Sample records for human response capabilities
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IRBs, conflict and liability: will we see IRBs in court? Or is it when?
Icenogle, Daniel L
2003-01-01
The entire human research infrastructure is under intense and increasing financial pressure. These pressures may have been responsible for several errors in judgment by those responsible for managing human research and protecting human subjects. The result of these errors has been some terrible accidents, some of which have cost the lives of human research volunteers. This, in turn, is producing both increased liability risk for those who manage the various aspects of human research and increasing scrutiny as to the capability of the human research protection structure as currently constituted. It is the author's contention that the current structure is fully capable of offering sufficient protection for participants in human research-if Institutional Review Board (IRB) staff and members are given sufficient resources and perform their tasks with sufficient responsibility. The status quo alternative is that IRBs and their members will find themselves at great risk of becoming defendants in lawsuits seeking compensation for damages resulting from human experimentation gone awry.
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A Human Development and Capabilities "Prospective Analysis" of Global Higher Education Policy
ERIC Educational Resources Information Center
Walker, Melanie
2010-01-01
In global times, university education policy that holds the greatest promise for social responsibility is the focus here; the argument made is that such policy ought to be conceptualised using a normative human development and capabilities approach, drawing on the work of Amartya Sen and Martha Nussbaum. Their ideas offer a values-based way of…
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More About Hazard-Response Robot For Combustible Atmospheres
NASA Technical Reports Server (NTRS)
Stone, Henry W.; Ohm, Timothy R.
1995-01-01
Report presents additional information about design and capabilities of mobile hazard-response robot called "Hazbot III." Designed to operate safely in combustible and/or toxic atmosphere. Includes cameras and chemical sensors helping human technicians determine location and nature of hazard so human emergency team can decide how to eliminate hazard without approaching themselves.
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Bernardo, Lidice; Denomme, Gregory A.; Shah, Kunjlata; Lazarus, Alan H.
2014-01-01
The ability to study the immune response to the RhD antigen in the prevention of hemolytic disease of the fetus and newborn has been hampered by the lack of a mouse model of RhD immunization. However, the ability of transgenic mice expressing human HLA DRB1*1501 to respond to immunization with purified RhD has allowed this question to be revisited. In this work we aimed at inducing anti-RhD antibodies by administering human RhD+ RBCs to mice transgenic for the human HLA DRB1*1501 as well as to several standard inbred and outbred laboratory strains including C57BL/6, DBA1/J, CFW(SW), CD1(ICR), and NSA(CF-1). DRB1*1501 mice were additionally immunized with putative extracellular immunogenic RhD peptides. DRB1*1501 mice immunized with RhD+ erythrocytes developed an erythrocyte-reactive antibody response. Antibodies specific for RhD could not however be detected by flow cytometry. Despite this, DRB1*1501 mice were capable of recognizing immunogenic sequences of Rh as injection with Rh peptides induced antibodies reactive with RhD sequences, consistent with the presence of B cell repertoires capable of recognizing RhD. We conclude that while HLA DRB1*1501 transgenic mice may have the capability of responding to immunogenic sequences within RhD, an immune response to human RBC expressing RhD is not directly observed. PMID:25628657
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Device for rapid quantification of human carotid baroreceptor-cardiac reflex responses
NASA Technical Reports Server (NTRS)
Sprenkle, J. M.; Eckberg, D. L.; Goble, R. L.; Schelhorn, J. J.; Halliday, H. C.
1986-01-01
A new device has been designed, constructed, and evaluated to characterize the human carotid baroreceptor-cardiac reflex response relation rapidly. This system was designed for study of reflex responses of astronauts before, during, and after space travel. The system comprises a new tightly sealing silicon rubber neck chamber, a stepping motor-driven electrodeposited nickel bellows pressure system, capable of delivering sequential R-wave-triggered neck chamber pressure changes between +40 and -65 mmHg, and a microprocessor-based electronics system for control of pressure steps and analysis and display of responses. This new system provokes classic sigmoid baroreceptor-cardiac reflex responses with threshold, linear, and saturation ranges in most human volunteers during one held expiration.
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Graphical Visualization of Human Exploration Capabilities
NASA Technical Reports Server (NTRS)
Rodgers, Erica M.; Williams-Byrd, Julie; Arney, Dale C.; Simon, Matthew A.; Williams, Phillip A.; Barsoum, Christopher; Cowan, Tyler; Larman, Kevin T.; Hay, Jason; Burg, Alex
2016-01-01
NASA's pioneering space strategy will require advanced capabilities to expand the boundaries of human exploration on the Journey to Mars (J2M). The Evolvable Mars Campaign (EMC) architecture serves as a framework to identify critical capabilities that need to be developed and tested in order to enable a range of human exploration destinations and missions. Agency-wide System Maturation Teams (SMT) are responsible for the maturation of these critical exploration capabilities and help formulate, guide and resolve performance gaps associated with the EMC-identified capabilities. Systems Capability Organization Reporting Engine boards (SCOREboards) were developed to integrate the SMT data sets into cohesive human exploration capability stories that can be used to promote dialog and communicate NASA's exploration investments. Each SCOREboard provides a graphical visualization of SMT capability development needs that enable exploration missions, and presents a comprehensive overview of data that outlines a roadmap of system maturation needs critical for the J2M. SCOREboards are generated by a computer program that extracts data from a main repository, sorts the data based on a tiered data reduction structure, and then plots the data according to specified user inputs. The ability to sort and plot varying data categories provides the flexibility to present specific SCOREboard capability roadmaps based on customer requests. This paper presents the development of the SCOREboard computer program and shows multiple complementary, yet different datasets through a unified format designed to facilitate comparison between datasets. Example SCOREboard capability roadmaps are presented followed by a discussion of how the roadmaps are used to: 1) communicate capability developments and readiness of systems for future missions, and 2) influence the definition of NASA's human exploration investment portfolio through capability-driven processes. The paper concludes with a description of planned future work to modify the computer program to include additional data and of alternate capability roadmap formats currently under consideration.
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State-level emergency preparedness and response capabilities.
Watkins, Sharon M; Perrotta, Dennis M; Stanbury, Martha; Heumann, Michael; Anderson, Henry; Simms, Erin; Huang, Monica
2011-03-01
Prior assessments of public health readiness had identified gaps in radiation preparedness. In recent years, preparedness planning has involved an "all-hazards" approach. Current assessment of the national status related to radiation public health emergency preparedness capabilities at the state and local health department levels was needed. A survey of state health departments related to radiation readiness was undertaken in 2010 by the Council of State and Territorial Epidemiologists (CSTE). States with nuclear power plants were instructed to consider their responses exclusive of capabilities and resources related to the plants given that the emergency response plans for nuclear power plants are specific and unique. Thirty-eight (76%) state health departments responded to the survey, including 26 of the 31 states with nuclear power plants. Specific strengths noted at the state level included that the majority of states had a written radiation response plan and most plans include a detailed section for communications issues during a radiation emergency. In addition, more than half of the states indicated that their relationship with federal partners is sufficient to provide resources for radiation emergencies, indicating the importance states placed on federal resources and expertise. Specific weaknesses are discussed and include that most states had completed little to no planning for public health surveillance to assess potential human health impacts of a radiation event; less than half had written plans to address exposure assessment, environmental sampling, human specimen collection and analysis, and human health assessment. Few reported having sufficient resources to do public health surveillance, radiation exposure assessment, laboratory functions and other capabilities. Levels of planning, resources and partnerships varied among states, those with nuclear power plants were better prepared. Gaps were evident in all states; however and additional training and resources are needed to ensure adequate levels of preparedness. Overall results of this assessment indicate that in most measures of public health capacity and capability, states are poorly prepared to adequately respond to a major radiation emergency event. Specific recommendations are noted in the discussion.
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Maintaining Situation Awareness with Autonomous Airborne Observation Platforms
NASA Technical Reports Server (NTRS)
Freed, Michael; Fitzgerald, Will
2005-01-01
Unmanned Aerial Vehicles (UAVs) offer tremendous potential as intelligence, surveillance and reconnaissance (ISR) platforms for early detection of security threats and for acquisition and maintenance of situation awareness in crisis conditions. However, using their capabilities effectively requires addressing a range of practical and theoretical problems. The paper will describe progress by the "Autonomous Rotorcraft Project," a collaborative effort between NASA and the U.S. Army to develop a practical, flexible capability for UAV-based ISR. Important facets of the project include optimization methods for allocating scarce aircraft resources to observe numerous, distinct sites of interest; intelligent flight automation software than integrates high-level plan generation capabilities with executive control, failure response and flight control functions; a system architecture supporting reconfiguration of onboard sensors to address different kinds of threats; and an advanced prototype vehicle designed to allow large-scale production at low cost. The paper will also address human interaction issues including an empirical method for determining how to allocate roles and responsibilities between flight automation and human operations.
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Lozito, Thomas P; Tuan, Rocky S
2017-03-01
The ability to regenerate damaged or lost tissues has remained the lofty goal of regenerative medicine. Unfortunately, humans, like most mammals, suffer from very minimal natural regenerative capabilities. Certain non-mammalian animal species, however, are not so limited in their healing capabilities, and several have attracted the attention of researchers hoping to recreate enhanced healing responses in humans. This review focuses on one such animal group with remarkable regenerative abilities, the lizards. As the closest relatives of mammals that exhibit enhanced regenerative abilities as adults, lizards potentially represent the most relevant model for direct comparison and subsequent improvement of mammalian healing. Lizards are able to regenerate amputated tails and exhibit adaptations that both limit tissue damage in response to injury and initiate coordinated regenerative responses. This review summarizes the salient aspects of lizard tail regeneration as they relate to the overall regenerative process and also presents the relevant information pertaining to regrowth of specific tissues, including skeletal, muscular, nervous, and vascular tissues. The goal of this review is to introduce the topic of lizard tail regeneration to new audiences with the hope of expanding the knowledge base of this underutilized but potentially powerful model organism.
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The Lunar Environment: Determining the Health Effects of Exposure to Moon Dusts
NASA Technical Reports Server (NTRS)
Khan-Mayberry, Noreen
2007-01-01
The moon's surface is covered with a thin layer of fine, charged, reactive dust capable of layer of fine, charged, reactive dust capable of capable of entering habitats and vehicle compartments, where it can result in crewmember health problems. NASA formed the Lunar Airborne Dust Toxicity Advisory Group (LADTAG) to study the effects of exposure to Lunar Dust on human health. To date, no scientifically defensible toxicological studies have been performed on lunar dusts, specifically the determination of exposure limits and their affect on human health. The multi-center LADTAG (Lunar Airborne Dust Toxicology center LADTAG (Lunar Airborne Dust Toxicology Advisory Group) was formed in response to the Office of the Chief Health and Medical Office s (OCHMO) request to develop recommendations for defining risk (OCHMO) request to develop recommendations for defining risk defining risk criteria for human lunar dust exposure.
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NASA Astrophysics Data System (ADS)
Hubbard, H. H.; Powell, C. A.
1981-06-01
A number of facilities were developed which provide a unique test capability for psychoacoustics and related human factors research. The design philosophy, physical layouts, dimensions, construction features, operating capabilities, and example applications for these facilities are described. In the exterior effects room, human subjects are exposed to the types of noises that are experienced outdoors, and in the interior effects room, subjects are exposed to the types of noises and noise-induced vibrations that are experience indoors. Subjects are also exposed to noises in an echo-free environment in the anechoic listening room. An aircraft noise synthesis system, which simulates aircraft flyover noise at an observer position on the ground, is used in conjunction with these three rooms. The passenger ride quality apparatus, a device for studying passenger response to noise and vibration in aircraft, or in other vehicles, is described.
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NASA Technical Reports Server (NTRS)
Hubbard, H. H.; Powell, C. A.
1981-01-01
A number of facilities were developed which provide a unique test capability for psychoacoustics and related human factors research. The design philosophy, physical layouts, dimensions, construction features, operating capabilities, and example applications for these facilities are described. In the exterior effects room, human subjects are exposed to the types of noises that are experienced outdoors, and in the interior effects room, subjects are exposed to the types of noises and noise-induced vibrations that are experience indoors. Subjects are also exposed to noises in an echo-free environment in the anechoic listening room. An aircraft noise synthesis system, which simulates aircraft flyover noise at an observer position on the ground, is used in conjunction with these three rooms. The passenger ride quality apparatus, a device for studying passenger response to noise and vibration in aircraft, or in other vehicles, is described.
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A Hybrid Robotic Control System Using Neuroblastoma Cultures
NASA Astrophysics Data System (ADS)
Ferrández, J. M.; Lorente, V.; Cuadra, J. M.; Delapaz, F.; Álvarez-Sánchez, José Ramón; Fernández, E.
The main objective of this work is to analyze the computing capabilities of human neuroblastoma cultured cells and to define connection schemes for controlling a robot behavior. Multielectrode Array (MEA) setups have been designed for direct culturing neural cells over silicon or glass substrates, providing the capability to stimulate and record simultaneously populations of neural cells. This paper describes the process of growing human neuroblastoma cells over MEA substrates and tries to modulate the natural physiologic responses of these cells by tetanic stimulation of the culture. We show that the large neuroblastoma networks developed in cultured MEAs are capable of learning: establishing numerous and dynamic connections, with modifiability induced by external stimuli and we propose an hybrid system for controlling a robot to avoid obstacles.
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NASA Astrophysics Data System (ADS)
Vakoch, Douglas A.
2011-02-01
With recently growing interest in the Active Search for Extraterrestrial Intelligence (SETI), in which humankind would send intentional signals to extraterrestrial civilizations, there have been increased concerns about appropriate policy, as well as the role of space law and ethics in guiding such activities. Implicit in these discussions are notions of responsibility and capability that affect judgments about whether humans or other civilizations should initiate transmissions. Existing protocols that guide SETI research address transmissions from Earth, but there is debate over whether these guidelines should inform de novo transmissions as well. Relevant responsibilities to address include (1) looking out for the interests of humankind as a whole, (2) being truthful in interstellar messages, and (3) benefiting extraterrestrial civilizations. Our capabilities as a species and a civilization affect how well we can fulfill responsibilities, as seen when we consider whether we will be able to reach consensus about message contents (and whether that would be desirable), and whether we have the capacity to decode messages from beings that rely on different sensory modalities. The interplay of these responsibilities and capabilities suggests that humankind should place increased emphasis on Active SETI.
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Instant messages vs. speech: hormones and why we still need to hear each other.
Seltzer, Leslie J; Prososki, Ashley R; Ziegler, Toni E; Pollak, Seth D
2012-01-01
Human speech evidently conveys an adaptive advantage, given its apparently rapid dissemination through the ancient world and global use today. As such, speech must be capable of altering human biology in a positive way, possibly through those neuroendocrine mechanisms responsible for strengthening the social bonds between individuals. Indeed, speech between trusted individuals is capable of reducing levels of salivary cortisol, often considered a biomarker of stress, and increasing levels of urinary oxytocin, a hormone involved in the formation and maintenance of positive relationships. It is not clear, however, whether it is the uniquely human grammar, syntax, content and/or choice of words that causes these physiological changes, or whether the prosodic elements of speech, which are present in the vocal cues of many other species, are responsible. In order to tease apart these elements of human communication, we examined the hormonal responses of female children who instant messaged their mothers after undergoing a stressor. We discovered that unlike children interacting with their mothers in person or over the phone, girls who instant messaged did not release oxytocin; instead, these participants showed levels of salivary cortisol as high as control subjects who did not interact with their parents at all. We conclude that the comforting sound of a familiar voice is responsible for the hormonal differences observed and, hence, that similar differences may be seen in other species using vocal cues to communicate.
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Quantifying human response capabilities towards tsunami threats at community level
NASA Astrophysics Data System (ADS)
Post, J.; Mück, M.; Zosseder, K.; Wegscheider, S.; Taubenböck, H.; Strunz, G.; Muhari, A.; Anwar, H. Z.; Birkmann, J.; Gebert, N.
2009-04-01
Decision makers at the community level need detailed information on tsunami risks in their area. Knowledge on potential hazard impact, exposed elements such as people, critical facilities and lifelines, people's coping capacity and recovery potential are crucial to plan precautionary measures for adaptation and to mitigate potential impacts of tsunamis on society and the environment. A crucial point within a people-centred tsunami risk assessment is to quantify the human response capabilities towards tsunami threats. Based on this quantification and spatial representation in maps tsunami affected and safe areas, difficult-to-evacuate areas, evacuation target points and evacuation routes can be assigned and used as an important contribution to e.g. community level evacuation planning. Major component in the quantification of human response capabilities towards tsunami impacts is the factor time. The human response capabilities depend on the estimated time of arrival (ETA) of a tsunami, the time until technical or natural warning signs (ToNW) can be received, the reaction time (RT) of the population (human understanding of a tsunami warning and the decision to take appropriate action), the evacuation time (ET, time people need to reach a safe area) and the actual available response time (RsT = ETA - ToNW - RT). If RsT is larger than ET, people in the respective areas are able to reach a safe area and rescue themselves. Critical areas possess RsT values equal or even smaller ET and hence people whin these areas will be directly affected by a tsunami. Quantifying the factor time is challenging and an attempt to this is presented here. The ETA can be derived by analyzing pre-computed tsunami scenarios for a respective area. For ToNW we assume that the early warning center is able to fulfil the Indonesian presidential decree to issue a warning within 5 minutes. RT is difficult as here human intrinsic factors as educational level, believe, tsunami knowledge and experience besides others play a role. An attempt to quantify this variable under high uncertainty is also presented. Quantifying ET is based on a GIS modelling using a Cost Weighted Distance approach. Basic principle is to define the best evacuation path from a given point to the next safe area (shelter location). Here the fastest path from that point to the shelter location has to be found. Thereby the impact of land cover, slope, population density, population age and gender distribution are taken into account as literature studies prove these factors as highly important. Knowing the fastest path and the distance to the next safe area together with a spatially distributed pattern of evacuation speed delivers the time needed from each location to a safe area. By considering now the obtained time value for RsT the coverage area of an evacuation target point (safe area) can be assigned. Incorporating knowledge on people capacity of an evacuation target point the respective coverage area is refined. Hence areas with weak, moderate and good human response capabilities can be detected. This allows calculation of potential amount of people affected (dead or injured) and amount of people dislocated. First results for Kuta (Bali) for a worst case tsunami event deliver people affected of approx. 25 000 when RT = 0 minutes (direct evacuation when receiving a tsunami warning to 120 000 when RT > ETA (no evacuation action until tsunami hits the land). Additionally fastest evacuation routes to the evacuation target points can be assigned. Areas with weak response capabilities can be assigned as priority areas to install e.g. additional evacuation target points or to increase tsunami knowledge and awareness to promote a faster reaction time. Especially in analyzing underlying socio-economic properties causing deficiencies in responding to a tsunami threat can lead to valuable information and direct planning of adaptation measures. Keywords: Community level, Risk and vulnerability assessment, Early warning, Disaster management, Tsunami, Indonesia
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Zika viral infection and neutralizing human antibody response in a BLT humanized mouse model.
Schmitt, Kimberly; Charlins, Paige; Veselinovic, Milena; Kinner-Bibeau, Lauren; Hu, Shuang; Curlin, James; Remling-Mulder, Leila; Olson, Ken E; Aboellail, Tawfik; Akkina, Ramesh
2018-02-01
Many murine and non-human primate animal models have been recently developed to understand Zika viral pathogenesis. However, a major limitation with these models is the inability to directly examine the human-specific immune response. Here, we utilized a BLT humanized mouse model endowed with a transplanted human immune system. Plasma viremia could be detected within 48h after viral challenge and viremia persisted for as long as 220 days in some mice. Neutralizing human antibody was detected in infected mice and mouse sera showed reactivity with the viral envelope and capsid proteins in a radio-immunoprecipitation assay. Human monocytes/macrophages, B cells and hematopoietic stem cells in the bone marrow were found to be virus infected. These data establish that BLT mice are permissive for Zika viral infection and are capable of generating viral-specific human immune responses thus providing a human surrogate model for future testing of vaccine and antiviral therapeutic candidates. Copyright © 2017 Elsevier Inc. All rights reserved.
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Generation of a transplantable erythropoietin-producer derived from human mesenchymal stem cells.
Yokoo, Takashi; Fukui, Akira; Matsumoto, Kei; Ohashi, Toya; Sado, Yoshikazu; Suzuki, Hideaki; Kawamura, Tetsuya; Okabe, Masataka; Hosoya, Tatsuo; Kobayashi, Eiji
2008-06-15
Differentiation of autologous stem cells into functional transplantable tissue for organ regeneration is a promising regenerative therapeutic approach for cancer, diabetes, and many human diseases. Yet to be established, however, is differentiation into tissue capable of producing erythropoietin (EPO), which has a critical function in anemia. We report a novel EPO-producing organ-like structure (organoid) derived from human mesenchymal stem cells. Using our previously established relay culture system, a human mesenchymal stem cell-derived, human EPO-competent organoid was established in rat omentum. The organoid-derived levels of human EPO increased in response to anemia induced by rapid blood withdrawal. In addition, the presence of an organoid in rats suppressed for native (rat) EPO production enhanced recovery from anemia when compared with control animals lacking the organoid. Together these results confirmed the generation of a stem cell-derived organoid that is capable of producing EPO and sensitive to physiological regulation.
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Avian Influenza Viruses, Inflammation, and CD8+ T Cell Immunity
Wang, Zhongfang; Loh, Liyen; Kedzierski, Lukasz; Kedzierska, Katherine
2016-01-01
Avian influenza viruses (AIVs) circulate naturally in wild aquatic birds, infect domestic poultry, and are capable of causing sporadic bird-to-human transmissions. AIVs capable of infecting humans include a highly pathogenic AIV H5N1, first detected in humans in 1997, and a low pathogenic AIV H7N9, reported in humans in 2013. Both H5N1 and H7N9 cause severe influenza disease in humans, manifested by acute respiratory distress syndrome, multi-organ failure, and high mortality rates of 60% and 35%, respectively. Ongoing circulation of H5N1 and H7N9 viruses in wild birds and poultry, and their ability to infect humans emphasizes their epidemic and pandemic potential and poses a public health threat. It is, thus, imperative to understand the host immune responses to the AIVs so we can control severe influenza disease caused by H5N1 or H7N9 and rationally design new immunotherapies and vaccines. This review summarizes our current knowledge on AIV epidemiology, disease symptoms, inflammatory processes underlying the AIV infection in humans, and recent studies on universal pre-existing CD8+ T cell immunity to AIVs. Immune responses driving the host recovery from AIV infection in patients hospitalized with severe influenza disease are also discussed. PMID:26973644
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Federal Register 2010, 2011, 2012, 2013, 2014
2010-08-30
... enhance the lab capabilities to handle human pathogenic bacteria in animal feed. DATES: Important dates... supplemental grant funds will enable analyses of human pathogenic bacteria found in animal feed, for samples... bacteria in animal feed. This additional program will be compatible with other FERN Cooperative Agreement...
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BACKGROUND: An in vitro steroidogenesis assay using the human adrenocortical carcinoma cells H295R is being evaluated as a possible toxicity screening approach to detect and assess the impact of endocrine active chemicals (EAC) capable of altering steroid biosynthesis. Interpreta...
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Summer Prostate Cancer Research Training Program
2017-09-01
Biology, and Human Toxicology Graduate Programs. Michael Henry, PhD; Associate Professor, Department of Physiology & Biophysics (319-335- 7886) http...addition, PSA has also been demonstrated to be antigenic and capable of inducing specific immune responses in both humans and mice. However, up to...for animal immunization. Both BCG and Ad microbes have been demonstrated to be safe and effective for antigen delivery in humans and mice. Since
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Willinger, Tim; Rongvaux, Anthony; Takizawa, Hitoshi; Yancopoulos, George D.; Valenzuela, David M.; Murphy, Andrew J.; Auerbach, Wojtek; Eynon, Elizabeth E.; Stevens, Sean; Manz, Markus G.; Flavell, Richard A.
2011-01-01
Mice with a functional human immune system have the potential to allow in vivo studies of human infectious diseases and to enable vaccine testing. To this end, mice need to fully support the development of human immune cells, allow infection with human pathogens, and be capable of mounting effective human immune responses. A major limitation of humanized mice is the poor development and function of human myeloid cells and the absence of human immune responses at mucosal surfaces, such as the lung. To overcome this, we generated human IL-3/GM-CSF knock-in (hIL-3/GM-CSF KI) mice. These mice faithfully expressed human GM-CSF and IL-3 and developed pulmonary alveolar proteinosis because of elimination of mouse GM-CSF. We demonstrate that hIL-3/GM-CSF KI mice engrafted with human CD34+ hematopoietic cells had improved human myeloid cell reconstitution in the lung. In particular, hIL-3/GM-CSF KI mice supported the development of human alveolar macrophages that partially rescued the pulmonary alveolar proteinosis syndrome. Moreover, human alveolar macrophages mounted correlates of a human innate immune response against influenza virus. The hIL-3/GM-CSF KI mice represent a unique mouse model that permits the study of human mucosal immune responses to lung pathogens. PMID:21262803
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Human Factors Research for Space Exploration: Measurement, Modeling, and Mitigation
NASA Technical Reports Server (NTRS)
Kaiser, Mary K.; Allen, Christopher S.; Barshi, Immanuel; Billman, Dorrit; Holden, Kritina L.
2010-01-01
As part of NASA's Human Research Program, the Space Human Factors Engineering Project serves as the bridge between Human Factors research and Human Spaceflight applications. Our goal is to be responsive to the operational community while addressing issues at a sufficient level of abstraction to ensure that our tools and solutions generalize beyond the point design. In this panel, representatives from four of our research domains will discuss the challenges they face in solving current problems while also enabling future capabilities.
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NASA Astrophysics Data System (ADS)
Baran, Utku; Choi, Woo J.; Wang, Ruikang K.
2015-03-01
Tape stripping on human skin induces mechanical disruptions of the epidermal barrier that lead to minor skin inflammation which leads to temporary changes in microvasculature. On the other hand, when mosquitoes probe the skin for blood feeding, they inject saliva in dermal tissue. Mosquito saliva is known to exert various biological activities, such as dermal mast cell degranulation, leading to fluid extravasation and neutrophil influx. This inflammatory response remain longer than the tape stripping caused inflammation. In this study, we demonstrate the capabilities of swept-source optical coherence tomography (OCT) in detecting in vivo microvascular response of inflammatory human skin. Optical microangiography (OMAG), noninvasive volumetric microvasculature in vivo imaging method, has been used to track the vascular responses after tape stripping and mosquito bite. Vessel density has been quantified and used to correlate with the degree of skin irritation. The proved capability of OMAG technique in visualizing the microvasculature network under inflamed skin condition can play an important role in clinical trials of treatment and diagnosis of inflammatory skin disorders as well as studying mosquito bite's perception by the immune system and its role in parasite transmission.
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USDA-ARS?s Scientific Manuscript database
The epithelium lining the airway tract and allergen-specific IgE are considered essential controllers of inflammatory responses to allergens. The human IgE receptor, CD23 (Fc'RII), is capable of transporting IgE or IgE-allergen complexes across the polarized human airway epithelial cell (AEC) monola...
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Safe traffic : Vision Zero on the move
DOT National Transportation Integrated Search
2006-03-01
Vision Zero is composed of several basic : elements, each of which affects safety in : road traffic. These concerns ethics, human : capability and tolerance, responsibility, : scientific facts and a realisation that the : different components in the ...
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The International Space Station: New Capabilities for Disaster Response and Humanitarian Aid
NASA Technical Reports Server (NTRS)
Stefanov, William
2012-01-01
The International Space Station (ISS) has been acquiring Earth imagery since 2000, primarily in the form of astronaut photography using hand-held film and digital cameras. Recent additions of more sophisticated multispectral and hyperspectral sensor systems have expanded both the capabilities and relevance of the ISS to basic research, applied Earth science, and development of new sensor technologies. Funding opportunities established within NASA, the US National Laboratories and the international partner organizations have generated instrument proposals that will further enhance these capabilities. With both internal and external sensor location options, and the availability of both automated and human-tended operational environments, the ISS is a unique platform within the constellation of Earth-observing satellites currently in orbit. Current progress and challenges associated with development of ISS terrestrial remote sensing capabilities in the area of disaster response and support of relief efforts will be presented. The ISS orbit allows for imaging of the Earth's surface at varying times of day and night, providing opportunities for data collection over approximately 95% of the populated regions. These opportunities are distinct from--yet augment--the data collection windows for the majority of sensors on polar-orbiting satellites. In addition to this potential for "being in the right place at the right time" to collect critical information on an evolving disaster, the presence of a human crew also allows for immediate recognition of an event from orbit, notification of relevant organizations on the ground, and re-tasking of available remote sensing resources to support humanitarian response and relief efforts. Challenges to establishing an integrated response capability are both technical (coordination of sensor targeting and data collection, rapid downlink and posting of data to a central accessible hub, timely generation and distribution of relevant data products) and operational (notification and engagement of sensor support teams, international partner agency sanction of astronaut support activities). To better collaborate on common issues and strengthen applications, including using the data to support disaster response, we established an ISS Program Science Forum Working Group for Earth Observations comprised of representatives from the international partner agencies. This international forum welcomes input and support from relevant United Nations task groups regarding our disaster response and humanitarian aid to enable development of the ISS capabilities in this area for greatest value to the international community.
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NASA Technical Reports Server (NTRS)
Chu, Y.-Y.; Rouse, W. B.
1979-01-01
As human and computer come to have overlapping decisionmaking abilities, a dynamic or adaptive allocation of responsibilities may be the best mode of human-computer interaction. It is suggested that the computer serve as a backup decisionmaker, accepting responsibility when human workload becomes excessive and relinquishing responsibility when workload becomes acceptable. A queueing theory formulation of multitask decisionmaking is used and a threshold policy for turning the computer on/off is proposed. This policy minimizes event-waiting cost subject to human workload constraints. An experiment was conducted with a balanced design of several subject runs within a computer-aided multitask flight management situation with different task demand levels. It was found that computer aiding enhanced subsystem performance as well as subjective ratings. The queueing model appears to be an adequate representation of the multitask decisionmaking situation, and to be capable of predicting system performance in terms of average waiting time and server occupancy. Server occupancy was further found to correlate highly with the subjective effort ratings.
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Instant messages vs. speech: hormones and why we still need to hear each other
Seltzer, Leslie J.; Prososki, Ashley R.; Ziegler, Toni E.; Pollak, Seth D.
2012-01-01
Human speech evidently conveys an adaptive advantage, given its apparently rapid dissemination through the ancient world and global use today. As such, speech must be capable of altering human biology in a positive way, possibly through those neuroendocrine mechanisms responsible for strengthening the social bonds between individuals. Indeed, speech between trusted individuals is capable of reducing levels of salivary cortisol, often considered a biomarker of stress, and increasing levels of urinary oxytocin, a hormone involved in the formation and maintenance of positive relationships. It is not clear, however, whether it is the uniquely human grammar, syntax, content and/or choice of words that causes these physiological changes, or whether the prosodic elements of speech, which are present in the vocal cues of many other species, are responsible. In order to tease apart these elements of human communication, we examined the hormonal responses of female children who instant messaged their mothers after undergoing a stressor. We discovered that unlike children interacting with their mothers in person or over the phone, girls who instant messaged did not release oxytocin; instead, these participants showed levels of salivary cortisol as high as control subjects who did not interact with their parents at all. We conclude that the comforting sound of a familiar voice is responsible for the hormonal differences observed and, hence, that similar differences may be seen in other species using vocal cues to communicate. PMID:22337755
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McGowan, E; Elliott, N; Stokes, E
2018-05-07
Investigation of the leadership capabilities of physiotherapy managers found that they report predominantly demonstrating capabilities associated with the human resource and structural frames. However, little is known about the leadership capabilities of clinical specialists and advanced physiotherapy practitioners (APPs) who also are identified as having responsibility for leadership. To explore clinical specialists´ and APPs' perceptions of their leadership capabilities and compare them with the reported leadership capabilities of physiotherapy managers. Semi-structured interviews were conducted with a purposive sample of 17 physiotherapy clinical specialists and APPs from a range of practice settings across Ireland. The interviews were analyzed using template analysis and the coding template was based on the Bolman and Deal Leadership framework. The participants described demonstrating leadership capabilities associated with each of the four leadership frames. However, the language used by the clinical specialists/APPs suggested that they work predominantly through the human resource frame. Structural frame capabilities were reported by the clinical specialists/APPs and there were some differences to those reported by the managers. In keeping with the reported leadership capabilities of the physiotherapy managers, the employment of capabilities associated with the political frame varied between participants and symbolic frame capabilities were underused. There are many similarities in the self-reported leadership capabilities of managers and clinical specialists/APPs. However, differences were also noted. Both cohorts of physiotherapy leaders may benefit from specific development programs to develop leadership capabilities associated with the political and symbolic frames.
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Mathematical modeling of human cardiovascular system for simulation of orthostatic response
NASA Technical Reports Server (NTRS)
Melchior, F. M.; Srinivasan, R. S.; Charles, J. B.
1992-01-01
This paper deals with the short-term response of the human cardiovascular system to orthostatic stresses in the context of developing a mathematical model of the overall system. It discusses the physiological issues involved and how these issues have been handled in published cardiovascular models for simulation of orthostatic response. Most of the models are stimulus specific with no demonstrated capability for simulating the responses to orthostatic stimuli of different types. A comprehensive model incorporating all known phenomena related to cardiovascular regulation would greatly help to interpret the various orthostatic responses of the system in a consistent manner and to understand the interactions among its elements. This paper provides a framework for future efforts in mathematical modeling of the entire cardiovascular system.
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The Human Nervous System: A Framework for Teaching and the Teaching Brain
ERIC Educational Resources Information Center
Rodriguez, Vanessa
2013-01-01
The teaching brain is a new concept that mirrors the complex, dynamic, and context-dependent nature of the learning brain. In this article, I use the structure of the human nervous system and its sensing, processing, and responding components as a framework for a re-conceptualized teaching system. This teaching system is capable of responses on an…
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Understanding Challenges in the Front Lines of Home Health Care: A Human-Systems Approach
Beer, Jenay M.; McBride, Sara E.; Mitzner, Tracy L.; Rogers, Wendy A.
2014-01-01
A human-systems perspective is a fruitful approach to understanding home health care because it emphasizes major individual components of the system – persons, equipment/technology, tasks, and environments –as well as the interaction between these components. The goal of this research was to apply a human-system perspective to consider the capabilities and limitations of the persons, in relation to the demands of the tasks and equipment/technology in home health care. Identification of challenges and mismatches between the person(s) capabilities and the demands of providing care provide guidance for human factors interventions. A qualitative study was conducted with 8 home health Certified Nursing Assistants and 8 home health Registered Nurses interviewed about challenges they encounter in their jobs. A systematic categorization of the challenges the care providers reported was conducted and human factors recommendations were proposed in response, to improve home health. The challenges inform a human-systems model of home health care. PMID:24958610
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Canadian Forces in Joint Fires Support - Human Factors Analysis: Coalition Operations
2010-08-01
mesure/l’estimation des dommages collatéraux (EDC). Outil pour comprendre l’EDC de certains pays comparativement à celle des membres de l’OTAN et...Program (TDP). The TDP is aimed at concept development, evaluation for force design , and the demonstration of technologies fostered by Defence Research...logistics and the designation of targets on the joint targeting list. • Tactical capability / response time / training. The tactical capability of a fire
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Federal Register 2010, 2011, 2012, 2013, 2014
2012-12-12
...) Emergency Response Organization Augmentation at Alternate Facility--capability for staging emergency... significant effect on the quality of the human environment (77 FR 71198; November 29, 2012). This exemption is...
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Boucher, Jean-David; Pattacini, Ugo; Lelong, Amelie; Bailly, Gerrard; Elisei, Frederic; Fagel, Sascha; Dominey, Peter Ford; Ventre-Dominey, Jocelyne
2012-01-01
Human-human interaction in natural environments relies on a variety of perceptual cues. Humanoid robots are becoming increasingly refined in their sensorimotor capabilities, and thus should now be able to manipulate and exploit these social cues in cooperation with their human partners. Previous studies have demonstrated that people follow human and robot gaze, and that it can help them to cope with spatially ambiguous language. Our goal is to extend these findings into the domain of action, to determine how human and robot gaze can influence the speed and accuracy of human action. We report on results from a human-human cooperation experiment demonstrating that an agent's vision of her/his partner's gaze can significantly improve that agent's performance in a cooperative task. We then implement a heuristic capability to generate such gaze cues by a humanoid robot that engages in the same cooperative interaction. The subsequent human-robot experiments demonstrate that a human agent can indeed exploit the predictive gaze of their robot partner in a cooperative task. This allows us to render the humanoid robot more human-like in its ability to communicate with humans. The long term objectives of the work are thus to identify social cooperation cues, and to validate their pertinence through implementation in a cooperative robot. The current research provides the robot with the capability to produce appropriate speech and gaze cues in the context of human-robot cooperation tasks. Gaze is manipulated in three conditions: Full gaze (coordinated eye and head), eyes hidden with sunglasses, and head fixed. We demonstrate the pertinence of these cues in terms of statistical measures of action times for humans in the context of a cooperative task, as gaze significantly facilitates cooperation as measured by human response times.
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Th1 and Th17 Immunocompetence in Humanized NOD/SCID/γC-KO mice
Rajesh, Deepika; Zhou, Ying; Jankowska-Gan, Ewa; Ronneburg, Drew Allan; Dart, Melanie M; Torrealba, Jose; Burlingham, William J
2010-01-01
We evaluated the immunocompetence of human T cells in humanized NOD-scid IL2r-γ-null (Hu—NSG) mice bearing a human thymic organoid, after multilinegage reconstitution with isogeneic human leukocytes. Delayed type hypersensitivity (DTH) response was assessed by a direct footpad challenge of the immunized hu-NSG host, or by transfer of splenocytes from immunized hu-NSG, along with antigen, into footpads of CB17 SCID mice [trans-vivo (tv) DTH]. Both methods revealed cellular immunity to tetanus toxoid (TT) or collagen type V (ColV). Immunohistochemical analysis of the swollen footpads revealed infiltration of human CD45+ cells, including CD3+ T cells, CD68+ macrophages and murine Ly6G+ neutrophils. We observed a significant correlation between % circulating human CD4+ cells and the direct DTH swelling response to TT. The tvDTH response to TT was inhibited by anti-IFNγ, while the tvDTH response to collagen V was inhibited by anti IL-17 antibody, mimicking the cytokine bias of adult human T cells to these antigens. Hu-NSG mice were also capable of mounting a B cell response (primarily IgM) to TT antigen. The activation of either Th1- or Th17 - dependent cellular immune response supports the utility of Hu-NSG mice as a surrogate model of allograft rejection and autoimmunity. PMID:20298731
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Mooij, Petra; Balla-Jhagjhoorsingh, Sunita S; Beenhakker, Niels; van Haaften, Patricia; Baak, Ilona; Nieuwenhuis, Ivonne G; Heidari, Shirin; Wolf, Hans; Frachette, Marie-Joelle; Bieler, Kurt; Sheppard, Neil; Harari, Alexandre; Bart, Pierre-Alexandre; Liljeström, Peter; Wagner, Ralf; Pantaleo, Giuseppe; Heeney, Jonathan L
2009-06-01
Rhesus macaques (Macaca mulatta) have played a valuable role in the development of human immunodeficiency virus (HIV) vaccine candidates prior to human clinical trials. However, changes and/or improvements in immunogen quality in the good manufacturing practice (GMP) process or changes in adjuvants, schedule, route, dose, or readouts have compromised the direct comparison of T-cell responses between species. Here we report a comparative study in which T-cell responses from humans and macaques to HIV type 1 antigens (Gag, Pol, Nef, and Env) were induced by the same vaccine batches prepared under GMP and administered according to the same schedules in the absence and presence of priming. Priming with DNA (humans and macaques) or alphavirus (macaques) and boosting with NYVAC induced robust and broad antigen-specific responses, with highly similar Env-specific gamma interferon (IFN-gamma) enzyme-linked immunospot assay responses in rhesus monkeys and human volunteers. Persistent cytokine responses of antigen-specific CD4(+) and CD8(+) T cells of the central memory as well as the effector memory phenotype, capable of simultaneously eliciting multiple cytokines (IFN-gamma, interleukin 2, and tumor necrosis factor alpha), were induced. Responses were highly similar in humans and primates, confirming earlier data indicating that priming is essential for inducing robust NYVAC-boosted IFN-gamma T-cell responses. While significant similarities were observed in Env-specific responses in both species, differences were also observed with respect to responses to other HIV antigens. Future studies with other vaccines using identical lots, immunization schedules, and readouts will establish a broader data set of species similarities and differences with which increased confidence in predicting human responses may be achieved.
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Mooij, Petra; Balla-Jhagjhoorsingh, Sunita S.; Beenhakker, Niels; van Haaften, Patricia; Baak, Ilona; Nieuwenhuis, Ivonne G.; Heidari, Shirin; Wolf, Hans; Frachette, Marie-Joelle; Bieler, Kurt; Sheppard, Neil; Harari, Alexandre; Bart, Pierre-Alexandre; Liljeström, Peter; Wagner, Ralf; Pantaleo, Giuseppe; Heeney, Jonathan L.
2009-01-01
Rhesus macaques (Macaca mulatta) have played a valuable role in the development of human immunodeficiency virus (HIV) vaccine candidates prior to human clinical trials. However, changes and/or improvements in immunogen quality in the good manufacturing practice (GMP) process or changes in adjuvants, schedule, route, dose, or readouts have compromised the direct comparison of T-cell responses between species. Here we report a comparative study in which T-cell responses from humans and macaques to HIV type 1 antigens (Gag, Pol, Nef, and Env) were induced by the same vaccine batches prepared under GMP and administered according to the same schedules in the absence and presence of priming. Priming with DNA (humans and macaques) or alphavirus (macaques) and boosting with NYVAC induced robust and broad antigen-specific responses, with highly similar Env-specific gamma interferon (IFN-γ) enzyme-linked immunospot assay responses in rhesus monkeys and human volunteers. Persistent cytokine responses of antigen-specific CD4+ and CD8+ T cells of the central memory as well as the effector memory phenotype, capable of simultaneously eliciting multiple cytokines (IFN-γ, interleukin 2, and tumor necrosis factor alpha), were induced. Responses were highly similar in humans and primates, confirming earlier data indicating that priming is essential for inducing robust NYVAC-boosted IFN-γ T-cell responses. While significant similarities were observed in Env-specific responses in both species, differences were also observed with respect to responses to other HIV antigens. Future studies with other vaccines using identical lots, immunization schedules, and readouts will establish a broader data set of species similarities and differences with which increased confidence in predicting human responses may be achieved. PMID:19321612
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Seeing responsibility: can neuroimaging teach us anything about moral and legal responsibility?
Wasserman, David; Johnston, Josephine
2014-01-01
As imaging technologies help us understand the structure and function of the brain, providing insight into human capabilities as basic as vision and as complex as memory, and human conditions as impairing as depression and as fraught as psychopathy, some have asked whether they can also help us understand human agency. Specifically, could neuroimaging lead us to reassess the socially significant practice of assigning and taking responsibility? While responsibility itself is not a psychological process open to investigation through neuroimaging, decision-making is. Over the past decade, different researchers and scholars have sought to use neuroimaging (or the results of neuroimaging studies) to investigate what is going on in the brain when we make decisions. The results of this research raise the question whether neuroscience-especially now that it includes neuroimaging-can and should alter our understandings of responsibility and our related practice of holding people responsible. It is this question that we investigate here. © 2014 by The Hastings Center.
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Hill, David R; Huang, Sha; Nagy, Melinda S; Yadagiri, Veda K; Fields, Courtney; Mukherjee, Dishari; Bons, Brooke; Dedhia, Priya H; Chin, Alana M; Tsai, Yu-Hwai; Thodla, Shrikar; Schmidt, Thomas M; Walk, Seth
2017-01-01
The human gastrointestinal tract is immature at birth, yet must adapt to dramatic changes such as oral nutrition and microbial colonization. The confluence of these factors can lead to severe inflammatory disease in premature infants; however, investigating complex environment-host interactions is difficult due to limited access to immature human tissue. Here, we demonstrate that the epithelium of human pluripotent stem-cell-derived human intestinal organoids is globally similar to the immature human epithelium and we utilize HIOs to investigate complex host-microbe interactions in this naive epithelium. Our findings demonstrate that the immature epithelium is intrinsically capable of establishing a stable host-microbe symbiosis. Microbial colonization leads to complex contact and hypoxia driven responses resulting in increased antimicrobial peptide production, maturation of the mucus layer, and improved barrier function. These studies lay the groundwork for an improved mechanistic understanding of how colonization influences development of the immature human intestine. PMID:29110754
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Tracking and imaging humans on heterogeneous infrared sensor arrays for law enforcement applications
NASA Astrophysics Data System (ADS)
Feller, Steven D.; Zheng, Y.; Cull, Evan; Brady, David J.
2002-08-01
We present a plan for the integration of geometric constraints in the source, sensor and analysis levels of sensor networks. The goal of geometric analysis is to reduce the dimensionality and complexity of distributed sensor data analysis so as to achieve real-time recognition and response to significant events. Application scenarios include biometric tracking of individuals, counting and analysis of individuals in groups of humans and distributed sentient environments. We are particularly interested in using this approach to provide networks of low cost point detectors, such as infrared motion detectors, with complex imaging capabilities. By extending the capabilities of simple sensors, we expect to reduce the cost of perimeter and site security applications.
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Experimental and numerical study of physiological responses in hot environments.
Yang, Jie; Weng, Wenguo; Zhang, Baoting
2014-10-01
This paper proposed a multi-node human thermal model to predict human thermal responses in hot environments. The model was extended based on the Tanabe's work by considering the effects of high temperature on heat production, blood flow rate, and heat exchange coefficients. Five healthy men dressed in shorts were exposed in thermal neutral (29 °C) and high temperature (45 °C) environments. The rectal temperatures and skin temperatures of seven human body segments were continuously measured during the experiment. Validation of this model was conducted with experimental data. The results showed that the current model could accurately predict the skin and core temperatures in terms of the tendency and absolute values. In the human body segments expect calf and trunk, the temperature differences between the experimental data and the predicted results in high temperature environment were smaller than those in the thermally neutral environment conditions. The extended model was proved to be capable of predicting accurately human physiological responses in hot environments. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Control system software, simulation, and robotic applications
NASA Technical Reports Server (NTRS)
Frisch, Harold P.
1991-01-01
All essential existing capabilities needed to create a man-machine interaction dynamics and performance (MMIDAP) capability are reviewed. The multibody system dynamics software program Order N DISCOS will be used for machine and musculo-skeletal dynamics modeling. The program JACK will be used for estimating and animating whole body human response to given loading situations and motion constraints. The basic elements of performance (BEP) task decomposition methodologies associated with the Human Performance Institute database will be used for performance assessment. Techniques for resolving the statically indeterminant muscular load sharing problem will be used for a detailed understanding of potential musculotendon or ligamentous fatigue, pain, discomfort, and trauma. The envisioned capacity is to be used for mechanical system design, human performance assessment, extrapolation of man/machine interaction test data, biomedical engineering, and soft prototyping within a concurrent engineering (CE) system.
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An Evaluation of Human Thermal Models for the Study of Immersion Hypothermia Protection Equipment
1979-10-12
exhibited by the five experimental observations, largely due to somatotype differences among the subjects. None of the individual responses Is represented...not less than 35°C). A mathematical model capable of accurately simulating the thermal responses of a protected man in a cold environment would be an...flow) responses . The models are most generally expressed as a set of differential equa- tions. Early models were solved using analog computers. The
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Knowledge-based load leveling and task allocation in human-machine systems
NASA Technical Reports Server (NTRS)
Chignell, M. H.; Hancock, P. A.
1986-01-01
Conventional human-machine systems use task allocation policies which are based on the premise of a flexible human operator. This individual is most often required to compensate for and augment the capabilities of the machine. The development of artificial intelligence and improved technologies have allowed for a wider range of task allocation strategies. In response to these issues a Knowledge Based Adaptive Mechanism (KBAM) is proposed for assigning tasks to human and machine in real time, using a load leveling policy. This mechanism employs an online workload assessment and compensation system which is responsive to variations in load through an intelligent interface. This interface consists of a loading strategy reasoner which has access to information about the current status of the human-machine system as well as a database of admissible human/machine loading strategies. Difficulties standing in the way of successful implementation of the load leveling strategy are examined.
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An Overview of Virtual Acoustic Simulation of Aircraft Flyover Noise
NASA Technical Reports Server (NTRS)
Rizzi, Stephen A.
2013-01-01
Methods for testing human subject response to aircraft flyover noise have greatly advanced in recent years as a result of advances in simulation technology. Capabilities have been developed which now allow subjects to be immersed both visually and aurally in a three-dimensional, virtual environment. While suitable for displaying recorded aircraft noise, the true potential is found when synthesizing aircraft flyover noise because it allows the flexibility and freedom to study sounds from aircraft not yet flown. A virtual acoustic simulation method is described which is built upon prediction-based source noise synthesis, engineering-based propagation modeling, and empirically-based receiver modeling. This source-path-receiver paradigm allows complete control over all aspects of flyover auralization. With this capability, it is now possible to assess human response to flyover noise by systematically evaluating source noise reductions within the context of a system level simulation. Examples of auralized flyover noise and movie clips representative of an immersive aircraft flyover environment are made in the presentation.
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Improving Emergency Response and Human-Robotic Performance
DOE Office of Scientific and Technical Information (OSTI.GOV)
David I. Gertman; David J. Bruemmer; R. Scott Hartley
2007-08-01
Preparedness for chemical, biological, and radiological/nuclear incidents at nuclear power plants (NPPs) includes the deployment of well trained emergency response teams. While teams are expected to do well, data from other domains suggests that the timeliness and accuracy associated with incident response can be improved through collaborative human-robotic interaction. Many incident response scenarios call for multiple, complex procedure-based activities performed by personnel wearing cumbersome personal protective equipment (PPE) and operating under high levels of stress and workload. While robotic assistance is postulated to reduce workload and exposure, limitations associated with communications and the robot’s ability to act independently have servedmore » to limit reliability and reduce our potential to exploit human –robotic interaction and efficacy of response. Recent work at the Idaho National Laboratory (INL) on expanding robot capability has the potential to improve human-system response during disaster management and recovery. Specifically, increasing the range of higher level robot behaviors such as autonomous navigation and mapping, evolving new abstractions for sensor and control data, and developing metaphors for operator control have the potential to improve state-of-the-art in incident response. This paper discusses these issues and reports on experiments underway intelligence residing on the robot to enhance emergency response.« less
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NASA Intelligent Systems Project: Results, Accomplishments and Impact on Science Missions.
NASA Astrophysics Data System (ADS)
Coughlan, J. C.
2005-12-01
The Intelligent Systems Project was responsible for much of NASA's programmatic investment in artificial intelligence and advanced information technologies. IS has completed three major project milestones which demonstrated increased capabilities in autonomy, human centered computing, and intelligent data understanding. Autonomy involves the ability of a robot to place an instrument on a remote surface with a single command cycle, human centered computing supported a collaborative, mission centric data and planning system for the Mars Exploration Rovers and data understanding has produced key components of a terrestrial satellite observation system with automated modeling and data analysis capabilities. This paper summarizes the technology demonstrations and metrics which quantify and summarize these new technologies which are now available for future NASA missions.
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NASA Intelligent Systems Project: Results, Accomplishments and Impact on Science Missions
NASA Technical Reports Server (NTRS)
Coughlan, Joseph C.
2005-01-01
The Intelligent Systems Project was responsible for much of NASA's programmatic investment in artificial intelligence and advanced information technologies. IS has completed three major project milestones which demonstrated increased capabilities in autonomy, human centered computing, and intelligent data understanding. Autonomy involves the ability of a robot to place an instrument on a remote surface with a single command cycle. Human centered computing supported a collaborative, mission centric data and planning system for the Mars Exploration Rovers and data understanding has produced key components of a terrestrial satellite observation system with automated modeling and data analysis capabilities. This paper summarizes the technology demonstrations and metrics which quantify and summarize these new technologies which are now available for future Nasa missions.
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Infectious Disease in the Twenty-First Century: The Need for a Comprehensive Strategy
1999-04-26
diseases also’appeared within the U.S., Including Lyme disease , Legionnaires disease , and hantavlrus pulmonary syndrome, and Ebola bneflv reappeared in...response mechanisms. U.S. support for further I8 U S Department of Health & Human Services, Centers for Disease Control and Prevention Preventzng Enzergzng...the strategy calls for strengthening the Infectious disease surveillance and response capabilities In the U S and InternatIonally. Surveillance data
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The Science of Climate Responsibility
NASA Astrophysics Data System (ADS)
Mitchell, D.; Frumhoff, P. C.; Sparrow, S.; Allen, M. R.
2015-12-01
Extreme events linked with human induced climate change have now been reported around the globe. Among the most troublesome impacts are increased wild fires, failed crop yields, extreme flooding and increase human mortality (Hansen and Cramer, 2015). Many of these impacts are predicted to increase into the future. Non-industrialised communities around the world will be the least capable of adapting, while the industrial communities, who are often responsible for historical carbon emissions, will find adaptation easier. Such a situation lends itself to the issue of responsibility. In order to assess responsibility, it must first be established where the major carbon and methane emissions are originating. It must then be estimated how these emissions project onto localised climate, which is often the primary indicator behind impacts on society. In this study, we address this question using a 25 km regional climate model capable of simulating climate thousands of times under the Weather@home citizen science project. The use of this framework allows us to generate huge data sample sizes, which can be put in the context of very low sample sizes of observational data. We concentrate on the 2003 heat wave over Europe, but show how this method could be applied to less data rich regions, including the Middle East and the Horn of Africa.
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Wang, Raymond M; Johnson, Todd D; He, Jingjin; Rong, Zhili; Wong, Michelle; Nigam, Vishal; Behfar, Atta; Xu, Yang; Christman, Karen L
2017-06-01
Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared. Three days and one week after subcutaneous injection, the hydrogels were analyzed for early and mid-phase immune responses, respectively. Immune cells in the humanized mouse model, particularly T-helper cells, responded distinctly between the xenogeneic and allogeneic biomaterials. The allogeneic extracellular matrix derived hydrogels elicited significantly reduced total, human specific, and CD4 + T-helper cell infiltration in humanized mice compared to xenogeneic extracellular matrix hydrogels, which was not recapitulated in wild type mice. T-helper cells, in response to the allogeneic hydrogel material, were also less polarized towards a pro-remodeling Th2 phenotype compared to xenogeneic extracellular matrix hydrogels in humanized mice. In both models, both biomaterials induced the infiltration of macrophages polarized towards a M2 phenotype and T-helper cells polarized towards a Th2 phenotype. In conclusion, these studies showed the importance of testing naturally derived biomaterials in immune competent animals and the potential of utilizing this humanized mouse model for further studying human immune cell responses to biomaterials in an in vivo environment. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Nutrition and muscle loss in humans during spaceflight
NASA Technical Reports Server (NTRS)
Stein, T. P.
1999-01-01
The protein loss in humans during spaceflight is partly due to a normal adaptive response to a decreased work load on the muscles involved in weight bearing. The process is mediated by changes in prostaglandin release, secondary to the decrease in tension on the affected muscles. On missions, where there is a high level of physical demands on the astronauts, there tends to be an energy deficit, which adds to the muscle protein loss and depletes the body fat reserves. While the adaptive response is a normal part of homeostasis, the additional protein loss from an energy deficit can, in the long run, have a negative effect on health and capability of humans to live and work in space and afterward return to Earth.
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Virtual agents in a simulated virtual training environment
NASA Technical Reports Server (NTRS)
Achorn, Brett; Badler, Norman L.
1993-01-01
A drawback to live-action training simulations is the need to gather a large group of participants in order to train a few individuals. One solution to this difficulty is the use of computer-controlled agents in a virtual training environment. This allows a human participant to be replaced by a virtual, or simulated, agent when only limited responses are needed. Each agent possesses a specified set of behaviors and is capable of limited autonomous action in response to its environment or the direction of a human trainee. The paper describes these agents in the context of a simulated hostage rescue training session, involving two human rescuers assisted by three virtual (computer-controlled) agents and opposed by three other virtual agents.
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Carbone, Eric G.; Lynch, Molly; Wang, Z. Joan; Jones, Terrance; Rose, Dale A.
2017-01-01
Objectives. To assess how health department contextual factors influence perceptions of the 15 Public Health Preparedness Capabilities, developed by the Centers for Disease Control and Prevention (CDC) to provide guidance on organizing preparedness activities. Methods. We conducted an online survey and focus group between September 2015 and May 2016 with directors of preparedness programs in state, metropolitan, and territorial jurisdictions funded by CDC’s Public Health Emergency Preparedness (PHEP) cooperative agreement. The survey collected demographic information and data on contextual factors including leadership, partnerships, organizational structure, resources and structural capacity, and data and evaluation. Results. Seventy-seven percent (48 of 62) of PHEP directors completed the survey and 8 participated in the focus group. Respondents were experienced directors (mean = 10.6 years), and 58% led 7 or more emergency responses. Leadership, partnerships, and access to fiscal and human resources were associated with perception and use of the capabilities. Conclusions. Despite some deficiencies, PHEP awardees believe the capabilities provide useful guidance and a flexible framework for organizing their work. Contextual factors affect perceptions of the capabilities and possibly the effectiveness of their use. Public Health Implications. The capabilities can be used to address challenges in preparedness, including identifying evidence-based practices, developing performance measures, and improving responses. PMID:28892447
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Horney, Jennifer A; Carbone, Eric G; Lynch, Molly; Wang, Z Joan; Jones, Terrance; Rose, Dale A
2017-09-01
To assess how health department contextual factors influence perceptions of the 15 Public Health Preparedness Capabilities, developed by the Centers for Disease Control and Prevention (CDC) to provide guidance on organizing preparedness activities. We conducted an online survey and focus group between September 2015 and May 2016 with directors of preparedness programs in state, metropolitan, and territorial jurisdictions funded by CDC's Public Health Emergency Preparedness (PHEP) cooperative agreement. The survey collected demographic information and data on contextual factors including leadership, partnerships, organizational structure, resources and structural capacity, and data and evaluation. Seventy-seven percent (48 of 62) of PHEP directors completed the survey and 8 participated in the focus group. Respondents were experienced directors (mean = 10.6 years), and 58% led 7 or more emergency responses. Leadership, partnerships, and access to fiscal and human resources were associated with perception and use of the capabilities. Despite some deficiencies, PHEP awardees believe the capabilities provide useful guidance and a flexible framework for organizing their work. Contextual factors affect perceptions of the capabilities and possibly the effectiveness of their use. Public Health Implications. The capabilities can be used to address challenges in preparedness, including identifying evidence-based practices, developing performance measures, and improving responses.
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No Evidence for a Low Linear Energy Transfer Adaptive Response in Irradiated RKO Cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sowa, Marianne B.; Goetz, Wilfried; Baulch, Janet E.
2011-01-06
It has become increasingly evident from reports in the literature that there are many confounding factors that are capable of modulating radiation induced non-targeted responses such as the bystander effect and the adaptive response. In this paper we examine recent data that suggest that the observation of non-targeted responses may not be universally observable for differing radiation qualities. We have conducted a study of the adaptive response following low LET exposures for human colon carcinoma cells and failed to observe adaption for the endpoints of clonogenic survival or micronucleus formation.
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Human olfactory receptor responses to odorants
Mainland, Joel D; Li, Yun R; Zhou, Ting; Liu, Wen Ling L; Matsunami, Hiroaki
2015-01-01
Although the human olfactory system is capable of discriminating a vast number of odors, we do not currently understand what chemical features are encoded by olfactory receptors. In large part this is due to a paucity of data in a search space covering the interactions of hundreds of receptors with billions of odorous molecules. Of the approximately 400 intact human odorant receptors, only 10% have a published ligand. Here we used a heterologous luciferase assay to screen 73 odorants against a clone library of 511 human olfactory receptors. This dataset will allow other researchers to interrogate the combinatorial nature of olfactory coding. PMID:25977809
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Host response to Brucella infection: review and future perspective.
Elfaki, Mohamed G; Alaidan, Alwaleed Abdullah; Al-Hokail, Abdullah Abdulrahman
2015-07-30
Brucellosis is a zoonotic and contagious infectious disease caused by infection with Brucella species. The infecting brucellae are capable of causing a devastating multi-organ disease in humans with serious health complications. The pathogenesis of Brucella infection is influenced largely by host factors, Brucella species/strain, and the ability of invading brucellae to survive and replicate within mononuclear phagocytic cells, preferentially macrophages (Mf). Consequently, the course of human infection may appear as an acute fatal or progress into chronic debilitating infection with periodical episodes that leads to bacteremia and death. The existence of brucellae inside Mf represents one of the strategies used by Brucella to evade the host immune response and is responsible for treatment failure in certain human populations treated with anti-Brucella drugs. Moreover, the persistence of brucellae inside Mf complicates the diagnosis and may affect the host cell signaling pathways with consequent alterations in both innate and adaptive immune responses. Therefore, there is an urgent need to pursue the development of novel drugs and/or vaccine targets against human brucellosis using high throughput technologies in genomics, proteomics, and immunology.
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Immune evasion in ebolavirus infections.
Audet, Jonathan; Kobinger, Gary P
2015-02-01
Ebola virus (EBOV) infects humans as well as several animal species. It can lead to a highly lethal disease, with mortality rates approaching 90% in primates. Recent advances have deepened our understanding of how this virus is able to prevent the development of protective immune responses. The EBOV genome encodes eight proteins, four of which were shown to interact with the host in ways that counteract the immune response. The viral protein 35 (VP35) is capable of capping dsRNA and interacts with IRF7 to prevent detection of the virus by immune cells. The main role of the soluble glycoprotein (sGP) is still unclear, but it is capable of subverting the anti-GP1,2 antibody response. The GP1,2 protein has shown anti-tetherin activity and the ability to hide cell-surface proteins. Finally, VP24 interferes with the production of interferons (IFNs) and with IFN signaling in infected cells. Taken together, these data point to extensive adaptation of EBOV to evade the immune system of dead end hosts. While our understanding of the interactions between the human and viral proteins increases, details of those interactions in other hosts remain largely unclear and represent a gap in our knowledge.
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Feedbacks in human-landscape systems
NASA Astrophysics Data System (ADS)
Chin, Anne
2015-04-01
As human interactions with Earth systems intensify in the "Anthropocene", understanding the complex relationships among human activity, landscape change, and societal responses to those changes is increasingly important. Interdisciplinary research centered on the theme of "feedbacks" in human-landscape systems serves as a promising focus for unraveling these interactions. Deciphering interacting human-landscape feedbacks extends our traditional approach of considering humans as unidirectional drivers of change. Enormous challenges exist, however, in quantifying impact-feedback loops in landscapes with significant human alterations. This paper illustrates an example of human-landscape interactions following a wildfire in Colorado (USA) that elicited feedback responses. After the 2012 Waldo Canyon Fire, concerns for heightened flood potential and debris flows associated with post-fire hydrologic changes prompted local landowners to construct tall fences at the base of a burned watershed. These actions changed the sediment transport regime and promoted further landscape change and human responses in a positive feedback cycle. The interactions ultimately increase flood and sediment hazards, rather than dampening the effects of fire. A simple agent-based model, capable of integrating social and hydro-geomorphological data, demonstrates how such interacting impacts and feedbacks could be simulated. Challenges for fully capturing human-landscape feedback interactions include the identification of diffuse and subtle feedbacks at a range of scales, the availability of data linking impact with response, the identification of multiple thresholds that trigger feedback mechanisms, and the varied metrics and data needed to represent both the physical and human systems. By collaborating with social scientists with expertise in the human causes of landscape change, as well as the human responses to those changes, geoscientists could more fully recognize and anticipate the coupled human-landscape interactions that will drive the evolution of Earth systems into the future.
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Chiriva-Internati, Maurizio; Cobos, Everardo; Da Silva, Diane M.
2008-01-01
Cancer vaccines have been demonstrated to be a promising strategy for treating human neoplastic disease, but one of the limitations of these vaccines remains the paucity of target antigens to which to direct an effective immune response. We hypothesize that sperm fibrous sheath proteins may be a new class of useful antigens for developing successful cancer vaccines. This hypothesis is supported by the expression of two sperm fibrous sheath proteins, called sperm protein 17 and calcium-binding tyrosine-phosphorylation regulated protein, in tumors of unrelated histological origin and their capability to induce T cell-based immune responses. PMID:18433090
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Enduring Influences of Early Experience.
ERIC Educational Resources Information Center
Lipsitt, Lewis P.
Implications of three basic facts about very young infants are delineated in this summary. Normally, human infants are capable of a wide range of functions, such as "appetitive responses" (e.g., the rooting reflex) and defensive maneuvers. They experience pleasure and feel pain. Additionally, they undergo a transition from subcortical to…
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Structural impact detection with vibro-haptic interfaces
NASA Astrophysics Data System (ADS)
Jung, Hwee-Kwon; Park, Gyuhae; Todd, Michael D.
2016-07-01
This paper presents a new sensing paradigm for structural impact detection using vibro-haptic interfaces. The goal of this study is to allow humans to ‘feel’ structural responses (impact, shape changes, and damage) and eventually determine health conditions of a structure. The target applications for this study are aerospace structures, in particular, airplane wings. Both hardware and software components are developed to realize the vibro-haptic-based impact detection system. First, L-shape piezoelectric sensor arrays are deployed to measure the acoustic emission data generated by impacts on a wing. Unique haptic signals are then generated by processing the measured acoustic emission data. These haptic signals are wirelessly transmitted to human arms, and with vibro-haptic interface, human pilots could identify impact location, intensity and possibility of subsequent damage initiation. With the haptic interface, the experimental results demonstrate that human could correctly identify such events, while reducing false indications on structural conditions by capitalizing on human’s classification capability. Several important aspects of this study, including development of haptic interfaces, design of optimal human training strategies, and extension of the haptic capability into structural impact detection are summarized in this paper.
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IntelliTable: Inclusively-Designed Furniture with Robotic Capabilities.
Prescott, Tony J; Conran, Sebastian; Mitchinson, Ben; Cudd, Peter
2017-01-01
IntelliTable is a new proof-of-principle assistive technology system with robotic capabilities in the form of an elegant universal cantilever table able to move around by itself, or under user control. We describe the design and current capabilities of the table and the human-centered design methodology used in its development and initial evaluation. The IntelliTable study has delivered robotic platform programmed by a smartphone that can navigate around a typical home or care environment, avoiding obstacles, and positioning itself at the user's command. It can also be configured to navigate itself to pre-ordained places positions within an environment using ceiling tracking, responsive optical guidance and object-based sonar navigation.
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Boots on Mars: Earth Independent Human Exploration of Mars
NASA Technical Reports Server (NTRS)
Burnett, Josephine; Gill, Tracy R.; Ellis, Kim Gina
2017-01-01
This package is for the conduct of a workshop during the International Space University Space Studies Program in the summer of 2017 being held in Cork, Ireland. It gives publicly available information on NASA and international plans to move beyond low Earth orbit to Mars and discusses challenges and capabilities. This information will provide the participants a basic level of insight to develop a response on their perceived obstacles to a future vision of humans on Mars.
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A Human Capabilities Framework for Evaluating Student Learning
ERIC Educational Resources Information Center
Walker, Melanie
2008-01-01
This paper proposes a human capabilities approach for evaluating student learning and the social and pedagogical arrangements that support equality in capabilities for all students. It outlines the focus on valuable beings and doings in the capability approach developed by Amartya Sen, and Martha Nussbaum's capabilities focus on human flourishing.…
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NASA Technical Reports Server (NTRS)
Culbert, Christopher J.; Mongrard, Olivier; Satoh, Naoki; Goodliff, Kandyce; Seaman, Calvin H.; Troutman, Patrick; Martin, Eric
2011-01-01
The International Space Exploration Coordination Group (ISECG) was established in response to The Global Exploration Strategy (GES): The Framework for Coordination developed by fourteen space agencies* and released in May 2007. This GES Framework Document recognizes that preparing for human space exploration is a stepwise process, starting with basic knowledge and culminating in a sustained human presence in deep space. ISECG has developed several optional global exploration mission scenarios enabling the phased transition from human operations in Low Earth Orbit (LEO) and utilization of the International Space Station (ISS) to human missions beyond LEO leading ultimately to human missions to cis-lunar space, the Moon, Near Earth Asteroids, Mars and its environs. Mission scenarios provide the opportunity for judging various exploration approaches in a manner consistent with agreed international goals and strategies. Each ISECG notional mission scenario reflects a series of coordinated human and robotic exploration missions over a 25-year horizon. Mission scenarios are intended to provide insights into next steps for agency investments, following on the success of the ISS. They also provide a framework for advancing the definition of Design Reference Missions (DRMs) and the concepts for capabilities contained within. Each of the human missions contained in the scenarios has been characterized by a DRM which is a top level definition of mission sequence and the capabilities needed to execute that mission. While DRMs are generally destination focused, they will comprise capabilities which are reused or evolved from capabilities used at other destinations. In this way, an evolutionary approach to developing a robust set of capabilities to sustainably explore our solar system is defined. Agencies also recognize that jointly planning for our next steps, building on the accomplishments of ISS, is important to ensuring the robustness and sustainability of any human exploration plan. Developing a shared long-term vision is important, but agencies recognize this is an evolutionary process and requires consideration of many strategic factors. Strategic factors such as the implications of an emerging commercial space industry in LEO, the opportunity provided by extending ISS lifetime to at least 2020, and the importance of defining a plan which is sustainable in light of inevitable domestic policy shifts are timely for agency consideration.
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NASA Technical Reports Server (NTRS)
Williams-Byrd, Julie; Arney, Dale; Rodgers, Erica; Antol, Jeff; Simon, Matthew; Hay, Jason; Larman, Kevin
2015-01-01
NASA is engaged in transforming human spaceflight. The Agency is shifting from an exploration-based program with human activities focused on low Earth orbit (LEO) and targeted robotic missions in deep space to a more sustainable and integrated pioneering approach. Through pioneering, NASA seeks to address national goals to develop the capacity for people to work, learn, operate, live, and thrive safely beyond the Earth for extended periods of time. However, pioneering space involves more than the daunting technical challenges of transportation, maintaining health, and enabling crew productivity for long durations in remote, hostile, and alien environments. This shift also requires a change in operating processes for NASA. The Agency can no longer afford to engineer systems for specific missions and destinations and instead must focus on common capabilities that enable a range of destinations and missions. NASA has codified a capability driven approach, which provides flexible guidance for the development and maturation of common capabilities necessary for human pioneers beyond LEO. This approach has been included in NASA policy and is captured in the Agency's strategic goals. It is currently being implemented across NASA's centers and programs. Throughout 2014, NASA engaged in an Agency-wide process to define and refine exploration-related capabilities and associated gaps, focusing only on those that are critical for human exploration beyond LEO. NASA identified 12 common capabilities ranging from Environmental Control and Life Support Systems to Robotics, and established Agency-wide teams or working groups comprised of subject matter experts that are responsible for the maturation of these exploration capabilities. These teams, called the System Maturation Teams (SMTs) help formulate, guide and resolve performance gaps associated with the identified exploration capabilities. The SMTs are defining performance parameters and goals for each of the 12 capabilities, developing maturation plans and roadmaps for the identified performance gaps, specifying the interfaces between the various capabilities, and ensuring that the capabilities mature and integrate to enable future pioneering missions. By managing system development through the SMTs instead of traditional NASA programs and projects, the Agency is shifting from mission-driven development to a more flexible, capability-driven development. The process NASA uses to establish, integrate, prioritize, and manage the SMTs and associated capabilities is iterative. NASA relies on the Human Exploration and Operation Mission Directorate's SMT Integration Team within Advanced Exploration Systems to coordinate and facilitate the SMT process. The SMT Integration team conducts regular reviews and coordination meetings among the SMTs and has developed a number of tools to help the Agency implement capability driven processes. The SMT Integration team is uniquely positioned to help the Agency coordinate the SMTs and other processes that are making the capability-driven approach a reality. This paper will introduce the SMTs and the 12 key capabilities they represent. The role of the SMTs will be discussed with respect to Agency-wide processes to shift from mission-focused exploration to a capability-driven pioneering approach. Specific examples will be given to highlight systems development and testing within the SMTs. These examples will also show how NASA is using current investments in the International Space Station and future investments to develop and demonstrate capabilities. The paper will conclude by describing next steps and a process for soliciting feedback from the space exploration community to refine NASA's process for developing common exploration capabilities.
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Using APEX to Model Anticipated Human Error: Analysis of a GPS Navigational Aid
NASA Technical Reports Server (NTRS)
VanSelst, Mark; Freed, Michael; Shefto, Michael (Technical Monitor)
1997-01-01
The interface development process can be dramatically improved by predicting design facilitated human error at an early stage in the design process. The approach we advocate is to SIMULATE the behavior of a human agent carrying out tasks with a well-specified user interface, ANALYZE the simulation for instances of human error, and then REFINE the interface or protocol to minimize predicted error. This approach, incorporated into the APEX modeling architecture, differs from past approaches to human simulation in Its emphasis on error rather than e.g. learning rate or speed of response. The APEX model consists of two major components: (1) a powerful action selection component capable of simulating behavior in complex, multiple-task environments; and (2) a resource architecture which constrains cognitive, perceptual, and motor capabilities to within empirically demonstrated limits. The model mimics human errors arising from interactions between limited human resources and elements of the computer interface whose design falls to anticipate those limits. We analyze the design of a hand-held Global Positioning System (GPS) device used for radical and navigational decisions in small yacht recalls. The analysis demonstrates how human system modeling can be an effective design aid, helping to accelerate the process of refining a product (or procedure).
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On the formal definition of the systems' interoperability capability: an anthropomorphic approach
NASA Astrophysics Data System (ADS)
Zdravković, Milan; Luis-Ferreira, Fernando; Jardim-Goncalves, Ricardo; Trajanović, Miroslav
2017-03-01
The extended view of enterprise information systems in the Internet of Things (IoT) introduces additional complexity to the interoperability problems. In response to this, the problem of systems' interoperability is revisited by taking into the account the different aspects of philosophy, psychology, linguistics and artificial intelligence, namely by analysing the potential analogies between the processes of human and system communication. Then, the capability to interoperate as a property of the system, is defined as a complex ability to seamlessly sense and perceive a stimulus from its environment (assumingly, a message from any other system), make an informed decision about this perception and consequently, articulate a meaningful and useful action or response, based on this decision. Although this capability is defined on the basis of the existing interoperability theories, the proposed approach to its definition excludes the assumption on the awareness of co-existence of two interoperating systems. Thus, it establishes the links between the research of interoperability of systems and intelligent software agents, as one of the systems' digital identities.
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[Ethical challenges of genetic manipulation and research with animals].
Rodríguez Yunta, Eduardo
2012-01-01
Research with animals presents ethical questions both for being used as models of human diseases and for being a prerequisite for trials in humans, as in the introduction of genetic modifications. Some of these questions refer to the fact that, as models, they do not fully represent the human condition; that conducting toxicity tests causes great harm to animals; that their nature is altered by genetic modifications and that introducing genetically modified organisms is a risk. The use of animals in research for the benefit of humans imposes the moral responsibility to respect them, not making them suffer unnecessarily, since they are living beings capable of feeling.
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A Response to Joel Bowman on "Beyond the You-Attitude."
ERIC Educational Resources Information Center
Johnson, Eldon C.
1985-01-01
States that Bowman has identified a number of serious problems in our social and business environments and supports his adaptation of Maslow's model of human motivation as a communication theory and his interpretation of self-actualization beyond its popularized notion as simply a self-centered desire to develop one's own capabilities. (EL)
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Social Responsiveness of Infants. Pediatric Round Table: 2.
ERIC Educational Resources Information Center
Thoman, Evelyn B., Ed.; Trotter, Sharland, Ed.
Conference papers and discussions presented in this volume reflect recent research results that suggest the human infant is not a tabula rasa but an organism endowed at birth with an array of capabilities. Contents focus on several issues, including the possibility that infants have a rich affective life from their earliest days and that even…
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Effect of chemical compounds on electronic tongue response to citrus juices
USDA-ARS?s Scientific Manuscript database
The electronic tongue system mimics the process of taste detection by human taste buds and recognition by the brain, hence helping in prediction of taste. With this unique capability, the electronic tongue has been used for taste detection of a wide range of food products. As a preliminary step in p...
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Using Service Learning to Improve Interviewer and Interviewee Effectiveness
ERIC Educational Resources Information Center
Mann, Melissa J.; Yanson, Regina; Lambert, Alysa D.
2018-01-01
Interviews are a critical component of assessing a candidate's fit in an organization. Students aspiring to be managers or human resource professionals will need to complete an interview to successfully gain employment and then, in turn, will be responsible for conducting interviews to effectively ascertain the capabilities and motivation of job…
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Boucher, Jean-David; Pattacini, Ugo; Lelong, Amelie; Bailly, Gerard; Elisei, Frederic; Fagel, Sascha; Dominey, Peter Ford; Ventre-Dominey, Jocelyne
2012-01-01
Human–human interaction in natural environments relies on a variety of perceptual cues. Humanoid robots are becoming increasingly refined in their sensorimotor capabilities, and thus should now be able to manipulate and exploit these social cues in cooperation with their human partners. Previous studies have demonstrated that people follow human and robot gaze, and that it can help them to cope with spatially ambiguous language. Our goal is to extend these findings into the domain of action, to determine how human and robot gaze can influence the speed and accuracy of human action. We report on results from a human–human cooperation experiment demonstrating that an agent’s vision of her/his partner’s gaze can significantly improve that agent’s performance in a cooperative task. We then implement a heuristic capability to generate such gaze cues by a humanoid robot that engages in the same cooperative interaction. The subsequent human–robot experiments demonstrate that a human agent can indeed exploit the predictive gaze of their robot partner in a cooperative task. This allows us to render the humanoid robot more human-like in its ability to communicate with humans. The long term objectives of the work are thus to identify social cooperation cues, and to validate their pertinence through implementation in a cooperative robot. The current research provides the robot with the capability to produce appropriate speech and gaze cues in the context of human–robot cooperation tasks. Gaze is manipulated in three conditions: Full gaze (coordinated eye and head), eyes hidden with sunglasses, and head fixed. We demonstrate the pertinence of these cues in terms of statistical measures of action times for humans in the context of a cooperative task, as gaze significantly facilitates cooperation as measured by human response times. PMID:22563315
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Svandra, Philippe
2008-12-01
Trying to define the nature of care when you are a health care professional, means, inevitably, going back to the very source of your professional commitment. Caring, an essential form of responsibility for the other, is thus revealed as a way of behaving towards other people, as an active and concrete commitment testifying as much to the humanity of the one who gives it as to that of the one who receives it. Starting with the notion of the phenomenology of human capacity, Paul Ricoeur thinks of independence in terms of capacity. He calls upon work of the Indian economist Amartya Sen published in the 1980s on the notion of capabilities. This leads to conceiving disease or disability as a lack of elementary or basic capacity. According to Ricoeur, this notion of capacity can only be understood by looking at its contrary: vulnerability. In this way, only a weakened frail person can be called upon to become independent. Thus the human being, and particularly the ill human being, must be looked upon as both vulnerable, and thus suffering, and capable, and thus active.
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Social Bots: Human-Like by Means of Human Control?
Grimme, Christian; Preuss, Mike; Adam, Lena; Trautmann, Heike
2017-12-01
Social bots are currently regarded an influential but also somewhat mysterious factor in public discourse and opinion making. They are considered to be capable of massively distributing propaganda in social and online media, and their application is even suspected to be partly responsible for recent election results. Astonishingly, the term social bot is not well defined and different scientific disciplines use divergent definitions. This work starts with a balanced definition attempt, before providing an overview of how social bots actually work (taking the example of Twitter) and what their current technical limitations are. Despite recent research progress in Deep Learning and Big Data, there are many activities bots cannot handle well. We then discuss how bot capabilities can be extended and controlled by integrating humans into the process and reason that this is currently the most promising way to realize meaningful interactions with other humans. This finally leads to the conclusion that hybridization is a challenge for current detection mechanisms and has to be handled with more sophisticated approaches to identify political propaganda distributed with social bots.
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Human cytokine responses induced by Gram-positive cell walls of normal intestinal microbiota
Chen, T; Isomäki, P; Rimpiläinen, M; Toivanen, P
1999-01-01
The normal microbiota plays an important role in the health of the host, but little is known of how the human immune system recognizes and responds to Gram-positive indigenous bacteria. We have investigated cytokine responses of peripheral blood mononuclear cells (PBMC) to Gram-positive cell walls (CW) derived from four common intestinal indigenous bacteria, Eubacterium aerofaciens (Eu.a.), Eubacterium limosum(Eu.l.), Lactobacillus casei(L.c.), and Lactobacillus fermentum (L.f.). Our results indicate that Gram-positive CW of the normal intestinal microbiota can induce cytokine responses of the human PBMC. The profile, level and kinetics of these responses are similar to those induced by lipopolysaccharide (LPS) or CW derived from a pathogen, Streptococcus pyogenes (S.p.). Bacterial CW are capable of inducing production of a proinflammatory cytokine, tumour necrosis factor-alpha (TNF-α), and an anti-inflammatory cytokine, IL-10, but not that of IL-4 or interferon-gamma (IFN-γ). Monocytes are the main cell population in PBMC to produce TNF-α and IL-10. Induction of cytokine secretion is serum-dependent; both CD14-dependent and -independent pathways are involved. These findings suggest that the human cytokine responses induced by Gram-positive CW of the normal intestinal microbiota are similar to those induced by LPS or Gram-positive CW of the pathogens. PMID:10540188
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Comprehension and engagement in survey interviews with virtual agents
Conrad, Frederick G.; Schober, Michael F.; Jans, Matt; Orlowski, Rachel A.; Nielsen, Daniel; Levenstein, Rachel
2015-01-01
This study investigates how an onscreen virtual agent's dialog capability and facial animation affect survey respondents' comprehension and engagement in “face-to-face” interviews, using questions from US government surveys whose results have far-reaching impact on national policies. In the study, 73 laboratory participants were randomly assigned to respond in one of four interviewing conditions, in which the virtual agent had either high or low dialog capability (implemented through Wizard of Oz) and high or low facial animation, based on motion capture from a human interviewer. Respondents, whose faces were visible to the Wizard (and videorecorded) during the interviews, answered 12 questions about housing, employment, and purchases on the basis of fictional scenarios designed to allow measurement of comprehension accuracy, defined as the fit between responses and US government definitions. Respondents answered more accurately with the high-dialog-capability agents, requesting clarification more often particularly for ambiguous scenarios; and they generally treated the high-dialog-capability interviewers more socially, looking at the interviewer more and judging high-dialog-capability agents as more personal and less distant. Greater interviewer facial animation did not affect response accuracy, but it led to more displays of engagement—acknowledgments (verbal and visual) and smiles—and to the virtual interviewer's being rated as less natural. The pattern of results suggests that a virtual agent's dialog capability and facial animation differently affect survey respondents' experience of interviews, behavioral displays, and comprehension, and thus the accuracy of their responses. The pattern of results also suggests design considerations for building survey interviewing agents, which may differ depending on the kinds of survey questions (sensitive or not) that are asked. PMID:26539138
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Simplified human model and pedestrian simulation in the millimeter-wave region
NASA Astrophysics Data System (ADS)
Han, Junghwan; Kim, Seok; Lee, Tae-Yun; Ka, Min-Ho
2016-02-01
The 24 GHz and 77 GHz radar sensors have been studied as a strong candidate for advanced driver assistance systems(ADAS) because of their all-weather capability and accurate range and radial velocity measuring scheme. However, developing a reliable pedestrian recognition system hasmany obstacles due to the inaccurate and non-trivial radar responses at these high frequencies and the many combinations of clothes and accessories. To overcome these obstacles, many researchers used electromagnetic (EM) simulation to characterize the radar scattering response of a human. However, human simulation takes so long time because of the electrically huge size of a human in the millimeter-wave region. To reduce simulation time, some researchers assumed the skin of a human is the perfect electric conductor (PEC) and have simulated the PEC human model using physical optics (PO) algorithm without a specific explanation about how the human body could be modeled with PEC. In this study, the validity of the assumption that the surface of the human body is considered PEC in the EM simulation is verified, and the simulation result of the dry skin human model is compared with that of the PEC human model.
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Cysteine cathepsin S processes leptin, inactivating its biological activity.
Oliveira, Marcela; Assis, Diego M; Paschoalin, Thaysa; Miranda, Antonio; Ribeiro, Eliane B; Juliano, Maria A; Brömme, Dieter; Christoffolete, Marcelo Augusto; Barros, Nilana M T; Carmona, Adriana K
2012-08-01
Leptin is a 16 kDa hormone mainly produced by adipocytes that plays an important role in many biological events including the regulation of appetite and energy balance, atherosclerosis, osteogenesis, angiogenesis, the immune response, and inflammation. The search for proteolytic enzymes capable of processing leptin prompted us to investigate the action of cysteine cathepsins on human leptin degradation. In this study, we observed high cysteine peptidase expression and hydrolytic activity in white adipose tissue (WAT), which was capable of degrading leptin. Considering these results, we investigated whether recombinant human cysteine cathepsins B, K, L, and S were able to degrade human leptin. Mass spectrometry analysis revealed that among the tested enzymes, cathepsin S exhibited the highest catalytic activity on leptin. Furthermore, using a Matrigel assay, we observed that the leptin fragments generated by cathepsin S digestion did not exhibit angiogenic action on endothelial cells and were unable to inhibit food intake in Wistar rats after intracerebroventricular administration. Taken together, these results suggest that cysteine cathepsins may be putative leptin activity regulators in WAT.
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Modeling occupants in far-side impacts.
Douglas, Clay; Fildes, Brian; Gibson, Tom
2011-10-01
Far-side impacts are not part of any regulated NCAP, FMVSS, or similar test regime despite accounting for 43 percent of the seriously injured persons and 30 percent of the harm in U.S. side impact crashes. Furthermore, injuries to the head and thorax account for over half of the serious injuries sustained by occupants in far-side crashes. Despite this, there is no regulated or well-accepted anthropomorphic test device (ATD) or computer model available to investigate far-side impacts. As such, this presents an opportunity to assess a computer model that can be used to measure the effect of varying restraint parameters on occupant biomechanics in far-side impacts. This study sets out to demonstrate the modified TASS human facet model's (MOTHMO) capabilities in modeling whole-body response in far-side impacts. MOTHMO's dynamic response was compared to that of postmortem human subjects (PMHS), WorldSID, and Thor-NT in a series of far-side sled tests. The advantages, disadvantages, and differences of using MOTHMO compared to ATDs were highlighted and described in terms of model design and instrumentation. Potential applications and improvements for MOTHMO were also recommended. The results showed that MOTHMO is capable of replicating the seat belt-to-shoulder complex interaction, pelvis impacts, head displacement, neck and shoulder belt loading from inboard mounted belts, and impacts from multiple directions. Overall, the model performed better than Thor-NT and at least as well as WorldSID when compared to PMHS results. Though WorldSID and Thor-NT ATDs were capable of reproducing many of these impact loads, measuring the seat belt-to-shoulder complex interaction and thoracic deflection at multiple sites and directions was less accurately handled. This study demonstrated that MOTHMO is capable of modeling whole-body response in far-side impacts. Furthermore, MOTHMO can be used as a virtual design tool to explore the effect of varying restraint parameters on occupant kinematics in far-side crash configurations.
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2011-01-01
Substantial improvements have been made in recent years in the ability to engraft human cells and tissues into immunodeficient mice. The use of human hematopoietic stem cells (HSCs) leads to multi-lineage human hematopoiesis accompanied by production of a variety of human immune cell types. Population of murine primary and secondary lymphoid organs with human cells occurs, and long-term engraftment has been achieved. Engrafted cells are capable of producing human innate and adaptive immune responses, making these models the most physiologically relevant humanized animal models to date. New models have been successfully infected by a variety of strains of Human Immunodeficiency Virus Type 1 (HIV-1), accompanied by virus replication in lymphoid and non-lymphoid organs, including the gut-associated lymphoid tissue, the male and female reproductive tracts, and the brain. Multiple forms of virus-induced pathogenesis are present, and human T cell and antibody responses to HIV-1 are detected. These humanized mice are susceptible to a high rate of rectal and vaginal transmission of HIV-1 across an intact epithelium, indicating the potential to study vaccines and microbicides. Antiviral drugs, siRNAs, and hematopoietic stem cell gene therapy strategies have all been shown to be effective at reducing viral load and preventing or reversing helper T cell loss in humanized mice, indicating that they will serve as an important preclinical model to study new therapeutic modalities. HIV-1 has also been shown to evolve in response to selective pressures in humanized mice, thus showing that the model will be useful to study and/or predict viral evolution in response to drug or immune pressures. The purpose of this review is to summarize the findings reported to date on all new humanized mouse models (those transplanted with human HSCs) in regards to HIV-1 sexual transmission, pathogenesis, anti-HIV-1 immune responses, viral evolution, pre- and post-exposure prophylaxis, and gene therapeutic strategies. PMID:21835012
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Sonic Boom Modeling Technical Challenge
NASA Technical Reports Server (NTRS)
Sullivan, Brenda M.
2007-01-01
This viewgraph presentation reviews the technical challenges in modeling sonic booms. The goal of this program is to develop knowledge, capabilities and technologies to enable overland supersonic flight. The specific objectives of the modeling are: (1) Develop and validate sonic boom propagation model through realistic atmospheres, including effects of turbulence (2) Develop methods enabling prediction of response of and acoustic transmission into structures impacted by sonic booms (3) Develop and validate psychoacoustic model of human response to sonic booms under both indoor and outdoor listening conditions, using simulators.
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New generation humanized mice for virus research: Comparative aspects and future prospects
Akkina, Ramesh
2014-01-01
Work with human specific viruses will greatly benefit from the use of an in vivo system that provides human target cells and tissues in a physiological setting. In this regard humanized mice (hu-Mice) have played an important role in our understanding of viral pathogenesis and testing of therapeutic strategies. Limitations with earlier versions of hu-Mice that lacked a functioning human immune system are currently being overcome. The new generation hu-Mouse models are capable of multilineage human hematopoiesis and generate T cells, B cells, macrophages and dendritic cells required for an adaptive human immune response. Now any human specific pathogen that can infect humanized mice can be studied in the context of ongoing infection and immune responses. Two leading humanized mouse models are currently employed: the hu-HSC model is created by transplantation of human hematopoietic stem cells (HSC), whereas the BLT mouse model is prepared by transplantation of human fetal liver, thymus and HSC. A number of human specific viruses such as HIV-1, dengue, EBV and HCV are being studied intensively in these systems. Both models permit infection by mucosal routes with viruses such as HIV-1 thus allowing transmission prevention studies. Cellular and humoral immune responses are seen in both the models. While there is efficient antigen specific IgM production, IgG responses are suboptimal due to inefficient immunoglobulin class switching. With the maturation of T cells occurring in the autologous human thymus, BLT mice permit human HLA restricted T cell responses in contrast to hu-HSC mice. However, the strength of the immune responses needs further improvement in both models to reach the levels seen in humans. The scope of hu-Mice use is further broadened by transplantation of additional tissues like human liver thus permitting immunopathogenesis studies on hepatotropic viruses such as HCV. Numerous studies that encompass antivirals, gene therapy, viral evolution, and the generation of human monoclonal antibodies have been conducted with promising results in these mice. For further improvement of the new hu-Mouse models, ongoing work is focused on generating new strains of immunodeficient mice transgenic for human HLA molecules to strengthen immune responses and human cytokines and growth factors to improve human cell reconstitution and their homeostatic maintenance. PMID:23217612
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Passenger comfort response times as a function of aircraft motion
NASA Technical Reports Server (NTRS)
Rinalducci, E. J.
1975-01-01
The relationship between a passenger's response time of changes in level of comfort experienced as a function of aircraft motion was examined. The aircraft used in this investigation was capable of providing a wide range of vertical and transverse accelerations by means of direct lift flap control surfaces and side force generator surfaces in addition to normal control surfaces. Response times to changes in comfort were recorded along with the passenger's rating of comfort on a five point scale. In addition, a number of aircraft motion variables including vertical and transverse accelerations were also recorded. Results indicate some relationship between human comfort response times to reaction time data.
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ERIC Educational Resources Information Center
Uzgiris, Ina C.; Hunt, J. McV.
The human infant is now considered capable of active informational interaction with the environment. This study tested certain hypotheses concerning the nature of that interaction. These hypotheses, developed partly from Piaget's work, are (1) that repeated visual encounters with a stimulus pattern leads first to attentional preference for that…
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Virus-like particles as nanovaccine candidates
NASA Astrophysics Data System (ADS)
Guillen, G.; Aguilar, J. C.; Dueñas, S.; Hermida, L.; Iglesias, E.; Penton, E.; Lobaina, Y.; Lopez, M.; Mussachio, A.; Falcon, V.; Alvarez, L.; Martinez, G.; Gil, L.; Valdes, I.; Izquierdo, A.; Lazo, L.; Marcos, E.; Guzman, G.; Muzio, V.; Herrera, L.
2013-03-01
The existing vaccines are mainly limited to the microorganisms we are able to culture and produce and/or to those whose killing is mediated by humoral response (antibody mediated). It has been more difficult to develop vaccines capable of inducing a functional cellular response needed to prevent or cure chronic diseases. New strategies should be taken into account in the improvement of cell-based immune responses in order to prevent and control the infections and eventually clear the virus. Preclinical and clinical results with vaccine candidates developed as a vaccine platform based on virus-like particles (VLPs) evidenced their ability to stimulate mucosal as well as systemic immunity. Particles based on envelope, membrane or nucleocapsid microbial proteins induce a strong immune response after nasal or parenteral administration in mice, non-human primates and humans. In addition, the immune response obtained was modulated in a Th1 sense. The VLPs were also able to immunoenhance the humoral and cellular immune responses against several viral pathogens. Studies in animals and humans with nasal and systemic formulations evidenced that it is possible to induce functional immune response against HBV, HCV, HIV and dengue virus. Invited talk at the 6th International Workshop on Advanced Materials Science and Nanotechnology, 30 October - 2 November 2012, Ha Long, Vietnam.
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Immunoregulation by Taenia crassiceps and its antigens.
Peón, Alberto N; Espinoza-Jiménez, Arlett; Terrazas, Luis I
2013-01-01
Taenia crassiceps is a cestode parasite of rodents (in its larval stage) and canids (in its adult stage) that can also parasitize immunocompromised humans. We have studied the immune response elicited by this helminth and its antigens in mice and human cells, and have discovered that they have a strong capacity to induce chronic Th2-type responses that are primarily characterized by high levels of Th2 cytokines, low proliferative responses in lymphocytes, an immature and LPS-tolerogenic profile in dendritic cells, the recruitment of myeloid-derived suppressor cells and, specially, alternatively activated macrophages. We also have utilized the immunoregulatory capabilities of this helminth to successfully modulate autoimmune responses and the outcome of other infectious diseases. In the present paper, we review the work of others and ourselves with regard to the immune response induced by T. crassiceps and its antigens, and we compare the advances in our understanding of this parasitic infection model with the knowledge that has been obtained from other selected models.
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Investigation of Cellular Interactions of Nanoparticles by Helium Ion Microscopy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Arey, Bruce W.; Shutthanandan, V.; Xie, Yumei
The helium ion mircroscope (HIM) probes light elements (e.g. C, N, O, P) with high contrast due to the large variation in secondary electron yield, which minimizes the necessity of specimen staining. A defining characteristic of HIM is its remarkable capability to neutralize charge by the implementation of an electron flood gun, which eliminates the need for coating non-conductive specimens for imaging at high resolution. In addition, the small convergence angle in HeIM offers a large depth of field (~5x FE-SEM), enabling tall structures to be viewed in focus within a single image. Taking advantage of these capabilities, we investigatemore » the interactions of engineered nanoparticles (NPs) at the surface of alveolar type II epithelial cells grown at the air-liquid interface (ALI). The increasing use of nanomaterials in a wide range of commercial applications has the potential to increase human exposure to these materials, but the impact of such exposure on human health is still unclear. One of the main routs of exposure is the respiratory tract, where alveolar epithelial cells present a vulnerable target at the interface with ambient air. Since the cellular interactions of NPs govern the cellular response and ultimately determine the impact on human health, our studies will help delineating relationships between particle properties and cellular interactions and response to better evaluate NP toxicity or biocompatibility. The Rutherford backscattered ion (RBI) is a helium ions imaging mode, which backscatters helium ions from every element except hydrogen, with a backscatter yield that depends on the atomic number of the target. Energy-sensitive backscatter analysis is being developed, which when combined with RBI image information, supports elemental identification at helium ion nanometer resolution. This capability will enable distinguishing NPs from cell surface structures with nanometer resolution.« less
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Investigation of cellular interactions of nanoparticles by helium ion microscopy
NASA Astrophysics Data System (ADS)
Arey, B. W.; Shutthanandan, V.; Xie, Y.; Tolic, A.; Williams, N.; Orr, G.
2011-06-01
The helium ion microscope (HIM) probes light elements (e.g. C, N, O, P) with high contrast due to the large variation in secondary electron yield, which minimizes the necessity of specimen staining. A defining characteristic of HIM is its remarkable capability to neutralize charge by the implementation of an electron flood gun, which eliminates the need for coating non-conductive specimens for imaging at high resolution. In addition, the small convergence angle in HeIM offers a large depth of field (~5× FE-SEM), enabling tall structures to be viewed in focus within a single image. Taking advantage of these capabilities, we investigate the interactions of engineered nanoparticles (NPs) at the surface of alveolar type II epithelial cells grown at the airliquid interface (ALI). The increasing use of nanomaterials in a wide range of commercial applications has the potential to increase human exposure to these materials, but the impact of such exposure on human health is still unclear. One of the main routs of exposure is the respiratory tract, where alveolar epithelial cells present a vulnerable target at the interface with ambient air. Since the cellular interactions of NPs govern the cellular response and ultimately determine the impact on human health, our studies will help delineating relationships between particle properties and cellular interactions and response to better evaluate NP toxicity or biocompatibility. The Rutherford backscattered ion (RBI) is a helium ions imaging mode, which backscatters helium ions from every element except hydrogen, with a backscatter yield that depends on the atomic number of the target. Energy-sensitive backscatter analysis is being developed, which when combined with RBI image information, supports elemental identification at helium ion nanometer resolution. This capability will enable distinguishing NPs from cell surface structures with nanometer resolution.
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Heckman, James J.; Corbin, Chase O.
2016-01-01
This paper discusses the relevance of recent research on the economics of human development to the work of the Human Development and Capability Association. The recent economics of human development brings insights about the dynamics of skill accumulation to an otherwise static literature on capabilities. Skills embodied in agents empower people. Enhanced skills enhance opportunities and hence promote capabilities. We address measurement problems common to both the economics of human development and the capability approach. The economics of human development analyzes the dynamics of preference formation, but is silent about which preferences should be used to evaluate alternative policies. This is both a strength and a limitation of the approach. PMID:28261378
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Discrimination of human and dog faces and inversion responses in domestic dogs (Canis familiaris).
Racca, Anaïs; Amadei, Eleonora; Ligout, Séverine; Guo, Kun; Meints, Kerstin; Mills, Daniel
2010-05-01
Although domestic dogs can respond to many facial cues displayed by other dogs and humans, it remains unclear whether they can differentiate individual dogs or humans based on facial cues alone and, if so, whether they would demonstrate the face inversion effect, a behavioural hallmark commonly used in primates to differentiate face processing from object processing. In this study, we first established the applicability of the visual paired comparison (VPC or preferential looking) procedure for dogs using a simple object discrimination task with 2D pictures. The animals demonstrated a clear looking preference for novel objects when simultaneously presented with prior-exposed familiar objects. We then adopted this VPC procedure to assess their face discrimination and inversion responses. Dogs showed a deviation from random behaviour, indicating discrimination capability when inspecting upright dog faces, human faces and object images; but the pattern of viewing preference was dependent upon image category. They directed longer viewing time at novel (vs. familiar) human faces and objects, but not at dog faces, instead, a longer viewing time at familiar (vs. novel) dog faces was observed. No significant looking preference was detected for inverted images regardless of image category. Our results indicate that domestic dogs can use facial cues alone to differentiate individual dogs and humans and that they exhibit a non-specific inversion response. In addition, the discrimination response by dogs of human and dog faces appears to differ with the type of face involved.
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NASA Astrophysics Data System (ADS)
Dobrev, Ivo; Furlong, Cosme; Cheng, Jeffrey T.; Rosowski, John J.
2014-09-01
Understanding the human hearing process would be helped by quantification of the transient mechanical response of the human ear, including the human tympanic membrane (TM or eardrum). We propose a new hybrid high-speed holographic system (HHS) for acquisition and quantification of the full-field nanometer transient (i.e., >10 kHz) displacement of the human TM. We have optimized and implemented a 2+1 frame local correlation (LC) based phase sampling method in combination with a high-speed (i.e., >40 K fps) camera acquisition system. To our knowledge, there is currently no existing system that provides such capabilities for the study of the human TM. The LC sampling method has a displacement difference of <11 nm relative to measurements obtained by a four-phase step algorithm. Comparisons between our high-speed acquisition system and a laser Doppler vibrometer indicate differences of <10 μs. The high temporal (i.e., >40 kHz) and spatial (i.e., >100 k data points) resolution of our HHS enables parallel measurements of all points on the surface of the TM, which allows quantification of spatially dependent motion parameters, such as modal frequencies and acoustic delays. Such capabilities could allow inferring local material properties across the surface of the TM.
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Human Vascular Microphysiological System for in vitro Drug Screening.
Fernandez, C E; Yen, R W; Perez, S M; Bedell, H W; Povsic, T J; Reichert, W M; Truskey, G A
2016-02-18
In vitro human tissue engineered human blood vessels (TEBV) that exhibit vasoactivity can be used to test human toxicity of pharmaceutical drug candidates prior to pre-clinical animal studies. TEBVs with 400-800 μM diameters were made by embedding human neonatal dermal fibroblasts or human bone marrow-derived mesenchymal stem cells in dense collagen gel. TEBVs were mechanically strong enough to allow endothelialization and perfusion at physiological shear stresses within 3 hours after fabrication. After 1 week of perfusion, TEBVs exhibited endothelial release of nitric oxide, phenylephrine-induced vasoconstriction, and acetylcholine-induced vasodilation, all of which were maintained up to 5 weeks in culture. Vasodilation was blocked with the addition of the nitric oxide synthase inhibitor L-N(G)-Nitroarginine methyl ester (L-NAME). TEBVs elicited reversible activation to acute inflammatory stimulation by TNF-α which had a transient effect upon acetylcholine-induced relaxation, and exhibited dose-dependent vasodilation in response to caffeine and theophylline. Treatment of TEBVs with 1 μM lovastatin for three days prior to addition of Tumor necrosis factor - α (TNF-α) blocked the injury response and maintained vasodilation. These results indicate the potential to develop a rapidly-producible, endothelialized TEBV for microphysiological systems capable of producing physiological responses to both pharmaceutical and immunological stimuli.
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Langerhans Cells and Their Role in Oral Mucosal Diseases
Upadhyay, Juhi; Upadhyay, Ram B; Agrawal, Pankaj; Jaitley, Shweta; Shekhar, Rhitu
2013-01-01
Dendritic cells are arguably the most potent antigen-presenting cells and may be the only cells capable of initiating the adaptive immune response. The epithelial residents of dendritic cells are Langerhans cells, which serve as the “sentinels” of the mucosa, altering the immune system not only to pathogen entry but also of tolerance to self antigen and commensal microbes. Oral mucosal Langerhans cells are capable of engaging and internalizing a wide variety of pathogens and have been found responsive to nickel in patients with nickel allergies, oral Candida species, oral lichen planus, lichenoid drug eruptions, graft versus host diseases, periodontal diseases median rhomboid glossitis, human immunodeficiency virus infection, hairy leukoplakia of the tongue, and oral squamous cell carcinoma. Review focuses on the role of antigen-presenting cells in particular Langerhans cells to better understand the mechanisms underlying immune responses. In this review, comprehensive detail about mucosal diseases has been compiled using the PubMed database and through textbooks. PMID:24251267
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NASA Astrophysics Data System (ADS)
Chang, Ying; Li, Yang; Yu, Shirong; Mao, Jie; Liu, Cheng; Li, Qi; Yuan, Conghui; He, Ning; Luo, Weiang; Dai, Lizong
2015-01-01
Polymer assemblies with good biocompatibility, stimuli-responsive properties and clinical imaging capability are desirable carriers for future biomedical applications. Herein, we report on the synthesis of a novel anthracenecarboxaldehyde-decorated poly(N-(4-aminophenyl) methacryl amide-oligoethyleneglycolmonomethylether methacrylate) (P(MAAPAC-MAAP-MAPEG)) copolymer, comprising fluorescent chromophore and acid-labile moiety. This copolymer can assemble into micelles in aqueous solution and shows a spherical shape with well-defined particle size and narrow particle size distribution. The pH-responsive property of the micelles has been evaluated by the change of particle size and the controlled release of guest molecules. The intrinsic fluorescence property endows the micelles with excellent cell/tissue imaging capability. Cell viability evaluation with human hepatocellular carcinoma BEL-7402 cells demonstrates that the micelles are nontoxic. The cellular uptake of the micelles indicates a time-dependent behavior. The H22-tumor bearing mice treated with the micelles clearly exhibits the tumor accumulation. These multi-functional nanocarriers may be of great interest in the application of drug delivery.
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Lorgelly, Paula K; Lorimer, Karen; Fenwick, Elisabeth A L; Briggs, Andrew H; Anand, Paul
2015-10-01
There is growing interest in operationalising the capability approach to measure quality of life. This paper reports the results of a research project undertaken in 2007 that sought to reduce and refine a longer survey in order to provide a summary measure of wellbeing and capability in the realm of public health. The reduction and refinement of the questionnaire took place across a number of stages, using both qualitative (five focus group discussions and 17 in-depth interviews) and quantitative (secondary data analysis, N = 1048 and primary data collection using postal surveys and interviews, N = 45) approaches. The questionnaire was reduced from its original 60+ questions to 24 questions (including demographic questions). Each of Nussbaum's ten Central Human Capabilities are measured using one (or more) of the 18 specific capability items which are included in the questionnaire (referred to as the OCAP-18). Analysis of the questionnaire responses (N = 198) found that respondents differed with respect to the levels of capabilities they reported, and that these capabilities appear to be sensitive to one's gender, age, income and deprivation decile. An index of capability, estimated by assuming equal weight for each capability question, found that the average level of capability amongst respondents was 12.44 (range 3-17.75). This index was found to be highly correlated with a measure of health (EQ-5D) and wellbeing (global QoL), although some differences were apparent. This project operationalised the capability approach to produce an instrument to measure the effectiveness (and cost effectiveness) of public health interventions; the resulting OCAP-18 appears to be responsive and measure something supplementary to health and wellbeing, thus offers a promising addition to the current suite of outcome measures that are available. Copyright © 2015 Elsevier Ltd. All rights reserved.
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HIV-1 Tat-based vaccines: from basic science to clinical trials.
Fanales-Belasio, Emanuele; Cafaro, Aurelio; Cara, Andrea; Negri, Donatella R M; Fiorelli, Valeria; Butto, Stefano; Moretti, Sonia; Maggiorella, Maria Teresa; Baroncelli, Silvia; Michelini, Zuleika; Tripiciano, Antonella; Sernicola, Leonardo; Scoglio, Arianna; Borsetti, Alessandra; Ridolfi, Barbara; Bona, Roberta; Ten Haaft, Peter; Macchia, Iole; Leone, Pasqualina; Pavone-Cossut, Maria Rosaria; Nappi, Filomena; Vardas, Eftyhia; Magnani, Mauro; Laguardia, Elena; Caputo, Antonella; Titti, Fausto; Ensoli, Barbara
2002-09-01
Vaccination against human immunodeficiency virus (HIV)-1 infection requires candidate antigen(s) (Ag) capable of inducing an effective, broad, and long-lasting immune response against HIV-1 despite mutation events leading to differences in virus clades. The HIV-1 Tat protein is more conserved than envelope proteins, is essential in the virus life cycle and is expressed very early upon virus entry. In addition, both humoral and cellular responses to Tat have been reported to correlate with a delayed progression to disease in both humans and monkeys. This suggested that Tat is an optimal target for vaccine development aimed at controlling virus replication and blocking disease onset. Here are reviewed the results of our studies including the effects of the Tat protein on monocyte-derived dendritic cells (MDDCs) that are key antigen-presenting cells (APCs), and the results from vaccination trials with both the Tat protein or tat DNA in monkeys. We provide evidence that the HIV-1 Tat protein is very efficiently taken up by MDDCs and promotes T helper (Th)-1 type immune responses against itself as well as other Ag. In addition, a Tat-based vaccine elicits an immune response capable of controlling primary infection of monkeys with the pathogenic SHIV89.6P at its early stages allowing the containment of virus spread. Based on these results and on data of Tat conservation and immune cross-recognition in field isolates from different clades, phase I clinical trials are being initiated in Italy for both preventive and therapeutic vaccination.
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Orach, Christopher Garimol; Mayega, Roy William; Woboya, Vincent; William, Bazeyo
2013-06-01
Uganda is vulnerable to several natural, man-made and a hybrid of disasters including drought, famine, floods, warfare, and disease outbreaks. We assessed the district disaster team's performance, roles and experiences following the training. The disasters most commonly experienced by the district teams were epidemics of diseases in humans (7 of 12), animals (epizoonotics) (3 of 12) and crops (3 of 12); hailstorms and floods (3 of 12). The capabilities viewed most useful for management of disasters were provision of health care services (9/12) and response management (8 of 12). The capability domains most often consulted during the disasters were general response management (31%), health services (29%) and water and sanitation (17%). The skills areas perceived to be vital following the training were response to epidemics 10/12, disaster management planning 8/12, hazards and vulnerability analysis 7/12 and principles of disaster planning 7/12 respectively. Main challenges mentioned by district teams were inadequacy of finance and logistics, lack of commitment by key partners towards disaster preparedness and response. The most common disaster experienced disasters related to outbreaks of diseases in man, animals and crops. The most frequently applied capabilities were response management and provision of emergency health services. The activities most frequently implemented following disaster management teams training were conducting planning meetings, refinement of plans and dissemination of skills gained. The main challenges were related to limited budget allocations and legal frameworks for disaster management that should be addressed by both central and local governments.
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Ancient typhoid epidemic reveals possible ancestral strain of Salmonella enterica serovar Typhi.
Papagrigorakis, Manolis J; Synodinos, Philippos N; Yapijakis, Christos
2007-01-01
In contrast to other serotypes of Salmonella enterica, S. Typhi is exclusively adapted to human hosts. Recently, S. Typhi was identified in ancient skeletal material, thereby incriminating typhoid fever for the Plague of Athens. Since, according to Thucydides' report, animals were also affected by the disease, a working hypothesis is constituted that the causative agent of the Plague might be the anticipated original strain of S. Typhi, purportedly capable of infecting animals as well as humans. Possible future sequencing of the discovered ancient strain of S. Typhi may help towards identifying its genomic differences responsible for its modern specification to humans.
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NASA Technical Reports Server (NTRS)
Mitchell, Christine M.
1990-01-01
The design, implementation, and empirical evaluation of task-analytic models and intelligent aids for operators in the control of complex dynamic systems, specifically aerospace systems, are studied. Three related activities are included: (1) the models of operator decision making in complex and predominantly automated space systems were used and developed; (2) the Operator Function Model (OFM) was used to represent operator activities; and (3) Operator Function Model Expert System (OFMspert), a stand-alone knowledge-based system was developed, that interacts with a human operator in a manner similar to a human assistant in the control of aerospace systems. OFMspert is an architecture for an operator's assistant that uses the OFM as its system and operator knowledge base and a blackboard paradigm of problem solving to dynamically generate expectations about upcoming operator activities and interpreting actual operator actions. An experiment validated the OFMspert's intent inferencing capability and showed that it inferred the intentions of operators in ways comparable to both a human expert and operators themselves. OFMspert was also augmented with control capabilities. An interface allowed the operator to interact with OFMspert, delegating as much or as little control responsibility as the operator chose. With its design based on the OFM, OFMspert's control capabilities were available at multiple levels of abstraction and allowed the operator a great deal of discretion over the amount and level of delegated control. An experiment showed that overall system performance was comparable for teams consisting of two human operators versus a human operator and OFMspert team.
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Simulation of wave propagation inside a human eye: acoustic eye model (AEM)
NASA Astrophysics Data System (ADS)
Požar, T.; Halilovič, M.; Horvat, D.; Petkovšek, R.
2018-02-01
The design and development of the acoustic eye model (AEM) is reported. The model consists of a computer-based simulation that describes the propagation of mechanical disturbance inside a simplified model of a human eye. The capabilities of the model are illustrated with examples, using different laser-induced initial loading conditions in different geometrical configurations typically occurring in ophthalmic medical procedures. The potential of the AEM is to predict the mechanical response of the treated eye tissue in advance, thus complementing other preliminary procedures preceding medical treatments.
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Li, Yan; Wang, Guo-Dong; Wang, Ming-Shan; Irwin, David M; Wu, Dong-Dong; Zhang, Ya-Ping
2014-11-05
Dogs shared a much closer relationship with humans than any other domesticated animals, probably due to their unique social cognitive capabilities, which were hypothesized to be a by-product of selection for tameness toward humans. Here, we demonstrate that genes involved in glutamate metabolism, which account partially for fear response, indeed show the greatest population differentiation by whole-genome comparison of dogs and wolves. However, the changing direction of their expression supports a role in increasing excitatory synaptic plasticity in dogs rather than reducing fear response. Because synaptic plasticity are widely believed to be cellular correlates of learning and memory, this change may alter the learning and memory abilities of ancient scavenging wolves, weaken the fear reaction toward humans, and prompt the initial interspecific contact. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
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Amartya Sen's Capability Approach and Education
ERIC Educational Resources Information Center
Walker, Melanie
2005-01-01
The human capabilities approach developed by the economist Amartya Sen links development, quality of life and freedom. This article explores the key ideas in the capability approach of: capability, functioning, agency, human diversity and public participation in generating valued capabilities. It then considers how these ideas relate specifically…
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The role of beliefs in lexical alignment: evidence from dialogs with humans and computers.
Branigan, Holly P; Pickering, Martin J; Pearson, Jamie; McLean, Janet F; Brown, Ash
2011-10-01
Five experiments examined the extent to which speakers' alignment (i.e., convergence) on words in dialog is mediated by beliefs about their interlocutor. To do this, we told participants that they were interacting with another person or a computer in a task in which they alternated between selecting pictures that matched their 'partner's' descriptions and naming pictures themselves (though in reality all responses were scripted). In both text- and speech-based dialog, participants tended to repeat their partner's choice of referring expression. However, they showed a stronger tendency to align with 'computer' than with 'human' partners, and with computers that were presented as less capable than with computers that were presented as more capable. The tendency to align therefore appears to be mediated by beliefs, with the relevant beliefs relating to an interlocutor's perceived communicative capacity. Copyright © 2011 Elsevier B.V. All rights reserved.
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Asteroid Redirect Mission - Next Major stepping-stone to Human Exploration of NEOs and beyond
NASA Astrophysics Data System (ADS)
Sanchez, Natalia
2016-07-01
In response to NASA's Asteroid Initiative, an Asteroid Redirect and Robotic Mission (ARRM) is being studied by a NASA cohort, led by JPL, to enable the capture a multi-ton boulder from the surface of a Near-Earth Asteroid and return it to cislunar space for subsequent human and robotic exploration. The mission would boost our understanding of NEOs and develop technological capabilities for Planetary Defense, shall a NEO come up on a collision course. The benefits of this mission can extend our capabilities to explore farther into space, as well as create a new commercial sector in Space Mining, which would make materials in Space available for our use. ARRM would leverage and advance current knowledge of higher-efficiency propulsion systems with a new Solar Electric Propulsion demonstration (similar to that on the Dawn spacecraft) to be incorporated into future Mars Missions.
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Host response to Staphylococcus aureus cytotoxins in children with cystic fibrosis.
Chadha, Ashley D; Thomsen, Isaac P; Jimenez-Truque, Natalia; Soper, Nicole R; Jones, Lauren S; Sokolow, Andrew G; Torres, Victor J; Creech, C Buddy
2016-09-01
Staphylococcus aureus is one of the earliest bacterial pathogens to colonize the lungs of children with cystic fibrosis and is an important contributor to pulmonary exacerbations. The adaptive host response to S. aureus in cystic fibrosis remains inadequately defined and has important implications for pathogenesis and potential interventions. The objectives of this study were to determine the functional antibody response to select staphylococcal exotoxins (LukAB, alpha-hemolysin, and PVL) in children with cystic fibrosis and to evaluate the relationship of this response with pulmonary exacerbations. Fifty children with cystic fibrosis were enrolled and followed prospectively for 12months. Clinical characteristics and serologic profiles were assessed at routine visits and during pulmonary exacerbations, and functional antibody assessments were performed to measure neutralization of LukAB-mediated cytotoxicity. For each antigen, geometric mean titers were significantly higher if S. aureus was detected at the time of exacerbation. For LukAB, geometric mean titers were significantly higher at exacerbation follow-up compared to titers during the exacerbation, consistent with expression during human disease, and the humoral response capably neutralized LukAB-mediated cytotoxicity. Moreover, the presence of a positive S. aureus culture during a pulmonary exacerbation was associated with 31-fold higher odds of having a LukA titer ≥1:160, suggesting potential diagnostic capability of this assay. The leukotoxin LukAB is expressed by S. aureus and recognized by the human adaptive immune response in the setting of pulmonary infection in cystic fibrosis. Anti-LukAB antibodies were not only predictive of positive staphylococcal culture during exacerbation, but also functional in the neutralization of this toxin. Copyright © 2016 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.
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Cellular Sites of Immunologic Unresponsiveness*
Chiller, Jacques M.; Habicht, Gail S.; Weigle, William O.
1970-01-01
The reconstitution of the immune response of lethally irradiated mice to human γ-globulin is dependent on the synergistic action of bone marrow with thymus cells. Immunologic unresponsiveness appears to involve a functional defect at each of these cellular levels, inasmuch as neither bone marrow nor thymus cells from unresponsive donors are capable of demonstrating synergism in combination with their normal counterpart. PMID:4192271
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The human adrenocortical carcinoma cell line H295R is being used as an in vitro steroidogenesis screening assay to assess the impact of endocrine active chemicals (EACs) capable of altering steroid biosynthesis. To enhance the interpretation and quantitative application of measur...
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Fault Management Techniques in Human Spaceflight Operations
NASA Technical Reports Server (NTRS)
O'Hagan, Brian; Crocker, Alan
2006-01-01
This paper discusses human spaceflight fault management operations. Fault detection and response capabilities available in current US human spaceflight programs Space Shuttle and International Space Station are described while emphasizing system design impacts on operational techniques and constraints. Preflight and inflight processes along with products used to anticipate, mitigate and respond to failures are introduced. Examples of operational products used to support failure responses are presented. Possible improvements in the state of the art, as well as prioritization and success criteria for their implementation are proposed. This paper describes how the architecture of a command and control system impacts operations in areas such as the required fault response times, automated vs. manual fault responses, use of workarounds, etc. The architecture includes the use of redundancy at the system and software function level, software capabilities, use of intelligent or autonomous systems, number and severity of software defects, etc. This in turn drives which Caution and Warning (C&W) events should be annunciated, C&W event classification, operator display designs, crew training, flight control team training, and procedure development. Other factors impacting operations are the complexity of a system, skills needed to understand and operate a system, and the use of commonality vs. optimized solutions for software and responses. Fault detection, annunciation, safing responses, and recovery capabilities are explored using real examples to uncover underlying philosophies and constraints. These factors directly impact operations in that the crew and flight control team need to understand what happened, why it happened, what the system is doing, and what, if any, corrective actions they need to perform. If a fault results in multiple C&W events, or if several faults occur simultaneously, the root cause(s) of the fault(s), as well as their vehicle-wide impacts, must be determined in order to maintain situational awareness. This allows both automated and manual recovery operations to focus on the real cause of the fault(s). An appropriate balance must be struck between correcting the root cause failure and addressing the impacts of that fault on other vehicle components. Lastly, this paper presents a strategy for using lessons learned to improve the software, displays, and procedures in addition to determining what is a candidate for automation. Enabling technologies and techniques are identified to promote system evolution from one that requires manual fault responses to one that uses automation and autonomy where they are most effective. These considerations include the value in correcting software defects in a timely manner, automation of repetitive tasks, making time critical responses autonomous, etc. The paper recommends the appropriate use of intelligent systems to determine the root causes of faults and correctly identify separate unrelated faults.
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Dobrev, I.; Furlong, C.; Cheng, J. T.; Rosowski, J. J.
2014-01-01
In this paper, we propose a multi-pulsed double exposure (MPDE) acquisition method to quantify in full-field-of-view the transient (i.e., >10 kHz) acoustically induced nanometer scale displacements of the human tympanic membrane (TM or eardrum). The method takes advantage of the geometrical linearity and repeatability of the TM displacements to enable high-speed measurements with a conventional camera (i.e., <20 fps). The MPDE is implemented on a previously developed digital holographic system (DHS) to enhance its measurement capabilities, at a minimum cost, while avoiding constraints imposed by the spatial resolutions and dimensions of high-speed (i.e., >50 kfps) cameras. To our knowledge, there is currently no existing system to provide such capabilities for the study of the human TM. The combination of high temporal (i.e., >50 kHz) and spatial (i.e., >500k data points) resolutions enables measurements of the temporal and frequency response of all points across the surface of the TM simultaneously. The repeatability and accuracy of the MPDE method are verified against a Laser Doppler Vibrometer (LDV) on both artificial membranes and ex-vivo human TMs that are acoustically excited with a sharp (i.e., <100 μs duration) click. The measuring capabilities of the DHS, enhanced by the MPDE acquisition method, allow for quantification of spatially dependent motion parameters of the TM, such as modal frequencies, time constants, as well as inferring local material properties. PMID:25780271
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A polyvalent inactivated rhinovirus vaccine is broadly immunogenic in rhesus macaques
Lee, Sujin; Nguyen, Minh Trang; Currier, Michael G.; Jenkins, Joe B.; Strobert, Elizabeth A.; Kajon, Adriana E.; Madan-Lala, Ranjna; Bochkov, Yury A.; Gern, James E.; Roy, Krishnendu; Lu, Xiaoyan; Erdman, Dean D.; Spearman, Paul; Moore, Martin L.
2016-01-01
As the predominant aetiological agent of the common cold, human rhinovirus (HRV) is the leading cause of human infectious disease. Early studies showed that a monovalent formalin-inactivated HRV vaccine can be protective, and virus-neutralizing antibodies (nAb) correlated with protection. However, co-circulation of many HRV types discouraged further vaccine efforts. Here, we test the hypothesis that increasing virus input titres in polyvalent inactivated HRV vaccine may result in broad nAb responses. We show that serum nAb against many rhinovirus types can be induced by polyvalent, inactivated HRVs plus alhydrogel (alum) adjuvant. Using formulations up to 25-valent in mice and 50-valent in rhesus macaques, HRV vaccine immunogenicity was related to sufficient quantity of input antigens, and valency was not a major factor for potency or breadth of the response. Thus, we have generated a vaccine capable of inducing nAb responses to numerous and diverse HRV types. PMID:27653379
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Organic light emitting board for dynamic interactive display
Kim, Eui Hyuk; Cho, Sung Hwan; Lee, Ju Han; Jeong, Beomjin; Kim, Richard Hahnkee; Yu, Seunggun; Lee, Tae-Woo; Shim, Wooyoung; Park, Cheolmin
2017-01-01
Interactive displays involve the interfacing of a stimuli-responsive sensor with a visual human-readable response. Here, we describe a polymeric electroluminescence-based stimuli-responsive display method that simultaneously detects external stimuli and visualizes the stimulant object. This organic light-emitting board is capable of both sensing and direct visualization of a variety of conductive information. Simultaneous sensing and visualization of the conductive substance is achieved when the conductive object is coupled with the light emissive material layer on application of alternating current. A variety of conductive materials can be detected regardless of their work functions, and thus information written by a conductive pen is clearly visualized, as is a human fingerprint with natural conductivity. Furthermore, we demonstrate that integration of the organic light-emitting board with a fluidic channel readily allows for dynamic monitoring of metallic liquid flow through the channel, which may be suitable for biological detection and imaging applications. PMID:28406151
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Organic light emitting board for dynamic interactive display
NASA Astrophysics Data System (ADS)
Kim, Eui Hyuk; Cho, Sung Hwan; Lee, Ju Han; Jeong, Beomjin; Kim, Richard Hahnkee; Yu, Seunggun; Lee, Tae-Woo; Shim, Wooyoung; Park, Cheolmin
2017-04-01
Interactive displays involve the interfacing of a stimuli-responsive sensor with a visual human-readable response. Here, we describe a polymeric electroluminescence-based stimuli-responsive display method that simultaneously detects external stimuli and visualizes the stimulant object. This organic light-emitting board is capable of both sensing and direct visualization of a variety of conductive information. Simultaneous sensing and visualization of the conductive substance is achieved when the conductive object is coupled with the light emissive material layer on application of alternating current. A variety of conductive materials can be detected regardless of their work functions, and thus information written by a conductive pen is clearly visualized, as is a human fingerprint with natural conductivity. Furthermore, we demonstrate that integration of the organic light-emitting board with a fluidic channel readily allows for dynamic monitoring of metallic liquid flow through the channel, which may be suitable for biological detection and imaging applications.
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CD1a presentation of endogenous antigens by group 2 innate lymphoid cells.
Hardman, Clare S; Chen, Yi-Ling; Salimi, Maryam; Jarrett, Rachael; Johnson, David; Järvinen, Valtteri J; Owens, Raymond J; Repapi, Emmanouela; Cousins, David J; Barlow, Jillian L; McKenzie, Andrew N J; Ogg, Graham
2017-12-22
Group 2 innate lymphoid cells (ILC2) are effectors of barrier immunity, with roles in infection, wound healing, and allergy. A proportion of ILC2 express MHCII (major histocompatibility complex II) and are capable of presenting peptide antigens to T cells and amplifying the subsequent adaptive immune response. Recent studies have highlighted the importance of CD1a-reactive T cells in allergy and infection, activated by the presentation of endogenous neolipid antigens and bacterial components. Using a human skin challenge model, we unexpectedly show that human skin-derived ILC2 can express CD1a and are capable of presenting endogenous antigens to T cells. CD1a expression is up-regulated by TSLP (thymic stromal lymphopoietin) at levels observed in the skin of patients with atopic dermatitis, and the response is dependent on PLA2G4A. Furthermore, this pathway is used to sense Staphylococcus aureus by promoting Toll-like receptor-dependent CD1a-reactive T cell responses to endogenous ligands. These findings define a previously unrecognized role for ILC2 in lipid surveillance and identify shared pathways of CD1a- and PLA2G4A-dependent ILC2 inflammation amenable to therapeutic intervention. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Paris, Juan L; de la Torre, Paz; Victoria Cabañas, M; Manzano, Miguel; Grau, Montserrat; Flores, Ana I; Vallet-Regí, María
2017-05-04
A new platform constituted by engineered responsive nanoparticles transported by human mesenchymal stem cells is here presented as a proof of concept. Ultrasound-responsive mesoporous silica nanoparticles are coated with polyethylenimine to favor their effective uptake by decidua-derived mesenchymal stem cells. The responsive-release ability of the designed nanoparticles is confirmed, both in vial and in vivo. In addition, this capability is maintained inside the cells used as carriers. The migration capacity of the nanoparticle-cell platform towards mammary tumors is assessed in vitro. The efficacy of this platform for anticancer therapy is shown against mammary tumor cells by inducing the release of doxorubicin only when the cell vehicles are exposed to ultrasound.
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Natural mutagenesis of human genomes by endogenous retrotransposons.
Iskow, Rebecca C; McCabe, Michael T; Mills, Ryan E; Torene, Spencer; Pittard, W Stephen; Neuwald, Andrew F; Van Meir, Erwin G; Vertino, Paula M; Devine, Scott E
2010-06-25
Two abundant classes of mobile elements, namely Alu and L1 elements, continue to generate new retrotransposon insertions in human genomes. Estimates suggest that these elements have generated millions of new germline insertions in individual human genomes worldwide. Unfortunately, current technologies are not capable of detecting most of these young insertions, and the true extent of germline mutagenesis by endogenous human retrotransposons has been difficult to examine. Here, we describe technologies for detecting these young retrotransposon insertions and demonstrate that such insertions indeed are abundant in human populations. We also found that new somatic L1 insertions occur at high frequencies in human lung cancer genomes. Genome-wide analysis suggests that altered DNA methylation may be responsible for the high levels of L1 mobilization observed in these tumors. Our data indicate that transposon-mediated mutagenesis is extensive in human genomes and is likely to have a major impact on human biology and diseases.
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Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology.
Enright, Heather A; Malfatti, Michael A; Zimmermann, Maike; Ognibene, Ted; Henderson, Paul; Turteltaub, Kenneth W
2016-12-19
Accelerator mass spectrometry (AMS) has been adopted as a powerful bioanalytical method for human studies in the areas of pharmacology and toxicology. The exquisite sensitivity (10 -18 mol) of AMS has facilitated studies of toxins and drugs at environmentally and physiologically relevant concentrations in humans. Such studies include risk assessment of environmental toxicants, drug candidate selection, absolute bioavailability determination, and more recently, assessment of drug-target binding as a biomarker of response to chemotherapy. Combining AMS with complementary capabilities such as high performance liquid chromatography (HPLC) can maximize data within a single experiment and provide additional insight when assessing drugs and toxins, such as metabolic profiling. Recent advances in the AMS technology at Lawrence Livermore National Laboratory have allowed for direct coupling of AMS with complementary capabilities such as HPLC via a liquid sample moving wire interface, offering greater sensitivity compared to that of graphite-based analysis, therefore enabling the use of lower 14 C and chemical doses, which are imperative for clinical testing. The aim of this review is to highlight the recent efforts in human studies using AMS, including technological advancements and discussion of the continued promise of AMS for innovative clinical based research.
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Global justice, capabilities approach and commercial surrogacy in India.
Saravanan, Sheela
2015-08-01
Inequalities, ineffective governance, unclear surrogacy regulations and unethical practices make India an ideal environment for global injustice in the process of commercial surrogacy. This article aims to apply the 'capabilities approach' to find possibilities of global justice through human fellowship in the context of commercial surrogacy. I draw primarily on my research findings supplemented by other relevant empirical research and documentary films on surrogacy. The paper reveals inequalities and inadequate basic entitlements among surrogate mothers as a consequence of which they are engaged in unjust contracts. Their limited entitlements also limit their opportunities to engage in enriching goals. It is the role of the state to provide all its citizens with basic entitlements and protect their basic human rights. Individuals in India evading their basic duty also contribute to the existing inequalities. Individual responsibilities of the medical practitioners and the intended parents are in question here as they are more inclined towards self-interest rather than commitment towards human fellowship. At the global level, the injustice in transnational commercial surrogacy practices in developing countries calls for an international declaration of women and child rights in third party reproduction with a normative vision of mutual fellowship and human dignity.
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The Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology
Enright, Heather A.; Malfatti, Michael A.; Zimmermann, Maike; Ognibene, Ted; Henderson, Paul; Turteltaub, Kenneth W.
2016-01-01
Accelerator Mass Spectrometry (AMS) has been adopted as a powerful bio-analytical method for human studies in the areas of pharmacology and toxicology. The exquisite sensitivity (10−18 mol) of AMS has facilitated studies of toxins and drugs at environmentally and physiologically relevant concentrations in humans. Such studies include: risk assessment of environmental toxicants, drug candidate selection, absolute bioavailability determination, and more recently, assessment of drug-target binding as a biomarker of response to chemotherapy. Combining AMS with complementary capabilities such as high performance liquid chromatography (HPLC) can maximize data within a single experiment and provide additional insight when assessing drugs and toxins, such as metabolic profiling. Recent advances in the AMS technology at Lawrence Livermore National Laboratory have allowed for direct coupling of AMS with complementary capabilities such as HPLC via a liquid sample moving wire interface, offering greater sensitivity compared to graphite-based analysis therefore, enabling the use of lower 14C and chemical doses, which are imperative for clinical testing. The aim of this review is to highlight the recent efforts in human studies using AMS, including technological advancements and discussion of the continued promise of AMS for innovative clinical based research. PMID:27726383
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NASA Technical Reports Server (NTRS)
Clarke, M. S.; Feeback, D. L.
1996-01-01
The transduction mechanism (or mechanisms) responsible for converting a mechanical load into a skeletal muscle growth response are unclear. In this study we have used a mechanically active tissue culture model of differentiated human skeletal muscle cells to investigate the relationship between mechanical load, sarcolemma wounding, fibroblast growth factor release, and skeletal muscle cell growth. Using the Flexcell Strain Unit we demonstrate that as mechanical load increases, so too does the amount of sarcolemma wounding. A similar relationship was also observed between the level of mechanical load inflicted on the cells and the amount of bFGF (FGF2) released into the surrounding medium. In addition, we demonstrate that the muscle cell growth response induced by chronic mechanical loading in culture can be inhibited by the presence of an antibody capable of neutralizing the biological activity of FGF. This study provides direct evidence that mechanically induced, sarcolemma wound-mediated FGF release is an important autocrine mechanism for transducing the stimulus of mechanical load into a skeletal muscle growth response.
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NASA Technical Reports Server (NTRS)
Sanders, Gerald B.
2000-01-01
In a letter to the NASA Administrator, Dan Goldin, in January of 1999, the Office of Management and Budget (OMB) stated the following . OMB recommends that NASA consider commercialization in a broader context than the more focused efforts to date on space station and space shuttle commercialization. We suggest that NASA examine architectures that take advantage of a potentially robust future commercial infrastructure that could dramatically lower the cost of future human exploration." In response to this letter, the NASA Human Exploration and Development of Space (HEDS) Enterprise launched the BEDS Technology & Commercialization Initiative (HTCI) to link technology and system development for human exploration with the commercial development of space to emphasize the "D" (Development) in BEDS. The development of technologies and capabilities to utilize space resources is the first of six primary focus areas in this program. It is clear that Space Resources Development (SRD) is key for both long-term human exploration of our solar system and to the long-term commercialization of space since: a) it provides the technologies, products, and raw materials to support efficient space transportation and in-space construction and manufacturing, and b) it provides the capabilities and infrastructure to allow outpost growth, self-sufficiency, and commercial space service and utility industry activities.
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Human influenza is more effective than avian influenza at antiviral suppression in airway cells.
Hsu, Alan Chen-Yu; Barr, Ian; Hansbro, Philip M; Wark, Peter A
2011-06-01
Airway epithelial cells are the initial site of infection with influenza viruses. The innate immune responses of airway epithelial cells to infection are important in limiting virus replication and spread. However, relatively little is known about the importance of this innate antiviral response to infection. Avian influenza viruses are a potential source of future pandemics; therefore, it is critical to examine the effectiveness of the host antiviral system to different influenza viruses. We used a human influenza (H3N2) and a low-pathogenic avian influenza (H11N9) to assess and compare the antiviral responses of Calu-3 cells. After infection, H3N2 replicated more effectively than the H11N9 in Calu-3 cells. This was not due to differential expression of sialic acid residues on Calu-3 cells, but was attributed to the interference of host antiviral responses by H3N2. H3N2 induced a delayed antiviral signaling and impaired type I and type III IFN induction compared with the H11N9. The gene encoding for nonstructural (NS) 1 protein was transfected into the bronchial epithelial cells (BECs), and the H3N2 NS1 induced a greater inhibition of antiviral responses compared with the H11N9 NS1. Although the low-pathogenic avian influenza virus was capable of infecting BECs, the human influenza virus replicated more effectively than avian influenza virus in BECs, and this was due to a differential ability of the two NS1 proteins to inhibit antiviral responses. This suggests that the subversion of human antiviral responses may be an important requirement for influenza viruses to adapt to the human host and cause disease.
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Our responsibility in a developing world: from ethics to pragmatism.
La Nauze, Jamie
2002-04-01
If development is defined as a process of enhancing human capabilities, that is, to expand choices and opportunities so that each person can lead a life of respect and value, then poverty is the deprivation of these capabilities. Nobel Laureate for Economics, Amartya Sen, states: 'as people who live minus sign in a broad sense minus sign together, we cannot escape the thought that the terrible occurrences that we see around us are quintessentially our problems'. This year's Council Lecture examines issues of individual and institutional responsibility in a developing world. Aspects of development relevant to ophthalmology are discussed and a review of Australian efforts undertaken. With a view to encouraging Fellows to take a more active role in development, it is demonstrated that there are a range of contributions that can be made. Appropriate practice models are explored and a strategy for College involvement presented.
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Organ-specific physiological responses to acute physical exercise and long-term training in humans.
Heinonen, Ilkka; Kalliokoski, Kari K; Hannukainen, Jarna C; Duncker, Dirk J; Nuutila, Pirjo; Knuuti, Juhani
2014-11-01
Virtually all tissues in the human body rely on aerobic metabolism for energy production and are therefore critically dependent on continuous supply of oxygen. Oxygen is provided by blood flow, and, in essence, changes in organ perfusion are also closely associated with alterations in tissue metabolism. In response to acute exercise, blood flow is markedly increased in contracting skeletal muscles and myocardium, but perfusion in other organs (brain and bone) is only slightly enhanced or is even reduced (visceral organs). Despite largely unchanged metabolism and perfusion, repeated exposures to altered hemodynamics and hormonal milieu produced by acute exercise, long-term exercise training appears to be capable of inducing effects also in tissues other than muscles that may yield health benefits. However, the physiological adaptations and driving-force mechanisms in organs such as brain, liver, pancreas, gut, bone, and adipose tissue, remain largely obscure in humans. Along these lines, this review integrates current information on physiological responses to acute exercise and to long-term physical training in major metabolically active human organs. Knowledge is mostly provided based on the state-of-the-art, noninvasive human imaging studies, and directions for future novel research are proposed throughout the review. ©2014 Int. Union Physiol. Sci./Am. Physiol. Soc.
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Monteiro Gil, Octávia; Vaz, Pedro; Romm, Horst; De Angelis, Cinzia; Antunes, Ana Catarina; Barquinero, Joan-Francesc; Beinke, Christina; Bortolin, Emanuela; Burbidge, Christopher Ian; Cucu, Alexandra; Della Monaca, Sara; Domene, Mercedes Moreno; Fattibene, Paola; Gregoire, Eric; Hadjidekova, Valeria; Kulka, Ulrike; Lindholm, Carita; Meschini, Roberta; M'Kacher, Radhia; Moquet, Jayne; Oestreicher, Ursula; Palitti, Fabrizio; Pantelias, Gabriel; Montoro Pastor, Alegria; Popescu, Irina-Anca; Quattrini, Maria Cristina; Ricoul, Michelle; Rothkamm, Kai; Sabatier, Laure; Sebastià, Natividad; Sommer, Sylwester; Terzoudi, Georgia; Testa, Antonella; Trompier, François; Vral, Anne
2017-01-01
To identify and assess, among the participants in the RENEB (Realizing the European Network of Biodosimetry) project, the emergency preparedness, response capabilities and resources that can be deployed in the event of a radiological or nuclear accident/incident affecting a large number of individuals. These capabilities include available biodosimetry techniques, infrastructure, human resources (existing trained staff), financial and organizational resources (including the role of national contact points and their articulation with other stakeholders in emergency response) as well as robust quality control/assurance systems. A survey was prepared and sent to the RENEB partners in order to acquire information about the existing, operational techniques and infrastructure in the laboratories of the different RENEB countries and to assess the capacity of response in the event of radiological or nuclear accident involving mass casualties. The survey focused on several main areas: laboratory's general information, country and staff involved in biological and physical dosimetry; retrospective assays used, the number of assays available per laboratory and other information related to biodosimetry and emergency preparedness. Following technical intercomparisons amongst RENEB members, an update of the survey was performed one year later concerning the staff and the available assays. The analysis of RENEB questionnaires allowed a detailed assessment of existing capacity of the RENEB network to respond to nuclear and radiological emergencies. This highlighted the key importance of international cooperation in order to guarantee an effective and timely response in the event of radiological or nuclear accidents involving a considerable number of casualties. The deployment of the scientific and technical capabilities existing within the RENEB network members seems mandatory, to help other countries with less or no capacity for biological or physical dosimetry, or countries overwhelmed in case of a radiological or nuclear accident involving a large number of individuals.
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Human Health and Support Systems Capability Roadmap Progress Review
NASA Technical Reports Server (NTRS)
Grounds, Dennis; Boehm, Al
2005-01-01
The Human Health and Support Systems Capability Roadmap focuses on research and technology development and demonstration required to ensure the health, habitation, safety, and effectiveness of crews in and beyond low Earth orbit. It contains three distinct sub-capabilities: Human Health and Performance. Life Support and Habitats. Extra-Vehicular Activity.
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The Impact of Place in Building Human Capability
ERIC Educational Resources Information Center
Garlick, Steve
2014-01-01
While it is accepted that there are "sensitive" and "critical" periods of life during which certain human capabilities are more readily acquired, and where the multiplied returns on our investment in human capability building are more significant, it is also argued that there are place-based contexts (society, nature, culture,…
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Regulation of endogenous human gene expression by ligand-inducible TALE transcription factors.
Mercer, Andrew C; Gaj, Thomas; Sirk, Shannon J; Lamb, Brian M; Barbas, Carlos F
2014-10-17
The construction of increasingly sophisticated synthetic biological circuits is dependent on the development of extensible tools capable of providing specific control of gene expression in eukaryotic cells. Here, we describe a new class of synthetic transcription factors that activate gene expression in response to extracellular chemical stimuli. These inducible activators consist of customizable transcription activator-like effector (TALE) proteins combined with steroid hormone receptor ligand-binding domains. We demonstrate that these ligand-responsive TALE transcription factors allow for tunable and conditional control of gene activation and can be used to regulate the expression of endogenous genes in human cells. Since TALEs can be designed to recognize any contiguous DNA sequence, the conditional gene regulatory system described herein will enable the design of advanced synthetic gene networks.
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Human Reliability and the Cost of Doing Business
NASA Technical Reports Server (NTRS)
DeMott, D. L.
2014-01-01
Human error cannot be defined unambiguously in advance of it happening, it often becomes an error after the fact. The same action can result in a tragic accident for one situation or a heroic action given a more favorable outcome. People often forget that we employ humans in business and industry for the flexibility and capability to change when needed. In complex systems, operations are driven by their specifications of the system and the system structure. People provide the flexibility to make it work. Human error has been reported as being responsible for 60%-80% of failures, accidents and incidents in high-risk industries. We don't have to accept that all human errors are inevitable. Through the use of some basic techniques, many potential human error events can be addressed. There are actions that can be taken to reduce the risk of human error.
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Neurophysiological Estimates of Human Performance Capabilities in Aerospace Systems
1975-01-27
effects on the visual system (in lateral geniculate bodies and optic cortex) depending on the frequency of auditory stimulation. 27 SECTION VI...of spa- tial positions. Correct responses were rewarded with food. EEG activity was recorded in the hippocampus, hypothalamus and lateral geniculate ...movement or an object movement reduce transmission of visual information through the lateral geniculate nucleus. This may be a mechanism for saccadic
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Dobrev, Ivo; Furlong, Cosme; Cheng, Jeffrey T.; Rosowski, John J.
2014-01-01
Abstract. Understanding the human hearing process would be helped by quantification of the transient mechanical response of the human ear, including the human tympanic membrane (TM or eardrum). We propose a new hybrid high-speed holographic system (HHS) for acquisition and quantification of the full-field nanometer transient (i.e., >10 kHz) displacement of the human TM. We have optimized and implemented a 2+1 frame local correlation (LC) based phase sampling method in combination with a high-speed (i.e., >40 K fps) camera acquisition system. To our knowledge, there is currently no existing system that provides such capabilities for the study of the human TM. The LC sampling method has a displacement difference of <11 nm relative to measurements obtained by a four-phase step algorithm. Comparisons between our high-speed acquisition system and a laser Doppler vibrometer indicate differences of <10 μs. The high temporal (i.e., >40 kHz) and spatial (i.e., >100 k data points) resolution of our HHS enables parallel measurements of all points on the surface of the TM, which allows quantification of spatially dependent motion parameters, such as modal frequencies and acoustic delays. Such capabilities could allow inferring local material properties across the surface of the TM. PMID:25191832
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Generation of Hepatocytes from Pluripotent Stem Cells for Drug Screening and Developmental Modeling.
Gieseck, Richard L; Vallier, Ludovic; Hannan, Nicholas R F
2015-01-01
Hepatocytes produced from the differentiation of human pluripotent stem cells can be used to study human development and liver disease, to investigate the toxicological response of novel drug candidates, and as an alternative source of primary cells for transplantation therapies. Here, we describe a method to produce hepatocytes by differentiating human pluripotent stem cells into definitive endoderm, patterning definitive endoderm into anterior definitive endoderm, specifying anterior definitive endoderm into hepatic endoderm, and differentiating hepatic endoderm into immature hepatocytes. These cells are further matured in either two-dimensional or three-dimensional culture conditions to produce cells capable of metabolizing xenobiotics and generating liver-specific proteins, such as albumin and alpha 1 antitrypsin.
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Humanized Mouse Models for the Study of Human Malaria Parasite Biology, Pathogenesis, and Immunity.
Minkah, Nana K; Schafer, Carola; Kappe, Stefan H I
2018-01-01
Malaria parasite infection continues to inflict extensive morbidity and mortality in resource-poor countries. The insufficiently understood parasite biology, continuously evolving drug resistance and the lack of an effective vaccine necessitate intensive research on human malaria parasites that can inform the development of new intervention tools. Humanized mouse models have been greatly improved over the last decade and enable the direct study of human malaria parasites in vivo in the laboratory. Nevertheless, no small animal model developed so far is capable of maintaining the complete life cycle of Plasmodium parasites that infect humans. The ultimate goal is to develop humanized mouse systems in which a Plasmodium infection closely reproduces all stages of a parasite infection in humans, including pre-erythrocytic infection, blood stage infection and its associated pathology, transmission as well as the human immune response to infection. Here, we discuss current humanized mouse models and the future directions that should be taken to develop next-generation models for human malaria parasite research.
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Wong, Kuan Y; Baron, Rebecca; Seldon, Therese A; Jones, Martina L; Rice, Alison M; Munster, David J
2018-05-15
Anti-CD83 Ab capable of Ab-dependent cellular cytotoxicity can deplete activated CD83 + human dendritic cells, thereby inhibiting CD4 T cell-mediated acute graft-versus-host disease. As CD83 is also expressed on the surface of activated B lymphocytes, we hypothesized that anti-CD83 would also inhibit B cell responses to stimulation. We found that anti-CD83 inhibited total IgM and IgG production in vitro by allostimulated human PBMC. Also, Ag-specific Ab responses to immunization of SCID mice xenografted with human PBMC were inhibited by anti-CD83 treatment. This inhibition occurred without depletion of all human B cells because anti-CD83 lysed activated CD83 + B cells by Ab-dependent cellular cytotoxicity and spared resting (CD83 - ) B cells. In cultured human PBMC, anti-CD83 inhibited tetanus toxoid-stimulated B cell proliferation and concomitant dendritic cell-mediated CD4 T cell proliferation and expression of IFN-γ and IL-17A, with minimal losses of B cells (<20%). In contrast, the anti-CD20 mAb rituximab depleted >80% of B cells but had no effect on CD4 T cell proliferation and cytokine expression. By virtue of the ability of anti-CD83 to selectively deplete activated, but not resting, B cells and dendritic cells, with the latter reducing CD4 T cell responses, anti-CD83 may be clinically useful in autoimmunity and transplantation. Advantages might include inhibited expansion of autoantigen- or alloantigen-specific B cells and CD4 T cells, thus preventing further production of pathogenic Abs and inflammatory cytokines while preserving protective memory and regulatory cells. Copyright © 2018 by The American Association of Immunologists, Inc.
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Human Capital, (Human) Capabilities and Higher Education
ERIC Educational Resources Information Center
Le Grange, L.
2011-01-01
In this article I initiate a debate into the (de)merits of human capital theory and human capability theory and discuss implications of the debate for higher education. Human capital theory holds that economic growth depends on investment in education and that economic growth is the basis for improving the quality of human life. Human capable…
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NASA Technical Reports Server (NTRS)
Wallace, Sarah
2017-01-01
Why do we need a DNA sequencer to support the human exploration of space? (A) Operational environmental monitoring; (1) Identification of contaminating microbes, (2) Infectious disease diagnosis, (3) Reduce down mass (sample return for environmental monitoring, crew health, etc.). (B) Research; (1) Human, (2) Animal, (3) Microbes/Cell lines, (4) Plant. (C) Med Ops; (1) Response to countermeasures, (2) Radiation, (3) Real-time analysis can influence medical intervention. (C) Support astrobiology science investigations; (1) Technology superiorly suited to in situ nucleic acid-based life detection, (2) Functional testing for integration into robotics for extraplanetary exploration mission.
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2010-03-23
foundation of our S&T portfolio by developing a broad base of scientific knowledge from which INP, FNC, and quick reaction efforts are generated...optimally tailoring experiences, in real-time, to current cognitive and physiological states of the learner. A unique human systems design approach is...efforts include modeling human responses to blast, ballistic, and blunt trauma, as well as modeling physical and cognitive effects of blast exposure and
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Kellner, Aaron; Freeman, Elizabeth B.; Carlson, Arthur S.
1958-01-01
Specific neutralizing antibodies directed against streptococcal DPNase were induced experimentally in rabbits and guinea pigs by the injection of partially purified preparations of the enzyme. Similar antibodies capable of inhibiting the biological activity of the enzyme were found to occur naturally in the serum of a very high percentage of human beings, and the titer of these antibodies often rose sharply following streptococcal infections. The antibody response to streptococcal DPNase in general paralleled that to streptolysin O, though in some instances antibodies to one increased when those to the other did not. PMID:13575667
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Magnetite in human tissues: A mechanism for the biological effects of weak ELF magnetic fields
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kirschvink, J.L.; Kobayashi-Kirschvink, A.; Diaz-Ricci, J.C.
1992-01-01
Due to the apparent lack of a biophysical mechanism, the question of whether weak, low-frequency magnetic fields are able to influence living organisms has long been one of the most controversial subjects in any field of science. However, two developments during the past decade have changed this perception dramatically, the first being the discovery that many organisms, including humans, biochemically precipitate the ferrimagnetic mineral magnetite (Fe3O4). In the magnetotactic bacteria, the geomagnetic response is based on either biogenic magnetite or greigite (Fe3S4), and reasonably good evidence exists that this is also the case in higher animals such as the honeymore » bee. Second, the development of simple behavioral conditioning experiments for training honey bees to discriminate magnetic fields demonstrates conclusively that at least one terrestrial animal is capable of detecting earth-strength magnetic fields through a sensory process. In turn, the existence of this ability implies the presence of specialized receptors which interact at the cellular level with weak magnetic fields in a fashion exceeding thermal noise. A simple calculation shows that magnetosomes moving in response to earth-strength ELF fields are capable of opening trans-membrane ion channels, in a fashion similar to those predicted by ionic resonance models. Hence, the presence of trace levels of biogenic magnetite in virtually all human tissues examined suggests that similar biophysical processes may explain a variety of weak field ELF bioeffects. 61 refs.« less
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Leung, T M; Xu, J M; Chau, C K; Tang, S K; Pun-Cheng, L S C
2017-04-01
The importance of non-acoustical factors including the type of visual environment on human noise perception becomes increasingly recognized. In order to reveal the relationships between long-term noise annoyance and different types of neighborhood views, 2033 questionnaire responses were collected for studying the effect of perceptions of different combinations of views of sea, urban river, greenery, and/or noise barrier on the annoyance responses from residents living in high-rise apartments in Hong Kong. The collected responses were employed to formulate a multivariate model to predict the probability of invoking a high annoyance response from residents. Results showed that views of sea, urban river, or greenery could lower the probability, while views of noise barrier could increase the probability. Views of greenery had a stronger noise moderation capability than views of sea or urban river. The presence of an interaction effect between views of water and views of noise barrier exerted a negative influence on the noise annoyance moderation capability. The probability due to exposure to an environment containing views of noise barriers and urban rivers would be even higher than that due to exposure to an environment containing views of noise barriers alone.
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A Novel Ex Vivo Method for Visualizing Live-Cell Calcium Response Behavior in Intact Human Tumors.
Koh, James; Hogue, Joyce A; Sosa, Julie A
2016-01-01
The functional impact of intratumoral heterogeneity has been difficult to assess in the absence of a means to interrogate dynamic, live-cell biochemical events in the native tissue context of a human tumor. Conventional histological methods can reveal morphology and static biomarker expression patterns but do not provide a means to probe and evaluate tumor functional behavior and live-cell responsiveness to experimentally controlled stimuli. Here, we describe an approach that couples vibratome-mediated viable tissue sectioning with live-cell confocal microscopy imaging to visualize human parathyroid adenoma tumor cell responsiveness to extracellular calcium challenge. Tumor sections prepared as 300 micron-thick tissue slices retain viability throughout a >24 hour observation period and retain the native architecture of the parental tumor. Live-cell observation of biochemical signaling in response to extracellular calcium challenge in the intact tissue slices reveals discrete, heterogeneous kinetic waveform categories of calcium agonist reactivity within each tumor. Plotting the proportion of maximally responsive tumor cells as a function of calcium concentration yields a sigmoid dose-response curve with a calculated calcium EC50 value significantly elevated above published reference values for wild-type calcium-sensing receptor (CASR) sensitivity. Subsequent fixation and immunofluorescence analysis of the functionally evaluated tissue specimens allows alignment and mapping of the physical characteristics of individual cells within the tumor to specific calcium response behaviors. Evaluation of the relative abundance of intracellular PTH in tissue slices challenged with variable calcium concentrations demonstrates that production of the hormone can be dynamically manipulated ex vivo. The capability of visualizing live human tumor tissue behavior in response to experimentally controlled conditions opens a wide range of possibilities for personalized ex vivo therapeutic testing. This highly adaptable system provides a unique platform for live-cell ex vivo provocative testing of human tumor responsiveness to a range of physiological agonists or candidate therapeutic compounds.
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Zou, Zhen; He, Dinggeng; Cai, Linli; He, Xiaoxiao; Wang, Kemin; Yang, Xue; Li, Liling; Li, Siqi; Su, Xiaoya
2016-04-06
The outstanding progress of nanoparticles-based delivery systems capable of releasing hypoglycemic drugs in response to glucose has dramatically changed the outlook of diabetes management. However, the developed glucose-responsive systems have not offered real-time monitoring capabilities for accurate quantifying hypoglycemic drugs released. In this study, we present a multifunctional delivery system that integrates both delivery and monitoring issues using glucose-triggered competitive binding scheme on alizarin complexone (ALC) functionalized mesoporous silica nanoparticles (MSN). In this system, ALC is modified on the surface of MSN as the signal reporter. Gluconated insulin (G-Ins) is then introduced onto MSN-ALC via benzene-1,4-diboronic acid (BA) mediated esterification reaction, where G-Ins not only blocks drugs inside the mesopores but also works as a hypoglycemic drug. In the absence of glucose, the sandwich-type boronate ester structure formed by BA binding to the diols of ALC and G-Ins remains intact, resulting in an fluorescence emission peak at 570 nm and blockage of pores. Following a competitive binding, the presence of glucose cause the dissociation of boronate ester between ALC and BA, which lead to the pores opening and disappearance of fluorescence. As proof of concept, rosiglitazone maleate (RSM), an insulin-sensitizing agent, was doped into the MSN to form a multifunctional MSN (RSM@MSN-ALC-BA-Ins), integrating with double-drugs loading, glucose-responsive performance, and real-time monitoring capability. It has been demonstrated that the glucose-responsive release behaviors of insulin and RSM in buffer or in human serum can be quantified in real-time through evaluating the changes of fluorescence signal. We believe that this developed multifunctional system can shed light on the invention of a new generation of smart nanoformulations for optical diagnosis, individualized treatment, and noninvasive monitoring of diabetes management.
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Al-Armaghany, Allann; Tong, Kenneth; Highton, David; Leung, Terence S
2016-01-01
We have previously developed a hybrid microwave-optical system to monitor microvascular changes in response to thermal provocation in muscle. The hybrid probe is capable of inducing deep heat from the skin surface using mild microwaves (1-3 W) and raises the tissue temperature by a few degrees Celsius. This causes vasodilation and the subsequent increase in blood volume is detected by the hybrid probe using near infrared spectroscopy. The hybrid probe is also equipped with a skin cooling system which lowers the skin temperature while allowing microwaves to warm up deeper tissues. The hybrid system can be used to assess the condition of the vasculature in response to thermal stimulation. In this validation study, thermal imaging has been used to assess the temperature distribution on the surface of phantoms and human calf, following microwave warming. The results show that the hybrid system is capable of changing the skin temperature with a combination of microwave warming and skin cooling. It can also detect thermal responses in terms of changes of oxy/deoxy-hemoglobin concentrations.
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NASA Technical Reports Server (NTRS)
Thronson, Harley; Carberry, Chris; Cassady, R. J.; Cooke, Doug; Hopkins, Joshua; Perino, Maria A.; Kirkpatrick, Jim; Raftery, Michael; Westenberg, Artemis; Zucker, Richard
2013-01-01
There is a growing consensus that within two decades initial human missions to Mars are affordable under plausible budget assumptions and with sustained international participation. In response to this idea, a distinguished group of experts from the Mars exploration stakeholder communities attended the "Affording Mars" workshop at George Washington University in December, 2013. Participants reviewed and discussed scenarios for affordable and sustainable human and robotic exploration of Mars, the role of the International Space Station over the coming decade as the essential early step toward humans to Mars, possible "bridge" missions in the 2020s, key capabilities required for affordable initial missions, international partnerships, and a usable definition of affordability and sustainability. We report here the findings, observations, and recommendations that were agreed to at that workshop.
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Training & Personnel Systems Technology. R&D Program Description FY 84-85.
1984-04-01
performance requirements in terms of rapid response times, high rates of information processing, and complex decision making that tax the capabilities...makers to make linguistic and format changes to texts to enhance general literacy rates , (d) begin integrating human and animal data on stress ;ffects...systems are being Integrated Into the force at unprecedented rates , arrival of this sophisticated, high-technology equipment will coincide with increased
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Freedom and the State: Kant on Revolution and International Interface
1999-11-11
physical and psychological nature and many of them make us selfish and disagreeable beings. In fact, Kant contends that human beings are naturally...circumstances include a "defective education, bad company,... the viciousness of a natural disposition insensitive to shame,... levity and thoughtlessness...possibility of ethical action. Unless we are capable of choosing duty over inclinations, we cannot be held responsible for our actions (GMM 49). This
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Investigation of the Human Response to Upper Torso Retraction with Weighted Helmets
2013-09-01
coverage of each test. The Kodak system is capable of recording high-speed motion up to a rate of 1000 frames per second. For this study , the video...the measured center-of-gravity (CG) of the worst- case test helmet fell outside the current limits and no injuries were observed, it can be stated...8 Figure 7. T-test Cases 1-9 (0 lb Added Helmet Weight
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Aircraft Emergencies: Challenge and Response
NASA Technical Reports Server (NTRS)
Burian, Barbara K.
2010-01-01
Emergency and abnormal situations in aviation present flight crews with a number of challenges. Checklists are essential tools that have been developed to assist them to meet these challenges. However, in order for checklists to be most effective in these situations they must be designed with the operational and situational demands of emergencies and abnormal conditions in mind as well as human performance capabilities and limitations under high stress and workload.
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Human facial skin detection in thermal video to effectively measure electrodermal activity (EDA)
NASA Astrophysics Data System (ADS)
Kaur, Balvinder; Hutchinson, J. Andrew; Leonard, Kevin R.; Nelson, Jill K.
2011-06-01
In the past, autonomic nervous system response has often been determined through measuring Electrodermal Activity (EDA), sometimes referred to as Skin Conductance (SC). Recent work has shown that high resolution thermal cameras can passively and remotely obtain an analog to EDA by assessing the activation of facial eccrine skin pores. This paper investigates a method to distinguish facial skin from non-skin portions on the face to generate a skin-only Dynamic Mask (DM), validates the DM results, and demonstrates DM performance by removing false pore counts. Moreover, this paper shows results from these techniques using data from 20+ subjects across two different experiments. In the first experiment, subjects were presented with primary screening questions for which some had jeopardy. In the second experiment, subjects experienced standard emotion-eliciting stimuli. The results from using this technique will be shown in relation to data and human perception (ground truth). This paper introduces an automatic end-to-end skin detection approach based on texture feature vectors. In doing so, the paper contributes not only a new capability of tracking facial skin in thermal imagery, but also enhances our capability to provide non-contact, remote, passive, and real-time methods for determining autonomic nervous system responses for medical and security applications.
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Mard-Soltani, Maysam; Rasaee, Mohamad Javad; Khalili, Saeed; Sheikhi, Abdol-Karim; Hedayati, Mehdi; Ghaderi-Zefrehi, Hossein; Alasvand, Milad
2018-04-01
The production of human thyroid stimulating hormone (hTSH) immunoassays requires specific antibodies against hTSH which is a cumbersome process. Therefore, producing specific polyclonal antibodies against engineered recombinant fusion hTSH antigens would be of great significance. The best immunogenic region of the hTSH was selected based on in silico analyses and equipped with two different fusions. Standard methods were used for protein expression, purification, verification, structural evaluation, and immunizations of the white New Zealand rabbits. Ultimately, immunized serums were used for antibody titration, purification and characterization (specificity, sensitivity and cross reactivity). The desired antigens were successfully designed, sub-cloned, expressed, confirmed and used for in vivo immunization. Structural analyses indicated that only the bigger antigen has showed changed 2 dimensional (2D) and 3D structural properties in comparison to the smaller antigen. The raised polyclonal antibodies were capable of specific and sensitive hTSH detection, while the cross reactivity with the other members of the glycoprotein hormone family was minimum and negligible. The fusion which was solely composed of the tetanus toxin epitopes led to better protein folding and was capable of immunizing the host animals resulting into high titer antibody. Therefore, the minimal fusion sequences seem to be more effective in eliciting specific antibody responses.
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Scaling Pharmacodynamics from In Vitro and Preclinical Animal Studies to Humans
Mager, Donald E.; Woo, Sukyung; Jusko, William J.
2013-01-01
Summary An important feature of mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) models is the identification of drug- and system-specific factors that determine the intensity and time-course of pharmacological effects. This provides an opportunity to integrate information obtained from in vitro bioassays and preclinical pharmacological studies in animals to anticipate the clinical and adverse responses to drugs in humans. The fact that contemporary PK/PD modeling continues to evolve and seeks to emulate systems level properties should provide enhanced capabilities to scale-up pharmacodynamic data. Critical steps in drug discovery and development, such as lead compound and first in human dose selection, may become more efficient with the implementation and further refinement of translational PK/PD modeling. In this review, we highlight fundamental principles in pharmacodynamics and the basic expectations for in vitro bioassays and traditional allometric scaling in PK/PD modeling. Discussion of PK/PD modeling efforts for recombinant human erythropoietin is also included as a case study showing the potential for advanced systems analysis to facilitate extrapolations and improve understanding of inter-species differences in drug responses. PMID:19252333
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Dogs respond appropriately to cues of humans' attentional focus.
Virányi, Zsófia; Topál, József; Gácsi, Márta; Miklósi, Adám; Csányi, Vilmos
2004-05-31
Dogs' ability to recognise cues of human visual attention was studied in different experiments. Study 1 was designed to test the dogs' responsiveness to their owner's tape-recorded verbal commands (Down!) while the Instructor (who was the owner of the dog) was facing either the dog or a human partner or none of them, or was visually separated from the dog. Results show that dogs were more ready to follow the command if the Instructor attended them during instruction compared to situations when the Instructor faced the human partner or was out of sight of the dog. Importantly, however, dogs showed intermediate performance when the Instructor was orienting into 'empty space' during the re-played verbal commands. This suggests that dogs are able to differentiate the focus of human attention. In Study 2 the same dogs were offered the possibility to beg for food from two unfamiliar humans whose visual attention (i.e. facing the dog or turning away) was systematically varied. The dogs' preference for choosing the attentive person shows that dogs are capable of using visual cues of attention to evaluate the human actors' responsiveness to solicit food-sharing. The dogs' ability to understand the communicatory nature of the situations is discussed in terms of their social cognitive skills and unique evolutionary history.
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The NASA Auralization Framework and Plugin Architecture
NASA Technical Reports Server (NTRS)
Aumann, Aric R.; Tuttle, Brian C.; Chapin, William L.; Rizzi, Stephen A.
2015-01-01
NASA has a long history of investigating human response to aircraft flyover noise and in recent years has developed a capability to fully auralize the noise of aircraft during their design. This capability is particularly useful for unconventional designs with noise signatures significantly different from the current fleet. To that end, a flexible software architecture has been developed to facilitate rapid integration of new simulation techniques for noise source synthesis and propagation, and to foster collaboration amongst researchers through a common releasable code base. The NASA Auralization Framework (NAF) is a skeletal framework written in C++ with basic functionalities and a plugin architecture that allows users to mix and match NAF capabilities with their own methods through the development and use of dynamically linked libraries. This paper presents the NAF software architecture and discusses several advanced auralization techniques that have been implemented as plugins to the framework.
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NASA Technical Reports Server (NTRS)
Crocker, Alan R.
2011-01-01
As we push toward new and diverse space transportation capabilities, reduction in operations cost becomes increasingly important. Achieving affordable and safe human spaceflight capabilities will be the mark of success for new programs and new providers. The ability to perceive the operational implications of design decisions is crucial in developing safe yet cost competitive space transportation systems. Any human spaceflight program - government or commercial - must make countless decisions either to implement spacecraft system capabilities or adopt operational constraints or workarounds to account for the lack of such spacecraft capabilities. These decisions can benefit from the collective experience that NASA has accumulated in building and operating crewed spacecraft over the last five decades. This paper reviews NASA s history in developing and operating human rated spacecraft, reviewing the key aspects of spacecraft design and their resultant impacts on operations phase complexity and cost. Specific examples from current and past programs - including the Space Shuttle and International Space Station - are provided to illustrate design traits that either increase or increase cost and complexity associated with spacecraft operations. These examples address factors such as overall design performance margins, levels of redundancy, degree of automated failure response, type and quantity of command and telemetry interfaces, and the definition of reference scenarios for analysis and test. Each example - from early program requirements, design implementation and resulting real-time operations experience - to tell the end-to-end "story" Based on these experiences, specific techniques are recommended to enable earlier and more effective assessment of operations concerns during the design process. A formal method for the assessment of spacecraft operability is defined and results of such operability assessments for recent spacecraft designs are provided. Recent experience in applying these techniques to Orion spacecraft development is reviewed to highlight the direct benefits of early operational assessment and collaborative development efforts.
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Bosi, Emanuele; Monk, Jonathan M.; Aziz, Ramy K.; Fondi, Marco; Nizet, Victor; Palsson, Bernhard Ø.
2016-01-01
Staphylococcus aureus is a preeminent bacterial pathogen capable of colonizing diverse ecological niches within its human host. We describe here the pangenome of S. aureus based on analysis of genome sequences from 64 strains of S. aureus spanning a range of ecological niches, host types, and antibiotic resistance profiles. Based on this set, S. aureus is expected to have an open pangenome composed of 7,411 genes and a core genome composed of 1,441 genes. Metabolism was highly conserved in this core genome; however, differences were identified in amino acid and nucleotide biosynthesis pathways between the strains. Genome-scale models (GEMs) of metabolism were constructed for the 64 strains of S. aureus. These GEMs enabled a systems approach to characterizing the core metabolic and panmetabolic capabilities of the S. aureus species. All models were predicted to be auxotrophic for the vitamins niacin (vitamin B3) and thiamin (vitamin B1), whereas strain-specific auxotrophies were predicted for riboflavin (vitamin B2), guanosine, leucine, methionine, and cysteine, among others. GEMs were used to systematically analyze growth capabilities in more than 300 different growth-supporting environments. The results identified metabolic capabilities linked to pathogenic traits and virulence acquisitions. Such traits can be used to differentiate strains responsible for mild vs. severe infections and preference for hosts (e.g., animals vs. humans). Genome-scale analysis of multiple strains of a species can thus be used to identify metabolic determinants of virulence and increase our understanding of why certain strains of this deadly pathogen have spread rapidly throughout the world. PMID:27286824
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Enhancing the effectiveness of human-robot teaming with a closed-loop system.
Teo, Grace; Reinerman-Jones, Lauren; Matthews, Gerald; Szalma, James; Jentsch, Florian; Hancock, Peter
2018-02-01
With technological developments in robotics and their increasing deployment, human-robot teams are set to be a mainstay in the future. To develop robots that possess teaming capabilities, such as being able to communicate implicitly, the present study implemented a closed-loop system. This system enabled the robot to provide adaptive aid without the need for explicit commands from the human teammate, through the use of multiple physiological workload measures. Such measures of workload vary in sensitivity and there is large inter-individual variability in physiological responses to imposed taskload. Workload models enacted via closed-loop system should accommodate such individual variability. The present research investigated the effects of the adaptive robot aid vs. imposed aid on performance and workload. Results showed that adaptive robot aid driven by an individualized workload model for physiological response resulted in greater improvements in performance compared to aid that was simply imposed by the system. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology
Enright, Heather A.; Malfatti, Michael A.; Zimmermann, Maike; ...
2016-10-11
Accelerator mass spectrometry (AMS) has been adopted as a powerful bioanalytical method for human studies in the areas of pharmacology and toxicology. The exquisite sensitivity (10–18 mol) of AMS has facilitated studies of toxins and drugs at environmentally and physiologically relevant concentrations in humans. Such studies include risk assessment of environmental toxicants, drug candidate selection, absolute bioavailability determination, and more recently, assessment of drug-target binding as a biomarker of response to chemotherapy. Combining AMS with complementary capabilities such as high performance liquid chromatography (HPLC) can maximize data within a single experiment and provide additional insight when assessing drugs and toxins,more » such as metabolic profiling. Recent advances in the AMS technology at Lawrence Livermore National Laboratory have allowed for direct coupling of AMS with complementary capabilities such as HPLC via a liquid sample moving wire interface, offering greater sensitivity compared to that of graphite-based analysis, therefore enabling the use of lower 14C and chemical doses, which are imperative for clinical testing. In conclusion, the aim of this review is to highlight the recent efforts in human studies using AMS, including technological advancements and discussion of the continued promise of AMS for innovative clinical based research.« less
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Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology
DOE Office of Scientific and Technical Information (OSTI.GOV)
Enright, Heather A.; Malfatti, Michael A.; Zimmermann, Maike
Accelerator mass spectrometry (AMS) has been adopted as a powerful bioanalytical method for human studies in the areas of pharmacology and toxicology. The exquisite sensitivity (10–18 mol) of AMS has facilitated studies of toxins and drugs at environmentally and physiologically relevant concentrations in humans. Such studies include risk assessment of environmental toxicants, drug candidate selection, absolute bioavailability determination, and more recently, assessment of drug-target binding as a biomarker of response to chemotherapy. Combining AMS with complementary capabilities such as high performance liquid chromatography (HPLC) can maximize data within a single experiment and provide additional insight when assessing drugs and toxins,more » such as metabolic profiling. Recent advances in the AMS technology at Lawrence Livermore National Laboratory have allowed for direct coupling of AMS with complementary capabilities such as HPLC via a liquid sample moving wire interface, offering greater sensitivity compared to that of graphite-based analysis, therefore enabling the use of lower 14C and chemical doses, which are imperative for clinical testing. In conclusion, the aim of this review is to highlight the recent efforts in human studies using AMS, including technological advancements and discussion of the continued promise of AMS for innovative clinical based research.« less
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Fujimuro, Masahiro; Nakaso, Kazuhiro; Nakashima, Kenji; Sadanari, Hidetaka; Hisanori, Inoue; Teishikata, Yasuhiro; Hayward, S Diane; Yokosawa, Hideyoshi
2006-04-01
Human lymphotropic herpesviruses, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are responsible for a wide variety of human diseases. Due to an increase in diseased states associated with immunosuppression, more instances of co-morbid infections with these herpesviruses have resulted in viral reactivations that have caused numerous fatalities. Therefore, the development of rapid and accurate method to detect these viruses in immunocompromised patients is vital for immediate treatment with antiviral prophylactic drugs. In this study, we developed a new multiplex PCR method coupled to DNA array hybridization, which can simultaneously detect all three human herpesviruses in one single cell sample. Multiplex PCR primers were designed to amplify specific regions of the EBV (EBER1), CMV (IE) and KSHV (LANA) viral genomes. Pre-clinical application of this method revealed that this approach is capable of detecting as few as 1 copy of the viral genomes for KSHV and CMV and 100 copies of the genome for EBV. Furthermore, this highly sensitive test showed no cross-reactivity among the three viruses and is capable of detecting both KSHV and EBV viral genomes simultaneously in the lymphoblastoid cells that have been double infected with both viruses. Thus, this array-based approach serves as a rapid and reliable diagnostic tool for clinical applications.
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Paucity of PD-L1 expression in prostate cancer: innate and adaptive immune resistance.
Martin, A M; Nirschl, T R; Nirschl, C J; Francica, B J; Kochel, C M; van Bokhoven, A; Meeker, A K; Lucia, M S; Anders, R A; DeMarzo, A M; Drake, C G
2015-12-01
Primary prostate cancers are infiltrated with programmed death-1 (PD-1) expressing CD8+ T-cells. However, in early clinical trials, men with metastatic castrate-resistant prostate cancer did not respond to PD-1 blockade as a monotherapy. One explanation for this unresponsiveness could be that prostate tumors generally do not express programmed death ligand-1 (PD-L1), the primary ligand for PD-1. However, lack of PD-L1 expression in prostate cancer would be surprising, given that phosphatase and tensin homolog (PTEN) loss is relatively common in prostate cancer and several studies have shown that PTEN loss correlates with PD-L1 upregulation--constituting a mechanism of innate immune resistance. This study tested whether prostate cancer cells were capable of expressing PD-L1, and whether the rare PD-L1 expression that occurs in human specimens correlates with PTEN loss. Human prostate cancer cell lines were evaluated for PD-L1 expression and loss of PTEN by flow cytometry and western blotting, respectively. Immunohistochemical (IHC) staining for PTEN was correlated with PD-L1 IHC using a series of resected human prostate cancer samples. In vitro, many prostate cancer cell lines upregulated PD-L1 expression in response to inflammatory cytokines, consistent with adaptive immune resistance. In these cell lines, no association between PTEN loss and PD-L1 expression was apparent. In primary prostate tumors, PD-L1 expression was rare, and was not associated with PTEN loss. These studies show that some prostate cancer cell lines are capable of expressing PD-L1. However, in human prostate cancer, PTEN loss is not associated with PD-L1 expression, arguing against innate immune resistance as a mechanism that mitigates antitumor immune responses in this disease.
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Santhanam, Navaneetha; Kumanchik, Lee; Guo, Xiufang; Sommerhage, Frank; Cai, Yunqing; Jackson, Max; Martin, Candace; Saad, George; McAleer, Christopher W; Wang, Ying; Lavado, Andrea; Long, Christopher J; Hickman, James J
2018-06-01
There are currently no functional neuromuscular junction (hNMJ) systems composed of human cells that could be used for drug evaluations or toxicity testing in vitro. These systems are needed to evaluate NMJs for diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy or other neurodegenerative diseases or injury states. There are certainly no model systems, animal or human, that allows for isolated treatment of motoneurons or muscle capable of generating dose response curves to evaluate pharmacological activity of these highly specialized functional units. A system was developed in which human myotubes and motoneurons derived from stem cells were cultured in a serum-free medium in a BioMEMS construct. The system is composed of two chambers linked by microtunnels to enable axonal outgrowth to the muscle chamber that allows separate stimulation of each component and physiological NMJ function and MN stimulated tetanus. The muscle's contractions, induced by motoneuron activation or direct electrical stimulation, were monitored by image subtraction video recording for both frequency and amplitude. Bungarotoxin, BOTOX ® and curare dose response curves were generated to demonstrate pharmacological relevance of the phenotypic screening device. This quantifiable functional hNMJ system establishes a platform for generating patient-specific NMJ models by including patient-derived iPSCs. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Health, vital goals, and central human capabilities.
Venkatapuram, Sridhar
2013-06-01
I argue for a conception of health as a person's ability to achieve or exercise a cluster of basic human activities. These basic activities are in turn specified through free-standing ethical reasoning about what constitutes a minimal conception of a human life with equal human dignity in the modern world. I arrive at this conception of health by closely following and modifying Lennart Nordenfelt's theory of health which presents health as the ability to achieve vital goals. Despite its strengths I transform Nordenfelt's argument in order to overcome three significant drawbacks. Nordenfelt makes vital goals relative to each community or context and significantly reflective of personal preferences. By doing so, Nordenfelt's conception of health faces problems with both socially relative concepts of health and subjectively defined wellbeing. Moreover, Nordenfelt does not ever explicitly specify a set of vital goals. The theory of health advanced here replaces Nordenfelt's (seemingly) empty set of preferences and society-relative vital goals with a human species-wide conception of basic vital goals, or 'central human capabilities and functionings'. These central human capabilities come out of the capabilities approach (CA) now familiar in political philosophy and economics, and particularly reflect the work of Martha Nussbaum. As a result, the health of an individual should be understood as the ability to achieve a basic cluster of beings and doings-or having the overarching capability, a meta-capability, to achieve a set of central or vital inter-related capabilities and functionings. © 2012 John Wiley & Sons Ltd.
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HEALTH, VITAL GOALS, AND CENTRAL HUMAN CAPABILITIES
Venkatapuram, Sridhar
2013-01-01
I argue for a conception of health as a person's ability to achieve or exercise a cluster of basic human activities. These basic activities are in turn specified through free-standing ethical reasoning about what constitutes a minimal conception of a human life with equal human dignity in the modern world. I arrive at this conception of health by closely following and modifying Lennart Nordenfelt's theory of health which presents health as the ability to achieve vital goals. Despite its strengths I transform Nordenfelt's argument in order to overcome three significant drawbacks. Nordenfelt makes vital goals relative to each community or context and significantly reflective of personal preferences. By doing so, Nordenfelt's conception of health faces problems with both socially relative concepts of health and subjectively defined wellbeing. Moreover, Nordenfelt does not ever explicitly specify a set of vital goals. The theory of health advanced here replaces Nordenfelt's (seemingly) empty set of preferences and society-relative vital goals with a human species-wide conception of basic vital goals, or ‘central human capabilities and functionings’. These central human capabilities come out of the capabilities approach (CA) now familiar in political philosophy and economics, and particularly reflect the work of Martha Nussbaum. As a result, the health of an individual should be understood as the ability to achieve a basic cluster of beings and doings—or having the overarching capability, a meta-capability, to achieve a set of central or vital inter-related capabilities and functionings. PMID:22420910
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Healable thermoset polymer composite embedded with stimuli-responsive fibres
Li, Guoqiang; Meng, Harper; Hu, Jinlian
2012-01-01
Severe wounds in biological systems such as human skin cannot heal themselves, unless they are first stitched together. Healing of macroscopic damage in thermoset polymer composites faces a similar challenge. Stimuli-responsive shape-changing polymeric fibres with outstanding mechanical properties embedded in polymers may be able to close macro-cracks automatically upon stimulation such as heating. Here, a stimuli-responsive fibre (SRF) with outstanding mechanical properties and supercontraction capability was fabricated for the purpose of healing macroscopic damage. The SRFs and thermoplastic particles (TPs) were incorporated into regular thermosetting epoxy for repeatedly healing macroscopic damages. The system works by mimicking self-healing of biological systems such as human skin, close (stitch) then heal, i.e. close the macroscopic crack through the thermal-induced supercontraction of the SRFs, and bond the closed crack through melting and diffusing of TPs at the crack interface. The healing efficiency determined using tapered double-cantilever beam specimens was 94 per cent. The self-healing process was reasonably repeatable. PMID:22896563
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Human Immunodeficiency Virus-Specific CD8+ T Cells in Human Breast Milk
Sabbaj, Steffanie; Edwards, Bradley H.; Ghosh, Mrinal K.; Semrau, Katherine; Cheelo, Sanford; Thea, Donald M.; Kuhn, Louise; Ritter, G. Douglas; Mulligan, Mark J.; Goepfert, Paul A.; Aldrovandi, Grace M.
2002-01-01
Breast-feeding infants of human immunodeficiency virus (HIV)-infected women ingest large amounts of HIV, but most escape infection. While the factors affecting transmission risk are poorly understood, HIV-specific cytotoxic T-lymphocyte (CTL) responses play a critical role in controlling HIV levels in blood. We therefore investigated the ability of breast milk cells (BMC) from HIV-infected women from the United States and Zambia to respond to HIV-1 peptides in a gamma interferon enzyme-linked immunospot assay. All (n = 11) HIV-infected women had responses to pools of Gag peptide (range, 105 to 1,400 spot-forming cells/million; mean = 718), 8 of 11 reacted to Pol, 7 reacted to Nef, and 2 of 5 reacted to Env. Conversely, of four HIV-negative women, none responded to any of the tested HIV peptide pools. Depletion and tetramer staining studies demonstrated that CD8+ T cells mediated these responses, and a chromium-release assay showed that these BMC were capable of lysing target cells in an HIV-specific manner. These data demonstrate the presence of HIV-specific major histocompatibility complex class I-restricted CD8+ CTLs in breast milk. Their presence suggests a role in limiting transmission and provides a rationale for vaccine strategies to enhance these responses. PMID:12097549
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Therapeutic Properties and Biological Benefits of Marine-Derived Anticancer Peptides
Kang, Hee Kyoung; Choi, Moon-Chang; Seo, Chang Ho; Park, Yoonkyung
2018-01-01
Various organisms exist in the oceanic environment. These marine organisms provide an abundant source of potential medicines. Many marine peptides possess anticancer properties, some of which have been evaluated for treatment of human cancer in clinical trials. Marine anticancer peptides kill cancer cells through different mechanisms, such as apoptosis, disruption of the tubulin-microtubule balance, and inhibition of angiogenesis. Traditional chemotherapeutic agents have side effects and depress immune responses. Thus, the research and development of novel anticancer peptides with low toxicity to normal human cells and mechanisms of action capable of avoiding multi-drug resistance may provide a new method for anticancer treatment. This review provides useful information on the potential of marine anticancer peptides for human therapy. PMID:29558431
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NASA Astrophysics Data System (ADS)
Borgwardt, Derek S.; Martin, Aaron D.; van Hemert, Jonathan R.; Yang, Jianyi; Fischer, Carol L.; Recker, Erica N.; Nair, Prashant R.; Vidva, Robinson; Chandrashekaraiah, Shwetha; Progulske-Fox, Ann; Drake, David; Cavanaugh, Joseph E.; Vali, Shireen; Zhang, Yang; Brogden, Kim A.
2014-01-01
Histatins are human salivary gland peptides with anti-microbial and anti-inflammatory activities. In this study, we hypothesized that histatin 5 binds to Porphyromonas gingivalis hemagglutinin B (HagB) and attenuates HagB-induced chemokine responses in human myeloid dendritic cells. Histatin 5 bound to immobilized HagB in a surface plasmon resonance (SPR) spectroscopy-based biosensor system. SPR spectroscopy kinetic and equilibrium analyses, protein microarray studies, and I-TASSER structural modeling studies all demonstrated two histatin 5 binding sites on HagB. One site had a stronger affinity with a KD1 of 1.9 μM and one site had a weaker affinity with a KD2 of 60.0 μM. Binding has biological implications and predictive modeling studies and exposure of dendritic cells both demonstrated that 20.0 μM histatin 5 attenuated (p < 0.05) 0.02 μM HagB-induced CCL3/MIP-1α, CCL4/MIP-1β, and TNFα responses. Thus histatin 5 is capable of attenuating chemokine responses, which may help control oral inflammation.
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Evolutionary distance from human homologs reflects allergenicity of animal food proteins.
Jenkins, John A; Breiteneder, Heimo; Mills, E N Clare
2007-12-01
In silico analysis of allergens can identify putative relationships among protein sequence, structure, and allergenic properties. Such systematic analysis reveals that most plant food allergens belong to a restricted number of protein superfamilies, with pollen allergens behaving similarly. We have investigated the structural relationships of animal food allergens and their evolutionary relatedness to human homologs to define how closely a protein must resemble a human counterpart to lose its allergenic potential. Profile-based sequence homology methods were used to classify animal food allergens into Pfam families, and in silico analyses of their evolutionary and structural relationships were performed. Animal food allergens could be classified into 3 main families--tropomyosins, EF-hand proteins, and caseins--along with 14 minor families each composed of 1 to 3 allergens. The evolutionary relationships of each of these allergen superfamilies showed that in general, proteins with a sequence identity to a human homolog above approximately 62% were rarely allergenic. Single substitutions in otherwise highly conserved regions containing IgE epitopes in EF-hand parvalbumins may modulate allergenicity. These data support the premise that certain protein structures are more allergenic than others. Contrasting with plant food allergens, animal allergens, such as the highly conserved tropomyosins, challenge the capability of the human immune system to discriminate between foreign and self-proteins. Such immune responses run close to becoming autoimmune responses. Exploiting the closeness between animal allergens and their human homologs in the development of recombinant allergens for immunotherapy will need to consider the potential for developing unanticipated autoimmune responses.
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Augustine, Swinburne A. J.; Simmons, Kaneatra J.; Eason, Tarsha N.; Curioso, Clarissa L.; Griffin, Shannon M.; Wade, Timothy J.; Dufour, Alfred; Fout, G. Shay; Grimm, Ann C.; Oshima, Kevin H.; Sams, Elizabeth A.; See, Mary Jean; Wymer, Larry J.
2017-01-01
Waterborne infectious diseases are a major public health concern worldwide. Few methods have been established that are capable of measuring human exposure to multiple waterborne pathogens simultaneously using non-invasive samples such as saliva. Most current methods measure exposure to only one pathogen at a time, require large volumes of individual samples collected using invasive procedures, and are very labor intensive. In this article, we applied a multiplex bead-based immunoassay capable of measuring IgG antibody responses to six waterborne pathogens simultaneously in human saliva to estimate immunoprevalence in beachgoers at Boquerón Beach, Puerto Rico. Further, we present approaches for determining cutoff points to assess immunoprevalence to the pathogens in the assay. For the six pathogens studied, our results show that IgG antibodies against antigens from noroviruses GI.I and GII.4 were more prevalent (60 and 51.6%, respectively) than Helicobacter pylori (21.4%), hepatitis A virus (20.2%), Campylobacter jejuni (8.7%), and Toxoplasma gondii (8%) in the saliva of the study participants. The salivary antibody multiplex immunoassay can be used to examine immunoprevalence of specific pathogens in human populations. PMID:28507984
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Cong, Yu; McArthur, Monica A.; Cohen, Melanie; Jahrling, Peter B.; Janosko, Krisztina B.; Josleyn, Nicole; Kang, Kai; Zhang, Tengfei; Holbrook, Michael R.
2016-01-01
Humans infected with yellow fever virus (YFV), a mosquito-borne flavivirus, can develop illness ranging from a mild febrile disease to hemorrhagic fever and death. The 17D vaccine strain of YFV was developed in the 1930s, has been used continuously since development and has proven very effective. Genetic differences between vaccine and wild-type viruses are few, yet viral or host mechanisms associated with protection or disease are not fully understood. Over the past 20 years, a number of cases of vaccine-associated disease have been identified following vaccination with 17D; these cases have been correlated with reduced immune status at the time of vaccination. Recently, several studies have evaluated T cell responses to vaccination in both humans and non-human primates, but none have evaluated the response to wild-type virus infection. In the studies described here, monocyte-derived macrophages (MDM) and dendritic cells (MoDC) from both humans and rhesus macaques were evaluated for their ability to support infection with either wild-type Asibi virus or the 17D vaccine strain and the host cytokine and chemokine response characterized. Human MoDC and MDM were also evaluated for their ability to stimulate CD4+ T cells. It was found that MoDC and MDM supported viral replication and that there were differential cytokine responses to infection with either wild-type or vaccine viruses. Additionally, MoDCs infected with live 17D virus were able to stimulate IFN-γ and IL-2 production in CD4+ T cells, while cells infected with Asibi virus were not. These data demonstrate that wild-type and vaccine YFV stimulate different responses in target antigen presenting cells and that wild-type YFV can inhibit MoDC activation of CD4+ T cells, a critical component in development of protective immunity. These data provide initial, but critical insight into regulatory capabilities of wild-type YFV in development of disease. PMID:27191161
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Cong, Yu; McArthur, Monica A; Cohen, Melanie; Jahrling, Peter B; Janosko, Krisztina B; Josleyn, Nicole; Kang, Kai; Zhang, Tengfei; Holbrook, Michael R
2016-05-01
Humans infected with yellow fever virus (YFV), a mosquito-borne flavivirus, can develop illness ranging from a mild febrile disease to hemorrhagic fever and death. The 17D vaccine strain of YFV was developed in the 1930s, has been used continuously since development and has proven very effective. Genetic differences between vaccine and wild-type viruses are few, yet viral or host mechanisms associated with protection or disease are not fully understood. Over the past 20 years, a number of cases of vaccine-associated disease have been identified following vaccination with 17D; these cases have been correlated with reduced immune status at the time of vaccination. Recently, several studies have evaluated T cell responses to vaccination in both humans and non-human primates, but none have evaluated the response to wild-type virus infection. In the studies described here, monocyte-derived macrophages (MDM) and dendritic cells (MoDC) from both humans and rhesus macaques were evaluated for their ability to support infection with either wild-type Asibi virus or the 17D vaccine strain and the host cytokine and chemokine response characterized. Human MoDC and MDM were also evaluated for their ability to stimulate CD4+ T cells. It was found that MoDC and MDM supported viral replication and that there were differential cytokine responses to infection with either wild-type or vaccine viruses. Additionally, MoDCs infected with live 17D virus were able to stimulate IFN-γ and IL-2 production in CD4+ T cells, while cells infected with Asibi virus were not. These data demonstrate that wild-type and vaccine YFV stimulate different responses in target antigen presenting cells and that wild-type YFV can inhibit MoDC activation of CD4+ T cells, a critical component in development of protective immunity. These data provide initial, but critical insight into regulatory capabilities of wild-type YFV in development of disease.
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Data and Geocomputation: Time Critical Mission Support for the 2017 Hurricane Season
NASA Astrophysics Data System (ADS)
Bhaduri, B. L.; Tuttle, M.; Rose, A.; Sanyal, J.; Thakur, G.; White, D.; Yang, H. H.; Laverdiere, M.; Whitehead, M.; Taylor, H.; Jacob, M.
2017-12-01
A strong spatial data infrastructure and geospatial analysis capabilities are nucleus to the decision-making process during emergency preparedness, response, and recovery operations. For over a decade, the U.S. Department of Energy's Oak Ridge National Laboratory has been developing critical data and analytical capabilities that provide the Federal Emergency Management Agency (FEMA) and the rest of the federal response community assess and evaluate impacts of natural hazards on population and critical infrastructures including the status of the national electricity and oil and natural gas networks. These capabilities range from identifying structures or buildings from very high-resolution satellite imagery, utilizing machine learning and high-performance computing, to daily assessment of electricity restoration highlighting changes in nighttime lights for the impacted region based on the analysis of NOAA JPSS VIIRS Day/Night Band (DNB) imagery. This presentation will highlight our time critical mission support efforts for the 2017 hurricane season that witnessed unprecedented devastation from hurricanes Harvey, Irma, and Maria. ORNL provided 90m resolution LandScan USA population distribution data for identifying vulnerable population as well as structure (buildings) data extracted from 1m imagery for damage assessment. Spatially accurate data for solid waste facilities were developed and delivered to the response community. Human activity signatures were assessed from large scale collection of open source social media data around points of interests (POI) to ascertain level of destruction. The electricity transmission system was monitored in real time from data integration from hundreds of utilities and electricity outage information were provided back to the response community via standardized web-services.
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Sollims Sampler Targeting Peace & Stability Operations Lessons & Best Practices. Volume 1, Issue 1
2010-07-01
training, human trafficking, and civil strife, all of which have damaging spillover effects for the entire world. Second, genocide and mass atrocities...deployed to a conflict or post-conflict area. [ Read More ... ] • The military can be part of a whole-of-government response to threats of genocide and...mass atrocities. Although most militaries do not train specifically for counter- genocide operations, they often have the skills and capabilities to
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NASA Technical Reports Server (NTRS)
1973-01-01
Ways in which human intelligence might be simulated onboard an unmanned mission to achieve some of the decision making capability or adaptability of the manned mission are examined. The relative cost and simplicity advantages of the unmanned spacecraft missions are emphasized. Reliable techniques for making onboard decisions and for modifying mission science operations in response to the findings are analyzed.
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Indoleacrylic Acid Produced by Commensal Peptostreptococcus Species Suppresses Inflammation.
Wlodarska, Marta; Luo, Chengwei; Kolde, Raivo; d'Hennezel, Eva; Annand, John W; Heim, Cortney E; Krastel, Philipp; Schmitt, Esther K; Omar, Abdifatah S; Creasey, Elizabeth A; Garner, Ashley L; Mohammadi, Sina; O'Connell, Daniel J; Abubucker, Sahar; Arthur, Timothy D; Franzosa, Eric A; Huttenhower, Curtis; Murphy, Leon O; Haiser, Henry J; Vlamakis, Hera; Porter, Jeffrey A; Xavier, Ramnik J
2017-07-12
Host factors in the intestine help select for bacteria that promote health. Certain commensals can utilize mucins as an energy source, thus promoting their colonization. However, health conditions such as inflammatory bowel disease (IBD) are associated with a reduced mucus layer, potentially leading to dysbiosis associated with this disease. We characterize the capability of commensal species to cleave and transport mucin-associated monosaccharides and identify several Clostridiales members that utilize intestinal mucins. One such mucin utilizer, Peptostreptococcus russellii, reduces susceptibility to epithelial injury in mice. Several Peptostreptococcus species contain a gene cluster enabling production of the tryptophan metabolite indoleacrylic acid (IA), which promotes intestinal epithelial barrier function and mitigates inflammatory responses. Furthermore, metagenomic analysis of human stool samples reveals that the genetic capability of microbes to utilize mucins and metabolize tryptophan is diminished in IBD patients. Our data suggest that stimulating IA production could promote anti-inflammatory responses and have therapeutic benefits. Copyright © 2017 Elsevier Inc. All rights reserved.
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Zhang, Kai; Cao, Libo; Wang, Yulong; Hwang, Eunjoo; Reed, Matthew P; Forman, Jason; Hu, Jingwen
2017-10-01
Field data analyses have shown that obesity significantly increases the occupant injury risks in motor vehicle crashes, but the injury assessment tools for people with obesity are largely lacking. The objectives of this study were to use a mesh morphing method to rapidly generate parametric finite element models with a wide range of obesity levels and to evaluate their biofidelity against impact tests using postmortem human subjects (PMHS). Frontal crash tests using three PMHS seated in a vehicle rear seat compartment with body mass index (BMI) from 24 to 40 kg/m 2 were selected. To develop the human models matching the PMHS geometry, statistical models of external body shape, rib cage, pelvis, and femur were applied to predict the target geometry using age, sex, stature, and BMI. A mesh morphing method based on radial basis functions was used to rapidly morph a baseline human model into the target geometry. The model-predicted body excursions and injury measures were compared to the PMHS tests. Comparisons of occupant kinematics and injury measures between the tests and simulations showed reasonable correlations across the wide range of BMI levels. The parametric human models have the capability to account for the obesity effects on the occupant impact responses and injury risks. © 2017 The Obesity Society.
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Pongrácz, Péter; Ujvári, Vera; Faragó, Tamás; Miklósi, Ádám; Péter, András
2017-07-01
The visual sense of dogs is in many aspects different than that of humans. Unfortunately, authors do not explicitly take into consideration dog-human differences in visual perception when designing their experiments. With an image manipulation program we altered stationary images, according to the present knowledge about dog-vision. Besides the effect of dogs' dichromatic vision, the software shows the effect of the lower visual acuity and brightness discrimination, too. Fifty adult humans were tested with pictures showing a female experimenter pointing, gazing or glancing to the left or right side. Half of the pictures were shown after they were altered to a setting that approximated dog vision. Participants had difficulty to find out the direction of glancing when the pictures were in dog-vision mode. Glances in dog-vision setting were followed less correctly and with a slower response time than other cues. Our results are the first that show the visual performance of humans under circumstances that model how dogs' weaker vision would affect their responses in an ethological experiment. We urge researchers to take into consideration the differences between perceptual abilities of dogs and humans, by developing visual stimuli that fit more appropriately to dogs' visual capabilities. Copyright © 2017 Elsevier B.V. All rights reserved.
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Neonatal innate TLR-mediated responses are distinct from those of adults.
Kollmann, Tobias R; Crabtree, Juliet; Rein-Weston, Annie; Blimkie, Darren; Thommai, Francis; Wang, Xiu Yu; Lavoie, Pascal M; Furlong, Jeff; Fortuno, Edgardo S; Hajjar, Adeline M; Hawkins, Natalie R; Self, Steven G; Wilson, Christopher B
2009-12-01
The human neonate and infant are unduly susceptible to infection with a wide variety of microbes. This susceptibility is thought to reflect differences from adults in innate and adaptive immunity, but the nature of these differences is incompletely characterized. The innate immune response directs the subsequent adaptive immune response after integrating information from TLRs and other environmental sensors. We set out to provide a comprehensive analysis defining differences in response to TLR ligation between human neonates and adults. In response to most TLR ligands, neonatal innate immune cells, including monocytes and conventional and plasmacytoid dendritic cells produced less IL-12p70 and IFN-alpha (and consequently induced less IFN-gamma), moderately less TNF-alpha, but as much or even more IL-1beta, IL-6, IL-23, and IL-10 than adult cells. At the single-cell level, neonatal innate cells generally were less capable of producing multiple cytokines simultaneously, i.e., were less polyfunctional. Overall, our data suggest a robust if not enhanced capacity of the neonate vs the adult white-blood cell TLR-mediated response to support Th17- and Th2-type immunity, which promotes defense against extracellular pathogens, but a reduced capacity to support Th1-type responses, which promote defense against intracellular pathogens.
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Tool making, hand morphology and fossil hominins.
Marzke, Mary W
2013-11-19
Was stone tool making a factor in the evolution of human hand morphology? Is it possible to find evidence in fossil hominin hands for this capability? These questions are being addressed with increasingly sophisticated studies that are testing two hypotheses; (i) that humans have unique patterns of grip and hand movement capabilities compatible with effective stone tool making and use of the tools and, if this is the case, (ii) that there exist unique patterns of morphology in human hands that are consistent with these capabilities. Comparative analyses of human stone tool behaviours and chimpanzee feeding behaviours have revealed a distinctive set of forceful pinch grips by humans that are effective in the control of stones by one hand during manufacture and use of the tools. Comparative dissections, kinematic analyses and biomechanical studies indicate that humans do have a unique pattern of muscle architecture and joint surface form and functions consistent with the derived capabilities. A major remaining challenge is to identify skeletal features that reflect the full morphological pattern, and therefore may serve as clues to fossil hominin manipulative capabilities. Hominin fossils are evaluated for evidence of patterns of derived human grip and stress-accommodation features.
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Tool making, hand morphology and fossil hominins
Marzke, Mary W.
2013-01-01
Was stone tool making a factor in the evolution of human hand morphology? Is it possible to find evidence in fossil hominin hands for this capability? These questions are being addressed with increasingly sophisticated studies that are testing two hypotheses; (i) that humans have unique patterns of grip and hand movement capabilities compatible with effective stone tool making and use of the tools and, if this is the case, (ii) that there exist unique patterns of morphology in human hands that are consistent with these capabilities. Comparative analyses of human stone tool behaviours and chimpanzee feeding behaviours have revealed a distinctive set of forceful pinch grips by humans that are effective in the control of stones by one hand during manufacture and use of the tools. Comparative dissections, kinematic analyses and biomechanical studies indicate that humans do have a unique pattern of muscle architecture and joint surface form and functions consistent with the derived capabilities. A major remaining challenge is to identify skeletal features that reflect the full morphological pattern, and therefore may serve as clues to fossil hominin manipulative capabilities. Hominin fossils are evaluated for evidence of patterns of derived human grip and stress-accommodation features. PMID:24101624
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Hood, D C; Birch, D G
1990-10-01
An electrical potential recorded from the cornea, the a-wave of the ERG, is evaluated as a measure of human photoreceptor activity by comparing its behavior to a model derived from in vitro recordings from rod photoreceptors. The leading edge of the ERG exhibits both the linear and nonlinear behavior predicted by this model. The capability for recording the electrical activity of human photoreceptors in vivo opens new avenues for assessing normal and abnormal receptor activity in humans. Furthermore, the quantitative model of the receptor response can be used to isolate the inner retinal contribution, Granit's PII, to the gross ERG. Based on this analysis, the practice of using the trough-to-peak amplitude of the b-wave as a proxy for the amplitude of the inner nuclear layer activity is evaluated.
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Hidalgo-Cantabrana, Claudio; Moro-García, Marco A.; Blanco-Míguez, Aitor; Fdez-Riverola, Florentino; Lourenço, Anália; Alonso-Arias, Rebeca; Sánchez, Borja
2017-01-01
Scientific studies focused on the role of the human microbiome over human health have generated billions of gigabits of genetic information during the last decade. Nowadays integration of all this information in public databases and development of pipelines allowing us to biotechnologically exploit this information are urgently needed. Prediction of the potential bioactivity of the products encoded by the human gut microbiome, or metaproteome, is the first step for identifying proteins responsible for the molecular interaction between microorganisms and the immune system. We have recently published the Mechanism of Action of the Human Microbiome (MAHMI) database (http://www.mahmi.org), conceived as a resource compiling peptide sequences with a potential immunomodulatory activity. Fifteen out of the 300 hundred million peptides contained in the MAHMI database were synthesized. These peptides were identified as being encrypted in proteins produced by gut microbiota members, they do not contain cleavage points for the major intestinal endoproteases and displayed high probability to have immunomodulatory bioactivity. The bacterial peptides FR-16 and LR-17 encrypted in proteins from Bifidobacterium longum DJ010A and Bifidobacterium fragilis YCH46 respectively, showed the higher immune modulation capability over human peripheral blood mononuclear cells. Both peptides modulated the immune response toward increases in the Th17 and decreases in the Th1 cell response, together with an induction of IL-22 production. These results strongly suggest the combined use of bioinformatics and in vitro tools as a first stage in the screening of bioactive peptides encrypted in the human gut metaproteome. PMID:28943872
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Kilic, Tugba; Zhang, Yu Shrike; Avci, Huseyin; Hu, Ning; Kim, Duckjin; Branco, Cristina; Aleman, Julio; Massa, Solange; Silvestri, Antonia; Kang, Jian; Desalvo, Anna; Hussaini, Mohammed Abdullah; Chae, Su‐Kyoung; Polini, Alessandro; Bhise, Nupura; Hussain, Mohammad Asif; Lee, HeaYeon
2017-01-01
Development of an efficient sensing platform capable of continual monitoring of biomarkers is needed to assess the functionality of the in vitro organoids and to evaluate their biological responses toward pharmaceutical compounds or chemical species over extended periods of time. Here, a novel label‐free microfluidic electrochemical (EC) biosensor with a unique built‐in on‐chip regeneration capability for continual measurement of cell‐secreted soluble biomarkers from an organoid culture in a fully automated manner without attenuating the sensor sensitivity is reported. The microfluidic EC biosensors are integrated with a human liver‐on‐a‐chip platform for continual monitoring of the metabolic activity of the organoids by measuring the levels of secreted biomarkers for up to 7 d, where the metabolic activity of the organoids is altered by a systemically applied drug. The variations in the biomarker levels are successfully measured by the microfluidic regenerative EC biosensors and agree well with cellular viability and enzyme‐linked immunosorbent assay analyses, validating the accuracy of the unique sensing platform. It is believed that this versatile and robust microfluidic EC biosensor that is capable of automated and continual detection of soluble biomarkers will find widespread use for long‐term monitoring of human organoids during drug toxicity studies or efficacy assessments of in vitro platforms. PMID:28546915
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Can Monkeys (Macaca mulatta) Represent Invisible Displacement?
NASA Technical Reports Server (NTRS)
Filion, Christine M.; Washburn, David A.; Gulledge, Jonathan P.
1996-01-01
Four experiments were conducted to assess whether or not rhesus macaques (Macaca mulatta) could represent the unperceived movements of a stimulus. Subjects were tested on 2 computerized tasks, HOLE (monkeys) and LASER (humans and monkeys), in which subjects needed to chase or shoot at, respectively, a moving target that either remained visible or became invisible for a portion of its path of movement. Response patterns were analyzed and compared between target-visible and target-invisible conditions. Results of Experiments 1, 2, and 3 demonstrated that the monkeys are capable of extrapolating movement. That this extrapolation involved internal representation of the target's invisible movement was suggested but not confirmed. Experiment 4, however, demonstrated that the monkeys are capable of representing the invisible displacements of a stimulus.
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A Reasoning Hardware Platform for Real-Time Common-Sense Inference
Barba, Jesús; Santofimia, Maria J.; Dondo, Julio; Rincón, Fernando; Sánchez, Francisco; López, Juan Carlos
2012-01-01
Enabling Ambient Intelligence systems to understand the activities that are taking place in a supervised context is a rather complicated task. Moreover, this task cannot be successfully addressed while overlooking the mechanisms (common-sense knowledge and reasoning) that entitle us, as humans beings, to successfully undertake it. This work is based on the premise that Ambient Intelligence systems will be able to understand and react to context events if common-sense capabilities are embodied in them. However, there are some difficulties that need to be resolved before common-sense capabilities can be fully deployed to Ambient Intelligence. This work presents a hardware accelerated implementation of a common-sense knowledge-base system intended to improve response time and efficiency. PMID:23012540
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Man-vehicle systems research facility: Design and operating characteristics
NASA Technical Reports Server (NTRS)
1983-01-01
The Man-Vehicle Systems Research Facility (MVSRF) provides the capability of simulating aircraft (two with full crews), en route and terminal air traffic control and aircrew interactions, and advanced cockpit (1995) display representative of future generations of aircraft, all within the full mission context. The characteristics of this facility derive from research, addressing critical human factors issues that pertain to: (1) information requirements for the utilization and integration of advanced electronic display systems, (2) the interaction and distribution of responsibilities between aircrews and ground controllers, and (3) the automation of aircrew functions. This research has emphasized the need for high fidelity in simulations and for the capability to conduct full mission simulations of relevant aircraft operations. This report briefly describes the MVSRF design and operating characteristics.
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Animals Remember Previous Facial Expressions that Specific Humans Have Exhibited.
Proops, Leanne; Grounds, Kate; Smith, Amy Victoria; McComb, Karen
2018-05-07
For humans, facial expressions are important social signals, and how we perceive specific individuals may be influenced by subtle emotional cues that they have given us in past encounters. A wide range of animal species are also capable of discriminating the emotions of others through facial expressions [1-5], and it is clear that remembering emotional experiences with specific individuals could have clear benefits for social bonding and aggression avoidance when these individuals are encountered again. Although there is evidence that non-human animals are capable of remembering the identity of individuals who have directly harmed them [6, 7], it is not known whether animals can form lasting memories of specific individuals simply by observing subtle emotional expressions that they exhibit on their faces. Here we conducted controlled experiments in which domestic horses were presented with a photograph of an angry or happy human face and several hours later saw the person who had given the expression in a neutral state. Short-term exposure to the facial expression was enough to generate clear differences in subsequent responses to that individual (but not to a different mismatched person), consistent with the past angry expression having been perceived negatively and the happy expression positively. Both humans were blind to the photograph that the horses had seen. Our results provide clear evidence that some non-human animals can effectively eavesdrop on the emotional state cues that humans reveal on a moment-to-moment basis, using their memory of these to guide future interactions with particular individuals. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Tumor necrosis factor-inducing activities of Cryptococcus neoformans components.
Delfino, D; Cianci, L; Migliardo, M; Mancuso, G; Cusumano, V; Corradini, C; Teti, G
1996-01-01
Cryptococcus neoformans-induced tumor necrosis factor alpha (TNF-alpha) production may lead to increased human immunodeficiency virus replication in patients with AIDS. In order to identify cryptococcal components that are predominantly responsible for stimulating TNF production, various concentrations of glucuronoxylomannan (GXM), galactoxylomannan (GalXM), mannoproteins (MP), and alpha(1-3) [corrected] glucan were added to whole-blood cultures. All of the cryptococcal components tested, as well as whole heat-killed cryptococci, were capable of inducing TNF-alpha release in a dose-dependent manner. MP were significantly more potent than any of the other cryptococcal components tested or heat-killed cryptococci in stimulating TNF-alpha production (P < 0.05). GXM, in contrast, was significantly less potent in this activity than either GalXM or MP (P < 0.05). As little as 0.5 microg of MP per ml was sufficient to produce moderate but significant elevations of TNF-alpha release. Maximal MP-induced TNF-alpha levels were similar to those induced by Salmonella enteritidis lipopolysaccharide, our positive control. Further experiments using isolated leukocytes suggested that monocytes were the cell population mainly responsible for TNF-alpha production, although the participation of other cell types could not be excluded. The presence of complement-sufficient plasma was a necessary requirement for TNF-alpha induction by GXM, GalXM, and low doses of MP. High MP concentrations (100 microg/ml) were also capable of stimulating TNF-alpha production in the absence of plasma. These data indicate that soluble products released by C. neoformans are capable of inducing TNF-alpha secretion in human leukocytes. This may be clinically relevant, since high concentrations of such products are frequently found in the body fluids of AIDS patients infected with C. neoformans. PMID:8945566
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A visual study of chemotaxis of human lymphocytes using a collagen-gel assay.
Wilkinson, P C
1985-01-21
Time-lapse cinematography was used to study the chemotactic responsiveness of human blood lymphocytes as defined by morphological orientation and directional locomotion in gradients. At present, evidence for lymphocyte chemotaxis is indirect since neither of these essential features can be demonstrated with Boyden filter assays. Few lymphocytes direct from blood were motile, but culture in vitro for 1-3 days increased the proportion of locomotor forms to 30-40%. These cells were placed on 3-D collagen gels, and a chemotactic source was presented nearby on a small filter placed on the surface of, or within, the gel. The minority of lymphocytes that were capable of locomotion showed chemotactic responses to filters soaked in lipopolysaccharide if fresh human serum (20%), but not heat-inactivated serum, was present. Lymphocytes responded by protrusion of a lamella in the direction of the gradient source: 76% of locomotor lymphocytes showed their first orientation into the 180 degrees sector facing the source. They then moved directionally towards the source. The response to purified C5 peptides was equivocal. The locomotor lymphocytes showed a chemotactic response to supernatant fluids derived from cultures of the adherent mononuclear cell fraction from human blood (greater than 80% monocytes), judged by the same criteria. No particular lymphocyte type constituted the locomotor population. After exposure to LPS-activated serum, both T and B lymphocytes showed locomotor forms. There were slightly more T4+ cells among the locomotor population than among the population as a whole.
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NASA Astrophysics Data System (ADS)
Nakamura, Christopher M.; Murphy, Sytil K.; Christel, Michael G.; Stevens, Scott M.; Zollman, Dean A.
2016-06-01
Computer-automated assessment of students' text responses to short-answer questions represents an important enabling technology for online learning environments. We have investigated the use of machine learning to train computer models capable of automatically classifying short-answer responses and assessed the results. Our investigations are part of a project to develop and test an interactive learning environment designed to help students learn introductory physics concepts. The system is designed around an interactive video tutoring interface. We have analyzed 9 with about 150 responses or less. We observe for 4 of the 9 automated assessment with interrater agreement of 70% or better with the human rater. This level of agreement may represent a baseline for practical utility in instruction and indicates that the method warrants further investigation for use in this type of application. Our results also suggest strategies that may be useful for writing activities and questions that are more appropriate for automated assessment. These strategies include building activities that have relatively few conceptually distinct ways of perceiving the physical behavior of relatively few physical objects. Further success in this direction may allow us to promote interactivity and better provide feedback in online learning systems. These capabilities could enable our system to function more like a real tutor.
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The evolution of music and human social capability
Schulkin, Jay; Raglan, Greta B.
2014-01-01
Music is a core human experience and generative processes reflect cognitive capabilities. Music is often functional because it is something that can promote human well-being by facilitating human contact, human meaning, and human imagination of possibilities, tying it to our social instincts. Cognitive systems also underlie musical performance and sensibilities. Music is one of those things that we do spontaneously, reflecting brain machinery linked to communicative functions, enlarged and diversified across a broad array of human activities. Music cuts across diverse cognitive capabilities and resources, including numeracy, language, and space perception. In the same way, music intersects with cultural boundaries, facilitating our “social self” by linking our shared experiences and intentions. This paper focuses on the intersection between the neuroscience of music, and human social functioning to illustrate the importance of music to human behaviors. PMID:25278827
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In vitro responses to avian influenza H5 by human CD4 T-cells*
Cusick, Matthew F; Wang, Shuping; Eckels, David D
2009-01-01
To address the question of whether human T-cells are capable of recognizing novel isolates of influenza virus, in vitro responses to recombinant antigens and synthetic peptides derived from the sequences of H1, H3, and H5 were examined in a cohort of 64 individuals selected from a healthy blood donor population. Humans respond in vitro to H1 and H3 following exposure through natural infection and vaccination. Responses to H5 were well correlated with those to H1 or H3 and thus a significant repertoire of H5-responsive T-cells is present in many individuals; clear non-responders to H1, H3, and H5, however, do exist. Differences were observed in the cytokine responses to H1, H3, and H5; whereas both IL-2 and IFN-γ production characteristic of memory responses were observed for H1 and H3, H5-specific responses elicited primarily IL-2 and little or no IFN-γ consistent with a naïve T cell phenotype. Responses to all influenza HA were restricted by HLA-DR molecules. To address the structural basis for T-cell recognition of H1 and H5, overlapping synthetic peptides were used to identify epitopes and to determine whether recognition of H5 was limited to homologous sequences in H1, the most closely related HA phylogenetically. Although responses were generally correlated, no complete structural overlap was observed. These results suggest that helper T cell cross reactivity between different influenza strains may impart cross-protection to H5N1 strain of influenza. PMID:19841175
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NASA Astrophysics Data System (ADS)
Lee, Jeonghun; Oh, Eun-Taex; Yoon, Haerry; Kim, Hyunmi; Park, Heon Joo; Kim, Chulhee
2016-04-01
Mesoporous silica nanocontainers (MSNs) with biologically responsive gatekeepers have great potential for effective delivery of cargo molecules to the desired sites. For that purpose, peptides could be effective candidates as gatekeepers because of their bioresponsiveness and targeting capability. Taking advantage of the zinc finger domain peptide (CXXC), we designed a biocompatible all-peptide gatekeeper (WCGKC) with on-off gatekeeping capability through stimulus-responsive conformational conversion and the steric bulkiness of the tryptophan unit. The turn structure induced by an intramolecular disulfide bond of the peptide gatekeeper (WCGKC-SS) completely inhibited the release of the entrapped doxorubicin (DOX). However, upon reduction of the disulfide bond by glutathione (GSH), the peptide conformation was converted to a random structure, which opened the orifice of the mesopore leading to the release of DOX. The amine moiety of the lysine of the peptide gatekeeper was PEGylated to enhance dispersion stability and biocompatibility of the nanocontainer. Furthermore, the MSNs with the peptide gatekeeper (PEG-WCGKC-SS-Si) selectively released the entrapped DOX in A549 human lung cancer cells in a controlled manner triggered by intracellular GSH, but not in CCD normal lung cells containing a low intracellular GSH level. In A549 cells, DOX-loaded PEG-WCGKC-SS-Si exhibited about 10-times higher cytotoxicity induced by apoptosis than that in CCD cells.Mesoporous silica nanocontainers (MSNs) with biologically responsive gatekeepers have great potential for effective delivery of cargo molecules to the desired sites. For that purpose, peptides could be effective candidates as gatekeepers because of their bioresponsiveness and targeting capability. Taking advantage of the zinc finger domain peptide (CXXC), we designed a biocompatible all-peptide gatekeeper (WCGKC) with on-off gatekeeping capability through stimulus-responsive conformational conversion and the steric bulkiness of the tryptophan unit. The turn structure induced by an intramolecular disulfide bond of the peptide gatekeeper (WCGKC-SS) completely inhibited the release of the entrapped doxorubicin (DOX). However, upon reduction of the disulfide bond by glutathione (GSH), the peptide conformation was converted to a random structure, which opened the orifice of the mesopore leading to the release of DOX. The amine moiety of the lysine of the peptide gatekeeper was PEGylated to enhance dispersion stability and biocompatibility of the nanocontainer. Furthermore, the MSNs with the peptide gatekeeper (PEG-WCGKC-SS-Si) selectively released the entrapped DOX in A549 human lung cancer cells in a controlled manner triggered by intracellular GSH, but not in CCD normal lung cells containing a low intracellular GSH level. In A549 cells, DOX-loaded PEG-WCGKC-SS-Si exhibited about 10-times higher cytotoxicity induced by apoptosis than that in CCD cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr09280a
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On the sulfation of O-desmethyltramadol by human cytosolic sulfotransferases.
Rasool, Mohammed I; Bairam, Ahsan F; Kurogi, Katsuhisa; Liu, Ming-Cheh
2017-10-01
Previous studies have demonstrated that sulfate conjugation is involved in the metabolism of the active metabolite of tramadol, O-desmethyltramadol (O-DMT). The current study aimed to systematically identify the human cytosolic sulfotransferases (SULTs) that are capable of mediating the sulfation of O-DMT. The sulfation of O-DMT under metabolic conditions was demonstrated using HepG2 hepatoma cells and Caco-2 human colon carcinoma cells. O-DMT-sulfating activity of thirteen known human SULTs and four human organ specimens was examined using an established sulfotransferase assay. pH-Dependency and kinetic parameters were also analyzed using, respectively, buffers at different pHs and varying O-DMT concentrations in the assays. Of the thirteen human SULTs tested, only SULT1A3 and SULT1C4 were found to display O-DMT-sulfating activity, with different pH-dependency profiles. Kinetic analysis revealed that SULT1C4 was 60 times more catalytically efficient in mediating the sulfation of O-DMT than SULT1A3 at respective optimal pH. Of the four human organ specimens tested, the cytosol prepared from the small intestine showed much higher O-DMT-sulfating activity than cytosols prepared from liver, lung, and kidney. Both cultured HepG2 and Caco-2 cells were shown to be capable of sulfating O-DMT and releasing sulfated O-DMT into cultured media. SULT1A3 and SULT1C4 were the major SULTs responsible for the sulfation of O-DMT. Collectively, the results obtained provided a molecular basis underlying the sulfation of O-DMT and contributed to a better understanding about the pharmacokinetics and pharmacodynamics of tramadol in humans. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
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NASA Astrophysics Data System (ADS)
O'Brien, Benjamin M.; McKay, Thomas G.; Xie, Sheng Q.; Calius, Emilio P.; Anderson, Iain A.
2011-04-01
Life shows us that the distribution of intelligence throughout flexible muscular networks is a highly successful solution to a wide range of challenges, for example: human hearts, octopi, or even starfish. Recreating this success in engineered systems requires soft actuator technologies with embedded sensing and intelligence. Dielectric Elastomer Actuator(s) (DEA) are promising due to their large stresses and strains, as well as quiet flexible multimodal operation. Recently dielectric elastomer devices were presented with built in sensor, driver, and logic capability enabled by a new concept called the Dielectric Elastomer Switch(es) (DES). DES use electrode piezoresistivity to control the charge on DEA and enable the distribution of intelligence throughout a DEA device. In this paper we advance the capabilities of DES further to form volatile memory elements. A set reset flip-flop with inverted reset line was developed based on DES and DEA. With a 3200V supply the flip-flop behaved appropriately and demonstrated the creation of dielectric elastomer memory capable of changing state in response to 1 second long set and reset pulses. This memory opens up applications such as oscillator, de-bounce, timing, and sequential logic circuits; all of which could be distributed throughout biomimetic actuator arrays. Future work will include miniaturisation to improve response speed, implementation into more complex circuits, and investigation of longer lasting and more sensitive switching materials.
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The HAL 9000 Space Operating System Real-Time Planning Engine Design and Operations Requirements
NASA Technical Reports Server (NTRS)
Stetson, Howard; Watson, Michael D.; Shaughnessy, Ray
2012-01-01
In support of future deep space manned missions, an autonomous/automated vehicle, providing crew autonomy and an autonomous response planning system, will be required due to the light time delays in communication. Vehicle capabilities as a whole must provide for tactical response to vehicle system failures and space environmental effects induced failures, for risk mitigation of permanent loss of communication with Earth, and for assured crew return capabilities. The complexity of human rated space systems and the limited crew sizes and crew skills mix drive the need for a robust autonomous capability on-board the vehicle. The HAL 9000 Space Operating System[2] designed for such missions and space craft includes the first distributed real-time planning / re-planning system. This paper will detail the software architecture of the multiple planning engine system, and the interface design for plan changes, approval and implementation that is performed autonomously. Operations scenarios will be defined for analysis of the planning engines operations and its requirements for nominal / off nominal activities. An assessment of the distributed realtime re-planning system, in the defined operations environment, will be provided as well as findings as it pertains to the vehicle, crew, and mission control requirements needed for implementation.
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EOSINOPHILS: MULTIFACETED BIOLOGIC PROPERTIES AND ROLES IN HEALTH AND DISEASE
Kita, Hirohito
2011-01-01
Summary Eosinophils are leukocytes resident in mucosal tissues. During Th2-type inflammation, eosinophils are recruited from bone marrow and blood to the sites of immune response. While eosinophils have been considered end-stage cells involved in host protection against parasite infection and immunopathology in hypersensitivity disease, recent studies changed this perspective. Eosinophils are now considered multifunctional leukocytes involved in tissue homeostasis, modulation of adaptive immune responses, and innate immunity to certain microbes. Eosinophils are capable of producing immunoregulatory cytokines and are actively involved in regulation of Th2-type immune responses. However, such new information does not preclude earlier observations showing that eosinophils, in particular human eosinophils, are also effector cells with pro-inflammatory and destructive capabilities. Eosinophils with activation phenotypes are observed in biological specimens from patients with disease, and deposition of eosinophil products is readily seen in the affected tissues from these patients. Therefore, it would be reasonable to consider the eosinophil a multifaceted leukocyte that contributes to various physiological and pathological processes depending on their location and activation status. This review summarizes the emerging concept of the multifaceted immunobiology of eosinophils and discusses the roles of eosinophils in health and disease and the challenges and perspectives in the field. PMID:21682744
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Human Rating Requirements for NASA's Constellation Program
NASA Technical Reports Server (NTRS)
Berdich, Debbie
2008-01-01
NASA s Constellation Program (CxP) will conduct a series of human space expeditions of increasing scope, starting with missions supporting the International Space Station and expanding to encompass the Moon and Mars. Although human-rating is an integral part of all CxP activities throughout their life cycle, NASA Procedural Requirements document NPR 8705.2B, Human-Rating Requirements (HRR) for Space Flight Systems, defines the additional processes, procedures, and requirements necessary to produce human-rated space systems that protect the safety of crew members and passengers on these NASA missions. In order to be in compliance with 8705.2B the CxP must show appropriate implementation or progression toward the HRR, or justification for an exception. Compliance includes an explanation of how the CxP intends to meet the HRR, analyses to be performed to determine implementation; and a matrix to trace the HRR to CxP requirements. The HRR requires the CxP to establish a human system integration team (HSIT), consisting of astronauts, mission operations personnel, training personnel, ground processing personnel, human factors personnel, and human engineering experts, with clearly defined authority, responsibility, and accountability to lead the human-system integration. For example, per the HRR the HSIT is involved in the evaluation of crew workload, human-in-the-loop usability evaluations, determining associated criteria, and in assessment of how these activities influenced system design. In essence, the HSIT is invaluable in CxP s ability to meet the three fundamental tenets of human rating: the process of designing, evaluating, and assuring that the total system can safely conduct the required human missions; the incorporation of design features and capabilities that accommodate human interaction with the system to enhance overall safety and mission success; and the incorporation of design features and capabilities to enable safe recovery of the crew from hazardous situations.
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Neurophysiological Estimates of Human Performance Capabilities in Aerospace Systems
1976-11-30
different nights. These stages correspond descriptively to light , medium, deep, sleep and the dream state. Upon awakening, the subjects performed a series of...of usual in terms of the nervous systems response to the light -dark cycle and who are alert at night for those operations which require skill and judge...some strik- ing exceptions, mankind is tied to the light -dark cycle - rising with the onset of light and retiring for nocturnal sleep in the hours of
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Functional and Cellular Responses to Laser Injury in the Rat Snake Retina
2007-01-01
snake retina, previous studies have documented the role of photo-oxidative stress in inducing photoreceptor damage . 20 The present research was designed...Tyrrell, "Activation of NF-kappa B in human skin fibroblasts by the oxidative stress generated by UVA radiation," Photochem. Photobiol., 62, pp. 463-468...induced retinal photoreceptor damage .9. 10 In addition to its imaging capabilities, the cSLO can also be modulated externally to produce stimulus patterns
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Novel Low-Cost Sensor for Human Bite Force Measurement
Fastier-Wooller, Jarred; Phan, Hoang-Phuong; Dinh, Toan; Nguyen, Tuan-Khoa; Cameron, Andrew; Öchsner, Andreas; Dao, Dzung Viet
2016-01-01
This paper presents the design and development of a low cost and reliable maximal voluntary bite force sensor which can be manufactured in-house by using an acrylic laser cutting machine. The sensor has been designed for ease of fabrication, assembly, calibration, and safe use. The sensor is capable of use within an hour of commencing production, allowing for rapid prototyping/modifications and practical implementation. The measured data shows a good linear relationship between the applied force and the electrical resistance of the sensor. The output signal has low drift, excellent repeatability, and a large measurable range of 0 to 700 N. A high signal-to-noise response to human bite forces was observed, indicating the high potential of the proposed sensor for human bite force measurement. PMID:27509496
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Żuradzki, Tomasz
2014-12-01
In this article, I present a new interpretation of the pro-life view on the status of early human embryos. In my understanding, this position is based not on presumptions about the ontological status of embryos and their developmental capabilities but on the specific criteria of rational decisions under uncertainty and on a cautious response to the ambiguous status of embryos. This view, which uses the decision theory model of moral reasoning, promises to reconcile the uncertainty about the ontological status of embryos with the certainty about normative obligations. I will demonstrate that my interpretation of the pro-life view, although seeming to be stronger than the standard one, has limited scope and cannot be used to limit destructive research on human embryos.
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Fatherhood, childism, and the creation of society.
Wall, John
2007-01-01
This essay argues for a new religious ethical approach to fatherhood centered on children and their expanding capabilities for participation in society. Under the notion of "childism"—in analogy to feminism, womanism, humanism, and the like—it takes the perspective of the experiences and concerns of childhood as such. In contrast with a soft patriarchal argument for fatherhood that dominates much religious discourse today, it argues for a larger and more hopeful vision of fatherhood as directed toward the human social good. This requires, methodologically, a richer hermeneutical circle between religion and the social sciences. Substantively, it calls for Christian and other religious ethicists to re-imagine fatherhood as an integrated public–private responsibility that aims to cultivate children’s fully human social creativity as images of their Creator.
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Researching pharmacist managerial capability: philosophical perspectives and paradigms of inquiry.
Woods, Phillip; Gapp, Rod; King, Michelle A
2015-01-01
In successful community pharmacy business enterprises suitably responsive actions to meet ever-increasing change require capable pharmacy managers who readily learn and adapt. Capability as a concept is generally understood to be the ability of a manager to identify and act to solve unfamiliar problems in unfamiliar situations. Capability is characterized by adaptability and flexibility. However, different understandings of the concept 'capability' and what it means to be 'capable' are indirect and incomplete. This paper aims to clarify current theories regarding the concept of 'capability' at the level of the individual, and through this to make more explicit what is known about the phenomenon, but more particularly, how we know what we know. The analysis includes the concept of 'competence' because explanations of capability include competence, and the two concepts are not clearly separated in the literature. By probing the epistemological origins of current theory concerning both concepts, the limiting taken for granted assumptions are revealed. Assumptions about context and time, and the psychological theory through which individuals are assumed to perceive, know and learn, are illuminated. The analysis, in connection with the literature, shows how the interpretive philosophic research approach may reveal a different and useful theoretical perspective for explaining capability as a dynamic performance. It is suggested that such a perspective may narrow the gap between the theory of capability and its practice. The interpretive perspective holds potential to reveal how capability, as performed by successful community pharmacy managers, might be further researched and strengthened. This paper supports the challenging suggestion that pharmacy social research needs to rebalance the dominance of purely empirical research by exploring interpretive methodologies to better understand human actions and relations in the context of pharmacy. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.
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Next Gen NEAR: Near Earth Asteroid Human Robotic Precursor Mission Concept
NASA Technical Reports Server (NTRS)
Rivkin, Andrew S.; Kirby, Karen; Cheng, Andrew F.; Gold, Robert; Kelly, Daniel; Reed, Cheryl; Abell, Paul; Garvin, James; Landis, Rob
2012-01-01
Asteroids have long held the attention of the planetary science community. In particular, asteroids that evolve into orbits near that of Earth, called near-Earth objects (NEO), are of high interest as potential targets for exploration due to the relative ease (in terms of delta V) to reach them. NASA's Flexible Path calls for missions and experiments to be conducted as intermediate steps towards the eventual goal of human exploration of Mars; piloted missions to NEOs are such example. A human NEO mission is a valuable exploratory step beyond the Earth-Moon system enhancing capabilities that surpass our current experience, while also developing infrastructure for future mars exploration capabilities. To prepare for a human rendezvous with an NEO, NASA is interested in pursuing a responsible program of robotic NEO precursor missions. Next Gen NEAR is such a mission, building on the NEAR Shoemaker mission experience at the JHU/APL Space Department, to provide an affordable, low risk solution with quick data return. Next Gen NEAR proposes to make measurements needed for human exploration to asteroids: to demonstrate proximity operations, to quantify hazards for human exploration and to characterize an environment at a near-Earth asteroid representative of those that may be future human destinations. The Johns Hopkins University Applied Physics Laboratory has demonstrated exploration-driven mission feasibility by developing a versatile spacecraft design concept using conventional technologies that satisfies a set of science, exploration and mission objectives defined by a concept development team in the summer of 2010. We will describe the mission concept and spacecraft architecture in detail. Configuration options were compared with the mission goals and objectives in order to select the spacecraft design concept that provides the lowest cost, lowest implementation risk, simplest operation and the most benefit for the mission implementation. The Next Gen NEAR spacecraft was designed to support rendezvous with a range of candidate asteroid targets and could easily be launched with one of several NASA launch vehicles. The Falcon 9 launch vehicle supports a Next Gen NEAR launch to target many near-Earth asteroids under consideration that could be reached with a C3 of 18 km2/sec2 or less, and the Atlas V-401 provides added capability supporting launch to NEAs that require more lift capacity while at the same time providing such excess lift capability that another payload of opportunity could be launch in conjunction with Next Gen NEAR. Next Gen NEAR will measure and interact with the target surface in ways never undertaken at an asteroid, and will prepare for first human precursor mission by demonstrating exploration science operations at an accessible NEO. This flexible mission and spacecraft design concept supports target selection based on upcoming Earth-based observations and also provides opportunities for co-manifest & international partnerships. JHU/APL has demonstrated low cost, low risk, high impact missions and this mission will help to prepare NASA for human NEO exploration by combining the best of NASA s human and robotic exploration capabilities.
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Food or threat? Wild capuchin monkeys (Sapajus libidinosus) as both predators and prey of snakes.
Falótico, Tiago; Verderane, Michele P; Mendonça-Furtado, Olívia; Spagnoletti, Noemi; Ottoni, Eduardo B; Visalberghi, Elisabetta; Izar, Patrícia
2018-01-01
Snakes present a hazard to primates, both as active predators and by defensive envenomation. This risk might have been a selective pressure on the evolution of primate visual and cognitive systems, leading to several behavioral traits present in human and non-human primates, such as the ability to quickly learn to fear snakes. Primates seldom prey on snakes, and humans are one of the few primate species that do. We report here another case, the wild capuchin monkey (Sapajus libidinosus), which preys on snakes. We hypothesized that capuchin monkeys, due to their behavioral plasticity, and cognitive and visual skills, would be capable of discriminating dangerous and non-dangerous snakes and behave accordingly. We recorded the behavioral patterns exhibited toward snakes in two populations of S. libidinosus living 320 km apart in Piauí, Brazil. As expected, capuchins have a fear reaction to dangerous snakes (usually venomous or constricting snakes), presenting mobbing behavior toward them. In contrast, they hunt and consume non-dangerous snakes without presenting the fear response. Our findings support the tested hypothesis that S. libidinosus are capable of differentiating snakes by level of danger: on the one hand they protect themselves from dangerous snakes, on the other hand they take opportunities to prey on non-dangerous snakes. Since capuchins and humans are both predators and prey of snakes, further studies of this complex relationship may shed light on the evolution of these traits in the human lineage.
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Li, Ping; Ann, Jason; Akk, Gustav
2013-01-01
Neonicotinoids are synthetic, nicotine-derived insecticides used for agricultural and household pest control. While highly effective at activating insect nicotinic receptors, many neonicotinoids are also capable of directly activating and/or modulating the activation of vertebrate nicotinic receptors. In this study, we have investigated the actions of the neonicotinoids clothianidin (CTD) and imidacloprid (IMI) on human neuronal α4β2 nicotinic acetylcholine receptors. The data demonstrate that the compounds are weak agonists of the human receptors with relative peak currents of 1–4 % of the response to 1 mM acetylcholine (ACh). Coapplication of IMI strongly inhibited currents elicited by ACh. From Schild plot analysis, we estimate that the affinity of IMI to the human α4β2 receptor is 18 µM. The application of low concentrations of CTD potentiated responses to low concentrations of ACh, suggesting that receptors occupied by one ACh and one CTD molecule have a higher gating efficacy than receptors with one ACh bound. Interestingly, subunit stoichiometry affected inhibition by CTD, with (α4)2(β2)3 receptors significantly more strongly inhibited than the (α4)3(β2)2 receptors. PMID:21538459
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Deciphering microbial interactions in synthetic human gut microbiome communities.
Venturelli, Ophelia S; Carr, Alex C; Fisher, Garth; Hsu, Ryan H; Lau, Rebecca; Bowen, Benjamin P; Hromada, Susan; Northen, Trent; Arkin, Adam P
2018-06-21
The ecological forces that govern the assembly and stability of the human gut microbiota remain unresolved. We developed a generalizable model-guided framework to predict higher-dimensional consortia from time-resolved measurements of lower-order assemblages. This method was employed to decipher microbial interactions in a diverse human gut microbiome synthetic community. We show that pairwise interactions are major drivers of multi-species community dynamics, as opposed to higher-order interactions. The inferred ecological network exhibits a high proportion of negative and frequent positive interactions. Ecological drivers and responsive recipient species were discovered in the network. Our model demonstrated that a prevalent positive and negative interaction topology enables robust coexistence by implementing a negative feedback loop that balances disparities in monospecies fitness levels. We show that negative interactions could generate history-dependent responses of initial species proportions that frequently do not originate from bistability. Measurements of extracellular metabolites illuminated the metabolic capabilities of monospecies and potential molecular basis of microbial interactions. In sum, these methods defined the ecological roles of major human-associated intestinal species and illuminated design principles of microbial communities. © 2018 The Authors. Published under the terms of the CC BY 4.0 license.
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Activation of Latent HIV Using Drug-loaded Nanoparticles
NASA Astrophysics Data System (ADS)
Kovochich, Michael
Antiretroviral therapy is currently only capable of controlling human immunodeficiency virus (HIV) replication, rather than completely eradicating virus from patients. This is due in part to the establishment of a latent virus reservoir in resting CD4+ T-cells, which persists even in the presence of highly active antiretroviral therapy (HAART). It is thought that forced activation of latently infected cells could induce virus production, allowing targeting of the cell by the immune response. A variety of molecules are able to stimulate HIV from latency. However, no tested purging strategy has proven capable of eliminating the infection completely or preventing viral rebound if therapy is stopped. Hence, novel latency activation approaches are required. Nanoparticles can offer several advantages over more traditional drug delivery methods, including improved drug solubility, stability, and the ability to simultaneously target multiple different molecules to particular cell or tissue types. Here we describe the development of a novel lipid nanoparticle with the protein kinase C activator bryostatin-2 incorporated (LNP-Bry). These particles can target, activate primary human CD4+ T-cells, and stimulate latent virus production from human T-cell lines in vitro and from latently infected cells in a humanized mouse model ex vivo. This activation was synergistically enhanced by the histone deacetylase inhibitor (HDACi) sodium butyrate. Furthermore, LNP-Bry can also be loaded with the protease inhibitor nelfinavir (LNP-Bry-Nel), producing a particle capable of both activating latent virus and inhibiting viral spread. LNP-Bry was further tested for its in vivo biodistribution in both wild type mice (C57 black 6), as well as humanized mice (SCID-hu Thy/Liv, and bone marrow-liver-thymus [BLT]). LNP-Bry accumulated in the spleen and induced the early activation marker CD69 in wild type mice. Taken together, these data demonstrate the ability of nanotechnological approaches to provide improved methods for activating latent HIV and provide key proof-of-principle experiments showing how novel delivery systems may enhance future HIV therapy.
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Human-machine interface hardware: The next decade
NASA Technical Reports Server (NTRS)
Marcus, Elizabeth A.
1991-01-01
In order to understand where human-machine interface hardware is headed, it is important to understand where we are today, how we got there, and what our goals for the future are. As computers become more capable, faster, and programs become more sophisticated, it becomes apparent that the interface hardware is the key to an exciting future in computing. How can a user interact and control a seemingly limitless array of parameters effectively? Today, the answer is most often a limitless array of controls. The link between these controls and human sensory motor capabilities does not utilize existing human capabilities to their full extent. Interface hardware for teleoperation and virtual environments is now facing a crossroad in design. Therefore, we as developers need to explore how the combination of interface hardware, human capabilities, and user experience can be blended to get the best performance today and in the future.
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Critical systems for public health management of floods, North Dakota.
Wiedrich, Tim W; Sickler, Juli L; Vossler, Brenda L; Pickard, Stephen P
2013-01-01
Availability of emergency preparedness funding between 2002 and 2009 allowed the North Dakota Department of Health to build public health response capabilities. Five of the 15 public health preparedness capability areas identified by the Centers for Disease Control and Prevention in 2011 have been thoroughly tested by responses to flooding in North Dakota in 2009, 2010, and 2011; those capability areas are information sharing, emergency operations coordination, medical surge, material management and distribution, and volunteer management. Increasing response effectiveness has depended on planning, implementation of new information technology, changes to command and control procedures, containerized response materials, and rapid contract procedures. Continued improvement in response and maintenance of response capabilities is dependent on ongoing funding.
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The human oxytocin gene promoter is regulated by estrogens.
Richard, S; Zingg, H H
1990-04-15
Gonadal steroids affect brain function primarily by altering the expression of specific genes, yet the specific mechanisms by which neuronal target genes undergo such regulation are unknown. Recent evidence suggests that the expression of the neuropeptide gene for oxytocin (OT) is modulated by estrogens. We therefore examined the possibility that this regulation occurred via a direct interaction of the estrogen-receptor complex with cis-acting elements flanking the OT gene. DNA-mediated gene transfer experiments were performed using Neuro-2a neuroblastoma cells and chimeric plasmids containing portions of the human OT gene 5'-glanking region linked to the chloramphenicol acetyltransferase gene. We identified a 19-base pair region located at -164 to -146 upstream of the transcription start site which is capable of conferring estrogen responsiveness to the homologous as well as to a heterologous promoter. The hormonal response is strictly dependent on the presence of intracellular estrogen receptors, since estrogen induced stimulation occurred only in Neuro-2a cells co-transfected with an expression vector for the human estrogen receptor. The identified region contains a novel imperfect palindrome (GGTGACCTTGACC) with sequence similarity to other estrogen response elements (EREs). To define cis-acting elements that function in synergism with the ERE, sequences 3' to the ERE were deleted, including the CCAAT box, two additional motifs corresponding to the right half of the ERE palindrome (TGACC), as well as a CTGCTAA heptamer similar to the "elegans box" found in Caenorhabditis elegans. Interestingly, optimal function of the identified ERE was fully independent of these elements and only required a short promoter region (-49 to +36). Our studies define a molecular mechanism by which estrogens can directly modulate OT gene expression. However, only a subset of OT neurons are capable of binding estrogens, therefore, direct action of estrogens on the OT gene may be restricted to a subpopulation of OT neurons.
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Identification of cells initiating human melanomas.
Schatton, Tobias; Murphy, George F; Frank, Natasha Y; Yamaura, Kazuhiro; Waaga-Gasser, Ana Maria; Gasser, Martin; Zhan, Qian; Jordan, Stefan; Duncan, Lyn M; Weishaupt, Carsten; Fuhlbrigge, Robert C; Kupper, Thomas S; Sayegh, Mohamed H; Frank, Markus H
2008-01-17
Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies and solid cancers. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant-melanoma-initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 (refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5+ tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human-to-mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5- bulk populations and re-establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ subpopulations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5- progeny, whereas ABCB5- tumour populations give rise, at lower rates, exclusively to ABCB5- cells. In an initial proof-of-principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumour-inhibitory effects. Identification of tumour-initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy.
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Processing of hierarchical syntactic structure in music.
Koelsch, Stefan; Rohrmeier, Martin; Torrecuso, Renzo; Jentschke, Sebastian
2013-09-17
Hierarchical structure with nested nonlocal dependencies is a key feature of human language and can be identified theoretically in most pieces of tonal music. However, previous studies have argued against the perception of such structures in music. Here, we show processing of nonlocal dependencies in music. We presented chorales by J. S. Bach and modified versions in which the hierarchical structure was rendered irregular whereas the local structure was kept intact. Brain electric responses differed between regular and irregular hierarchical structures, in both musicians and nonmusicians. This finding indicates that, when listening to music, humans apply cognitive processes that are capable of dealing with long-distance dependencies resulting from hierarchically organized syntactic structures. Our results reveal that a brain mechanism fundamental for syntactic processing is engaged during the perception of music, indicating that processing of hierarchical structure with nested nonlocal dependencies is not just a key component of human language, but a multidomain capacity of human cognition.
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Asymmetric adaptation in human walking using the Tethered Pelvic Assist Device (TPAD).
Vashista, Vineet; Reisman, Darcy S; Agrawal, Sunil K
2013-06-01
Human nervous system is capable of modifying motor commands in response to alterations in walking conditions. Previous research has shown that external perturbations that induce gait asymmetry can lead to adaptation in gait parameters. Such strategies have also been shown to temporarily restore gait symmetry in subjects with post stroke hemiparesis. This work aims to develop an experimental paradigm to induce gait asymmetry in human subjects by applying external asymmetric forces on the pelvis through the Tethered Pelvic Assist Device (TPAD). These external forces on the pelvis have the potential to influence the swing and the stance phases of both legs. Eight healthy subjects participated in the experiment where a higher resistive force was applied on the pelvis during the swing phase of the left leg as compared to the right leg. We hypothesized that such asymmetrically applied forces on the pelvis will lead to asymmetric adaptation in the human walking.
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Viskontas, Indre V
2008-12-01
To gain a complete understanding of how the brain functions, both in illness and good health, data from multiple levels of analysis must be integrated. Technical advances have made direct recordings of neuronal activity deep inside the human brain tractable, providing a rare glimpse into cellular processes during long-term memory formation. Recent findings using intracranial recordings in the medial temporal lobe inform current neural network models of memory, and may lead to a more comprehensive understanding of the neural basis of memory-related processes. These recordings have shown that cells in the hippocampus appear to support declarative learning by distinguishing novel and familiar stimuli via changes in firing patterns. Some cells with highly selective and invariant responses have also been described, and these responses seem to represent abstract concepts such as identity, rather than superficial perceptual features of items. Importantly, however, both selective and globally responsive cells are capable of changing their preferred stimulus depending on the conscious demands of the task. Firing patterns of human medial temporal lobe neurons indicate that cells can be both plastic and stable in terms of the information that they code; although some cells show highly selective and reproducible excitatory responses when presented with a familiar object, other cells change their receptive fields in line with changes in experience and the cognitive environment.
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Selective Activation of Human Dendritic Cells by OM-85 through a NF-kB and MAPK Dependent Pathway
Scutera, Sara; Somma, Paolo; Salvi, Valentina; Musso, Tiziana; Tabbia, Giuseppe; Bardessono, Marco; Pasquali, Christian; Mantovani, Alberto; Sozzani, Silvano; Bosisio, Daniela
2013-01-01
OM-85 (Broncho-Vaxom®, Broncho-Munal®, Ommunal®, Paxoral®, Vaxoral®), a product made of the water soluble fractions of 21 inactivated bacterial strain patterns responsible for respiratory tract infections, is used for the prevention of recurrent upper respiratory tract infections and acute exacerbations in chronic obstructive pulmonary disease patients. OM-85 is able to potentiate both innate and adaptive immune responses. However, the molecular mechanisms responsible for OM-85 activation are still largely unknown. Purpose of this study was to investigate the impact of OM-85 stimulation on human dendritic cell functions. We show that OM-85 selectively induced NF-kB and MAPK activation in human DC with no detectable action on the interferon regulatory factor (IRF) pathway. As a consequence, chemokines (i.e. CXCL8, CXCL6, CCL3, CCL20, CCL22) and B-cell activating cytokines (i.e. IL-6, BAFF and IL-10) were strongly upregulated. OM-85 also synergized with the action of classical pro-inflammatory stimuli used at suboptimal concentrations. Peripheral blood mononuclear cells from patients with COPD, a pathological condition often associated with altered PRR expression pattern, fully retained the capability to respond to OM-85. These results provide new insights on the molecular mechanisms of OM-85 activation of the immune response and strengthen the rational for its use in clinical settings. PMID:24386121
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Saccharomyces boulardii interferes with Shigella pathogenesis by postinvasion signaling events
Mumy, Karen L.; Chen, Xinhua; Kelly, Ciarán P.; McCormick, Beth A.
2011-01-01
Saccharomyces boulardii is gaining in popularity as a treatment for a variety of diarrheal diseases as well as inflammatory bowel disease. This study was designed to examine the effect of this yeast on infection by Shigella flexneri, a highly infectious and human host-adapted enteric pathogen. We investigated key interactions between the bacteria and host cells in the presence of the yeast in addition to a number of host responses including proinflammatory events and markers. Although the presence of the yeast during infection did not alter the number of bacteria that was able to attach or invade human colon cancer-derived T-84 cells, it did positively impact the tight junction protein zonula occluden-2 and significantly increase the barrier integrity of model epithelia. The yeast also decreased ERK, JNK, and NF-κB activation in response to S. flexneri, events likely responsible for the observed reductions in IL-8 secretion and the transepithelial migration of polymorphonuclear leukocytes across T-84 monolayers. These results, suggesting that the yeast allowed for a dampened inflammatory response, were confirmed in vivo utilizing a highly relevant model of human fetal colonic tissue transplanted into scid mice. Furthermore, a cell-free S. boulardii culture supernatant was also capable of reducing IL-8 secretion by infected T-84 cells. These data suggest that although the use of S. boulardii during infection with S. flexneri may alleviate symptoms associated with the inflammatory response of the host, it would not prevent infection. PMID:18032477
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Transcranial focused ultrasound stimulation of human primary visual cortex
NASA Astrophysics Data System (ADS)
Lee, Wonhye; Kim, Hyun-Chul; Jung, Yujin; Chung, Yong An; Song, In-Uk; Lee, Jong-Hwan; Yoo, Seung-Schik
2016-09-01
Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.
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In Vitro Desensitization of Human Skin Mast Cells
Zhao, Wei; Gomez, Gregorio; Macey, Matthew; Kepley, Christopher L.
2013-01-01
Desensitization is a clinical procedure whereby incremental doses of a drug are administered over several hours to a sensitive patient until a therapeutic dose and clinical tolerance are achieved. Clinical tolerance may occur in part by attenuating the mast cell response. In the present study, primary human skin mast cells were used to establish and characterize an in vitro model of desensitization. Mast cells in culture were armed with allergen-specific (4-hydroxy-3-nitro-phenylacety and Der p2) and non-specific IgE antibodies, and then desensitized by incremental exposures to 4-hydroxy-3-nitrophenylacety-BSA. This desensitization procedure abrogated the subsequent degranulation response to the desensitizing allergen, to an unrelated allergen, and to IgG anti-FcεRI, but not to C5a, substance P, compound 48/80, and calcium ionophore. Desensitized cells regained their FcεRI-dependent degranulation capability by 24–48 h after free allergen had been removed. Therefore, sensitized human skin mast cells are reversibly desensitized in vitro by exposure to incremental doses of that allergen, which also cross-desensitizes them to an unrelated allergen. PMID:22009002
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The clinical chemistry and immunology of long-duration space missions.
Wu, A H; Taylor, G R; Graham, G A; McKinley, B A
1993-01-01
Clinical laboratory diagnostic capabilities are needed to guide health and medical care of astronauts during long-duration space missions. Clinical laboratory diagnostics, as defined for medical care on Earth, offers a model for space capabilities. Interpretation of laboratory results for health and medical care of humans in space requires knowledge of specific physiological adaptations that occur, primarily because of the absence of gravity, and how these adaptations affect reference values. Limited data from American and Russian missions have indicated shifts of intra- and extracellular fluids and electrolytes, changes in hormone concentrations related to fluid shifts and stresses of the missions, reductions in bone and muscle mass, and a blunting of the cellular immune response. These changes could increase susceptibility to space-related illness or injury during a mission and after return to Earth. We review physiological adaptations and the risk of medical problems that occur during space missions. We describe the need for laboratory diagnostics as a part of health and medical care in space, and how this capability might be delivered.
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Winterton, Rachel; Clune, Samantha; Warburton, Jeni; Martin, John
2014-09-01
To explore how local governance enables access to resources, creates opportunities and increases capability for older people in rural communities to experience social inclusion. Twenty-six semi-structured interviews were undertaken with community stakeholders across two rural communities in north-east Victoria. Stakeholders were drawn from local government, and a range of community groups and organisations, as identified in a scoping study. Through the provision of community resources (e.g. physical and human infrastructure, organisational partnerships), local services and supports offer social and productive environments for participation. They also build individual resources (e.g. health, skills, finances, networks) to enable older people to participate within these environments, and provide assistance to allow older people to use individual and community resources. Community resources are integral in facilitating the development of older people's individual resources, and opportunities and capabilities for participation. These enable greater choice in participation, and contribute to the sustainability of community resources serving ageing populations. © 2013 The Authors. Australasian Journal on Ageing © 2013 ACOTA.
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Geometry and gravity influences on strength capability
NASA Technical Reports Server (NTRS)
Poliner, Jeffrey; Wilmington, Robert P.; Klute, Glenn K.
1994-01-01
Strength, defined as the capability of an individual to produce an external force, is one of the most important determining characteristics of human performance. Knowledge of strength capabilities of a group of individuals can be applied to designing equipment and workplaces, planning procedures and tasks, and training individuals. In the manned space program, with the high risk and cost associated with spaceflight, information pertaining to human performance is important to ensuring mission success and safety. Knowledge of individual's strength capabilities in weightlessness is of interest within many areas of NASA, including workplace design, tool development, and mission planning. The weightless environment of space places the human body in a completely different context. Astronauts perform a variety of manual tasks while in orbit. Their ability to perform these tasks is partly determined by their strength capability as demanded by that particular task. Thus, an important step in task planning, development, and evaluation is to determine the ability of the humans performing it. This can be accomplished by utilizing quantitative techniques to develop a database of human strength capabilities in weightlessness. Furthermore, if strength characteristics are known, equipment and tools can be built to optimize the operators' performance. This study examined strength in performing a simple task, specifically, using a tool to apply a torque to a fixture.
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Barnett, Ralph L; Liber, Theodore
2006-02-22
Use of unassisted human push capability arises from time to time in the areas of crowd and animal control, the security of locked doors, the integrity of railings, the removal of tree stumps and entrenched vehicles, the manoeuvering of furniture, and athletic pursuits such as US football or wrestling. Depending on the scenario, human push capability involves strength, weight, weight distribution, push angle, footwear/floor friction, and the friction between the upper body and the pushed object. Simple models are used to establish the relationships among these factors.
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Fire regimes and vegetation responses in two Mediterranean-climate regions
Montenegro, G.; Ginocchio, R.; Segura, A.; Keely, J.E.; Gomez, M.
2004-01-01
Wildfires resulting from thunderstorms are common in some Mediterranean-climate regions, such as southern California, and have played an important role in the ecology and evolution of the flora. Mediterranean-climate regions are major centers for human population and thus anthropogenic impacts on fire regimes may have important consequences on these plant formations. However, changes in fire regimes may have different impacts on Mediterranean type-ecosystems depending on the capability of plants to respond to such perturbations. Therefore, we compare here fire regimes and vegetation responses of two Mediterranean-climate regions which differ in wildfire regimes and history of human occupation, the central zone of Chile (matorral) and the southern area of California in United States (chaparral). In Chile almost all fires result from anthropogenic activities, whereas lightning fires resulting from thunderstorms are frequent in California. In both regions fires are more frequent in summer, due to high accumulation of dry plant biomass for ignition. Humans have markedly increased fires frequency both in the matorral and chaparral, but extent of burned areas has remained unaltered, probably due to better fire suppression actions and a decline in the built-up of dry plant fuel associated to increased landscape fragmentation with less flammable agricultural and urban developments. As expected, post-fire plant regeneration responses differs between the matorral and chaparral due to differences in the importance of wildfires as a natural evolutionary force in the system. Plants from the chaparral show a broader range of post-fire regeneration responses than the matorral, from basal resprouting, to lignotuber resprouting, and to fire-stimulated germination and flowering with fire-specific clues such as heat shock, chemicals from smoke or charred wood. Plants from the matorral have some resprouting capabilities after fire, but these probably evolved from other environmental pressures, such as severe and long summer droughts, herbivory, and volcanism. Although both Mediterranean-type ecosystems have shown to be resilient to anthropogenic fires, increasing fire frequency may be an important factor that needs to be considered as it may result in strong negative effects on plant successional trends and on plant diversity.
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Pepper, D A; Lada, Hania; Thomson, James R; Bakar, K Shuvo; Lake, P S; Mac Nally, Ralph
2017-01-15
Most natural assets, including native biodiversity (our focus), are under increasing threat from direct (loss of habitat, hunting) and indirect (climate change) human actions. Most human impacts arise from increasing human populations coupled with rises in per capita resource use. The rates of change of human actions generally outpace those to which the biota can respond or adapt. If we are to maintain native biodiversity, then we must develop ways to envisage how the biota may be affected over the next several decades to guide management and policy responses. We consider the future for Australia's native biodiversity in the context of two assumptions. First, the human population in Australia will be 40million by 2050, which has been mooted by federal government agencies. Second, greenhouse gas emissions will track the highest rates considered by the Intergovernmental Panel on Climate Change. The scenarios are based on major drivers of change, which were constructed from seven key drivers of change pertinent to native biodiversity. Five scenarios deal with differing distributions of the human population driven by uncertainties in climate change and in the human responses to climate change. Other scenarios are governed largely by global change and explore different rates of resource use, unprecedented rates of technological change, capabilities and societal values. A narrative for each scenario is provided. The set of scenarios spans a wide range of possible future paths for Australia, with different implications for the future of native biodiversity. Copyright © 2016 Elsevier B.V. All rights reserved.
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Energy Expenditure During Extravehicular Activity: Apollo Skylab Through STS-135
NASA Technical Reports Server (NTRS)
Paul, Heather L.
2011-01-01
The importance of real-time metabolic rate monitoring during extravehicular activities (EVAs) came into question during the Gemini missions, when the energy expenditure required to conduct an EVA over-tasked the crewmember and exceeded the capabilities of vehicle and space suit life support systems. Energy expenditure was closely evaluated through the Apollo lunar surface EVAs, resulting in modifications to space suit design and EVA operations. After the Apollo lunar surface missions were completed, the United States shifted its focus to long duration human space flight, to study the human response to living and working in a microgravity environment. This paper summarizes the energy expenditure during EVA from Apollo Skylab through STS-135.
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Research in progress: FY 1992. Summaries of projects
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
1993-08-01
The Biological and Environmental Research (BER) Program of OHER has two main missions: (1) to develop the knowledge base necessary to identify, understand, and anticipate the long-term health and environmental consequences of energy use and development and (2) to utilize the Department`s unique scientific and technological capabilities to solve major scientific problems in medicine, biology, and the environment. These missions reflect a commitment to develop the beneficial uses of advanced energy technologies while at the same time assuring that any potentially adverse health and environmental impacts of the Nation`s energy policies are fully identified and understood. The BER Program includesmore » research in atmospheric, marine, and terrestrial processes, including the linkage between the use in greenhouse gases, carbon dioxide, and regional and global climate change; in molecular and subcellular mechanisms underlying human somatic and genetic processes and their responses to energy-related environmental toxicants; in nuclear medicine, structural biology, the human genome, measurement sciences and instrumentation, and other areas that require the unique capabilities of the Department`s laboratory system. The principal areas of research are Health Research and Environmental Research.« less
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Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection.
Wang, Kun; Langevin, Stanley; O'Hern, Corey S; Shattuck, Mark D; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G; Kirby, Michael
2016-01-01
Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical diagnostic tools to distinguish between acute viral and bacterial respiratory infections is critical to improve patient care and limit the overuse of antibiotics in the medical community. The identification of prognostic respiratory virus biomarkers provides an early warning system that is capable of predicting which subjects will become symptomatic to expand our medical diagnostic capabilities and treatment options for acute infectious diseases. The host response to acute infection may be viewed as a deterministic signaling network responsible for maintaining the health of the host organism. We identify pathway signatures that reflect the very earliest perturbations in the host response to acute infection. These pathways provide a monitor the health state of the host using anomaly detection to quantify and predict health outcomes to pathogens.
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Anomaly Detection in Host Signaling Pathways for the Early Prognosis of Acute Infection
O’Hern, Corey S.; Shattuck, Mark D.; Ogle, Serenity; Forero, Adriana; Morrison, Juliet; Slayden, Richard; Katze, Michael G.
2016-01-01
Clinical diagnosis of acute infectious diseases during the early stages of infection is critical to administering the appropriate treatment to improve the disease outcome. We present a data driven analysis of the human cellular response to respiratory viruses including influenza, respiratory syncytia virus, and human rhinovirus, and compared this with the response to the bacterial endotoxin, Lipopolysaccharides (LPS). Using an anomaly detection framework we identified pathways that clearly distinguish between asymptomatic and symptomatic patients infected with the four different respiratory viruses and that accurately diagnosed patients exposed to a bacterial infection. Connectivity pathway analysis comparing the viral and bacterial diagnostic signatures identified host cellular pathways that were unique to patients exposed to LPS endotoxin indicating this type of analysis could be used to identify host biomarkers that can differentiate clinical etiologies of acute infection. We applied the Multivariate State Estimation Technique (MSET) on two human influenza (H1N1 and H3N2) gene expression data sets to define host networks perturbed in the asymptomatic phase of infection. Our analysis identified pathways in the respiratory virus diagnostic signature as prognostic biomarkers that triggered prior to clinical presentation of acute symptoms. These early warning pathways correctly predicted that almost half of the subjects would become symptomatic in less than forty hours post-infection and that three of the 18 subjects would become symptomatic after only 8 hours. These results provide a proof-of-concept for utility of anomaly detection algorithms to classify host pathway signatures that can identify presymptomatic signatures of acute diseases and differentiate between etiologies of infection. On a global scale, acute respiratory infections cause a significant proportion of human co-morbidities and account for 4.25 million deaths annually. The development of clinical diagnostic tools to distinguish between acute viral and bacterial respiratory infections is critical to improve patient care and limit the overuse of antibiotics in the medical community. The identification of prognostic respiratory virus biomarkers provides an early warning system that is capable of predicting which subjects will become symptomatic to expand our medical diagnostic capabilities and treatment options for acute infectious diseases. The host response to acute infection may be viewed as a deterministic signaling network responsible for maintaining the health of the host organism. We identify pathway signatures that reflect the very earliest perturbations in the host response to acute infection. These pathways provide a monitor the health state of the host using anomaly detection to quantify and predict health outcomes to pathogens. PMID:27532264
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Occupational Therapists' Views of Nussbaum's Life Capability: An Exploratory Study.
Mousavi, Tahmineh; Dharamsi, Shafik; Forwell, Susan; Dean, Elizabeth
2015-10-01
Life Capability is the first and most fundamental of Nussbaum's 10 Central Human Functional Capabilities (CHFCs). This capability refers to a person having a quality life of normal duration. The purpose of this study was to explore the views' of occupational therapists about Life Capability, specifically, their perspectives of this capability and its perceived relevance to practice. Semi-structured interviews with 14 occupational therapists in British Columbia, Canada, were conducted and thematically analyzed. Within this Canadian context, three themes emerged regarding occupational therapists' views about Life Capability: basic human right, quality of life, and longevity. Occupational therapists appear to view Life Capability as being consistent with the values of the occupational therapy profession. Nussbaum's other CHFCs warrant study to explore the degree to which the Capabilities Approach could complement existing occupational therapy theories, science, and practice. © The Author(s) 2015.
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Vaccines for Canine Leishmaniasis
Palatnik-de-Sousa, Clarisa B.
2012-01-01
Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL) is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global warming, coinfection with immunosuppressive diseases, and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL) in the Americas, the Middle East, Central Asia, China, and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases, and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost–effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine VL. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans and dogs against VL. PMID:22566950
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Immune Recognition of Gene Transfer Vectors: Focus on Adenovirus as a Paradigm
Aldhamen, Yasser Ali; Seregin, Sergey S.; Amalfitano, Andrea
2011-01-01
Recombinant Adenovirus (Ad) based vectors have been utilized extensively as a gene transfer platform in multiple pre-clinical and clinical applications. These applications are numerous, and inclusive of both gene therapy and vaccine based approaches to human or animal diseases. The widespread utilization of these vectors in both animal models, as well as numerous human clinical trials (Ad-based vectors surpass all other gene transfer vectors relative to numbers of patients treated, as well as number of clinical trials overall), has shed light on how this virus vector interacts with both the innate and adaptive immune systems. The ability to generate and administer large amounts of this vector likely contributes not only to their ability to allow for highly efficient gene transfer, but also their elicitation of host immune responses to the vector and/or the transgene the vector expresses in vivo. These facts, coupled with utilization of several models that allow for full detection of these responses has predicted several observations made in human trials, an important point as lack of similar capabilities by other vector systems may prevent detection of such responses until only after human trials are initiated. Finally, induction of innate or adaptive immune responses by Ad vectors may be detrimental in one setting (i.e., gene therapy) and be entirely beneficial in another (i.e., prophylactic or therapeutic vaccine based applications). Herein, we review the current understanding of innate and adaptive immune responses to Ad vectors, as well some recent advances that attempt to capitalize on this understanding so as to further broaden the safe and efficient use of Ad-based gene transfer therapies in general. PMID:22566830
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NASA Technical Reports Server (NTRS)
Kucuk, Senol
1988-01-01
Importance of the role of human operator in control systems has led to the particular area of manual control theory. Human describing functions were developed to model human behavior for manual control studies to take advantage of the successful and safe human operations. A single variable approach is presented that can be extended for multi-variable tasks where a low order human response model is used together with its rules, to adapt the model on-line, being capable of responding to the changes in the controlled element dynamics. Basic control theory concepts are used to combine the model, constrained with the physical observations, particularly, for the case of aircraft control. Pilot experience is represented as the initial model parameters. An adaptive root-locus method is presented as the adaptation law of the model where the closed loop bandwidth of the system is to be preserved in a stable manner with the adjustments of the pilot handling qualities which relate the latter to the closed loop bandwidth and damping of the closed loop pilot aircraft combination. A Kalman filter parameter estimator is presented as the controlled element identifier of the adaptive model where any discrepancies of the open loop dynamics from the presented one, are sensed to be compensated.
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2014-12-12
nexus of intelligence and technology is like a new toy for a small child . The President, the CIA, and the entire intelligence community have become...that could. The espionage trade was developed by using the technology available at the time, and incorporating any means available to collect relevant...reduced immediate need, such as an ongoing or developing conflict or war, is it responsible to maintain a capability just in case, where there may be an
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NASA Astrophysics Data System (ADS)
Hart, Mary Kate; Weinhold, Kent J.; Scearce, Richard M.; Washburn, Eileen M.; Clark, Cynthia A.; Palker, Thomas J.; Haynes, Barton F.
1991-11-01
The generation of antiviral cytotoxic T lymphocytes (CTLs) is a critical component of the immune response to viral infections. A safe and nontoxic vaccine for AIDS would optimally use a carrier-free synthetic peptide immunogen containing only components of HIV necessary for induction of protective immune responses. We report that hybrid synthetic peptides containing either a HIV envelope gp120 T-cell determinant (T1) or the envelope gp41 fusion domain (F) N-terminal to HIV CTL determinants are capable of priming murine CD8^+, major histocompatibility complex class I-restricted anti-HIV CTLs in vivo. These data demonstrate that carrier-free, nonderivatized synthetic peptides can be used in vivo to induce anti-HIV CTL responses.
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Space Medicine: A Surgeon's Perspective
NASA Technical Reports Server (NTRS)
Dawson, David L.
1999-01-01
For the first four decades of human space flight NASA's priorities in life sciences and medical programs have been preventative medicine (astronaut selection and training); assessment of the physiologic effects of microgravity and other unique aspects of space flight, implementation of countermeasures to protect against adverse effects, and amelioration of these adverse effects. Because most of the U.S. space flight experience has been on short duration missions, the need for medical and diagnostic treatment capabilities have been limited.The first long-term crews will arrive on the International Space Station (ISS) in early 2000. This will usher in a new era, an era of sustained human presence in Low Earth Orbit. One of the principal purposes of the ISS program is to increase the knowledge of the effects of long duration space flight on humans, a pre-requisite to future exploration class missions beyond Low Earth Orbit (e.g., a return to the Moon or an exploration of Mars). Areas of particular interest include protection from radiation, muscle atrophy, bone loss, cardiovascular alterations, immune dysfunction, adverse psychological response to hazards and confinement, and neurovestibular alterations. In addition, long duration space flight requires the development of autonomous medical care capabilities, as the distances involved eliminate the possibility of real-time telemedicine or robotic intervention, and prevent a mission abort and a rapid return to Earth. The objectives of this presentation include: 1. A description of the International Space Station project, including its research facilities and on-orbit medical capabilities; 2. An overview of the physiological and medical problems associated with microgravity in space flight; 3. A review of NASA's biomedical research priorities and ongoing work to develop clinical care capabilities for space flight crews (including surgical interventions) and; 4. An overview of current and proposed research priorities for NASA Research Announcements, NASA Space Biomedical Research Institute, Small Business Innovation Research Grant, and other funding sources.
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Bansal, Arjun K.; Singer, Jedediah M.; Anderson, William S.; Golby, Alexandra; Madsen, Joseph R.
2012-01-01
The cerebral cortex needs to maintain information for long time periods while at the same time being capable of learning and adapting to changes. The degree of stability of physiological signals in the human brain in response to external stimuli over temporal scales spanning hours to days remains unclear. Here, we quantitatively assessed the stability across sessions of visually selective intracranial field potentials (IFPs) elicited by brief flashes of visual stimuli presented to 27 subjects. The interval between sessions ranged from hours to multiple days. We considered electrodes that showed robust visual selectivity to different shapes; these electrodes were typically located in the inferior occipital gyrus, the inferior temporal cortex, and the fusiform gyrus. We found that IFP responses showed a strong degree of stability across sessions. This stability was evident in averaged responses as well as single-trial decoding analyses, at the image exemplar level as well as at the category level, across different parts of visual cortex, and for three different visual recognition tasks. These results establish a quantitative evaluation of the degree of stationarity of visually selective IFP responses within and across sessions and provide a baseline for studies of cortical plasticity and for the development of brain-machine interfaces. PMID:22956795
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D'Sa, Raechelle A; Raj, Jog; Dickinson, Peter J; McCabe, Fiona; Meenan, Brian J
2016-06-22
Recent advances in materials sciences have allowed for the development and fabrication of biomaterials that are capable of providing requisite cues to instigate cells to respond in a predictable fashion. We have developed a series of poly(methyl methacrylate)/polystyrene (PMMA/PS) polymer demixed thin films with nanotopographies ranging from nanoislands to nanopits to study the response of human fetal osteoblast cells (hFOBs). When PMMA was in excess in the blend composition, a nanoisland topography dominated, whereas a nanopit topography dominated when PS was in excess. PMMA was found to segregate to the top of the nanoisland morphology with PS preferring the substrate interface. To further ascertain the effects of surface chemistry vs topography, we plasma treated the polymer demixed films using an atmospheric pressure dielectric barrier discharge reactor to alter the surface chemistry. Our results have shown that hFOBs did not have an increased short-term cellular response on pristine polymer demixed surfaces. However, increasing the hydrophilicty/wettability of the surfaces by oxygen functionalization causes an increase in the cellular response. These results indicate that topography alone is not sufficient to induce a positive cellular response, but the underlying surface chemistry is also important in regulating cell function.
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Mechanisms underlying differential food allergy response to heated egg.
Martos, Gustavo; Lopez-Exposito, Ivan; Bencharitiwong, Ramon; Berin, M Cecilia; Nowak-Węgrzyn, Anna
2011-04-01
Egg white proteins are usually subjected to heating, making them edible for the majority of children with egg allergy. We sought to investigate the underlying mechanisms responsible for the reduced allergenicity displayed by heat-treated egg white allergens. C3H/HeJ mice were orally sensitized with ovalbumin (OVA) or ovomucoid and challenged with native or heated proteins to evaluate their allergenicity. Immunoreactivity was assessed by immunoblotting using sera from children with egg allergy. In vitro gastrointestinal digestion of native and heated OVA and ovomucoid was studied by SDS-PAGE and liquid chromatography. Intestinal uptake of intact native and heated OVA and ovomucoid by human intestinal epithelial (Caco-2) cells was investigated. Rat basophil leukemia cells passively sensitized with mouse serum and human basophils passively sensitized with serum from children with egg allergy were used to assess the effector cell activation by heated, digested, and transported OVA and ovomucoid. Heated OVA and ovomucoid did not induce symptoms of anaphylaxis in sensitized mice when administered orally. Heating did not completely destroy IgE-binding capacity of OVA or ovomucoid but enhanced in vitro digestibility of OVA. Digestion of both OVA and ovomucoid diminished mediator release in rat basophil leukemia assay and basophil activation. Heating of allergens prevented transport across human intestinal epithelial cells in a form capable of triggering basophil activation or T-cell activation. Heat treatment reduces allergenicity of OVA and ovomucoid. This is partially a result of the enhanced gastrointestinal digestibility of heated OVA and the inability of heated OVA or ovomucoid to be absorbed in a form capable of triggering basophils. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.
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How feasible is the rapid development of artificial superintelligence?
NASA Astrophysics Data System (ADS)
Sotala, Kaj
2017-11-01
What kinds of fundamental limits are there in how capable artificial intelligence (AI) systems might become? Two questions in particular are of interest: (1) How much more capable could AI become relative to humans, and (2) how easily could superhuman capability be acquired? To answer these questions, we will consider the literature on human expertise and intelligence, discuss its relevance for AI, and consider how AI could improve on humans in two major aspects of thought and expertise, namely simulation and pattern recognition. We find that although there are very real limits to prediction, it seems like AI could still substantially improve on human intelligence.
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Mase, William A; Bickford, Beth; Thomas, Casey L; Jones, Shamika D; Bisesi, Michael
In early 2009, H1N1 influenza was identified within the human population. Centers for Disease Control and Prevention (CDC) officials responded with focused assessment, policy development, and assurances. The response was mobilized through efforts including procurement of adequate vaccine supply, local area span of control, materials acquisition, and facilities and resource identification. Qualitative evaluation of the assurance functions specific to the system's ability to assure safe and healthy conditions are reported. The methodology mirrors the Homeland Security Exercise and Evaluation Program used to assess system capability. Findings demonstrate the effectiveness of community responsive disease prevention efforts in partnership with the public health systems mission to unify traditional public sector systems, for-profit systems, and local area systems was accomplished. As a result of this response pharmaceutical industries, healthcare providers, healthcare agencies, police/safety, colleges, and health and human service agencies were united. Findings demonstrate the effectiveness of community response strategies utilizing feedback from system stakeholders. After-action review processes are critical in all-hazards preparedness. This analysis of local health district response to the H1N1 influenza outbreak informs future public health service delivery. Results provide a synthesis of local health department's emergency response strategies, challenges encountered, and future-focused emergency response strategy implementation. A synthesis is provided as to policy and practice developments which have emerged over the past seven years with regard to lessons learned from the 2009-10 H1N1 influenza outbreak and response.
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Research on the human genome and patentability--the ethical consequences.
Pompidou, A
1995-01-01
The genome is one of the primordial elements of the human being and is responsible for human identity and its transmission to descendants. The gene as such ought not be appropriated or owned by man. However, any sufficiently complete description of a gene should be capable of being protected as intellectual property. Furthermore, all utilisations of a gene or its elements that permit development of processes or new products should be patentable. Ethics, in the sense of moral action, should come into play from the very first stages of research into the human genome. Protection of intellectual and industrial property is of purely legal concern and need not provoke ethical consideration. By contrast, the use of the results of, and in particular the commercialisation of products deriving from, research into the human genome, ought to be subjected to ethical consideration and control. Considering the economic and societal stakes of such research, ethical analysis ought to be at an international level if mistakes and unforeseen risks of conflict are to be avoided. PMID:7608941
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ERIC Educational Resources Information Center
Galliott, Natal'ya; Graham, Linda J.
2014-01-01
In this paper, we seek to operationalize Amartya Sen's concept of human capability to guide a scholarly investigation of student career choice capability. We begin by outlining factors affecting youth labour markets in Australia; a prosperous country that is affected by a "two-speed" national economy. We then examine recent government…
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Zebrafish and Streptococcal Infections.
Saralahti, A; Rämet, M
2015-09-01
Streptococcal bacteria are a versatile group of gram-positive bacteria capable of infecting several host organisms, including humans and fish. Streptococcal species are common colonizers of the human respiratory and gastrointestinal tract, but they also cause some of the most common life-threatening, invasive infections in humans and aquaculture. With its unique characteristics and efficient tools for genetic and imaging applications, the zebrafish (Danio rerio) has emerged as a powerful vertebrate model for infectious diseases. Several zebrafish models introduced so far have shown that zebrafish are suitable models for both zoonotic and human-specific infections. Recently, several zebrafish models mimicking human streptococcal infections have also been developed. These models show great potential in providing novel information about the pathogenic mechanisms and host responses associated with human streptococcal infections. Here, we review the zebrafish infection models for the most relevant streptococcal species: the human-specific Streptococcus pneumoniae and Streptococcus pyogenes, and the zoonotic Streptococcus iniae and Streptococcus agalactiae. The recent success and the future potential of these models for the study of host-pathogen interactions in streptococcal infections are also discussed. © 2015 The Foundation for the Scandinavian Journal of Immunology.
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Robotic astrobiology - prospects for enhancing scientific productivity of mars rover missions
NASA Astrophysics Data System (ADS)
Ellery, A. A.
2018-07-01
Robotic astrobiology involves the remote projection of intelligent capabilities to planetary missions in the search for life, preferably with human-level intelligence. Planetary rovers would be true human surrogates capable of sophisticated decision-making to enhance their scientific productivity. We explore several key aspects of this capability: (i) visual texture analysis of rocks to enable their geological classification and so, astrobiological potential; (ii) serendipitous target acquisition whilst on the move; (iii) continuous extraction of regolith properties, including water ice whilst on the move; and (iv) deep learning-capable Bayesian net expert systems. Individually, these capabilities will provide enhanced scientific return for astrobiology missions, but together, they will provide full autonomous science capability.
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[Application to allergic diseases].
Saito, Hirohisa
2005-04-01
The increasing prevalence of allergic diseases in developed countries is considered to be caused, at least in part, by rapid improvement of human hygiene. In human beings, the immune system developed as an ingenious device for defending against frequent attacks by microbes. Therefore, our immune system seems to have become deranged in our recent, unprecedentedly hygienic environment. It is now necessary to understand the total functional elements comprising the immune system, not just a single molecule present in an immunocyte working in our immune system. Microarray analysis is now becoming capable of detecting the whole transcripts present in a cell. It is anticipated that we can understand the deranged human immunity using the system biology. It is also expected to predict previously unexpected drug-related adverse events caused by interaction of a drug with responsible molecules present in vital organs.
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Supercomputer use in orthopaedic biomechanics research: focus on functional adaptation of bone.
Hart, R T; Thongpreda, N; Van Buskirk, W C
1988-01-01
The authors describe two biomechanical analyses carried out using numerical methods. One is an analysis of the stress and strain in a human mandible, and the other analysis involves modeling the adaptive response of a sheep bone to mechanical loading. The computing environment required for the two types of analyses is discussed. It is shown that a simple stress analysis of a geometrically complex mandible can be accomplished using a minicomputer. However, more sophisticated analyses of the same model with dynamic loading or nonlinear materials would require supercomputer capabilities. A supercomputer is also required for modeling the adaptive response of living bone, even when simple geometric and material models are use.
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Measurement of erythema and tanning responses in human skin using a tri-stimulus colorimeter.
Seitz, J C; Whitmore, C G
1988-01-01
A 'Minolta Tri-Stimulus Colorimeter II' was evaluated for obtaining objective measurements of early changes in erythema and tanning. The meter showed a subtle, continuous transition between the primary erythematous response and the delayed tanning of skin which was below the visual threshold for detection. Thereafter, the a* (redness) value of the meter showed a significant linear correlation with the dermatologist's perception of erythema while the b* (yellow) value showed a significant correlation with the perception of tanning. This capability of the tri-stimulus colorimeter to simultaneously evaluate the hue and saturation of skin color affords an improved opportunity to quantitate the transition from erythema to tanning without subjective bias.
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Tackling the Global Challenge: Humanitarian Catastrophes
Iserson, Kenneth V.
2014-01-01
“Humanitarian catastrophes,” conflicts and calamities generating both widespread human suffering and destructive events, require a wide range of emergency resources. This paper answers a number of questions that humanitarian catastrophes generate: Why and how do the most-developed countries—those with the resources, capabilities, and willingness to help—intervene in specific types of disasters? What ethical and legal guidelines shape our interventions? How well do we achieve our goals? It then suggests a number of changes to improve humanitarian responses, including better NGO-government cooperation, increased research on the best disaster response methods, clarification of the criteria and roles for humanitarian (military) interventions, and development of post-2015 Millennium Development Goals with more accurate progress measures. PMID:24672618
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XPD-dependent activation of apoptosis in response to triplex-induced DNA damage
Kaushik Tiwari, Meetu; Rogers, Faye A.
2013-01-01
DNA sequences capable of forming triplexes are prevalent in the human genome and have been found to be intrinsically mutagenic. Consequently, a balance between DNA repair and apoptosis is critical to counteract their effect on genomic integrity. Using triplex-forming oligonucleotides to synthetically create altered helical distortions, we have determined that pro-apoptotic pathways are activated by the formation of triplex structures. Moreover, the TFIIH factor, XPD, occupies a central role in triggering apoptosis in response to triplex-induced DNA strand breaks. Here, we show that triplexes are capable of inducing XPD-independent double strand breaks, which result in the formation of γH2AX foci. XPD was subsequently recruited to the triplex-induced double strand breaks and co-localized with γH2AX at the damage site. Furthermore, phosphorylation of H2AX tyrosine 142 was found to stimulate the signaling pathway of XPD-dependent apoptosis. We suggest that this mechanism may play an active role in minimizing genomic instability induced by naturally occurring noncanonical structures, perhaps protecting against cancer initiation. PMID:23913414
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Capabilities Roadmap Briefings to the National Research Council
NASA Technical Reports Server (NTRS)
2005-01-01
High energy power and propulsion capability roadmap - general background and introduction. Advanced telescopes and observatories and scientific instruments and sensors capability roadmaps - general background and introduction. Space communications capability roadmap interim review. Robotic access to planetary surface capability roadmap. Human health and support systems capability roadmap progress review.
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Self-reported Preparedness to Respond to Mass Fatality Incidents in 38 State Health Departments.
Merrill, Jacqueline; Zhi, Qi; Gershon, Robyn R
Public health departments play an important role in the preparation and response to mass fatality incidents (MFIs). To describe MFI response capabilities of US state health departments. The data are part of a multisector cross-sectional study aimed at 5 sectors that comprise the US mass fatality infrastructure. Data were collected over a 6-week period via a self-administered, anonymous Web-based survey. In 2014, a link to the survey was distributed via e-mail to health departments in 50 states and the District of Columbia. State health department representatives responsible for their state's MFI plans. Preparedness was assessed using 3 newly developed metrics: organizational capabilities (n = 19 items); operational capabilities (n = 19 items); and resource-sharing capabilities (n = 13 items). Response rate was 75% (n = 38). Among 38 responses, 37 rated their workplace moderately or well prepared; 45% reported MFI training, but only 30% reported training on MFI with hazardous contaminants; 58% estimated high levels of staff willingness to respond, but that dropped to 40% if MFIs involved hazardous contaminants; and 84% reported a need for more training. On average, 76% of operational capabilities were present. Resource sharing was most prevalent with state Office of Emergency Management but less evident with faith-based organizations and agencies within the medical examiner sector. Overall response capability was adequate, with gaps found in capabilities where public health shares responsibility with other sectors. Collaborative training with other sectors is critical to ensure optimal response to future MFIs, but recent funding cuts in public health preparedness may adversely impact this critical preparedness element. In order for the sector to effectively meet its public health MFI responsibilities as delineated in the National Response Framework, resources to support training and other elements of preparedness must be maintained.
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Germ-line engineering, freedom, and future generations.
Cooke, Elizabeth F
2003-02-01
New technologies in germ-line engineering have raised many questions about obligations to future generations. In this article, I focus on the importance of increasing freedom and the equality of freedom for present and future generations, because these two ideals are necessary for a just society and because they are most threatened by the wide-scale privatisation of GLE technologies. However, there are ambiguities in applying these ideals to the issue of genetic technologies. I argue that Amartya Sen's capability theory can be used as a framework to ensure freedom and equality in the use of GLE technology. Capability theory articulates the goal of equalising real freedom by bringing all people up to a threshold of basic human capabilities. Sen's capability theory can clarify the proper moral goal of GLE insofar as this technology could be used to bring people up to certain basic human capabilities, thereby increasing their real freedom. And by increasing the freedom of those who lack basic human capabilities, GLE can aid in decreasing the inequalities of freedom among classes of people.
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Can a Humanoid Face be Expressive? A Psychophysiological Investigation
Lazzeri, Nicole; Mazzei, Daniele; Greco, Alberto; Rotesi, Annalisa; Lanatà, Antonio; De Rossi, Danilo Emilio
2015-01-01
Non-verbal signals expressed through body language play a crucial role in multi-modal human communication during social relations. Indeed, in all cultures, facial expressions are the most universal and direct signs to express innate emotional cues. A human face conveys important information in social interactions and helps us to better understand our social partners and establish empathic links. Latest researches show that humanoid and social robots are becoming increasingly similar to humans, both esthetically and expressively. However, their visual expressiveness is a crucial issue that must be improved to make these robots more realistic and intuitively perceivable by humans as not different from them. This study concerns the capability of a humanoid robot to exhibit emotions through facial expressions. More specifically, emotional signs performed by a humanoid robot have been compared with corresponding human facial expressions in terms of recognition rate and response time. The set of stimuli included standardized human expressions taken from an Ekman-based database and the same facial expressions performed by the robot. Furthermore, participants’ psychophysiological responses have been explored to investigate whether there could be differences induced by interpreting robot or human emotional stimuli. Preliminary results show a trend to better recognize expressions performed by the robot than 2D photos or 3D models. Moreover, no significant differences in the subjects’ psychophysiological state have been found during the discrimination of facial expressions performed by the robot in comparison with the same task performed with 2D photos and 3D models. PMID:26075199
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Synthesising empirical results to improve predictions of post-wildfire runoff and erosion response
Shakesby, Richard A.; Moody, John A.; Martin, Deborah A.; Robichaud, Peter R.
2016-01-01
Advances in research into wildfire impacts on runoff and erosion have demonstrated increasing complexity of controlling factors and responses, which, combined with changing fire frequency, present challenges for modellers. We convened a conference attended by experts and practitioners in post-wildfire impacts, meteorology and related research, including modelling, to focus on priority research issues. The aim was to improve our understanding of controls and responses and the predictive capabilities of models. This conference led to the eight selected papers in this special issue. They address aspects of the distinctiveness in the controls and responses among wildfire regions, spatiotemporal rainfall variability, infiltration, runoff connectivity, debris flow formation and modelling applications. Here we summarise key findings from these papers and evaluate their contribution to improving understanding and prediction of post-wildfire runoff and erosion under changes in climate, human intervention and population pressure on wildfire-prone areas.
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An Overview of Power Capability Requirements for Exploration Missions
NASA Technical Reports Server (NTRS)
Davis, Jose M.; Cataldo, Robert L.; Soeder, James F.; Manzo, Michelle A.; Hakimzadeh, Roshanak
2005-01-01
Advanced power is one of the key capabilities that will be needed to achieve NASA's missions of exploration and scientific advancement. Significant gaps exist in advanced power capabilities that are on the critical path to enabling human exploration beyond Earth orbit and advanced robotic exploration of the solar system. Focused studies and investment are needed to answer key development issues for all candidate technologies before down-selection. The viability of candidate power technology alternatives will be a major factor in determining what exploration mission architectures are possible. Achieving the capabilities needed to enable the CEV, Moon, and Mars missions is dependent on adequate funding. Focused investment in advanced power technologies for human and robotic exploration missions is imperative now to reduce risk and to make informed decisions on potential exploration mission decisions beginning in 2008. This investment would begin the long lead-time needed to develop capabilities for human exploration missions in the 2015 to 2030 timeframe. This paper identifies some of the key technologies that will be needed to fill these power capability gaps. Recommendations are offered to address capability gaps in advanced power for Crew Exploration Vehicle (CEV) power, surface nuclear power systems, surface mobile power systems, high efficiency power systems, and space transportation power systems. These capabilities fill gaps that are on the critical path to enabling robotic and human exploration missions. The recommendations address the following critical technology areas: Energy Conversion, Energy Storage, and Power Management and Distribution.
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Waples, Robin S; Zabel, Richard W; Scheuerell, Mark D; Sanderson, Beth L
2008-01-01
The human footprint is now large in all the Earth's ecosystems, and construction of large dams in major river basins is among the anthropogenic changes that have had the most profound ecological consequences, particularly for migratory fishes. In the Columbia River basin of the western USA, considerable effort has been directed toward evaluating demographic effects of dams, yet little attention has been paid to evolutionary responses of migratory salmon to altered selective regimes. Here we make a first attempt to address this information gap. Transformation of the free-flowing Columbia River into a series of slack-water reservoirs has relaxed selection for adults capable of migrating long distances upstream against strong flows; conditions now favour fish capable of migrating through lakes and finding and navigating fish ladders. Juveniles must now be capable of surviving passage through multiple dams or collection and transportation around the dams. River flow patterns deliver some groups of juvenile salmon to the estuary later than is optimal for ocean survival, but countervailing selective pressures might constrain an evolutionary response toward earlier migration timing. Dams have increased the cost of migration, which reduces energy available for sexual selection and favours a nonmigratory life history. Reservoirs are a benign environment for many non-native species that are competitors with or predators on salmon, and evolutionary responses are likely (but undocumented). More research is needed to tease apart the relative importance of evolutionary vs. plastic responses of salmon to these environmental changes; this research is logistically challenging for species with life histories like Pacific salmon, but results should substantially improve our understanding of key processes. If the Columbia River is ever returned to a quasinatural, free-flowing state, remaining populations might face a Darwinian debt (and temporarily reduced fitness) as they struggle to re-evolve historical adaptations.
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Yang, Zhao; Li, Chong; Fan, Zusen; Liu, Hongjie; Zhang, Xiaolong; Cai, Zhiming; Xu, Liqin; Luo, Jian; Huang, Yi; He, Luyun; Liu, Chunxiao; Wu, Song
2017-01-01
Cancer stem cells are considered responsible for many important aspects of tumors such as their self-renewal, tumor-initiating, drug-resistance and metastasis. However, the genetic basis and origination of human bladder cancer stem cells (BCSCs) remains unknown. Here, we conducted single-cell sequencing on 59 cells including BCSCs, bladder cancer non-stem cells (BCNSCs), bladder epithelial stem cells (BESCs) and bladder epithelial non-stem cells (BENSCs) from three bladder cancer (BC) specimens. Specifically, BCSCs demonstrate clonal homogeneity and suggest their origin from BESCs or BCNSCs through phylogenetic analysis. Moreover, 21 key altered genes were identified in BCSCs including six genes not previously described in BC (ETS1, GPRC5A, MKL1, PAWR, PITX2 and RGS9BP). Co-mutations of ARID1A, GPRC5A and MLL2 introduced by CRISPR/Cas9 significantly enhance the capabilities of self-renewal and tumor-initiating of BCNSCs. To our knowledge, our study first provides an overview of the genetic basis of human BCSCs with single-cell sequencing and demonstrates the biclonal origin of human BCSCs via evolution analysis. Human bladder cancer stem cells show the high level of consistency and may derived from bladder epithelial stem cells or bladder cancer non-stem cells. Mutations of ARID1A, GPRC5A and MLL2 grant bladder cancer non-stem cells the capability of self-renewal. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.
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Guidelines and Capabilities for Designing Human Missions
NASA Technical Reports Server (NTRS)
Allen, Christopher S.; Burnett, Rebeka; Charles, John; Cucinotta, Frank; Fullerton, Richard; Goodman, Jerry R.; Griffith, Anthony D., Sr.; Kosmo, Joseph J.; Perchonok, Michele; Railsback, Jan;
2003-01-01
These guidelines and capabilities identify the points of intersection between human spaceflight crews and mission considerations such as architecture, vehicle design, technologies, operations, and science requirements. In these chapters, we will provide clear, top-level guidelines for human-related exploration studies and technology research that will address common questions and requirements. As a result, we hope that ongoing mission trade studies will consider common, standard, and practical criteria for human interfaces.
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Hiolle, Antoine; Lewis, Matthew; Cañamero, Lola
2014-01-01
In the context of our work in developmental robotics regarding robot-human caregiver interactions, in this paper we investigate how a "baby" robot that explores and learns novel environments can adapt its affective regulatory behavior of soliciting help from a "caregiver" to the preferences shown by the caregiver in terms of varying responsiveness. We build on two strands of previous work that assessed independently (a) the differences between two "idealized" robot profiles-a "needy" and an "independent" robot-in terms of their use of a caregiver as a means to regulate the "stress" (arousal) produced by the exploration and learning of a novel environment, and (b) the effects on the robot behaviors of two caregiving profiles varying in their responsiveness-"responsive" and "non-responsive"-to the regulatory requests of the robot. Going beyond previous work, in this paper we (a) assess the effects that the varying regulatory behavior of the two robot profiles has on the exploratory and learning patterns of the robots; (b) bring together the two strands previously investigated in isolation and take a step further by endowing the robot with the capability to adapt its regulatory behavior along the "needy" and "independent" axis as a function of the varying responsiveness of the caregiver; and (c) analyze the effects that the varying regulatory behavior has on the exploratory and learning patterns of the adaptive robot.
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The Economics and Psychology of Inequality and Human Development*
Cunha, Flavio; Heckman, James J.
2009-01-01
Recent research on the economics of human development deepens understanding of the origins of inequality and excellence. It draws on and contributes to personality psychology and the psychology of human development. Inequalities in family environments and investments in children are substantial. They causally affect the development of capabilities. Both cognitive and noncognitive capabilities determine success in life but to varying degrees for different outcomes. An empirically determined technology of capability formation reveals that capabilities are self-productive and cross-fertilizing and can be enhanced by investment. Investments in capabilities are relatively more productive at some stages of a child’s life cycle than others. Optimal child investment strategies differ depending on target outcomes of interest and on the nature of adversity in a child’s early years. For some configurations of early disadvantage and for some desired outcomes, it is efficient to invest relatively more in the later years of childhood than in the early years. PMID:20209045
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Building Airport Surface HITL Simulation Capability
NASA Technical Reports Server (NTRS)
Chinn, Fay Cherie
2016-01-01
FutureFlight Central is a high fidelity, real-time simulator designed to study surface operations and automation. As an air traffic control tower simulator, FFC allows stakeholders such as the FAA, controllers, pilots, airports, and airlines to develop and test advanced surface and terminal area concepts and automation including NextGen and beyond automation concepts and tools. These technologies will improve the safety, capacity and environmental issues facing the National Airspace system. FFC also has extensive video streaming capabilities, which combined with the 3-D database capability makes the facility ideal for any research needing an immersive virtual and or video environment. FutureFlight Central allows human in the loop testing which accommodates human interactions and errors giving a more complete picture than fast time simulations. This presentation describes FFCs capabilities and the components necessary to build an airport surface human in the loop simulation capability.
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Delgado-García, José M; Gruart, Agnès
2008-12-01
The availability of transgenic mice mimicking selective human neurodegenerative and psychiatric disorders calls for new electrophysiological and microstimulation techniques capable of being applied in vivo in this species. In this article, we will concentrate on experiments and techniques developed in our laboratory during the past few years. Thus we have developed different techniques for the study of learning and memory capabilities of wild-type and transgenic mice with deficits in cognitive functions, using classical conditioning procedures. These techniques include different trace (tone/SHOCK and shock/SHOCK) conditioning procedures ? that is, a classical conditioning task involving the cerebral cortex, including the hippocampus. We have also developed implantation and recording techniques for evoking long-term potentiation (LTP) in behaving mice and for recording the evolution of field excitatory postsynaptic potentials (fEPSP) evoked in the hippocampal CA1 area by the electrical stimulation of the commissural/Schaffer collateral pathway across conditioning sessions. Computer programs have also been developed to quantify the appearance and evolution of eyelid conditioned responses and the slope of evoked fEPSPs. According to the present results, the in vivo recording of the electrical activity of selected hippocampal sites during classical conditioning of eyelid responses appears to be a suitable experimental procedure for studying learning capabilities in genetically modified mice, and an excellent model for the study of selected neuropsychiatric disorders compromising cerebral cortex functioning.
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Unmanned and Unattended Response Capability for Homeland Defense
DOE Office of Scientific and Technical Information (OSTI.GOV)
BENNETT, PHIL C.
2002-11-01
An analysis was conducted of the potential for unmanned and unattended robotic technologies for forward-based, immediate response capabilities that enables access and controlled task performance. The authors analyze high-impact response scenarios in conjunction with homeland security organizations, such as the NNSA Office of Emergency Response, the FBI, the National Guard, and the Army Technical Escort Unit, to cover a range of radiological, chemical and biological threats. They conducted an analysis of the potential of forward-based, unmanned and unattended robotic technologies to accelerate and enhance emergency and crisis response by Homeland Defense organizations. Response systems concepts were developed utilizing new technologiesmore » supported by existing emerging threats base technologies to meet the defined response scenarios. These systems will pre-position robotic and remote sensing capabilities stationed close to multiple sites for immediate action. Analysis of assembled systems included experimental activities to determine potential efficacy in the response scenarios, and iteration on systems concepts and remote sensing and robotic technologies, creating new immediate response capabilities for Homeland Defense.« less
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ERIC Educational Resources Information Center
Khandekar, Aradhana; Sharma, Anuradha
2005-01-01
Purpose: The purpose of this article is to examine the role of human resource capability (HRC) in organisational performance and sustainable competitive advantage (SCA) in Indian global organisations. Design/Methodology/Approach: To carry out the present study, an empirical research on a random sample of 300 line or human resource managers from…
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Salient Feature of Haptic-Based Guidance of People in Low Visibility Environments Using Hard Reins.
Ranasinghe, Anuradha; Sornkarn, Nantachai; Dasgupta, Prokar; Althoefer, Kaspar; Penders, Jacques; Nanayakkara, Thrishantha
2016-02-01
This paper presents salient features of human-human interaction where one person with limited auditory and visual perception of the environment (a follower) is guided by an agent with full perceptual capabilities (a guider) via a hard rein along a given path. We investigate several salient features of the interaction between the guider and follower such as: 1) the order of an autoregressive (AR) control policy that maps states of the follower to actions of the guider; 2) how the guider may modulate the pulling force in response to the trust level of the follower; and 3) how learning may successively apportion the responsibility of control across different muscles of the guider. Based on experimental systems identification on human demonstrations from ten pairs of naive subjects, we show that guiders tend to adopt a third-order AR predictive control policy and followers tend to adopt second-order reactive control policy. Moreover, the extracted guider's control policy was implemented and validated by human-robot interaction experiments. By modeling the follower's dynamics with a time varying virtual damped inertial system, we found that it is the coefficient of virtual damping which is most sensitive to the trust level of the follower. We used these experimental insights to derive a novel controller that integrates an optimal order control policy with a push/pull force modulator in response to the trust level of the follower monitored using a time varying virtual damped inertial model.
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A Vision for the Future of Environmental Research: Creating Environmental Intelligence Centers
NASA Astrophysics Data System (ADS)
Barron, E. J.
2002-12-01
The nature of the environmental issues facing our nation demands a capability that allows us to enhance economic vitality, maintain environmental quality, and limit threats to life and property through more fundamental understanding of the Earth. It is "advanced" knowledge of how the system may respond that gives environmental information most of its power and utility. This fact is evident in the demand for new forecasting products, involving air quality, energy demand, water quality and quantity, ultraviolet radiation, and human health indexes. As we demonstrate feasibility and benefit, society is likely to demand a growing number of new operational forecast products on prediction time scales of days to decades into the future. The driving forces that govern our environment are widely recognized, involving primarily weather and climate, patterns of land use and land cover, and resource use with its associated waste products. The importance of these driving forces has been demonstrated by a decade of research on greenhouse gas emissions, ozone depletion and deforestation, and through the birth of Earth System Science. But, there are also major challenges. We find the strongest intersection between human activity, environmental stresses, system interactions and human decision-making in regional analysis coupled to larger spatial scales. In addition, most regions are influenced by multiple-stresses. Multiple, cumulative, and interactive stresses are clearly the most difficult to understand and hence the most difficult to assess and to manage. Currently, we are incapable of addressing these issues in a truly integrated fashion at global scales. The lack of an ability to combine global and regional forcing and to assess the response of the system to multiple stresses at the spatial and temporal scales of interest to humans limits our ability to assess the impacts of specific human perturbations, to assess advantages and risks, and to enhance economic and societal well being in the context of global, national and regional stewardship. These societal needs lead to a vision that uses a regional framework as a stepping-stone to a comprehensive national or global capability. The development of a comprehensive regional framework depends on a new approach to environmental research - the creation of regional Environmental Intelligence Centers. A key objective is to bring a demanding level of discipline to "forecasting" in a broad arena of environmental issues. The regional vision described above is designed to address a broad range of current and future environmental issues by creating a capability based on integrating diverse observing systems, making data readily accessible, developing an increasingly comprehensive predictive capability at the spatial and temporal scales appropriate for examining societal issues, and creating a vigorous intersection with decision-makers. With demonstrated success over a few large-scale regions of the U.S., this strategy will very likely grow into a national capability that far exceeds current capabilities.
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Identification of cells initiating human melanomas
Schatton, Tobias; Murphy, George F.; Frank, Natasha Y.; Yamaura, Kazuhiro; Waaga-Gasser, Ana Maria; Gasser, Martin; Zhan, Qian; Jordan, Stefan; Duncan, Lyn M.; Weishaupt, Carsten; Fuhlbrigge, Robert C.; Kupper, Thomas S.; Sayegh, Mohamed H.; Frank, Markus H.
2012-01-01
Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies1,2 and solid cancers3–6. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant-melanoma-initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 (refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5+ tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human-to-mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5− bulk populations and re-establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ sub-populations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5− progeny, whereas ABCB5− tumour populations give rise, at lower rates, exclusively to ABCB5− cells. In an initial proof-of-principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumour-inhibitory effects. Identification of tumour-initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy. PMID:18202660
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Capabilities of electrodynamic shakers when used for mechanical shock testing
NASA Technical Reports Server (NTRS)
Keegan, W. B.
1973-01-01
The results of a research task to investigate the capabilities of electrodynamic vibrators (shakers) to perform mechanical shock tests are presented. The simulation method employed was that of developing a transient whose shock response spectrum matched the desired shock response spectrum. Areas investigated included the maximum amplitude capabilities of the shaker systems, the ability to control the shape of the resultant shock response spectrum, the response levels induced at frequencies outside the controlled bandwidth, and the nonlinearities in structural response induced by a change in test level.
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2000-12-15
over many years, for responses to natural disasters, disease outbreaks, and accidents. Those capabilities can and should be used as a base for...terminated. 57 Many response entities had used those services and had included that capability in their response plans. This is one more example of... Many Federal entities 58 conduct or facilitate various exercises and offer State and local response entities opportunities to participate. Most agencies
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NASA Technical Reports Server (NTRS)
Williams-Byrd, Julie; Arney, Dale C.; Hay, Jason; Reeves, John D.; Craig, Douglas
2016-01-01
NASA is transforming human spaceflight. The Agency is shifting from an exploration-based program with human activities in low Earth orbit (LEO) and targeted robotic missions in deep space to a more sustainable and integrated pioneering approach. Through pioneering, NASA seeks to address national goals to develop the capacity for people to work, learn, operate, live, and thrive safely beyond Earth for extended periods of time. However, pioneering space involves daunting technical challenges of transportation, maintaining health, and enabling crew productivity for long durations in remote, hostile, and alien environments. Prudent investments in capability and technology developments, based on mission need, are critical for enabling a campaign of human exploration missions. There are a wide variety of capabilities and technologies that could enable these missions, so it is a major challenge for NASA's Human Exploration and Operations Mission Directorate (HEOMD) to make knowledgeable portfolio decisions. It is critical for this pioneering initiative that these investment decisions are informed with a prioritization process that is robust and defensible. It is NASA's role to invest in targeted technologies and capabilities that would enable exploration missions even though specific requirements have not been identified. To inform these investments decisions, NASA's HEOMD has supported a variety of analysis activities that prioritize capabilities and technologies. These activities are often based on input from subject matter experts within the NASA community who understand the technical challenges of enabling human exploration missions. This paper will review a variety of processes and methods that NASA has used to prioritize and rank capabilities and technologies applicable to human space exploration. The paper will show the similarities in the various processes and showcase instances were customer specified priorities force modifications to the process. Specifically, this paper will describe the processes that the NASA Langley Research Center (LaRC) Technology Assessment and Integration Team (TAIT) has used for several years and how those processes have been customized to meet customer needs while staying robust and defensible. This paper will show how HEOMD uses these analyses results to assist with making informed portfolio investment decisions. The paper will also highlight which human exploration capabilities and technologies typically rank high regardless of the specific design reference mission. The paper will conclude by describing future capability and technology ranking activities that will continue o leverage subject matter experts (SME) input while also incorporating more model-based analysis.
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Terrestrial Planet Finder: Technology Development Plans
NASA Technical Reports Server (NTRS)
Lindensmith, Chris
2004-01-01
One of humanity's oldest questions is whether life exists elsewhere in the universe. The Terrestrial Planet Finder (TPF) mission will survey stars in our stellar neighborhood to search for planets and perform spectroscopic measurements to identify potential biomarkers in their atmospheres. In response to the recently published President's Plan for Space Exploration, TPF has plans to launch a visible-light coronagraph in 2014, and a separated-spacecraft infrared interferometer in 2016. Substantial funding has been committed to the development of the key technologies that are required to meet these goals for launch in the next decade. Efforts underway through industry and university contracts and at JPL include a number of system and subsystem testbeds, as well as components and numerical modeling capabilities. The science, technology, and design efforts are closely coupled to ensure that requirements and capabilities will be consistent and meet the science goals.
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The first dedicated life sciences Spacelab mission
NASA Technical Reports Server (NTRS)
Perry, T. W.; Rummel, J. A.; Griffiths, L. D.; White, R. J.; Leonard, J. I.
1984-01-01
JIt is pointed out that the Shuttle-borne Spacelab provides the capability to fly large numbers of life sciences experiments, to retrieve and rescue experimental equipment, and to undertake multiple-flight studies. A NASA Life Sciences Flight Experiments Program has been organized with the aim to take full advantages of this capability. A description is provided of the scientific aspects of the most ambitious Spacelab mission currently being conducted in connection with this program, taking into account the First Dedicated Life Sciences Spacelab Mission. The payload of this mission will contain the equipment for 24 separate investigations. It is planned to perform the mission on two separate seven-day Spacelab flights, the first of which is currently scheduled for early 1986. Some of the mission objectives are related to the study of human and animal responses which occur promptly upon achieving weightlessness.
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Patiño, Tania; Soriano, Jorge; Barrios, Lleonard; Ibáñez, Elena; Nogués, Carme
2015-01-01
The use of micro- and nanodevices as multifunctional systems for biomedical applications has experienced an exponential growth during the past decades. Although a large number of studies have focused on the design and fabrication of new micro- and nanosystems capable of developing multiple functions, a deeper understanding of their interaction with cells is required. In the present study, we evaluated the effect of different microparticle surfaces on their interaction with normal and tumoral human breast epithelial cell lines. For this, AlexaFluor488 IgG functionalized polystyrene microparticles (3 μm) were coated with Polyethyleneimine (PEI) at two different molecular weights, 25 and 750 kDa. The effect of microparticle surface properties on cytotoxicity, cellular uptake and endocytic pathways were assessed for both normal and tumoral cell lines. Results showed a differential response between the two cell lines regarding uptake efficiency and mechanisms of endocytosis, highlighting the potential role of microparticle surface tunning for specific cell targeting. PMID:26068810
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Zivcec, Marko; Safronetz, David; Scott, Dana; Robertson, Shelly; Ebihara, Hideki; Feldmann, Heinz
2013-06-15
Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed viral hemorrhagic fever characterized by rapid onset of flu-like symptoms often followed by hemorrhagic manifestations. CCHF virus (CCHFV), a bunyavirus in the Nairovirus genus, is capable of infecting a wide range of mammalian hosts in nature but so far only causes disease in humans. Recently, immunocompromised mice have been reported as CCHF disease models, but detailed characterization is lacking. Here, we closely followed infection and disease progression in CCHFV-infected interferon α/β receptor knockout (IFNAR(-/-)) mice and age-matched wild-type (WT) mice. WT mice quickly clear CCHFV without developing any disease signs. In contrast, CCHFV infected IFNAR(-/-) mice develop an acute fulminant disease with high viral loads leading to organ pathology (liver and lymphoid tissues), marked proinflammatory host responses, severe thrombocytopenia, coagulopathy, and death. Disease progression closely mimics hallmarks of human CCHF disease, making IFNAR(-/-) mice an excellent choice to assess medical countermeasures.
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Antibacterial titanium nano-patterned arrays inspired by dragonfly wings
NASA Astrophysics Data System (ADS)
Bhadra, Chris M.; Khanh Truong, Vi; Pham, Vy T. H.; Al Kobaisi, Mohammad; Seniutinas, Gediminas; Wang, James Y.; Juodkazis, Saulius; Crawford, Russell J.; Ivanova, Elena P.
2015-11-01
Titanium and its alloys remain the most popular choice as a medical implant material because of its desirable properties. The successful osseointegration of titanium implants is, however, adversely affected by the presence of bacterial biofilms that can form on the surface, and hence methods for preventing the formation of surface biofilms have been the subject of intensive research over the past few years. In this study, we report the response of bacteria and primary human fibroblasts to the antibacterial nanoarrays fabricated on titanium surfaces using a simple hydrothermal etching process. These fabricated titanium surfaces were shown to possess selective bactericidal activity, eliminating almost 50% of Pseudomonas aeruginosa cells and about 20% of the Staphylococcus aureus cells coming into contact with the surface. These nano-patterned surfaces were also shown to enhance the aligned attachment behavior and proliferation of primary human fibroblasts over 10 days of growth. These antibacterial surfaces, which are capable of exhibiting differential responses to bacterial and eukaryotic cells, represent surfaces that have excellent prospects for biomedical applications.
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Antibacterial titanium nano-patterned arrays inspired by dragonfly wings
Bhadra, Chris M.; Khanh Truong, Vi; Pham, Vy T. H.; Al Kobaisi, Mohammad; Seniutinas, Gediminas; Wang, James Y.; Juodkazis, Saulius; Crawford, Russell J.; Ivanova, Elena P.
2015-01-01
Titanium and its alloys remain the most popular choice as a medical implant material because of its desirable properties. The successful osseointegration of titanium implants is, however, adversely affected by the presence of bacterial biofilms that can form on the surface, and hence methods for preventing the formation of surface biofilms have been the subject of intensive research over the past few years. In this study, we report the response of bacteria and primary human fibroblasts to the antibacterial nanoarrays fabricated on titanium surfaces using a simple hydrothermal etching process. These fabricated titanium surfaces were shown to possess selective bactericidal activity, eliminating almost 50% of Pseudomonas aeruginosa cells and about 20% of the Staphylococcus aureus cells coming into contact with the surface. These nano-patterned surfaces were also shown to enhance the aligned attachment behavior and proliferation of primary human fibroblasts over 10 days of growth. These antibacterial surfaces, which are capable of exhibiting differential responses to bacterial and eukaryotic cells, represent surfaces that have excellent prospects for biomedical applications. PMID:26576662
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Continuous Improvement in Battery Testing at the NASA/JSC Energy System Test Area
NASA Technical Reports Server (NTRS)
Boyd, William; Cook, Joseph
2003-01-01
The Energy Systems Test Area (ESTA) at the Lyndon B. Johnson Space Center in Houston, Texas conducts development and qualification tests to fulfill Energy System Division responsibilities relevant to ASA programs and projects. EST A has historically called upon a variety of fluid, mechanical, electrical, environmental, and data system capabilities spread amongst five full-service facilities to test human and human supported spacecraft in the areas of propulsion systems, fluid systems, pyrotechnics, power generation, and power distribution and control systems. Improvements at ESTA are being made in full earnest of offering NASA project offices an option to choose a thorough test regime that is balanced with cost and schedule constraints. In order to continue testing of enabling power-related technologies utilized by the Energy System Division, an especially proactive effort has been made to increase the cost effectiveness and schedule responsiveness for battery testing. This paper describes the continuous improvement in battery testing at the Energy Systems Test Area being made through consolidation, streamlining, and standardization.
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NASA Astrophysics Data System (ADS)
Ghosh, Sreya
2017-02-01
This article proposes a new six-model architecture for an intelligent tutoring system to be incorporated in a learning management system with domain-independence feature and individualized dissemination. The present six model architecture aims to simulate a human tutor. Some recent extensions of using intelligent tutoring system (ITS) explores learning management systems to behave as a real teacher during a teaching-learning process, by taking care of, mainly, the dynamic response system. However, the present paper argues that to mimic a human teacher it needs not only the dynamic response but also the incorporation of the teacher's dynamic review of students' performance and keeping track of their current level of understanding. Here, the term individualization has been used to refer to tailor making of contents and its dissemination fitting to the individual needs and capabilities of learners who is taking a course online and is subjected to teaching in absentia. This paper describes how the individual models of the proposed architecture achieves the features of ITS.
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NASA Astrophysics Data System (ADS)
Patiño, Tania; Soriano, Jorge; Barrios, Lleonard; Ibáñez, Elena; Nogués, Carme
2015-06-01
The use of micro- and nanodevices as multifunctional systems for biomedical applications has experienced an exponential growth during the past decades. Although a large number of studies have focused on the design and fabrication of new micro- and nanosystems capable of developing multiple functions, a deeper understanding of their interaction with cells is required. In the present study, we evaluated the effect of different microparticle surfaces on their interaction with normal and tumoral human breast epithelial cell lines. For this, AlexaFluor488 IgG functionalized polystyrene microparticles (3 μm) were coated with Polyethyleneimine (PEI) at two different molecular weights, 25 and 750 kDa. The effect of microparticle surface properties on cytotoxicity, cellular uptake and endocytic pathways were assessed for both normal and tumoral cell lines. Results showed a differential response between the two cell lines regarding uptake efficiency and mechanisms of endocytosis, highlighting the potential role of microparticle surface tunning for specific cell targeting.
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Patiño, Tania; Soriano, Jorge; Barrios, Lleonard; Ibáñez, Elena; Nogués, Carme
2015-06-12
The use of micro- and nanodevices as multifunctional systems for biomedical applications has experienced an exponential growth during the past decades. Although a large number of studies have focused on the design and fabrication of new micro- and nanosystems capable of developing multiple functions, a deeper understanding of their interaction with cells is required. In the present study, we evaluated the effect of different microparticle surfaces on their interaction with normal and tumoral human breast epithelial cell lines. For this, AlexaFluor488 IgG functionalized polystyrene microparticles (3 μm) were coated with Polyethyleneimine (PEI) at two different molecular weights, 25 and 750 kDa. The effect of microparticle surface properties on cytotoxicity, cellular uptake and endocytic pathways were assessed for both normal and tumoral cell lines. Results showed a differential response between the two cell lines regarding uptake efficiency and mechanisms of endocytosis, highlighting the potential role of microparticle surface tunning for specific cell targeting.
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Bozzi, Fabio; Manenti, Giacomo; Conca, Elena; Stacchiotti, Silvia; Messina, Antonella; Dagrada, GianPaolo; Gronchi, Alessandro; Panizza, Pietro; Pierotti, Marco A; Tamborini, Elena; Pilotti, Silvana
2014-01-01
Chordomas are rare and indolent bone tumors that arise in the skull base and mobile spine. Distant metastases occur in >20% of cases, but morbidity and mortality are mainly related to local relapses that affect the majority of patients. Standard chemotherapy has modest activity, whereas new targeted therapies (alone or in combination) have some activity in controlling disease progression. However, the scarcity of preclinical models capable of testing in vivo responses to these therapies hampers the development of new medical strategies. In this study, 8 chordoma samples taken from 8 patients were implanted in nude mice. Four engrafted successfully and gave rise to tumor masses that were analyzed histologically, by means of fluorescence in situ hybridization and biochemical techniques. The data relating to each of the mouse tumors were compared with those obtained from the corresponding human tumor. All 4 engraftments retained the histological, genetic and biochemical features of the human tumors they came from. In one epidermal growth factor receptor(EGFR)-positive xenograft, responsiveness to lapatinib was evaluated by comparing the pre- and post treatment findings. The treatment induced a low-level, heterogeneous switching off of EGFR and its downstream signaling effectors. Overall, this model is very close to human chordoma and represents a new means of undertaking preclinical investigations and developing tailored therapies.
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Kaufmann, Andreas; Musset, Boris; Limberg, Sven H; Renigunta, Vijay; Sus, Rainer; Dalpke, Alexander H; Heeg, Klaus M; Robaye, Bernard; Hanley, Peter J
2005-09-16
The activation of Toll-like receptors (TLRs) by lipopolysaccharide or other ligands evokes a proinflammatory immune response, which is not only capable of clearing invading pathogens but can also inflict damage to host tissues. It is therefore important to prevent an overshoot of the TLR-induced response where necessary, and here we show that extracellular ATP is capable of doing this in human monocytes. Using reverse transcription-PCR, we showed that monocytes express P2Y(1), P2Y(2), P2Y(4), P2Y(11), and P2Y(13) receptors, as well as several P2X receptors. To elucidate the function of these receptors, we first studied Ca(2+) signaling in single cells. ATP or UTP induced a biphasic increase in cytosolic Ca(2+), which corresponded to internal Ca(2+) release followed by activation of store-operated Ca(2+) entry. The evoked Ca(2+) signals stimulated Ca(2+)-activated K(+) channels, producing transient membrane hyperpolarization. In addition, ATP promoted cytoskeleton reorganization and cell migration; however, unlike chemoattractants, the migration was non-directional and further analysis showed that ATP did not activate Akt, essential for sensing gradients. When TLR2, TLR4, or TLR2/6 were stimulated with their respective ligands, ATPgammaS profoundly inhibited secretion of proinflammatory cytokines (tumor necrosis factor-alpha and monocyte chemoattractant protein-1) but increased the production of interleukin-10, an anti-inflammatory cytokine. In radioimmune assays, we found that ATP (or ATPgammaS) strongly increased cAMP levels, and, moreover, the TLR-response was inhibited by forskolin, whereas UTP neither increased cAMP nor inhibited the TLR-response. Thus, our data suggest that ATP promotes non-directional migration and, importantly, acts as a "host tissue damage" signal via the G(s) protein-coupled P2Y(11) receptor and increased cAMP to negatively regulate TLR signaling.
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Low-dose non-targeted radiation effects in human esophageal adenocarcinoma cell lines.
Hanu, Christine; Wong, Raimond; Sur, Ranjan K; Hayward, Joseph E; Seymour, Colin; Mothersill, Carmel
2017-02-01
To investigate non-targeted radiation effects in esophageal adenocarcinoma cell lines (OE19 and OE33) using human keratinocyte and colorectal cancer cell reporters following γ-ray exposure. Both clonogenic assays and ratiometric calcium endpoints were used to check for the occurrence of bystander signals in reporter cells. We report data suggesting that γ-irradiation increases cell killing over the expected linear quadratic (LQ) model levels in the OE19 cell line exposed to doses below 1 Gy, i.e. which may be suggestive to be a low hyper-radiosensitive (HRS) response to direct irradiation. Both EAC cell lines (OE19 and OE33) have the ability to produce bystander signals when irradiated cell conditioned medium (ICCM) is placed onto human keratinocyte reporters, but do not seem to be capable of responding to bystander signals when placed on their autologous reporters. Further work with human keratinocyte reporter models showed statistically significant intracellular calcium fluxes following exposure of the reporters to ICCM harvested from both EAC cell lines exposed to 0.5 Gy. These experiments suggest that the OE19 and OE33 cell lines produce bystander signals in human keratinocyte reporter cells. However, the radiosensitivity of the EAC cell lines used in this study cannot be enhanced by the bystander response since both cell lines could not respond to bystander signals.
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Cabrera Trujillo, Laura Yenisa; Engel-Glatter, Sabrina
2015-06-01
Research with human-animal chimera raises a number of ethical concerns, especially when neural stem cells are transplanted into the brains of non-human primates (NHPs). Besides animal welfare concerns and ethical issues associated with the use of embryonic stem cells, the research is also regarded as controversial from the standpoint of NHPs developing cognitive or behavioural capabilities that are regarded as "unique" to humans. However, scientists are urging to test new therapeutic approaches for neurological diseases in primate models as they better mimic human physiology than all current animal models. As a response, various countries have issued reports on the topic. Our paper summarizes the ethical issues raised by research with human-animal brain chimeras and compares the relevant regulatory instruments and different recommendations issued in national reports from three important European research nations: Germany, Switzerland and the United Kingdom. We assess and discuss the focus and priorities set by the different reports, review various reasons for and perspectives on the importance of the brain in chimera research, and identify critical points in the reports that warrant further specification and debate.
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Body-on-a-chip systems for animal-free toxicity testing.
Mahler, Gretchen J; Esch, Mandy B; Stokol, Tracy; Hickman, James J; Shuler, Michael L
2016-10-01
Body-on-a-chip systems replicate the size relationships of organs, blood distribution and blood flow, in accordance with human physiology. When operated with tissues derived from human cell sources, these systems are capable of simulating human metabolism, including the conversion of a prodrug to its effective metabolite, as well as its subsequent therapeutic actions and toxic side-effects. The system also permits the measurement of human tissue electrical and mechanical reactions, which provide a measure of functional response. Since these devices can be operated with human tissue samples or with in vitro tissues derived from induced pluripotent stem cells (iPS), they can play a significant role in determining the success of new pharmaceuticals, without resorting to the use of animals. By providing a platform for testing in the context of human metabolism, as opposed to animal models, the systems have the potential to eliminate the use of animals in preclinical trials. This article will review progress made and work achieved as a direct result of the 2015 Lush Science Prize in support of animal-free testing. 2016 FRAME.
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Experimental models in vaccine research: malaria and leishmaniasis.
Teixeira, C; Gomes, R
2013-02-01
Animal models have a long history of being useful tools, not only to test and select vaccines, but also to help understand the elaborate details of the immune response that follows infection. Different models have been extensively used to investigate putative immunological correlates of protection against parasitic diseases that are important to reach a successful vaccine. The greatest challenge has been the improvement and adaptation of these models to reflect the reality of human disease and the screening of vaccine candidates capable of overcoming the challenge of natural transmission. This review will discuss the advantages and challenges of using experimental animal models for vaccine development and how the knowledge achieved can be extrapolated to human disease by looking into two important parasitic diseases: malaria and leishmaniasis.
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NASA Astrophysics Data System (ADS)
Lucena, P.; Gaona, I.; Moros, J.; Laserna, J. J.
2013-07-01
Detection of explosive-contaminated human fingerprints constitutes an analytical challenge of high significance in security issues and in forensic sciences. The use of a laser-induced breakdown spectroscopy (LIBS) sensor working at 31 m distance to the target, fitted with 2D scanning capabilities and designed for capturing spectral information from laser-induced plasmas of fingerprints is presented. Distribution chemical maps based on Na and CN emissions are used to locate and detect chloratite, DNT, TNT, RDX and PETN residues that have been deposited on the surface of aluminum and glass substrates. An effectiveness of 100% on fingerprints detection, regardless the substrate scanned, is reached. Environmental factors that affect the prevalence of the fingerprint LIBS response are discussed.
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NASA Technical Reports Server (NTRS)
Davis, Jeffrey R.; Fitts, David J.
2009-01-01
This viewgraph presentation reviews the standards for space flight hardware based on human capabilities and limitations. The contents include: 1) Scope; 2) Applicable documents; 3) General; 4) Human Physical Characteristics and Capabilities; 5) Human Performance and Cognition; 6) Natural and Induced Environments; 7) Habitability Functions; 8) Architecture; 9) Hardware and Equipment; 10) Crew Interfaces; 11) Spacesuits; 12) Operatons: Reserved; 13) Ground Maintenance and Assembly: Reserved; 14) Appendix A-Reference Documents; 15) Appendix N-Acronyms and 16) Appendix C-Definition. Volume 2 is supported by the Human Integration Design Handbook (HIDH)s.
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Machine Learning and Quantum Mechanics
NASA Astrophysics Data System (ADS)
Chapline, George
The author has previously pointed out some similarities between selforganizing neural networks and quantum mechanics. These types of neural networks were originally conceived of as away of emulating the cognitive capabilities of the human brain. Recently extensions of these networks, collectively referred to as deep learning networks, have strengthened the connection between self-organizing neural networks and human cognitive capabilities. In this note we consider whether hardware quantum devices might be useful for emulating neural networks with human-like cognitive capabilities, or alternatively whether implementations of deep learning neural networks using conventional computers might lead to better algorithms for solving the many body Schrodinger equation.
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Compliant Task Execution and Learning for Safe Mixed-Initiative Human-Robot Operations
NASA Technical Reports Server (NTRS)
Dong, Shuonan; Conrad, Patrick R.; Shah, Julie A.; Williams, Brian C.; Mittman, David S.; Ingham, Michel D.; Verma, Vandana
2011-01-01
We introduce a novel task execution capability that enhances the ability of in-situ crew members to function independently from Earth by enabling safe and efficient interaction with automated systems. This task execution capability provides the ability to (1) map goal-directed commands from humans into safe, compliant, automated actions, (2) quickly and safely respond to human commands and actions during task execution, and (3) specify complex motions through teaching by demonstration. Our results are applicable to future surface robotic systems, and we have demonstrated these capabilities on JPL's All-Terrain Hex-Limbed Extra-Terrestrial Explorer (ATHLETE) robot.
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Nicolaou, Anna; Estdale, Sian E; Tsatmali, Marina; Herrero, Daniel Pascual; Thody, Anthony J
2004-07-16
Prostaglandins are potent mediators of the inflammatory response and are also involved in cancer development. In this study, we show that human melanocytes and FM55 melanoma cells express cyclooxygenase-1 and -2 (COX-1 and -2) and thus have the capability to produce prostaglandins. The FM55 cells produced predominantly PGE2 and PGF2alpha, whereas the HaCaT keratinocyte cell line produced mainly PGE2. The anti-inflammatory peptide, alpha-melanocyte stimulating hormone (alpha-MSH), reduced prostaglandin production in FM55 and HaCaT cells and reversed the effect of the pro-inflammatory cytokine TNF-alpha in the former. These results indicate that melanocytes produce prostaglandins and that alpha-MSH, by inhibiting this response, may play an important role in regulating inflammatory responses in the skin.
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Human melanoma immunotherapy using tumor antigen-specific T cells generated in humanized mice
Hu, Zheng; Xia, Jinxing; Fan, Wei; Wargo, Jennifer; Yang, Yong-Guang
2016-01-01
A major factor hindering the exploration of adoptive immunotherapy in preclinical settings is the limited availability of tumor-reactive human T cells. Here we developed a humanized mouse model that permits large-scale production of human T cells expressing the engineered melanoma antigen MART-1-specific TCR. Humanized mice, made by transplantation of human fetal thymic tissue and CD34+ cells virally-transduced with HLA class I-restricted melanoma antigen (MART-1)-specific TCR gene, showed efficient development of MART-1-TCR+ human T cells with predominantly CD8+ cells. Importantly, MART-1-TCR+CD8+ T cells developing in these mice were capable of mounting antigen-specific responses in vivo, as evidenced by their proliferation, phenotypic conversion and IFN-γ production following MART-1 peptide immunization. Moreover, these MART-1-TCR+CD8+ T cells mediated efficient killing of melanoma cells in an HLA/antigen-dependent manner. Adoptive transfer of in vitro expanded MART-1-TCR+CD8+ T cells induced potent antitumor responses that were further enhanced by IL-15 treatment in melanoma-bearing recipients. Finally, a short incubation of MART-1-specific T cells with rapamycin acted synergistically with IL-15, leading to significantly improved tumor-free survival in recipients with metastatic melanoma. These data demonstrate the practicality of using humanized mice to produce potentially unlimited source of tumor-specific human T cells for experimental and preclinical exploration of cancer immunotherapy. This study also suggests that pretreatment of tumor-reactive T cells with rapamycin in combination with IL-15 administration may be a novel strategy to improve the efficacy of adoptive T cell therapy. PMID:26824989
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Integrated Human-Robotic Missions to the Moon and Mars: Mission Operations Design Implications
NASA Technical Reports Server (NTRS)
Mishkin, Andrew; Lee, Young; Korth, David; LeBlanc, Troy
2007-01-01
For most of the history of space exploration, human and robotic programs have been independent, and have responded to distinct requirements. The NASA Vision for Space Exploration calls for the return of humans to the Moon, and the eventual human exploration of Mars; the complexity of this range of missions will require an unprecedented use of automation and robotics in support of human crews. The challenges of human Mars missions, including roundtrip communications time delays of 6 to 40 minutes, interplanetary transit times of many months, and the need to manage lifecycle costs, will require the evolution of a new mission operations paradigm far less dependent on real-time monitoring and response by an Earthbound operations team. Robotic systems and automation will augment human capability, increase human safety by providing means to perform many tasks without requiring immediate human presence, and enable the transfer of traditional mission control tasks from the ground to crews. Developing and validating the new paradigm and its associated infrastructure may place requirements on operations design for nearer-term lunar missions. The authors, representing both the human and robotic mission operations communities, assess human lunar and Mars mission challenges, and consider how human-robot operations may be integrated to enable efficient joint operations, with the eventual emergence of a unified exploration operations culture.
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Integrated Human-Robotic Missions to the Moon and Mars: Mission Operations Design Implications
NASA Technical Reports Server (NTRS)
Korth, David; LeBlanc, Troy; Mishkin, Andrew; Lee, Young
2006-01-01
For most of the history of space exploration, human and robotic programs have been independent, and have responded to distinct requirements. The NASA Vision for Space Exploration calls for the return of humans to the Moon, and the eventual human exploration of Mars; the complexity of this range of missions will require an unprecedented use of automation and robotics in support of human crews. The challenges of human Mars missions, including roundtrip communications time delays of 6 to 40 minutes, interplanetary transit times of many months, and the need to manage lifecycle costs, will require the evolution of a new mission operations paradigm far less dependent on real-time monitoring and response by an Earthbound operations team. Robotic systems and automation will augment human capability, increase human safety by providing means to perform many tasks without requiring immediate human presence, and enable the transfer of traditional mission control tasks from the ground to crews. Developing and validating the new paradigm and its associated infrastructure may place requirements on operations design for nearer-term lunar missions. The authors, representing both the human and robotic mission operations communities, assess human lunar and Mars mission challenges, and consider how human-robot operations may be integrated to enable efficient joint operations, with the eventual emergence of a unified exploration operations culture.
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Steward, Wayne T; Koester, Kimberly A; Collins, Shane P; Maiorana, Andre; Myers, Janet J
2012-10-01
To understand the dynamic capabilities that enabled the six demonstration projects of the Information Technology Networks of Care Initiative to implement health information exchanges (HIEs) tailored to their local HIV epidemics and regional care systems. We conducted 111 semi-structured interviews with project staff and information technology (IT) specialists associated with the demonstration projects, staff from community-based organizations and public health agencies collaborating in the design and implementation of the HIEs, and providers who used each HIE. The dynamic capability framework guided analyses. In the context of a HIE, the framework's components include information systems (the actual technological exchange systems and capacity to update them), absorptive capacity (the ability to implement an operating HIE), reconfiguration capacity (the ability to adapt workflows and clinical practices in response to a HIE), and organizational size and human resources (characteristics likely to affect a clinic's ability to respond). Across the projects, we found evidence for the importance of three dynamic capabilities: information systems, reconfiguration capacity, and organizational size and human resources. However, of these three, reconfiguration capacity was the most salient. Implementation outcomes at all six of the projects were shaped substantially by the degree of attention dedicated to reworking procedures and practices so that HIE usage became routine. Electronic information exchange offers the promise of improved coordination of care. However, implementation of HIEs goes beyond programing and hardware installation challenges, and requires close attention to the needs of the HIEs end-users. Providers need to discern value from a HIE because their active participation is essential to ensuring that clinic and agency practices and procedures are reconfigured to incorporate new systems into daily work processes. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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Singh, Susmita K.; McKay, Derek M.
2017-01-01
Background In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis. Principal findings We investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb. Measuring cytokine output, macrophage surface markers with flow cytometry, and assessing bacterial replication and phagosomal maturation revealed that antigens from different species of helminth directly affect macrophage responses to Mtb. Antigens from the tapeworm Hymenolepis diminuta and the nematode Trichuris muris caused an anti-inflammatory response with M2-type polarization, reduced macrophage phagosome maturation and ability to activate T cells, along with increased Mtb burden, especially in T. muris exposed cells which also induced the highest IL-10 production upon co-infection. However, antigens from the trematode Schistosoma mansoni had the opposite effect causing a decrease in IL-10 production, M1-type polarization and increased control of Mtb. Conclusion We conclude that, independent of any adaptive immune response, infection with helminth parasites, in a species-specific manner can influence the outcome of tuberculosis by either enhancing or diminishing the bactericidal function of macrophages. PMID:28192437
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Functional Differences between Human NKp44(-) and NKp44(+) RORC(+) Innate Lymphoid Cells.
Hoorweg, Kerim; Peters, Charlotte P; Cornelissen, Ferry; Aparicio-Domingo, Patricia; Papazian, Natalie; Kazemier, Geert; Mjösberg, Jenny M; Spits, Hergen; Cupedo, Tom
2012-01-01
Human RORC(+) lymphoid tissue inducer cells are part of a rapidly expanding family of innate lymphoid cells (ILC) that participate in innate and adaptive immune responses as well as in lymphoid tissue (re) modeling. The assessment of a potential role for innate lymphocyte-derived cytokines in human homeostasis and disease is hampered by a poor characterization of RORC(+) innate cell subsets and a lack of knowledge on the distribution of these cells in adults. Here we show that functionally distinct subsets of human RORC(+) innate lymphoid cells are enriched for secretion of IL-17a or IL-22. Both subsets have an activated phenotype and can be distinguished based on the presence or absence of the natural cytotoxicity receptor NKp44. NKp44(+) IL-22 producing cells are present in tonsils while NKp44(-) IL-17a producing cells are present in fetal developing lymph nodes. Development of human intestinal NKp44(+) ILC is a programmed event that is independent of bacterial colonization and these cells colonize the fetal intestine during the first trimester. In the adult intestine, NKp44(+) ILC are the main ILC subset producing IL-22. NKp44(-) ILC remain present throughout adulthood in peripheral non-inflamed lymph nodes as resting, non-cytokine producing cells. However, upon stimulation lymph node ILC can swiftly initiate cytokine transcription suggesting that secondary human lymphoid organs may function as a reservoir for innate lymphoid cells capable of participating in inflammatory responses.
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A New Genetic Vaccine Platform Based on an Adeno-Associated Virus Isolated from a Rhesus Macaque ▿
Lin, Jianping; Calcedo, Roberto; Vandenberghe, Luk H.; Bell, Peter; Somanathan, Suryanarayan; Wilson, James M.
2009-01-01
We created a hybrid adeno-associated virus (AAV) from two related rhesus macaque isolates, called AAVrh32.33, and evaluated it as a vaccine carrier for human immunodeficiency virus type 1 (HIV-1) and type A influenza virus antigens. The goal was to overcome the limitations of vaccines based on other AAVs, which generate dysfunctional T-cell responses and are inhibited by antibodies found in human sera. Injection of a Gag-expressing AAVrh32.33 vector into mice resulted in a high-quality CD8+ T-cell response. The resulting Gag-specific T cells express multiple cytokines at high levels, including interleukin-2, with many having memory phenotypes; a subsequent boost with an adenovirus vector yielded a brisk expansion of Gag-specific T cells. A priming dose of AAVrh32.33 led to high levels of Gag antibodies, which exceed levels found after injection of adenovirus vectors. Importantly, passive transfer of pooled human immunoglobulin into mice does not interfere with the efficacy of AAVrh32.33 expressing nucleoproteins from influenza virus, as measured by protection to a lethal dose of influenza virus, which is consistent with the very low seroprevalence to this virus in humans. Studies of macaques with vectors expressing gp140 from HIV-1 (i.e., with AAVrh32.33 as the prime and simian adenovirus type 24 as the boost) demonstrated results similar to those for mice with high-level and high-quality CD8+ T-cell responses to gp140 and high-titered neutralizing antibodies to homologous HIV-1. The biology of this novel AAV hybrid suggests that it should be a preferred genetic vaccine carrier, capable of generating robust T- and B-cell responses. PMID:19812149
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Pathogen-Sensing and Regulatory T Cells: Integrated Regulators of Immune Responses
Grossman, Zvi; Paul, William E.
2014-01-01
We present the concept that pathogen-sensing and Tregs mutually regulate immune responses to conventional and tumor antigens through countervailing effects on dendritic cells. Normally, conventional CD4 T cells recognizing their cognate antigen-presented by a dendritic cell will respond only if the dendritic cell also receives a signal through its pathogen-sensing/ danger / adjuvant recognition systems (the pathogen-sensing triad). However, if Tregs capable of interacting with the same DC are absent, dendritic cells are competent to present antigens, both foreign and self, even without the stimulation provided by the pathogen-sensing triad. Tregs recognizing an antigen presented by the DC that is also presenting antigen to a conventional CD4 T cell will prevent such responses but a signal delivered by a member of the pathogen-sensing traid will overcome the Tregs’inhibitory action and will allow responses to go forward. These considerations take on special meaning for responses to “weak antigens” such as many of the antigens displayed by spontaneous human tumors. PMID:24894087
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Functional analysis of HPV-like particle-activated Langerhans cells in vitro.
Yan, Lisa; Woodham, Andrew W; Da Silva, Diane M; Kast, W Martin
2015-01-01
Langerhans cells (LCs) are antigen-presenting cells responsible for initiating an immune response against human papillomaviruses (HPVs) entering the epithelial layer in vivo as they are the first immune cell that HPV comes into contact with. LCs become activated in response to foreign antigens, which causes internal signaling resulting in the increased expression of co-stimulatory molecules and the secretion of inflammatory cytokines. Functionally activated LCs are then capable of migrating to the lymph nodes where they interact with antigen-specific T cells and initiate an adaptive T-cell response in vivo. However, HPV has evolved in a manner that suppresses LC function, and thus the induction of antigen-specific T cells is hindered. While many methods exist to monitor the activity of LCs in vitro, the migration and induction of cytotoxic T cells is ultimately indicative of a functional immune response. Here, methods in analyzing functional migration and induction of antigen-specific T cells after stimulation of LCs with HPV virus-like particles in vitro are described.
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Lowell, Jr., James R.; Edlund, David J.; Friesen, Dwayne T.; Rayfield, George W.
1991-01-01
Sensors responsive to small changes in the concentration of chemical species are disclosed, comprising (a) a mechanochemically responsive polymeric film capable of expansion or contraction in response to a change in its chemical environment, operatively coupled to (b) a transducer capable of directly converting said expansion or contraction to a measurable electrical response.
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The colibactin warhead crosslinks DNA
NASA Astrophysics Data System (ADS)
Vizcaino, Maria I.; Crawford, Jason M.
2015-05-01
Members of the human microbiota are increasingly being correlated to human health and disease states, but the majority of the underlying microbial metabolites that regulate host-microbe interactions remain largely unexplored. Select strains of Escherichia coli present in the human colon have been linked to the initiation of inflammation-induced colorectal cancer through an unknown small-molecule-mediated process. The responsible non-ribosomal peptide-polyketide hybrid pathway encodes ‘colibactin’, which belongs to a largely uncharacterized family of small molecules. Genotoxic small molecules from this pathway that are capable of initiating cancer formation have remained elusive due to their high instability. Guided by metabolomic analyses, here we employ a combination of NMR spectroscopy and bioinformatics-guided isotopic labelling studies to characterize the colibactin warhead, an unprecedented substituted spirobicyclic structure. The warhead crosslinks duplex DNA in vitro, providing direct experimental evidence for colibactin's DNA-damaging activity. The data support unexpected models for both colibactin biosynthesis and its mode of action.
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The NASA Ames Fatigue Countermeasures Program: The Next Generation
NASA Technical Reports Server (NTRS)
Rosekind, Mark R.; Neri, David F.; Miller, Donna L.; Gregory, Kevin B.; Webbon, Lissa L.; Oyung, Ray L.
1997-01-01
Twenty-four hour, global aviation operations pose unique challenges to humans. Physiological requirements related to sleep, the internal circadian clock, and human fatigue are critical factors that are known to affect safety, performance, and productivity. Understanding the human operators' physiological capabilities, and limitations, will be important to address these issues as global demand for aviation activities continues to increase. In 1980, in response to a Congressional request, the National Aeronautics and Space Administration (NASA) Ames Research Center initiated a Fatigue/Jet Lag Program to examine the role of fatigue in flight operations. Originally established by Dr. John K. Lauber and Dr. Charles E. Billings, the Program was designed to address three objectives: (1) determine the extent of fatigue, sleep loss, and circadian disruption in flight operations; (2) determine how fatigue affected flight crew performance; and (3) develop strategies to maximize performance and alertness during flight operations.
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The role of pars flaccida in human middle ear sound transmission.
Aritomo, H; Goode, R L; Gonzalez, J
1988-04-01
The role of the pars flaccida in middle ear sound transmission was studied with the use of twelve otoscopically normal, fresh, human temporal bones. Peak-to-peak umbo displacement in response to a constant sound pressure level at the tympanic membrane was measured with a noncontacting video measuring system capable of repeatable measurements down to 0.2 micron. Measurements were made before and after pars flaccida modifications at 18 frequencies between 100 and 4000 Hz. Four pars flaccida modifications were studied: (1) acoustic insulation of the pars flaccida to the ear canal with a silicone rubber baffle, (2) stiffening the pars flaccida with cyanoacrylate cement, (3) decreasing the tension of the pars flaccida with a nonperforating incision, and (4) perforation of the pars flaccida. All of the modifications (except the perforation) had a minimal effect on umbo displacement; this seems to imply that the pars flaccida has a minor acoustic role in human beings.
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Classification of human pathogen bacteria for early screening using electronic nose
NASA Astrophysics Data System (ADS)
Zulkifli, Syahida Amani; Mohamad, Che Wan Syarifah Robiah; Abdullah, Abu Hassan
2017-10-01
This paper present human pathogen bacteria for early screening using electronic nose. Electronic nose (E-nose) known as gas sensor array is a device that analyze the odor measurement give the fast response and less time consuming for clinical diagnosis. Many bacterial pathogens could lead to life threatening infections. Accurate and rapid diagnosis is crucial for the successful management of these infections disease. The conventional method need more time to detect the growth of bacterial. Alternatively, the bacteria are Pseudomonas aeruginosa and Shigella cultured on different media agar can be detected and classifies according to the volatile compound in shorter time using electronic nose (E-nose). Then, the data from electronic nose (E-nose) is processed using statistical method which is principal component analysis (PCA). The study shows the capability of electronic nose (E-nose) for early screening for bacterial infection in human stomach.
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Lockheed Martin Response to the OSP Challenge
NASA Technical Reports Server (NTRS)
Sullivan, Robert T.; Munkres, Randy; Megna, Thomas D.; Beckham, Joanne
2003-01-01
The Lockheed Martin Orbital Space Plane System provides crew transfer and rescue for the International Space Station more safely and affordably than current human space transportation systems. Through planned upgrades and spiral development, it is also capable of satisfying the Nation's evolving space transportation requirements and enabling the national vision for human space flight. The OSP System, formulated through rigorous requirements definition and decomposition, consists of spacecraft and launch vehicle flight elements, ground processing facilities and existing transportation, launch complex, range, mission control, weather, navigation, communication and tracking infrastructure. The concept of operations, including procurement, mission planning, launch preparation, launch and mission operations and vehicle maintenance, repair and turnaround, is structured to maximize flexibility and mission availability and minimize program life cycle cost. The approach to human rating and crew safety utilizes simplicity, performance margin, redundancy, abort modes and escape modes to mitigate credible hazards that cannot be designed out of the system.
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Acute sun damage and photoprotective responses in whales
Martinez-Levasseur, Laura M.; Gendron, Diane; Knell, Rob J.; O'Toole, Edel A.; Singh, Manuraj; Acevedo-Whitehouse, Karina
2011-01-01
Rising levels of ultraviolet radiation (UVR) secondary to ozone depletion are an issue of concern for public health. Skin cancers and intraepidermal dysplasia are increasingly observed in individuals that undergo chronic or excessive sun exposure. Such alterations of skin integrity and function are well established for humans and laboratory animals, but remain unexplored for mammalian wildlife. However, effects are unlikely to be negligible, particularly for species such as whales, whose anatomical or life-history traits force them to experience continuous sun exposure. We conducted photographic and histological surveys of three seasonally sympatric whale species to investigate sunburn and photoprotection. We find that lesions commonly associated with acute severe sun damage in humans are widespread and that individuals with fewer melanocytes have more lesions and less apoptotic cells. This suggests that the pathways used to limit and resolve UVR-induced damage in humans are shared by whales and that darker pigmentation is advantageous to them. Furthermore, lesions increased significantly in time, as would be expected under increasing UV irradiance. Apoptosis and melanocyte proliferation mirror this trend, suggesting that whales are capable of quick photoprotective responses. We conclude that the thinning ozone layer may pose a risk to the health of whales and other vulnerable wildlife. PMID:21068035
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NASA Astrophysics Data System (ADS)
Bruinen, Anne L.; Fisher, Gregory L.; Balez, Rachelle; van der Sar, Astrid M.; Ooi, Lezanne; Heeren, Ron M. A.
2018-06-01
A unique method for identification of biomolecular components in different biological specimens, while preserving the capability for high speed 2D and 3D molecular imaging, is employed to investigate cellular response to oxidative stress. The employed method enables observing the distribution of the antioxidant α-tocopherol and other molecules in cellular structures via time-of-flight secondary ion mass spectrometry (TOF-SIMS (MS1)) imaging in parallel with tandem mass spectrometry (MS2) imaging, collected simultaneously. The described method is employed to examine a network formed by neuronal cells differentiated from human induced pluripotent stem cells (iPSCs), a model for investigating human neurons in vitro. The antioxidant α-tocopherol is identified in situ within different cellular layers utilizing a 3D TOF-SIMS tandem MS imaging analysis. As oxidative stress also plays an important role in mediating inflammation, the study was expanded to whole body tissue sections of M. marinum-infected zebrafish, a model organism for tuberculosis. The TOF-SIMS tandem MS imaging results reveal an increased presence of α-tocopherol in response to the pathogen. [Figure not available: see fulltext.
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Building human resources capability in health care: a global analysis of best practice--Part III.
Zairi, M
1998-01-01
This is the last part of a series of three papers which discussed very comprehensively best practice applications in human resource management by drawing special inferences to the healthcare context. It emerged from parts I and II that high performing organisations plan and intend to build sustainable capability through a systematic consideration of the human element as the key asset and through a continuous process of training, developing, empowering and engaging people in all aspects of organisational excellence. Part III brings this debate to a close by demonstrating what brings about organisational excellence and proposes a road map for effective human resource development and management, based on world class standards. Healthcare human resource professionals can now rise to the challenge and plan ahead for building organisational capability and sustainable performance.
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Nara, P L; Robey, W G; Arthur, L O; Asher, D M; Wolff, A V; Gibbs, C J; Gajdusek, D C; Fischinger, P J
1987-01-01
Persistent infection by human immunodeficiency virus (HIV-1) in the chimpanzee may be valuable for immunopathologic and potential vaccine evaluation. Two HIV strains, the tissue culture-derived human T-cell lymphotropic virus type IIIB (HTLV-IIIB) and in vivo serially passaged lymphadenopathy-associated virus type 1 (LAV-1), were injected intravenously into chimpanzees. Two animals received HTLV-IIIB as either virus-infected H9 cells or cell-free virus. A third animal received chimpanzee-passaged LAV-1. Evaluation of their sera for virus-specific serologic changes, including neutralizations, was done during a 2-year period. During this period all animals had persistently high titers of antibodies to viral core and envelope antigens. All three animals developed a progressively increasing type-specific neutralizing LAV-1 versus HTLV-IIIB antibody titer during the 2-year observation period which broadened in specificity to include HTLV-HIRF, HTLV-IIIMN, and HTLV-IIICC after 6 to 12 months. The antibody titers against both viruses were still increasing by 2 years after experimental virus inoculation. Sera from all animals were capable of neutralizing both homologously and heterologously reisolated virus from chimpanzees. A slightly more rapid type-specific neutralizing response was noted for the animal receiving HTLV-IIIB-infected cells compared with that for cell-free HTLV-IIIB. Sera from all persistently infected chimpanzees were capable of mediating group-specific antibody-mediated complement-dependent cytolysis of HIV-infected cells derived from all isolates tested. Viruses reisolated from all three animals at 20 months after inoculation revealed very similar peptide maps of their respective envelope gp120s, as determined by two-dimensional chymotrypsin oligopeptide analysis. One peptide, however, from the original HTLV-IIIB-inoculated virus was deleted in viruses from all three animals, and in addition, we noted the appearance of a new or modified peptide which was common to LAV-1 as well as to HTLV-IIIB reisolated from infected chimpanzees. It thus appears that a group-specific neutralizing antibody response as well as a group-specific cytotoxic response can develop in chimpanzees after an inoculation of a single HIV variant. This finding suggests that a common, less immunodominant determinant(s) is present on a single HIV strain which could induce group-specific antibodies during viral infection and replication. The identification of this group-specific epitope and the induction of analogous immunity may be relevant to vaccine development against human acquired immunodeficiency syndrome. Images PMID:2442411
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Omega-3 Fatty Acids and Skeletal Muscle Health
Jeromson, Stewart; Gallagher, Iain J.; Galloway, Stuart D. R.; Hamilton, D. Lee
2015-01-01
Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle. PMID:26610527
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Functional polymorphisms associated with human muscle size and strength.
Thompson, Paul D; Moyna, Niall; Seip, Richard; Price, Thomas; Clarkson, Priscilla; Angelopoulos, Theodore; Gordon, Paul; Pescatello, Linda; Visich, Paul; Zoeller, Robert; Devaney, Joseph M; Gordish, Heather; Bilbie, Stephen; Hoffman, Eric P
2004-07-01
Skeletal muscle is critically important to human performance and health, but little is known of the genetic factors influencing muscle size, strength, and its response to exercise training. The Functional single nucleotide polymorphisms (SNP) Associated with Muscle Size and Strength, or FAMuSS, Study is a multicenter, NIH-funded program to examine the influence of gene polymorphisms on skeletal muscle size and strength before and after resistance exercise training. One thousand men and women, age 18 - 40 yr, will train their nondominant arm for 12 wk. Skeletal muscle size (magnetic resonance imaging) and isometric and dynamic strength will be measured before and after training. Individuals whose baseline values or response to training deviate > or = 1.5 SD will be defined as outliers and examined for genetic variants. Initially candidate genes previously associated with muscle performance will be examined, but the study will ultimately attempt to identify genes associated with muscle performance. FAMuSS should help identify genetic factors associated with muscle performance and the response to exercise training. Such insight should contribute to our ability to predict the individual response to exercise training but may also contribute to understanding better muscle physiology, to identifying individuals who are susceptible to muscle loss with environmental challenge, and to developing pharmacologic agents capable of preserving muscle size and function.
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NASA Astrophysics Data System (ADS)
Koujalagi, V.; Ramesh, S. L.; Gunarathne, G. P. P.; Semple, S.; Ayres, J. G.
2009-02-01
This study presents the work carried out in developing a precision bolus injection system in order to understand the regional deposition of nanoparticles (NP) in human lung. A real-time control system has been developed that is capable of storing graphite NP, assessing human breathing pattern and delivering a bolus of the stored NP at a pre-determined instance of the inhalation phase of breathing. This will form the basis for further development of a system to deliver radioactive nanoparticles to enable 3-dimensional lung imaging using techniques such as positron emission tomography (PET). The system may then be used to better understand the actual regional deposition in human lung, which could validate or challenge the current computational lung models such as that published by the International Commission for Radiation Protection (ICRP-1994). A dose related response to inhaled PM can possibly be shown, which can be used to review the current workplace exposure limits (WELs).
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Singhal, Sunil; Bhojnagarwala, Pratik S; O'Brien, Shaun; Moon, Edmund K; Garfall, Alfred L; Rao, Abhishek S; Quatromoni, Jon G; Stephen, Tom Li; Litzky, Leslie; Deshpande, Charuhas; Feldman, Michael D; Hancock, Wayne W; Conejo-Garcia, Jose R; Albelda, Steven M; Eruslanov, Evgeniy B
2016-07-11
Based on studies in mouse tumor models, granulocytes appear to play a tumor-promoting role. However, there are limited data about the phenotype and function of tumor-associated neutrophils (TANs) in humans. Here, we identify a subset of TANs that exhibited characteristics of both neutrophils and antigen-presenting cells (APCs) in early-stage human lung cancer. These APC-like "hybrid neutrophils," which originate from CD11b(+)CD15(hi)CD10(-)CD16(low) immature progenitors, are able to cross-present antigens, as well as trigger and augment anti-tumor T cell responses. Interferon-γ and granulocyte-macrophage colony-stimulating factor are requisite factors in the tumor that, working through the Ikaros transcription factor, synergistically exert their APC-promoting effects on the progenitors. Overall, these data demonstrate the existence of a specialized TAN subset with anti-tumor capabilities in human cancer. Copyright © 2016 Elsevier Inc. All rights reserved.
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Affordable Exploration of Mars: Recommendations from a Community Workshop
NASA Technical Reports Server (NTRS)
Thronson, Harley A.; Carberry, Chris; Cassady, R. Joseph; Cooke, Doug; Kirkpatrick, Jim; Perino, Maria Antonietta; Raftery, Michael; Westenberg, Artemis; Zucker, Richard
2014-01-01
There is a growing opinion that within two decades initial human missions to Mars are affordable under plausible budget scenarios, with sustained international participation, and --- especially --- without requiring those first missions to achieve a burdensome number of goals. In response to this view, a group of experts from the Mars exploration stakeholder communities attended the "Affording Mars" workshop at George Washington University in December 2013. Participants reviewed scenarios for proposed affordable and sustainable human and robotic exploration of Mars, the role of the International Space Station as the essential early step toward humans to Mars, possible "bridge" or "transition" missions in the 2020s, key capabilities required for affordable initial missions, international partnerships, and usable definitions of affordability and sustainability. We report here the findings, observations, and recommendations that were agreed to at that workshop. In the context of affordable early missions to Mars, we also discuss the recent report of the National Research Council on human space flight and a pair of recent scenarios that appear to promise reduced costs.
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Effect of solar irradiation on extracellular enzymes of Aeromonas proteolytica
NASA Technical Reports Server (NTRS)
Foster, B. G.
1973-01-01
The bacterium Aeromonas proteolytica was selected for studying the effects of solar irradiation on extracellular enzymes because it produces an endopeptidase that is capable of degrading proteins and a hemolysin that is active in lysing human erythrocytes. Possible alterations in the rate of enzyme production in response to the test conditions are currently underway and are not available for this preliminary report. Completed viability studies are indicative that little difference exists among the survival curves derived for cells exposed to various components of ultraviolet irradiation in space.
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NASA Technical Reports Server (NTRS)
Salazar, Giovanni; Droba, Justin C.; Oliver, Brandon; Amar, Adam J.
2016-01-01
With the recent development of multi-dimensional thermal protection system (TPS) material response codes including the capabilities to account for radiative heating is a requirement. This paper presents the recent efforts to implement such capabilities in the CHarring Ablator Response (CHAR) code developed at NASA's Johnson Space Center. This work also describes the different numerical methods implemented in the code to compute view factors for radiation problems involving multiple surfaces. Furthermore, verification and validation of the code's radiation capabilities are demonstrated by comparing solutions to analytical results, to other codes, and to radiant test data.
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Lowell, J.R. Jr.; Edlund, D.J.; Friesen, D.T.; Rayfield, G.W.
1991-07-02
Sensors responsive to small changes in the concentration of chemical species are disclosed. The sensors comprise a mechanochemically responsive polymeric film capable of expansion or contraction in response to a change in its chemical environment. They are operatively coupled to a transducer capable of directly converting the expansion or contraction to a measurable electrical response. 9 figures.
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An agent-based model for Leishmania major infection
NASA Astrophysics Data System (ADS)
Dancik, Garrett M.; Jones, Douglas E.; Dorman, Karin S.
Leishmania are protozoan parasites transmitted by bites of infected sandflies. Over 20 species of Leishmania, endemic in 88 countries, are capable of causing human disease. Disease is either cutaneous, where skin ulcers occur on exposed surfaces of the body, or visceral, with near certain mortality if untreated. C3HeB/FeJ mice are resistant to L. major, but develop chronic cutaneous lesions when infected with another species L. amazonensis. The well-characterized mechanism of resistance to L. major depends on a CD4+ Thl immune response, macrophage activation, and elimination of the parasite [Sacks 2002]. The factors that account for host susceptibility to L. Amazonensis, however, are not completely understood, despite being generally attributed to a weakened Th1 response [Vanloubbeck 2004].
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An agent-based model for Leishmania major infection
NASA Astrophysics Data System (ADS)
Dancik, Garrett M.; Jones, Douglas E.; Dorman, Karin S.
Leishmania are protozoan parasites transmitted by bites of infected sandflies. Over 20 species of Leishmania, endemic in 88 countries, are capable of causing human disease. Disease is either cutaneous, where skin ulcers occur on exposed surfaces of the body, or visceral, with near certain mortality if left untreated. C3HeB/FeJ mice are resistant to L. major, but develop chronic cutaneous lesions when infected with another species L. amazonensis. The well-characterized mechanism of resistance to L. major depends on a CD4+ Thl immune response, macrophage activation, and elimination of the parasite [Sacks 2002]. The factors that account for host susceptibility to L. Amazonensis, however, are not completely understood, despite being generally attributed to a weakened Th1 response [Vanloubbeck 2004].
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DNA damage and ageing: new-age ideas for an age-old problem
Garinis, George A.; van der Horst, Gijsbertus T. J.; Vijg, Jan; Hoeijmakers, Jan H. J.
2015-01-01
Loss of genome maintenance may causally contribute to ageing, as exemplified by the premature appearance of multiple symptoms of ageing in a growing family of human syndromes and in mice with genetic defects in genome maintenance pathways. Recent evidence revealed a similarity between such prematurely ageing mutants and long-lived mice harbouring mutations in growth signalling pathways. At first sight this seems paradoxical as they represent both extremes of ageing yet show a similar ‘survival’ response that is capable of delaying age-related pathology and extending lifespan. Understanding the mechanistic basis of this response and its connection with genome maintenance would open exciting possibilities for counteracting cancer or age-related diseases, and for promoting longevity. PMID:18978832
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Resistance of Actin to Cleavage during Apoptosis
NASA Astrophysics Data System (ADS)
Song, Qizhong; Wei, Tie; Lees-Miller, Susan; Alnemri, Emad; Watters, Dianne; Lavin, Martin F.
1997-01-01
A small number of cellular proteins present in the nucleus, cytosol, and membrane fraction are specifically cleaved by the interleukin-1β -converting enzyme (ICE)-like family of proteases during apoptosis. Previous results have demonstrated that one of these, the cytoskeletal protein actin, is degraded in rat PC12 pheochromocytoma cells upon serum withdrawal. Extracts from etoposide-treated U937 cells are also capable of cleaving actin. It was assumed that cleavage of actin represented a general phenomenon, and a mechanism coordinating proteolytic, endonucleolytic, and morphological aspects of apoptosis was proposed. We demonstrate here that actin is resistant to degradation in several different human cells induced to undergo apoptosis in response to a variety of stimuli, including Fas ligation, serum withdrawal, cytotoxic T-cell killing, and DNA damage. On the other hand, cell-free extracts from these cells and the ICE-like protease CPP32 were capable of cleaving actin in vitro. We conclude that while actin contains cleavage sites for ICE-like proteases, it is not degraded in vivo in human cells either because of lack of access of these proteases to actin or due to the presence of other factors that prevent degradation.
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Selective Distance-Based K+ Quantification on Paper-Based Microfluidics.
Gerold, Chase T; Bakker, Eric; Henry, Charles S
2018-04-03
In this study, paper-based microfluidic devices (μPADs) capable of K + quantification in aqueous samples, as well as in human serum, using both colorimetric and distance-based methods are described. A lipophilic phase containing potassium ionophore I (valinomycin) was utilized to achieve highly selective quantification of K + in the presence of Na + , Li + , and Mg 2+ ions. Successful addition of a suspended lipophilic phase to a wax printed paper-based device is described and offers a solution to current approaches that rely on organic solvents, which damage wax barriers. The approach provides an avenue for future alkali/alkaline quantification utilizing μPADs. Colorimetric spot tests allowed for K + quantification from 0.1-5.0 mM using only 3.00 μL of sample solution. Selective distance-based quantification required small sample volumes (6.00 μL) and gave responses sensitive enough to distinguish between 1.0 and 2.5 mM of sample K + . μPADs using distance-based methods were also capable of differentiating between 4.3 and 6.9 mM K + in human serum samples. Distance-based methods required no digital analysis, electronic hardware, or pumps; any steps required for quantification could be carried out using the naked eye.
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NASA Technical Reports Server (NTRS)
Mueller, Rob
2005-01-01
General Background and Introduction of Capability Roadmaps Agency Objective. Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Purpose of NRC Review. Capability Roadmap Development (Progress to Date)
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A Clinical Feasibility Study of Atrial and Ventricular Electromechanical Wave Imaging
Provost, Jean; Gambhir, Alok; Vest, John; Garan, Hasan; Konofagou, Elisa E.
2014-01-01
Background Cardiac Resynchronization Therapy (CRT) and atrial ablation currently lack a noninvasive imaging modality for reliable treatment planning and monitoring. Electromechanical Wave Imaging (EWI) is an ultrasound-based method that has previously been shown to be capable of noninvasively and transmurally mapping the activation sequence of the heart in animal studies by estimating and imaging the electromechanical wave, i.e., the transient strains occurring in response to the electrical activation, at both very high temporal and spatial resolution. Objective Demonstrate the feasibility of noninvasive transthoracic EWI for mapping the activation sequence during different cardiac rhythms in humans. Methods EWI was performed in CRT patients with a left bundle-branch block (LBBB), during sinus rhythm, left-ventricular pacing, and right-ventricular pacing and in atrial flutter (AFL) patients before intervention and correlated with results from invasive intracardiac electrical mapping studies during intervention. Additionally, the feasibility of single-heartbeat EWI at 2000 frames/s, is demonstrated in humans for the first time in a subject with both AFL and right bundle-branch-block. Results The electromechanical activation maps demonstrated the capability of EWI to localize the pacing sites and characterize the LBBB activation sequence transmurally in CRT patients. In AFL patients, the propagation patterns obtained with EWI were in agreement with results obtained from invasive intracardiac mapping studies. Conclusion Our findings demonstrate the potential capability of EWI to aid in monitoring and follow-up of patients undergoing CRT pacing therapy and atrial ablation with preliminary validation in vivo. PMID:23454060
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NASA Technical Reports Server (NTRS)
Dinges, David F.
1999-01-01
This project is concerned with identifying ways to prevent neurobehavioral and physical deterioration due to inadequate sleep in astronauts during long-duration manned space flight. The performance capability of astronauts during extended-duration space flight depends heavily on achieving recovery through adequate sleep. Even with appropriate circadian alignment, sleep loss can erode fundamental elements of human performance capability including vigilance, cognitive speed and accuracy, working memory, reaction time, and physiological alertness. Adequate sleep is essential during manned space flight not only to ensure high levels of safe and effective human performance, but also as a basic regulatory biology critical to healthy human functioning. There is now extensive objective evidence that astronaut sleep is frequently restricted in space flight to averages between 4 hr and 6.5 hr/day. Chronic sleep restriction during manned space flight can occur in response to endogenous disturbances of sleep (motion sickness, stress, circadian rhythms), environmental disruptions of sleep (noise, temperature, light), and curtailment of sleep due to the work demands and other activities that accompany extended space flight operations. The mechanism through which this risk emerges is the development of cumulative homeostatic pressure for sleep across consecutive days of inadequate sleep. Research has shown that the physiological sleepiness and performance deficits engendered by sleep debt can progressively worsen (i.e., accumulate) over consecutive days of sleep restriction, and that sleep limited to levels commonly experienced by astronauts (i.e., 4 - 6 hr per night) for as little as 1 week, can result in increased lapses of attention, degradation of response times, deficits in complex problem solving, reduced learning, mood disturbance, disruption of essential neuroendocrine, metabolic, and neuroimmune responses, and in some vulnerable persons, the emergence of uncontrolled sleep attacks. The prevention of cumulative performance deficits and neuroendocrine disruption from sleep restriction during extended duration space flight involves finding the most effective ways to obtain sleep in order to maintain the high-level cognitive and physical performance functions required for manned space flight. There is currently a critical deficiency in knowledge of the effects of how variations in sleep duration and timing relate to the most efficient return of performance per unit time invested in sleep during long-duration missions, and how the nature of sleep physiology (i.e., sleep stages, sleep electroencephalographic [EEG] power spectral analyses) change as a function of sleep restriction and performance degradation. The primary aim of this project is to meet these critical deficiencies through utilization of a response surface experimental paradigm, testing in a dose-response manner, varying combinations of sleep duration and timing, for the purpose of establishing how to most effectively limit the cumulative adverse effects on human performance and physiology of chronic sleep restriction in space operations.
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The CD8 T Cell Response to Respiratory Virus Infections.
Schmidt, Megan E; Varga, Steven M
2018-01-01
Humans are highly susceptible to infection with respiratory viruses including respiratory syncytial virus (RSV), influenza virus, human metapneumovirus, rhinovirus, coronavirus, and parainfluenza virus. While some viruses simply cause symptoms of the common cold, many respiratory viruses induce severe bronchiolitis, pneumonia, and even death following infection. Despite the immense clinical burden, the majority of the most common pulmonary viruses lack long-lasting efficacious vaccines. Nearly all current vaccination strategies are designed to elicit broadly neutralizing antibodies, which prevent severe disease following a subsequent infection. However, the mucosal antibody response to many respiratory viruses is not long-lasting and declines with age. CD8 T cells are critical for mediating clearance following many acute viral infections in the lung. In addition, memory CD8 T cells are capable of providing protection against secondary infections. Therefore, the combined induction of virus-specific CD8 T cells and antibodies may provide optimal protective immunity. Herein, we review the current literature on CD8 T cell responses induced by respiratory virus infections. Additionally, we explore how this knowledge could be utilized in the development of future vaccines against respiratory viruses, with a special emphasis on RSV vaccination.
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Varanat, M; Haase, E M; Kay, J G; Scannapieco, F A
2017-08-01
Periodontitis is a highly prevalent disease caused in part by an aberrant host response to the oral multi-species biofilm. A balance between the oral bacteria and host immunity is essential for oral health. Imbalances in the oral microbiome lead to an uncontrolled host inflammatory response and subsequent periodontal disease (i.e. gingivitis and periodontitis). TREM-1 is a signaling receptor present on myeloid cells capable of acting synergistically with other pattern recognition receptors leading to amplification of inflammatory responses. The aim of this study was to investigate the activation of the TREM-1 pathway in the human monocyte-like cell line THP-1 exposed to both oral pathogens and commensals. The relative expression of the genes encoding TREM-1 and its adapter protein DAP12 were determined by quantitative real-time polymerase chain reaction. The surface expression of TREM-1 was determined by flow cytometry. Soluble TREM-1 and cytokines were measured by enzyme-linked immunosorbent assay. The results demonstrate that both commensal and pathogenic oral bacteria activate the TREM-1 pathway, resulting in a proinflammatory TREM-1 activity-dependent increase in proinflammatory cytokine production. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Henning, Jill D; Karamchandani, Jaideep M; Bonachea, Luis A; Bunker, Clareann H; Patrick, Alan L; Jenkins, Frank J
2017-05-01
Serum-prostate specific antigen (PSA) levels have been used for many years as a biomarker for prostate cancer. This usage is under scrutiny due to the fact that elevated PSA levels can be caused by other conditions such as benign prostatic hyperplasia and infections of or injury to the prostate. As a result, the identification of specific pathogens capable of increasing serum levels of PSA is important. A potential candidate responsible for elevated PSA is human herpesvirus 8 (HHV-8). We have reported previously that HHV-8 is capable of infecting and establishing a latent infection in the prostate. In this current study we test the hypothesis that HHV-8 infection is associated with elevated PSA levels. Circulating cytokine levels between men with elevated PSA and controls are also compared. HHV-8 serostatus was determined among men with elevated serum PSA (≥4 ng/ml; n = 168, no prostate cancer on biopsy) and age-matched controls (PSA <4 ng/ml; n = 234), Circulating cytokine levels were determined among a subset of each group (116 with elevated PSA and 85 controls). Men with an elevated serum PSA were significantly more likely to be HHV-8 seropositive (42.9%) than the age-matched cancer-free men (22.2%; OR 2.51; 95%CI 1.48-4.29, P = 00001). Comparison of circulating cytokine levels between men with elevated serum PSA and controls indicated that elevated serum PSA is associated with a pro-inflammatory response with a mixed Th1/Th2 response while HHV-8 infection was associated with significantly higher levels of IL12p70, IL-10, and IL-13 indicating a Th2 immune response. We found a significant association between HHV-8 infection and increased levels of serum PSA. In an age of patient-centered medicine, men with an elevated serum PSA should be considered for HHV-8 serology testing to determine if HHV-8 is responsible for the elevated PSA. Prostate 77: 617-624, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
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Chen, Ching-Yun; Tseng, Kuo-Yun; Lai, Yen-Liang; Chen, Yo-Shen; Lin, Feng-Huei; Lin, Shankung
2017-01-01
Many studies have indicated that loss of the osteoblastogenic potential in bone marrow mesenchymal stem cells (bmMSCs) is the major component in the etiology of the aging-related bone deficit. But how the bmMSCs lose osteogenic capability in aging is unclear. Using 2-dimentional cultures, we examined the dose response of human bmMSCs, isolated from adult and aged donors, to exogenous insulin-like growth factor 1 (IGF-1), a growth factor regulating bone formation. The data showed that the mitogenic activity and the osteoblastogenic potential of bmMSCs in response to IGF-1 were impaired with aging, whereas higher doses of IGF-1 increased the proliferation rate and osteogenic potential of aging bmMSCs. Subsequently, we seeded IGF-1-overexpressing aging bmMSCs into calcium-alginate scaffolds and incubated in a bioreactor with constant perfusion for varying time periods to examine the effect of IGF-1 overexpression to the bone-forming capability of aging bmMSCs. We found that IGF-1 overexpression in aging bmMSCs facilitated the formation of cell clusters in scaffolds, increased the cell survival inside the cell clusters, induced the expression of osteoblast markers, and enhanced the biomineralization of cell clusters. These results indicated that IGF-1 overexpression enhanced cells' osteogenic capability. Thus, our data suggest that the aging-related loss of osteogenic potential in bmMSCs can be attributed in part to the impairment in bmMSCs' IGF-1 signaling, and support possible application of IGF-1-overexpressing autologous bmMSCs in repairing bone defect of the elderly and in producing bone graft materials for repairing large scale bone injury in the elderly.
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Robust control of dielectric elastomer diaphragm actuator for human pulse signal tracking
NASA Astrophysics Data System (ADS)
Ye, Zhihang; Chen, Zheng; Asmatulu, Ramazan; Chan, Hoyin
2017-08-01
Human pulse signal tracking is an emerging technology that is needed in traditional Chinese medicine. However, soft actuation with multi-frequency tracking capability is needed for tracking human pulse signal. Dielectric elastomer (DE) is one type of soft actuating that has great potential in human pulse signal tracking. In this paper, a DE diaphragm actuator was designed and fabricated to track human pulse pressure signal. A physics-based and control-oriented model has been developed to capture the dynamic behavior of DE diaphragm actuator. Using the physical model, an H-infinity robust control was designed for the actuator to reject high-frequency sensing noises and disturbances. The robust control was then implemented in real-time to track a multi-frequency signal, which verified the tracking capability and robustness of the control system. In the human pulse signal tracking test, a human pulse signal was measured at the City University of Hong Kong and then was tracked using DE actuator at Wichita State University in the US. Experimental results have verified that the DE actuator with its robust control is capable of tracking human pulse signal.
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Human B cells fail to secrete type I interferons upon cytoplasmic DNA exposure.
Gram, Anna M; Sun, Chenglong; Landman, Sanne L; Oosenbrug, Timo; Koppejan, Hester J; Kwakkenbos, Mark J; Hoeben, Rob C; Paludan, Søren R; Ressing, Maaike E
2017-11-01
Most cells are believed to be capable of producing type I interferons (IFN I) as part of an innate immune response against, for instance, viral infections. In macrophages, IFN I is potently induced upon cytoplasmic exposure to foreign nucleic acids. Infection of these cells with herpesviruses leads to triggering of the DNA sensors interferon-inducible protein 16 (IFI16) and cyclic GMP-AMP (cGAMP) synthase (cGAS). Thereby, the stimulator of interferon genes (STING) and the downstream molecules TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) are sequentially activated culminating in IFN I secretion. Human gamma-herpesviruses, such as Epstein-Barr virus (EBV), exploit B cells as a reservoir for persistent infection. In this study, we investigated whether human B cells, similar to macrophages, engage the cytoplasmic DNA sensing pathway to induce an innate immune response. We found that the B cells fail to secrete IFN I upon cytoplasmic DNA exposure, although they express the DNA sensors cGAS and IFI16 and the signaling components TBK1 and IRF3. In primary human B lymphocytes and EBV-negative B cell lines, this deficiency is explained by a lack of detectable levels of the central adaptor protein STING. In contrast, EBV-transformed B cell lines did express STING, yet both these lines as well as STING-reconstituted EBV-negative B cells did not produce IFN I upon dsDNA or cGAMP stimulation. Our combined data show that the cytoplasmic DNA sensing pathway is dysfunctional in human B cells. This exemplifies that certain cell types cannot induce IFN I in response to cytoplasmic DNA exposure providing a potential niche for viral persistence. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Long-Duration Human Habitation Beyond Low-Earth Orbit: Why is the Near Future Critical?
NASA Technical Reports Server (NTRS)
Thronson, Harley A.; Lester, Daniel; Hatfield, C. A.
2011-01-01
For more than a decade, habitation systems capable of comfortable human occupation and effective operations beyond low-Earth orbit (LEO) for more than a few weeks have been a priority recommendation to NASA. This capability is a lynch pin for human exploration beyond the Earth-Moon system. Here we describe briefly some relevant concepts and discuss justifications in the current political and financial environment for why near-term human habitation systems beyond LEO is an imperative.
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Advanced Technologies for Future Spacecraft Cockpits and Space-based Control Centers
NASA Technical Reports Server (NTRS)
Garcia-Galan, Carlos; Uckun, Serdar; Gregory, William; Williams, Kerry
2006-01-01
The National Aeronautics and Space Administration (NASA) is embarking on a new era of Space Exploration, aimed at sending crewed spacecraft beyond Low Earth Orbit (LEO), in medium and long duration missions to the Lunar surface, Mars and beyond. The challenges of such missions are significant and will require new technologies and paradigms in vehicle design and mission operations. Current roles and responsibilities of spacecraft systems, crew and the flight control team, for example, may not be sustainable when real-time support is not assured due to distance-induced communication lags, radio blackouts, equipment failures, or other unexpected factors. Therefore, technologies and applications that enable greater Systems and Mission Management capabilities on-board the space-based system will be necessary to reduce the dependency on real-time critical Earth-based support. The focus of this paper is in such technologies that will be required to bring advance Systems and Mission Management capabilities to space-based environments where the crew will be required to manage both the systems performance and mission execution without dependence on the ground. We refer to this concept as autonomy. Environments that require high levels of autonomy include the cockpits of future spacecraft such as the Mars Exploration Vehicle, and space-based control centers such as a Lunar Base Command and Control Center. Furthermore, this paper will evaluate the requirements, available technology, and roadmap to enable full operational implementation of onboard System Health Management, Mission Planning/re-planning, Autonomous Task/Command Execution, and Human Computer Interface applications. The technology topics covered by the paper include enabling technology to perform Intelligent Caution and Warning, where the systems provides directly actionable data for human understanding and response to failures, task automation applications that automate nominal and Off-nominal task execution based on human input or integrated health state-derived conditions. Shifting from Systems to Mission Management functions, we discuss the role of automated planning applications (tactical planning) on-board, which receive data from the other cockpit automation systems and evaluate the mission plan against the dynamic systems and mission states and events, to provide the crew with capabilities that enable them to understand, change, and manage the timeline of their mission. Lastly, we discuss the role of advanced human interface technologies that organize and provide the system md mission information to the crew in ways that maximize their situational awareness and ability to provide oversight and control of aLl the automated data and functions.
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The Ares Launch Vehicles: Critical Capabilities for America's Continued Leadership in Space
NASA Technical Reports Server (NTRS)
Cook, Stephen A.
2009-01-01
The Constellation Program renews the nation's commitment to human space exploration a) Access to ISS. b) Human explorers to the Moon and beyond. c) Large telescopes and other hardware to LEO . Hardware is being built today. Development made easier by applying lessons learned from 50 years of spaceflight experience. Ares V heavy-lift capability will be a strategic asset for the nation. Constellation provides a means for world leadership through inspiration and strategic capability.
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How Multi-Organ Microdevices Can Help Foster Drug Development
Esch, Mandy B.; Smith, Alec; Prot, Jean-Matthieu; Sancho, Carlotta Oleaga; Hickman, James; Shuler, Michael L.
2014-01-01
Multi-organ microdevices can mimic tissue-tissue interactions that occur as a result of metabolite travel from one tissue to other tissues in vitro. These systems are capable of simulating human metabolism, including the conversion of a pro-drug to its effective metabolite as well as its subsequent therapeutic actions and toxic side effects. Since tissue-tissue interactions in the human body can play a significant role in determining the success of new pharmaceuticals, the development and use of multi-organ microdevices presents an opportunity to improve the drug development process. The goals are to predict potential toxic side effects with higher accuracy before a drug enters the expensive phase of clinical trials as well as to estimate efficacy and dose response. Multi-organ microdevices also have the potential to aid in the development of new therapeutic strategies by providing a platform for testing in the context of human metabolism (as opposed to animal models). Further, when operated with human biopsy samples, the devices could be a gateway for the development of individualized medicine. Here we review studies in which multi-organ microdevices have been developed and used in a ways that demonstrate how the devices’ capabilities can present unique opportunities for the study of drug action. We also discuss the challenges that are inherent in the development of multi-organ microdevices. Among these are how to design the devices, and how to create devices that mimic the human metabolism with high authenticity. Since single organ devices are testing platforms for tissues that can later be combined with other tissues within multi-organ devices, we will also mention single organ devices where appropriate in the discussion. PMID:24412641
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Belser, Jessica A.; Davis, C. Todd; Balish, Amanda; Edwards, Lindsay E.; Zeng, Hui; Maines, Taronna R.; Gustin, Kortney M.; Martínez, Irma López; Fasce, Rodrigo; Cox, Nancy J.; Katz, Jacqueline M.
2013-01-01
H7 subtype influenza A viruses, responsible for numerous outbreaks in land-based poultry in Europe and the Americas, have caused over 100 cases of confirmed or presumed human infection over the last decade. The emergence of a highly pathogenic avian influenza H7N3 virus in poultry throughout the state of Jalisco, Mexico, resulting in two cases of human infection, prompted us to examine the virulence of this virus (A/Mexico/InDRE7218/2012 [MX/7218]) and related avian H7 subtype viruses in mouse and ferret models. Several high- and low-pathogenicity H7N3 and H7N9 viruses replicated efficiently in the respiratory tract of mice without prior adaptation following intranasal inoculation, but only MX/7218 virus caused lethal disease in this species. H7N3 and H7N9 viruses were also detected in the mouse eye following ocular inoculation. Virus from both H7N3 and H7N9 subtypes replicated efficiently in the upper and lower respiratory tracts of ferrets; however, only MX/7218 virus infection caused clinical signs and symptoms and was capable of transmission to naive ferrets in a direct-contact model. Similar to other highly pathogenic H7 viruses, MX/7218 replicated to high titers in human bronchial epithelial cells, yet it downregulated numerous genes related to NF-κB-mediated signaling transduction. These findings indicate that the recently isolated North American lineage H7 subtype virus associated with human conjunctivitis is capable of causing severe disease in mice and spreading to naive-contact ferrets, while concurrently retaining the ability to replicate within ocular tissue and allowing the eye to serve as a portal of entry. PMID:23487452
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Advances in neuroscience imply that harmful experiments in dogs are unethical
Pereira, Shiranee
2018-01-01
Functional MRI (fMRI) of fully awake and unrestrained dog ’volunteers' has been proven an effective tool to understand the neural circuitry and functioning of the canine brain. Although every dog owner would vouch that dogs are perceptive, cognitive, intuitive and capable of positive emotions/empathy, as indeed substantiated by ethological studies for some time, neurological investigations now corroborate this. These studies show that there exists a striking similarity between dogs and humans in the functioning of the caudate nucleus (associated with pleasure and emotion), and dogs experience positive emotions, empathic-like responses and demonstrate human bonding which, some scientists claim, may be at least comparable with human children. There exists an area analogous to the ’voice area' in the canine brain, enabling dogs to comprehend and respond to emotional cues/valence in human voices, and evidence of a region in the temporal cortex of dogs involved in the processing of faces, as also observed in humans and monkeys. We therefore contend that using dogs in invasive and/or harmful research, and toxicity testing, cannot be ethically justifiable. PMID:28739639
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Kurita, N; Terao, K; Brummer, E; Ito, E; Nishimura, K; Miyaji, M
1991-09-01
The basis for resistance of yeast form of Histoplasma capsulatum to antifungal activity of human neutrophils was studied. In limiting dilution assays and short term coculture assays human neutrophils were ineffective in killing H. capsulatum whereas Candida albicans was readily killed. By contrast, in a cell free hydrogen peroxide-peroxidase-halide system H. capsulatum was as sensitive to killing as C. albicans. Moreover, lysate of human neutrophils effectively substituted for horse-radish peroxidase in a cell free system for killing H. capsulatum. H. capsulatum elicited significant products of the oxidative burst in human neutrophils as detected by luminol-enhanced chemiluminescence. However, the response was two-fold less (p less than 0.05) than that induced by C. albicans. Transmission electron microscopy studies showed that phagosome-lysosome fusion took place when neutrophils phagocytosed C. albicans or H. capsulatum. Taken together, these findings indicate that, even though H. capsulatum elicits an oxidative burst and phagosome-lysosome fusion within the phagosome, it is capable of evading damage in short term assays.
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3D Holographic Observatory for Long-term Monitoring of Complex Behaviors in Drosophila
NASA Astrophysics Data System (ADS)
Kumar, S. Santosh; Sun, Yaning; Zou, Sige; Hong, Jiarong
2016-09-01
Drosophila is an excellent model organism towards understanding the cognitive function, aging and neurodegeneration in humans. The effects of aging and other long-term dynamics on the behavior serve as important biomarkers in identifying such changes to the brain. In this regard, we are presenting a new imaging technique for lifetime monitoring of Drosophila in 3D at spatial and temporal resolutions capable of resolving the motion of limbs and wings using holographic principles. The developed system is capable of monitoring and extracting various behavioral parameters, such as ethograms and spatial distributions, from a group of flies simultaneously. This technique can image complicated leg and wing motions of flies at a resolution, which allows capturing specific landing responses from the same data set. Overall, this system provides a unique opportunity for high throughput screenings of behavioral changes in 3D over a long term in Drosophila.
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Demonstrating artificial intelligence for space systems - Integration and project management issues
NASA Technical Reports Server (NTRS)
Hack, Edmund C.; Difilippo, Denise M.
1990-01-01
As part of its Systems Autonomy Demonstration Project (SADP), NASA has recently demonstrated the Thermal Expert System (TEXSYS). Advanced real-time expert system and human interface technology was successfully developed and integrated with conventional controllers of prototype space hardware to provide intelligent fault detection, isolation, and recovery capability. Many specialized skills were required, and responsibility for the various phases of the project therefore spanned multiple NASA centers, internal departments and contractor organizations. The test environment required communication among many types of hardware and software as well as between many people. The integration, testing, and configuration management tools and methodologies which were applied to the TEXSYS project to assure its safe and successful completion are detailed. The project demonstrated that artificial intelligence technology, including model-based reasoning, is capable of the monitoring and control of a large, complex system in real time.
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Pridans, Clare; Lillico, Simon; Whitelaw, Bruce; Hume, David A
2014-01-01
The development of macrophages requires signaling through the lineage-restricted receptor Csf1r. Macrophage-restricted expression of transgenic reporters based upon Csf1r requires the highly conserved Fms-intronic regulatory element (FIRE). We have created a lentiviral construct containing mouse FIRE and promoter. The lentivirus is capable of directing macrophage-restricted reporter gene expression in mouse, rat, human, pig, cow, sheep, and even chicken. Rat bone marrow cells transduced with the lentivirus were capable of differentiating into macrophages expressing the reporter gene in vitro. Macrophage-restricted expression may be desirable for immunization or immune response modulation, and for gene therapy for lysosomal storage diseases and some immunodeficiencies. The small size of the Csf1r transcription control elements will allow the insertion of large “cargo” for applications in gene therapy and vaccine delivery. PMID:26015955
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Leadership capabilities of physiotherapy leaders in Ireland: Part 1 physiotherapy managers.
McGowan, Emer; Elliott, Naomi; Stokes, Emma
2018-05-07
Investigation of the leadership capabilities of physiotherapists is needed to allow understanding of current leadership practice and to enable appropriate training programs to be developed. To explore physiotherapy managers´ perceptions of their leadership capabilities. Semi-structured interviews were conducted with a purposive sample of 18 physiotherapy managers from a range of public services and private practices in Ireland. The interviews were analyzed using template analysis and the coding template was based on the Bolman and Deal Leadership framework which details four leadership frames: structural, human resource, political, and symbolic. The physiotherapy managers described demonstrating leadership capabilities associated with each of the four leadership frames. However, the language used by the physiotherapy managers suggested that they work predominantly through the structural and human resource frames. The employment of capabilities associated with the political frame varied between participants; some participants described working through this frame while others reported difficulties. The symbolic frame was underused; there were fewer examples given of capabilities such as communicating their vision, demonstrating passion and facilitating a positive workplace culture. Physiotherapy managers work predominantly through the structural and human resource frames. To successfully meet the leadership requirements of their roles physiotherapy managers may benefit from specific leadership development training to develop leadership capabilities in the political and symbolic frames.
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Low-Latency Telerobotics from Mars Orbit: The Case for Synergy Between Science and Human Exploration
NASA Technical Reports Server (NTRS)
Valinia, A.; Garvin, J. B.; Vondrak, R.; Thronson, H.; Lester, D.; Schmidt, G.; Fong, T.; Wilcox, B.; Sellers, P.; White, N.
2012-01-01
Initial, science-directed human exploration of Mars will benefit from capabilities in which human explorers remain in orbit to control telerobotic systems on the surface (Figure 1). Low-latency, high-bandwidth telerobotics (LLT) from Mars orbit offers opportunities for what the terrestrial robotics community considers to be high-quality telepresence. Such telepresence would provide high quality sensory perception and situation awareness, and even capabilities for dexterous manipulation as required for adaptive, informed selection of scientific samples [1]. Astronauts on orbit in close communication proximity to a surface exploration site (in order to minimize communication latency) represent a capability that would extend human cognition to Mars (and potentially for other bodies such as asteroids, Venus, the Moon, etc.) without the challenges, expense, and risk of putting those humans on hazardous surfaces or within deep gravity wells. Such a strategy may be consistent with goals for a human space flight program that, are currently being developed within NASA.
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ERIC Educational Resources Information Center
Masataka, Nobuo
2007-01-01
Darwin (1871) noted that the human musical faculty "must be ranked amongst the most mysterious with which he is endowed". Indeed, previous research with human infants and young children has revealed that we are born with variable musical capabilities. Here, the adaptive purpose served by these differing capabilities is discussed with reference to…
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Three Models of Education: Rights, Capabilities and Human Capital
ERIC Educational Resources Information Center
Robeyns, Ingrid
2006-01-01
This article analyses three normative accounts that can underlie educational policies, with special attention to gender issues. These three models of education are human capital theory, rights discourses and the capability approach. I first outline five different roles that education can play. Then I analyse these three models of educational…
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NASA's Applied Sciences: Natural Disasters Program
NASA Technical Reports Server (NTRS)
Kessler, Jason L.
2010-01-01
Fully utilize current and near-term airborne and spaceborne assets and capabilities. NASA spaceborne instruments are for research but can be applied to natural disaster response as appropriate. NASA airborne instruments can be targeted specifically for disaster response. Could impact research programs. Better flow of information improves disaster response. Catalog capability, product, applicable disaster, points of contact. Ownership needs to come from the highest level of NASA - unpredictable and irregular nature of disasters requires contingency funding for disaster response. Build-in transfer of applicable natural disaster research capabilities to operational functionality at other agencies (e.g., USFS, NOAA, FEMA...) at the outset, whenever possible. For the Decadal Survey Missions, opportunities exist to identify needs and requirements early in the mission design process. Need to understand additional needs and commitments for meeting the needs of the disaster community. Opportunity to maximize disaster response and mitigation from the Decadal Survey Missions. Additional needs or capabilities may require agency contributions.
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Radiation-induced genomic instability: radiation quality and dose response
NASA Technical Reports Server (NTRS)
Smith, Leslie E.; Nagar, Shruti; Kim, Grace J.; Morgan, William F.
2003-01-01
Genomic instability is a term used to describe a phenomenon that results in the accumulation of multiple changes required to convert a stable genome of a normal cell to an unstable genome characteristic of a tumor. There has been considerable recent debate concerning the importance of genomic instability in human cancer and its temporal occurrence in the carcinogenic process. Radiation is capable of inducing genomic instability in mammalian cells and instability is thought to be the driving force responsible for radiation carcinogenesis. Genomic instability is characterized by a large collection of diverse endpoints that include large-scale chromosomal rearrangements and aberrations, amplification of genetic material, aneuploidy, micronucleus formation, microsatellite instability, and gene mutation. The capacity of radiation to induce genomic instability depends to a large extent on radiation quality or linear energy transfer (LET) and dose. There appears to be a low dose threshold effect with low LET, beyond which no additional genomic instability is induced. Low doses of both high and low LET radiation are capable of inducing this phenomenon. This report reviews data concerning dose rate effects of high and low LET radiation and their capacity to induce genomic instability assayed by chromosomal aberrations, delayed lethal mutations, micronuclei and apoptosis.
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Chen, Huipeng; Poulard, David; Forman, Jason; Crandall, Jeff; Panzer, Matthew B
2018-07-04
Evaluating the biofidelity of pedestrian finite element models (PFEM) using postmortem human subjects (PMHS) is a challenge because differences in anthropometry between PMHS and PFEM could limit a model's capability to accurately capture cadaveric responses. Geometrical personalization via morphing can modify the PFEM geometry to match the specific PMHS anthropometry, which could alleviate this issue. In this study, the Total Human Model for Safety (THUMS) PFEM (Ver 4.01) was compared to the cadaveric response in vehicle-pedestrian impacts using geometrically personalized models. The AM50 THUMS PFEM was used as the baseline model, and 2 morphed PFEM were created to the anthropometric specifications of 2 obese PMHS used in a previous pedestrian impact study with a mid-size sedan. The same measurements as those obtained during the PMHS tests were calculated from the simulations (kinematics, accelerations, strains), and biofidelity metrics based on signals correlation (correlation and analysis, CORA) were established to compare the response of the models to the experiments. Injury outcomes were predicted deterministically (through strain-based threshold) and probabilistically (with injury risk functions) and compared with the injuries reported in the necropsy. The baseline model could not accurately capture all aspects of the PMHS kinematics, strain, and injury risks, whereas the morphed models reproduced biofidelic response in terms of trajectory (CORA score = 0.927 ± 0.092), velocities (0.975 ± 0.027), accelerations (0.862 ± 0.072), and strains (0.707 ± 0.143). The personalized THUMS models also generally predicted injuries consistent with those identified during posttest autopsy. The study highlights the need to control for pedestrian anthropometry when validating pedestrian human body models against PMHS data. The information provided in the current study could be useful for improving model biofidelity for vehicle-pedestrian impact scenarios.
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Experimental models in vaccine research: malaria and leishmaniasis
Teixeira, C.; Gomes, R.
2013-01-01
Animal models have a long history of being useful tools, not only to test and select vaccines, but also to help understand the elaborate details of the immune response that follows infection. Different models have been extensively used to investigate putative immunological correlates of protection against parasitic diseases that are important to reach a successful vaccine. The greatest challenge has been the improvement and adaptation of these models to reflect the reality of human disease and the screening of vaccine candidates capable of overcoming the challenge of natural transmission. This review will discuss the advantages and challenges of using experimental animal models for vaccine development and how the knowledge achieved can be extrapolated to human disease by looking into two important parasitic diseases: malaria and leishmaniasis. PMID:23369975
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Cardiac-Activity Measures for Assessing Airport Ramp-Tower Controller's Workload
NASA Technical Reports Server (NTRS)
Hayashi, Miwa; Dulchinos, Victoria
2016-01-01
Heart rate (HR) and heart rate variability (HRV) potentially offer objective, continuous, and non-intrusive measures of human-operators mental workload. Such measurement capability is attractive for workload assessment in complex laboratory simulations or safety-critical field testing. The present study compares mean HR and HRV data with self-reported subjective workload ratings collected during a high-fidelity human-in-the-loop simulation of airport ramp traffic control operations, which involve complex cognitive and coordination tasks. Mean HR was found to be weakly sensitive to the workload ratings, while HRV was not sensitive or even contradictory to the assumptions. Until more knowledge on stress response mechanisms of the autonomic nervous system is obtained, it is recommended that these cardiac-activity measures be used with other workload assessment tools, such as subjective measures.
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Playing to our human strengths to prepare medical students for the future.
Chen, Julie
2017-09-01
We are living in an age where artificial intelligence and astounding technological advances are bringing truly remarkable change to healthcare. Medical knowledge and skills which form the core responsibility of doctors such as making diagnoses may increasingly be delivered by robots. Machines are gradually acquiring human abilities such as deep learning and empathy. What, then is the role of doctors in future healthcare? And what direction should medical schools be taking to prepare their graduates? This article will give an overview of the evolving technological landscape of healthcare and examine the issues undergraduate medical education may have to address. The experience at The University of Hong Kong will serve as a case study featuring several curricular innovations that aim to empower medical graduates with the capabilities to thrive in the future.
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Cardiac-Activity Measures for Assessing Airport Ramp-Tower Controller's Workload
NASA Technical Reports Server (NTRS)
Hayashi, Miwa; Dulchinos, Victoria L.
2016-01-01
Heart rate (HR) and heart rate variability (HRV) potentially offer objective, continuous, and non-intrusive measures of human-operator's mental workload. Such measurement capability is attractive for workload assessment in complex laboratory simulations or safety-critical field testing. The present study compares mean HR and HRV data with self-reported subjective workload ratings collected during a high-fidelity human-in-the-loop simulation of airport ramp traffic control operations, which involve complex cognitive and coordination tasks. Mean HR was found to be weakly sensitive to the workload ratings, while HRV was not sensitive or even contradictory to the assumptions. Until more knowledge on stress response mechanisms of the autonomic nervous system is obtained, it is recommended that these cardiac-activity measures be used with other workload assessment tools, such as subjective measures.
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Proteomic analysis of Aspergillus fumigatus - clinical implications.
Moloney, Nicola M; Owens, Rebecca A; Doyle, Sean
2016-07-01
Aspergillus fumigatus is a ubiquitous saprophytic fungus capable of producing small airborne spores, which are frequently inhaled by humans. In healthy individuals, the fungus is rapidly cleared by innate mechanisms, including immune cells. However, in individuals with impaired lung function or immunosuppression the spores can germinate and prompt severe allergic responses, and disease with limited or extensive invasiveness. The traits that make A. fumigatus a successful colonizer and pathogen of humans are multi-factorial. Thus, a global investigative approach is required to elucidate the mechanisms utilized by the fungus to cause disease. Expert commentary: In doing so, a better understanding of disease pathology can be achieved with improved therapeutic/diagnostic solutions, thereby improving patient outcome. Proteomic analysis permits such investigations and recent work has yielded insight into these mechanisms.
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A Human Factors Approach to Bridging Systems and Introducing New Technologies
NASA Technical Reports Server (NTRS)
Kanki, Barbara G.
2011-01-01
The application of human factors in aviation has grown to cover a wide range of disciplines and methods capable of assessing human-systems integration at many levels. For example, at the individual level, pilot workload may be studied while at the team level, coordinated workload distribution may be the focal point. At the organizational level, the way in which individuals and teams are supported by training and standards, policies and procedures may introduce additional, relevant topics. A consideration of human factors at each level contributes to our understanding of successes and failures in pilot performance, but this system focused on the flight deck alone -- is only one part of the airspace system. In the FAA's NextGen plan to overhaul the National Airspace System (NAS), new capabilities will enhance flightdeck systems (pilots), flight operations centers (dispatchers) and air traffic control systems (controllers and air traffic managers). At a minimum, the current roles and responsibilities of these three systems are likely to change. Since increased automation will be central to many of the enhancements, the role of automation is also likely to change. Using NextGen examples, a human factors approach for bridging complex airspace systems will be the main focus of this presentation. It is still crucial to consider the human factors within each system, but the successful implementation of new technologies in the NAS requires an understanding of the collaborations that occur when these systems intersect. This human factors approach to studying collaborative systems begins with detailed task descriptions within each system to establish a baseline of the current operations. The collaborative content and context are delineated through the review of regulatory and advisory materials, letters of agreement, policies, procedures and documented practices. Field observations and interviews also help to fill out the picture. Key collaborative functions across systems are identified and placed on a phase-of-flight timeline including information requirements, decision authority and use of automation, as well as level of frequency and criticality.
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Human Mars Entry, Descent and Landing Architectures Study Overview
NASA Technical Reports Server (NTRS)
Polsgrove, Tara T.; Dwyer Cianciolo, Alicia
2016-01-01
Landing humans on Mars will require entry, descent and landing (EDL) capability beyond the current state of the art. Nearly twenty times more delivered payload and an order of magnitude improvement in precision landing capability will be necessary. Several EDL technologies capable of meeting the human class payload delivery requirements are being considered. The EDL technologies considered include low lift-to-drag vehicles like Hypersonic Inflatable Aerodynamic Decelerators (HIAD), Adaptable Deployable Entry and Placement Technology (ADEPT), and mid range lift-to-drag vehicles like rigid aeroshell configurations. To better assess EDL technology options and sensitivities to future human mission design variations, a series of design studies has been conducted. The design studies incorporate EDL technologies with conceptual payload arrangements defined by the Evolvable Mars Campaign to evaluate the integrated system with higher fidelity than have been performed to date. This paper describes the results of the design studies for a lander design using the HIAD, ADEPT and rigid shell entry technologies and includes system and subsystem design details including mass and power estimates. This paper will review the point design for three entry configurations capable of delivering a 20 t human class payload to the surface of Mars.
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Human Planetary Landing System (HPLS) Capability Roadmap NRC Progress Review
NASA Technical Reports Server (NTRS)
Manning, Rob; Schmitt, Harrison H.; Graves, Claude
2005-01-01
Capability Roadmap Team. Capability Description, Scope and Capability Breakdown Structure. Benefits of the HPLS. Roadmap Process and Approach. Current State-of-the-Art, Assumptions and Key Requirements. Top Level HPLS Roadmap. Capability Presentations by Leads. Mission Drivers Requirements. "AEDL" System Engineering. Communication & Navigation Systems. Hypersonic Systems. Super to Subsonic Decelerator Systems. Terminal Descent and Landing Systems. A Priori In-Situ Mars Observations. AEDL Analysis, Test and Validation Infrastructure. Capability Technical Challenges. Capability Connection Points to other Roadmaps/Crosswalks. Summary of Top Level Capability. Forward Work.
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Autonomous Agents on Expedition: Humans and Progenitor Ants and Planetary Exploration
NASA Astrophysics Data System (ADS)
Rilee, M. L.; Clark, P. E.; Curtis, S. A.; Truszkowski, W. F.
2002-01-01
The Autonomous Nano-Technology Swarm (ANTS) is an advanced mission architecture based on a social insect analog of many specialized spacecraft working together to achieve mission goals. The principal mission concept driving the ANTS architecture is a Main Belt Asteroid Survey in the 2020s that will involve a thousand or more nano-technology enabled, artificially intelligent, autonomous pico-spacecraft (< 1 kg). The objective of this survey is to construct a compendium of composition, shape, and other physical parameter observations of a significant fraction of asteroid belt objects. Such an atlas will be of primary scientific importance for the understanding of Solar System origins and evolution and will lay the foundation for future exploration and capitalization of space. As the capabilities enabling ANTS are developed over the next two decades, these capabilities will need to be proven. Natural milestones for this process include the deployment of progenitors to ANTS on human expeditions to space and remote missions with interfaces for human interaction and control. These progenitors can show up in a variety of forms ranging from spacecraft subsystems and advanced handheld sensors, through complete prototypical ANTS spacecraft. A critical capability to be demonstrated is reliable, long-term autonomous operations across the ANTS architecture. High level, mission-oriented behaviors are to be managed by a control / communications layer of the swarm, whereas common low level functions required of all spacecraft, e.g. attitude control and guidance and navigation, are handled autonomically on each spacecraft. At the higher levels of mission planning and social interaction deliberative techniques are to be used. For the asteroid survey, ANTS acts as a large community of cooperative agents while for precursor missions there arises the intriguing possibility of Progenitor ANTS and humans acting together as agents. For optimal efficiency and responsiveness for individual spacecraft at the lowest levels of control we have been studying control methods based on nonlinear dynamical systems. We describe the critically important autonomous control architecture of the ANTS mission concept and a sequence of partial implementations that feature increasingly autonomous behaviors. The scientific and engineering roles that these Progenitor ANTS could play in human missions or remote missions with near real time human interactions, particularly to the Moon and Mars, will be discussed.
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Serologic Cross-Reactivity of Human IgM and IgG Antibodies to Five Species of Ebola Virus
MacNeil, Adam; Reed, Zachary; Rollin, Pierre E.
2011-01-01
Five species of Ebola virus (EBOV) have been identified, with nucleotide differences of 30–45% between species. Four of these species have been shown to cause Ebola hemorrhagic fever (EHF) in humans and a fifth species (Reston ebolavirus) is capable of causing a similar disease in non-human primates. While examining potential serologic cross-reactivity between EBOV species is important for diagnostic assays as well as putative vaccines, the nature of cross-reactive antibodies following EBOV infection has not been thoroughly characterized. In order to examine cross-reactivity of human serologic responses to EBOV, we developed antigen preparations for all five EBOV species, and compared serologic responses by IgM capture and IgG enzyme-linked immunosorbent assay (ELISA) in groups of convalescent diagnostic sera from outbreaks in Kikwit, Democratic Republic of Congo (n = 24), Gulu, Uganda (n = 20), Bundibugyo, Uganda (n = 33), and the Philippines (n = 18), which represent outbreaks due to four different EBOV species. For groups of samples from Kikwit, Gulu, and Bundibugyo, some limited IgM cross-reactivity was noted between heterologous sera-antigen pairs, however, IgM responses were largely stronger against autologous antigen. In some instances IgG responses were higher to autologous antigen than heterologous antigen, however, in contrast to IgM responses, we observed strong cross-reactive IgG antibody responses to heterologous antigens among all sets of samples. Finally, we examined autologous IgM and IgG antibody levels, relative to time following EHF onset, and observed early peaking and declining IgM antibody levels (by 80 days) and early development and persistence of IgG antibodies among all samples, implying a consistent pattern of antibody kinetics, regardless of EBOV species. Our findings demonstrate limited cross-reactivity of IgM antibodies to EBOV, however, the stronger tendency for cross-reactive IgG antibody responses can largely circumvent limitations in the utility of heterologous antigen for diagnostic assays and may assist in the development of antibody-mediated vaccines to EBOV. PMID:21666792
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Pyoverdine and proteases affect the response of Pseudomonas aeruginosa to gallium in human serum.
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. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
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Pyoverdine and Proteases Affect the Response of Pseudomonas aeruginosa to Gallium in Human Serum
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
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Charles-Niño, Claudia; Pedroza-Roldan, Cesar; Viveros, Monica; Gevorkian, Goar; Manoutcharian, Karen
2011-07-18
The extreme antigenic variability of human immunodeficiency virus (HIV) leads to immune escape of the virus, representing a major challenge in the design of effective vaccine. We have developed a novel concept for immunogen construction based on introduction of massive mutations within the epitopes targeting antigenically variable pathogens and diseases. Previously, we showed that these immunogens carrying large combinatorial libraries of mutated epitope variants, termed as variable epitope libraries (VELs), induce potent, broad and long lasting CD8+IFN-γ+ T-cell response. Moreover, we demonstrated that these T cells recognize more than 50% of heavily mutated variants (5 out of 10 amino acid positions were mutated in each epitope variant) of HIV-1 gp120 V3 loop-derived cytotoxic T lymphocyte epitope (RGPGRAFVTI) in mice. The constructed VELs had complexities of 10000 and 12500 individual members, generated as plasmid DNA or as M13 phage display combinatorial libraries, respectively, and with structural composition RGPGXAXXXX or XGXGXAXVXI, where X is any of 20 natural amino acids. Here, we demonstrated that sera from mice immunized with these VELs are capable of neutralizing 5 out of 10 viral isolates from Tier 2 reference panel of subtype B envelope clones, including HIV-1 isolates which are known to be resistant to neutralization by several potent monoclonal antibodies, described previously. These data indicate the feasibility of the application of immunogens based on VEL concept as an alternative approach for the development of molecular vaccines against antigenically variable pathogens. Copyright © 2011 Elsevier Ltd. All rights reserved.
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NASA Technical Reports Server (NTRS)
Bleacher, Jacob E.; Hurtado, J. M., Jr.; Meyer, J. A.
2012-01-01
Desert Research and Technology Studies (DRATS) is a multi-year series of NASA tests that deploy planetary surface hardware and exercise mission and science operations in difficult conditions to advance human and robotic exploration capabilities. DRATS 2011 (Aug. 30-Sept. 9, 2011) tested strategies for human exploration of microgravity targets such as near-Earth asteroids (NEAs). Here we report the crew perspective on the impact of simulated microgravity operations on our capability to conduct field geology.
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Human Research Program Exploration Medical Capability
NASA Technical Reports Server (NTRS)
Barsten, Kristina
2010-01-01
NASA s Human Research Program (HRP) conducts and coordinates research projects that provide human health and performance countermeasures, knowledge, technologies, and tools to enable safe, reliable, and productive human space exploration. The Program is divided into 6 major elements, which a) Provide the Program s knowledge and capabilities to conduct research, addressing the human health and performance risks. b) Advance the readiness levels of technology and countermeasures to the point of transfer to the customer programs and organizations. The National Space Biomedical Research Institute (NSBRI) is a partner with the HRP in developing a successful research program. 3
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NASA Astrophysics Data System (ADS)
Coyne, Kevin Anthony
The safe operation of complex systems such as nuclear power plants requires close coordination between the human operators and plant systems. In order to maintain an adequate level of safety following an accident or other off-normal event, the operators often are called upon to perform complex tasks during dynamic situations with incomplete information. The safety of such complex systems can be greatly improved if the conditions that could lead operators to make poor decisions and commit erroneous actions during these situations can be predicted and mitigated. The primary goal of this research project was the development and validation of a cognitive model capable of simulating nuclear plant operator decision-making during accident conditions. Dynamic probabilistic risk assessment methods can improve the prediction of human error events by providing rich contextual information and an explicit consideration of feedback arising from man-machine interactions. The Accident Dynamics Simulator paired with the Information, Decision, and Action in a Crew context cognitive model (ADS-IDAC) shows promise for predicting situational contexts that might lead to human error events, particularly knowledge driven errors of commission. ADS-IDAC generates a discrete dynamic event tree (DDET) by applying simple branching rules that reflect variations in crew responses to plant events and system status changes. Branches can be generated to simulate slow or fast procedure execution speed, skipping of procedure steps, reliance on memorized information, activation of mental beliefs, variations in control inputs, and equipment failures. Complex operator mental models of plant behavior that guide crew actions can be represented within the ADS-IDAC mental belief framework and used to identify situational contexts that may lead to human error events. This research increased the capabilities of ADS-IDAC in several key areas. The ADS-IDAC computer code was improved to support additional branching events and provide a better representation of the IDAC cognitive model. An operator decision-making engine capable of responding to dynamic changes in situational context was implemented. The IDAC human performance model was fully integrated with a detailed nuclear plant model in order to realistically simulate plant accident scenarios. Finally, the improved ADS-IDAC model was calibrated, validated, and updated using actual nuclear plant crew performance data. This research led to the following general conclusions: (1) A relatively small number of branching rules are capable of efficiently capturing a wide spectrum of crew-to-crew variabilities. (2) Compared to traditional static risk assessment methods, ADS-IDAC can provide a more realistic and integrated assessment of human error events by directly determining the effect of operator behaviors on plant thermal hydraulic parameters. (3) The ADS-IDAC approach provides an efficient framework for capturing actual operator performance data such as timing of operator actions, mental models, and decision-making activities.
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NASA Astrophysics Data System (ADS)
Sun, Chi-Kuang; Wei, Ming-Liang; Su, Yu-Hsiang; Weng, Wei-Hung; Liao, Yi-Hua
2017-02-01
Harmonic generation microscopy is a noninvasive repetitive imaging technique that provides real-time 3D microscopic images of human skin with a sub-femtoliter resolution and high penetration down to the reticular dermis. In this talk, we show that with a strong resonance effect, the third-harmonic-generation (THG) modality provides enhanced contrast on melanin and allows not only differential diagnosis of various pigmented skin lesions but also quantitative imaging for longterm tracking. This unique capability makes THG microscopy the only label-free technique capable of identifying the active melanocytes in human skin and to image their different dendriticity patterns. In this talk, we will review our recent efforts to in vivo image melanin distribution and quantitatively diagnose pigmented skin lesions using label-free harmonic generation biopsy. This talk will first cover the spectroscopic study on the melanin enhanced THG effect in human cells and the calibration strategy inside human skin for quantitative imaging. We will then review our recent clinical trials including: differential diagnosis capability study on pigmented skin tumors; as well as quantitative virtual biopsy study on pre- and post- treatment evaluation on melasma and solar lentigo. Our study indicates the unmatched capability of harmonic generation microscopy to perform virtual biopsy for noninvasive histopathological diagnosis of various pigmented skin tumors, as well as its unsurpassed capability to noninvasively reveal the pathological origin of different hyperpigmentary diseases on human face as well as to monitor the efficacy of laser depigmentation treatments. This work is sponsored by National Health Research Institutes.
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Aulik, Nicole A.; Hellenbrand, Katrina M.; Klos, Heather; Czuprynski, Charles J.
2010-01-01
Mannheimia haemolytica is an important member of the bovine respiratory disease complex, which is characterized by abundant neutrophil infiltration into the alveoli and fibrin deposition. Recently several authors have reported that human neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of trapping and killing pathogens. Here, we demonstrate that the leukotoxin (LKT) of M. haemolytica causes NET formation by bovine neutrophils in a CD18-dependent manner. Using an unacylated, noncytotoxic pro-LKT produced by an ΔlktC mutant of M. haemolytica, we show that binding of unacylated pro-LKT stimulates NET formation despite a lack of cytotoxicity. Inhibition of LKT binding to the CD18 chain of lymphocyte function-associated antigen 1 (LFA-1) on bovine neutrophils reduced NET formation in response to LKT or M. haemolytica cells. Further investigation revealed that NETs formed in response to M. haemolytica are capable of trapping and killing a portion of the bacterial cells. NET formation was confirmed by confocal microscopy and by scanning and transmission electron microscopy. Prior exposure of bovine neutrophils to LKT enhanced subsequent trapping and killing of M. haemolytica cells in bovine NETs. Understanding NET formation in response to M. haemolytica and its LKT provides a new perspective on how neutrophils contribute to the pathogenesis of bovine respiratory disease. PMID:20823211
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A Highly Capable Year 6 Student's Response to a Challenging Mathematical Task
ERIC Educational Resources Information Center
Livy, Sharyn; Holmes, Marilyn; Ingram, Naomi; Linsell, Chris; Sullivan, Peter
2016-01-01
Highly capable mathematics students are not usually considered strugglers. This paper reports on a case study of a Year 6 student, Debbie, her response to a lesson, and her learning involving a challenging mathematical task. Debbie, usually a highly capable student, struggled to complete a challenging mathematical task by herself, but as the…
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Human-Centered Design Capability
NASA Technical Reports Server (NTRS)
Fitts, David J.; Howard, Robert
2009-01-01
For NASA, human-centered design (HCD) seeks opportunities to mitigate the challenges of living and working in space in order to enhance human productivity and well-being. Direct design participation during the development stage is difficult, however, during project formulation, a HCD approach can lead to better more cost-effective products. HCD can also help a program enter the development stage with a clear vision for product acquisition. HCD tools for clarifying design intent are listed. To infuse HCD into the spaceflight lifecycle the Space and Life Sciences Directorate developed the Habitability Design Center. The Center has collaborated successfully with program and project design teams and with JSC's Engineering Directorate. This presentation discusses HCD capabilities and depicts the Center's design examples and capabilities.
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Trans-species learning of cellular signaling systems with bimodal deep belief networks
Chen, Lujia; Cai, Chunhui; Chen, Vicky; Lu, Xinghua
2015-01-01
Motivation: Model organisms play critical roles in biomedical research of human diseases and drug development. An imperative task is to translate information/knowledge acquired from model organisms to humans. In this study, we address a trans-species learning problem: predicting human cell responses to diverse stimuli, based on the responses of rat cells treated with the same stimuli. Results: We hypothesized that rat and human cells share a common signal-encoding mechanism but employ different proteins to transmit signals, and we developed a bimodal deep belief network and a semi-restricted bimodal deep belief network to represent the common encoding mechanism and perform trans-species learning. These ‘deep learning’ models include hierarchically organized latent variables capable of capturing the statistical structures in the observed proteomic data in a distributed fashion. The results show that the models significantly outperform two current state-of-the-art classification algorithms. Our study demonstrated the potential of using deep hierarchical models to simulate cellular signaling systems. Availability and implementation: The software is available at the following URL: http://pubreview.dbmi.pitt.edu/TransSpeciesDeepLearning/. The data are available through SBV IMPROVER website, https://www.sbvimprover.com/challenge-2/overview, upon publication of the report by the organizers. Contact: xinghua@pitt.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25995230
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Trans-species learning of cellular signaling systems with bimodal deep belief networks.
Chen, Lujia; Cai, Chunhui; Chen, Vicky; Lu, Xinghua
2015-09-15
Model organisms play critical roles in biomedical research of human diseases and drug development. An imperative task is to translate information/knowledge acquired from model organisms to humans. In this study, we address a trans-species learning problem: predicting human cell responses to diverse stimuli, based on the responses of rat cells treated with the same stimuli. We hypothesized that rat and human cells share a common signal-encoding mechanism but employ different proteins to transmit signals, and we developed a bimodal deep belief network and a semi-restricted bimodal deep belief network to represent the common encoding mechanism and perform trans-species learning. These 'deep learning' models include hierarchically organized latent variables capable of capturing the statistical structures in the observed proteomic data in a distributed fashion. The results show that the models significantly outperform two current state-of-the-art classification algorithms. Our study demonstrated the potential of using deep hierarchical models to simulate cellular signaling systems. The software is available at the following URL: http://pubreview.dbmi.pitt.edu/TransSpeciesDeepLearning/. The data are available through SBV IMPROVER website, https://www.sbvimprover.com/challenge-2/overview, upon publication of the report by the organizers. xinghua@pitt.edu Supplementary data are available at Bioinformatics online. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Bozzi, Fabio; Manenti, Giacomo; Conca, Elena; Stacchiotti, Silvia; Messina, Antonella; Dagrada, GianPaolo; Gronchi, Alessandro; Panizza, Pietro; Pierotti, Marco A.; Tamborini, Elena; Pilotti, Silvana
2014-01-01
Background Chordomas are rare and indolent bone tumors that arise in the skull base and mobile spine. Distant metastases occur in >20% of cases, but morbidity and mortality are mainly related to local relapses that affect the majority of patients. Standard chemotherapy has modest activity, whereas new targeted therapies (alone or in combination) have some activity in controlling disease progression. However, the scarcity of preclinical models capable of testing in vivo responses to these therapies hampers the development of new medical strategies. Methods In this study, 8 chordoma samples taken from 8 patients were implanted in nude mice. Four engrafted successfully and gave rise to tumor masses that were analyzed histologically, by means of fluorescence in situ hybridization and biochemical techniques. The data relating to each of the mouse tumors were compared with those obtained from the corresponding human tumor. Results All 4 engraftments retained the histological, genetic and biochemical features of the human tumors they came from. In one epidermal growth factor receptor(EGFR)-positive xenograft, responsiveness to lapatinib was evaluated by comparing the pre- and posttreatment findings. The treatment induced a low-level, heterogeneous switching off of EGFR and its downstream signaling effectors. Conclusions Overall, this model is very close to human chordoma and represents a new means of undertaking preclinical investigations and developing tailored therapies. PMID:24366975
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NASA Technical Reports Server (NTRS)
Inman, Thomas
2005-01-01
General Background and Introduction of Capability Roadmaps: Agency Objective. Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Technology and Capability Readiness Levels. Relationships Between Roadmaps. Purpose of NRC Review. Capability Roadmap Development (Team Progress to Date).
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Aviation System Analysis Capability Quick Response System Report for Fiscal Year 1998
NASA Technical Reports Server (NTRS)
Ege, Russell; Villani, James; Ritter, Paul
1999-01-01
This document presents the additions and modifications made to the Quick Response System (QRS) in FY 1998 in support of the ASAC QRS development effort. this Document builds upon the Aviation System Analysis Capability Quick Responses System Report for Fiscal Year 1997.
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The association of allergic sensitization in mother and child in breast-fed and formula-fed infants.
Wright, A L; Stern, D A; Halonen, M
2001-01-01
Human milk contains immunologically active substances potentially capable of altering infant immune response. As part of the prospective Children's Respiratory Study, we assessed whether the association between maternal allergic status and allergic status of the child was altered by breast-feeding. Skin-prick tests for 7 common allergens were administered to 702 6-year-old children and their mothers. The percentage of children sensitized to specific allergens, maternal skin test response to that allergen, and whether or not the child was ever breast-fed was determined. Findings indicated that specific sensitization in the mother was associated with specific sensitization in the child only if the child was breast-fed. This indirectly supports the hypothesis that contents of milk differ with maternal allergic status, and appear to affect allergic status in the child. These results suggest that milk from allergic mothers either promotes a Th2 type immune response or suppresses Th1 immune response in the child.
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Public Health Crisis Preparedness and Response in Korea
Lee, Hye-Young; Oh, Mi-Na; Park, Yong-Shik; Chu, Chaeshin; Son, Tae-Jong
2013-01-01
Since the 2006 Pandemic Influenza Preparedness and Response Plan according to the World Health Organization’s recommendation, the Republic of Korea has prepared and periodically evaluated the plan to respond to various public health crises including pandemic influenza. Korea has stockpiled 13,000,000 doses of antiviral drugs covering 26% of the Korean population and runs 519 isolated beds in 16 medical institutions. The division of public health crisis response in Korea Centers for Disease Control and Prevention are in charge of responding to public health crises caused by emerging infectious diseases including severe acute respiratory syndrome, avian influenza human infection, and pandemic influenza. Its job description includes preparing for emerging infectious diseases, securing medical resources during a crisis, activating the emergency response during the crisis, and fortification of capabilities of public health personnel. It could evolve into a comprehensive national agency to deal with public health crisis based on the experience of previous national emerging infectious diseases. PMID:24298444
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Surgical Capabilities for Exploration and Colonization Space Flight - An Exploratory Symposium
NASA Technical Reports Server (NTRS)
Pantalos, George; Strangman, Gary; Doarn, Charles R.; Broderick, Timothy; Antonsen, Erik
2015-01-01
Identify realistic and achievable pathways for surgical capabilities during exploration and colonization space operations and develop a list of recommendations to the NASA Human Research Program to address challenges to developing surgical capabilities.
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High-speed holographic system for full-field transient vibrometry of the human tympanic membrane
NASA Astrophysics Data System (ADS)
Dobrev, I.; Harrington, E. J.; Cheng, T.; Furlong, C.; Rosowski, J. J.
2014-07-01
Understanding of the human hearing process requires the quantification of the transient response of the human ear and the human tympanic membrane (TM or eardrum) in particular. Current state-of-the-art medical methods to quantify the transient acousto-mechanical response of the TM provide only averaged acoustic or local information at a few points. This may be insufficient to fully describe the complex patterns unfolding across the full surface of the TM. Existing engineering systems for full-field nanometer measurements of transient events, typically based on holographic methods, constrain the maximum sampling speed and/or require complex experimental setups. We have developed and implemented of a new high-speed (i.e., > 40 Kfps) holographic system (HHS) with a hybrid spatio-temporal local correlation phase sampling method that allows quantification of the full-field nanometer transient (i.e., > 10 kHz) displacement of the human TM. The HHS temporal accuracy and resolution is validated versus a LDV on both artificial membranes and human TMs. The high temporal (i.e., < 24 μs) and spatial (i.e., >100k data points) resolution of our HHS enables simultaneous measurement of the time waveform of the full surface of the TM. These capabilities allow for quantification of spatially-dependent motion parameters such as energy propagation delays surface wave speeds, which can be used to infer local material properties across the surface of the TM. The HHS could provide a new tool for the investigation of the auditory system with applications in medical research, in-vivo clinical diagnosis as well as hearing aids design.
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Human Capability, Mild Perfectionism and Thickened Educational Praxis
ERIC Educational Resources Information Center
Walker, Melanie
2008-01-01
This paper argues for a mild perfectionism in applying Amartya Sen's capability approach for an education transformative of student agency and well-being. Key to the paper is the significance of education as a process of being and becoming in the future, and education's fundamental objective of a positively changed human being. The capability…
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Zhang, Liying; Makwana, Rahul; Sharma, Sumit
2013-01-01
Blast-induced traumatic brain injury has emerged as a “signature injury” in combat casualty care. Present combat helmets are designed primarily to protect against ballistic and blunt impacts, but the current issue with helmets is protection concerning blasts. In order to delineate the blast wave attenuating capability of the Advanced Combat Helmet (ACH), a finite element (FE) study was undertaken to evaluate the head response against blast loadings with and without helmet using a partially validated FE model of the human head and ACH. Four levels of overpressures (0.27–0.66 MPa) from the Bowen’s lung iso-damage threshold curves were used to simulate blast insults. Effectiveness of the helmet with respect to head orientation was also investigated. The resulting biomechanical responses of the brain to blast threats were compared for human head with and without the helmet. For all Bowen’s cases, the peak intracranial pressures (ICP) in the head ranged from 0.68 to 1.8 MPa in the coup cortical region. ACH was found to mitigate ICP in the head by 10–35%. Helmeted head resulted in 30% lower average peak brain strains and product of strain and strain rate. Among three blast loading directions with ACH, highest reduction in peak ICP (44%) was due to backward blasts whereas the lowest reduction in peak ICP and brain strains was due to forward blast (27%). The biomechanical responses of a human head to primary blast insult exhibited directional sensitivity owing to the different geometry contours and coverage of the helmet construction and asymmetric anatomy of the head. Thus, direction-specific tolerances are needed in helmet design in order to offer omni-directional protection for the human head. The blasts of varying peak overpressures and durations that are believed to produce the same level of lung injury produce different levels of mechanical responses in the brain, and hence “iso-damage” curves for brain injury are likely different than the Bowen curves for lung injury. PMID:23935591
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Emergence of Antimicrobial-Resistant Escherichia coli of Animal Origin Spreading in Humans
Skurnik, David; Clermont, Olivier; Guillard, Thomas; Launay, Adrien; Danilchanka, Olga; Pons, Stéphanie; Diancourt, Laure; Lebreton, François; Kadlec, Kristina; Roux, Damien; Jiang, Deming; Dion, Sara; Aschard, Hugues; Denamur, Maurice; Cywes-Bentley, Colette; Schwarz, Stefan; Tenaillon, Olivier; Andremont, Antoine; Picard, Bertrand; Mekalanos, John; Brisse, Sylvain; Denamur, Erick
2016-01-01
In the context of the great concern about the impact of human activities on the environment, we studied 403 commensal Escherichia coli/Escherichia clade strains isolated from several animal and human populations that have variable contacts to one another. Multilocus sequence typing (MLST) showed a decrease of diversity 1) in strains isolated from animals that had an increasing contact with humans and 2) in all strains that had increased antimicrobial resistance. A specific B1 phylogroup clonal complex (CC87, Institut Pasteur schema nomenclature) of animal origin was identified and characterized as being responsible for the increased antimicrobial resistance prevalence observed in strains from the environments with a high human-mediated antimicrobial pressure. CC87 strains have a high capacity of acquiring and disseminating resistance genes with specific metabolic and genetic determinants as demonstrated by high-throughput sequencing and phenotyping. They are good mouse gut colonizers but are not virulent. Our data confirm the predominant role of human activities in the emergence of antimicrobial resistance in the environmental bacterial strains and unveil a particular E. coli clonal complex of animal origin capable of spreading antimicrobial resistance to other members of microbial communities. PMID:26613786
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NASA Technical Reports Server (NTRS)
Arneson, Heather; Evans, Antony D.; Li, Jinhua; Wei, Mei Yueh
2017-01-01
Integrated Demand Management (IDM) is a near- to mid-term NASA concept that proposes to address mismatches in air traffic system demand and capacity by using strategic flow management capabilities to pre-condition demand into the more tactical Time-Based Flow Management System (TBFM). This paper describes an automated simulation capability to support IDM concept development. The capability closely mimics existing human-in-the-loop (HITL) capabilities, while automating both the human components and collaboration between operational systems, and speeding up the real-time aircraft simulations. Such a capability allows for parametric studies to be carried out that can inform the HITL simulations, identifying breaking points and parameter values at which significant changes in system behavior occur. The paper describes the initial validation of the automated simulation capability against results from previous IDM HITL experiments, quantifying the differences. The simulator is then used to explore the performance of the IDM concept under the simple scenario of a capacity constrained airport under a wide range of wind conditions.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lukens, Michael V.; Claassen, Erwin A.W.; Graaff, Patricia M.A. de
2006-08-15
The BALB/c mouse model for human respiratory syncytial virus infection has contributed significantly to our understanding of the relative role for CD4{sup +} and CD8{sup +} T cells to immune protection and pathogenic immune responses. To enable comparison of RSV-specific T cell responses in different mouse strains and allow dissection of immune mechanisms by using transgenic and knockout mice that are mostly available on a C57BL/6 background, we characterized the specificity, level and functional capabilities of CD8{sup +} T cells during primary and secondary responses in lung parenchyma, airways and spleens of C57BL/6 mice. During the primary response, epitopes weremore » recognized originating from the matrix, fusion, nucleo- and attachment proteins, whereas the secondary response focused predominantly on the matrix epitope. C57BL/6 mice are less permissive for hRSV infection than BALB/c mice, yet we found CD8{sup +} T cell responses in the lungs and bronchoalveolar lavage, comparable to the responses described for BALB/c mice.« less
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NASA Technical Reports Server (NTRS)
Salazar, Giovanni; Droba, Justin C.; Oliver, Brandon; Amar, Adam J.
2016-01-01
With the recent development of multi-dimensional thermal protection system (TPS) material response codes, the capability to account for surface-to-surface radiation exchange in complex geometries is critical. This paper presents recent efforts to implement such capabilities in the CHarring Ablator Response (CHAR) code developed at NASA's Johnson Space Center. This work also describes the different numerical methods implemented in the code to compute geometric view factors for radiation problems involving multiple surfaces. Verification of the code's radiation capabilities and results of a code-to-code comparison are presented. Finally, a demonstration case of a two-dimensional ablating cavity with enclosure radiation accounting for a changing geometry is shown.
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O’Kell, Allison L.; Wasserfall, Clive; Catchpole, Brian; Davison, Lucy J.; Hess, Rebecka S.; Kushner, Jake A.
2017-01-01
Despite decades of research in humans and mouse models of disease, substantial gaps remain in our understanding of pathogenic mechanisms underlying the development of type 1 diabetes. Furthermore, translation of therapies from preclinical efforts capable of delaying or halting β-cell destruction has been limited. Hence, a pressing need exists to identify alternative animal models that reflect human disease. Canine insulin deficiency diabetes is, in some cases, considered to follow autoimmune pathogenesis, similar to NOD mice and humans, characterized by hyperglycemia requiring lifelong exogenous insulin therapy. Also similar to human type 1 diabetes, the canonical canine disorder appears to be increasing in prevalence. Whereas islet architecture in rodents is distinctly different from humans, canine pancreatic endocrine cell distribution is more similar. Differences in breed susceptibility alongside associations with MHC and other canine immune response genes parallel that of different ethnic groups within the human population, a potential benefit over NOD mice. The impact of environment on disease development also favors canine over rodent models. Herein, we consider the potential for canine diabetes to provide valuable insights for human type 1 diabetes in terms of pancreatic histopathology, impairment of β-cell function and mass, islet inflammation (i.e., insulitis), and autoantibodies specific for β-cell antigens. PMID:28533295
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Andra, Syam S; Austin, Christine; Patel, Dhavalkumar; Dolios, Georgia; Awawda, Mahmoud; Arora, Manish
2017-03-01
Global profiling of xenobiotics in human matrices in an untargeted mode is gaining attention for studying the environmental chemical space of the human exposome. Defined as the study of a comprehensive inclusion of environmental influences and associated biological responses, human exposome science is currently evolving out of the metabolomics science. In analogy to the latter, the development and applications of high resolution mass spectrometry (HRMS) has shown potential and promise to greatly expand our ability to capture the broad spectrum of environmental chemicals in exposome studies. HRMS can perform both untargeted and targeted analysis because of its capability of full- and/or tandem-mass spectrum acquisition at high mass accuracy with good sensitivity. The collected data from target, suspect and non-target screening can be used not only for the identification of environmental chemical contaminants in human matrices prospectively but also retrospectively. This review covers recent trends and advances in this field. We focus on advances and applications of HRMS in human biomonitoring studies, and data acquisition and mining. The acquired insights provide stepping stones to improve understanding of the human exposome by applying HRMS, and the challenges and prospects for future research. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Subthalamic nucleus detects unnatural android movement.
Ikeda, Takashi; Hirata, Masayuki; Kasaki, Masashi; Alimardani, Maryam; Matsushita, Kojiro; Yamamoto, Tomoyuki; Nishio, Shuichi; Ishiguro, Hiroshi
2017-12-19
An android, i.e., a realistic humanoid robot with human-like capabilities, may induce an uncanny feeling in human observers. The uncanny feeling about an android has two main causes: its appearance and movement. The uncanny feeling about an android increases when its appearance is almost human-like but its movement is not fully natural or comparable to human movement. Even if an android has human-like flexible joints, its slightly jerky movements cause a human observer to detect subtle unnaturalness in them. However, the neural mechanism underlying the detection of unnatural movements remains unclear. We conducted an fMRI experiment to compare the observation of an android and the observation of a human on which the android is modelled, and we found differences in the activation pattern of the brain regions that are responsible for the production of smooth and natural movement. More specifically, we found that the visual observation of the android, compared with that of the human model, caused greater activation in the subthalamic nucleus (STN). When the android's slightly jerky movements are visually observed, the STN detects their subtle unnaturalness. This finding suggests that the detection of unnatural movements is attributed to an error signal resulting from a mismatch between a visual input and an internal model for smooth movement.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Dewair, M.
1989-01-01
Hypersensitivity pneumonitis (HP), an immunologically mediated chronic pulmonary disease, is the result of an inflammatory response of the lung initiated by the inhalation of environmental organic dusts. These organic dusts usually contain substances (antigens) capable of eliciting immune responses in humans. The symptoms of HP generally present as recurrent flu-like episodes which makes it difficult to establish the proper diagnosis. However, detection in patients' sera of high-titer antibodies against the environmental antigens could be of great help in identifying those materials causing the disease and which must be avoided. A highly specific and sensitive serodiagnostic test, a radioimmuno assay (RIA),more » was developed for measurement of antibodies against antigens relevant to Farmer's Lung Disease (FLD), a type of HP affecting farmers.« less
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Connecting Environmental Observations with Cholera Outbreaks in Bangladesh
NASA Astrophysics Data System (ADS)
Stack, D.; Sandborn, A.; Widmeyer, P. A.; Escobar, V. M.
2011-12-01
Research has demonstrated that cholera epidemics in Bangladesh occur seasonally. This bimodal outbreak pattern closely follows times when large monsoon events are most frequent (spring and fall). While these patterns are presented in regional data, this knowledge alone cannot forecast the severity and location of cholera outbreaks until a monsoon event occurs, or an outbreak is reported. Therefore, there can only be reactive responses to cholera outbreaks. A heightened understanding of the link between environmental factors and outbreak occurrence will greatly enhance disease management capabilities. A predictive tool capable of giving an advanced warning of the environmental hazards that lead to location specific outbreaks allows for proactive and preventative responses, minimizing negative effects. A specific goal of this research was to relate latitude-longitude data with existing points associated with V. cholerae human case data collected from four cities in Bangladesh. Remotely sensed products were used to better understand the correlation between human outbreak occurrences, chlorophyll-a estimates, sea surface temperature (SST), and rainfall. Using MODIS, SeaWiFS, and TRMM satellite data, a gridded regional image was developed. Correlation analyses of the data were studied within the context of geographically diverse locations for the four cities of interest. Seasonal relationships were found between the cholera case data and all three of the chosen remotely sensed parameters. The strongest correlation found was between chlorophyll-a concentrations and reported human cases. The primary deliverable of this project was the production of an interactive Google Earth base map for use in a pilot design study that will lead to the development of applications to connect earth science products with water and health studies. The base map, with its inherent value of merging remotely sensed data with in situ observation points, can be used as a basis for constructing better models of disease outbreaks. This effort will build upon current research at University of Maryland, College Park, which focuses on the impacts of climate on both water and health.
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Strengthening the Federal Emergency Management Agency's disaster response capabilities.
Cannon, Glenn M
2008-04-01
The Federal Emergency Management Agency's (FEMA) Disaster Operations Directorate provides the core federal response capability to save lives and to protect property in US communities that have been overwhelmed by the impact of a major disaster or emergency. The directorate executes its mission through three main programme areas: operational direction, command and control; operational teams; and operational planning. Based on lessons learned from years of disaster response experience, FEMA is now taking a more proactive and collaborative approach with its partners. This paper discusses how FEMA is placing a greater emphasis on response operations and strengthening capabilities across the full range of operational and support missions by comprehensively revamping its disaster operations model; enhancing its headquarters and regional operations centres; enhancing its headquarters and regional operational planning capabilities; and addressing catastrophic disaster planning and related critical preparedness issues.
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Lowell, Jr., James R.; Edlund, David J.; Friesen, Dwayne T.; Rayfield, George W.
1992-01-01
Sensors responsive to small changes in the concentration of chemical species are disclosed, comprising a mechanicochemically responsive polymeric film capable of expansion or contraction in response to a change in its chemical environment, either operatively coupled to a transducer capable of directly converting the expansion or contraction to a measurable electrical or optical response, or adhered to a second inert polymeric strip, or doped with a conductive material.
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NASA Technical Reports Server (NTRS)
Aikins, Jan
2005-01-01
Contents include the following: General Background and Introduction of Capability Roadmaps. Agency Objective. Strategic Planning Transformation. Advanced Planning Organizational Roles. Public Involvement in Strategic Planning. Strategic Roadmaps and Schedule. Capability Roadmaps and Schedule. Purpose of NRC Review. Capability Roadmap Development (Progress to Date).
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ERIC Educational Resources Information Center
Seeberg, Vilma
2014-01-01
This study proposes an elaboration of the human development capability approach by theorizing empowerment capabilities as an essential aspect of the education of excluded village girls. Seeking to explain Chinese village girls' demand for schooling, the article identifies intangible and instrumental capabilities that have often been overlooked and…
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NASA Technical Reports Server (NTRS)
Arneson, Heather; Evans, Antony D.; Li, Jinhua; Wei, Mei Yueh
2017-01-01
Integrated Demand Management (IDM) is a near- to mid-term NASA concept that proposes to address mismatches in air traffic system demand and capacity by using strategic flow management capabilities to pre-condition demand into the more tactical Time-Based Flow Management System (TBFM). This paper describes an automated simulation capability to support IDM concept development. The capability closely mimics existing human-in-the-loop (HITL) capabilities, automating both the human components and collaboration between operational systems, and speeding up the real-time aircraft simulations. Such a capability allows for parametric studies that will inform the HITL simulations, identifying breaking points and parameter values at which significant changes in system behavior occur. This paper also describes the initial validation of individual components of the automated simulation capability, and an example application comparing the performance of the IDM concept under two TBFM scheduling paradigms. The results and conclusions from this simulation compare closely to those from previous HITL simulations using similar scenarios, providing an initial validation of the automated simulation capability.
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NASA Space Launch System: A Cornerstone Capability for Exploration
NASA Technical Reports Server (NTRS)
Creech, Stephen D.; Robinson, Kimberly F.
2014-01-01
Under construction today, the National Aeronautics and Space Administration's (NASA) Space Launch System (SLS), managed at the Marshall Space Flight Center, will provide a robust new capability for human and robotic exploration beyond Earth orbit. The vehicle's initial configuration, sched will enable human missions into lunar space and beyond, as well as provide game-changing benefits for space science missions, including offering substantially reduced transit times for conventionally designed spacecraft. From there, the vehicle will undergo a series of block upgrades via an evolutionary development process designed to expedite mission capture as capability increases. The Space Launch System offers multiple benefits for a variety of utilization areas. From a mass-lift perspective, the initial configuration of the vehicle, capable of delivering 70 metric tons (t) to low Earth orbit (LEO), will be the world's most powerful launch vehicle. Optimized for missions beyond Earth orbit, it will also be the world's only exploration-class launch vehicle capable of delivering 25 t to lunar orbit. The evolved configuration, with a capability of 130 t to LEO, will be the most powerful launch vehicle ever flown. From a volume perspective, SLS will be compatible with the payload envelopes of contemporary launch vehicles, but will also offer options for larger fairings with unprecedented volume-lift capability. The vehicle's mass-lift capability also means that it offers extremely high characteristic energy for missions into deep space. This paper will discuss the impacts that these factors - mass-lift, volume, and characteristic energy - have on a variety of mission classes, particularly human exploration and space science. It will address the vehicle's capability to enable existing architectures for deep-space exploration, such as those documented in the Global Exploration Roadmap, a capabilities-driven outline for future deep-space voyages created by the International Space Exploration Coordination Group, which represents 14 of the world's space agencies. In addition, this paper will detail this new rocket's capability to support missions beyond the human exploration roadmap, including robotic precursor missions to other worlds or uniquely high-mass space operation facilities in Earth orbit. As this paper will explain, the SLS Program is currently building a global infrastructure asset that will provide robust space launch capability to deliver sustainable solutions for exploration.
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NASA's Space Launch System: A Cornerstone Capability for Exploration
NASA Technical Reports Server (NTRS)
Creech, Stephen D.
2014-01-01
Under construction today, the National Aeronautics and Space Administration's (NASA) Space Launch System (SLS), managed at the Marshall Space Flight Center, will provide a robust new capability for human and robotic exploration beyond Earth orbit. The vehicle's initial configuration, scheduled for first launch in 2017, will enable human missions into lunar space and beyond, as well as provide game-changing benefits for space science missions, including offering substantially reduced transit times for conventionally designed spacecraft. From there, the vehicle will undergo a series of block upgrades via an evolutionary development process designed to expedite mission capture as capability increases. The Space Launch System offers multiple benefits for a variety of utilization areas. From a mass-lift perspective, the initial configuration of the vehicle, capable of delivering 70 metric tons (t) to low Earth orbit (LEO), will be the world's most powerful launch vehicle. Optimized for missions beyond Earth orbit, it will also be the world's only exploration-class launch vehicle capable of delivering 25 t to lunar orbit. The evolved configuration, with a capability of 130 t to LEO, will be the most powerful launch vehicle ever flown. From a volume perspective, SLS will be compatible with the payload envelopes of contemporary launch vehicles, but will also offer options for larger fairings with unprecedented volume-lift capability. The vehicle's mass-lift capability also means that it offers extremely high characteristic energy for missions into deep space. This paper will discuss the impacts that these factors - mass-lift, volume, and characteristic energy - have on a variety of mission classes, particularly human exploration and space science. It will address the vehicle's capability to enable existing architectures for deep-space exploration, such as those documented in the Global Exploration Roadmap, a capabilities-driven outline for future deep-space voyages created by the International Space Exploration Coordination Group, which represents 12 of the world's space agencies. In addition, this paper will detail this new rocket's capability to support missions beyond the human exploration roadmap, including robotic precursor missions to other worlds or uniquely high-mass space operation facilities in Earth orbit. As this paper will explain, the SLS Program is currently building a global infrastructure asset that will provide robust space launch capability to deliver sustainable solutions for exploration.
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Human Factors Directions for Civil Aviation
NASA Technical Reports Server (NTRS)
Hart, Sandra G.
2002-01-01
Despite considerable progress in understanding human capabilities and limitations, incorporating human factors into aircraft design, operation, and certification, and the emergence of new technologies designed to reduce workload and enhance human performance in the system, most aviation accidents still involve human errors. Such errors occur as a direct or indirect result of untimely, inappropriate, or erroneous actions (or inactions) by apparently well-trained and experienced pilots, controllers, and maintainers. The field of human factors has solved many of the more tractable problems related to simple ergonomics, cockpit layout, symbology, and so on. We have learned much about the relationships between people and machines, but know less about how to form successful partnerships between humans and the information technologies that are beginning to play a central role in aviation. Significant changes envisioned in the structure of the airspace, pilots and controllers' roles and responsibilities, and air/ground technologies will require a similarly significant investment in human factors during the next few decades to ensure the effective integration of pilots, controllers, dispatchers, and maintainers into the new system. Many of the topics that will be addressed are not new because progress in crucial areas, such as eliminating human error, has been slow. A multidisciplinary approach that capitalizes upon human studies and new classes of information, computational models, intelligent analytical tools, and close collaborations with organizations that build, operate, and regulate aviation technology will ensure that the field of human factors meets the challenge.
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Interleukin 6 stimulates hepatic glucose release from prelabeled glycogen pools
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ritchie, D.G.
1990-01-01
Cytokines, derived from a wide variety of cell types, are now believed to initiate many of the physiological responses accompanying the inflammatory phase that follows either Gram-negative septicemia or thermal injury. Because hypoglycemia (after endotoxic challenge) and hyperglycemia (after thermal injury) represent well-characterized responses to these injuries, we sought to determine whether hepatic glycogen metabolism could be altered by specific cytokines. Cultured adult rat hepatocytes were prelabeled with ({sup 14}C)glucose for 24 h, a procedure that resulted in the labeling of hepatic glycogen pools that subsequently could be depleted (with concomitant ({sup 14}C)glucose release) by either glucagon or norepinephrine. Aftermore » the addition of a highly concentrated human monocyte-conditioned medium (MCM) or various cytokines to these prelabeled cells, ({sup 14}C)glucose release was stimulated by MCM and recombinant human interleukin 6 (IL-6) but was not stimulated by other cytokines tested. Furthermore, only antisera to IL-6 were capable of reducing the glucose-releasing factor activity found in MCM. These data therefore suggest a novel glucoregulatory role for IL-6.« less
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Zivcec, Marko; Safronetz, David; Scott, Dana; Robertson, Shelly; Ebihara, Hideki; Feldmann, Heinz
2013-01-01
Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed viral hemorrhagic fever characterized by rapid onset of flu-like symptoms often followed by hemorrhagic manifestations. CCHF virus (CCHFV), a bunyavirus in the Nairovirus genus, is capable of infecting a wide range of mammalian hosts in nature but so far only causes disease in humans. Recently, immunocompromised mice have been reported as CCHF disease models, but detailed characterization is lacking. Here, we closely followed infection and disease progression in CCHFV-infected interferon α/β receptor knockout (IFNAR−/−) mice and age-matched wild-type (WT) mice. WT mice quickly clear CCHFV without developing any disease signs. In contrast, CCHFV infected IFNAR−/− mice develop an acute fulminant disease with high viral loads leading to organ pathology (liver and lymphoid tissues), marked proinflammatory host responses, severe thrombocytopenia, coagulopathy, and death. Disease progression closely mimics hallmarks of human CCHF disease, making IFNAR−/− mice an excellent choice to assess medical countermeasures. PMID:23417661
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Using video playbacks to study visual communication in a marine fish, Salaria pavo.
Gonçalves; Oliveira; Körner; Poschadel; Schlupp
2000-09-01
Video playbacks have been successfully applied to the study of visual communication in several groups of animals. However, this technique is controversial as video monitors are designed with the human visual system in mind. Differences between the visual capabilities of humans and other animals will lead to perceptually different interpretations of video images. We simultaneously presented males and females of the peacock blenny, Salaria pavo, with a live conspecific male and an online video image of the same individual. Video images failed to elicit appropriate responses. Males were aggressive towards the live male but not towards video images of the same male. Similarly, females courted only the live male and spent more time near this stimulus. In contrast, females of the gynogenetic poecilid Poecilia formosa showed an equal preference for a live and video image of a P. mexicana male, suggesting a response to live animals as strong as to video images. We discuss differences between the species that may explain their opposite reaction to video images. Copyright 2000 The Association for the Study of Animal Behaviour.
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Genetic polymorphisms of molecules involved in host immune response to dengue virus infection.
Fang, Xin; Hu, Zhen; Shang, Weilong; Zhu, Junmin; Xu, Chuanshan; Rao, Xiancai
2012-11-01
The dengue virus (DENV) belongs to the flavivirus family. Each of the four distinct serotypes of this virus is capable of causing human disease, especially in tropical and subtropical areas. The majority of people infected with DENV manifest asymptomatic or dengue fever with flu-like self-limited symptoms. However, a small portion of patients emerge with severe manifestations referred to as dengue hemorrhagic fever, which has a high mortality rate if not treated promptly. The host immune system, which plays important roles throughout the whole process of DENV infection, has been confirmed to have double-edged effects on DENV infection. Recently, much attention has been paid to the genetic heterogeneity of molecules involved in the host immune response to DENV infection. This heterogeneity has been proved to be the determining factor for DENV disease orientation. The present review discusses the primary functions and single nucleotide polymorphisms of some critical molecules in the human DENV immunological defense, especially the polymorphism locus associated with the DENV pathogenesis and disease susceptibility. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.
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Using machine learning to emulate human hearing for predictive maintenance of equipment
NASA Astrophysics Data System (ADS)
Verma, Dinesh; Bent, Graham
2017-05-01
At the current time, interfaces between humans and machines use only a limited subset of senses that humans are capable of. The interaction among humans and computers can become much more intuitive and effective if we are able to use more senses, and create other modes of communicating between them. New machine learning technologies can make this type of interaction become a reality. In this paper, we present a framework for a holistic communication between humans and machines that uses all of the senses, and discuss how a subset of this capability can allow machines to talk to humans to indicate their health for various tasks such as predictive maintenance.
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Glassman, E Katelyn; Hughes, Michelle L
2013-01-01
Current cochlear implants (CIs) have telemetry capabilities for measuring the electrically evoked compound action potential (ECAP). Neural Response Telemetry (Cochlear) and Neural Response Imaging (Advanced Bionics [AB]) can measure ECAP responses across a range of stimulus levels to obtain an amplitude growth function. Software-specific algorithms automatically mark the leading negative peak, N1, and the following positive peak/plateau, P2, and apply linear regression to estimate ECAP threshold. Alternatively, clinicians may apply expert judgments to modify the peak markers placed by the software algorithms, or use visual detection to identify the lowest level yielding a measurable ECAP response. The goals of this study were to: (1) assess the variability between human and computer decisions for (a) marking N1 and P2 and (b) determining linear-regression threshold (LRT) and visual-detection threshold (VDT); and (2) compare LRT and VDT methods within and across human- and computer-decision methods. ECAP amplitude-growth functions were measured for three electrodes in each of 20 ears (10 Cochlear Nucleus® 24RE/CI512, and 10 AB CII/90K). LRT, defined as the current level yielding an ECAP with zero amplitude, was calculated for both computer- (C-LRT) and human-picked peaks (H-LRT). VDT, defined as the lowest level resulting in a measurable ECAP response, was also calculated for both computer- (C-VDT) and human-picked peaks (H-VDT). Because Neural Response Imaging assigns peak markers to all waveforms but does not include waveforms with amplitudes less than 20 μV in its regression calculation, C-VDT for AB subjects was defined as the lowest current level yielding an amplitude of 20 μV or more. Overall, there were significant correlations between human and computer decisions for peak-marker placement, LRT, and VDT for both manufacturers (r = 0.78-1.00, p < 0.001). For Cochlear devices, LRT and VDT correlated equally well for both computer- and human-picked peaks (r = 0.98-0.99, p < 0.001), which likely reflects the well-defined Neural Response Telemetry algorithm and the lower noise floor in the 24RE and CI512 devices. For AB devices, correlations between LRT and VDT for both peak-picker methods were weaker than for Cochlear devices (r = 0.69-0.85, p < 0.001), which likely reflect the higher noise floor of the system. Disagreement between computer and human decisions regarding the presence of an ECAP response occurred for 5 % of traces for Cochlear devices and 2.1 % of traces for AB devices. Results indicate that human and computer peak-picking methods can be used with similar accuracy for both Cochlear and AB devices. Either C-VDT or C-LRT can be used with equal confidence for Cochlear 24RE and CI512 recipients because both methods are strongly correlated with human decisions. However, for AB devices, greater variability exists between different threshold-determination methods. This finding should be considered in the context of using ECAP measures to assist with programming CIs.
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Science strategy for human exploration of Mars.
Stoker, C R; McKay, C P; Haberle, R M; Andersen, D T
1992-01-01
The scientific objectives of Mars exploration can be framed within the overarching theme of exploring Mars as another home for life, both for evidence of past or present life on Mars, and as a potential future home for human life. The two major areas of research within this theme are: 1) determining the relationship between planetary evolution, climate change, and life, and 2) determining the habitability of Mars. Within this framework, this paper discusses the exploration objectives for exobiology, climatology and atmospheric science, geology, and martian resource assessment. Human exploration will proceed in four major phases: 1) Precursor missions which will obtain environmental knowledge necessary for human exploration, 2) Emplacement phase which includes the first few human landings where crews will explore the local area of the landing site; 3) Consolidation phase missions where a permanent base will be constructed and crews will be capable of detailed exploration over regional scales; 4) Utilization phase, in which a continuously occupied permanent Mars base exists and humans will be capable of detailed global exploration of the martian surface. The phases of exploration differ primarily in the range and capabilities of human mobility. In the emplacement phase, an unpressurized rover, similar to the Apollo lunar rover, will be used and will have a range of a few tens of kilometers. In the Consolidation phase, mobility will be via a pressurized all-terrain vehicle capable of expeditions from the base site of several weeks duration. In the Utilization phase, humans will be capable of several months long expeditions to any point on the surface of Mars using a suborbital rocket equipped with habitat, lab, and return vehicle. Because of human mobility limitations, it is important to extend the range and duration of exploration in all phases by using teleoperated rover vehicles. Site selection for human missions to Mars must consider the multi-decade time frame of these four phases. We suggest that operations in the first two phases be focused in the regional area containing the Coprates Quadrangle and adjacent areas.
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Human Factors Lessons Learned from Flight Testing Wingless Lifting Body Vehicles
NASA Technical Reports Server (NTRS)
Merlin, Peter William
2014-01-01
Since the 1960s, NASA, the Air Force, and now private industry have attempted to develop an operational human crewed reusable spacecraft with a wingless, lifting body configuration. This type of vehicle offers increased mission flexibility and greater reentry cross range than capsule type craft, and is particularly attractive due to the capability to land on a runway. That capability, however, adds complexity to the human factors engineering requirements of developing such aircraft.
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Critical Questions for Space Human Factors
NASA Technical Reports Server (NTRS)
Woolford, Barbara; Bagian, Tandi
2000-01-01
Traditional human factors contributions to NASA's crewed space programs have been rooted in the classic approaches to quantifying human physical and cognitive capabilities and limitations in the environment of interest, and producing recommendations and standards for the selection or design of mission equipment. Crews then evaluate the interfaces, displays, or equipment, and with the assistance of human factors experts, improvements are made as funds, time, control documentation, and weight allow. We have come a long way from the early spaceflight days, where men with the ' right stuff were the solution to operating whatever equipment was given to them. The large and diverse Shuttle astronaut corps has impacted mission designs to accommodate a wide range of human capabilities and preferences. Yet with existing long duration experience, we have seen the need to address a different set of dynamics when designing for optimal crew performance: critical equipment and mission situations degrade, and human function changes with mission environment, situation, and duration. Strategies for quantifying the critical nature of human factors requirements are being worked by NASA. Any exploration-class mission will place new responsibilities on mission designers to provide the crew with the information and resources to accomplish the mission. The current duties of a Mission Control Center to monitor system status, detect degradation or malfunction, and provide a proven solution, will need to be incorporated into on-board systems to allow the crew autonomous decision-making. The current option to resupply and replace mission systems and resources, including both vehicle equipment and human operators, will be removed, so considerations of maintenance, onboard training, and proficiency assessment are critical to providing a self-sufficient crew. As we 'move in' to the International Space Station, there are tremendous opportunities to investigate our ability to design for autonomous crews. Yet prioritizing the research that can and should be done by NASA will be based on the critical nature of the issues, and the impact of the individual research questions on mission design. The risks to crew health and safety associated with answering critical human factors issues must be properly included and communicated in order to support the Agency's decisions regarding future space programs.
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The Interplay of IL-21 and BAFF in the Formation and Maintenance of Human B Cell Memory
Karnell, Jodi L.; Ettinger, Rachel
2011-01-01
To date, IL-21 stands out as the most influential cytokine for human B cell activation and differentiation. Indeed, when compared to other important B cell tropic cytokines such as IL-2, IL-4, IL-6 and IL-10, IL-21 is clearly the most potent in terms of its ability to influence humoral immune responses in humans. IL-21 has wide reaching actions in determining how B cells will respond to co-stimulation ranging from induction of cell death upon BCR crosslinking to potent induction of class switch recombination and plasma cell differentiation when CD40 molecules are co-engaged. Another crucial B cell factor, exemplified in recent clinical trials, is BAFF/BLys. BAFF plays a critical role in the survival of human B cells and plasma blasts and influences B cell expansion and migration. Recent evidence has shown that IL-21 and BAFF can work in concert to promote and perhaps maintain humoral immunity in humans. Notably, BAFF has the unique ability to substitute for CD40L activities in regard to IL-21-co-stimulation and differentiation of a specific B cell subpopulation located in the human splenic marginal zone. However, and perhaps surprisingly, BAFF signals do not have the capability to override IL-21-driven cell death events when BCR is engaged. In stark contrast, anti-CD40 ligation of B cells co-activated with IL-21 and anti-IgM not only reverses this aforementioned activation-induced cell death, but transforms this death signal into one that drives plasma cell differentiation. Here we will discuss these two critical B cell factors, IL-21 and BAFF, and their distinct and complimentary effects on human B cell responses. PMID:22566888
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Proteomic analyses of host and pathogen responses during bovine mastitis.
Boehmer, Jamie L
2011-12-01
The pursuit of biomarkers for use as clinical screening tools, measures for early detection, disease monitoring, and as a means for assessing therapeutic responses has steadily evolved in human and veterinary medicine over the past two decades. Concurrently, advances in mass spectrometry have markedly expanded proteomic capabilities for biomarker discovery. While initial mass spectrometric biomarker discovery endeavors focused primarily on the detection of modulated proteins in human tissues and fluids, recent efforts have shifted to include proteomic analyses of biological samples from food animal species. Mastitis continues to garner attention in veterinary research due mainly to affiliated financial losses and food safety concerns over antimicrobial use, but also because there are only a limited number of efficacious mastitis treatment options. Accordingly, comparative proteomic analyses of bovine milk have emerged in recent years. Efforts to prevent agricultural-related food-borne illness have likewise fueled an interest in the proteomic evaluation of several prominent strains of bacteria, including common mastitis pathogens. The interest in establishing biomarkers of the host and pathogen responses during bovine mastitis stems largely from the need to better characterize mechanisms of the disease, to identify reliable biomarkers for use as measures of early detection and drug efficacy, and to uncover potentially novel targets for the development of alternative therapeutics. The following review focuses primarily on comparative proteomic analyses conducted on healthy versus mastitic bovine milk. However, a comparison of the host defense proteome of human and bovine milk and the proteomic analysis of common veterinary pathogens are likewise introduced.
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The Anopheles innate immune system in the defense against malaria infection
Clayton, April M.; Dong, Yuemei; Dimopoulos, George
2014-01-01
The multifaceted innate immune system of insects is capable of fighting infection by a variety of pathogens including those causing human malaria. Malaria transmission by the Anopheles mosquito depends on the Plasmodium parasite’s successful completion of its lifecycle in the insect vector, a process that involves interactions with several tissues and cell types as well as with the mosquito’s innate immune system. This review will discuss our current understanding of the Anopheles mosquito’s innate immune responses against the malaria parasite Plasmodium and the influence of the insect’s intestinal microbiota on parasite infection. PMID:23988482
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Minimal olfactory perception during sleep: why odor alarms will not work for humans.
Carskadon, Mary A; Herz, Rachel S
2004-05-01
To examine olfactory arousal threshold during sleep in comparison to an auditory tone. On night 1, participants rated odor intensity when awake and experienced olfactory stimuli during stage 1 sleep. Night 2 involved stage 2, stage 4, and rapid-eye-movement (REM) sleep trials using the "staircase" threshold-detection method. Electroencephalogram, electrooculogram, electromyogram, electrocardiogram, and respiration were recorded along with behavioral response. An 800-Hz tone was given on trials when odors failed to arouse. Participants slept in individual rooms. Stimulus-delivery systems were operated from a separate room, where an experimenter observed physiologic recordings and behavioral responses. Three healthy men and 3 women aged 20 to 25 years (mean, 22 years). Two odorants, peppermint and pyridine, at 4 concentrations were presented through nasal cannulas using an air-dilution olfactometer. Tones were played over a speaker. Behavioral (button press and oral) responses, electroencephalographic activation, and changes in breathing and heart rate were assessed. Participants responded to odors on 92% of stage 1 sleep trials. Peppermint was ineffective in stages 2, 4, and REM sleep. Pyridine produced behavioral threshold on 45% of stage 2 trials, none in stage 4, and one third of REM sleep trials. Tones were effective on at least 75% of trials. Heart rate increased significantly only following behavioral responses to odors or tones across sleep stages. The data indicate that human olfaction is not reliably capable of alerting a sleeper.
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Human-Robot Teaming in a Multi-Agent Space Assembly Task
NASA Technical Reports Server (NTRS)
Rehnmark, Fredrik; Currie, Nancy; Ambrose, Robert O.; Culbert, Christopher
2004-01-01
NASA's Human Space Flight program depends heavily on spacewalks performed by pairs of suited human astronauts. These Extra-Vehicular Activities (EVAs) are severely restricted in both duration and scope by consumables and available manpower. An expanded multi-agent EVA team combining the information-gathering and problem-solving skills of humans with the survivability and physical capabilities of robots is proposed and illustrated by example. Such teams are useful for large-scale, complex missions requiring dispersed manipulation, locomotion and sensing capabilities. To study collaboration modalities within a multi-agent EVA team, a 1-g test is conducted with humans and robots working together in various supporting roles.
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A multimodal interface for real-time soldier-robot teaming
NASA Astrophysics Data System (ADS)
Barber, Daniel J.; Howard, Thomas M.; Walter, Matthew R.
2016-05-01
Recent research and advances in robotics have led to the development of novel platforms leveraging new sensing capabilities for semantic navigation. As these systems becoming increasingly more robust, they support highly complex commands beyond direct teleoperation and waypoint finding facilitating a transition away from robots as tools to robots as teammates. Supporting future Soldier-Robot teaming requires communication capabilities on par with human-human teams for successful integration of robots. Therefore, as robots increase in functionality, it is equally important that the interface between the Soldier and robot advances as well. Multimodal communication (MMC) enables human-robot teaming through redundancy and levels of communications more robust than single mode interaction. Commercial-off-the-shelf (COTS) technologies released in recent years for smart-phones and gaming provide tools for the creation of portable interfaces incorporating MMC through the use of speech, gestures, and visual displays. However, for multimodal interfaces to be successfully used in the military domain, they must be able to classify speech, gestures, and process natural language in real-time with high accuracy. For the present study, a prototype multimodal interface supporting real-time interactions with an autonomous robot was developed. This device integrated COTS Automated Speech Recognition (ASR), a custom gesture recognition glove, and natural language understanding on a tablet. This paper presents performance results (e.g. response times, accuracy) of the integrated device when commanding an autonomous robot to perform reconnaissance and surveillance activities in an unknown outdoor environment.
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Lesterhuis, W Joost; Punt, Cornelis J A; Hato, Stanleyson V; Eleveld-Trancikova, Dagmar; Jansen, Bastiaan J H; Nierkens, Stefan; Schreibelt, Gerty; de Boer, Annemiek; Van Herpen, Carla M L; Kaanders, Johannes H; van Krieken, Johan H J M; Adema, Gosse J; Figdor, Carl G; de Vries, I Jolanda M
2011-08-01
Tumor microenvironments feature immune inhibitory mechanisms that prevent T cells from generating effective antitumor immune responses. Therapeutic interventions aimed at disrupting these inhibitory mechanisms have been shown to enhance antitumor immunity, but they lack direct cytotoxic effects. Here, we investigated the effect of cytotoxic cancer chemotherapeutics on immune inhibitory pathways. We observed that exposure to platinum-based chemotherapeutics markedly reduced expression of the T cell inhibitory molecule programmed death receptor-ligand 2 (PD-L2) on both human DCs and human tumor cells. Downregulation of PD-L2 resulted in enhanced antigen-specific proliferation and Th1 cytokine secretion as well as enhanced recognition of tumor cells by T cells. Further analysis revealed that STAT6 controlled downregulation of PD-L2. Consistent with these data, patients with STAT6-expressing head and neck cancer displayed enhanced recurrence-free survival upon treatment with cisplatin-based chemoradiation compared with patients with STAT6-negative tumors, demonstrating the clinical relevance of platinum-induced STAT6 modulation. We therefore conclude that platinum-based anticancer drugs can enhance the immunostimulatory potential of DCs and decrease the immunosuppressive capability of tumor cells. This dual action of platinum compounds may extend their therapeutic application in cancer patients and provides a rationale for their use in combination with immunostimulatory compounds.
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Chang, Hochan; Kim, Sungwoong; Jin, Sumin; Lee, Seung-Woo; Yang, Gil-Tae; Lee, Ki-Young; Yi, Hyunjung
2018-01-10
Flexible piezoresistive sensors have huge potential for health monitoring, human-machine interfaces, prosthetic limbs, and intelligent robotics. A variety of nanomaterials and structural schemes have been proposed for realizing ultrasensitive flexible piezoresistive sensors. However, despite the success of recent efforts, high sensitivity within narrower pressure ranges and/or the challenging adhesion and stability issues still potentially limit their broad applications. Herein, we introduce a biomaterial-based scheme for the development of flexible pressure sensors that are ultrasensitive (resistance change by 5 orders) over a broad pressure range of 0.1-100 kPa, promptly responsive (20 ms), and yet highly stable. We show that employing biomaterial-incorporated conductive networks of single-walled carbon nanotubes as interfacial layers of contact-based resistive pressure sensors significantly enhances piezoresistive response via effective modulation of the interlayer resistance and provides stable interfaces for the pressure sensors. The developed flexible sensor is capable of real-time monitoring of wrist pulse waves under external medium pressure levels and providing pressure profiles applied by a thumb and a forefinger during object manipulation at a low voltage (1 V) and power consumption (<12 μW). This work provides a new insight into the material candidates and approaches for the development of wearable health-monitoring and human-machine interfaces.
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Peng, Bing; Koga, Kaori; Cardenas, Ingrid; Aldo, Paulomi; Mor, Gil
2011-01-01
Problem Apoptosis is a normal constituent of trophoblast turnover in the placenta; however in some cases, this process is related to pregnancy complications such as preeclampsia. Recognition and engulfment of these apoptotic trophoblast cells is important for clearance of dying cells. The aim of this study was to show the cross talk between human endometrial endothelial cells (HEECs) and apoptotic trophoblast cells in an in vitro coculture model and its effect on cytokine production by HEECs. Method of study Fluorescent-labeled HEECs were cocultured with fluorescent-labeled apoptotic human trophoblast cells. Confocal microscopy and flowcytometry were used to show the interaction between these two types of cells. Cytokine profiles were determined using multiplex analysis. Results HEECs are capable to phagocytose apoptotic trophoblasts. This activity is inhibited by the phagocytosis inhibitor cytochalasin B. Phagocytosis of apoptotic trophoblast cells induced the secretion of the proinflammatory cytokines interleukin-6 and monocyte chemoattractant protein-1 by HEECs. Conclusion This study provides the first evidence that HEECs have an ability to phagocytose apoptotic trophoblasts. Furthermore, we demonstrated an inflammatory response of HEECs after phagocytosing the apoptotic trophoblast cells. This event may contribute to the inflammatory response in both normal pregnancy and pathologic pregnancy such as preeclampsia. PMID:20219062
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Applications of virtual reality technology in pathology.
Grimes, G J; McClellan, S A; Goldman, J; Vaughn, G L; Conner, D A; Kujawski, E; McDonald, J; Winokur, T; Fleming, W
1997-01-01
TelePath(SM) a telerobotic system utilizing virtual microscope concepts based on high quality still digital imaging and aimed at real-time support for surgery by remote diagnosis of frozen sections. Many hospitals and clinics have an application for the remote practice of pathology, particularly in the area of reading frozen sections in support of surgery, commonly called anatomic pathology. The goal is to project the expertise of the pathologist into the remote setting by giving the pathologist access to the microscope slides with an image quality and human interface comparable to what the pathologist would experience at a real rather than a virtual microscope. A working prototype of a virtual microscope has been defined and constructed which has the needed performance in both the image quality and human interface areas for a pathologist to work remotely. This is accomplished through the use of telerobotics and an image quality which provides the virtual microscope the same diagnostic capabilities as a real microscope. The examination of frozen sections is performed a two-dimensional world. The remote pathologist is in a virtual world with the same capabilities as a "real" microscope, but response times may be slower depending on the specific computing and telecommunication environments. The TelePath system has capabilities far beyond a normal biological microscope, such as the ability to create a low power image of the entire sample using multiple images digitally matched together; the ability to digitally retrace a viewing trajectory; and the ability to archive images using CD ROM and other mass storage devices.
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Human Factors Research for Space Exploration: Measurement, Modeling, and Mitigation
NASA Technical Reports Server (NTRS)
Kaiser, Mary K.; Allen, Christopher S.; Barshi, Immanuel; Billman, Dorrit; Holden, Kritina L.
2010-01-01
As part of NASA's Human Research Program, the Space Human Factors Engineering Project serves as the bridge between Human Factors research and Human Spaceflight applications. Our goal is to be responsive to the operational community while addressing issues at a sufficient level of abstraction to ensure that our tools and solutions generalize beyond the point design. In this panel, representatives from four of our research domains will discuss the challenges they face in solving current problems while also enabling future capabilities. Historically, engineering-dominated organizations have tended to view good Human Factors (HF) as a desire rather than a requirement in system design and development. Our field has made significant gains in the past decade, however; the Department of Defense, for example, now recognizes Human-System Integration (HSI), of which HF is a component, as an integral part of their divisions hardware acquisition processes. And our own agency was far more accepting of HF/HSI requirements during the most recent vehicle systems definition than in any prior cycle. Nonetheless, HF subject matter experts at NASA often find themselves in catch up mode... coping with legacy systems (hardware and software) and procedures that were designed with little regard for the human element, and too often with an attitude of we can deal with any operator issues during training. Our challenge, then, is to segregate the true knowledge gaps in Space Human Factors from the prior failures to incorporate best (or even good) HF design principles. Further, we strive to extract the overarching core HF issues from the point-design-specific concerns that capture the operators (and managers) attention. Generally, our approach embraces a 3M approach to Human Factors: Measurement, Modeling, and Mitigation. Our first step is to measure human performance, to move from subjective anecdotes to objective, quantified data. Next we model the phenomenon, using appropriate methods in our field, modifying them to suit the unique aspects of the space environment. Finally, we develop technologies, tools, and procedures to mitigate the decrements in human performance and capabilities that occur in space environments. When successful, we decrease risks to crew safety and to mission success. When extremely successful (or lucky), we devise generalizable solutions that advance the state of our practice. Our panel is composed of researchers from diverse domains of our project... from different boxes, if you will, of the Human Factors Analysis and Classification System (HFACS).
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Akao, T; Che, Q M; Kobashi, K; Yang, L; Hattori, M; Namba, T
1994-01-01
A strictly anaerobic bacterium capable of metabolizing sennosides was isolated from human feces and identified as Bifidobacterium sp., named strain SEN. The bacterium hydrolyzed sennosides A and B to sennidins A and B via sennidin A and B 8-monoglucosides, respectively. Among nine species of Bifidobacterium having beta-glucosidase activity, only Bifidobacterium dentium and B. adolescentis metabolized sennoside B to sennidin B, suggesting that the sennoside-metabolizing bacteria produce a novel type of beta-glucosidase capable of hydrolyzing sennosides to sennidins. PMID:8161172
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This Neural Implant is designed to be implanted in the Human Central and Nervous System
DOE Office of Scientific and Technical Information (OSTI.GOV)
None
A new class of neural implants being developed at the Livermore Lab are the first clinical quality devices capable of two-way conversations with the human nervous systems. Unlike existing interfaces that only sense or only stimulate, these devices are capable of stimulating and sensing using both electric and chemical signals.
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This Neural Implant is designed to be implanted in the Human Central and Nervous System
None
2018-06-12
A new class of neural implants being developed at the Livermore Lab are the first clinical quality devices capable of two-way conversations with the human nervous systems. Unlike existing interfaces that only sense or only stimulate, these devices are capable of stimulating and sensing using both electric and chemical signals.
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ERIC Educational Resources Information Center
Matheny, W. G.; And Others
The document presents a summary description of the Air Force Human Resource Laboratory's Flying Training Division (AFHRL/FT) research capabilities for undergraduate pilot training. One of the research devices investigated is the Advanced Simulator for Undergraduate Pilot Training (ASUPT). The equipment includes the ASUPT, the instrumented T-37…
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Stijlemans, Benoit; Radwanska, Magdalena; De Trez, Carl; Magez, Stefan
2017-01-01
African trypanosomosis is a debilitating disease of great medical and socioeconomical importance. It is caused by strictly extracellular protozoan parasites capable of infecting all vertebrate classes including human, livestock, and game animals. To survive within their mammalian host, trypanosomes have evolved efficient immune escape mechanisms and manipulate the entire host immune response, including the humoral response. This report provides an overview of how trypanosomes initially trigger and subsequently undermine the development of an effective host antibody response. Indeed, results available to date obtained in both natural and experimental infection models show that trypanosomes impair homeostatic B-cell lymphopoiesis, B-cell maturation and survival and B-cell memory development. Data on B-cell dysfunctioning in correlation with parasite virulence and trypanosome-mediated inflammation will be discussed, as well as the impact of trypanosomosis on heterologous vaccine efficacy and diagnosis. Therefore, new strategies aiming at enhancing vaccination efficacy could benefit from a combination of (i) early parasite diagnosis, (ii) anti-trypanosome (drugs) treatment, and (iii) anti-inflammatory treatment that collectively might allow B-cell recovery and improve vaccination. PMID:28596768
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Screening Immunomodulators To Skew the Antigen-Specific Autoimmune Response.
Northrup, Laura; Sullivan, Bradley P; Hartwell, Brittany L; Garza, Aaron; Berkland, Cory
2017-01-03
Current therapies to treat autoimmune diseases often result in side effects such as nonspecific immunosuppression. Therapies that can induce antigen-specific immune tolerance provide an opportunity to reverse autoimmunity and mitigate the risks associated with global immunosuppression. In an effort to induce antigen-specific immune tolerance, co-administration of immunomodulators with autoantigens has been investigated in an effort to reprogram autoimmunity. To date, identifying immunomodulators that may skew the antigen-specific immune response has been ad hoc at best. To address this need, we utilized splenocytes obtained from mice with experimental autoimmune encephalomyelitis (EAE) in order to determine if certain immunomodulators may induce markers of immune tolerance following antigen rechallenge. Of the immunomodulatory compounds investigated, only dexamethasone modified the antigen-specific immune response by skewing the cytokine response and decreasing T-cell populations at a concentration corresponding to a relevant in vivo dose. Thus, antigen-educated EAE splenocytes provide an ex vivo screen for investigating compounds capable of skewing the antigen-specific immune response, and this approach could be extrapolated to antigen-educated cells from other diseases or human tissues.
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Activated stress response pathways within multicellular aggregates utilize an autocrine component.
Jack, Graham D; Cabrera, M Carla; Manning, Michael L; Slaughter, Stephen M; Potts, Malcolm; Helm, Richard F
2007-04-01
Multicellular aggregates (spheroids) of primary human foreskin fibroblasts (HFF-2) and a glioblastoma cell line (T98G) entered and exited from long term (2 weeks) metabolic arrest utilizing an autocrine response. Cytokine production (specifically IFN-gamma) activated a Gadd45alpha/p38 pathway that led to increased AP-1 (c-jun and ATF3) transcription factor levels, augmenting cytokine production in an autocrine fashion. Whereas HFF-2 aggregates were capable of surviving long term arrest and recovery during NF-kappaB inhibition independent of JNK activation, T98G aggregates were not. Such endogenous processes are not easily observed with adherent monolayer cell culturing systems, strongly suggesting that more emphasis needs to be placed on determining the operational signal transduction cascades within multicellular aggregates. Extracellular inputs such as spheroid formation, arrest, and regrowth as monolayers invoke intracellular signaling responses converging at the AP-1 transcription factor level. Variations in responses are both cell type and transformation state dependent and require an autocrine cytokine component. The data are discussed in relation to the wounding response and avascular tumor growth mechanisms.
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Lowell, J.R. Jr.; Edlund, D.J.; Friesen, D.T.; Rayfield, G.W.
1992-06-09
Sensors responsive to small changes in the concentration of chemical species are disclosed, comprising a mechanicochemically responsive polymeric film capable of expansion or contraction in response to a change in its chemical environment, either operatively coupled to a transducer capable of directly converting the expansion or contraction to a measurable electrical or optical response, or adhered to a second inert polymeric strip, or doped with a conductive material. 12 figs.
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Strengthening global health security capacity--Vietnam demonstration project, 2013.
Tran, Phu Dac; Vu, Long Ngoc; Nguyen, Hien Tran; Phan, Lan Trong; Lowe, Wayne; McConnell, Michelle S; Iademarco, Michael F; Partridge, Jeffrey M; Kile, James C; Do, Trang; Nadol, Patrick J; Bui, Hien; Vu, Diep; Bond, Kyle; Nelson, David B; Anderson, Lauren; Hunt, Kenneth V; Smith, Nicole; Giannone, Paul; Klena, John; Beauvais, Denise; Becknell, Kristi; Tappero, Jordan W; Dowell, Scott F; Rzeszotarski, Peter; Chu, May; Kinkade, Carl
2014-01-31
Over the past decade, Vietnam has successfully responded to global health security (GHS) challenges, including domestic elimination of severe acute respiratory syndrome (SARS) and rapid public health responses to human infections with influenza A(H5N1) virus. However, new threats such as Middle East respiratory syndrome coronavirus (MERS-CoV) and influenza A(H7N9) present continued challenges, reinforcing the need to improve the global capacity to prevent, detect, and respond to public health threats. In June 2012, Vietnam, along with many other nations, obtained a 2-year extension for meeting core surveillance and response requirements of the 2005 International Health Regulations (IHR). During March-September 2013, CDC and the Vietnamese Ministry of Health (MoH) collaborated on a GHS demonstration project to improve public health emergency detection and response capacity. The project aimed to demonstrate, in a short period, that enhancements to Vietnam's health system in surveillance and early detection of and response to diseases and outbreaks could contribute to meeting the IHR core capacities, consistent with the Asia Pacific Strategy for Emerging Diseases. Work focused on enhancements to three interrelated priority areas and included achievements in 1) establishing an emergency operations center (EOC) at the General Department of Preventive Medicine with training of personnel for public health emergency management; 2) improving the nationwide laboratory system, including enhanced testing capability for several priority pathogens (i.e., those in Vietnam most likely to contribute to public health emergencies of international concern); and 3) creating an emergency response information systems platform, including a demonstration of real-time reporting capability. Lessons learned included awareness that integrated functions within the health system for GHS require careful planning, stakeholder buy-in, and intradepartmental and interdepartmental coordination and communication.
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Viral Vaccine Immunogenicity in Relation to Host Cell-Mediated and Humoral Immune Responses.
1976-05-01
adjuvants, particularly complete Freund’s adjuvant or Bordetella pertussis , were donors capable of consistently transferring adoptive immunity...vac- cine combined with adjuvants, particularly complete Freund’s adjuvant or Bordetella pertussis , were donors capable of consistently transferring...Freund’s adjuvant and Bordetella pertussis , are consistently capable of producing early and brisk serum neutralizing antibody responses in adoptively
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NASA Technical Reports Server (NTRS)
Shaffer, Lisa Robock
1992-01-01
The restructuring of the NASA Earth Observing System (EOS), designed to provide comprehensive long term observations from space of changes occurring on the Earth from natural and human causes in order to have a sound scientific basis for policy decisions on protection of the future, is reported. In response to several factors, the original program approved in the fiscal year 1991 budget was restructured and somewhat reduced in scope. The resulting program uses three different sized launch vehicles to put six different spacecraft in orbit in the first phase, followed by two replacement launches for each of five of the six satellites to maintain a long term observing capability to meet the needs of global climate change research and other science objectives. The EOS system, including the space observatories, the data and information system, and the interdisciplinary global change research effort, are approved and proceeding. Elements of EOS are already in place, such as the research investigations and initial data system capabilities. The flights of precursor satellite and Shuttle missions, the ongoing data analysis, and the evolutionary enhancements to the integrated Earth science data management capabilities are all important building blocks to the full EOS program.
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NASA Technical Reports Server (NTRS)
Gunasekara, Onalli; Wong, Uland Y.; Furlong, Michael P.; Dille, Michael
2017-01-01
Current technologies of exploring habitable areas of icy moons are limited to flybys of space probes. This research project addresses long-term navigation of icy moons by developing a MATLAB adjustable trajectory based on the volume of plume material observed. Plumes expose materials from the sub-surface without accessing the subsurface. Aerial vehicles capable of scouting vapor plumes and detecting maximum plume material volumes, which are considered potentially habitable in inhospitable environments, would enable future deep-space missions to search for extraterrestrial organisms on the surface of icy moons. Although this platform is still a prototype, it demonstrates the potential aerial vehicles can have in improving the capabilities of long-term space navigation and enabling technology for detecting life in extreme environments. Additionally, this work is developing the capabilities that could be utilized as a platform for space biology research. For example, aerial vehicles that are sent to map extreme environments of icy moons or the planet Mars, could also carry small payloads with automated cell-biology experiments, designed to probe the biological response of low-gravity and high-radiation planetary environments, serving as a pathfinder for future human missions.
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A capability model of individual differences in frontal EEG asymmetry.
Coan, James A; Allen, John J B; McKnight, Patrick E
2006-05-01
Researchers interested in measuring individual differences in affective style via asymmetries in frontal brain activity have depended almost exclusively upon the resting state for EEG recording. This reflects an implicit conceptualization of affective style as a response predisposition that is manifest in frontal EEG asymmetry, with the goal to describe individuals in terms of their general approach or withdrawal tendencies. Alternatively, the response capability conceptualization seeks to identify individual capabilities for approach versus withdrawal responses during emotionally salient events. The capability approach confers a variety of advantages to the study of affective style and personality, and suggests new possibilities for the approach/withdrawal motivational model of frontal EEG asymmetry and emotion. Logical as well as empirical arguments supportive of this conclusion are presented.
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Baj-Rossi, Camilla; De Micheli, Giovanni; Carrara, Sandro
2012-01-01
We report on the electrochemical detection of anti-cancer drugs in human serum with sensitivity values in the range of 8–925 nA/μM. Multi-walled carbon nanotubes were functionalized with three different cytochrome P450 isoforms (CYP1A2, CYP2B6, and CYP3A4). A model used to effectively describe the cytochrome P450 deposition onto carbon nanotubes was confirmed by Monte Carlo simulations. Voltammetric measurements were performed in phosphate buffer saline (PBS) as well as in human serum, giving well-defined current responses upon addition of increasing concentrations of anti-cancer drugs. The results assert the capability to measure concentration of drugs in the pharmacological ranges in human serum. Another important result is the possibility to detect pairs of drugs present in the same sample, which is highly required in case of therapies with high side-effects risk and in anti-cancer pharmacological treatments based on mixtures of different drugs. Our technology holds potentials for inexpensive multi-panel drug-monitoring in personalized therapy. PMID:22778656
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Study of Galfenol direct cytotoxicity and remote microactuation in cells.
Vargas-Estevez, Carolina; Blanquer, Andreu; Dulal, Prabesh; Pérez Del Real, Rafael; Duch, Marta; Ibáñez, Elena; Barrios, Leonardo; Murillo, Gonzalo; Torras, Núria; Nogués, Carme; Stadler, Bethanie J H; Plaza, José A; Esteve, Jaume
2017-09-01
Remote microactuators are of great interest in biology and medicine as minimally-invasive tools for cellular stimulation. Remote actuation can be achieved by active magnetostrictive transducers which are capable of changing shape in response to external magnetic fields thereby creating controlled displacements. Among the magnetostrictive materials, Galfenol, the multifaceted iron-based smart material, offers high magnetostriction with robust mechanical properties. In order to explore these capabilities for biomedical applications, it is necessary to study the feasibility of material miniaturization in standard fabrication processes as well as evaluate the biocompatibility. Here we develop a technology to fabricate, release, and suspend Galfenol-based microparticles, without affecting the integrity of the material. The morphology, composition and magnetic properties of the material itself are characterized. The direct cytotoxicity of Galfenol is evaluated in vitro using human macrophages, osteoblast and osteosarcoma cells. In addition, cytotoxicity and actuation of Galfenol microparticles in suspension are evaluated using human macrophages. The biological parameters analyzed indicate that Galfenol is not cytotoxic, even after internalization of some of the particles by macrophages. The microparticles were remotely actuated forming intra- and extracellular chains that did not impact the integrity of the cells. The results propose Galfenol as a suitable material to develop remote microactuators for cell biology studies and intracellular applications. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Faber, Milosz; Li, Jianwei; Kean, Rhonda B; Hooper, D Craig; Alugupalli, Kishore R; Dietzschold, Bernhard
2009-07-07
Rabies remains an important public health problem with more than 95% of all human rabies cases caused by exposure to rabid dogs in areas where effective, inexpensive vaccines are unavailable. Because of their ability to induce strong innate and adaptive immune responses capable of clearing the infection from the CNS after a single immunization, live-attenuated rabies virus (RV) vaccines could be particularly useful not only for the global eradication of canine rabies but also for late-stage rabies postexposure prophylaxis of humans. To overcome concerns regarding the safety of live-attenuated RV vaccines, we developed the highly attenuated triple RV G variant, SPBAANGAS-GAS-GAS. In contrast to most attenuated recombinant RVs generated thus far, SPBAANGAS-GAS-GAS is completely nonpathogenic after intracranial infection of mice that are either developmentally immunocompromised (e.g., 5-day-old mice) or have inherited deficits in immune function (e.g., antibody production or type I IFN signaling), as well as normal adult animals. In addition, SPBAANGAS-GAS-GAS induces immune mechanisms capable of containing a CNS infection with pathogenic RV, thereby preventing lethal rabies encephalopathy. The lack of pathogenicity together with excellent immunogenicity and the capacity to deliver immune effectors to CNS tissues makes SPBAANGAS-GAS-GAS a promising vaccine candidate for both the preexposure and postexposure prophylaxis of rabies.
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Saharan dust nutrients promote Vibrio bloom formation in marine surface waters.
Westrich, Jason R; Ebling, Alina M; Landing, William M; Joyner, Jessica L; Kemp, Keri M; Griffin, Dale W; Lipp, Erin K
2016-05-24
Vibrio is a ubiquitous genus of marine bacteria, typically comprising a small fraction of the total microbial community in surface waters, but capable of becoming a dominant taxon in response to poorly characterized factors. Iron (Fe), often restricted by limited bioavailability and low external supply, is an essential micronutrient that can limit Vibrio growth. Vibrio species have robust metabolic capabilities and an array of Fe-acquisition mechanisms, and are able to respond rapidly to nutrient influx, yet Vibrio response to environmental pulses of Fe remains uncharacterized. Here we examined the population growth of Vibrio after natural and simulated pulses of atmospherically transported Saharan dust, an important and episodic source of Fe to tropical marine waters. As a model for opportunistic bacterial heterotrophs, we demonstrated that Vibrio proliferate in response to a broad range of dust-Fe additions at rapid timescales. Within 24 h of exposure, strains of Vibrio cholerae and Vibrio alginolyticus were able to directly use Saharan dust-Fe to support rapid growth. These findings were also confirmed with in situ field studies; arrival of Saharan dust in the Caribbean and subtropical Atlantic coincided with high levels of dissolved Fe, followed by up to a 30-fold increase of culturable Vibrio over background levels within 24 h. The relative abundance of Vibrio increased from ∼1 to ∼20% of the total microbial community. This study, to our knowledge, is the first to describe Vibrio response to Saharan dust nutrients, having implications at the intersection of marine ecology, Fe biogeochemistry, and both human and environmental health.
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Building Organisational Capability the Private Provider Way
ERIC Educational Resources Information Center
Guthrie, Hugh
2008-01-01
Organisational capability is recognised as a key to organisational success. The combination of human capital (peoples' skills and knowledge), social capital (relationships between people) and organisational capital (the organisation's processes), is central to building an organisation's capability. This paper, presented at the 2008 annual…
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Widening Participation; Widening Capability
ERIC Educational Resources Information Center
Walker, Melanie
2008-01-01
This paper proposes that widening participation in higher education might distinctively be conceptualised beyond economically driven human capital outcomes, as a matter of widening capability. Specifically, the paper proposes forming the capability of students to become and to be "strong evaluators", able to make reflexive and informed…
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Playing to our human strengths to prepare medical students for the future
2017-01-01
We are living in an age where artificial intelligence and astounding technological advances are bringing truly remarkable change to healthcare. Medical knowledge and skills which form the core responsibility of doctors such as making diagnoses may increasingly be delivered by robots. Machines are gradually acquiring human abilities such as deep learning and empathy. What, then is the role of doctors in future healthcare? And what direction should medical schools be taking to prepare their graduates? This article will give an overview of the evolving technological landscape of healthcare and examine the issues undergraduate medical education may have to address. The experience at The University of Hong Kong will serve as a case study featuring several curricular innovations that aim to empower medical graduates with the capabilities to thrive in the future. PMID:28870022
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Ernstberger, Markus; Sichting, Freddy; Baselt, Tobias; Hartmann, Peter; Aust, Gabriela; Hammer, Niels
2013-06-01
Strain-dependent transmission data of nine iliotibial tract specimens are determined using a custom-built optical setup with a halogen light source and an industrial norm material testing machine. Polarized light microscopy and hematoxylin-eosin staining indicated that lateral contraction of collagen structures is responsible for total intensity variations during a 20-cycle preconditioning and a 5-cycle tensile test. Tensile force progress is opposite to total transmission progress. Due to dehydration, wavelength-specific radiation intensity shifting is determined during the test, primarily noticeable in a water absorption band between 1400 and 1500 nm. The results show the capability of integrating spectrophotometry technology into biomechanics for determining structural alterations of human collagen due to applied strain. Being more sensitive to drying, spectrophotometry may likely serve as a quality control in stress-strain testing of biological structures.
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Human-assisted sound event recognition for home service robots.
Do, Ha Manh; Sheng, Weihua; Liu, Meiqin
This paper proposes and implements an open framework of active auditory learning for a home service robot to serve the elderly living alone at home. The framework was developed to realize the various auditory perception capabilities while enabling a remote human operator to involve in the sound event recognition process for elderly care. The home service robot is able to estimate the sound source position and collaborate with the human operator in sound event recognition while protecting the privacy of the elderly. Our experimental results validated the proposed framework and evaluated auditory perception capabilities and human-robot collaboration in sound event recognition.
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NASA Technical Reports Server (NTRS)
Moffitt, William L.
2003-01-01
As missions have become increasingly more challenging over the years, the most adaptable and capable element of space shuttle operations has proven time and again to be human beings. Human space flight provides unique aspects of observation. interaction and intervention that can reduce risk and improve mission success. No other launch vehicle - in development or in operation today - can match the space shuttle's human space flight capabilities. Preserving U.S. leadership in human space flight requires a strategy to meet those challenges. The ongoing development of next generation vehicles, along with upgrades to the space shuttle, is the most effective means for assuring our access to space.
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Lunar base as a precursor to Mars exploration and settlement
NASA Technical Reports Server (NTRS)
Mendell, Wendell W.
1991-01-01
A well planned program of human exploration of the moon is suggested which would provide a base for increasing human capabilities and experience to levels required for Mars exploration. A strategy intended for immediate Mars exploration and settlement is considered to incur serious programmatic risks from current lack of knowledge on human performance on long-duration deep space missions and lack of experience in designing human space systems. The lunar program provides an opportunity to build up space capability in an evolutionary way and to broaden the participation of the educational system in the space exploration.
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Iannino, Florencia; Herrmann, Claudia K; Roset, Mara S; Briones, Gabriel
2015-05-05
Zoonoses that affect human and animal health have an important economic impact. In the study now presented, a bivalent vaccine has been developed that has the potential for preventing the transmission from cattle to humans of two bacterial pathogens: Brucella abortus and Shiga toxin-producing Escherichia coli (STEC). A 66kDa chimeric antigen, composed by EspA, Intimin, Tir, and H7 flagellin (EITH7) from STEC, was constructed and expressed in B. abortus Δpgm vaccine strain (BabΔpgm). Mice orally immunized with BabΔpgm(EITH7) elicited an immune response with the induction of anti-EITH7 antibodies (IgA) that clears an intestinal infection of E. coli O157:H7 three times faster (t=4 days) than mice immunized with BabΔpgm carrier strain (t=12 days). As expected, mice immunized with BabΔpgm(EITH7) strain also elicited a protective immune response against B. abortus infection. A Brucella-based vaccine platform is described capable of eliciting a combined protective immune response against two bacterial pathogens with diverse lifestyles-the intracellular pathogen B. abortus and the intestinal extracellular pathogen STEC. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Strange, Daniel P; Green, Richard; Siemann, David N; Gale, Michael; Verma, Saguna
2018-06-07
Confirmed reports of Zika virus (ZIKV) in seminal fluid months after clearance of viremia suggests that ZIKV can establish persistent infection in the seminiferous tubules, an immune privileged site of the testis. The seminiferous tubule epithelium is mainly composed of Sertoli cells that function to nourish and protect developing germ cells. We recently demonstrated that primary human Sertoli cells (hSeC) were highly susceptible to ZIKV as compared to dengue virus without causing cell death and thus may act as a reservoir for ZIKV in the testes. However, the cellular and immune responses of hSeC to infection with ZIKV or any other virus are not yet characterized. Using genome-wide RNA-seq to compare immunoprofiles of hSeC, we show that the most prominent response to ZIKV at early stage of infection was suppression of cell growth and proliferation functional pathways. Peak virus replication was associated with induction of multiple antiviral defense pathways. Unique ZIKV-associated signatures included dysregulation of germ cell-Sertoli cell junction signaling. This study demonstrates that hSeC are capable of signaling through canonical pro-inflammatory pathways and provides insights into unique cell-type-specific response induced by ZIKV in association with viral persistence in the testes.
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Inhibition of antigen- and mitogen-induced human lymphocyte proliferation by gold compounds.
Lipsky, P E; Ziff, M
1977-01-01
Gold sodium thiomalate (GST) inhibited in vitro antigen- and mitogen-triggered human lymphocyte DNA synthesis. Inhibition of responsiveness was observed with concentrations of GST equivalent to gold levels found in serum or tissues of patients receiving chrysotherapy, Inhibition was dependent upon the gold ion itself since GST and gold chloride were both inhibitory whereas thiomalic acid was not. Inhibition could not be explained by nonspecific killing of cells or by an alteration in the kinetics of the responses. GST inhibited mitogen-induced proliferation most effectively when present from the initiation of culture and could not inhibit the responsiveness of cells which previously had been activated by concanvalin A. These findings indicated that GST blocked a critical early step in lymphocyte activation. The degree of GST-induced inhibition of proliferation was increased in cultures of cells partially depleted of monocytes. Moreover, inhibition was reversed by supplementation of these cultures with purified monocytes. These observations suggested that GST blocked thymus-derived (T)-lymphocyte activation by interfering with a requisite function of the monocyte population in initiating such responses. Prolonged incubation of peripheral blood mononuclear cells with GST resulted in diminished mitogen responsiveness upon subsequent culture in the absence of gold. The addition of fresh monocytes restored responsiveness to these populations. Furthermore, preincubation of purified monocytes with GST rendered them deficient in their ability to support mitogen-induced T-lymphocyte proliferation on subsequent culture. These observations indicate that the major effect of GST results from interference with the functional capability of the monocyte population. PMID:838859
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Melatonin and its precursors in Y79 human retinoblastoma cells - Effect of sodium butyrate
NASA Technical Reports Server (NTRS)
Deng, Mei H.; Lopez G.-Coviella, Ignacio; Lynch, Harry J.; Wurtman, Richard J.
1991-01-01
We studied the release of melatonin and the production of its precursors, 5-hydroxytryptophan and serotonin, in cultured Y79 human retinoblastoma cells. This biosynthetic capability was found to be dependent on cell differentiation, which was initiated by culturing Y79 cells for 7 days in dishes coated with poly-D-lysine to promote cell adhesion to the surface of the culture dishes. Differentiation was further induced by exposing the cell monolayer to sodium butyrate (3 mM) for three days. This protocol dramatically increased the release of melatonin, and the syntheses of 5-hydroxytryptophan and serotonin in response to forskolin stimulation. Exposure to dopamine or L-DOPA markedly diminished the forskolin-stimulated release of melatonin, as well as the production of 5-hydroxytryptophan and serotonin. These observations indicate that Y79 cells represent a primitive cell line which, following appropriate differentiation can display biochemical characteristics similar to those of the human retina. Moreover, serotonin synthesis and melatonin release appear to be coupled in Y79 ceils.
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Human performance under two different command and control paradigms.
Walker, Guy H; Stanton, Neville A; Salmon, Paul M; Jenkins, Daniel P
2014-05-01
The paradoxical behaviour of a new command and control concept called Network Enabled Capability (NEC) provides the motivation for this paper. In it, a traditional hierarchical command and control organisation was pitted against a network centric alternative on a common task, played thirty times, by two teams. Multiple regression was used to undertake a simple form of time series analysis. It revealed that whilst the NEC condition ended up being slightly slower than its hierarchical counterpart, it was able to balance and optimise all three of the performance variables measured (task time, enemies neutralised and attrition). From this it is argued that a useful conceptual response is not to consider NEC as an end product comprised of networked computers and standard operating procedures, nor to regard the human system interaction as inherently stable, but rather to view it as a set of initial conditions from which the most adaptable component of all can be harnessed: the human. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.
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Scalable Algorithms for Global Scale Remote Sensing Applications
NASA Astrophysics Data System (ADS)
Vatsavai, R. R.; Bhaduri, B. L.; Singh, N.
2015-12-01
Recent decade has witnessed major changes on the Earth, for example, deforestation, varying cropping and human settlement patterns, and crippling damages due to disasters. Accurate damage assessment caused by major natural and anthropogenic disasters is becoming critical due to increases in human and economic loss. This increase in loss of life and severe damages can be attributed to the growing population, as well as human migration to the disaster prone regions of the world. Rapid assessment of these changes and dissemination of accurate information is critical for creating an effective emergency response. Change detection using high-resolution satellite images is a primary tool in assessing damages, monitoring biomass and critical infrastructures, and identifying new settlements. Existing change detection methods suffer from registration errors and often based on pixel (location) wise comparison of spectral observations from single sensor. In this paper we present a novel probabilistic change detection framework based on patch comparison and a GPU implementation that supports near real-time rapid damage exploration capability.
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Doell, Elizabeth; Clendon, Sally
2018-02-01
New Zealand Ministry of Education's proposal for an updated service to support children experiencing communication difficulties provides an opportunity to consider the essential criteria required for children to express their opinion, information and ideas as outlined under Article 19 of the Universal Declaration of Human Rights. This commentary begins with a summary of key policies that provide strategic direction for enhancing children's rights to be actively involved in the development of services designed to support them and to communicate and participate in inclusive environments. The authors use a human rights lens to inform the development of speech-language pathology services that facilitate individuals' contribution and engagement and are responsive to their needs. A review of international literature describing the lived experience of children and young people identifies key factors related to accessible information, service coordination, holistic practice, and partnerships that facilitate co-constructed understanding and decision-making. The commentary concludes with suggested recommendations for structuring services, establishing partnership models, and capability building.
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Baldridge, Jory R; McGowan, Patrick; Evans, Jay T; Cluff, Christopher; Mossman, Sally; Johnson, David; Persing, David
2004-07-01
Toll-like receptor (TLR) agonists are being developed for use as vaccine adjuvants and as stand-alone immunomodulators because of their ability to stimulate innate and adaptive immune responses. Among the most thoroughly studied TLR agonists are the lipid A molecules that target the TLR4 complex. One promising candidate, monophosphoryl lipid A, which is a derivative of lipid A from Salmonella minnesota, has proven to be safe and effective as a vaccine adjuvant in > 120,000 human doses. A new class of synthetic lipid A mimetics, the aminoalkyl glucosaminide 4-phosphates (AGPs), have been engineered specifically to target human TLR4 and are showing promise as vaccine adjuvants and as monotherapeutic agents capable of eliciting nonspecific protection against a wide range of infectious pathogens. In this review, the authors provide an update of the preclinical and clinical experiences with the TLR4 agonists, MPL (Corixa Corporation) adjuvant and the AGPs.
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Chicha, Laurie; Jarrossay, David; Manz, Markus G
2004-12-06
Because of different cytokine responsiveness, surface receptor, and transcription factor expression, human CD11c(-) natural type I interferon-producing cells (IPCs) and CD11c(+) dendritic cells were thought to derive through lymphoid and myeloid hematopoietic developmental pathways, respectively. To directly test this hypothesis, we used an in vitro assay allowing simultaneous IPC, dendritic cell, and B cell development and we tested lymphoid and myeloid committed hematopoietic progenitor cells for their developmental capacity. Lymphoid and common myeloid and granulocyte/macrophage progenitors were capable of developing into both functional IPCs, expressing gene transcripts thought to be associated with lymphoid lineage development, and into dendritic cells. However, clonal progenitors for both populations were about fivefold more frequent within myeloid committed progenitor cells. Thus, in humans as in mice, natural IPC and dendritic cell development robustly segregates with myeloid differentiation. This would fit with natural interferon type I-producing cell and dendritic cell activity in innate immunity, the evolutionary older arm of the cellular immune system.
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NASA Technical Reports Server (NTRS)
Mercer, Joey; Gomez, Ashley; Gabets, Cynthia; Bienert, Nancy; Edwards, Tamsyn; Martin, Lynne; Gujral, Vimmy; Homola, Jeffrey
2016-01-01
To determine the capabilities and limitations of human operators and automation in separation assurance roles, the second of three Human-in-the-Loop (HITL) part-task studies investigated air traffic controllers ability to detect and resolve conflicts under varying task sets, traffic densities, and run lengths. Operations remained within a single sector, staffed by a single controller, and explored, among other things, the controllers responsibility for conflict resolution with or without their involvement in the conflict detection task. Furthermore, these conditions were examined across two different traffic densities; 1x (current-day traffic) and a 20 increase above current-day traffic levels (1.2x). Analyses herein offer an examination of the conflict resolution strategies employed by controllers. In particular, data in the form of elapsed time between conflict detection and conflict resolution are used to assess if, and how, the controllers involvement in the conflict detection task affected the way in which they resolved traffic conflicts.
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Ultraviolet radiation directly induces pigment production by cultured human melanocytes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Friedmann, P.S.; Gilchrest, B.A.
1987-10-01
In humans the major stimulus for cutaneous pigmentation is ultraviolet radiation (UVR). Little is known about the mechanism underlying this response, in part because of the complexity of interactions in whole epidermis. Using a recently developed culture system, human melanocytes were exposed daily to a physiologic range of UVR doses from a solar simulator. Responses were determined 24 hours after the last exposure. There was a dose-related increase in melanin content per cell and uptake of /sup 14/C-DOPA, accompanied by growth inhibition. Cells from donors of different racial origin gave proportionately similar increases in melanin, although there were approximately tenfoldmore » differences in basal values. Light and electron microscopy revealed UVR-stimulated increases in dendricity as well as melanosome number and degree of melanization, analogous to the well-recognized melanocyte changes following sun exposure of intact skin. Similar responses were seen with Cloudman S91 melanoma cells, although this murine cell line required lower UVR dosages and fewer exposures for maximal stimulation. These data establish that UVR is capable of directly stimulating melanogenesis. Because cyclic AMP elevation has been associated in some settings with increased pigment production by cultured melanocytes, preliminary experiments were conducted to see if the effects of UVR were mediated by cAMP. Both alpha-MSH and isobutylmethylxanthine (IBMX), as positive controls, caused a fourfold increase in cAMP level in human melanocytes and/or S91 cells, but following a dose of UVR sufficient to stimulate pigment production there was no change in cAMP level up to 4 hours after exposure. Thus, it appears that the UVR-induced melanogenesis is mediated by cAMP-independent mechanisms.« less
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Model-based metrics of human-automation function allocation in complex work environments
NASA Astrophysics Data System (ADS)
Kim, So Young
Function allocation is the design decision which assigns work functions to all agents in a team, both human and automated. Efforts to guide function allocation systematically has been studied in many fields such as engineering, human factors, team and organization design, management science, and cognitive systems engineering. Each field focuses on certain aspects of function allocation, but not all; thus, an independent discussion of each does not address all necessary issues with function allocation. Four distinctive perspectives emerged from a review of these fields: technology-centered, human-centered, team-oriented, and work-oriented. Each perspective focuses on different aspects of function allocation: capabilities and characteristics of agents (automation or human), team structure and processes, and work structure and the work environment. Together, these perspectives identify the following eight issues with function allocation: 1) Workload, 2) Incoherency in function allocations, 3) Mismatches between responsibility and authority, 4) Interruptive automation, 5) Automation boundary conditions, 6) Function allocation preventing human adaptation to context, 7) Function allocation destabilizing the humans' work environment, and 8) Mission Performance. Addressing these issues systematically requires formal models and simulations that include all necessary aspects of human-automation function allocation: the work environment, the dynamics inherent to the work, agents, and relationships among them. Also, addressing these issues requires not only a (static) model, but also a (dynamic) simulation that captures temporal aspects of work such as the timing of actions and their impact on the agent's work. Therefore, with properly modeled work as described by the work environment, the dynamics inherent to the work, agents, and relationships among them, a modeling framework developed by this thesis, which includes static work models and dynamic simulation, can capture the issues with function allocation. Then, based on the eight issues, eight types of metrics are established. The purpose of these metrics is to assess the extent to which each issue exists with a given function allocation. Specifically, the eight types of metrics assess workload, coherency of a function allocation, mismatches between responsibility and authority, interruptive automation, automation boundary conditions, human adaptation to context, stability of the human's work environment, and mission performance. Finally, to validate the modeling framework and the metrics, a case study was conducted modeling four different function allocations between a pilot and flight deck automation during the arrival and approach phases of flight. A range of pilot cognitive control modes and maximum human taskload limits were also included in the model. The metrics were assessed for these four function allocations and analyzed to validate capability of the metrics to identify important issues in given function allocations. In addition, the design insights provided by the metrics are highlighted. This thesis concludes with a discussion of mechanisms for further validating the modeling framework and function allocation metrics developed here, and highlights where these developments can be applied in research and in the design of function allocations in complex work environments such as aviation operations.
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The human role in space: Technology, economics and optimization
NASA Technical Reports Server (NTRS)
Hall, S. B. (Editor)
1985-01-01
Man-machine interactions in space are explored in detail. The role and the degree of direct involvement of humans that will be required in future space missions are investigated. An attempt is made to establish valid criteria for allocating functional activities between humans and machines and to provide insight into the technological requirements, economics, and benefits of the human presence in space. Six basic categories of man-machine interactions are considered: manual, supported, augmented, teleoperated, supervised, and independent. Appendices are included which provide human capability data, project analyses, activity timeline profiles and data sheets for 37 generic activities, support equipment and human capabilities required in these activities, and cumulative costs as a function of activity for seven man-machine modes.
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SDI Software Technology Program Plan Version 1.5
1987-06-01
computer generation of auditory communication of meaningful speech. Most speech synthesizers are based on mathematical models of the human vocal tract, but...oral/ auditory and multimodal communications. Although such state-of-the-art interaction technology has not fully matured, user experience has...superior I pattern matching capabilities and the subliminal intuitive deduction capability. The error performance of humans can be helped by careful
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DoD Autonomy Roadmap: Autonomy Community of Interest
2015-03-24
Initiative 27 Exploiting Priming Effects Team (Navy) Develop machine perception relatable to the manner in which a human perceives the ...and trust among the team members; understanding of each member’s tasks, intentions, capabilities, and progress; and ensuring effective and timely...learning capabilities to greatly reduce the need for human interventions, while enabling effective teaming with the warfighter Machine Perception
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NASA Technical Reports Server (NTRS)
Linne, Diane L.; Sanders, Gerald B.; Taminger, Karen M.
2015-01-01
The capability for living off the land, commonly called in-situ resource utilization, is finally gaining traction in space exploration architectures. Production of oxygen from the Martian atmosphere is called an enabling technology for human return from Mars, and a flight demonstration to be flown on the Mars 2020 robotic lander is in development. However, many of the individual components still require technical improvements, and system-level trades will be required to identify the best combination of technology options. Based largely on work performed for two recent roadmap activities, this paper defines the capability and technology requirements that will need to be achieved before this game-changing capability can reach its full potential.
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Remote effects of intermittent theta burst stimulation of the human pharyngeal motor system
Mistry, Satish; Michou, Emilia; Rothwell, John; Hamdy, Shaheen
2015-01-01
Intermittent theta burst stimulation (iTBS) is a novel, non-invasive form of brain stimulation capable of facilitating excitability of the human primary motor cortex with therapeutic potential in the treatment of neurological conditions, such as multiple sclerosis. The objectives of this study were to evaluate the effects of iTBS on cortical properties in the human pharyngeal motor system. Transcranial magnetic stimulation (TMS)-evoked pharyngeal motor responses were recorded via a swallowed intra-luminal catheter and used to assess motor cortical pathways to the pharynx in both hemispheres before and for up to 90 min after iTBS in 15 healthy adults (nine male/six female, 22–59 years old). Active/sham iTBS comprised 600 intermittent repetitive TMS pulses, delivered in a double-blind pseudo-randomised order over each hemisphere on separate days at least 1 week apart. Abductor pollicis brevis (APB) recordings were used as control. Hemispheric interventional data were compared with sham using repeated-measures anova. iTBS was delivered at an average intensity of 43 ± 1% of stimulator output. Compared with sham, iTBS to the hemisphere with stronger pharyngeal projections induced increased responses only in the contralateral weaker projection 60–90 min post-iTBS (maximum 54 ± 19%, P ≤ 0.007), with no change in stronger hemisphere responses. By contrast, iTBS to weaker projections had no significant effects (P = 0.39) on either hemisphere. APB responses similarly did not change significantly (P = 0.78) across all study arms. We conclude that iTBS can induce remote changes in corticobulbar excitability. While further studies will clarify the extent of these changes, iTBS holds promise as a potential treatment for dysphagia after unilateral brain damage. PMID:22640033
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Getting Ahead of Oneself: Anticipation and the Vestibulo-ocular Reflex (VOR)
King, W. Michael
2014-01-01
Compensatory counter-rotations of the eyes provoked by head turns are commonly attributed to the vestibulo-ocular reflex (VOR). A recent study in guinea pigs demonstrates, however, that this assumption is not always valid. During voluntary head turns, guinea pigs make highly accurate compensatory eye movements that occur with zero or even negative latencies with respect to the onset of the provoking head movements. Furthermore, the anticipatory eye movements occur in animals with bilateral peripheral vestibular lesions, thus confirming that they have an extra vestibular origin. This discovery suggests the possibility that anticipatory responses might also occur in other species including humans and non-human primates, but have been overlooked and mistakenly identified as being produced by the VOR. This review will compare primate and guinea pig vestibular physiology in light of these new findings. A unified model of vestibular and cerebellar pathways will be presented that is consistent with current data in primates and guinea pigs. The model is capable of accurately simulating compensatory eye movements to active head turns (anticipatory responses) and to passive head perturbations (VOR induced eye movements) in guinea pigs and in human subjects who use coordinated eye and head movements to shift gaze direction in space. Anticipatory responses provide new evidence and opportunities to study the role of extra vestibular signals in motor control and sensory-motor transformations. Exercises that employ voluntary head turns are frequently used to improve visual stability in patients with vestibular hypofunction. Thus, a deeper understanding of the origin and physiology of anticipatory responses could suggest new translational approaches to rehabilitative training of patients with bilateral vestibular loss. PMID:23370320
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Pihlavisto, M; Scheinin, M
1999-12-03
We applied the Cytosensor Microphysiometry system to study the three human alpha(2)-adrenoceptor subtypes, alpha(2A), alpha(2B) and alpha(2C), expressed in Chinese hamster ovary (CHO) cells, and assessed its potential in the quantitative monitoring of agonist activity. The natural full agonist, (-)-noradrenaline, was used to define agonist efficacy. The imidazole derivative dexmedetomidine was a potent full agonist of all three receptor subtypes. The imidazolines clonidine and UK 14,304 (5-bromo-N-(4, 5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine) appeared to be partial agonists at alpha(2B)-adrenoceptors (E(max) approximately 60% of (-)-noradrenaline) but full agonists at alpha(2A)- and alpha(2C)-adrenoceptors. The responses mediated by all three alpha(2)-adrenoceptor subtypes were partly inhibited by the sodium-hydrogen (Na(+)/H(+)) exchange inhibitor, MIA (5-(N-methyl-N-isobutyl)-amiloride). The agonist responses were totally abolished by pretreatment with pertussis toxin in cells with alpha(2A)- and alpha(2C)-adrenoceptors, and partly abolished in cells with alpha(2B)-adrenoceptors. The residual signal in alpha(2B)-cells was sensitive to the intracellular Ca(2+)chelator, BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid acetoxymethyl ester). Cholera toxin (which acts on G(s)-proteins) had no effect on the agonist responses. The results suggest that the extracellular acidification responses mediated by all three human alpha(2)-adrenoceptor subtypes are dependent on Na(+)/H(+)exchange and G(i/o) pathways, and that alpha(2B)-adrenoceptors are capable of coupling to another, G(i/o)-independent and Ca(2+)-dependent signaling pathway.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Nara, P.L.; Robey, W.G.; Gonda, M.A.
1987-06-01
The presence of antibody-dependent complement-mediated cytotoxicity (ACC) was assessed in humans and chimpanzees, which are capable of infection with human immunodeficiency virus isolate HTLV-IIIb, and examined in the goat after immunization with the major viral glycoprotein (gp120) of HTLV-IIIb. In infected humans no antibody mediating ACC was observed regardless of the status of disease. Even healthy individuals with high-titer, broadly reactive, neutralizing antibodies has no ACC. In contrast, chimpanzees infected with HTLV-IIIb, from whom virus could be isolated, not only had neutralizing antibody but also antibodies broadly reactive in ACC, even against distantly related human immunodeficiency virus isolates, as wellmore » as against their own reisolated virus. In the goat, the gp120 of HTLV-IIIb induced a highly type-specific response as measured by both ACC and flow cytofluorometry of live infected H9 cells. Normal human cells were not subject to ACC by animal anti-HTLV-III gp120-specific sera. Induction of ACC and neutralizing antibody were closely correlated in the animal experimental models but not in humans. The presence of ACC in gp120-inoculated goats and HTLV-III-infected chimpanzees represent a qualitative difference that may be important in the quest for the elicitation of a protective immunity in humans.« less
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Bruin, Jennifer E; Rezania, Alireza; Xu, Jean; Narayan, Kavitha; Fox, Jessica K; O'Neil, John J; Kieffer, Timothy J
2013-09-01
Islet transplantation is a promising cell therapy for patients with diabetes, but it is currently limited by the reliance upon cadaveric donor tissue. We previously demonstrated that human embryonic stem cell (hESC)-derived pancreatic progenitor cells matured under the kidney capsule in a mouse model of diabetes into glucose-responsive insulin-secreting cells capable of reversing diabetes. However, the formation of cells resembling bone and cartilage was a major limitation of that study. Therefore, we developed an improved differentiation protocol that aimed to prevent the formation of off-target mesoderm tissue following transplantation. We also examined how variation within the complex host environment influenced the development of pancreatic progenitors in vivo. The hESCs were differentiated for 14 days into pancreatic progenitor cells and transplanted either under the kidney capsule or within Theracyte (TheraCyte, Laguna Hills, CA, USA) devices into diabetic mice. Our revised differentiation protocol successfully eliminated the formation of non-endodermal cell populations in 99% of transplanted mice and generated grafts containing >80% endocrine cells. Progenitor cells developed efficiently into pancreatic endocrine tissue within macroencapsulation devices, despite lacking direct contact with the host environment, and reversed diabetes within 3 months. The preparation of cell aggregates pre-transplant was critical for the formation of insulin-producing cells in vivo and endocrine cell development was accelerated within a diabetic host environment compared with healthy mice. Neither insulin nor exendin-4 therapy post-transplant affected the maturation of macroencapsulated cells. Efficient differentiation of hESC-derived pancreatic endocrine cells can occur in a macroencapsulation device, yielding glucose-responsive insulin-producing cells capable of reversing diabetes.
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The Exercise–Affect–Adherence Pathway: An Evolutionary Perspective
Lee, Harold H.; Emerson, Jessica A.; Williams, David M.
2016-01-01
The low rates of regular exercise and overall physical activity (PA) in the general population represent a significant public health challenge. Previous research suggests that, for many people, exercise leads to a negative affective response and, in turn, reduced likelihood of future exercise. The purpose of this paper is to examine this exercise–affect–adherence relationship from an evolutionary perspective. Specifically, we argue that low rates of physical exercise in the general population are a function of the evolved human tendency to avoid unnecessary physical exertion. This innate tendency evolved because it allowed our evolutionary ancestors to conserve energy for physical activities that had immediate adaptive utility such as pursuing prey, escaping predators, and engaging in social and reproductive behaviors. The commonly observed negative affective response to exercise is an evolved proximate psychological mechanism through which humans avoid unnecessary energy expenditure. The fact that the human tendencies toward negative affective response to and avoidance of unnecessary physical activities are innate does not mean that they are unchangeable. Indeed, it is only because of human-engineered changes in our environmental conditions (i.e., it is no longer necessary for us to work for our food) that our predisposition to avoid unnecessary physical exertion has become a liability. Thus, it is well within our capabilities to reengineer our environments to once again make PA necessary or, at least, to serve an immediate functional purpose. We propose a two-pronged approach to PA promotion based on this evolutionary functional perspective: first, to promote exercise and other physical activities that are perceived to have an immediate purpose, and second, to instill greater perceived purpose for a wider range of physical activities. We posit that these strategies are more likely to result in more positive (or less negative) affective responses to exercise, better adherence to exercise programs, and higher rates of overall PA. PMID:27610096
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Sensing Super-position: Visual Instrument Sensor Replacement
NASA Technical Reports Server (NTRS)
Maluf, David A.; Schipper, John F.
2006-01-01
The coming decade of fast, cheap and miniaturized electronics and sensory devices opens new pathways for the development of sophisticated equipment to overcome limitations of the human senses. This project addresses the technical feasibility of augmenting human vision through Sensing Super-position using a Visual Instrument Sensory Organ Replacement (VISOR). The current implementation of the VISOR device translates visual and other passive or active sensory instruments into sounds, which become relevant when the visual resolution is insufficient for very difficult and particular sensing tasks. A successful Sensing Super-position meets many human and pilot vehicle system requirements. The system can be further developed into cheap, portable, and low power taking into account the limited capabilities of the human user as well as the typical characteristics of his dynamic environment. The system operates in real time, giving the desired information for the particular augmented sensing tasks. The Sensing Super-position device increases the image resolution perception and is obtained via an auditory representation as well as the visual representation. Auditory mapping is performed to distribute an image in time. The three-dimensional spatial brightness and multi-spectral maps of a sensed image are processed using real-time image processing techniques (e.g. histogram normalization) and transformed into a two-dimensional map of an audio signal as a function of frequency and time. This paper details the approach of developing Sensing Super-position systems as a way to augment the human vision system by exploiting the capabilities of the human hearing system as an additional neural input. The human hearing system is capable of learning to process and interpret extremely complicated and rapidly changing auditory patterns. The known capabilities of the human hearing system to learn and understand complicated auditory patterns provided the basic motivation for developing an image-to-sound mapping system.
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Diaz, Francisco J.; McDonald, Peter R.; Pinter, Abraham; Chaguturu, Rathnam
2018-01-01
Biomolecular screening research frequently searches for the chemical compounds that are most likely to make a biochemical or cell-based assay system produce a strong continuous response. Several doses are tested with each compound and it is assumed that, if there is a dose-response relationship, the relationship follows a monotonic curve, usually a version of the median-effect equation. However, the null hypothesis of no relationship cannot be statistically tested using this equation. We used a linearized version of this equation to define a measure of pharmacological effect size, and use this measure to rank the investigated compounds in order of their overall capability to produce strong responses. The null hypothesis that none of the examined doses of a particular compound produced a strong response can be tested with this approach. The proposed approach is based on a new statistical model of the important concept of response detection limit, a concept that is usually neglected in the analysis of dose-response data with continuous responses. The methodology is illustrated with data from a study searching for compounds that neutralize the infection by a human immunodeficiency virus of brain glioblastoma cells. PMID:24905187
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Thompson, Jill C; Smith, Maria W; Yeh, Matthew M; Proll, Sean; Zhu, Lin-Fu; Gao, T. J; Kneteman, Norman M; Tyrrell, D. Lorne; Katze, Michael G
2006-01-01
The severe combined immunodeficiency disorder (SCID)-beige/albumin (Alb)-urokinase plasminogen activator (uPA) mouse containing a human-mouse chimeric liver is currently the only small animal model capable of supporting hepatitis C virus (HCV) infection. This model was utilized to characterize the host transcriptional response to HCV infection. The purpose of these studies was to investigate the genetic component of the host response to HCV infection and also to distinguish virus-induced gene expression changes from adaptive HCV-specific immune-mediated effects. Gene expression profiles from HCV-infected mice were also compared to those from HCV-infected patients. Analyses of the gene expression data demonstrate that host factors regulate the response to HCV infection, including the nature of the innate antiviral immune response. They also indicate that HCV mediates gene expression changes, including regulation of lipid metabolism genes, which have the potential to be directly cytopathic, indicating that liver pathology may not be exclusively mediated by HCV-specific adaptive immune responses. This effect appears to be inversely related to the activation of the innate antiviral immune response. In summary, the nature of the initial interferon response to HCV infection may determine the extent of viral-mediated effects on host gene expression. PMID:16789836
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A Therapeutic Uricase with Reduced Immunogenicity Risk and Improved Development Properties.
Nyborg, Andrew C; Ward, Chris; Zacco, Anna; Chacko, Benoy; Grinberg, Luba; Geoghegan, James C; Bean, Ryan; Wendeler, Michaela; Bartnik, Frank; O'Connor, Ellen; Gruia, Flaviu; Iyer, Vidyashankara; Feng, Hui; Roy, Varnika; Berge, Mark; Miner, Jeffrey N; Wilson, David M; Zhou, Dongmei; Nicholson, Simone; Wilker, Clynn; Wu, Chi Y; Wilson, Susan; Jermutus, Lutz; Wu, Herren; Owen, David A; Osbourn, Jane; Coats, Steven; Baca, Manuel
2016-01-01
Humans and higher primates are unique in that they lack uricase, the enzyme capable of oxidizing uric acid. As a consequence of this enzyme deficiency, humans have high serum uric acid levels. In some people, uric acid levels rise above the solubility limit resulting in crystallization in joints, acute inflammation in response to those crystals causes severe pain; a condition known as gout. Treatment for severe gout includes injection of non-human uricase to reduce serum uric acid levels. Krystexxa® is a hyper-PEGylated pig-baboon chimeric uricase indicated for chronic refractory gout that induces an immunogenic response in 91% of treated patients, including infusion reactions (26%) and anaphylaxis (6.5%). These properties limit its use and effectiveness. An innovative approach has been used to develop a therapeutic uricase with improved properties such as: soluble expression, neutral pH solubility, high E. coli expression level, thermal stability, and excellent activity. More than 200 diverse uricase sequences were aligned to guide protein engineering and reduce putative sequence liabilities. A single uricase lead candidate was identified, which showed low potential for immunogenicity in >200 human donor samples selected to represent diverse HLA haplotypes. Cysteines were engineered into the lead sequence for site specific PEGylation and studies demonstrated >95% PEGylation efficiency. PEGylated uricase retains enzymatic activity in vitro at neutral pH, in human serum and in vivo (rats and canines) and has an extended half-life. In canines, an 85% reduction in serum uric acid levels was observed with a single subcutaneous injection. This PEGylated, non-immunogenic uricase has the potential to provide meaningful benefits to patients with gout.
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Pathogenic Mechanisms and Host Interactions in Staphylococcus epidermidis Device-Related Infection.
Sabaté Brescó, Marina; Harris, Llinos G; Thompson, Keith; Stanic, Barbara; Morgenstern, Mario; O'Mahony, Liam; Richards, R Geoff; Moriarty, T Fintan
2017-01-01
Staphylococcus epidermidis is a permanent member of the normal human microbiota, commonly found on skin and mucous membranes. By adhering to tissue surface moieties of the host via specific adhesins, S. epidermidis is capable of establishing a lifelong commensal relationship with humans that begins early in life. In its role as a commensal organism, S. epidermidis is thought to provide benefits to human host, including out-competing more virulent pathogens. However, largely due to its capacity to form biofilm on implanted foreign bodies, S. epidermidis has emerged as an important opportunistic pathogen in patients receiving medical devices. S. epidermidis causes approximately 20% of all orthopedic device-related infections (ODRIs), increasing up to 50% in late-developing infections. Despite this prevalence, it remains underrepresented in the scientific literature, in particular lagging behind the study of the S. aureus . This review aims to provide an overview of the interactions of S. epidermidis with the human host, both as a commensal and as a pathogen. The mechanisms retained by S. epidermidis that enable colonization of human skin as well as invasive infection, will be described, with a particular focus upon biofilm formation. The host immune responses to these infections are also described, including how S. epidermidis seems to trigger low levels of pro-inflammatory cytokines and high levels of interleukin-10, which may contribute to the sub-acute and persistent nature often associated with these infections. The adaptive immune response to S. epidermidis remains poorly described, and represents an area which may provide significant new discoveries in the coming years.
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Bentley, Carol; Yates, Jenna; Salimi, Maryam; Greig, Jenny; Wiblin, Sarah; Hassanali, Tasneem; Banham, Alison H.
2017-01-01
Therapeutic monoclonal antibodies targeting cell surface or secreted antigens are among the most effective classes of novel immunotherapies. However, the majority of human proteins and established cancer biomarkers are intracellular. Peptides derived from these intracellular proteins are presented on the cell surface by major histocompatibility complex class I (MHC-I) and can be targeted by a novel class of T-cell receptor mimic (TCRm) antibodies that recognise similar epitopes to T-cell receptors. Humoural immune responses to MHC-I tetramers rarely generate TCRm antibodies and many antibodies recognise the α3 domain of MHC-I and β2 microglobulin (β2m) that are not directly involved in presenting the target peptide. Here we describe the production of functional chimeric human-murine HLA-A2-H2Dd tetramers and modifications that increase their bacterial expression and refolding efficiency. These chimeric tetramers were successfully used to generate TCRm antibodies against two epitopes derived from wild type tumour suppressor p53 (RMPEAAPPV and GLAPPQHLIRV) that have been used in vaccination studies. Immunisation with chimeric tetramers yielded no antibodies recognising the human α3 domain and β2m and generated TCRm antibodies capable of specifically recognising the target peptide/MHC-I complex in fully human tetramers and on the cell surface of peptide pulsed T2 cells. Chimeric tetramers represent novel immunogens for TCRm antibody production and may also improve the yield of tetramers for groups using these reagents to monitor CD8 T-cell immune responses in HLA-A2 transgenic mouse models of immunotherapy. PMID:28448627
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Palacios-González, César
2015-01-01
In this paper I explore some of the moral issues that could emerge from the creation of human-nonhuman chimeras (HNH-chimeras) capable of human gamete production and human pregnancy. First I explore whether there is a cogent argument against the creation of HNH-chimeras that could produce human gametes. I conclude that so far there is none, and that in fact there is at least one good moral reason for producing such types of creatures. Afterwards I explore some of the moral problems that could emerge from the fact that a HNH-chimera could become pregnant with a human conceptus. I focus on two sets of problems: problems that would arise by virtue of the fact that a human is gestated by a nonhuman creature, and problems that would emerge from the fact that such pregnancies could affect the health of the HNH-chimera.
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Pendulum Phenomena and the Assessment of Scientific Inquiry Capabilities
ERIC Educational Resources Information Center
Zachos, Paul
2004-01-01
Phenomena associated with the "pendulum" present numerous opportunities for assessing higher order human capabilities related to "scientific inquiry" and the "discovery" of natural law. This paper illustrates how systematic "assessment of scientific inquiry capabilities", using "pendulum" phenomena, can provide a useful tool for classroom teachers…
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The development of interior noise and vibration criteria
NASA Technical Reports Server (NTRS)
Leatherwood, J. D.; Clevenson, S. A.; Stephens, D. G.
1990-01-01
A generalized model was developed for estimating passenger discomfort response to combined noise and vibration. This model accounts for broadband noise and vibration spectra and multiple axes of vibration as well as the interactive effects of combined noise and vibration. The model has the unique capability of transforming individual components of noise/vibration environment into subjective comfort units and then combining these comfort units to produce a total index of passenger discomfort and useful sub-indices that typify passenger comfort within the environment. An overview of the model development is presented including the methodology employed, major elements of the model, model applications, and a brief description of a commercially available portable ride comfort meter based directly upon the model algorithms. Also discussed are potential criteria formats that account for the interactive effects of noise and vibration on human discomfort response.
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NASA Technical Reports Server (NTRS)
Fletcher, Rose; Knowlton, Kelly; Ryan, Robert E.
2007-01-01
This candidate solution proposes to use the night-imaging capabilities of the HSTC from SAC-C and of the HSC from SAC-D/Aquarius to detect bioluminescent events associated with HABs (harmful algal blooms). Once detected, this information could be fed to the NOAA CSCOR (Center for Sponsored Coastal Ocean Research) Harmful Algal Bloom Event Response Program, which acts quickly to fund the mobilization of research teams and to engage local agencies in a response. The HSC/HSTC data can serve as input to the HABSOS decision support system to provide information on location, extent, and duration of HAB events. Society will benefit from improved protection of the health of humans beings, aquatic ecosystems, and coastal economies. This work supports coastal management, public health, and homeland security applications.
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Climate, environment and transmission of malaria.
Rossati, Antonella; Bargiacchi, Olivia; Kroumova, Vesselina; Zaramella, Marco; Caputo, Annamaria; Garavelli, Pietro Luigi
2016-06-01
Malaria, the most common parasitic disease in the world, is transmitted to the human host by mosquitoes of the genus Anopheles. The transmission of malaria requires the interaction between the host, the vector and the parasite.The four species of parasites responsible for human malaria are Plasmodium falciparum, Plasmodium ovale, Plasmodium malariae and Plasmodium vivax. Occasionally humans can be infected by several simian species, like Plasmodium knowlesi, recognised as a major cause of human malaria in South-East Asia since 2004. While P. falciparum is responsible for most malaria cases, about 8% of estimated cases globally are caused by P. vivax. The different Plasmodia are not uniformly distributed although there are areas of species overlap. The life cycle of all species of human malaria parasites is characterised by an exogenous sexual phase in which multiplication occurs in several species of Anopheles mosquitoes, and an endogenous asexual phase in the vertebrate host. The time span required for mature oocyst development in the salivary glands is quite variable (7-30 days), characteristic of each species and influenced by ambient temperature. The vector Anopheles includes 465 formally recognised species. Approximately 70 of these species have the capacity to transmit Plasmodium spp. to humans and 41 are considered as dominant vector capable of transmitting malaria. The intensity of transmission is dependent on the vectorial capacity and competence of local mosquitoes. An efficient system for malaria transmission needs strong interaction between humans, the ecosystem and infected vectors. Global warming induced by human activities has increased the risk of vector-borne diseases such as malaria. Recent decades have witnessed changes in the ecosystem and climate without precedent in human history although the emphasis in the role of temperature on the epidemiology of malaria has given way to predisposing conditions such as ecosystem changes, political instability and health policies that have reduced the funds for vector control, combined with the presence of migratory flows from endemic countries.
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Activation of the unfolded protein response in sarcoma cells treated with rapamycin or temsirolimus
Ren, Ling; Chakrabarti, Kristi R.; Tsai, Yien Che; Weissman, Allan M.; Hansen, Ryan J.; Gustafson, Daniel L.; Khan, Yousuf A.; Dinman, Jonathan D.; Khanna, Chand
2017-01-01
Activation of the unfolded protein response (UPR) in eukaryotic cells represents an evolutionarily conserved response to physiological stress. Here, we report that the mTOR inhibitors rapamycin (sirolimus) and structurally related temsirolimus are capable of inducing UPR in sarcoma cells. However, this effect appears to be distinct from the classical role for these drugs as mTOR inhibitors. Instead, we detected these compounds to be associated with ribosomes isolated from treated cells. Specifically, temsirolimus treatment resulted in protection from chemical modification of several rRNA residues previously shown to bind rapamycin in prokaryotic cells. As an application for these findings, we demonstrate maximum tumor cell growth inhibition occurring only at doses which induce UPR and which have been shown to be safely achieved in human patients. These results are significant because they challenge the paradigm for the use of these drugs as anticancer agents and reveal a connection to UPR, a conserved biological response that has been implicated in tumor growth and response to therapy. As a result, eIF2 alpha phosphorylation and Xbp-1 splicing may serve as useful biomarkers of treatment response in future clinical trials using rapamycin and rapalogs. PMID:28926611
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The evolution of language and thought.
Lieberman, Philip
2016-06-20
Language primarily evolved as a vocal medium that transmits the attributes of human culture and the necessities of daily communication. Human language has a long, complex evolutionary history. Language also serves as an instrument of thought since it has become evident that in the course of this process neural circuits that initially evolved to regulate motor control, motor responses to external events, and ultimately talking were recycled to serve tasks such as working memory, cognitive flexibility linguistic tasks such as comprehending distinctions in meaning conveyed by syntax. This precludes the human brain possessing an organ devoted exclusively to language, such as the Faculty of Language proposed by Chomsky (1972, 2012). In essence like Fodor's (1983) modular model, a restatement of archaic phrenological theories (Spurzheim, 1815). The subcortical basal ganglia can be traced back to early anurans. Although our knowledge of the neural circuits of the human brain is at a very early stage and incomplete, the findings of independent studies over the past 40 years, discussed here, have identified circuits linking the basal ganglia with various areas of prefrontal cortex, posterior cortical regions and other subcortical structures. These circuits are active in linguistic tasks such as lexical access, comprehending distinctions in meaning conferred by syntax and the range of higher cognitive tasks involving executive control and play a critical role in conferring cognitive flexibility. The cingulate cortex which appeared in Therapsids, transitional mammal-like reptiles who lived in age of the dinosaurs, most likely enhanced mother-infant interaction, contributing to success in the Darwinian (1859) "Struggle for Existence" - the survival of progeny. They continue to fill that role in present-day mammals as well as being involved in controlling laryngeal phonation during speech and directing attention (Newman & MacLean, 1983; Cummings, 1993". The cerebellum and hippocampus, archaic structures, play role in cognition. Natural selection acting on genetic and epigenetic events in the last 500,000 years enhanced human cognitive and linguistic capabilities. It is clear that human language did not suddenly come into being 70,000 to 100,000 years as Noam Chomsky (Bolhuis et al., 2014) and others claim. The archeological record and analyses of fossil and genetic evidence shows that Neanderthals, who diverged from the human line at least 500,000 years ago possessed some form of language. Nor did the human population suddenly acquire the capability to relate two seemingly unrelated concepts by means of associative learning 100,000 years ago, re-coined "Merge" by Chomsky and his adherents, Merge supposedly is the key to syntax but associative learning, one of the cognitive processes by which children learn languages and the myriad complexities of their cultures, is a capability present in dogs and virtually all animals.
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Chen, Tan; Li, Dapeng; Song, Yufeng; Yang, Xi; Liu, Qingwei; Jin, Xia; Zhou, Dongming; Huang, Zhong
2017-09-01
Ebola virus (EBOV) is one of the most virulent pathogens known to humans. Neutralizing antibodies play a major role in the protection against EBOV infections. Thus, an EBOV vaccine capable of inducing a long-lasting neutralizing antibody response is highly desirable. We report here that a heterologous prime-boost vaccine regimen can elicit durable EBOV-neutralizing antibody response in mice. A chimpanzee serotype 7 adenovirus expressing EBOV GP (denoted AdC7-GP) was generated and used for priming. A truncated version of EBOV GP1 protein (denoted GP1t) was produced at high levels in Drosophila S2 cells and used for boosting. Mouse immunization studies showed that the AdC7-GP prime/GP1t boost vaccine regimen was more potent in eliciting neutralizing antibodies than either the AdC7-GP or GP1t alone. Neutralizing antibodies induced by the heterologous prime-boost regimen sustained at high titers for at least 18 weeks after immunization. Significantly, in vivo challenge studies revealed that the entry of reporter EBOV-like particles was efficiently blocked in mice receiving the heterologous prime-boost regimen even at 18 weeks after the final dose of immunization. These results suggest that this novel AdC7-GP prime/GP1t boost regimen represents an EBOV vaccine approach capable of establishing long-term protection, and therefore warrants further development. Copyright © 2017 Elsevier B.V. All rights reserved.
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[New insight into bacterial zoonotic pathogens posing health hazards to humans].
Ciszewski, Marcin; Czekaj, Tomasz; Szewczyk, Eligia Maria
2014-01-01
This article presents the problem of evolutionary changes of zoonotic pathogens responsible for human diseases. Everyone is exposed to the risk of zoonotic infection, particularly employees having direct contact with animals, i.e. veterinarians, breeders, butchers and workers of animal products' processing industry. The article focuses on pathogens monitored by the European Centre for Disease Prevention and Control (ECDC), which has been collecting statistical data on zoonoses from all European Union countries for 19 years and publishing collected data in annual epidemiological reports. Currently, the most important 11 pathogens responsible for causing human zoonotic diseases are being monitored, of which seven are bacteria: Salmonella spp., Campylobacter spp., Listeria monocytogenes, Mycobacterium bovis, Brucella spp., Coxiella burnetti and Verotoxin-producing E. coli (VTEC)/Shiga-like toxin producing E. coli (STEC). As particularly important are considered foodborne pathogens. The article also includes new emerging zoonotic bacteria, which are not currently monitored by ECDC but might pose a serious epidemiological problem in a foreseeable future: Streptococcus iniae, S. suis, S. dysgalactiae and staphylococci: Staphylococcus intermedius, S. pseudintermedius. Those species have just crossed the animal-human interspecies barrier. The exact mechanism of this phenomenon remains unknown, it is connected, however, with genetic variability, capability to survive in changing environment. These abilities derive from DNA rearrangement and horizontal gene transfer between bacterial cells. Substantial increase in the number of scientific publications on this subject, observed over the last few years, illustrates the importance of the problem.
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Hypoglossal canal size and hominid speech
DeGusta, David; Gilbert, W. Henry; Turner, Scott P.
1999-01-01
The mammalian hypoglossal canal transmits the nerve that supplies the motor innervation to the tongue. Hypoglossal canal size has previously been used to date the origin of human-like speech capabilities to at least 400,000 years ago and to assign modern human vocal abilities to Neandertals. These conclusions are based on the hypothesis that the size of the hypoglossal canal is indicative of speech capabilities. This hypothesis is falsified here by the finding of numerous nonhuman primate taxa that have hypoglossal canals in the modern human size range, both absolutely and relative to oral cavity volume. Specimens of Australopithecus afarensis, Australopithecus africanus, and Australopithecus boisei also have hypoglossal canals that, both absolutely and relative to oral cavity volume, are equal in size to those of modern humans. The basis for the hypothesis that hypoglossal canal size is indicative of speech was the assumption that hypoglossal canal size is correlated with hypoglossal nerve size, which in turn is related to tongue function. This assumption is probably incorrect, as we found no apparent correlation between the size of the hypoglossal nerve, or the number of axons it contains, and the size of the hypoglossal canal in a sample of cadavers. Our data demonstrate that the size of the hypoglossal canal does not reflect vocal capabilities or language usage. Thus the date of origin for human language and the speech capabilities of Neandertals remain open questions. PMID:9990105
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Human Exploration Science Office (KX) Overview
NASA Technical Reports Server (NTRS)
Calhoun, Tracy A.
2014-01-01
The Human Exploration Science Office supports human spaceflight, conducts research, and develops technology in the areas of space orbital debris, hypervelocity impact technology, image science and analysis, remote sensing, imagery integration, and human and robotic exploration science. NASA's Orbital Debris Program Office (ODPO) resides in the Human Exploration Science Office. ODPO provides leadership in orbital debris research and the development of national and international space policy on orbital debris. The office is recognized internationally for its measurement and modeling of the debris environment. It takes the lead in developing technical consensus across U.S. agencies and other space agencies on debris mitigation measures to protect users of the orbital environment. The Hypervelocity Impact Technology (HVIT) project evaluates the risks to spacecraft posed by micrometeoroid and orbital debris (MMOD). HVIT facilities at JSC and White Sands Test Facility (WSTF) use light gas guns, diagnostic tools, and high-speed imagery to quantify the response of spacecraft materials to MMOD impacts. Impact tests, with debris environment data provided by ODPO, are used by HVIT to predict risks to NASA and commercial spacecraft. HVIT directly serves NASA crew safety with MMOD risk assessments for each crewed mission and research into advanced shielding design for future missions. The Image Science and Analysis Group (ISAG) supports the International Space Station (ISS) and commercial spaceflight through the design of imagery acquisition schemes (ground- and vehicle-based) and imagery analyses for vehicle performance assessments and mission anomaly resolution. ISAG assists the Multi-Purpose Crew Vehicle (MPCV) Program in the development of camera systems for the Orion spacecraft that will serve as data sources for flight test objectives that lead to crewed missions. The multi-center Imagery Integration Team is led by the Human Exploration Science Office and provides expertise in the application of engineering imagery to spaceflight. The team links NASA programs and private industry with imagery capabilities developed and honed through decades of human spaceflight, including imagery integration, imaging assets, imagery data management, and photogrammetric analysis. The team is currently supporting several NASA programs, including commercial demonstration missions. The Earth Science and Remote Sensing Team is responsible for integrating the scientific use of Earth-observation assets onboard the ISS, which consist of externally mounted sensors and crew photography capabilities. This team facilitates collaboration on remote sensing and participates in research with academic organizations and other Government agencies, not only in conjunction with ISS science, but also for planetary exploration and regional environmental/geological studies. Human exploration science focuses on science strategies for future human exploration missions to the Moon, Mars, asteroids, and beyond. This function provides communication and coordination between the science community and mission planners. ARES scientists support the operation of robotic missions (i.e., Mars Exploration Rovers and the Mars Science Laboratory), contribute to the interpretation of returned mission data, and translate robotic mission technologies and techniques to human spaceflight.
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Concerning RNA-guided gene drives for the alteration of wild populations.
Esvelt, Kevin M; Smidler, Andrea L; Catteruccia, Flaminia; Church, George M
2014-07-17
Gene drives may be capable of addressing ecological problems by altering entire populations of wild organisms, but their use has remained largely theoretical due to technical constraints. Here we consider the potential for RNA-guided gene drives based on the CRISPR nuclease Cas9 to serve as a general method for spreading altered traits through wild populations over many generations. We detail likely capabilities, discuss limitations, and provide novel precautionary strategies to control the spread of gene drives and reverse genomic changes. The ability to edit populations of sexual species would offer substantial benefits to humanity and the environment. For example, RNA-guided gene drives could potentially prevent the spread of disease, support agriculture by reversing pesticide and herbicide resistance in insects and weeds, and control damaging invasive species. However, the possibility of unwanted ecological effects and near-certainty of spread across political borders demand careful assessment of each potential application. We call for thoughtful, inclusive, and well-informed public discussions to explore the responsible use of this currently theoretical technology.
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Role of bifidobacteria in the hydrolysis of chlorogenic acid
Raimondi, Stefano; Anighoro, Andrew; Quartieri, Andrea; Amaretti, Alberto; Tomás-Barberán, Francisco A; Rastelli, Giulio; Rossi, Maddalena
2015-01-01
This study aimed to explore the capability of potentially probiotic bifidobacteria to hydrolyze chlorogenic acid into caffeic acid (CA), and to recognize the enzymes involved in this reaction. Bifidobacterium strains belonging to eight species occurring in the human gut were screened. The hydrolysis seemed peculiar of Bifidobacterium animalis, whereas the other species failed to release CA. Intracellular feruloyl esterase activity capable of hydrolyzing chlorogenic acid was detected only in B. animalis. In silico research among bifidobacteria esterases identified Balat_0669 as the cytosolic enzyme likely responsible of CA release in B. animalis. Comparative modeling of Balat_0669 and molecular docking studies support its role in chlorogenic acid hydrolysis. Expression, purification, and functional characterization of Balat_0669 in Escherichia coli were obtained as further validation. A possible role of B. animalis in the activation of hydroxycinnamic acids was demonstrated and new perspectives were opened in the development of new probiotics, specifically selected for the enhanced bioconversion of phytochemicals into bioactive compounds. PMID:25515139
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Role of bifidobacteria in the hydrolysis of chlorogenic acid.
Raimondi, Stefano; Anighoro, Andrew; Quartieri, Andrea; Amaretti, Alberto; Tomás-Barberán, Francisco A; Rastelli, Giulio; Rossi, Maddalena
2015-02-01
This study aimed to explore the capability of potentially probiotic bifidobacteria to hydrolyze chlorogenic acid into caffeic acid (CA), and to recognize the enzymes involved in this reaction. Bifidobacterium strains belonging to eight species occurring in the human gut were screened. The hydrolysis seemed peculiar of Bifidobacterium animalis, whereas the other species failed to release CA. Intracellular feruloyl esterase activity capable of hydrolyzing chlorogenic acid was detected only in B. animalis. In silico research among bifidobacteria esterases identified Balat_0669 as the cytosolic enzyme likely responsible of CA release in B. animalis. Comparative modeling of Balat_0669 and molecular docking studies support its role in chlorogenic acid hydrolysis. Expression, purification, and functional characterization of Balat_0669 in Escherichia coli were obtained as further validation. A possible role of B. animalis in the activation of hydroxycinnamic acids was demonstrated and new perspectives were opened in the development of new probiotics, specifically selected for the enhanced bioconversion of phytochemicals into bioactive compounds. © 2014 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.
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NASA Astrophysics Data System (ADS)
Vestrand, W. T.; Theiler, J.; Woznia, P. R.
2004-10-01
The existence of rapidly slewing robotic telescopes and fast alert distribution via the Internet is revolutionizing our capability to study the physics of fast astrophysical transients. But the salient challenge that optical time domain surveys must conquer is mining the torrent of data to recognize important transients in a scene full of normal variations. Humans simply do not have the attention span, memory, or reaction time required to recognize fast transients and rapidly respond. Autonomous robotic instrumentation with the ability to extract pertinent information from the data stream in real time will therefore be essential for recognizing transients and commanding rapid follow-up observations while the ephemeral behavior is still present. Here we discuss how the development and integration of three technologies: (1) robotic telescope networks; (2) machine learning; and (3) advanced database technology, can enable the construction of smart robotic telescopes, which we loosely call ``thinking'' telescopes, capable of mining the sky in real time.
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3D printing of soft robotic systems
NASA Astrophysics Data System (ADS)
Wallin, T. J.; Pikul, J.; Shepherd, R. F.
2018-06-01
Soft robots are capable of mimicking the complex motion of animals. Soft robotic systems are defined by their compliance, which allows for continuous and often responsive localized deformation. These features make soft robots especially interesting for integration with human tissues, for example, the implementation of biomedical devices, and for robotic performance in harsh or uncertain environments, for example, exploration in confined spaces or locomotion on uneven terrain. Advances in soft materials and additive manufacturing technologies have enabled the design of soft robots with sophisticated capabilities, such as jumping, complex 3D movements, gripping and releasing. In this Review, we examine the essential soft material properties for different elements of soft robots, highlighting the most relevant polymer systems. Advantages and limitations of different additive manufacturing processes, including 3D printing, fused deposition modelling, direct ink writing, selective laser sintering, inkjet printing and stereolithography, are discussed, and the different techniques are investigated for their application in soft robotic fabrication. Finally, we explore integrated robotic systems and give an outlook for the future of the field and remaining challenges.
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Reinventing the International Space Station Payload Integration Processes and Capabilities
NASA Technical Reports Server (NTRS)
Jones, Rod; Price, Carmen; Copeland, Scott; Geiger, Wade; Geiger, Wade; Rice, Amanda; Lauchner, Adam
2011-01-01
The fundamental ISS payload integration philosophy, processes and capabilities were established in the context of how NASA science programs were conducted and executed in the early 1990 s. Today, with the designation of the United States (US) portion of ISS as a National Lab, the ISS payload customer base is growing to include other government agencies, private and commercial research. The fields of research are becoming more diverse expanding from the NASA centric physical, materials and human research sciences to test beds for exploration and technology demonstration, biology and biotechnology, and as an Earth and Space science platform. This new customer base has a broader more diverse set of expectations and requirements for payload design, verification, integration, test, training, and operations. One size fits all processes are not responsive to this broader customer base. To maintain an organization s effectiveness it must listen to its customers, understand their needs, learn from its mistakes, and foster an environment of continual process improvement. The ISS Payloads office is evolving to meet these new customer expectations.
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Crew systems: integrating human and technical subsystems for the exploration of space.
Connors, M M; Harrison, A A; Summit, J
1994-07-01
Space exploration missions will require combining human and technical subsystems into overall "crew systems" capable of performing under the rigorous conditions of outer space. This report describes substantive and conceptual relationships among humans, intelligent machines, and communication systems, and explores how these components may be combined to complement and strengthen one another. We identify key research issues in the combination of humans and technology and examine the role of individual differences, group processes, and environmental conditions. We conclude that a crew system is, in effect, a social cyborg, a living system consisting of multiple individuals whose capabilities are extended by advanced technology.
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Crew systems: integrating human and technical subsystems for the exploration of space
NASA Technical Reports Server (NTRS)
Connors, M. M.; Harrison, A. A.; Summit, J.
1994-01-01
Space exploration missions will require combining human and technical subsystems into overall "crew systems" capable of performing under the rigorous conditions of outer space. This report describes substantive and conceptual relationships among humans, intelligent machines, and communication systems, and explores how these components may be combined to complement and strengthen one another. We identify key research issues in the combination of humans and technology and examine the role of individual differences, group processes, and environmental conditions. We conclude that a crew system is, in effect, a social cyborg, a living system consisting of multiple individuals whose capabilities are extended by advanced technology.
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NASA Technical Reports Server (NTRS)
Smith, Bryan K.; Nazario, Margaret L.; Manzella, David H.
2012-01-01
Solar Electric Propulsion has evolved into a demonstrated operational capability performing station keeping for geosynchronous satellites, enabling challenging deep-space science missions, and assisting in the transfer of satellites from an elliptical orbit Geostationary Transfer Orbit (GTO) to a Geostationary Earth Orbit (GEO). Advancing higher power SEP systems will enable numerous future applications for human, robotic, and commercial missions. These missions are enabled by either the increased performance of the SEP system or by the cost reductions when compared to conventional chemical propulsion systems. Higher power SEP systems that provide very high payload for robotic missions also trade favorably for the advancement of human exploration beyond low Earth orbit. Demonstrated reliable systems are required for human space flight and due to their successful present day widespread use and inherent high reliability, SEP systems have progressively become a viable entrant into these future human exploration architectures. NASA studies have identified a 30 kW-class SEP capability as the next appropriate evolutionary step, applicable to wide range of both human and robotic missions. This paper describes the planning options, mission applications, and technology investments for representative 30kW-class SEP mission concepts under consideration by NASA
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ERIC Educational Resources Information Center
Tsai, Ming-Chang
2011-01-01
This review essay offers an institutional critique of the Stiglitz-Sen-Fitoussi Report. The notion of human capabilities and functionings advocated by the Report demonstrates an inspirational perspective to monitor human progress in quality of life (QoL). Several measurements the Report suggested remain inadequate. The personal diary techniques…
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The Should Be Goal of Education: What Should Be Taught? And How Should It Be Taught?
ERIC Educational Resources Information Center
Kayode, Bakare Kazeem; Nasirudeen, Abdulwasiu Isiaq; Al-Hasani, Syed Mahbubul Alam
2016-01-01
The role of education is to be reflective (about what? Why? and how?) in preserving the civilization identity and human capability of a nation. This is particularly true because education is the cornerstone to building human capability and capacity that can develop a country. A well-formulated educational goal will serve as a moral compass for…
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Cultivating Human Capabilities in Venturesome Learning Environments
ERIC Educational Resources Information Center
Hogan, Padraig
2013-01-01
The notion of competencies has been a familiar feature of educational reform policies for decades. In this essay, Padraig Hogan begins by highlighting the contrasting notion of capabilities, pioneered by the research of Amartya Sen and Martha Nussbaum. An educational variant of the notion of capabilities then becomes the basis for exploring…