PMID:25222038

  6. Microwaves from GSM Mobile Telephones Affect 53BP1 and γ-H2AX Foci in Human Lymphocytes from Hypersensitive and Healthy Persons

    PubMed Central

    Markovà, Eva; Hillert, Lena; Malmgren, Lars; Persson, Bertil R. R.; Belyaev, Igor Y.

    2005-01-01

    The data on biologic effects of nonthermal microwaves (MWs) from mobile telephones are diverse, and these effects are presently ignored by safety standards of the International Commission for Non-Ionizing Radiation Protection (ICNIRP). In the present study, we investigated effects of MWs of Global System for Mobile Communication (GSM) at different carrier frequencies on human lymphocytes from healthy persons and from persons reporting hypersensitivity to electromagnetic fields (EMFs). We measured the changes in chromatin conformation, which are indicative of stress response and genotoxic effects, by the method of anomalous viscosity time dependence, and we analyzed tumor suppressor p53-binding protein 1 (53BP1) and phosphorylated histone H2AX (γ-H2AX), which have been shown to colocalize in distinct foci with DNA double-strand breaks (DSBs), using immunofluorescence confocal laser microscopy. We found that MWs from GSM mobile telephones affect chromatin conformation and 53BP1/γ-H2AX foci similar to heat shock. For the first time, we report here that effects of MWs from mobile telephones on human lymphocytes are dependent on carrier frequency. On average, the same response was observed in lymphocytes from hypersensitive and healthy subjects. PMID:16140623

  7. The metabolome of [2-14C](−)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives

    PubMed Central

    Ottaviani, Javier I.; Borges, Gina; Momma, Tony Y.; Spencer, Jeremy P. E.; Keen, Carl L.; Crozier, Alan; Schroeter, Hagen

    2016-01-01

    Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack of fundamental data describing the absorption, distribution, metabolism and excretion (ADME) of bioactive compounds. Consequently, we selected the flavanol (−)-epicatechin (EC) as an example of a widely studied bioactive food constituent and investigated the ADME of [2-14C](−)-epicatechin (300 μCi, 60 mg) in humans (n = 8). We demonstrated that 82 ± 5% of ingested EC was absorbed. We also established pharmacokinetic profiles and identified and quantified >20 different metabolites. The gut microbiome proved to be a key driver of EC metabolism. Furthermore, we noted striking species-dependent differences in the metabolism of EC, an insight with significant consequences for investigating the mechanisms of action underlying the beneficial effects of EC. These differences need to be considered when assessing the safety of EC intake in humans. We also identified a potential biomarker for the objective assessment of EC intake that could help to strengthen epidemiological investigations. PMID:27363516

  8. Evaluation of safety and human tolerance of the oral probiotic Streptococcus salivarius K12: a randomized, placebo-controlled, double-blind study.

    PubMed

    Burton, J P; Cowley, S; Simon, R R; McKinney, J; Wescombe, P A; Tagg, J R

    2011-09-01

    Streptococcus salivarius is naturally a predominant member of the human oropharynx and the commercial probiotic strain K12 has been consumed for more than a decade. The present study examines the health responses of human volunteers to oral ingestion of high doses of S. salivarius K12. A randomized group of 53 subjects received a dose of 1 × 10(10)cfu S. salivarius K12 (N=25) or placebo (N=28) for 28 days, followed by a 28-day wash out period. Blood, urine and saliva samples were collected at baseline and following treatment and analyzed, while the oral and gastrointestinal tolerance of the subjects to the dosing regimen was determined by use of questionnaires. Adverse events (AE)s were recorded for both groups. No statistically significant differences between the probiotic and placebo treated groups were detected in either the blood clinical chemistry or hematology results (P>0.05). The questionnaire responses of the subjects indicated that both treatments were well tolerated. The frequency and intensity of AEs was similar in the two groups. This data demonstrates that the daily ingestion of S. salivarius K12 over a 28-day period does not adversely affect the human host and supports the safety of its oral delivery in a food-based carrier. PMID:21722694

  9. The metabolome of [2-(14)C](-)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives.

    PubMed

    Ottaviani, Javier I; Borges, Gina; Momma, Tony Y; Spencer, Jeremy P E; Keen, Carl L; Crozier, Alan; Schroeter, Hagen

    2016-01-01

    Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack of fundamental data describing the absorption, distribution, metabolism and excretion (ADME) of bioactive compounds. Consequently, we selected the flavanol (-)-epicatechin (EC) as an example of a widely studied bioactive food constituent and investigated the ADME of [2-(14)C](-)-epicatechin (300 μCi, 60 mg) in humans (n = 8). We demonstrated that 82 ± 5% of ingested EC was absorbed. We also established pharmacokinetic profiles and identified and quantified >20 different metabolites. The gut microbiome proved to be a key driver of EC metabolism. Furthermore, we noted striking species-dependent differences in the metabolism of EC, an insight with significant consequences for investigating the mechanisms of action underlying the beneficial effects of EC. These differences need to be considered when assessing the safety of EC intake in humans. We also identified a potential biomarker for the objective assessment of EC intake that could help to strengthen epidemiological investigations. PMID:27363516

  10. Cognitive performance-altering effects of electronic medical records: An application of the human factors paradigm for patient safety

    PubMed Central

    Holden, Richard J.

    2010-01-01

    According to the human factors paradigm for patient safety, health care work systems and innovations such as electronic medical records do not have direct effects on patient safety. Instead, their effects are contingent on how the clinical work system, whether computerized or not, shapes health care providers' performance of cognitive work processes. An application of the human factors paradigm to interview data from two hospitals in the Midwest United States yielded numerous examples of the performance-altering effects of electronic medical records, electronic clinical documentation, and computerized provider order entry. Findings describe both improvements and decrements in the ease and quality of cognitive performance, both for interviewed clinicians and for their colleagues and patients. Changes in cognitive performance appear to have desirable and undesirable implications for patient safety as well as for quality of care and other important outcomes. Cognitive performance can also be traced to interactions between work system elements, including new technology, allowing for the discovery of problems with “fit” to be addressed through design interventions. PMID:21479125

  11. An Inducible Caspase-9 Suicide Gene to Improve the Safety of Therapy Using Human Induced Pluripotent Stem Cells.

    PubMed

    Yagyu, Shigeki; Hoyos, Valentina; Del Bufalo, Francesca; Brenner, Malcolm K

    2015-09-01

    Human induced pluripotent stem cells (hiPSC) hold promise for regenerative therapies, though there are several safety concerns including the risk of oncogenic transformation or unwanted adverse effects associated with hiPSC or their differentiated progeny. Introduction of the inducible caspase-9 (iC9) suicide gene, which is activated by a specific chemical inducer of dimerization (CID), is one of the most appealing safety strategies for cell therapies and is currently being tested in multicenter clinical trials. Here, we show that the iC9 suicide gene with a human EF1α promoter can be introduced into hiPSC by lentiviral transduction. The transduced hiPSC maintain their pluripotency, including their capacity for unlimited self-renewal and the potential to differentiate into three germ layer tissues. Transduced hiPSC are eliminated within 24 hours of exposure to pharmacological levels of CID in vitro, with induction of apoptosis in 94-99% of the cells. Importantly, the iC9 suicide gene can eradicate tumors derived from hiPSC in vivo. In conclusion, we have developed a direct and efficient hiPSC killing system that provides a necessary safety mechanism for therapies using hiPSC. We believe that our iC9 suicide gene will be of value in clinical applications of hiPSC-based therapy. PMID:26022733

  12. Safety Psychology Applicating on Coal Mine Safety Management Based on Information System

    NASA Astrophysics Data System (ADS)

    Hou, Baoyue; Chen, Fei

    In recent years, with the increase of intensity of coal mining, a great number of major accidents happen frequently, the reason mostly due to human factors, but human's unsafely behavior are affected by insecurity mental control. In order to reduce accidents, and to improve safety management, with the help of application security psychology, we analyse the cause of insecurity psychological factors from human perception, from personality development, from motivation incentive, from reward and punishment mechanism, and from security aspects of mental training , and put forward countermeasures to promote coal mine safety production,and to provide information for coal mining to improve the level of safety management.

  13. An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy.

    PubMed

    Brownbill, Paul; Chernyavsky, Igor; Bottalico, Barbara; Desoye, Gernot; Hansson, Stefan; Kenna, Gerry; Knudsen, Lisbeth E; Markert, Udo R; Powles-Glover, Nicola; Schneider, Henning; Leach, Lopa

    2016-09-01

    The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures in pregnancy and how ex vivo and in vitro human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, "PlaNet", will bridge academia, industry and regulators to consider screen ability and standardisation issues surrounding these models, with proven reproducibility for introduction into industrial and clinical practice. PMID:27327413

  14. Fire safety applications for spacecraft

    NASA Technical Reports Server (NTRS)

    Friedman, Robert; Olson, Sandra L.

    1989-01-01

    Fire safety for spacecraft is reviewed by first describing current practices, many of which are adapted directly from aircraft. Then, current analyses and experimental knowledge in low-gravity combustion, with implications for fire safety are discussed. In orbiting spacecraft, the detection and suppression of flames are strongly affected by the large reduction in buoyant flows under low gravity. Generally, combustion intensity is reduced in low gravity. There are some notable exceptions, however, one example being the strong enhancement of flames by low-velocity ventilation flows in space. Finally, the future requirements in fire safety, particularly the needs of long-duration space stations in fire prevention, detection, extinguishment, and atmospheric control are examined. The goal of spacecraft fire-safety investigations is the establishment of trade-offs that promote maximum safety without hampering the useful human and scientific activities in space.

  15. Human erythrocytes are affected in vitro by flavonoids of Aristotelia chilensis (Maqui) leaves.

    PubMed

    Suwalsky, Mario; Vargas, Pedro; Avello, Marcia; Villena, Fernando; Sotomayor, Carlos P

    2008-11-01

    Aristotelia chilensis (Mol.) Stuntz (A. chilensis), also known as maqui, is a plant of the Elaeocarpaceae family that grows in central and southern Chile as well as southwestern Argentina. Infusions of its leaves have long been used in the traditional native herbal medicine to treat different ailments. Phytochemical studies of the plant's chemical composition of the plant indicate the presence of indolic alkaloids, flavonoids, cianidine glucosides, delfidine, malvidine, petunidine, cumarines and triterpenes. These compounds, particularly the flavonoids, have antioxidant properties. In order to evaluate the mechanisms of its toxicity and their antioxidant properties, the leaves' aqueous extracts were induced to interact with human red cells, their isolated unsealed membranes (IUM), and molecular models of the human erythrocyte membrane. These consisted of multibilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipids classes located in the outer and inner monolayers of the human erythrocyte membrane, and large unilamellar vesicles (LUV) of DMPC. The capacity of A. chilensis aqueous extracts to perturb the bilayer structure of DMPC and DMPE was evaluated by X-ray diffraction, DMPC LUV and IUM were studied by fluorescence spectroscopy, and intact human erythrocytes were observed by scanning electron microscopy (SEM). Results of the present study indicate that aqueous extracts of A. chilensis induced an alteration of human erythrocyte morphology from the normal discoid shape to an echinocytic form, changes that are explained in terms of the extract interaction with the membrane's outer phospholipid monolayer. PMID:18687390

  16. Human Impacts Affect Tree Community Features of 20 Forest Fragments of a Vanishing Neotropical Hotspot

    NASA Astrophysics Data System (ADS)

    Pereira, José Aldo Alves; de Oliveira-Filho, Ary Teixeira; Eisenlohr, Pedro V.; Miranda, Pedro L. S.; de Lemos Filho, José Pires

    2015-02-01

    The loss in forest area due to human occupancy is not the only threat to the remaining biodiversity: forest fragments are susceptible to additional human impact. Our aim was to investigate the effect of human impact on tree community features (species composition and abundance, and structural descriptors) and check if there was a decrease in the number of slender trees, an increase in the amount of large trees, and also a reduction in the number of tree species that occur in 20 fragments of Atlantic montane semideciduous forest in southeastern Brazil. We produced digital maps of each forest fragment using Landsat 7 satellite images and processed the maps to obtain morphometric variables. We used investigative questionnaires and field observations to survey the history of human impact. We then converted the information into scores given to the extent, severity, and duration of each impact, including proportional border area, fire, trails, coppicing, logging, and cattle, and converted these scores into categorical levels. We used linear models to assess the effect of impacts on tree species abundance distribution and stand structural descriptors. Part of the variation in floristic patterns was significantly correlated to the impacts of fire, logging, and proportional border area. Structural descriptors were influenced by cattle and outer roads. Our results provided, for the first time, strong evidence that tree species occurrence and abundance, and forest structure of Atlantic seasonal forest fragments respond differently to various modes of disturbance by humans.

  17. Human impacts affect tree community features of 20 forest fragments of a vanishing neotropical hotspot.

    PubMed

    Pereira, José Aldo Alves; de Oliveira-Filho, Ary Teixeira; Eisenlohr, Pedro V; Miranda, Pedro L S; de Lemos Filho, José Pires

    2015-02-01

    The loss in forest area due to human occupancy is not the only threat to the remaining biodiversity: forest fragments are susceptible to additional human impact. Our aim was to investigate the effect of human impact on tree community features (species composition and abundance, and structural descriptors) and check if there was a decrease in the number of slender trees, an increase in the amount of large trees, and also a reduction in the number of tree species that occur in 20 fragments of Atlantic montane semideciduous forest in southeastern Brazil. We produced digital maps of each forest fragment using Landsat 7 satellite images and processed the maps to obtain morphometric variables. We used investigative questionnaires and field observations to survey the history of human impact. We then converted the information into scores given to the extent, severity, and duration of each impact, including proportional border area, fire, trails, coppicing, logging, and cattle, and converted these scores into categorical levels. We used linear models to assess the effect of impacts on tree species abundance distribution and stand structural descriptors. Part of the variation in floristic patterns was significantly correlated to the impacts of fire, logging, and proportional border area. Structural descriptors were influenced by cattle and outer roads. Our results provided, for the first time, strong evidence that tree species occurrence and abundance, and forest structure of Atlantic seasonal forest fragments respond differently to various modes of disturbance by humans. PMID:25344658

  18. Foods and food constituents that affect the brain and human behavior

    NASA Technical Reports Server (NTRS)

    Lieberman, Harris R.; Wurtman, Richard J.

    1986-01-01

    Until recently, it was generally believed that brain function was usually independent of day-to-day metabolic changes associated with consumption of food. Although it was acknowledged that peripheral metabolic changes associated with hunger or satiety might affect brain function, other effects of foods on the brain were considered unlikely. However, in 1971, Fernstrom and Wurtman discovered that under certain conditions, the protein-to-carbohydrate ratio of a meal could affect the concentration of a particular brain neurotransmitter. That neurotransmitter, serotonin, participates in the regulation of a variety of central nervous system (CNS) functions including sleep, pain sensitivity, aggression, and patterns of nutrient selection. The activity of other neurotransmitter systems has also been shown to be, under certain conditions, affected by dietary constituents which are given either as ordinary foods or in purified form. For example, the CNS turnover of two catecholamine neurotransmitters, dopamine and norepinephrine, can be altered by ingestion of their amino acid precursor, tyrosine, when neurons that release these monoamines are firing frequently. Similarly, lecithin, a dietary source of choline, and choline itself have been shown to increase the synthesis of acetylcholine when cholinergic neurons are very active. It is possible that other neurotransmitters could also be affected by precursor availability or other, as yet undiscovered peripheral factors governed by food consumption. The effects of food on neurotransmitters and behavior are discussed.

  19. A single-nucleotide variation in a p53-binding site affects nutrient-sensitive human SIRT1 expression

    PubMed Central

    Naqvi, Asma; Hoffman, Timothy A.; DeRicco, Jeremy; Kumar, Ajay; Kim, Cuk-Seong; Jung, Saet-Byel; Yamamori, Tohru; Kim, Young-Rae; Mehdi, Fardeen; Kumar, Santosh; Rankinen, Tuomo; Ravussin, Eric; Irani, Kaikobad

    2010-01-01

    The SIRTUIN1 (SIRT1) deacetylase responds to changes in nutrient availability and regulates mammalian physiology and metabolism. Human and mouse SIRT1 are transcriptionally repressed by p53 via p53 response elements in their proximal promoters. Here, we identify a novel p53-binding sequence in the distal human SIRT1 promoter that is required for nutrient-sensitive SIRT1 transcription. In addition, we show that a common single-nucleotide (C/T) variation in this sequence affects nutrient deprivation-induced SIRT1 transcription, and calorie restriction-induced SIRT1 expression. The p53-binding sequence lies in a region of the SIRT1 promoter that also binds the transcriptional repressor Hypermethylated-In-Cancer-1 (HIC1). Nutrient deprivation increases occupancy by p53, while decreasing occupancy by HIC1, of this region of the promoter. HIC1 and p53 compete with each other for promoter occupancy. In comparison with the T variation, the C variation disrupts the mirror image symmetry of the p53-binding sequence, resulting in decreased binding to p53, decreased nutrient sensitivity of the promoter and impaired calorie restriction-stimulated tissue expression of SIRT1 and SIRT1 target genes AMPKα2 and PGC-1β. Thus, a common SNP in a novel p53-binding sequence in the human SIRT1 promoter affects nutrient-sensitive SIRT1 expression, and could have a significant impact on calorie restriction-induced, SIRT1-mediated, changes in human metabolism and physiology. PMID:20693263

  20. Did warfare among ancestral hunter-gatherers affect the evolution of human social behaviors?

    PubMed

    Bowles, Samuel

    2009-06-01

    Since Darwin, intergroup hostilities have figured prominently in explanations of the evolution of human social behavior. Yet whether ancestral humans were largely "peaceful" or "warlike" remains controversial. I ask a more precise question: If more cooperative groups were more likely to prevail in conflicts with other groups, was the level of intergroup violence sufficient to influence the evolution of human social behavior? Using a model of the evolutionary impact of between-group competition and a new data set that combines archaeological evidence on causes of death during the Late Pleistocene and early Holocene with ethnographic and historical reports on hunter-gatherer populations, I find that the estimated level of mortality in intergroup conflicts would have had substantial effects, allowing the proliferation of group-beneficial behaviors that were quite costly to the individual altruist. PMID:19498163

  1. Human erythrocytes and neuroblastoma cells are affected in vitro by Au(III) ions

    SciTech Connect

    Suwalsky, Mario; Gonzalez, Raquel; Villena, Fernando; Aguilar, Luis F.; Sotomayor, Carlos P.; Bolognin, Silvia; Zatta, Paolo

    2010-06-25

    Gold compounds are well known for their neurological and nephrotoxic implications. However, haematological toxicity is one of the most serious toxic and less studied effects. The lack of information on these aspects of Au(III) prompted us to study the structural effects induced on cell membranes, particularly that of human erythrocytes. AuCl{sub 3} was incubated with intact erythrocytes, isolated unsealed human erythrocyte membranes (IUM) and molecular models of the erythrocyte membrane. The latter consisted of multibilayers of dimyristoylphosphatidylcholine and dimyristoylphosphatidylethanolamine, phospholipids classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. This report presents evidence that Au(III) interacts with red cell membranes as follows: (a) in scanning electron microscopy studies on human erythrocytes it was observed that Au(III) induced shape changes at a concentration as low as 0.01 {mu}M; (b) in isolated unsealed human erythrocyte membranes Au(III) induced a decrease in the molecular dynamics and/or water content at the glycerol backbone level of the lipid bilayer polar groups in a 5-50 {mu}M concentration range, and (c) X-ray diffraction studies showed that Au(III) in the 10 {mu}m-1 mM range induced increasing structural perturbation only to dimyristoylphosphatidylcholine bilayers. Additional experiments were performed in human neuroblastoma cells SH-SY5Y. A statistically significant decrease of cell viability was observed with Au(III) ranging from 0.1 {mu}M to 100 {mu}M.

  2. Derivation of Huntington Disease affected Genea091 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Schaft, Julia; McKernan, Robert; Hu, Jesselyn; Schmidt, Uli

    2016-03-01

    The Genea091 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 40 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 92% of cells expressed Nanog, 97% Oct4, 79% Tra1-60 and 98% SSEA4 and gave a Pluritest pluripotency score of 38.36, Novelty of 1.35. The cell line was negative for Mycoplasma and visible contamination. PMID:27346013

  3. Derivation of DM1 affected human embryonic stem cell line Genea067.

    PubMed

    Dumevska, Biljana; Main, Heather; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea067 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying expansion of CTG repeats in the DMPK gene, indicative of Myotonic Dystrophy Type 1 (DM1). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 97% Oct4, 73% Tra1-60 and 98% SSEA4 and gave a Pluritest Pluripotency score of 25.75, Novelty of 1.46. The cell line was negative for Mycoplasma and visible contamination. PMID:27346009

  4. Derivation of DM2 affected human embryonic stem cell line Genea066.

    PubMed

    Dumevska, Biljana; Schaft, Julia; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea066 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying expansion of CCTG repeats in exon 1 of the ZNF9 gene, indicative of Myotonic Dystrophy Type 2 (DM2). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male Allele pattern. The hESC line had pluripotent cell morphology, 88% of cells expressed Nanog, 97% Oct4, 80% Tra1-60 and 99% SSEA4 and gave a Pluritest Pluripotency score of 31.3, Novelty of 1.22. The cell line was negative for Mycoplasma and visible contamination. PMID:27346023

  5. Derivation of Huntington Disease affected Genea046 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Chami, Omar; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea046 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying HTT gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 92% Oct4, 75% Tra1-60 and 99% SSEA4 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination. PMID:27346012

  6. Derivation of Huntington Disease affected Genea089 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Hu, Jesselyn; Schmidt, Uli

    2016-03-01

    The Genea089 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 41 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 91% of cells expressed Nanog, 95% Oct4, 90% Tra1-60 and 100% SSEA4 and gave a PluriTest Pluripotency score of 39.28, Novelty of 1.2. The cell line was negative for Mycoplasma and visible contamination. PMID:27346008

  7. Derivation of Huntington Disease affected Genea090 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Schaft, Julia; McKernan, Robert; Hu, Jesselyn; Schmidt, Uli

    2016-03-01

    The Genea090 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female allele pattern. The hESC line had pluripotent cell morphology, 91% of cells expressed Nanog, 95% Oct4, 90% Tra1-60 and 100% SSEA4 and gave a pluritest pluripotency score of 30.91, novelty of 1.23. The cell line was negative for Mycoplasma and visible contamination. PMID:27346026

  8. Derivation of Huntington disease affected Genea020 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Peura, Teija; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea020 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 48 repeats, indicative of Huntington disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female allele pattern. The hESC line had pluripotent cell morphology, 89% of cells expressed Nanog, 95% Oct4, 29% Tra1-60 and 99% SSEA4, gave a Pluritest pluripotency score of 27.51, novelty of 1.43 and demonstrated alkaline phosphatase activity. The cell line was negative for Mycoplasma and visible contamination. PMID:27346007

  9. How Do ICT Uses and New Human Resources Practices Affect SMEs' Efficiency?

    NASA Astrophysics Data System (ADS)

    Castillo-Merino, David; Serradell-Lopez, Enric; González-González, Inés

    In this paper we have analyzed both the main traits of efficient firms and the main sources of firms' efficiency, through a representative sample of 2.029 small and medium size Catalan firms. Our results demonstrate the importance for entrepreneurs of realizing that firms' efficiency shows a significant improvement when advanced ICT uses are combined with human resources practices focused on the promotion of workers autonomy, flexibility and decentralization of firm's decision making process, and with the adoption of employees assessment systems based on human values.

  10. Derivation of Trisomy 21 affected human embryonic stem cell line Genea053.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea053 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Trisomy 21, indicative of Down Syndrome. Following ICM outgrowth on inactivated human feeders, CGH and STR analysis demonstrated a 47, XY, +21 karyotype and male allele pattern. The hESC line had pluripotent cell morphology and expressed pluripotent cell markers including 83% Nanog positive, 87% Oct4, 88% Tra1-60 and 98% SSEA4. The cell line was negative for Mycoplasma and visible contamination. PMID:27346024

  11. Derivation of Trisomy 21 affected human embryonic stem cell line Genea021.

    PubMed

    Dumevska, Biljana; Bosman, Alexis; McKernan, Robert; Main, Heather; Schmidt, Uli; Peura, Teija

    2016-03-01

    The Genea021 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Trisomy 21, indicative of Down Syndrome. Following ICM outgrowth on inactivated human feeders, CGH and STR analyses demonstrated a 47, XY, +21 karyotype and male allele pattern. The hESC line had pluripotent cell morphology, 71% of cells expressed Nanog, 84% Oct4, 23% Tra1-60 and 95% SSEA4, gave a Pluritest Pluripotency score of 21.85, Novelty of 1.42, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination. PMID:27346003

  12. Immunogenetic Factors Affecting Susceptibility of Humans and Rodents to Hantaviruses and the Clinical Course of Hantaviral Disease in Humans

    PubMed Central

    Charbonnel, Nathalie; Pagès, Marie; Sironen, Tarja; Henttonen, Heikki; Vapalahti, Olli; Mustonen, Jukka; Vaheri, Antti

    2014-01-01

    We reviewed the associations of immunity-related genes with susceptibility of humans and rodents to hantaviruses, and with severity of hantaviral diseases in humans. Several class I and class II HLA haplotypes were linked with severe or benign hantavirus infections, and these haplotypes varied among localities and hantaviruses. The polymorphism of other immunity-related genes including the C4A gene and a high-producing genotype of TNF gene associated with severe PUUV infection. Additional genes that may contribute to disease or to PUUV infection severity include non-carriage of the interleukin-1 receptor antagonist (IL-1RA) allele 2 and IL-1β (-511) allele 2, polymorphisms of plasminogen activator inhibitor (PAI-1) and platelet GP1a. In addition, immunogenetic studies have been conducted to identify mechanisms that could be linked with the persistence/clearance of hantaviruses in reservoirs. Persistence was associated during experimental infections with an upregulation of anti-inflammatory responses. Using natural rodent population samples, polymorphisms and/or expression levels of several genes have been analyzed. These genes were selected based on the literature of rodent or human/hantavirus interactions (some Mhc class II genes, Tnf promoter, and genes encoding the proteins TLR4, TLR7, Mx2 and β3 integrin). The comparison of genetic differentiation estimated between bank vole populations sampled over Europe, at neutral and candidate genes, has allowed to evidence signatures of selection for Tnf, Mx2 and the Drb Mhc class II genes. Altogether, these results corroborated the hypothesis of an evolution of tolerance strategies in rodents. We finally discuss the importance of these results from the medical and epidemiological perspectives. PMID:24859344

  13. Human ergology that promotes participatory approach to improving safety, health and working conditions at grassroots workplaces: achievements and actions.

    PubMed

    Kawakami, Tsuyoshi

    2011-12-01

    Participatory approaches are increasingly applied to improve safety, health and working conditions of grassroots workplaces in Asia. The core concepts and methods in human ergology research such as promoting real work life studies, relying on positive efforts of local people (daily life-technology), promoting active participation of local people to identify practical solutions, and learning from local human networks to reach grassroots workplaces, have provided useful viewpoints to devise such participatory training programmes. This study was aimed to study and analyze how human ergology approaches were applied in the actual development and application of three typical participatory training programmes: WISH (Work Improvement for Safe Home) with home workers in Cambodia, WISCON (Work Improvement in Small Construction Sites) with construction workers in Thailand, and WARM (Work Adjustment for Recycling and Managing Waste) with waste collectors in Fiji. The results revealed that all the three programmes, in the course of their developments, commonly applied direct observation methods of the work of target workers before devising the training programmes, learned from existing local good examples and efforts, and emphasized local human networks for cooperation. These methods and approaches were repeatedly applied in grassroots workplaces by taking advantage of their the sustainability and impacts. It was concluded that human ergology approaches largely contributed to the developments and expansion of participatory training programmes and could continue to support the self-help initiatives of local people for promoting human-centred work. PMID:25665213

  14. Glucocorticoids affect 24 h clock genes expression in human adipose tissue explant cultures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To examine firstly whether CLOCK exhibits a circadian expression in human visceral (V) and subcutaneous (S) adipose tissue (AT) in vitro as compared with BMAL1 and PER2, and secondly to investigate the possible effect of the glucocorticoid analogue dexamethasone (DEX) on positive and negative clock ...

  15. CULTURE CONDITIONS AFFECT HUMAN AIRWAY EPITHELIAL CELL RESPONSE TO DIESEL PARTICLE EXPOSURE IN VITRO

    EPA Science Inventory

    Diesel exhaust particles (DEP) are a ubiquitous ambient air contaminant that may contribute to the health effects of particulate matter inhalation. In vitro studies have shown that DEP exposure induces pro-inflammatory proteins in human airway epithelial cells (HAEC) with varying...

  16. Chemical forms of selenium affect glutatione peroxidase activity in human Caco-2 cell model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The bioavailability of selenium (Se) is complicated because there are multiple naturally occurring chemical forms of this element in nature. Assessing the ability of a Se source to restore GPX1 activity in laboratory animals and humans is the most commonly used method. To search for an alternative (...

  17. High pressure treatment of human norovirus-like particles: factors affecting destruction efficacy

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human norovirus (HuNoV) is the leading cause of foodborne diseases worldwide. High pressure processing (HPP) is considered a promising non-thermal technology to inactivate viral pathogens in foods. However, the effectiveness of HPP on inactivating HuNoV remains poorly understood because it cannot be...

  18. Affective Bicultural and Global-Human Identity Scales for Mexican-American Adolescents.

    ERIC Educational Resources Information Center

    Der-Karabetian, Aghop; Ruiz, Yolanda

    Recent research in cultural diversity has concentrated on the complexity of ethnic and racial identity. This study measures the bicultural and global-human identities among first- and second-generation, Mexican-American adolescents. The participants, (84 male, 93 female) from Los Angeles high schools, had both parents of Mexican descent (60 of the…

  19. Muecas: a multi-sensor robotic head for affective human robot interaction and imitation.

    PubMed

    Cid, Felipe; Moreno, Jose; Bustos, Pablo; Núñez, Pedro

    2014-01-01

    This paper presents a multi-sensor humanoid robotic head for human robot interaction. The design of the robotic head, Muecas, is based on ongoing research on the mechanisms of perception and imitation of human expressions and emotions. These mechanisms allow direct interaction between the robot and its human companion through the different natural language modalities: speech, body language and facial expressions. The robotic head has 12 degrees of freedom, in a human-like configuration, including eyes, eyebrows, mouth and neck, and has been designed and built entirely by IADeX (Engineering, Automation and Design of Extremadura) and RoboLab. A detailed description of its kinematics is provided along with the design of the most complex controllers. Muecas can be directly controlled by FACS (Facial Action Coding System), the de facto standard for facial expression recognition and synthesis. This feature facilitates its use by third party platforms and encourages the development of imitation and of goal-based systems. Imitation systems learn from the user, while goal-based ones use planning techniques to drive the user towards a final desired state. To show the flexibility and reliability of the robotic head, the paper presents a software architecture that is able to detect, recognize, classify and generate facial expressions in real time using FACS. This system has been implemented using the robotics framework, RoboComp, which provides hardware-independent access to the sensors in the head. Finally, the paper presents experimental results showing the real-time functioning of the whole system, including recognition and imitation of human facial expressions. PMID:24787636

  20. Muecas: A Multi-Sensor Robotic Head for Affective Human Robot Interaction and Imitation

    PubMed Central

    Cid, Felipe; Moreno, Jose; Bustos, Pablo; Núñez, Pedro

    2014-01-01

    This paper presents a multi-sensor humanoid robotic head for human robot interaction. The design of the robotic head, Muecas, is based on ongoing research on the mechanisms of perception and imitation of human expressions and emotions. These mechanisms allow direct interaction between the robot and its human companion through the different natural language modalities: speech, body language and facial expressions. The robotic head has 12 degrees of freedom, in a human-like configuration, including eyes, eyebrows, mouth and neck, and has been designed and built entirely by IADeX (Engineering, Automation and Design of Extremadura) and RoboLab. A detailed description of its kinematics is provided along with the design of the most complex controllers. Muecas can be directly controlled by FACS (Facial Action Coding System), the de facto standard for facial expression recognition and synthesis. This feature facilitates its use by third party platforms and encourages the development of imitation and of goal-based systems. Imitation systems learn from the user, while goal-based ones use planning techniques to drive the user towards a final desired state. To show the flexibility and reliability of the robotic head, the paper presents a software architecture that is able to detect, recognize, classify and generate facial expressions in real time using FACS. This system has been implemented using the robotics framework, RoboComp, which provides hardware-independent access to the sensors in the head. Finally, the paper presents experimental results showing the real-time functioning of the whole system, including recognition and imitation of human facial expressions. PMID:24787636

  1. Ivermectin residue depletion in food producing species and its presence in animal foodstuffs with a view to human safety.

    PubMed

    Escribano, M; San Andrés, M I; de Lucas, J J; González-Canga, A

    2012-05-01

    From a human safety perspective, the administration of ivermectin to food producing animal species entails potential risks related to the presence of drug residues in edible tissues, milk, and other derived products. The European Medicines Agency has established the maximum residue limits for ivermectin in the European Union, with values of 100 μg·kg(-1) in fat and liver and 30 μg·kg(-1) in kidney for all mammalian food producing species, in order to ensure that the amount of ivermectin that can be found in animal foodstuff is below dangerous levels for the consumers. According to these values, withdrawal periods after subcutaneous injection were recently established in the European Union (2009), in 49 days for products containing ivermectin as a single active substance or in combination with closantel, and in 66 days when combined with clorsulon. The marker residue for ivermectin was found to be H(2)B(1a), which is the major component of the parent compound. The tissue distribution of residues and the overall ratios of marker to total residues were generally similar in most species, and the highest concentrations of ivermectin residues were found in fat and liver with high levels also detected in injection site muscles. Ivermectin is not licensed for use in animals from which milk is produced for human consumption, however its extra-label use should be considered regarding human safety, due to its long persistence in milk and milk-derived products. PMID:22039793

  2. Pervasive supply of therapeutic lysosomal enzymes in the CNS of normal and Krabbe-affected non-human primates by intracerebral lentiviral gene therapy.

    PubMed

    Meneghini, Vasco; Lattanzi, Annalisa; Tiradani, Luigi; Bravo, Gabriele; Morena, Francesco; Sanvito, Francesca; Calabria, Andrea; Bringas, John; Fisher-Perkins, Jeanne M; Dufour, Jason P; Baker, Kate C; Doglioni, Claudio; Montini, Eugenio; Bunnell, Bruce A; Bankiewicz, Krystof; Martino, Sabata; Naldini, Luigi; Gritti, Angela

    2016-01-01

    Metachromatic leukodystrophy (MLD) and globoid cell leukodystrophy (GLD or Krabbe disease) are severe neurodegenerative lysosomal storage diseases (LSD) caused by arylsulfatase A (ARSA) and galactosylceramidase (GALC) deficiency, respectively. Our previous studies established lentiviral gene therapy (GT) as a rapid and effective intervention to provide pervasive supply of therapeutic lysosomal enzymes in CNS tissues of MLD and GLD mice. Here, we investigated whether this strategy is similarly effective in juvenile non-human primates (NHP). To provide proof of principle for tolerability and biological efficacy of the strategy, we established a comprehensive study in normal NHP delivering a clinically relevant lentiviral vector encoding for the human ARSA transgene. Then, we injected a lentiviral vector coding for the human GALC transgene in Krabbe-affected rhesus macaques, evaluating for the first time the therapeutic potential of lentiviral GT in this unique LSD model. We showed favorable safety profile and consistent pattern of LV transduction and enzyme biodistribution in the two models, supporting the robustness of the proposed GT platform. We documented moderate inflammation at the injection sites, mild immune response to vector particles in few treated animals, no indication of immune response against transgenic products, and no molecular evidence of insertional genotoxicity. Efficient gene transfer in neurons, astrocytes, and oligodendrocytes close to the injection sites resulted in robust production and extensive spreading of transgenic enzymes in the whole CNS and in CSF, leading to supraphysiological ARSA activity in normal NHP and close to physiological GALC activity in the Krabbe NHP, in which biological efficacy was associated with preliminary indication of therapeutic benefit. These results support the rationale for the clinical translation of intracerebral lentiviral GT to address CNS pathology in MLD, GLD, and other neurodegenerative LSD. PMID

  3. 75 FR 56972 - Pipeline Safety: Control Room Management/Human Factors

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-17

    ... December 3, 2009, a final rule in the Federal Register (74 FR 63310) titled: ``Pipeline Safety: Control..., 2000 (65 FR 19477). Executive Order 12866 and DOT Policies and Procedures PHMSA considers this proposed rule a non-significant regulatory action under Section 3(f) of Executive Order 12866 (58 FR...

  4. Personalized medicine in human space flight: using Omics based analyses to develop individualized countermeasures that enhance astronaut safety and performance.

    PubMed

    Schmidt, Michael A; Goodwin, Thomas J

    2013-01-01

    Space flight is one of the most extreme conditions encountered by humans. Advances in Omics methodologies (genomics, transcriptomics, proteomics, and metabolomics) have revealed that unique differences exist between individuals. These differences can be amplified in extreme conditions, such as space flight. A better understanding of individual differences may allow us to develop personalized countermeasure packages that optimize the safety and performance of each astronaut. In this review, we explore the role of "Omics" in advancing our ability to: (1) more thoroughly describe the biological response of humans in space; (2) describe molecular attributes of individual astronauts that alter the risk profile prior to entering the space environment; (3) deploy Omics techniques in the development of personalized countermeasures; and (4) develop a comprehensive Omics-based assessment and countermeasure platform that will guide human space flight in the future. In this review, we advance the concept of personalized medicine in human space flight, with the goal of enhancing astronaut safety and performance. Because the field is vast, we explore selected examples where biochemical individuality might significantly impact countermeasure development. These include gene and small molecule variants associated with: (1) metabolism of therapeutic drugs used in space; (2) one carbon metabolism and DNA stability; (3) iron metabolism, oxidative stress and damage, and DNA stability; and (4) essential input (Mg and Zn) effects on DNA repair. From these examples, we advance the case that widespread Omics profiling should serve as the foundation for aerospace medicine and research, explore methodological considerations to advance the field, and suggest why personalized medicine may become the standard of care for humans in space. PMID:24273472

  5. Cdx2 Polymorphism Affects the Activities of Vitamin D Receptor in Human Breast Cancer Cell Lines and Human Breast Carcinomas

    PubMed Central

    Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  6. Cdx2 polymorphism affects the activities of vitamin D receptor in human breast cancer cell lines and human breast carcinomas.

    PubMed

    Pulito, Claudio; Terrenato, Irene; Di Benedetto, Anna; Korita, Etleva; Goeman, Frauke; Sacconi, Andrea; Biagioni, Francesca; Blandino, Giovanni; Strano, Sabrina; Muti, Paola; Mottolese, Marcella; Falvo, Elisabetta

    2015-01-01

    Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression. PMID:25849303

  7. First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Vesicular Stomatitis Virus Human Immunodeficiency Virus-1 gag Vaccine (HVTN 090)

    PubMed Central

    Fuchs, Jonathan D.; Frank, Ian; Elizaga, Marnie L.; Allen, Mary; Frahm, Nicole; Kochar, Nidhi; Li, Sue; Edupuganti, Srilatha; Kalams, Spyros A.; Tomaras, Georgia D.; Sheets, Rebecca; Pensiero, Michael; Tremblay, Marc A.; Higgins, Terry J.; Latham, Theresa; Egan, Michael A.; Clarke, David K.; Eldridge, John H.

    2015-01-01

    Background. We report the first-in-human safety and immunogenicity evaluation of a highly attenuated, replication-competent recombinant vesicular stomatitis virus (rVSV) human immunodeficiency virus (HIV)-1 vaccine. Methods. Sixty healthy, HIV-1-uninfected adults were enrolled in a randomized, double-blinded, placebo-controlled dose-escalation study. Groups of 12 participants received rVSV HIV-1 gag vaccine at 5 dose levels (4.6 × 103 to 3.4 × 107 particle forming units) (N = 10/group) or placebo (N = 2/group), delivered intramuscularly as bilateral injections at 0 and 2 months. Safety monitoring included VSV cultures from blood, urine, saliva, and swabs of oral lesions. Vesicular stomatitis virus-neutralizing antibodies, T-cell immunogenicity, and HIV-1 specific binding antibodies were assessed. Results. Local and systemic reactogenicity symptoms were mild to moderate and increased with dose. No severe reactogenicity or product-related serious adverse events were reported, and all rVSV cultures were negative. All vaccine recipients became seropositive for VSV after 2 vaccinations. gag-specific T-cell responses were detected in 63% of participants by interferon-γ enzyme-linked immunospot at the highest dose post boost. Conclusions. An attenuated replication-competent rVSV gag vaccine has an acceptable safety profile in healthy adults. This rVSV vector is a promising new vaccine platform for the development of vaccines to combat HIV-1 and other serious human diseases. PMID:26199949

  8. Derivation of NEM2 affected human embryonic stem cell line Genea080.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea080 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying compound heterozygous mutations in the NEB gene, exon 55 deletion & c.15110dupA, indicative of Nemaline Myopathy Type 2 (NEM2). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male allele pattern. The hESC line had pluripotent cell morphology, 90% of cells expressed Nanog, 95% Oct4, 54% Tra1-60 and 99% SSEA4 and gave a PluriTest Pluripotency score of 32.08, Novelty of 1.3. The cell line was negative for Mycoplasma and visible contamination. PMID:27346011

  9. Derivation of FSHD1 affected human embryonic stem cell line Genea049.

    PubMed

    Dumevska, Biljana; Chami, Omar; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea049 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying a deletion in 4q35 with only 5 D4Z4 repeats by PGD linkage analysis, indicative of FSHD1. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 90% of cells expressed Nanog, 96% Oct4, 80% Tra1-60 and 99% SSEA4, gave a Pluritest Pluripotency score of 23.16, Novelty of 1.43 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination. PMID:27346016

  10. Derivation of NEM2 affected human embryonic stem cell line Genea078.

    PubMed

    Dumevska, Biljana; Main, Heather; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea078 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying compound heterozygous mutations in the NEB gene, exon 55 deletion & c.15110dupA, indicative of Nemaline Myopathy Type 2 (NEM2). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 76% of cells expressed Nanog, 93% Oct4, 67% Tra1-60 and 97% SSEA4 and gave a Pluritest Pluripotency score of 42.18, Novelty of 1.37. The cell line was negative for Mycoplasma and visible contamination. PMID:27346006

  11. Derivation of Huntington Disease affected Genea017 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Goel, Divya; Schmidt, Uli; Peura, Teija

    2016-03-01

    The Genea017 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 40 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, genetic analysis confirmed a 46, XY karyotype and male allele pattern through CGH and STR analysis. The hESC line had pluripotent cell morphology, 87% of cells expressed Nanog, 95% Oct4, 88% Tra1-60 and 99% SSEA4, gave a PluriTest pluripotency score of 34.74, novelty of 1.27, demonstrated alkaline phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination. PMID:27346022

  12. Derivation of FSHD1 affected human embryonic stem cell line Genea050.

    PubMed

    Dumevska, Biljana; Chami, Omar; Main, Heather; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea050 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying a deletion in 4q35 with only 5 D4Z4 repeats by PGD linkage analysis, indicative of FSHD1. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male Allele pattern. The hESC line had pluripotent cell morphology, 92% of cells expressed Nanog, 97% Oct4, 79% Tra1-60 and 99% SSEA4, gave a Pluritest Pluripotency score of 25.45, Novelty of 1.45 demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination. PMID:27346025

  13. Derivation of FSHD1 affected human embryonic stem cell line Genea096.

    PubMed

    Dumevska, Biljana; Schaft, Julia; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea096 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying a deletion in 4q35 with only 6 D4Z4 repeats by PGD linkage analysis, indicative of FSHD1. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 64% of cells expressed Nanog, 93% Oct4, 58% Tra1-60 and 93% SSEA4 and a Pluritest Pluripotency score of 39.41, Novelty of 1.25. The cell line was negative for Mycoplasma and visible contamination. PMID:27346027

  14. Derivation of Huntington Disease affected Genea018 human embryonic stem cell line.

    PubMed

    Dumevska, Biljana; Main, Heather; McKernan, Robert; Goel, Divya; Schmidt, Uli; Peura, Teija

    2016-03-01

    The Genea018 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 46 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 75% of cells expressed Nanog, 91% Oct4, 73% Tra1-60 and 96% SSEA4, gave a Pluritest pluripotency score of 31.12, Novelty of 1.45, demonstrated Alkaline Phosphatase activity and tri-lineage teratoma formation. The cell line was negative for Mycoplasma and visible contamination. PMID:27346005

  15. Derivation of NEM2 affected human embryonic stem cell line Genea079.

    PubMed

    Dumevska, Biljana; McKernan, Robert; Goel, Divya; Schmidt, Uli

    2016-03-01

    The Genea079 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying compound heterozygous mutations in the NEB gene, exon 55 deletion & c.15110dupA, indicative of Nemaline Myopathy Type 2 (NEM2). Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XY and STR analysis demonstrated a male Allele pattern. The hESC line had pluripotent cell morphology, 86% of cells expressed Nanog, 95% Oct4, 54% Tra1-60 and 98% SSEA4 and gave a PluriTest Pluripotency score of 30.25, Novelty of 1.21. The cell line was negative for Mycoplasma and visible contamination. PMID:27346010

  16. Human health safety evaluation of cosmetics in the EU: A legally imposed challenge to science

    SciTech Connect

    Pauwels, M.; Rogiers, V.

    2010-03-01

    As stated in the European legislation, cosmetic products present on the European market must be safe for the consumer. Safety evaluation of the products is carried out by a qualified safety assessor who needs to consider potential exposure scenarios next to the physicochemical and toxicological profiles of all composing ingredients. Whereas, until recently, the tools to determine the toxicological profile of cosmetic ingredients mainly consisted of animal experiments, they have now been narrowed down substantially by the legally imposed animal testing ban on cosmetic ingredients, taken up in the Cosmetic Products Directive (76/768/EEC). This Directive, however, is not a stand-alone piece of European legislation, since as well directly as indirectly it is influenced by a complex web of related legislations. Vertical legislations deal with different categories of chemicals, including dangerous substances, biocides, plant protection products, food additives, medicinal products, and of course also cosmetics. Horizontal legislative texts, on the contrary, cover more general fields such as protection of experimental animals, consumer product safety, misleading of consumers, specific provisions for aerosols, and others. Experience has learnt that having a general overview of these related legislations is necessary to understand their impact on the cosmetic world in general terms and on cosmetic safety evaluation in particular. This goes for a variety of concerned parties, including national and European regulators/agencies, contract laboratories, raw material suppliers, cosmetic companies, research and educational centers. They all deal with a number of aspects important for the quality and toxicity of cosmetics and their ingredients. This review summarises the most relevant points of the legislative texts of different types of product categories and emphasises their impact on the safety evaluation of cosmetics.

  17. Key Performance Criteria Affecting the Most the Safety of a Nuclear Waste Long Term Storage : A Case Study Commissioned by CEA

    SciTech Connect

    Marvy, A.; Lioure, A; Heriard-Dubreuil, G.; Gadbois, S.; Schneider, T.; Schieber, C.

    2003-02-24

    As part of the work scope set in the French law on high level long lived waste R&D passed in 1991, CEA is conducting a research program to establish the scientific basis and assess the feasibility of long term storage as an option for the safe management of nuclear waste for periods as long as centuries. This goal is a significant departure from the current industrial practice where storage facilities are usually built to last only a few decades. From a technical viewpoint such an extension in time seems feasible provided care and maintenance is exercised. Considering such long periods of time, the risk for Society of loosing oversight and control of such a facility is real, which triggers the question of whether and how long term storage safety can be actually achieved. Therefore CEA commissioned a study (1) in which MUTADIS Consultants (2) and CEPN (3) were both involved. The case study looks into several past and actual human enterprises conducted over significant periods o f time, one of them dating back to the end of the 18th century, and all identified out of the nuclear field. Then-prevailing societal behavior and organizational structures are screened out to show how they were or are still able to cope with similar oversight and control goals. As a result, the study group formulated a set of performance criteria relating to issues like responsibility, securing funds, legal and legislative implications, economic sustainable development, all being areas which are not traditionally considered as far as technical studies are concerned. These criteria can be most useful from the design stage onward, first in an attempt to define the facility construction and operating guiding principles, and thereafter to substantiate the safety case for long term storage and get geared to the public dialogue on that undertaking should it become a reality.

  18. Clostridium difficile PCR ribotype 078 toxinotype V found in diarrhoeal pigs identical to isolates from affected humans.

    PubMed

    Debast, Sylvia B; van Leengoed, Leo A M G; Goorhuis, Abraham; Harmanus, Celine; Kuijper, Ed J; Bergwerff, Aldert A

    2009-02-01

    In diseased piglets from two Dutch pig-breeding farms with neonatal diarrhoea for more than a year, culture and PCR analyses identified the involved microorganism as Clostridium difficile PCR ribotype 078 harbouring toxin A (tcdA) and B (tcdB), and binary toxin genes. Isolated strains showed a 39 bp deletion in the tcdC gene and they were ermB gene-negative. A number of 11 porcine and 21 human isolated C. difficile PCR ribotype 078 toxinotype V strains were found genetically related by multiple-locus variable-number tandem-repeat analysis (MLVA). Moreover, a clonal complex was identified, containing both porcine and human isolates. The porcine isolates showed an antimicrobial susceptibility profile overlapping that of isolates from Dutch human patients. On the basis of these pheno- and genotypical analyses results, it was concluded that the strains from affected piglets were indistinguishable from increasingly encountered C. difficile PCR ribotype 078 strains of human C. difficile infections in the Dutch population and that a common origin of animal and humans strains should be considered. PMID:19196280

  19. Low concentrations of Bisphenol A and para-Nonylphenol affect extravillous pathway of human trophoblast cells.

    PubMed

    Spagnoletti, Antonella; Paulesu, Luana; Mannelli, Chiara; Ermini, Leonardo; Romagnoli, Roberta; Cintorino, Marcella; Ietta, Francesca

    2015-09-01

    Bisphenol A (BPA) and para-Nonylphenol (p-NP) are chemicals of industrial origin which may influence human reproductive health. The effects of these substances in the prenatal life is an important topic that is receiving greater attention in the developed countries. In this study, human trophoblast cells HTR-8/SVneo were exposed to BPA and p-NP (1 × 10(-15), 1 × 10(-13), 1 × 10(-11), 1 × 10(-9) and 1 × 10(-7) M) and incubated for 24, 48 and/or 72 h then, examined for the main physiological processes which characterize the extravillous trophoblast. Cell proliferation showed no changes while the processes of cell migration and invasion were both reduced by BPA and p-NP. For each chemical, the activity was higher at lower concentrations with a maximum activity between 1 × 10(-13) and 1 × 10(-11) M (p < 0.05 for 1 × 10(-9) and p < 0.001 for 1 × 10(-11) M). Co-culture studies with human umbilical cord endothelial cells (HUVEC) revealed that trophoblast/endothelial interaction was significantly reduced by p-NP at 1 × 10(-11) M. Moreover, both chemicals were inducing differentiation of HTR-8/SVneo toward polyploidy by the process of endoreduplication. The estrogen-receptor antagonist ICI significantly reduced p-NP action, while it had no effect on BPA treated cells. In conclusion, p-NP and BPA act on trophoblast cells altering key physiological processes in placenta development. The exact mechanism of action of the chemicals in human trophoblast still needs to be clarified. PMID:26027920

  20. Hundreds of variants clustered in genomic loci and biological pathways affect human height

    PubMed Central

    Lango Allen, Hana; Estrada, Karol; Lettre, Guillaume; Berndt, Sonja I.; Weedon, Michael N.; Rivadeneira, Fernando; Willer, Cristen J.; Jackson, Anne U.; Vedantam, Sailaja; Raychaudhuri, Soumya; Ferreira, Teresa; Wood, Andrew R.; Weyant, Robert J.; Segrè, Ayellet V.; Speliotes, Elizabeth K.; Wheeler, Eleanor; Soranzo, Nicole; Park, Ju-Hyun; Yang, Jian; Gudbjartsson, Daniel; Heard-Costa, Nancy L.; Randall, Joshua C.; Qi, Lu; Smith, Albert Vernon; Mägi, Reedik; Pastinen, Tomi; Liang, Liming; Heid, Iris M.; Luan, Jian'an; Thorleifsson, Gudmar; Winkler, Thomas W.; Goddard, Michael E.; Lo, Ken Sin; Palmer, Cameron; Workalemahu, Tsegaselassie; Aulchenko, Yurii S.; Johansson, Åsa; Zillikens, M.Carola; Feitosa, Mary F.; Esko, Tõnu; Johnson, Toby; Ketkar, Shamika; Kraft, Peter; Mangino, Massimo; Prokopenko, Inga; Absher, Devin; Albrecht, Eva; Ernst, Florian; Glazer, Nicole L.; Hayward, Caroline; Hottenga, Jouke-Jan; Jacobs, Kevin B.; Knowles, Joshua W.; Kutalik, Zoltán; Monda, Keri L.; Polasek, Ozren; Preuss, Michael; Rayner, Nigel W.; Robertson, Neil R.; Steinthorsdottir, Valgerdur; Tyrer, Jonathan P.; Voight, Benjamin F.; Wiklund, Fredrik; Xu, Jianfeng; Zhao, Jing Hua; Nyholt, Dale R.; Pellikka, Niina; Perola, Markus; Perry, John R.B.; Surakka, Ida; Tammesoo, Mari-Liis; Altmaier, Elizabeth L.; Amin, Najaf; Aspelund, Thor; Bhangale, Tushar; Boucher, Gabrielle; Chasman, Daniel I.; Chen, Constance; Coin, Lachlan; Cooper, Matthew N.; Dixon, Anna L.; Gibson, Quince; Grundberg, Elin; Hao, Ke; Junttila, M. Juhani; Kaplan, Lee M.; Kettunen, Johannes; König, Inke R.; Kwan, Tony; Lawrence, Robert W.; Levinson, Douglas F.; Lorentzon, Mattias; McKnight, Barbara; Morris, Andrew P.; Müller, Martina; Ngwa, Julius Suh; Purcell, Shaun; Rafelt, Suzanne; Salem, Rany M.; Salvi, Erika; Sanna, Serena; Shi, Jianxin; Sovio, Ulla; Thompson, John R.; Turchin, Michael C.; Vandenput, Liesbeth; Verlaan, Dominique J.; Vitart, Veronique; White, Charles C.; Ziegler, Andreas; Almgren, Peter; Balmforth, Anthony J.; Campbell, Harry; Citterio, Lorena; De Grandi, Alessandro; Dominiczak, Anna; Duan, Jubao; Elliott, Paul; Elosua, Roberto; Eriksson, Johan G.; Freimer, Nelson B.; Geus, Eco J.C.; Glorioso, Nicola; Haiqing, Shen; Hartikainen, Anna-Liisa; Havulinna, Aki S.; Hicks, Andrew A.; Hui, Jennie; Igl, Wilmar; Illig, Thomas; Jula, Antti; Kajantie, Eero; Kilpeläinen, Tuomas O.; Koiranen, Markku; Kolcic, Ivana; Koskinen, Seppo; Kovacs, Peter; Laitinen, Jaana; Liu, Jianjun; Lokki, Marja-Liisa; Marusic, Ana; Maschio, Andrea; Meitinger, Thomas; Mulas, Antonella; Paré, Guillaume; Parker, Alex N.; Peden, John F.; Petersmann, Astrid; Pichler, Irene; Pietiläinen, Kirsi H.; Pouta, Anneli; Ridderstråle, Martin; Rotter, Jerome I.; Sambrook, Jennifer G.; Sanders, Alan R.; Schmidt, Carsten Oliver; Sinisalo, Juha; Smit, Jan H.; Stringham, Heather M.; Walters, G.Bragi; Widen, Elisabeth; Wild, Sarah H.; Willemsen, Gonneke; Zagato, Laura; Zgaga, Lina; Zitting, Paavo; Alavere, Helene; Farrall, Martin; McArdle, Wendy L.; Nelis, Mari; Peters, Marjolein J.; Ripatti, Samuli; van Meurs, Joyce B.J.; Aben, Katja K.; Ardlie, Kristin G; Beckmann, Jacques S.; Beilby, John P.; Bergman, Richard N.; Bergmann, Sven; Collins, Francis S.; Cusi, Daniele; den Heijer, Martin; Eiriksdottir, Gudny; Gejman, Pablo V.; Hall, Alistair S.; Hamsten, Anders; Huikuri, Heikki V.; Iribarren, Carlos; Kähönen, Mika; Kaprio, Jaakko; Kathiresan, Sekar; Kiemeney, Lambertus; Kocher, Thomas; Launer, Lenore J.; Lehtimäki, Terho; Melander, Olle; Mosley, Tom H.; Musk, Arthur W.; Nieminen, Markku S.; O'Donnell, Christopher J.; Ohlsson, Claes; Oostra, Ben; Palmer, Lyle J.; Raitakari, Olli; Ridker, Paul M.; Rioux, John D.; Rissanen, Aila; Rivolta, Carlo; Schunkert, Heribert; Shuldiner, Alan R.; Siscovick, David S.; Stumvoll, Michael; Tönjes, Anke; Tuomilehto, Jaakko; van Ommen, Gert-Jan; Viikari, Jorma; Heath, Andrew C.; Martin, Nicholas G.; Montgomery, Grant W.; Province, Michael A.; Kayser, Manfred; Arnold, Alice M.; Atwood, Larry D.; Boerwinkle, Eric; Chanock, Stephen J.; Deloukas, Panos; Gieger, Christian; Grönberg, Henrik; Hall, Per; Hattersley, Andrew T.; Hengstenberg, Christian; Hoffman, Wolfgang; Lathrop, G.Mark; Salomaa, Veikko; Schreiber, Stefan; Uda, Manuela; Waterworth, Dawn; Wright, Alan F.; Assimes, Themistocles L.; Barroso, Inês; Hofman, Albert; Mohlke, Karen L.; Boomsma, Dorret I.; Caulfield, Mark J.; Cupples, L.Adrienne; Erdmann, Jeanette; Fox, Caroline S.; Gudnason, Vilmundur; Gyllensten, Ulf; Harris, Tamara B.; Hayes, Richard B.; Jarvelin, Marjo-Riitta; Mooser, Vincent; Munroe, Patricia B.; Ouwehand, Willem H.; Penninx, Brenda W.; Pramstaller, Peter P.; Quertermous, Thomas; Rudan, Igor; Samani, Nilesh J.; Spector, Timothy D.; Völzke, Henry; Watkins, Hugh; Wilson, James F.; Groop, Leif C.; Haritunians, Talin; Hu, Frank B.; Kaplan, Robert C.; Metspalu, Andres; North, Kari E.; Schlessinger, David; Wareham, Nicholas J.; Hunter, David J.; O'Connell, Jeffrey R.; Strachan, David P.; Wichmann, H.-Erich; Borecki, Ingrid B.; van Duijn, Cornelia M.; Schadt, Eric E.; Thorsteinsdottir, Unnur; Peltonen, Leena; Uitterlinden, André; Visscher, Peter M.; Chatterjee, Nilanjan; Loos, Ruth J.F.; Boehnke, Michael; McCarthy, Mark I.; Ingelsson, Erik; Lindgren, Cecilia M.; Abecasis, Gonçalo R.; Stefansson, Kari; Frayling, Timothy M.; Hirschhorn, Joel N

    2010-01-01

    Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence phenotype. Genome-wide association (GWA) studies have identified >600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the utility of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2,3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P=0.016), and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants, and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented amongst variants that alter amino acid structure of proteins and expression levels of nearby genes. Our data explain ∼10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to ∼16% of phenotypic variation (∼20% of heritable variation). Although additional approaches are needed to fully dissect the genetic architecture of polygenic human traits, our findings indicate that GWA studies can identify large numbers of loci that

  1. Regional paleofire regimes affected by non-uniform climate, vegetation and human drivers

    NASA Astrophysics Data System (ADS)

    Blarquez, Olivier; Ali, Adam A.; Girardin, Martin P.; Grondin, Pierre; Fréchette, Bianca; Bergeron, Yves; Hély, Christelle

    2015-09-01

    Climate, vegetation and humans act on biomass burning at different spatial and temporal scales. In this study, we used a dense network of sedimentary charcoal records from eastern Canada to reconstruct regional biomass burning history over the last 7000 years at the scale of four potential vegetation types: open coniferous forest/tundra, boreal coniferous forest, boreal mixedwood forest and temperate forest. The biomass burning trajectories were compared with regional climate trends reconstructed from general circulation models, tree biomass reconstructed from pollen series, and human population densities. We found that non-uniform climate, vegetation and human drivers acted on regional biomass burning history. In the open coniferous forest/tundra and dense coniferous forest, the regional biomass burning was primarily shaped by gradual establishment of less climate-conducive burning conditions over 5000 years. In the mixed boreal forest an increasing relative proportion of flammable conifers in landscapes since 2000 BP contributed to maintaining biomass burning constant despite climatic conditions less favourable to fires. In the temperate forest, biomass burning was uncoupled with climatic conditions and the main driver was seemingly vegetation until European colonization, i.e. 300 BP. Tree biomass and thus fuel accumulation modulated fire activity, an indication that biomass burning is fuel-dependent and notably upon long-term co-dominance shifts between conifers and broadleaf trees.

  2. Multiple factors affect immunogenicity of DNA plasmid HIV vaccines in human clinical trials

    PubMed Central

    Jin, Xia; Morgan, Cecilia; Yu, Xuesong; DeRosa, Stephen; Tomaras, Georgia D.; Montefiori, David C.; Kublin, James; Corey, Larry; Keefer, Michael C.

    2015-01-01

    Plasmid DNA vaccines have been licensed for use in domesticated animals because of their excellent immunogenicity, but none have yet been licensed for use in humans. Here we report a retrospective analysis of 1218 healthy human volunteers enrolled in 10 phase I clinical trials in which DNA plasmids encoding HIV antigens were administered. Elicited T-cell immune responses were quantified by validated intracellular cytokine staining (ICS) stimulated with HIV peptide pools. HIV-specific binding and neutralizing antibody activities were also analyzed using validated assays. Results showed that, in the absence of adjuvants and boosting with alternative vaccines, DNA vaccines elicited CD8+ and CD4+ T-cell responses in an average of 13.3% (95% CI: 9.8% to 17.8%) and 37.7% (95% CI: 31.9% to 43.8%) of vaccine recipients, respectively. Three vaccinations (versus 2) improved the proportion of subjects with antigen-specific CD8+ responses (p=0.02), as did increased DNA dosage (p=0.007). Furthermore, female gender and participants having a lower Body Mass Index were independently associated with higher CD4+ T-cell response rate (p=0.001 and p=0.008, respectively). These vaccines elicited minimal neutralizing and binding antibody responses. These findings of the immunogenicity of HIV DNA vaccines in humans can provide guidance for future clinical trials. PMID:25820067

  3. Atrazine Affects Phosphoprotein and Protein Expression in MCF-10A Human Breast Epithelial Cells

    PubMed Central

    Huang, Peixin; Yang, John; Song, Qisheng; Sheehan, David

    2014-01-01

    Atrazine, a member of the 2-chloro-s-triazine family of herbicides, is the most widely used pesticide in the world and often detected in agriculture watersheds. Although it was generally considered as an endocrine disruptor, posing a potential threat to human health, the molecular mechanisms of atrazine effects remain unclear. Using two-dimensional gel electrophoresis, we identified a panel of differentially expressed phosphoproteins and total proteins in human breast epithelial MCF-10A cells after being exposed to environmentally relevant concentrations of atrazine. Atrazine treatments for 6 h resulted in differential expression of 4 phosphoproteins and 8 total-proteins as compared to the control cells (>1.5-fold, p < 0.05). MALDI-TOF MS/MS analysis revealed that the differentially expressed proteins belong to various cellular compartments (nucleus, cytosol, membrane) and varied in function, including those regulating the stress response such as peroxiredoxin I, HSP70 and HSP27; structural proteins such as tropomyosin and profilin 1; and oncogenesis proteins such as ANP32A. Six of the 12 identified proteins were verified by quantitative PCR for their transcript levels. The most up-regulated phosphoprotein by atrazine treatment, ANP32A, was further analyzed for its expression, distribution and cellular localization using Western blot and immunocytochemical approaches. The results revealed that ANP32 expression after atrazine treatment increased dose and time dependently and was primarily located in the nucleus. This study may provide new evidence on the potential toxicity of atrazine in human cells. PMID:25275270

  4. Reducing the likelihood of future human activities that could affect geologic high-level waste repositories

    SciTech Connect

    Not Available

    1984-05-01

    The disposal of radioactive wastes in deep geologic formations provides a means of isolating the waste from people until the radioactivity has decayed to safe levels. However, isolating people from the wastes is a different problem, since we do not know what the future condition of society will be. The Human Interference Task Force was convened by the US Department of Energy to determine whether reasonable means exist (or could be developed) to reduce the likelihood of future human unintentionally intruding on radioactive waste isolation systems. The task force concluded that significant reductions in the likelihood of human interference could be achieved, for perhaps thousands of years into the future, if appropriate steps are taken to communicate the existence of the repository. Consequently, for two years the task force directed most of its study toward the area of long-term communication. Methods are discussed for achieving long-term communication by using permanent markers and widely disseminated records, with various steps taken to provide multiple levels of protection against loss, destruction, and major language/societal changes. Also developed is the concept of a universal symbol to denote Caution - Biohazardous Waste Buried Here. If used for the thousands of non-radioactive biohazardous waste sites in this country alone, a symbol could transcend generations and language changes, thereby vastly improving the likelihood of successful isolation of all buried biohazardous wastes.

  5. Host protein Snapin interacts with human cytomegalovirus pUL130 and affects viral DNA replication.

    PubMed

    Wang, Guili; Ren, Gaowei; Cui, Xin; Lu, Zhitao; Ma, Yanpin; Qi, Ying; Huang, Yujing; Liu, Zhongyang; Sun, Zhengrong; Ruan, Qiang

    2016-06-01

    The interplay between the host and Human cytomegalovirus (HCMV) plays a pivotal role in the outcome of an infection. HCMV growth in endothelial and epithelial cells requires expression of viral proteins UL128, UL130, and UL131 proteins (UL128-131), of which UL130 is the largest gene and the only one that is not interrupted by introns.Mutation of the C terminus of the UL130 protein causes reduced tropism of endothelial cells (EC). However, very few host factors have been identified that interact with the UL130 protein. In this study, HCMV UL130 protein was shown to directly interact with the human protein Snapin in human embryonic kidney HEK293 cells by Yeast two-hybrid screening, in vitro glutathione S-transferase (GST) pull-down, and co-immunoprecipitation. Additionally, heterologous expression of protein UL130 revealed co-localization with Snapin in the cell membrane and cytoplasm of HEK293 cells using fluorescence confocal microscopy. Furthermore, decreasing the level of Snapin via specific small interfering RNAs decreased the number of viral DNA copies and titer inHCMV-infected U373-S cells. Taken together, these results suggest that Snapin, the pUL130 interacting protein, has a role in modulating HCMV DNA synthesis. PMID:27240978

  6. Regional paleofire regimes affected by non-uniform climate, vegetation and human drivers

    PubMed Central

    Blarquez, Olivier; Ali, Adam A.; Girardin, Martin P.; Grondin, Pierre; Fréchette, Bianca; Bergeron, Yves; Hély, Christelle

    2015-01-01

    Climate, vegetation and humans act on biomass burning at different spatial and temporal scales. In this study, we used a dense network of sedimentary charcoal records from eastern Canada to reconstruct regional biomass burning history over the last 7000 years at the scale of four potential vegetation types: open coniferous forest/tundra, boreal coniferous forest, boreal mixedwood forest and temperate forest. The biomass burning trajectories were compared with regional climate trends reconstructed from general circulation models, tree biomass reconstructed from pollen series, and human population densities. We found that non-uniform climate, vegetation and human drivers acted on regional biomass burning history. In the open coniferous forest/tundra and dense coniferous forest, the regional biomass burning was primarily shaped by gradual establishment of less climate-conducive burning conditions over 5000 years. In the mixed boreal forest an increasing relative proportion of flammable conifers in landscapes since 2000 BP contributed to maintaining biomass burning constant despite climatic conditions less favourable to fires. In the temperate forest, biomass burning was uncoupled with climatic conditions and the main driver was seemingly vegetation until European colonization, i.e. 300 BP. Tree biomass and thus fuel accumulation modulated fire activity, an indication that biomass burning is fuel-dependent and notably upon long-term co-dominance shifts between conifers and broadleaf trees. PMID:26330162

  7. Regional paleofire regimes affected by non-uniform climate, vegetation and human drivers.

    PubMed

    Blarquez, Olivier; Ali, Adam A; Girardin, Martin P; Grondin, Pierre; Fréchette, Bianca; Bergeron, Yves; Hély, Christelle

    2015-01-01

    Climate, vegetation and humans act on biomass burning at different spatial and temporal scales. In this study, we used a dense network of sedimentary charcoal records from eastern Canada to reconstruct regional biomass burning history over the last 7000 years at the scale of four potential vegetation types: open coniferous forest/tundra, boreal coniferous forest, boreal mixedwood forest and temperate forest. The biomass burning trajectories were compared with regional climate trends reconstructed from general circulation models, tree biomass reconstructed from pollen series, and human population densities. We found that non-uniform climate, vegetation and human drivers acted on regional biomass burning history. In the open coniferous forest/tundra and dense coniferous forest, the regional biomass burning was primarily shaped by gradual establishment of less climate-conducive burning conditions over 5000 years. In the mixed boreal forest an increasing relative proportion of flammable conifers in landscapes since 2000 BP contributed to maintaining biomass burning constant despite climatic conditions less favourable to fires. In the temperate forest, biomass burning was uncoupled with climatic conditions and the main driver was seemingly vegetation until European colonization, i.e. 300 BP. Tree biomass and thus fuel accumulation modulated fire activity, an indication that biomass burning is fuel-dependent and notably upon long-term co-dominance shifts between conifers and broadleaf trees. PMID:26330162

  8. Human brain EEG indices of emotions: delineating responses to affective vocalizations by measuring frontal theta event-related synchronization.

    PubMed

    Bekkedal, Marni Y V; Rossi, John; Panksepp, Jaak

    2011-10-01

    At present there is no direct brain measure of basic emotional dynamics from the human brain. EEG provides non-invasive approaches for monitoring brain electrical activity to emotional stimuli. Event-related desynchronization/synchronization (ERD/ERS) analysis, based on power shifts in specific frequency bands, has some potential as a method for differentiating responses to basic emotions as measured during brief presentations of affective stimuli. Although there appears to be fairly consistent theta ERS in frontal regions of the brain during the earliest phases of processing affective auditory stimuli, the patterns do not readily distinguish between specific emotions. To date it has not been possible to consistently differentiate brain responses to emotion-specific affective states or stimuli, and some evidence to suggests the theta ERS more likely measures general arousal processes rather than yielding veridical indices of specific emotional states. Perhaps cortical EEG patterns will never be able to be used to distinguish discrete emotional states from the surface of the brain. The implications and limitations of such approaches for understanding human emotions are discussed. PMID:21596060

  9. Crucial Dimensions of Human Altruism. Affective vs. Conceptual Factors Leading to Helping or Reinforcing Others

    PubMed Central

    Szuster, Anna

    2016-01-01

    The aim of this article is to identify factors leading to favorable attitudes toward other people from different social categories. The parts of article reflect diverse levels of altruism regulation from primary affective responses to the environment, through social norms, to abstract moral concepts related to good and evil. The latter allow understanding of the perspective of other people (including those belonging to out-groups), acceptance of their values and engagement not only in helping behavior but also in supporting the development of others. PMID:27148127

  10. Crucial Dimensions of Human Altruism. Affective vs. Conceptual Factors Leading to Helping or Reinforcing Others.

    PubMed

    Szuster, Anna

    2016-01-01

    The aim of this article is to identify factors leading to favorable attitudes toward other people from different social categories. The parts of article reflect diverse levels of altruism regulation from primary affective responses to the environment, through social norms, to abstract moral concepts related to good and evil. The latter allow understanding of the perspective of other people (including those belonging to out-groups), acceptance of their values and engagement not only in helping behavior but also in supporting the development of others. PMID:27148127

  11. Development and Validation of the Total HUman Model for Safety (THUMS) Version 5 Containing Multiple 1D Muscles for Estimating Occupant Motions with Muscle Activation During Side Impacts.

    PubMed

    Iwamoto, Masami; Nakahira, Yuko

    2015-11-01

    Accurate prediction of occupant head kinematics is critical for better understanding of head/face injury mechanisms in side impacts, especially far-side occupants. In light of the fact that researchers have demonstrated that muscle activations, especially in neck muscles, can affect occupant head kinematics, a human body finite element (FE) model that considers muscle activation is useful for predicting occupant head kinematics in real-world automotive accidents. In this study, we developed a human body FE model called the THUMS (Total HUman Model for Safety) Version 5 that contains 262 one-dimensional (1D) Hill-type muscle models over the entire body. The THUMS was validated against 36 series of PMHS (Post Mortem Human Surrogate) and volunteer test data in this study, and 16 series of PMHS and volunteer test data on side impacts are presented. Validation results with force-time curves were also evaluated quantitatively using the CORA (CORrelation and Analysis) method. The validation results suggest that the THUMS has good biofidelity in the responses of the regional or full body for side impacts, but relatively poor biofidelity in its local level of responses such as brain displacements. Occupant kinematics predicted by the THUMS with a muscle controller using 22 PID (Proportional-Integral- Derivative) controllers were compared with those of volunteer test data on low-speed lateral impacts. The THUMS with muscle controller reproduced the head kinematics of the volunteer data more accurately than that without muscle activation, although further studies on validation of torso kinematics are needed for more accurate predictions of occupant head kinematics. PMID:26660740

  12. Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory

    PubMed Central

    Barman, Adriana; Assmann, Anne; Richter, Sylvia; Soch, Joram; Schütze, Hartmut; Wüstenberg, Torsten; Deibele, Anna; Klein, Marieke; Richter, Anni; Behnisch, Gusalija; Düzel, Emrah; Zenker, Martin; Seidenbecher, Constanze I.; Schott, Björn H.

    2014-01-01

    The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP) rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT) and the logical memory section of the Wechsler Memory Scale (WMS). Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI) studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e., the myopia risk allele) showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point toward pleitropic effects of RASGRF1 genetic variations on complex neural function in humans. PMID:24808846

  13. Genetic Polymorphisms Affect Mouse and Human Trace Amine-Associated Receptor 1 Function

    PubMed Central

    Shi, Xiao; Walter, Nicole A. R.; Harkness, John H.; Neve, Kim A.; Williams, Robert W.; Lu, Lu; Belknap, John K.; Eshleman, Amy J.; Phillips, Tamara J.; Janowsky, Aaron

    2016-01-01

    Methamphetamine (MA) and neurotransmitter precursors and metabolites such as tyramine, octopamine, and β-phenethylamine stimulate the G protein-coupled trace amine-associated receptor 1 (TAAR1). TAAR1 has been implicated in human conditions including obesity, schizophrenia, depression, fibromyalgia, migraine, and addiction. Additionally TAAR1 is expressed on lymphocytes and astrocytes involved in inflammation and response to infection. In brain, TAAR1 stimulation reduces synaptic dopamine availability and alters glutamatergic function. TAAR1 is also expressed at low levels in heart, and may regulate cardiovascular tone. Taar1 knockout mice orally self-administer more MA than wild type and are insensitive to its aversive effects. DBA/2J (D2) mice express a non-synonymous single nucleotide polymorphism (SNP) in Taar1 that does not respond to MA, and D2 mice are predisposed to high MA intake, compared to C57BL/6 (B6) mice. Here we demonstrate that endogenous agonists stimulate the recombinant B6 mouse TAAR1, but do not activate the D2 mouse receptor. Progeny of the B6XD2 (BxD) family of recombinant inbred (RI) strains have been used to characterize the genetic etiology of diseases, but contrary to expectations, BXDs derived 30–40 years ago express only the functional B6 Taar1 allele whereas some more recently derived BXD RI strains express the D2 allele. Data indicate that the D2 mutation arose subsequent to derivation of the original RIs. Finally, we demonstrate that SNPs in human TAAR1 alter its function, resulting in expressed, but functional, sub-functional and non-functional receptors. Our findings are important for identifying a predisposition to human diseases, as well as for developing personalized treatment options. PMID:27031617

  14. Genetic Polymorphisms Affect Mouse and Human Trace Amine-Associated Receptor 1 Function.

    PubMed

    Shi, Xiao; Walter, Nicole A R; Harkness, John H; Neve, Kim A; Williams, Robert W; Lu, Lu; Belknap, John K; Eshleman, Amy J; Phillips, Tamara J; Janowsky, Aaron

    2016-01-01

    Methamphetamine (MA) and neurotransmitter precursors and metabolites such as tyramine, octopamine, and β-phenethylamine stimulate the G protein-coupled trace amine-associated receptor 1 (TAAR1). TAAR1 has been implicated in human conditions including obesity, schizophrenia, depression, fibromyalgia, migraine, and addiction. Additionally TAAR1 is expressed on lymphocytes and astrocytes involved in inflammation and response to infection. In brain, TAAR1 stimulation reduces synaptic dopamine availability and alters glutamatergic function. TAAR1 is also expressed at low levels in heart, and may regulate cardiovascular tone. Taar1 knockout mice orally self-administer more MA than wild type and are insensitive to its aversive effects. DBA/2J (D2) mice express a non-synonymous single nucleotide polymorphism (SNP) in Taar1 that does not respond to MA, and D2 mice are predisposed to high MA intake, compared to C57BL/6 (B6) mice. Here we demonstrate that endogenous agonists stimulate the recombinant B6 mouse TAAR1, but do not activate the D2 mouse receptor. Progeny of the B6XD2 (BxD) family of recombinant inbred (RI) strains have been used to characterize the genetic etiology of diseases, but contrary to expectations, BXDs derived 30-40 years ago express only the functional B6 Taar1 allele whereas some more recently derived BXD RI strains express the D2 allele. Data indicate that the D2 mutation arose subsequent to derivation of the original RIs. Finally, we demonstrate that SNPs in human TAAR1 alter its function, resulting in expressed, but functional, sub-functional and non-functional receptors. Our findings are important for identifying a predisposition to human diseases, as well as for developing personalized treatment options. PMID:27031617

  15. Age and skeletal sites affect BMP-2 responsiveness of human bone marrow stromal cells.

    PubMed

    Osyczka, Anna Maria; Damek-Poprawa, Monika; Wojtowicz, Aleksandra; Akintoye, Sunday O

    2009-01-01

    Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular, and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be due partly to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible, and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin, and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells. PMID:19637063

  16. Age and Skeletal Sites Affect BMP-2 Responsiveness of Human Bone Marrow Stromal Cells

    PubMed Central

    Osyczka, Anna M.; Damek-Poprawa, Monika; Wojtowicz, Aleksandra; Akintoye, Sunday O.

    2010-01-01

    Bone marrow stromal cells (BMSCs) contain osteoprogenitors responsive to stimulation by osteogenic growth factors like bone morphogenetic proteins (BMPs). When used as grafts, BMSCs can be harvested from different skeletal sites such as axial, appendicular and orofacial bones, but the lower therapeutic efficacy of BMPs on BMSCs-responsiveness in humans compared to animal models may be partly due to effects of skeletal site and age of donor. We previously reported superior differentiation capacity and osteogenic properties of orofacial BMSCs relative to iliac crest BMSCs in same individuals. This study tested the hypothesis that recombinant human BMP-2 (rhBMP-2) stimulates human BMSCs differently based on age and skeletal site of harvest. Adult maxilla, mandible and iliac crest BMSCs from same individuals and pediatric iliac crest BMSCs were comparatively assessed for BMP-2 responsiveness under serum-containing and serum-free insulin-supplemented culture conditions. Adult orofacial BMSCs were more BMP-2-responsive than iliac crest BMSCs based on higher gene transcripts of alkaline phosphatase, osteopontin and osteogenic transcription factors MSX-2 and Osterix in serum-free insulin-containing medium. Pediatric iliac crest BMSCs were more responsive to rhBMP-2 than adult iliac crest BMSCs based on higher expression of alkaline phosphatase and osteopontin in serum-containing medium. Unlike orofacial BMSCs, MSX-2 and Osterix transcripts were similarly expressed by adult and pediatric iliac crest BMSCs in response to rhBMP-2. These data demonstrate that age and skeletal site-specific differences exist in BMSC osteogenic responsiveness to BMP-2 stimulation and suggest that MSX-2 and Osterix may be potential regulatory transcription factors in BMP-mediated osteogenesis of adult orofacial cells. PMID:19637063

  17. Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory.

    PubMed

    Barman, Adriana; Assmann, Anne; Richter, Sylvia; Soch, Joram; Schütze, Hartmut; Wüstenberg, Torsten; Deibele, Anna; Klein, Marieke; Richter, Anni; Behnisch, Gusalija; Düzel, Emrah; Zenker, Martin; Seidenbecher, Constanze I; Schott, Björn H

    2014-01-01

    The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP) rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT) and the logical memory section of the Wechsler Memory Scale (WMS). Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI) studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e., the myopia risk allele) showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point toward pleitropic effects of RASGRF1 genetic variations on complex neural function in humans. PMID:24808846

  18. Comparison of electrophysiological data from human-induced pluripotent stem cell-derived cardiomyocytes to functional preclinical safety assays.

    PubMed

    Harris, Kate; Aylott, Mike; Cui, Yi; Louttit, James B; McMahon, Nicholas C; Sridhar, Arun

    2013-08-01

    Human-induced pluripotent stem cell cardiomyocytes (hiPSC-CMs) are a potential source to develop assays for predictive electrophysiological safety screening. Published studies show that the relevant physiology and pharmacology exist but does not show the translation between stem cell cardiomyocyte assays and other preclinical safety screening assays, which is crucial for drug discovery and safety scientists and the regulators. Our studies are the first to show the pharmacology of ion channel blockade and compare them with existing functional cardiac electrophysiology studies. Ten compounds (a mixture of pure hERG [E-4031 and Cisapride], hERG and sodium [Flecainide, Mexiletine, Quinidine, and Terfenadine], calcium channel blockers [Nifedipine and Verapamil], and two proprietary compounds [GSK A and B]) were tested, and results from hiPSC-CMs studied on multielectrode arrays (MEA) were compared with other preclincial models and clinical drug concentrations and effects using integrated risk assessment plots. All ion channel blockers produced (1) functional effects on repolarization and depolarization around the IC25 and IC50 values and (2) excessive blockade of hERG and/or blockade of sodium current precipitated arrhythmias. Our MEA data show that hiPSC-CMs demonstrate relevant pharmacology and show excellent correlations to current functional cardiac electrophysiological studies. Based on these results, MEA assays using iPSC-CMs offer a reliable, cost effective, and surrogate to preclinical in vitro testing, in addition to the 3Rs (refine, reduce, and replace animals in research) benefit. PMID:23690542

  19. Perturbation of nucleo-cytoplasmic transport affects size of nucleus and nucleolus in human cells.

    PubMed

    Ganguly, Abira; Bhattacharjee, Chumki; Bhave, Madhura; Kailaje, Vaishali; Jain, Bhawik K; Sengupta, Isha; Rangarajan, Annapoorni; Bhattacharyya, Dibyendu

    2016-03-01

    Size regulation of human cell nucleus and nucleolus are poorly understood subjects. 3D reconstruction of live image shows that the karyoplasmic ratio (KR) increases by 30-80% in transformed cell lines compared to their immortalized counterpart. The attenuation of nucleo-cytoplasmic transport causes the KR value to increase by 30-50% in immortalized cell lines. Nucleolus volumes are significantly increased in transformed cell lines and the attenuation of nucleo-cytoplasmic transport causes a significant increase in the nucleolus volume of immortalized cell lines. A cytosol and nuclear fraction swapping experiment emphasizes the potential role of unknown cytosolic factors in nuclear and nucleolar size regulation. PMID:26813731

  20. Scorched earth: how will changes in ozone deposition caused by drought affect human health and ecosystems?

    NASA Astrophysics Data System (ADS)

    Emberson, L. D.; Kitwiroon, N.; Beevers, S.; Büker, P.; Cinderby, S.

    2012-10-01

    This unique study investigates the effect of ozone (O3) deposition on ground level O3 concentrations and subsequent human health and ecosystem risk under hot summer "heat wave" type meteorological events. Under such conditions, extended drought can effectively "turn off" the O3 vegetation sink leading to a substantial increase in ground level O3 concentrations. Two models that have been used for human health (the CMAQ chemical transport model) and ecosystem (the DO3SE O3 deposition model) risk assessment are combined to provide a powerful policy tool capable of novel integrated assessments of O3 risk using methods endorsed by the UNECE Convention on Long-Range Transboundary Air Pollution. This study investigates 2006, a particularly hot and dry year during which a heat wave occurred during the summer across much of the UK and Europe. To understand the influence of variable O3 dry deposition three different simulations were investigated during June and July: (i) actual conditions in 2006; (ii) conditions that assume a perfect vegetation sink for O3 deposition and (iii) conditions that assume an extended drought period that reduces the vegetation sink to a minimum. The risk of O3 to human health, assessed by estimating the number of days during which running 8-h mean O3 concentrations exceeded 100 μg m-3, show that on average across the UK, there is a difference of 16 days exceedance of the threshold between the perfect sink and drought conditions. These average results hide local variation with exceedances reaching as high as 20 days in the East Midlands and Eastern UK. Estimates of acute exposure effects show that O3 removed from the atmosphere through dry deposition during the June and July period would have been responsible for approximately 460 premature deaths. Conversely, reduced O3 dry deposition will decrease the amount of O3 taken up by vegetation and, according to flux-based assessments of vegetation damage, will lead to protection from O3 across the UK

  1. Orphans and Vulnerable Children Affected by Human Immunodeficiency Virus in Sub-Saharan Africa.

    PubMed

    Bryant, Malcolm; Beard, Jennifer

    2016-02-01

    In Sub-Saharan Africa, 15.1 million children have been orphaned because of human immunodeficiency virus (HIV). They face significant vulnerabilities, including stigma and discrimination, trauma and stress, illness, food insecurity, poverty, and difficulty accessing education. Millions of additional children who have living parents are vulnerable because their parents or other relatives are infected. This article reviews the current situation of orphans and vulnerable children, explores the underlying determinants of vulnerability and resilience, describes the response by the global community, and highlights the challenges as the HIV pandemic progresses through its fourth decade. PMID:26613693

  2. Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human primates✩

    PubMed Central

    Lukashevich, Igor S.; Carrion, Ricardo; Salvato, Maria S.; Mansfield, Keith; Brasky, Kathleen; Zapata, Juan; Cairo, Cristiana; Goicochea, Marco; Hoosien, Gia E.; Ticer, Anysha; Bryant, Joseph; Davis, Harry; Hammamieh, Rasha; Mayda, Maria; Jett, Marti; Patterson, Jean

    2008-01-01

    A single injection of ML29 reassortant vaccine for Lassa fever induces low, transient viremia, and low or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits specific immune responses and completely protects marmosets against fatal disease by induction of sterilizing cell-mediated immunity. DNA array analysis of human peripheral blood mononuclear cells from healthy donors exposed to ML29 revealed that gene expression patterns in ML29-exposed PBMC and control, media-exposed PBMC, clustered together confirming safety profile of the ML29 in non-human primates. The ML29 reassortant is a promising vaccine candidate for Lassa fever. PMID:18692539

  3. Safety, immunogenicity, and efficacy of the ML29 reassortant vaccine for Lassa fever in small non-human primates.

    PubMed

    Lukashevich, Igor S; Carrion, Ricardo; Salvato, Maria S; Mansfield, Keith; Brasky, Kathleen; Zapata, Juan; Cairo, Cristiana; Goicochea, Marco; Hoosien, Gia E; Ticer, Anysha; Bryant, Joseph; Davis, Harry; Hammamieh, Rasha; Mayda, Maria; Jett, Marti; Patterson, Jean

    2008-09-26

    A single injection of ML29 reassortant vaccine for Lassa fever induces low, transient viremia, and low or moderate levels of ML29 replication in tissues of common marmosets depending on the dose of the vaccination. The vaccination elicits specific immune responses and completely protects marmosets against fatal disease by induction of sterilizing cell-mediated immunity. DNA array analysis of human peripheral blood mononuclear cells from healthy donors exposed to ML29 revealed that gene expression patterns in ML29-exposed PBMC and control, media-exposed PBMC, clustered together confirming safety profile of the ML29 in non-human primates. The ML29 reassortant is a promising vaccine candidate for Lassa fever. PMID:18692539

  4. Phosphoproteomics profiling of human skin fibroblast cells reveals pathways and proteins affected by low doses of ionizing radiation

    SciTech Connect

    Yang, Feng; Waters, Katrina M.; Miller, John H.; Gritsenko, Marina A.; Zhao, Rui; Du, Xiuxia; Livesay, Eric A.; Purvine, Samuel O.; Monroe, Matthew E.; Wang, Yingchun; Camp, David G.; Smith, Richard D.; Stenoien, David L.

    2010-11-30

    Background: High doses of ionizing radiation result in biological damage, however the precise relationships between long term health effects, including cancer, and low dose exposures remain poorly understood and are currently extrapolated using high dose exposure data. Identifying the signaling pathways and individual proteins affected at the post-translational level by radiation should shed valuable insight into the molecular mechanisms that regulate dose dependent responses to radiation. Principle Findings: We have identified 6845 unique phosphopeptides (2566 phosphoproteins) from control and irradiated (2 and 50 cGy) primary human skin fibroblasts one hour post-exposure. Dual statistical analyses based on spectral counts and peak intensities identified 287 phosphopeptides (from 231 proteins) and 244 phosphopeptides (from 182 proteins) that varied significantly following exposure to 2 and 50 cGy respectively. This screen identified phosphorylation sites on proteins with known roles in radiation responses including TP53BP1 as well as previously unidentified radiation responsive proteins such as the candidate tumor suppressor SASH1. Bioinformatics analyses suggest that low and high doses of radiation affect both overlapping and unique biological processes and suggest a role of MAP kinase and protein kinase A (PKA) signaling in the radiation response as well as differential regulation of p53 networks at low and high doses of radiation. Conlcusions: Our results represent the most comprehensive analysis of the phosphoproteomes of human primary fibroblasts exposed to multiple doses of ionizing radiation published to date and provides a basis for the systems level identification of biological processes, molecular pathways and individual proteins regulated in a dose dependent manner by ionizing radiation. Further study of these modified proteins and affected networks should help to define the molecular mechanisms that regulate biological responses to radiation at

  5. Infrared radiation affects the mitochondrial pathway of apoptosis in human fibroblasts.

    PubMed

    Frank, Sandra; Oliver, Lisa; Lebreton-De Coster, Corinne; Moreau, Carole; Lecabellec, Marie-Thérèse; Michel, Laurence; Vallette, François M; Dubertret, Louis; Coulomb, Bernard

    2004-11-01

    We have previously observed that near-infrared (IR) pre-irradiation protects normal human dermal fibroblasts from ultraviolet (UV) cytotoxicity in vitro. Here, we show that IR pre-irradiation of human fibroblasts inhibited UVB activation of caspase-9 and -3, leading us to study early events in the mitochondrial apoptotic pathway after IR irradiation. IR irradiation led to a partial release of cytochrome c and Smac/Diablo but not apoptosis-inducing factor (AIF). This was accompanied by a slight but transient decrease in the mitochondrial membrane potential (Deltapsim) and by the insertion of Bax into mitochondrial membrane. Early apoptotic events in the mitochondrial pathway thus occurred after IR irradiation despite a lack of caspase-9 and -3 activation. This could be explained by the induction by IR of the expression of heat shock protein Hsp27, which is known to prevent apoptosome assembly. Furthermore, the balance between pro-apoptotic (i.e., Bax) and anti-apoptotic (i.e., Bcl-2 or Bcl-xL) proteins, which was rather pro-apoptotic after IR exposure, became anti-apoptotic 24 h later, suggesting a protective effect. Together, these actions could also contribute to prepare the cell to resist UVB-triggered apoptosis. Finally, isolated rat liver mitochondria-released cytochrome c in response to IR, demonstrating that mitochondria were a primary target of IR radiation. PMID:15482467

  6. MEK inhibition affects STAT3 signaling and invasion in human melanoma cell lines

    PubMed Central

    Vultur, Adina; Villanueva, Jessie; Krepler, Clemens; Rajan, Geena; Chen, Quan; Xiao, Min; Li, Ling; Gimotty, Phyllis A.; Wilson, Melissa; Hayden, James; Keeney, Frederick; Nathanson, Katherine L.; Herlyn, Meenhard

    2013-01-01

    Elevated activity of the MAPK signaling cascade is found in the majority of human melanomas and is known to regulate proliferation, survival, and invasion. Current targeted therapies focus on decreasing the activity of this pathway; however, we do not fully understand how these therapies impact tumor biology, especially given that melanoma is a heterogeneous disease. Using a three-dimensional (3D), collagen-embedded spheroid melanoma model, we observed that MEK and BRAF inhibitors can increase the invasive potential of approximately 20% of human melanoma cell lines. The invasive cell lines displayed increased receptor tyrosine kinase (RTK) activity and activation of the Src/FAK/STAT3 signaling axis, also associated with increased cell-to-cell adhesion and cadherin engagement following MEK inhibition. Targeting various RTKs, Src, FAK, and STAT3 with small molecule inhibitors in combination with a MEK inhibitor prevented the invasive phenotype, but only STAT3 inhibition caused cell death in the 3D context. We further show that STAT3 signaling is induced in BRAF-inhibitor resistant cells. Our findings suggest that MEK and BRAF inhibitors can induce STAT3 signaling, causing potential adverse effects such as increased invasion. We also provide the rationale for the combined targeting of the MAPK pathway along with inhibitors of RTKs, SRC, or STAT3 to counteract STAT3-mediated resistance phenotypes. PMID:23624919

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

    PubMed Central

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

    2014-01-01

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

  8. Disrupting mitochondrial-nuclear coevolution affects OXPHOS complex I integrity and impacts human health.

    PubMed

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

    2014-10-01

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

  9. NUTRIENT TRANSPORT IN HUMAN ANNULUS FIBROSUS IS AFFECTED BY COMPRESSIVE STRAIN AND ANISOTROPY

    PubMed Central

    Jackson, Alicia R.; Yuan, Tai-Yi; Huang, Chun-Yuh; Brown, Mark D.; Gu, Wei Yong

    2012-01-01

    The avascular intervertebral disc (IVD) receives nutrition via transport from surrounding vasculature; poor nutrition is believed to be a main cause of disc degeneration. In this study, we investigated the effects of mechanical deformation and anisotropy on the transport of two important nutrients – oxygen and glucose – in human annulus fibrosus (AF). The diffusivities of oxygen and glucose were measured under three levels of uniaxial confined compression – 0%, 10%, and 20% – and in three directions – axial, circumferential, and radial. The glucose partition coefficient was also measured at three compression levels. Results for glucose and oxygen diffusivity in AF ranged from 4.46×10−7 to 9.77×10−6 cm2/s and were comparable to previous studies; the glucose partition coefficient ranged from 0.71 to 0.82 and was also similar to previous results. Transport properties were found to decrease with increasing deformation, likely caused by fluid exudation during tissue compression and reduction in pore size. Furthermore, diffusivity in the radial direction was lower than in the axial or circumferential directions, indicating that nutrient transport in human AF is anisotropic. This behavior is likely a consequence of the layered structure and unique collagen architecture of AF tissue. These findings are important for better understanding nutritional supply in IVD and related disc degeneration. PMID:22669503

  10. Surveying wearable human assistive technology for life and safety critical applications: standards, challenges and opportunities.

    PubMed

    Alam, Muhammad Mahtab; Ben Hamida, Elyes

    2014-01-01

    In this survey a new application paradigm life and safety for critical operations and missions using wearable Wireless Body Area Networks (WBANs) technology is introduced. This paradigm has a vast scope of applications, including disaster management, worker safety in harsh environments such as roadside and building workers, mobile health monitoring, ambient assisted living and many more. It is often the case that during the critical operations and the target conditions, the existing infrastructure is either absent, damaged or overcrowded. In this context, it is envisioned that WBANs will enable the quick deployment of ad-hoc/on-the-fly communication networks to help save many lives and ensuring people's safety. However, to understand the applications more deeply and their specific characteristics and requirements, this survey presents a comprehensive study on the applications scenarios, their context and specific requirements. It explores details of the key enabling standards, existing state-of-the-art research studies, and projects to understand their limitations before realizing aforementioned applications. Application-specific challenges and issues are discussed comprehensively from various perspectives and future research and development directions are highlighted as an inspiration for new innovative solutions. To conclude, this survey opens up a good opportunity for companies and research centers to investigate old but still new problems, in the realm of wearable technologies, which are increasingly evolving and getting more and more attention recently. PMID:24859024

  11. Surveying Wearable Human Assistive Technology for Life and Safety Critical Applications: Standards, Challenges and Opportunities

    PubMed Central

    Alam, Muhammad Mahtab; Ben Hamida, Elyes

    2014-01-01

    In this survey a new application paradigm life and safety for critical operations and missions using wearable Wireless Body Area Networks (WBANs) technology is introduced. This paradigm has a vast scope of applications, including disaster management, worker safety in harsh environments such as roadside and building workers, mobile health monitoring, ambient assisted living and many more. It is often the case that during the critical operations and the target conditions, the existing infrastructure is either absent, damaged or overcrowded. In this context, it is envisioned that WBANs will enable the quick deployment of ad-hoc/on-the-fly communication networks to help save many lives and ensuring people's safety. However, to understand the applications more deeply and their specific characteristics and requirements, this survey presents a comprehensive study on the applications scenarios, their context and specific requirements. It explores details of the key enabling standards, existing state-of-the-art research studies, and projects to understand their limitations before realizing aforementioned applications. Application-specific challenges and issues are discussed comprehensively from various perspectives and future research and development directions are highlighted as an inspiration for new innovative solutions. To conclude, this survey opens up a good opportunity for companies and research centers to investigate old but still new problems, in the realm of wearable technologies, which are increasingly evolving and getting more and more attention recently. PMID:24859024

  12. A preliminary analysis of human factors affecting the recognition accuracy of a discrete word recognizer for C3 systems

    NASA Astrophysics Data System (ADS)

    Yellen, H. W.

    1983-03-01

    Literature pertaining to Voice Recognition abounds with information relevant to the assessment of transitory speech recognition devices. In the past, engineering requirements have dictated the path this technology followed. But, other factors do exist that influence recognition accuracy. This thesis explores the impact of Human Factors on the successful recognition of speech, principally addressing the differences or variability among users. A Threshold Technology T-600 was used for a 100 utterance vocubalary to test 44 subjects. A statistical analysis was conducted on 5 generic categories of Human Factors: Occupational, Operational, Psychological, Physiological and Personal. How the equipment is trained and the experience level of the speaker were found to be key characteristics influencing recognition accuracy. To a lesser extent computer experience, time or week, accent, vital capacity and rate of air flow, speaker cooperativeness and anxiety were found to affect overall error rates.

  13. Keeping Pace with Your Eating: Visual Feedback Affects Eating Rate in Humans.

    PubMed

    Wilkinson, Laura L; Ferriday, Danielle; Bosworth, Matthew L; Godinot, Nicolas; Martin, Nathalie; Rogers, Peter J; Brunstrom, Jeffrey M

    2016-01-01

    Deliberately eating at a slower pace promotes satiation and eating quickly has been associated with a higher body mass index. Therefore, understanding factors that affect eating rate should be given high priority. Eating rate is affected by the physical/textural properties of a food, by motivational state, and by portion size and palatability. This study explored the prospect that eating rate is also influenced by a hitherto unexplored cognitive process that uses ongoing perceptual estimates of the volume of food remaining in a container to adjust intake during a meal. A 2 (amount seen; 300 ml or 500 ml) x 2 (amount eaten; 300 ml or 500 ml) between-subjects design was employed (10 participants in each condition). In two 'congruent' conditions, the same amount was seen at the outset and then subsequently consumed (300 ml or 500 ml). To dissociate visual feedback of portion size and actual amount consumed, food was covertly added or removed from a bowl using a peristaltic pump. This created two additional 'incongruent' conditions, in which 300 ml was seen but 500 ml was eaten or vice versa. We repeated these conditions using a savoury soup and a sweet dessert. Eating rate (ml per second) was assessed during lunch. After lunch we assessed fullness over a 60-minute period. In the congruent conditions, eating rate was unaffected by the actual volume of food that was consumed (300 ml or 500 ml). By contrast, we observed a marked difference across the incongruent conditions. Specifically, participants who saw 300 ml but actually consumed 500 ml ate at a faster rate than participants who saw 500 ml but actually consumed 300 ml. Participants were unaware that their portion size had been manipulated. Nevertheless, when it disappeared faster or slower than anticipated they adjusted their rate of eating accordingly. This suggests that the control of eating rate involves visual feedback and is not a simple reflexive response to orosensory stimulation. PMID:26828922

  14. Keeping Pace with Your Eating: Visual Feedback Affects Eating Rate in Humans

    PubMed Central

    Bosworth, Matthew L.; Godinot, Nicolas; Martin, Nathalie; Rogers, Peter J.; Brunstrom, Jeffrey M.

    2016-01-01

    Deliberately eating at a slower pace promotes satiation and eating quickly has been associated with a higher body mass index. Therefore, understanding factors that affect eating rate should be given high priority. Eating rate is affected by the physical/textural properties of a food, by motivational state, and by portion size and palatability. This study explored the prospect that eating rate is also influenced by a hitherto unexplored cognitive process that uses ongoing perceptual estimates of the volume of food remaining in a container to adjust intake during a meal. A 2 (amount seen; 300ml or 500ml) x 2 (amount eaten; 300ml or 500ml) between-subjects design was employed (10 participants in each condition). In two ‘congruent’ conditions, the same amount was seen at the outset and then subsequently consumed (300ml or 500ml). To dissociate visual feedback of portion size and actual amount consumed, food was covertly added or removed from a bowl using a peristaltic pump. This created two additional ‘incongruent’ conditions, in which 300ml was seen but 500ml was eaten or vice versa. We repeated these conditions using a savoury soup and a sweet dessert. Eating rate (ml per second) was assessed during lunch. After lunch we assessed fullness over a 60-minute period. In the congruent conditions, eating rate was unaffected by the actual volume of food that was consumed (300ml or 500ml). By contrast, we observed a marked difference across the incongruent conditions. Specifically, participants who saw 300ml but actually consumed 500ml ate at a faster rate than participants who saw 500ml but actually consumed 300ml. Participants were unaware that their portion size had been manipulated. Nevertheless, when it disappeared faster or slower than anticipated they adjusted their rate of eating accordingly. This suggests that the control of eating rate involves visual feedback and is not a simple reflexive response to orosensory stimulation. PMID:26828922

  15. Human systemic exposure to [¹⁴C]-paraphenylenediamine-containing oxidative hair dyes: Absorption, kinetics, metabolism, excretion and safety assessment.

    PubMed

    Nohynek, Gerhard J; Skare, Julie A; Meuling, Wim J A; Wehmeyer, Kenneth R; de Bie, Albertus Th H J; Vaes, Wouter H J; Dufour, Eric K; Fautz, Rolf; Steiling, Winfried; Bramante, Mario; Toutain, Herve

    2015-07-01

    Systemic exposure was measured in humans after hair dyeing with oxidative hair dyes containing 2.0% (A) or 1.0% (B) [(14)C]-p-phenylenediamine (PPD). Hair was dyed, rinsed, dried, clipped and shaved; blood and urine samples were collected for 48 hours after application. [(14)C] was measured in all materials, rinsing water, hair, plasma, urine and skin strips. Plasma and urine were also analysed by HLPC/MS/MS for PPD and its metabolites (B). Total mean recovery of radioactivity was 94.30% (A) or 96.21% (B). Mean plasma Cmax values were 132.6 or 97.4 ng [(14)C]-PPDeq/mL, mean AUC(0-∞) values 1415 or 966 ng [(14)C]-PPDeq/mL*hr in studies A or B, respectively. Urinary excretion of [(14)C] mainly occurred within 24 hrs after hair colouring with a total excretion of 0.72 or 0.88% of applied radioactivity in studies A or B, respectively. Only N,N'-diacetylated-PPD was detected in plasma and the urine. A TK-based human safety assessment estimated margins of safety of 23.3- or 65-fold relative to respective plasma AUC or Cmax values in rats at the NOAEL of a toxicity study. Overall, hair dyes containing PPD are unlikely to pose a health risk since they are used intermittently and systemic exposure is limited to the detoxified metabolite N,N'-diacetyl-PPD. PMID:25846501

  16. Muscle Fatigue Affects the Interpolated Twitch Technique When Assessed Using Electrically-Induced Contractions in Human and Rat Muscles

    PubMed Central

    Neyroud, Daria; Cheng, Arthur J.; Bourdillon, Nicolas; Kayser, Bengt; Place, Nicolas; Westerblad, Håkan

    2016-01-01

    The interpolated twitch technique (ITT) is the gold standard to assess voluntary activation and central fatigue. Yet, its validity has been questioned. Here we studied how peripheral fatigue can affect the ITT. Repeated contractions at submaximal frequencies were produced by supramaximal electrical stimulations of the human adductor pollicis muscle in vivo and of isolated rat soleus fiber bundles; an extra stimulation pulse was given during contractions to induce a superimposed twitch. Human muscles fatigued by repeated 30-Hz stimulation trains (3 s on–1 s off) showed an ~80% reduction in the superimposed twitch force accompanied by a severely reduced EMG response (M-wave amplitude), which implies action potential failure. Subsequent experiments combined a less intense stimulation protocol (1.5 s on–3 s off) with ischemia to cause muscle fatigue, but which preserved M-wave amplitude. However, the superimposed twitch force still decreased markedly more than the potentiated twitch force; with ITT this would reflect increased “voluntary activation.” In contrast, the superimposed twitch force was relatively spared when a similar protocol was performed in rat soleus bundles. Force relaxation was slowed by >150% in fatigued human muscles, whereas it was unchanged in rat soleus bundles. Accordingly, results similar to those in the human muscle were obtained when relaxation was slowed by cooling the rat soleus muscles. In conclusion, our data demonstrate that muscle fatigue can confound the quantification of central fatigue using the ITT.

  17. I saw where you have been-The topography of human demonstration affects dogs' search patterns and perseverative errors.

    PubMed

    Péter, András; Topál, József; Miklósi, Ádám; Pongrácz, Péter

    2016-04-01

    Performance in object search tasks is not only influenced by the subjects' object permanence ability. For example, ostensive cues of the human manipulating the target markedly affect dogs' choices. However, the interference between the target's location and the spatial cues of the human hiding the object is still unknown. In a five-location visible displacement task, the experimental groups differed in the hiding route of the experimenter. In the 'direct' condition he moved straight towards the actual location, hid the object and returned to the dog. In the 'indirect' conditions, he additionally walked behind each screen before returning. The two 'indirect' conditions differed from each other in that the human either visited the previously baited locations before (proactive interference) or after (retroactive interference) hiding the object. In the 'indirect' groups, dogs' performance was significantly lower than in the 'direct' group, demonstrating that for dogs, in an ostensive context, spatial cues of the hider are as important as the observed location of the target. Based on their incorrect choices, dogs were most attracted to the previously baited locations that the human visited after hiding the object in the actual trial. This underlines the importance of retroactive interference in multiple choice tasks. PMID:26869220

  18. Acquisition and Extinction of Human Avoidance Behavior: Attenuating Effect of Safety Signals and Associations with Anxiety Vulnerabilities

    PubMed Central

    Sheynin, Jony; Beck, Kevin D.; Servatius, Richard J.; Myers, Catherine E.

    2014-01-01

    While avoidance behavior is often an adaptive strategy, exaggerated avoidance can be detrimental and result in the development of psychopathologies, such as anxiety disorders. A large animal literature shows that the acquisition and extinction of avoidance behavior in rodents depends on individual differences (e.g., sex, strain) and might be modulated by the presence of environmental cues. However, there is a dearth of such reports in human literature, mainly due to the lack of adequate experimental paradigms. In the current study, we employed a computer-based task, where participants control a spaceship and attempt to gain points by shooting an enemy spaceship that appears on the screen. Warning signals predict on-screen aversive events; the participants can learn a protective response to escape or avoid these events. This task has been recently used to reveal facilitated acquisition of avoidance behavior in individuals with anxiety vulnerability due to female sex or inhibited personality. Here, we extended the task to include an extinction phase, and tested the effect of signals that appeared during “safe” periods. Healthy young adults (n = 122) were randomly assigned to a testing condition with or without such signals. Results showed that the addition of safety signals during the acquisition phase impaired acquisition (in females) and facilitated extinction of the avoidance behavior. We also replicated our recent finding of an association between female sex and longer avoidance duration and further showed that females continued to demonstrate more avoidance behavior even on extinction trials when the aversive events no longer occurred. This study is the first to show sex differences on the acquisition and extinction of human avoidance behavior and to demonstrate the role of safety signals in such behavior, highlighting the potential relevance of safety signals for cognitive therapies that focus on extinction learning to treat anxiety symptoms. PMID

  19. Dry-heat treatment process for enhancing viral safety of an antihemophilic factor VIII concentrate prepared from human plasma.

    PubMed

    Kim, In Seop; Choi, Yong Woon; Kang, Yong; Sung, Hark Mo; Shin, Jeong Sup

    2008-05-01

    Viral safety is a prerequisite for manufacturing clinical antihemophilic factor VIII concentrates from human plasma. With particular regard to the hepatitis A virus (HAV), a terminal dry-heat treatment (100 degrees for 30 min) process, following lyophilization, was developed to improve the virus safety of a solvent/detergent-treated antihemophilic factor VIII concentrate. The loss of factor VIII activity during dry-heat treatment was of about 5%. No substantial changes were observed in the physical and biochemical characteristics of the dry-heat-treated factor VIII compared with those of the factor VIII before dry-heat treatment. The dry-heat-treated factor VIII was stable for up to 24 months at 4oC. The dry-heat treatment after lyophilization was an effective process for inactivating viruses. The HAV, murine encephalomyocarditis virus (EMCV), and human immunodeficiency virus (HIV) were completely inactivated to below detectable levels within 10 min of the dry-heat treatment. Bovine herpes virus (BHV) and bovine viral diarrhea virus (BVDV) were potentially sensitive to the treatment. However porcine parvovirus (PPV) was slightly resistant to the treatment. The log reduction factors achieved during lyophilization and dry-heat treatment were > or =5.55 for HAV, > or =5.87 for EMCV, > or =5.15 for HIV, 6.13 for BHV, 4.46 for BVDV, and 1.90 for PPV. These results indicate that dry-heat treatment improves the virus safety of factor VIII concentrates, without destroying the activity. Moreover, the treatment represents an effective measure for the inactivation of non-lipid-enveloped viruses, in particular HAV, which is resistant to solvent/detergent treatment. PMID:18633304

  20. Human genetics. The genetics of Mexico recapitulates Native American substructure and affects biomedical traits.

    PubMed

    Moreno-Estrada, Andrés; Gignoux, Christopher R; Fernández-López, Juan Carlos; Zakharia, Fouad; Sikora, Martin; Contreras, Alejandra V; Acuña-Alonzo, Victor; Sandoval, Karla; Eng, Celeste; Romero-Hidalgo, Sandra; Ortiz-Tello, Patricia; Robles, Victoria; Kenny, Eimear E; Nuño-Arana, Ismael; Barquera-Lozano, Rodrigo; Macín-Pérez, Gastón; Granados-Arriola, Julio; Huntsman, Scott; Galanter, Joshua M; Via, Marc; Ford, Jean G; Chapela, Rocío; Rodriguez-Cintron, William; Rodríguez-Santana, Jose R; Romieu, Isabelle; Sienra-Monge, Juan José; del Rio Navarro, Blanca; London, Stephanie J; Ruiz-Linares, Andrés; Garcia-Herrera, Rodrigo; Estrada, Karol; Hidalgo-Miranda, Alfredo; Jimenez-Sanchez, Gerardo; Carnevale, Alessandra; Soberón, Xavier; Canizales-Quinteros, Samuel; Rangel-Villalobos, Héctor; Silva-Zolezzi, Irma; Burchard, Esteban Gonzalez; Bustamante, Carlos D

    2014-06-13

    Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide. PMID:24926019

  1. Nef Does Not Affect the Efficiency of Human Immunodeficiency Virus Type 1 Fusion with Target Cells

    PubMed Central

    Tobiume, Minoru; Lineberger, Janet E.; Lundquist, Christopher A.; Miller, Michael D.; Aiken, Christopher

    2003-01-01

    The human immunodeficiency virus type 1 (HIV-1) accessory protein Nef stimulates viral infectivity by an unknown mechanism. Recent studies have suggested that Nef may act by regulating the efficiency of virus entry into cells. Here we provide evidence to the contrary. Using a quantitative assay of HIV-1 virus-cell fusion, we observed equivalent rates and extents of fusion of wild-type and Nef-defective HIV-1 particles with MT-4 cells and CD4-expressing HeLa cells. In studies using soluble CD4 (sCD4) to inhibit infection, wild-type and Nef-defective HIV-1 escaped the sCD4 block with similar kinetics. We conclude that Nef acts at a postentry step in infection, probably by facilitating intracellular transport of the HIV-1 ribonucleoprotein complex. PMID:12970449

  2. A factor in human seminal plasma which affects carnitine accumulation in bovine epididymal sperm.

    PubMed

    Carter, A L; Cho, S H; Bishop, E R; Boldt, J

    1988-05-01

    This study was initiated to determine whether factors are present in human sperm-free seminal plasma (HSP) that regulate the uptake and release of carnitine from sperm. Bovine caput epididymal sperm cells accumulated more carnitine than caudal sperm cells. A significant reduction in carnitine uptake by caput sperm was observed in the presence of HSP from normal subjects, but not from three subjects with reduced motility. A factor has been isolated from HSP that inhibits carnitine uptake by caput sperm and has the following properties: it is nondialyzable, stable to freeze-thawing, soluble in 60% ammonium sulfate, and has an approximate molecular weight of 158 kd. These data are consistent with the existence of a relatively high molecular weight protein in HSP responsible for the preservation of carnitine concentrations in sperm. PMID:3360180

  3. Antibiotics in ingested human blood affect the mosquito microbiota and capacity to transmit malaria

    PubMed Central

    Gendrin, Mathilde; Rodgers, Faye H.; Yerbanga, Rakiswendé S.; Ouédraogo, Jean Bosco; Basáñez, María-Gloria; Cohuet, Anna; Christophides, George K.

    2015-01-01

    Malaria reduction is most efficiently achieved by vector control whereby human populations at high risk of contracting and transmitting the disease are protected from mosquito bites. Here, we identify the presence of antibiotics in the blood of malaria-infected people as a new risk of increasing disease transmission. We show that antibiotics in ingested blood enhance the susceptibility of Anopheles gambiae mosquitoes to malaria infection by disturbing their gut microbiota. This effect is confirmed in a semi-natural setting by feeding mosquitoes with blood of children naturally infected with Plasmodium falciparum. Antibiotic exposure additionally increases mosquito survival and fecundity, which are known to augment vectorial capacity. These findings suggest that malaria transmission may be exacerbated in areas of high antibiotic usage, and that regions targeted by mass drug administration programs against communicable diseases may necessitate increased vector control. PMID:25562286

  4. Does tropicamide affect choroidal blood flow in humans? a laser Doppler flowmetry study

    NASA Astrophysics Data System (ADS)

    Palanisamy, Nithiyanantham; Riva, Charles E.; Rovati, Luigi; Cellini, Mauro; Gizzi, Corrado; Strobbe, Ernesto; Campos, Emilio C.

    2012-03-01

    The measurement of blood flow in the ocular fundus is of scientific and clinical interest. Investigating ocular blood flow in the choroid may be important to understand the pathogenesis of numerous ocular diseases, such as glaucoma or agerelated macular degeneration (AMD). Laser Doppler flowmetry (LDF) was applied to measure relative velocity, volume and flux of red blood cells in the tissues of human eye. Its main application lies in the possibility of assessing alterations in blood flow early in the course of diseases. The purpose of the present study was to investigate the effect of pupil dilatation with one drop of 1% tropicamide on blood flow in the foveal region of the choroid of the human fundus. The blood flow parameters were measured in 24 eyes during 30 minutes (one measurement in every 3 minutes) after the application of the drop. Since the Doppler parameters depend on the scattering geometry, which may change as the pupil dilates; an artificial pupil of 4mm in diameter was placed directly in front the eye. Following the administration of tropicamide the mean pupil diameter was increased from 3.29 mm to 8.25 mm (P<0.0001, Paired student t-test). In comparison to the baseline values, the data shows no significant increases were observed in velocity, volume, and flow with 4 mm artificial pupil (0.2%, 1.3%, 0.8% respectively) and a statistically significant increases were observed without artificial pupil (10.7%, 13.9%, 12.8% respectively) following the application of tropicamide.

  5. Age and Gender Affect the Composition of Fungal Population of the Human Gastrointestinal Tract.

    PubMed

    Strati, Francesco; Di Paola, Monica; Stefanini, Irene; Albanese, Davide; Rizzetto, Lisa; Lionetti, Paolo; Calabrò, Antonio; Jousson, Olivier; Donati, Claudio; Cavalieri, Duccio; De Filippo, Carlotta

    2016-01-01

    The fungal component of the human gut microbiota has been neglected for long time due to the low relative abundance of fungi with respect to bacteria, and only recently few reports have explored its composition and dynamics in health or disease. The application of metagenomics methods to the full understanding of fungal communities is currently limited by the under representation of fungal DNA with respect to the bacterial one, as well as by the limited ability to discriminate passengers from colonizers. Here, we investigated the gut mycobiota of a cohort of healthy subjects in order to reduce the gap of knowledge concerning fungal intestinal communities in the healthy status further screening for phenotypical traits that could reflect fungi adaptation to the host. We studied the fecal fungal populations of 111 healthy subjects by means of cultivation on fungal selective media and by amplicon-based ITS1 metagenomics analysis on a subset of 57 individuals. We then characterized the isolated fungi for their tolerance to gastrointestinal (GI) tract-like challenges and their susceptibility to antifungals. A total of 34 different fungal species were isolated showing several phenotypic characteristics associated with intestinal environment such as tolerance to body temperature (37°C), to acidic and oxidative stress, and to bile salts exposure. We found a high frequency of azoles resistance in fungal isolates, with potential and significant clinical impact. Analyses of fungal communities revealed that the human gut mycobiota differs in function of individuals' life stage in a gender-related fashion. The combination of metagenomics and fungal cultivation allowed an in-depth understanding of the fungal intestinal community structure associated to the healthy status and the commensalism-related traits of isolated fungi. We further discussed comparatively the results of sequencing and cultivation to critically evaluate the application of metagenomics-based approaches to

  6. Age and Gender Affect the Composition of Fungal Population of the Human Gastrointestinal Tract

    PubMed Central

    Strati, Francesco; Di Paola, Monica; Stefanini, Irene; Albanese, Davide; Rizzetto, Lisa; Lionetti, Paolo; Calabrò, Antonio; Jousson, Olivier; Donati, Claudio; Cavalieri, Duccio; De Filippo, Carlotta

    2016-01-01

    The fungal component of the human gut microbiota has been neglected for long time due to the low relative abundance of fungi with respect to bacteria, and only recently few reports have explored its composition and dynamics in health or disease. The application of metagenomics methods to the full understanding of fungal communities is currently limited by the under representation of fungal DNA with respect to the bacterial one, as well as by the limited ability to discriminate passengers from colonizers. Here, we investigated the gut mycobiota of a cohort of healthy subjects in order to reduce the gap of knowledge concerning fungal intestinal communities in the healthy status further screening for phenotypical traits that could reflect fungi adaptation to the host. We studied the fecal fungal populations of 111 healthy subjects by means of cultivation on fungal selective media and by amplicon-based ITS1 metagenomics analysis on a subset of 57 individuals. We then characterized the isolated fungi for their tolerance to gastrointestinal (GI) tract-like challenges and their susceptibility to antifungals. A total of 34 different fungal species were isolated showing several phenotypic characteristics associated with intestinal environment such as tolerance to body temperature (37°C), to acidic and oxidative stress, and to bile salts exposure. We found a high frequency of azoles resistance in fungal isolates, with potential and significant clinical impact. Analyses of fungal communities revealed that the human gut mycobiota differs in function of individuals' life stage in a gender-related fashion. The combination of metagenomics and fungal cultivation allowed an in-depth understanding of the fungal intestinal community structure associated to the healthy status and the commensalism-related traits of isolated fungi. We further discussed comparatively the results of sequencing and cultivation to critically evaluate the application of metagenomics-based approaches to

  7. Phase I pilot clinical trial of antenatal maternally administered melatonin to decrease the level of oxidative stress in human pregnancies affected by pre-eclampsia (PAMPR): study protocol

    PubMed Central

    Hobson, Sebastian R; Lim, Rebecca; Gardiner, Elizabeth E; Alers, Nicole O; Wallace, Euan M

    2013-01-01

    Introduction Pre-eclampsia is a common pregnancy condition affecting between 3% and 7% of women. Unfortunately, the exact pathophysiology of the disease is unknown and as such there are no effective treatments that exist notwithstanding prompt delivery of the fetus and culprit placenta. As many cases of pre-eclampsia occur in preterm pregnancies, it remains a significant cause of maternal and perinatal morbidity and mortality. Recently, in vitro and animal studies have highlighted the potential role of antioxidants in mitigating the effects of the disease. Melatonin is a naturally occurring antioxidant hormone and provides an excellent safety profile combined with ease of oral administration. We present the protocol for a phase I pilot clinical trial investigating the efficacy and side effects of maternal treatment with oral melatonin in pregnancies affected by preterm pre-eclampsia. Methods and analysis We propose undertaking a single-arm open label clinical trial recruiting 20 women with preterm pre-eclampsia (24+0–35+6 weeks). We will take baseline measurements of maternal and fetal well-being, levels of oxidative stress, ultrasound Doppler studies and other biomarkers of pre-eclampsia. Women will then be given oral melatonin (10 mg) three times daily until delivery. The primary outcome will be time interval between diagnosis and delivery compared to historical controls. Secondary outcomes will compare the baseline measurements previously mentioned with twice-weekly measurements during treatment and then 6 weeks postpartum. Ethics and dissemination Ethical approval has been obtained from Monash Health Human Research Ethics Committee B (HREC 13076B). Data will be presented at international conferences and published in peer-reviewed journals. Trial registration number ACTRN12613000476730 (ANZCTR). PMID:24056493

  8. Xenobiotics that affect oxidative phosphorylation alter differentiation of human adipose-derived stem cells at concentrations that are found in human blood

    PubMed Central

    Llobet, Laura; Toivonen, Janne M.; Montoya, Julio; Ruiz-Pesini, Eduardo; López-Gallardo, Ester

    2015-01-01

    ABSTRACT Adipogenesis is accompanied by differentiation of adipose tissue-derived stem cells to adipocytes. As part of this differentiation, biogenesis of the oxidative phosphorylation system occurs. Many chemical compounds used in medicine, agriculture or other human activities affect oxidative phosphorylation function. Therefore, these xenobiotics could alter adipogenesis. We have analyzed the effects on adipocyte differentiation of some xenobiotics that act on the oxidative phosphorylation system. The tested concentrations have been previously reported in human blood. Our results show that pharmaceutical drugs that decrease mitochondrial DNA replication, such as nucleoside reverse transcriptase inhibitors, or inhibitors of mitochondrial protein synthesis, such as ribosomal antibiotics, diminish adipocyte differentiation and leptin secretion. By contrast, the environmental chemical pollutant tributyltin chloride, which inhibits the ATP synthase of the oxidative phosphorylation system, can promote adipocyte differentiation and leptin secretion, leading to obesity and metabolic syndrome as postulated by the obesogen hypothesis. PMID:26398948

  9. Examination of the Safety of Pediatric Vaccine Schedules in a Non-Human Primate Model: Assessments of Neurodevelopment, Learning, and Social Behavior

    PubMed Central

    Curtis, Britni; Liberato, Noelle; Rulien, Megan; Morrisroe, Kelly; Kenney, Caroline; Yutuc, Vernon; Ferrier, Clayton; Marti, C. Nathan; Mandell, Dorothy; Burbacher, Thomas M.; Sackett, Gene P.

    2015-01-01

    Background In the 1990s, the mercury-based preservative thimerosal was used in most pediatric vaccines. Although there are currently only two thimerosal-containing vaccines (TCVs) recommended for pediatric use, parental perceptions that vaccines pose safety concerns are affecting vaccination rates, particularly in light of the much expanded and more complex schedule in place today. Objectives The objective of this study was to examine the safety of pediatric vaccine schedules in a non-human primate model. Methods We administered vaccines to six groups of infant male rhesus macaques (n = 12–16/group) using a standardized thimerosal dose where appropriate. Study groups included the recommended 1990s Pediatric vaccine schedule, an accelerated 1990s Primate schedule with or without the measles–mumps–rubella (MMR) vaccine, the MMR vaccine only, and the expanded 2008 schedule. We administered saline injections to age-matched control animals (n = 16). Infant development was assessed from birth to 12 months of age by examining the acquisition of neonatal reflexes, the development of object concept permanence (OCP), computerized tests of discrimination learning, and infant social behavior. Data were analyzed using analysis of variance, multilevel modeling, and survival analyses, where appropriate. Results We observed no group differences in the acquisition of OCP. During discrimination learning, animals receiving TCVs had improved performance on reversal testing, although some of these same animals showed poorer performance in subsequent learning-set testing. Analysis of social and nonsocial behaviors identified few instances of negative behaviors across the entire infancy period. Although some group differences in specific behaviors were reported at 2 months of age, by 12 months all infants, irrespective of vaccination status, had developed the typical repertoire of macaque behaviors. Conclusions This comprehensive 5-year case–control study, which closely examined

  10. Human Pluripotent Stem Cell Based Developmental Toxicity Assays for Chemical Safety Screening and Systems Biology Data Generation.

    PubMed

    Shinde, Vaibhav; Klima, Stefanie; Sureshkumar, Perumal Srinivasan; Meganathan, Kesavan; Jagtap, Smita; Rempel, Eugen; Rahnenführer, Jörg; Hengstler, Jan Georg; Waldmann, Tanja; Hescheler, Jürgen; Leist, Marcel; Sachinidis, Agapios

    2015-01-01

    Efficient protocols to differentiate human pluripotent stem cells to various tissues in combination with -omics technologies opened up new horizons for in vitro toxicity testing of potential drugs. To provide a solid scientific basis for such assays, it will be important to gain quantitative information on the time course of development and on the underlying regulatory mechanisms by systems biology approaches. Two assays have therefore been tuned here for these requirements. In the UKK test system, human embryonic stem cells (hESC) (or other pluripotent cells) are left to spontaneously differentiate for 14 days in embryoid bodies, to allow generation of cells of all three germ layers. This system recapitulates key steps of early human embryonic development, and it can predict human-specific early embryonic toxicity/teratogenicity, if cells are exposed to chemicals during differentiation. The UKN1 test system is based on hESC differentiating to a population of neuroectodermal progenitor (NEP) cells for 6 days. This system recapitulates early neural development and predicts early developmental neurotoxicity and epigenetic changes triggered by chemicals. Both systems, in combination with transcriptome microarray studies, are suitable for identifying toxicity biomarkers. Moreover, they may be used in combination to generate input data for systems biology analysis. These test systems have advantages over the traditional toxicological studies requiring large amounts of animals. The test systems may contribute to a reduction of the costs for drug development and chemical safety evaluation. Their combination sheds light especially on compounds that may influence neurodevelopment specifically. PMID:26132533

  11. Position and length of fatty acids strongly affect receptor selectivity pattern of human pancreatic polypeptide analogues.

    PubMed

    Mäde, Veronika; Bellmann-Sickert, Kathrin; Kaiser, Anette; Meiler, Jens; Beck-Sickinger, Annette G

    2014-11-01

    Pancreatic polypeptide (PP) is a satiety-inducing gut hormone targeting predominantly the Y4 receptor within the neuropeptide Y multiligand/multireceptor family. Palmitoylated PP-based ligands have already been reported to exert prolonged satiety-inducing effects in animal models. Here, we suggest that other lipidation sites and different fatty acid chain lengths may affect receptor selectivity and metabolic stability. Activity tests revealed significantly enhanced potency of long fatty acid conjugates on all four Y receptors with a preference of position 22 over 30 at Y1 , Y2 and Y5 receptors. Improved Y receptor selectivity was observed for two short fatty acid analogues. Moreover, [K(30)(E-Prop)]hPP2-36 (15) displayed enhanced stability in blood plasma and liver homogenates. Thus, short chain lipidation of hPP at key residue 30 is a promising approach for anti-obesity therapy because of maintained selectivity and a sixfold increased plasma half-life. PMID:25156249

  12. Opioid and nicotine receptors affect growth regulation of human lung cancer cell lines

    SciTech Connect

    Maneckjee, R.; Minna, J.D. Uniformed Services Univ. of the Health Sciences, Bethesda, MD )

    1990-05-01

    Using specific radioactively-labeled ligands, the authors find that lung cancer cell lines of diverse histologic types express multiple, high-affinity membrane receptors for {mu}, {delta}, and {kappa} opioid agonists and for nicotine and {alpha}-bungarotoxin. These receptors are biologically active because cAMP levels decreased in lung cancer cells after opioid and nicotine application. Nicotine at concentrations found in the blood of smokers had no effect on in vitro lung cancer cell growth, whereas {mu}, {delta}, and {kappa} opioid agonists at low concentrations inhibited lung cancer growth in vitro. They also found that lung cancer cells expressed various combinations of immunoreactive opioid peptides ({beta}-endorphin, enkephalin, or dynorphin), suggesting the participation of opioids in a negative autocrine loop or tumor-suppressing system. Due to the almost universal exposure of patients with lung cancer to nicotine, they tested whether nicotine affected the response of lung cancer cell growth to opioids and found that nicotine at concentrations of 100-200 nM partially or totally reversed opioid-induced growth inhibition in 9/14 lung cancer cell lines. These in vitro results for lung cancer cells suggest that opioids could function as part of a tumor suppressor system and that nicotine can function to circumvent this system in the pathogenesis of lung cancer.

  13. Human CalDAG-GEFI gene (RASGRP2) mutation affects platelet function and causes severe bleeding

    PubMed Central

    Canault, Matthias; Ghalloussi, Dorsaf; Grosdidier, Charlotte; Guinier, Marie; Perret, Claire; Chelghoum, Nadjim; Germain, Marine; Raslova, Hana; Peiretti, Franck; Morange, Pierre E.; Saut, Noemie; Pillois, Xavier; Nurden, Alan T.; Cambien, François; Pierres, Anne; van den Berg, Timo K.; Kuijpers, Taco W.; Tregouet, David-Alexandre

    2014-01-01

    The nature of an inherited platelet disorder was investigated in three siblings affected by severe bleeding. Using whole-exome sequencing, we identified the culprit mutation (cG742T) in the RAS guanyl-releasing protein-2 (RASGRP2) gene coding for calcium- and DAG-regulated guanine exchange factor-1 (CalDAG-GEFI). Platelets from individuals carrying the mutation present a reduced ability to activate Rap1 and to perform proper αIIbβ3 integrin inside-out signaling. Expression of CalDAG-GEFI mutant in HEK293T cells abolished Rap1 activation upon stimulation. Nevertheless, the PKC- and ADP-dependent pathways allow residual platelet activation in the absence of functional CalDAG-GEFI. The mutation impairs the platelet’s ability to form thrombi under flow and spread normally as a consequence of reduced Rac1 GTP-binding. Functional deficiencies were confined to platelets and megakaryocytes with no leukocyte alteration. This contrasts with the phenotype seen in type III leukocyte adhesion deficiency caused by the absence of kindlin-3. Heterozygous did not suffer from bleeding and have normal platelet aggregation; however, their platelets mimicked homozygous ones by failing to undergo normal adhesion under flow and spreading. Rescue experiments on cultured patient megakaryocytes corrected the functional deficiency after transfection with wild-type RASGRP2. Remarkably, the presence of a single normal allele is sufficient to prevent bleeding, making CalDAG-GEFI a novel and potentially safe therapeutic target to prevent thrombosis. PMID:24958846

  14. Factors affecting the aluminium content of human femoral head and neck.

    PubMed

    Zioła-Frankowska, Anetta; Dąbrowski, Mikołaj; Kubaszewski, Łukasz; Rogala, Piotr; Frankowski, Marcin

    2015-11-01

    Tissues for the study were obtained intraoperatively during hip replacement procedures from 96 patients. In all the cases, the indication for this treatment was primary or secondary degenerative changes in the hip joint. The subject of the study was the head and neck of the femur, resected in situ. Aluminium concentrations measured in femoral head and neck samples from patients aged between 25 and 91 were varied. Statistical methods were applied to determine the variations in relation to the parameters from the background survey. Significant differences in the aluminium content of femoral head samples were observed between patients under and over 60 years of age. Based on the results, it was confirmed that the aluminium accumulates in bones over a lifetime. The study showed that the content of aluminium in the head and neck of the femur depends on the factors such as: type of medicines taken, contact with chemicals at work, differences in body anatomy and sex. The study on the levels of aluminium in bones and the factors affecting its concentration is a valuable source of information for further research on the role of aluminium in bone diseases. Based on the investigations, it was found that the GF-AAS technique is the best analytical tool for routine analysis of aluminium in complex matrix samples. The use of femoral heads in the investigations was approved by the Bioethics Committee of the University of Medical Sciences in Poznań (Poland). PMID:26341598

  15. The theoretical underpinnings of affective temperaments: implications for evolutionary foundations of bipolar disorder and human nature.

    PubMed

    Akiskal, Kareen K; Akiskal, Hagop S

    2005-03-01

    We sketch out putative evolutionary roles for affective temperaments within the theoretical framework of mood disorders conceptualized as extremes in an oligogenic model of inheritance, whereby the constituent traits in their dilute phenotypes confer adaptive advantages to individuals and/or their social group. Depressive traits, among other functions, would subserve sensitivity to the suffering of other members of the species, overlapping with those of the generalized anxious temperament, thereby enhancing the survival of not only kin but also other conspecifics. The pursuit of romantic opportunities in cyclothymia suggests that it may have evolved as a mechanism in reproductive success; cyclothymics' creative bent in poetry, music, painting, cooking or fashion design (among men, in particular) also appears useful for sexual seduction. Hyperthymic traits would lend distinct advantages in leadership, exploration, territoriality and mating. These are just some of the possibilities of the rich and complex temperamental traits subserving bipolarity within an evolutionary framework. We test selected aspects of these hypotheses with the use of correlations between the constituent traits of the Temperament Evaluation of Memphis, Pisa, Paris and San Diego (TEMPS) and correlations between the TEMPS and the Temperament and Character Inventory (TCI). Such data support the counterbalancing protective influence of harm avoidance on the risk-taking behavior of cyclothymic individuals, in both men and women. Finally, we outline a hypothesis on the evolutionary function of anxious-depressive traits for women. PMID:15780693

  16. H2O2-Induced Oxidative Stress Affects SO4= Transport in Human Erythrocytes

    PubMed Central

    Morabito, Rossana; Romano, Orazio; La Spada, Giuseppa; Marino, Angela

    2016-01-01

    The aim of the present investigation was to verify the effect of H2O2-induced oxidative stress on SO4= uptake through Band 3 protein, responsible for Cl-/HCO3- as well as for cell membrane deformability, due to its cross link with cytoskeletal proteins. The role of cytoplasmic proteins binding to Band 3 protein has been also considered by assaying H2O2 effects on hemoglobin-free resealed ghosts of erythrocytes. Oxidative conditions were induced by 30 min exposure of human erythrocytes to different H2O2 concentrations (10 to 300 μM), with or without GSH (glutathione, 2 mM) or curcumin (10 μM), compounds with proved antioxidant properties. Since SO4= influx through Band 3 protein is slower and better controllable than Cl- or HCO3- exchange, the rate constant for SO4= uptake was measured to prove anion transport efficiency, while MDA (malondialdehyde) levels and –SH groups were estimated to quantify the effect of oxidative stress. H2O2 induced a significant decrease in rate constant for SO4= uptake at both 100 and 300 μM H2O2. This reduction, observed in erythrocytes but not in resealed ghosts and associated to increase in neither MDA levels nor in –SH groups, was impaired by both curcumin and GSH, whereas only curcumin effectively restored H2O2-induced changes in erythrocytes shape. Our results show that: i) 30 min exposure to 300 μM H2O2 reduced SO4= uptake in human erythrocytes; ii) oxidative damage was revealed by the reduction in rate constant for SO4= uptake, but not by MDA or –SH groups levels; iii) the damage was produced via cytoplasmic components which cross link with Band 3 protein; iv) the natural antioxidant curcumin may be useful in protecting erythrocytes from oxidative injury; v) SO4= uptake through Band 3 protein may be reasonably suggested as a tool to monitor erythrocytes function under oxidative conditions possibly deriving from alcohol consumption, use of drugs, radiographic contrast media administration, hyperglicemia or

  17. H2O2-Induced Oxidative Stress Affects SO4= Transport in Human Erythrocytes.

    PubMed

    Morabito, Rossana; Romano, Orazio; La Spada, Giuseppa; Marino, Angela

    2016-01-01

    The aim of the present investigation was to verify the effect of H2O2-induced oxidative stress on SO4= uptake through Band 3 protein, responsible for Cl-/HCO3- as well as for cell membrane deformability, due to its cross link with cytoskeletal proteins. The role of cytoplasmic proteins binding to Band 3 protein has been also considered by assaying H2O2 effects on hemoglobin-free resealed ghosts of erythrocytes. Oxidative conditions were induced by 30 min exposure of human erythrocytes to different H2O2 concentrations (10 to 300 μM), with or without GSH (glutathione, 2 mM) or curcumin (10 μM), compounds with proved antioxidant properties. Since SO4= influx through Band 3 protein is slower and better controllable than Cl- or HCO3- exchange, the rate constant for SO4= uptake was measured to prove anion transport efficiency, while MDA (malondialdehyde) levels and -SH groups were estimated to quantify the effect of oxidative stress. H2O2 induced a significant decrease in rate constant for SO4= uptake at both 100 and 300 μM H2O2. This reduction, observed in erythrocytes but not in resealed ghosts and associated to increase in neither MDA levels nor in -SH groups, was impaired by both curcumin and GSH, whereas only curcumin effectively restored H2O2-induced changes in erythrocytes shape. Our results show that: i) 30 min exposure to 300 μM H2O2 reduced SO4= uptake in human erythrocytes; ii) oxidative damage was revealed by the reduction in rate constant for SO4= uptake, but not by MDA or -SH groups levels; iii) the damage was produced via cytoplasmic components which cross link with Band 3 protein; iv) the natural antioxidant curcumin may be useful in protecting erythrocytes from oxidative injury; v) SO4= uptake through Band 3 protein may be reasonably suggested as a tool to monitor erythrocytes function under oxidative conditions possibly deriving from alcohol consumption, use of drugs, radiographic contrast media administration, hyperglicemia or neurodegenerative

  18. Safety and pharmacokinetics of oral cannabidiol when administered concomitantly with intravenous fentanyl in humans

    PubMed Central

    Manini, Alex F.; Yiannoulos, Georgia; Bergamaschi, Mateus M.; Hernandez, Stephanie; Olmedo, Ruben; Barnes, Allan J.; Winkel, Gary; Sinha, Rajita; Jutras-Aswad, Didier; Huestis, Marilyn A.; Hurd, Yasmin L.

    2015-01-01

    Objectives Cannabidiol (CBD) is hypothesized as a potential treatment for opioid addiction, with safety studies an important first step for medication development. We determined CBD safety and pharmacokinetics when administered concomitantly with a high-potency opioid in healthy subjects. Methods This double-blind, placebo-controlled cross-over study of CBD co-administered with intravenous fentanyl, was conducted at the Clinical Research Center in Mount Sinai Hospital, a tertiary care medical center in New York City. Participants were healthy volunteers aged 21–65 years with prior opioid exposure, regardless of route. Blood samples were obtained before and after 400 or 800 mg CBD pretreatment, followed by a single 0.5 (Session 1) or 1.0mcg/Kg (Session 2) intravenous fentanyl dose. The primary outcome was the Systematic Assessment for Treatment Emergent Events (SAFTEE) to assess safety and adverse effects. CBD peak plasma concentrations, time to reach peak plasma concentrations (tmax), and area under the curve (AUC) were measured. Results SAFTEE data were similar between groups without respiratory depression or cardiovascular complications during any test session. Following low dose CBD, tmax occurred at 3 and 1.5h (Sessions 1 and 2, respectively). Following high dose CBD, tmax occurred at 3 and 4h in Sessions 1 and 2, respectively. There were no significant differences in plasma CBD or cortisol (AUC p=NS) between sessions. Conclusions CBD does not exacerbate adverse effects associated with intravenous fentanyl administration. Co-administration of CBD and opioids was safe and well tolerated. These data provide the foundation for future studies examining CBD as a potential treatment for opioid abuse. PMID:25748562

  19. Occupational demand and human rights. Public safety officers and cardiorespiratory fitness.

    PubMed

    Shephard, R J

    1991-08-01

    The issue of discrimination in physically demanding employment, such as police, firefighters, prison guards and military personnel, is contentious. In terms of oxygen transport, the 'action limit' (calling for personnel selection or task redesign) is a steady oxygen consumption of 0.7 L/min, while the maximum permissible limit is 2.1 L/min. Note is taken of the commonly expressed belief that public safety duties are physically demanding, calling for personnel with an aerobic power of at least 3 L/min, or 42 to 45 ml/kg/min. The actual demands of such work can be assessed on small samples by physiological measurements (using heart rate or oxygen consumption meters), but the periods sampled may not be typical of a normal day. A Gestalt can also be formed as to the heaviness of a given job, or a detailed task analysis can be performed; most such analyses of public safety work list distance running and other aerobic activities infrequently. An arbitrary requirement of 'above average fitness' is no longer accepted by courts, but a further approach is to examine the characteristics of those currently meeting the demands of public safety jobs satisfactorily. Young men commonly satisfy the 3 L/min standard, but this is not usually the case for women or older men; in the case of female employees, it also seems unreasonable that they should be expected to satisfy the same standards as men, since a lower body mass reduces the energy cost of most of the tasks that they must perform. A second criterion sometimes applied to physically demanding work (a low vulnerability to heart attacks) is examined critically. It is concluded that the chances that a symptom-free public safety officer will develop a heart attack during a critical solo mission are so low that cardiac risk should not be a condition of employment. Arbitrary age- and sex-related employment criteria are plainly discriminatory, since some women and 65-year-old men have higher levels of physical fitness than the

  20. Human-rated Safety Certification of a High Voltage Robonaut Lithium-ion Battery

    NASA Technical Reports Server (NTRS)

    Jeevarajan, Judith; Yayathi, S.; Johnson, M.; Waligora, T.; Verdeyen, W.

    2013-01-01

    NASA's rigorous certification process is being followed for the R2 high voltage battery program for use of R2 on International Space Station (ISS). Rigorous development testing at appropriate levels to credible off-nominal conditions and review of test data led to design improvements for safety at the virtual cell, cartridge and battery levels. Tests were carried out at all levels to confirm that both hardware and software controls work. Stringent flight acceptance testing of the flight battery will be completed before launch for mission use on ISS.

  1. Bottom-up and top-down human impacts interact to affect a protected coastal Chilean marsh.

    PubMed

    Fariña, José M; He, Qiang; Silliman, Brian R; Bertness, Mark D

    2016-03-01

    Many ecosystems, even in protected areas, experience multiple anthropogenic impacts. While anthropogenic modification of bottom-up (e.g., eutrophication) and top-down (e.g., livestock grazing) forcing often co-occurs, whether these factors counteract or have additive or synergistic effects on ecosystems is poorly understood. In a Chilean bio-reserve, we examined the interactive impacts of eutrophication and illegal livestock grazing on plant growth with a 4-yr fertilization by cattle exclusion experiment. Cattle grazing generally decreased plant biomass, but had synergistic, additive, and antagonistic interactions with fertilization in the low, middle, and high marsh zones, respectively. In the low marsh, fertilization increased plant biomass by 112%, cattle grazing decreased it by 96%, and together they decreased plant biomass by 77%. In the middle marsh, fertilization increased plant biomass by 47%, cattle grazing decreased it by 37%, and together they did not affect plant biomass. In the high marsh, fertilization and cattle grazing decreased plant biomass by 81% and 92%, respectively, but together they increased plant biomass by 42%. These interactions were also found to be species specific. Different responses of plants to fertilization and cattle grazing were likely responsible for these variable interactions. Thus, common bottom-up and top-down human impacts can interact in different ways to affect communities even within a single ecosystem. Incorporating this knowledge into conservation actions will improve ecosystem management in a time when ecosystems are increasingly challenged by multiple interacting human impacts. PMID:27197391

  2. Additive effects of affective arousal and top-down attention on the event-related brain responses to human bodies.

    PubMed

    Hietanen, Jari K; Kirjavainen, Ilkka; Nummenmaa, Lauri

    2014-12-01

    The early visual event-related 'N170 response' is sensitive to human body configuration and it is enhanced to nude versus clothed bodies. We tested whether the N170 response as well as later EPN and P3/LPP responses to nude bodies reflect the effect of increased arousal elicited by these stimuli, or top-down allocation of object-based attention to the nude bodies. Participants saw pictures of clothed and nude bodies and faces. In each block, participants were asked to direct their attention towards stimuli from a specified target category while ignoring others. Object-based attention did not modulate the N170 amplitudes towards attended stimuli; instead N170 response was larger to nude bodies compared to stimuli from other categories. Top-down attention and affective arousal had additive effects on the EPN and P3/LPP responses reflecting later processing stages. We conclude that nude human bodies have a privileged status in the visual processing system due to the affective arousal they trigger. PMID:25224182

  3. Safety and side effects of ayahuasca in humans--an overview focusing on developmental toxicology.

    PubMed

    dos Santos, Rafael Guimarães

    2013-01-01

    Despite being relatively well studied from a botanical, chemical, and (acute) pharmacological perspective, little is known about the possible toxic effects of ayahuasca (an hallucinogenic brew used for magico-ritual purposes) in pregnant women and in their children, and the potential toxicity of long-term ayahuasca consumption. It is the main objective of the present text to do an overview of the risks and possible toxic effects of ayahuasca in humans, reviewing studies on the acute ayahuasca administration to humans, on the possible risks associated with long-term consumption by adults and adolescents, and on the possible toxic effects on pregnant animals and in their offspring. Acute ayahuasca administration, as well as long-term consumption of this beverage, does not seem to be seriously toxic to humans. Although some nonhuman developmental studies suggested possible toxic effects of ayahuasca or of some of its alkaloids, the limited human literature on adolescents exposed to ayahuasca as early as in the uterus reports no serious toxic effects of the ritual consumption of the brew. Researchers must take caution when extrapolating nonhuman data to humans and more data are needed in basic and human research before a definite opinion can be made regarding the possible toxic effects of ayahuasca in pregnant women and in their children. PMID:23662333

  4. Characterization of a cellular inhibitory activity affecting the human autologous mixed lymphocyte reaction

    SciTech Connect

    Haynes, M.K.

    1987-01-01

    The human autologous mixed lymphocyte reaction, peripheral blood T cells are stimulated to proliferate when co-cultured with irradiated, autologous, non-T cells was studied. ({sup 3}H)-thymidine uptake was maximal on day 7 and observable on day 9. Non-adherent and adherent fractions of non-T population and lectin-activated T cell blasts contributed. Unseparated non-T stimulator cells were used. Autologous T cells, when added as irradiated third party cells, reduced AMLR proliferative responses. Depletion of Fc IgG receptor-bearing cells (T{gamma}) from T cell population by (a) IgG-sensitized ox erythrocyte rosetting (EA-rosettes) or (b) adsorption of the T{gamma} cells onto a Sepharose 6MB {approximately} BSA/anti-BSA immune complex column resulted in enhanced AMLR proliferation not attributed solely to an increase in CD8+ AMLR responder cell phenotype. Isolated T{gamma} populations exhibited a reversed helper/suppressor phenotype containing HLA DR+ and CD8+ cells. Dual labeling studies demonstrated 7-24% of CD8+ cells expressed DR antigens. After separation, AMLR proliferative capacity was localized in T-depleted population.

  5. Nanofiber alignment and direction of mechanical strain affect the ECM production of human ACL fibroblast.

    PubMed

    Lee, Chang Hun; Shin, Ho Joon; Cho, In Hee; Kang, Young-Mi; Kim, In Ae; Park, Ki-Dong; Shin, Jung-Woog

    2005-04-01

    The effects of fiber alignment and direction of mechanical stimuli on the ECM generation of human ligament fibroblast (HLF) were assessed. The nanofiber matrix was fabricated using electrospinning technique. To align the nanofibers, a rotating target was used. The HLFs on the aligned nanofibers were spindle-shaped and oriented in the direction of the nanofibers. The degree of ECM production was evaluated by comparing the amount of collagen on aligned and randomly oriented structures. Significantly more collagen was synthesized on aligned nanofiber sheets, although the proliferation did not differ significantly. This suggests that the spindle-shape observable in intact ligaments is preferable in producing ECM. To evaluate the effect of strain direction on the ECM production, HLFs were seeded on parallel aligned, vertically aligned to the strain direction, and randomly oriented nanofiber sheets attached to Flexcell plates. After a 48-h culture, 5% uniaxial strain was applied for 24h at a frequency of 12 cycles/min. The amounts of collagen produced were measured 2 days after halting the strain application. The HLFs were more sensitive to strain in the longitudinal direction. In conclusion, the aligned nanofiber scaffold used in this study constitutes a promising base material for tissue-engineered ligament in that it provides more preferable biomimetic structure, along with proper mechanical environment. PMID:15475056

  6. Human erythrocytes are affected in vitro by extracts of Ugni molinae leaves.

    PubMed

    Suwalsky, M; Orellana, P; Avello, M; Villena, F; Sotomayor, C P

    2006-08-01

    Ugni molinae Turcz, also known as "Murtilla", is a plant that grows in the south of Chile. Infusions of their leaves have long been used in traditional native herbal medicine. The chemical composition of the leaves indicates the presence of polyphenols, which have antioxidant properties. In order to evaluate the mechanisms of their antioxidant properties and the toxicity of the aqueous extracts of leaves, the extracts were induced to interact with human red cells, their isolated unsealed membranes (IUM) and large unilamellar vesicles (LUV) of dimyristoylphosphatidyltidylcholine (DMPC), representative of phospholipid classes located in the outer monolayer of the erythrocyte membrane. Scanning electron microscopy (SEM) observations indicated that the extracts achieved a significant alteration in the shape of the erythrocytes as they changed their discoid shape to echinocytes. According to the bilayer couple hypothesis, the shape change indicates that the polyphenols were located in the outer moiety of the red cell membrane. This conclusion was confirmed by the fluorescence experiments performed in IUM and DMPC LUV. In fact, the extracts produced slight initial increases followed by sharp decreases at higher concentrations in the anisotropy and general polarization parameters. These results imply that the extracts induced structural perturbations in the acyl chain and polar group packing arrangements of the erythrocyte IUM and DMPC LUV lipid bilayers: first ordering and afterwards disordering them as the extract concentration increased. PMID:16716480

  7. Effect of tetracycline HCl on periodontally-affected human root surfaces.

    PubMed

    Trombelli, L; Scabbia, A; Zangari, F; Griselli, A; Wikesjö, U M; Calura, G

    1995-08-01

    Scanning electron microscopy was used to evaluate surface characteristics of periodontitis-exposed instrumented human cementum and dentin surfaces following topical application of tetracycline HCl (TTC). Specimens were randomly assigned to application of sterile saline for 1 minute (control); TTC (10 mg/ml) for 1 minute and 4 minutes, respectively; and TTC (100 mg/ml) for 1 minute and 4 minutes, respectively. Solutions were applied with a cotton pellet using a burnishing technique. Control specimens exhibited an amorphous irregular surface smear layer. TTC treatment of cementum for 1 minute resulted in a relatively debris-free, nonhomogeneous surface. The 4-minute application resulted in a surface exhibiting a densely fibrillar, mat-like texture. Dentin specimens conditioned for 1 minute showed a smooth surface with many tubule openings partially occluded by debris. The 4-minute treatment exposed a 3-dimensional network of intertubular and peritubular collagen fibrils. No consistent morphologic differences were observed between cementum or dentin specimens treated with TTC at concentrations of 10 and 100 mg/ml, respectively. The results suggest that topical application of TTC produces morphologic alterations of periodontitis-exposed cementum and dentin that appear related to application interval rather than concentration of the drug. PMID:7473011

  8. 902 MHz mobile phone does not affect short term memory in humans.

    PubMed

    Haarala, Christian; Ek, Maria; Björnberg, Linda; Laine, Matti; Revonsuo, Antti; Koivisto, Mika; Hämäläinen, Heikki

    2004-09-01

    We studied the effects of an electromagnetic field (EMF) as emitted by a 902 MHz mobile phone on human short term memory. This study was a replication with methodological improvements to our previous study. The improvements included multi-centre testing and a double blind design. A total of 64 subjects (32 men) in two independent laboratories performed a short term memory task (n-back) which poses a varying memory load (0-3 items) on the subjects' memory. They performed the task twice, once each under EMF and sham exposure. Reaction times (RTs) and accuracy of the responses were recorded. The order of exposure and memory load conditions were counterbalanced across subjects and gender. There were no statistically significant differences in performance between the two laboratories. We could not replicate our previous results: the EMF had no effect on RTs or on the accuracy of the subjects' answers. The inability to replicate previous findings could have been caused by lack of actual EMF effects or the magnitude of effects being at the sensitivity threshold of the test used. PMID:15300731

  9. No fear no risk! Human risk behavior is affected by chemosensory anxiety signals.

    PubMed

    Haegler, Katrin; Zernecke, Rebekka; Kleemann, Anna Maria; Albrecht, Jessica; Pollatos, Olga; Brückmann, Hartmut; Wiesmann, Martin

    2010-11-01

    An important aspect of cognitive functioning is decision-making, which depends on the correct interpretation of emotional processes. High trait anxiety has been associated with increased risk taking behavior in decision-making tasks. An interesting fact is that anxiety and anxiety-related chemosignals as well as decision-making share similar regions of neuronal activation. In order to ascertain if chemosensory anxiety signals have similar effects on risk taking behavior of healthy participants as high trait anxiety we used a novel computerized decision-making task, called Haegler's Risk Game (HRG). This task measures risk taking behavior based on contingencies and can be played repeatedly without a learning effect. To obtain chemosensory signals the sweat of 21 male donors was collected in a high rope course (anxiety condition). For the chemosensory control condition sweat was collected during an ergometer workout (exercise condition). In a double-blind study, 30 healthy recipients (16 females) had to play HRG while being exposed to sweat samples or empty control samples (control condition) in three sessions of randomized order. Comparison of the risk taking behavior of the three conditions showed significantly higher risk taking behavior in participants for the most risky choices during the anxiety condition compared to the control conditions. Additionally, recipients showed significantly higher latency before making their decision in the most risky choices during the anxiety condition. This experiment gives evidence that chemosensory anxiety signals are communicated between humans thereby increasing participants' risk taking behavior. PMID:20875438

  10. Purification and characterization of factors produced by Aspergillus fumigatus which affect human ciliated respiratory epithelium.

    PubMed Central

    Amitani, R; Taylor, G; Elezis, E N; Llewellyn-Jones, C; Mitchell, J; Kuze, F; Cole, P J; Wilson, R

    1995-01-01

    The mechanisms by which Aspergillus fumigatus colonizes the respiratory mucosa are unknown. Culture filtrates of eight of nine clinical isolates of A. fumigatus slowed ciliary beat frequency and damaged human respiratory epithelium in vitro. These changes appeared to occur concurrently. Culture filtrates of two clinical isolates of Candida albicans had no effect on ciliated epithelium. We have purified and characterized cilioinhibitory factors of a clinical isolate of A. fumigatus. The cilioinhibitory activity was heat labile, reduced by dialysis, and partially extractable into chloroform. The activity was associated with both high- and low-molecular-weight factors, as determined by gel filtration on Sephadex G-50. A low-molecular-weight cilioinhibitory factor was further purified by reverse-phase high-performance liquid chromatography and shown by mass spectrometry to be gliotoxin, a known metabolite of A. fumigatus. Gliotoxin significantly slowed ciliary beat frequency in association with epithelial damage at concentrations above 0.2 microgram/ml; other Aspergillus toxins, i.e., fumagillin and helvolic acid, were also cilioinhibitory but at much higher concentrations. High-molecular-weight (> or = 35,000 and 25,000) cilioinhibitory materials had neither elastolytic nor proteolytic activity and remain to be identified. Thus, A. fumigatus produces a number of biologically active substances which slow ciliary beating and damage epithelium and which may influence colonization of the airways. PMID:7543879

  11. Lip colour affects perceived sex typicality and attractiveness of human faces.

    PubMed

    Stephen, Ian D; McKeegan, Angela M

    2010-01-01

    The luminance contrast between facial features and facial skin is greater in women than in men, and women's use of make-up enhances this contrast. In black-and-white photographs, increased luminance contrast enhances femininity and attractiveness in women's faces, but reduces masculinity and attractiveness in men's faces. In Caucasians, much of the contrast between the lips and facial skin is in redness. Red lips have been considered attractive in women in geographically and temporally diverse cultures, possibly because they mimic vasodilation associated with sexual arousal. Here, we investigate the effects of lip luminance and colour contrast on the attractiveness and sex typicality (masculinity/femininity) of human faces. In a Caucasian sample, we allowed participants to manipulate the colour of the lips in colour-calibrated face photographs along CIELab L* (light--dark), a* (red--green), and b* (yellow--blue) axes to enhance apparent attractiveness and sex typicality. Participants increased redness contrast to enhance femininity and attractiveness of female faces, but reduced redness contrast to enhance masculinity of men's faces. Lip blueness was reduced more in female than male faces. Increased lightness contrast enhanced the attractiveness of both sexes, and had little effect on perceptions of sex typicality. The association between lip colour contrast and attractiveness in women's faces may be attributable to its association with oxygenated blood perfusion indicating oestrogen levels, sexual arousal, and cardiac and respiratory health. PMID:20942361

  12. Ethanol affects hepatitis C pathogenesis: humanized SCID Alb-uPA mouse model.

    PubMed

    Osna, Natalia A; Kharbanda, Kusum K; Sun, Yimin; Simpson, Ronda L; Poluektova, Larisa E; Ganesan, Murali; Wisecarver, James L; Mercer, David F

    2014-07-18

    Alcohol consumption exacerbates the course of hepatitis C viral (HCV) infection, worsens outcomes and contributes to the development of chronic infection that exhibits low anti-viral treatment efficiency. The lack of suitable in vivo models makes HCV-ethanol studies very difficult. Here, we examine whether chimeric SCID Alb-uPA mice transplanted with human hepatocytes and infected with HCV develop worsening pathology when fed ethanol. After 5 weeks of feeding, such mice fed chow+water (control) or chow+20% ethanol in water (EtOH) diets mice developed oxidative stress, decreased proteasome activity and increased steatosis. Importantly, HCV(+) mice in the control group cleared HCV RNA after 5 weeks, while the infection persisted in EtOH-fed mice at the same or even higher levels compared with pre-feeding HCV RNA. We conclude that in chimeric SCID Alb-uPA mice, EtOH exposure causes the complex biochemical and histological changes typical for alcoholic liver injury. In addition, ethanol feeding delays the clearance of HCV RNA thereby generating persistent infection and promoting liver injury. Overall, this model is appropriate for conducting HCV-ethanol studies. PMID:24953695

  13. Analysis of cell-cell junctions in human amnion and chorionic plate affected by chorioamnionitis.

    PubMed

    Licini, Caterina; Tossetta, Giovanni; Avellini, Chiara; Ciarmela, Pasquapina; Lorenzi, Teresa; Toti, Paolo; Gesuita, Rosaria; Voltolini, Chiara; Petraglia, Felice; Castellucci, Mario; Marzioni, Daniela

    2016-07-01

    Chorioamnionitis is an acute inflammatory reaction associated with the premature rupture of the fetal membranes. It is caused mainly by invasion of bacteria from the vaginal tract that can penetrate the intact membranes and invade the amnion cavity and the decidua. Tight junctions (TJs) and adherent junctions (AJs) are intercellular junctions crucial for epithelia adhesion and permeability regulation in a wide variety of tissues and organs. Our aim is to investigate if TJ and AJ molecules are involved in human chorioamnionitis. We studied the protein expression (by immunohistochemistry and western blotting) and the mRNA levels (by RT-PCR) of some junction proteins such as Zonula Occludens-1 (ZO-1), occludin, VE-cadherin and β-catenin in fetal membranes from women with chorioamnionitis compared to those membranes derived from idiopathic pregnancies. Western blotting and immunohistochemical data established that occludin expression was decreased in amnion with chorioamnionitis compared to amnion from idiopathic pregnancies. Samples tested for ZO-1, VE-cadherin and β-catenin (proteins and mRNAs) showed no differences between idiopathic and pathological membranes. One of the most relevant results is the decrease of occludin in membranes with chorioamnionitis. Since we have previously demonstrated that some cytokines, particularly elevated in the chorioamnionitis, cause the disruption of TJs in placental villi, we suggest that the decrease of occludin in amnion may be the first change that leads to the rupture of the amniotic membrane in this pathology. PMID:26739007

  14. Orally delivered sour cherry seed extract (SCSE) affects cardiovascular and hematological parameters in humans.

    PubMed

    Csiki, Zoltan; Papp-Bata, Agnes; Czompa, Attila; Nagy, Aniko; Bak, Istvan; Lekli, Istvan; Javor, Andras; Haines, David D; Balla, Gyorgy; Tosaki, Arpad

    2015-03-01

    In the present study, we investigated the effects of sour cherry seed extract (SCSE) on a variety of systemic processes that contribute to general health and viability of human subjects. The experiments were conducted according to a double-blind protocol in which six healthy individuals were administered 250-mg/day SCSE for 14 days, while four were treated with placebo. Peripheral blood was collected before and after the treatment period. Samples were analyzed for levels of selected cells, enzymes, or metabolites. Subjects that received SCSE showed increases in the values of mean cell volume, serum transferrin, mean peroxidase index, and representation of peripheral blood lymphocytes. On the other hand, decreases were observed in circulating neutrophils and ferritin levels. Changes observed in the present study do not fit into a clear pattern that might yield additional in-depth understanding of SCSE-mediated alterations in physiologic responses. The most encouraging result of the present study is the absence of any indication of toxicity by subjects consuming the extract. PMID:25640007

  15. Alcohol lowers the vasoconstriction threshold in humans without affecting core cooling rate during mild cold exposure.

    PubMed

    Johnston, C E; Bristow, G K; Elias, D A; Giesbrecht, G G

    1996-01-01

    Elevated blood alcohol levels are often seen in hypothermia and hyperthermia related deaths, leading to the belief that alcohol renders humans poikilothermic. We examined the core temperature (Tco) thresholds for sweating, vasoconstriction and shivering as well as core cooling rates of seven subjects immersed in 28 degrees C water. On two separate days, subjects exercised on an underwater cycle ergometer to elevate Tco above the sweating threshold. They then rested and cooled until they shivered vigorously. Subjects drank orange juice (7 ml.kg-1) prior to immersion during the control trial and 1 ml.kg-1 absolute ethanol, added to orange juice in a 1:6 ratio, during the alcohol trial. Mean blood alcohol concentration (breath analysis) was 0.097 +/- 0.010 g% at the start of cooling and 0.077 +/- 0.008 g% at the end of the cooling period. Alcohol lowered the vasoconstriction threshold by 0.32 +/- 0.2 degrees C and elevated finger tip blood flow, but had no effect on thresholds for sweating and shivering or core cooling rate. Considering these minor effects it is unlikely that moderate alcohol consumption predisposes individuals to hypothermia or hyperthermia via impaired thermoregulation, but rather likely due to behavioral factors. PMID:8897037

  16. LMNA Knock-Down Affects Differentiation and Progression of Human Neuroblastoma Cells

    PubMed Central

    Maresca, Giovanna; Natoli, Manuela; Nardella, Marta; Arisi, Ivan; Trisciuoglio, Daniela; Desideri, Marianna; Brandi, Rossella; D’Aguanno, Simona; Nicotra, Maria Rita; D’Onofrio, Mara; Urbani, Andrea; Natali, Pier Giorgio; Bufalo, Donatella Del

    2012-01-01

    Background Neuroblastoma (NB) is one of the most aggressive tumors that occur in childhood. Although genes, such as MYCN, have been shown to be involved in the aggressiveness of the disease, the identification of new biological markers is still desirable. The induction of differentiation is one of the strategies used in the treatment of neuroblastoma. A-type lamins are components of the nuclear lamina and are involved in differentiation. We studied the role of Lamin A/C in the differentiation and progression of neuroblastoma. Methodology/Principal Findings Knock-down of Lamin A/C (LMNA-KD) in neuroblastoma cells blocked retinoic acid-induced differentiation, preventing neurites outgrowth and the expression of neural markers. The genome-wide gene-expression profile and the proteomic analysis of LMNA-KD cells confirmed the inhibition of differentiation and demonstrated an increase of aggressiveness-related genes and molecules resulting in augmented migration/invasion, and increasing the drug resistance of the cells. The more aggressive phenotype acquired by LMNA-KD cells was also maintained in vivo after injection into nude mice. A preliminary immunohistochemistry analysis of Lamin A/C expression in nine primary stages human NB indicated that this protein is poorly expressed in most of these cases. Conclusions/Significance We demonstrated for the first time in neuroblastoma cells that Lamin A/C plays a central role in the differentiation, and that the loss of this protein gave rise to a more aggressive tumor phenotype. PMID:23049808

  17. The second-shell metal ligands of human arginase affect coordination of the nucleophile and substrate.

    PubMed

    Stone, Everett M; Chantranupong, Lynne; Georgiou, George

    2010-12-14

    The active sites of eukaryotic arginase enzymes are strictly conserved, especially the first- and second-shell ligands that coordinate the two divalent metal cations that generate a hydroxide molecule for nucleophilic attack on the guanidinium carbon of l-arginine and the subsequent production of urea and l-ornithine. Here by using comprehensive pairwise saturation mutagenesis of the first- and second-shell metal ligands in human arginase I, we demonstrate that several metal binding ligands are actually quite tolerant to amino acid substitutions. Of >2800 double mutants of first- and second-shell residues analyzed, we found more than 80 unique amino acid substitutions, of which four were in first-shell residues. Remarkably, certain second-shell mutations could modulate the binding of both the nucleophilic water/hydroxide molecule and substrate or product ligands, resulting in activity greater than that of the wild-type enzyme. The data presented here constitute the first comprehensive saturation mutagenesis analysis of a metallohydrolase active site and reveal that the strict conservation of the second-shell metal binding residues in eukaryotic arginases does not reflect kinetic optimization of the enzyme during the course of evolution. PMID:21053939

  18. Irradiation affects cellular properties and Eph receptor expression in human melanoma cells

    PubMed Central

    Mosch, Birgit; Pietzsch, Doreen; Pietzsch, Jens

    2012-01-01

    X-ray irradiation influences metastatic properties of tumor cells and, moreover, metastasis and cellular motility can be modified by members of the Eph receptor/ephrin family of receptor tyrosine kinases. We hypothesized that irradiation-induced changes in cellular properties relevant for metastasis in melanoma cells could be mediated by Eph receptor/ephrin signaling. In this pilot study, we analyzed one pre-metastatic (Mel-Juso) and three metastatic human melanoma (Mel-Juso-L3, A375, and A2058) cells lines and predominantly found anti-metastatic effects of X-ray irradiation with impaired cell growth, clonal growth and motility. Additionally, we observed an irradiation-induced increase in adhesion paralleled by a decrease in migration in Mel-Juso and Mel-Juso-L3 cells and, in part, also in A375 cells. We further demonstrate a decrease of EphA2 both in expression and activity at 7 d after irradiation paralleled by an upregulation of EphA3. Analyzing downstream signaling after irradiation, we detected decreased Src kinase phosphorylation, but unchanged focal adhesion kinase (FAK) phosphorylation, indicating, in part, irradiation-induced downregulation of signaling via the EphA2-Src-FAK axis in melanoma cells. However, to which extent this finding contributes to the modification of metastasis-relevant cellular properties remains to be elucidated. PMID:22568947

  19. Affective and cognitive prefrontal cortex projections to the lateral habenula in humans

    PubMed Central

    Vadovičová, Karin

    2014-01-01

    Anterior insula (AI) and dorsal ACC (dACC) are known to process information about pain, loss, adversities, bad, harmful or suboptimal choices and consequences that threaten survival or well-being. Also pregenual ACC (pgACC) is linked to loss and pain, being activated by sad thoughts and regrets. Lateral habenula (LHb) is stimulated by predicted and received pain, discomfort, aversive outcome, loss. Its chronic stimulation makes us feel worse/low and gradually stops us choosing and moving for the suboptimal or punished choices, by direct and indirect (via rostromedial tegmental nucleus, RMTg) inhibition of dorsal raphe nucleus (DRN) and VTA/SNc. The response selectivity of LHb neurons suggests their cortical input from affective and cognitive evaluative regions that make expectations about bad, unpleasant or suboptimal outcomes. Based on these facts I predicted direct dACC, pgACC and AI projections to LHb, which form part of an adversity processing circuit that learns to avoid bad outcomes by suppressing dopamine and serotonin signal. To test this connectivity I used Diffusion Tensor Imaging (DTI). I found dACC, pgACC, AI and caudolateral OFC (clOFC) projections to LHb. I predicted no corticohabenular projections from the reward processing regions: medial OFC (mOFC) and ventral ACC (vACC) because both respond most strongly to good, high valued stimuli and outcomes, inducing dopamine and serotonin release. This lack of LHb projections was confirmed for vACC and likely for mOFC. The surprising findings were the corticohabenular projections from the cognitive prefrontal cortex regions, known for flexible reasoning, planning and combining whatever information are relevant for reaching current goals. I propose that the prefrontohabenular projections provide a teaching signal for value-based choice behavior, to learn to deselect, avoid or inhibit the potentially harmful, low valued or wrong choices, goals, strategies, predictions and ways of doing things, to prevent bad

  20. Topical anaesthesia does not affect cutaneous vasomotor or sudomotor responses in human skin.

    PubMed

    Metzler-Wilson, K; Wilson, T E

    2013-10-01

    (1) The effects of local sensory blockade (topical anaesthesia) on eccrine sweat glands and cutaneous circulation are not well understood. This study aimed to determine whether topical lidocaine/prilocaine alters eccrine sweat gland and cutaneous blood vessel responses. (2) Sweating (capacitance hygrometry) was induced via forearm intradermal microdialysis of five acetylcholine (ACh) doses (1 × 10(-4) to 1 × 10(0) m, 10-fold increments) in control and treated forearm sites in six healthy subjects. Nitric oxide-mediated vasodilatory (sodium nitroprusside) and adrenergic vasoconstrictor (noradrenaline) agonists were iontophoresed in lidocaine/prilocaine-treated and control forearm skin in nine healthy subjects during blood flow assessment (laser Doppler flowmetry, expressed as% from baseline cutaneous vascular conductance; CVC; flux/mean arterial pressure). (3) Non-linear regression curve fitting identified no change in the ED50 of ACh-induced sweating after sensory blockade (-1.42 ± 0.23 logM) compared to control (-1.27 ± 0.23 logM; P > .05) or in Emax (0.43 ± 0.08 with, 0.53 ± 0.16 mg cm(-2) min(-1) without lidocaine/prilocaine; P > .05). Sensory blockade did not alter the vasodilator response to sodium nitroprusside (1280 ± 548% change from baseline CVC with, 1204 ± 247% without lidocaine/prilocaine) or vasoconstrictor response to noradrenaline (-14 ± 4% change from baseline CVC with, -22 ± 14% without lidocaine/prilocaine; P > 0.05). (4) Cutaneous sensory blockade does not appear to alter nitric oxide-mediated vasodilation, adrenergic vasoconstriction, or cholinergic eccrine sweating dose-response sensitivity or responsiveness to maximal dose. Thus, lidocaine/prilocaine treatment should not affect sweat gland function or have blood flow implications for subsequent research protocols or clinical procedures. PMID:23663206

  1. Analysis of mobile phone design features affecting radiofrequency power absorbed in a human head phantom.

    PubMed

    Kuehn, Sven; Kelsh, Michael A; Kuster, Niels; Sheppard, Asher R; Shum, Mona

    2013-09-01

    The US FCC mandates the testing of all mobile phones to demonstrate compliance with the rule requiring that the peak spatial SAR does not exceed the limit of 1.6 W/kg averaged over any 1 g of tissue. These test data, measured in phantoms with mobile phones operating at maximum antenna input power, permitted us to evaluate the variation in SARs across mobile phone design factors such as shape and antenna design, communication technology, and test date (over a 7-year period). Descriptive statistical summaries calculated for 850 MHz and 1900 MHz phones and ANOVA were used to evaluate the influence of the foregoing factors on SARs. Service technology accounted for the greatest variability in compliance test SARs that ranged from AMPS (highest) to CDMA, iDEN, TDMA, and GSM (lowest). However, the dominant factor for SARs during use is the time-averaged antenna input power, which may be much less than the maximum power used in testing. This factor is largely defined by the communication system; e.g., the GSM phone average output can be higher than CDMA by a factor of 100. Phone shape, antenna type, and orientation of a phone were found to be significant but only on the order of up to a factor of 2 (3 dB). The SAR in the tilt position was significantly smaller than for touch. The side of the head did not affect SAR levels significantly. Among the remaining factors, external antennae produced greater SARs than internal ones, and brick and clamshell phones produced greater SARs than slide phones. Assuming phone design and usage patterns do not change significantly over time, we have developed a normalization procedure and formula that permits reliable prediction of the relative SAR between various communication systems. This approach can be applied to improve exposure assessment in epidemiological research. PMID:23533135

  2. Different Factors Affecting Human ANP Amyloid Aggregation and Their Implications in Congestive Heart Failure

    PubMed Central

    Millucci, Lia; Paccagnini, Eugenio; Ghezzi, Lorenzo; Bernardini, Giulia; Braconi, Daniela; Laschi, Marcella; Consumi, Marco; Spreafico, Adriano; Tanganelli, Piero; Lupetti, Pietro; Magnani, Agnese; Santucci, Annalisa

    2011-01-01

    Aims Atrial Natriuretic Peptide (ANP)-containing amyloid is frequently found in the elderly heart. No data exist regarding ANP aggregation process and its link to pathologies. Our aims were: i) to experimentally prove the presumptive association of Congestive Heart Failure (CHF) and Isolated Atrial Amyloidosis (IAA); ii) to characterize ANP aggregation, thereby elucidating IAA implication in the CHF pathogenesis. Methods and Results A significant prevalence (85%) of IAA was immunohistochemically proven ex vivo in biopsies from CHF patients. We investigated in vitro (using Congo Red, Thioflavin T, SDS-PAGE, transmission electron microscopy, infrared spectroscopy) ANP fibrillogenesis, starting from α-ANP as well as the ability of dimeric β-ANP to promote amyloid formation. Different conditions were adopted, including those reproducing β-ANP prevalence in CHF. Our results defined the uncommon rapidity of α-ANP self-assembly at acidic pH supporting the hypothesis that such aggregates constitute the onset of a fibrillization process subsequently proceeding at physiological pH. Interestingly, CHF-like conditions induced the production of the most stable and time-resistant ANP fibrils suggesting that CHF affected people may be prone to develop IAA. Conclusions We established a link between IAA and CHF by ex vivo examination and assessed that β-ANP is, in vitro, the seed of ANP fibrils. Our results indicate that β-ANP plays a crucial role in ANP amyloid deposition under physiopathological CHF conditions. Overall, our findings indicate that early IAA-related ANP deposition may occur in CHF and suggest that these latter patients should be monitored for the development of cardiac amyloidosis. PMID:21814559

  3. Allergic inflammation in the human lower respiratory tract affected by exposure to diesel exhaust.

    PubMed

    Riedl, Marc A; Diaz-Sanchez, David; Linn, William S; Gong, Henry; Clark, Kenneth W; Effros, Richard M; Miller, J Wayne; Cocker, David R; Berhane, Kiros T

    2012-02-01

    To improve understanding of human health risks from exposure to diesel exhaust particles (DEP*), we tested whether immunologic effects previously observed in the human nose also occur in the lower airways. Our overall hypothesis was that cell influx and production of cytokines, chemokines, immunoglobulin E (IgE), and other mediators, which would be measurable in sputum and blood, occur in people with asthma after realistic controlled exposures to diesel exhaust (DE). In Phase 1 we tested for direct effects of DE in subjects with clinically undifferentiated mild asthma. In Phase 2 we tested whether DE exposure would exacerbate response to inhaled cat allergen in subjects with both asthma and cat sensitivity. The exposure facility was a controlled-environment chamber supplied with DE from an idling medium-duty truck with ultra-low-sulfur fuel and no catalytic converter. We exposed volunteers for 2 hours with intermittent exercise to exhaust with DEP mass concentration near 100 microg/m3. Exposures to nitrogen dioxide (NO2) near 0.35 ppm (similar to its concentration in DE) and to filtered air (FA) served as controls. Blood was drawn before exposure on day 1 and again the next morning (day 2). Sputum was induced only on day 2. Bronchial reactivity was measured -1 hour after exposure ended. Supplementary endpoints included measures of blood coagulation status, cardiopulmonary physiology, and symptoms. Each phase employed 15 subjects with asthma; 3 subjects participated in both phases. In Phase 1, airway reactivity was measured with inhaled methacholine; in Phase 2, with inhaled cat allergen. We found little biologic response to DE exposure compared with exposure to control atmospheres. In Phase 1, interleukin 4 (IL-4) in sputum showed an estimated 1.7-fold increase attributable to DE exposure, which was close to statistical significance; airway resistance increased modestly but significantly on day 2 after DE exposure; and nonspecific symptom scores increased

  4. Bifidobacteria isolated from infants and cultured on human milk oligosaccharides affect intestinal epithelial function

    PubMed Central

    Chichlowski, Maciej; De Lartigue, Guillaume; German, J. Bruce; Raybould, Helen E.; Mills, David A.

    2012-01-01

    Objectives Human milk oligosaccharides (HMO) are the third most abundant component of breast milk. Our laboratory has previously revealed gene clusters specifically linked to HMO metabolism in select bifidobacteria isolated from fecal samples of infants. Our objective was to test the hypothesis that growth of select bifidobacteria on HMO stimulates the intestinal epithelium. Methods Caco-2 and HT-29 cells were incubated with lactose (LAC) or HMO-grown Bifidobacterium longum subsp. infantis (B. infantis) or B. bifidum. Bacterial adhesion and translocation was measured by real-time quantitative PCR. Expression of pro- and anti-inflammatory cytokines and tight junction proteins was analyzed by real time reverse transcriptase. Distribution of tight junction proteins was measured using immunofluorescent microscopy. Results We showed that HMO-grown B. infantis had significantly higher rate of adhesion to HT-29 cells compared to B. bifidum. B. infantis also induced expression of a cell membrane glycoprotein, P-selectin glycoprotein ligand -1. Both B. infantis and B. bifidum grown on HMO caused less occludin relocalization and higher expression of anti-inflammatory cytokine, interleukin (IL)-10 compared to LAC-grown bacteria in Caco-2 cells. B. bifidum grown on HMO showed higher expression of junctional adhesion molecule and occludin in Caco-2 cell and HT-29 cells. There were no significant differences between LAC or HMO treatments in bacterial translocation. Conclusions This study provides evidence for the specific relationship between HMO-grown bifidobacteria and intestinal epithelial cells. To our knowledge, this is the first study describing HMO-induced changes in the bifidobacteria-intestinal cells