76 FR 28442 - Office of the Director, National Institutes of Health; Notice of Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2011-05-17
... DEPARTMENT OF HEALTH AND HUMAN SERVICES National Institutes of Health Office of the Director.... Agenda: The NIH Recombinant DNA Advisory Committee (RAC) will review and discuss selected human gene... Advisory Committee (RAC) will review and discuss selected human gene transfer protocols, including a...
ERIC Educational Resources Information Center
Wilson, Michael
The report summarizes the various job analysis techniques that have been developed, discusses their applications to selected human resource management activities, and suggests priorities for further research and developmental work. The introduction defines job analysis and discusses the applications of job analysis data, and the structure of the…
Human Mars Mission Overview and Dust Storm Impacts on Site Selection
NASA Astrophysics Data System (ADS)
Hoffman, S. J.
2017-06-01
This presentation briefly reviews NASA's current approach to human exploration of Mars and key features placed on locations (referred to as Exploration Zones) for these activities. Impacts of dust and dust storms on selecting an EZ are discussed.
Reproduction (II): Human Control of Reproductive Processes
ERIC Educational Resources Information Center
Jost, Alfred
1970-01-01
Describes methods of intervening in reproduction of animals and humans (artificial insemination, contraception, ovular and blastodisc transplants, pre selection of sex, cloning) and discusses the social implications of their use with humans. (AL)
The Unfortunate Human Factor: A Selective History of Human Factors for Technical Communicators.
ERIC Educational Resources Information Center
Johnson, Robert R.
1994-01-01
Reviews moments in the history of human factors that are especially relevant to the field of technical communications. Discusses human factors research that is applicable to technical communications. Focuses on qualitative usability research, minimalism, and human activity interface design. (HB)
A pilot modeling technique for handling-qualities research
NASA Technical Reports Server (NTRS)
Hess, R. A.
1980-01-01
A brief survey of the more dominant analysis techniques used in closed-loop handling-qualities research is presented. These techniques are shown to rely on so-called classical and modern analytical models of the human pilot which have their foundation in the analysis and design principles of feedback control. The optimal control model of the human pilot is discussed in some detail and a novel approach to the a priori selection of pertinent model parameters is discussed. Frequency domain and tracking performance data from 10 pilot-in-the-loop simulation experiments involving 3 different tasks are used to demonstrate the parameter selection technique. Finally, the utility of this modeling approach in handling-qualities research is discussed.
A Selective Critique of Animal Experiments in Human-Orientated Biological Research.
ERIC Educational Resources Information Center
Webb, G. P.
1990-01-01
The advantages and justifications for using small animals in human-oriented research are reviewed. Some of the pitfalls of extrapolating animal-derived data to humans are discussed. Several specific problems with animal experimentation are highlighted. (CW)
Human response to aircraft noise
NASA Technical Reports Server (NTRS)
Powell, Clemans A.; Fields, James M.
1991-01-01
The human auditory system and the perception of sound are discussed. The major concentration is on the annnoyance response and methods for relating the physical characteristics of sound to those psychosociological attributes associated with human response. Results selected from the extensive laboratory and field research conducted on human response to aircraft noise over the past several decades are presented along with discussions of the methodology commonly used in conducting that research. Finally, some of the more common criteria, regulations, and recommended practices for the control or limitation of aircraft noise are examined in light of the research findings on human response.
The Insertion of Human Factors Concerns into NextGen Programmatic Decisions
NASA Technical Reports Server (NTRS)
Beard, Bettina L.; Holbrook, Jon Brian; Seely, Rachel
2013-01-01
Since the costs of proposed improvements in air traffic management exceed available funding, FAA decision makers must select and prioritize what actually gets implemented. We discuss a set of methods to help forecast operational and human performance issues and benefits before new automation is introduced. This strategy could minimize the impact of politics, assist decision makers in selecting and prioritizing potential improvements, make the process more transparent and strengthen the link between the engineering and human factors domains.
Personnel Selection Influences on Remotely Piloted Aircraft Human-System Integration.
Carretta, Thomas R; King, Raymond E
2015-08-01
Human-system integration (HSI) is a complex process used to design and develop systems that integrate human capabilities and limitations in an effective and affordable manner. Effective HSI incorporates several domains, including manpower, personnel and training, human factors, environment, safety, occupational health, habitability, survivability, logistics, intelligence, mobility, and command and control. To achieve effective HSI, the relationships among these domains must be considered. Although this integrated approach is well documented, there are many instances where it is not followed. Human factors engineers typically focus on system design with little attention to the skills, abilities, and other characteristics needed by human operators. When problems with fielded systems occur, additional training of personnel is developed and conducted. Personnel selection is seldom considered during the HSI process. Complex systems such as aviation require careful selection of the individuals who will interact with the system. Personnel selection is a two-stage process involving select-in and select-out procedures. Select-in procedures determine which candidates have the aptitude to profit from training and represent the best investment. Select-out procedures focus on medical qualification and determine who should not enter training for medical reasons. The current paper discusses the role of personnel selection in the HSI process in the context of remotely piloted aircraft systems.
On the Fate of Distractor Representations
ERIC Educational Resources Information Center
Frings, Christian; Wentura, Dirk; Wuhr, Peter
2012-01-01
Research on the topic of distractor inhibition has used different empirical approaches to study how the human mind selects relevant information from the environment, and the results are controversially discussed. One key question that typically arises is how selection deals with the irrelevant information. We used a new selection task, in which…
Gerstein, Aleeza C; Nielsen, Kirsten
2017-04-01
Cryptococcus is predominantly an AIDS-related pathogen that causes significant morbidity and mortality in immunocompromised patients. Research studies have historically focused on understanding how the organism causes human disease through the use of in vivo and in vitro model systems to identify virulence factors. Cryptococcus is not an obligate pathogen, however, as human-human transmission is either absent or rare. Selection in the environment must thus be invoked to shape the evolution of this taxa, and directly influences genotypic and trait diversity. Importantly, the evolution and maintenance of pathogenicity must also stem directly from environmental selection. To that end, here we examine abiotic and biotic stresses in the environment, and discuss how they could shape the factors that are commonly identified as important virulence traits. We identify a number of important unanswered questions about Cryptococcus diversity and evolution that are critical for understanding this deadly pathogen, and discuss how implementation of modern sampling and genomic tools could be utilized to answer these questions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
Darwin's explanation of races by means of sexual selection.
Millstein, Roberta L
2012-09-01
In Darwin's Sacred Cause, Adrian Desmond and James Moore contend that "Darwin would put his utmost into sexual selection because the subject intrigued him, no doubt, but also for a deeper reason: the theory vindicated his lifelong commitment to human brotherhood" (2009: p. 360). Without questioning Desmond and Moore's evidence, I will raise some puzzles for their view. I will show that attention to the structure of Darwin's arguments in the Descent of Man shows that they are far from straightforward. As Desmond and Moore note, Darwin seems to have intended sexual selection in non-human animals to serve as evidence for sexual selection in humans. However, Darwin's account of sexual selection in humans was different from the canonical cases that Darwin described at great length. If explaining the origin of human races was the main reason for introducing sexual selection, and if sexual selection was a key piece of Darwin's anti-slavery arguments, then it is puzzling why Darwin would have spent so much time discussing cases that did not really support his argument for the origin of human races, and it is also puzzling that his argument for the origin of human races would be so (atypically) poor. Copyright © 2012 Elsevier Ltd. All rights reserved.
A Peer Counselling Program for Persons Testing H.I.V. Antibody Positive.
ERIC Educational Resources Information Center
Baiss, Alan
1989-01-01
Describes need for and development of a peer counseling program for persons who have tested positive for human immunodeficiency virus (HIV) antibodies. Discusses selection of peer counselors, training, and confidentiality. Includes discussion of future plans. (ABL)
Cultural Development through Human Resource Systems Integration.
ERIC Educational Resources Information Center
Albert, Michael
1985-01-01
Discusses the framework for developing a cultural human resources management (HRM) perspective. Central to this framework is modifying HRM programs to reinforce the organization's preferred practices. Modification occurs through selection, orientation, training and development, performance appraisal, career development, and compensation and…
The case for a multinational Mars Surveyor Program
NASA Astrophysics Data System (ADS)
Rea, D. G.; Carr, M. H.; Craig, M. K.
1989-10-01
A coordinated multinational Mars Surveyor Program involving a series of robotic missions is proposed in order to select worthwhile human landing sites for discoveries, for safe operations, and for testing and proving technologies for making human flight to Mars possible. Some characteristics motivating exploration of the planet are briefly discussed, including the possibility of life, geological features, and meteorological conditions. The necessity for preliminary exploration of Mars by robots prior to human exploration is discussed, and the rationale behind a multinational approach for a Mars Surveyor Program is presented.
A Whole New World of Interventions: The Performance Technologist as Integrating Generalist.
ERIC Educational Resources Information Center
Hutchison, Cathleen Smith; Stein, Faith S.
1997-01-01
The authors update an article on intervention, discussing career development, communications, feedback, financial, human development, information, instructional, labor relations, measurement and evaluation, quality improvement, resource, reward and recognition, and selection systems; documentation and standards; ergonomics and human factors;…
The Human Immunodeficiency Virus: Infectivity and Mechanisms of Pathogenesis.
ERIC Educational Resources Information Center
Fauci, Anthony S.
1988-01-01
Discusses how the infection of the human immunodeficiency virus (HIV) results in a profound immunosuppression due predominantly to a selective depletion of helper/inducer T lymphocytes that express the receptor for the virus, as well as neuropsychiatric abnormalities in the brain. (TW)
Selection signature in domesticated animals.
Pan, Zhang-yuan; He, Xiao-yun; Wang, Xiang-yu; Guo, Xiao-fei; Cao, Xiao-han; Hu, Wen-ping; Di, Ran; Liu, Qiu-yue; Chu, Ming-xing
2016-12-20
Domesticated animals play an important role in the life of humanity. All these domesticated animals undergo same process, first domesticated from wild animals, then after long time natural and artificial selection, formed various breeds that adapted to the local environment and human needs. In this process, domestication, natural and artificial selection will leave the selection signal in the genome. The research on these selection signals can find functional genes directly, is one of the most important strategies in screening functional genes. The current studies of selection signal have been performed in pigs, chickens, cattle, sheep, goats, dogs and other domestic animals, and found a great deal of functional genes. This paper provided an overview of the types and the detected methods of selection signal, and outlined researches of selection signal in domestic animals, and discussed the key issues in selection signal analysis and its prospects.
IMPLEMENTING NONPROFESSIONAL PROGRAMS IN HUMAN SERVICES. MANPOWER TRAINING SERIES.
ERIC Educational Resources Information Center
SCHMAIS, AARON
SPECIFIC PROCESSES FOR UTILIZING NONPROFESSIONAL EMPLOYEES IN HUMAN SERVICES ARE PRESENTED. THE BACKGROUND, CURRENT STATUS, AND PROBLEMS ARE DISCUSSED. THE ELEMENTS CONSIDERED ARE RECRUITMENT, SCREENING AND SELECTION, TRAINING, PLACEMENT, SUPERVISION, UPGRADING, AND EVALUATION. EXAMPLES OF NONPROFESSIONAL POSITIONS INCLUDE THE CASE AIDE IN SOCIAL…
ERIC Educational Resources Information Center
Robertson, Michelle M.
1992-01-01
Discusses ergonomic design considerations for library media centers. Specific design variables, including temperature and humidity, noise, illumination, color, and windows are discussed; and computer workstation design requirements are presented that address furniture and keyboard design, monitor and display features, software issues, and…
Humanities Programming in Public Libraries: The Connecticut Perspective.
ERIC Educational Resources Information Center
Rader, Barbara A.
1990-01-01
Describes how public libraries can plan, fund, and implement scholar-led, library-based, humanities book discussion programs using the example of the Southern Connecticut Library Council. Key steps in planning, funding, targeting the audience, selecting topics and books, obtaining community support, recruiting scholars, marketing, administration,…
Jabłońska-Trypuć, Agata; Wołejko, Elżbieta; Wydro, Urszula; Butarewicz, Andrzej
2017-07-03
Pesticides cause serious environmental and health problems both to humans and animals. The aim of this review is to discuss selected herbicides and fungicides regarding their mode of action and their influence on basic oxidative stress parameters and endocrine disruption properties tested in selected cell cultures in vitro. Because of numerous difficulties which animal studies are subject to, cell cultures are an excellent experimental model reflecting human exposure to different pesticides through all relevant routes. This experimental model can be used to monitor aggregate and cumulative pesticide exposures.
SPECIES, TEPEES, SCOTTIES, AND JOCKEYS: SELECTED BY CONSEQUENCES
Wasserman, Edward A
2012-01-01
“Ideas are like species: they must evolve.” This claim forms the conceptual core of an engaging book by Jonnie Hughes (2011), On the Origin of Tepees. Hughes asks: If evolution by natural selection explains the origin of the human species, then does selection by consequences also explain the origin of what we humans make and do? This question prompts consideration of three important analogies: between natural selection and artificial selection, between the law of natural selection and the law of effect, and between biological evolution and cultural evolution. These analogies in turn stimulate examination of the notions of purpose, design, and agency. Finally, discussion moves to the selectionism of Darwin and Skinner; although still controversial, this view remains the best way for natural science to understand the origins of adaptive behavior.
Fang, Hongqing; He, Lei; Si, Hao; Liu, Peng; Xie, Xiaolei
2014-09-01
In this paper, Back-propagation(BP) algorithm has been used to train the feed forward neural network for human activity recognition in smart home environments, and inter-class distance method for feature selection of observed motion sensor events is discussed and tested. And then, the human activity recognition performances of neural network using BP algorithm have been evaluated and compared with other probabilistic algorithms: Naïve Bayes(NB) classifier and Hidden Markov Model(HMM). The results show that different feature datasets yield different activity recognition accuracy. The selection of unsuitable feature datasets increases the computational complexity and degrades the activity recognition accuracy. Furthermore, neural network using BP algorithm has relatively better human activity recognition performances than NB classifier and HMM. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.
Our Experiment in Online, Real-Time Reference.
ERIC Educational Resources Information Center
Broughton, Kelly
2001-01-01
Describes experiences in providing real-time online reference services to users with remote Web access at the Bowling Green State University library. Discusses the decision making process first used to select HumanClick software to communicate via chat; and the selection of a fee-based customer service product, Virtual Reference Desk. (LRW)
Censorship in Schools: The Impact of Conservative Christian Pressure Groups.
ERIC Educational Resources Information Center
Dorrell, Larry D.; Busch, Anne
2000-01-01
Presents an historical overview of the rise of conservative pressure groups after 1980 and their association with an increase in censorship activities in schools. Discusses the influence of the Reagan administration; library materials selection; textbook selection; secular humanism; and trying to affect the curriculum rather than targeting…
Themes and Values in Selected Children's Literature.
ERIC Educational Resources Information Center
Shachter, Jaqueline
Children's books by successful writers may stimulate young people to think about philosophical questions, prompting lively discussions. Such books not only have literary value but also encourage children to consider matters central to the human condition. Teachers at the intermediate grade level and above can stimulate discussions of ethical…
Perspectives on Human-Computer Interface: Introduction and Overview.
ERIC Educational Resources Information Center
Harman, Donna; Lunin, Lois F.
1992-01-01
Discusses human-computer interfaces in information seeking that focus on end users, and provides an overview of articles in this section that (1) provide librarians and information specialists with guidelines for selecting information-seeking systems; (2) provide producers of information systems with directions for production or research; and (3)…
Humanism and the Sciences: Monogamy, Polygamy, and Sociobiology.
ERIC Educational Resources Information Center
Saladin, Kenneth S.
1981-01-01
Portrays sociobiology in a rational light and examines its human implications in the area of sexual selection and mating systems. Sociobiology is the analysis of social behavior in terms of its revolutionary and genetic origins and consequences. Concludes with a discussion of the potential contributions of sociobiology toward understanding of…
Effectiveness of the Sexual Attitude Restructuring Curriculum amongst Taiwanese Graduate Students
ERIC Educational Resources Information Center
Lin, Yi-Li; Lin, Yen-Chin
2018-01-01
This article discusses the effectiveness of the Sexual Attitude Restructuring (SAR) curriculum in developing positive sexual attitudes amongst Taiwanese graduate students in human sexuality. Through purposive sampling, 32 graduate students in human sexuality were selected to participate in the study. Before and after providing participants with a…
Environmental stress and adaptational responses: consequences for human health outcomes.
Garruto, Ralph M; Little, Michael A; Weitz, Charles A
2004-12-01
With the dramatic pace of modernization of the world's population, human adaptation as a theoretical construct and paradigm will likely become a focal scientific issue involving scientists from many disciplinary areas during the 21st Century. Macro and micro environments are in rapid flux and human populations are exposed to rapid change. The concept of adaptation, at least in the field of biological anthropology and human biology, will likely remain tied to evolutionary processes and concepts of selection and fitness. In this paper, we discuss the theoretical constructs of adaptation and adaptability and select three current examples from our ongoing research that involve studies of adaptation and evolutionary processes in modernizing populations in different locations worldwide.
Human Classification Based on Gestural Motions by Using Components of PCA
NASA Astrophysics Data System (ADS)
Aziz, Azri A.; Wan, Khairunizam; Za'aba, S. K.; B, Shahriman A.; Adnan, Nazrul H.; H, Asyekin; R, Zuradzman M.
2013-12-01
Lately, a study of human capabilities with the aim to be integrated into machine is the famous topic to be discussed. Moreover, human are bless with special abilities that they can hear, see, sense, speak, think and understand each other. Giving such abilities to machine for improvement of human life is researcher's aim for better quality of life in the future. This research was concentrating on human gesture, specifically arm motions for differencing the individuality which lead to the development of the hand gesture database. We try to differentiate the human physical characteristic based on hand gesture represented by arm trajectories. Subjects are selected from different type of the body sizes, and then acquired data undergo resampling process. The results discuss the classification of human based on arm trajectories by using Principle Component Analysis (PCA).
Ethical Issues in Health Services: A Report and Annotated Bibliography.
ERIC Educational Resources Information Center
Carmody, James
This publication identifies, discusses, and lists areas for further research for five ethical issues related to health services: 1) the right to health care; 2) death and euthanasia; 3) human experimentation; 4) genetic engineering; and, 5) abortion. Following a discussion of each issue is a selected annotated bibliography covering the years 1967…
Pilot interaction with automated airborne decision making systems
NASA Technical Reports Server (NTRS)
Rouse, W. B.; Hammer, J. M.; Morris, N. M.; Brown, E. N.; Yoon, W. C.
1983-01-01
The use of advanced software engineering methods (e.g., from artificial intelligence) to aid aircraft crews in procedure selection and execution is investigated. Human problem solving in dynamic environments as effected by the human's level of knowledge of system operations is examined. Progress on the development of full scale simulation facilities is also discussed.
Human-computer dialogue: Interaction tasks and techniques. Survey and categorization
NASA Technical Reports Server (NTRS)
Foley, J. D.
1983-01-01
Interaction techniques are described. Six basic interaction tasks, requirements for each task, requirements related to interaction techniques, and a technique's hardware prerequisites affective device selection are discussed.
New frontiers in the study of human cultural and genetic evolution.
Ross, Cody T; Richerson, Peter J
2014-12-01
In this review, we discuss the dynamic linkages between culture and the genetic evolution of the human species. We begin by briefly describing the framework of gene-culture coevolutionary (or dual-inheritance) models for human evolutionary change. Until recently, the literature on gene-culture coevolution was composed primarily of mathematical models and formalized theory describing the complex dynamics underlying human behavior, adaptation, and technological evolution, but had little empirical support concerning genetics. The rapid progress in the fields of molecular genetics and genomics, however, is now providing the kinds of data needed to produce rich empirical support for gene-culture coevolutionary models. We briefly outline how theoretical and methodological progress in genome sciences has provided ways for the strength of selection on genes to be evaluated, and then outline how evidence of selection on several key genes can be directly linked to human cultural practices. We then describe some exciting new directions in the empirical study of gene-culture coevolution, and conclude with a discussion of the role of gene-culture evolutionary models in the future integration of medical, biological, and social sciences. Copyright © 2014 Elsevier Ltd. All rights reserved.
Selection and Biosensor Application of Aptamers for Small Molecules
Pfeiffer, Franziska; Mayer, Günter
2016-01-01
Small molecules play a major role in the human body and as drugs, toxins, and chemicals. Tools to detect and quantify them are therefore in high demand. This review will give an overview about aptamers interacting with small molecules and their selection. We discuss the current state of the field, including advantages as well as problems associated with their use and possible solutions to tackle these. We then discuss different kinds of small molecule aptamer-based sensors described in literature and their applications, ranging from detecting drinking water contaminations to RNA imaging. PMID:27379229
An application of adaption-innovation theory to bioremediation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Guerin, L.J.; Guerin, T.F.
1995-12-31
This paper provides a discussion of the potential application of the Kirton Adaption-Innovation Inventory (KAI) for assessing the adaptive-innovative cognitive style of individuals and organizations within the bioremediation industry. Human-resource and line managers, or other individuals responsible for staff evaluation, selection, and project planning, should consider using the KAI to assist them in selecting individuals for specific roles requiring either an innovative or adaptive style. The KAI, a measure for assessing adaption-innovation at the individual employee level, is introduced and its potential value in the bioremediation industry is discussed.
Perceptual and neural responses to sweet taste in humans and rodents.
Lemon, Christian H
2015-08-01
This mini-review discusses some of the parallels between rodent neurophysiological and human psychophysical data concerning temperature effects on sweet taste. "Sweet" is an innately rewarding taste sensation that is associated in part with foods that contain calories in the form of sugars. Humans and other mammals can show unconditioned preference for select sweet stimuli. Such preference is poised to influence diet selection and, in turn, nutritional status, which underscores the importance of delineating the physiological mechanisms for sweet taste with respect to their influence on human health. Advances in our knowledge of the biology of sweet taste in humans have arisen in part through studies on mechanisms of gustatory processing in rodent models. Along this line, recent work has revealed there are operational parallels in neural systems for sweet taste between mice and humans, as indexed by similarities in the effects of temperature on central neurophysiological and psychophysical responses to sucrose in these species. Such association strengthens the postulate that rodents can serve as effective models of particular mechanisms of appetitive taste processing. Data supporting this link are discussed here, as are rodent and human data that shed light on relationships between mechanisms for sweet taste and ingestive disorders, such as alcohol abuse. Rodent models have utility for understanding mechanisms of taste processing that may pertain to human flavor perception. Importantly, there are limitations to generalizing data from rodents, albeit parallels across species do exist.
Potent Cytotoxic Peptides from the Australian Marine Sponge Pipestela candelabra
Tran, Trong D.; Pham, Ngoc B.; Fechner, Gregory A.; Hooper, John N. A.; Quinn, Ronald J.
2014-01-01
Two consecutive prefractionated fractions of the Australian marine sponge extract, Pipestela candelabra, were identified to be selectively active on the human prostate cancer cells (PC3) compared to the human neonatal foreskin fibroblast non-cancer cells (NFF). Twelve secondary metabolites were isolated in which four compounds are new small peptides. Their structures were characterized by spectroscopic and chemical analysis. These compounds inhibited selectively the growth of prostate cancer cells with IC50 values in the picomolar to sub-micromolar range. Structure-activity relationship of these compounds is discussed. PMID:24901701
Kamimura, Hidetaka; Ito, Satoshi
2016-01-01
1. Chimeric mice with humanized livers are expected to be a novel tool for new drug development. This review discusses four applications where these animals can be used efficiently to collect supportive data for selecting the best compound in the final stage of drug discovery. 2. The first application is selection of the final compound based on estimated pharmacokinetic parameters in humans. Since chimeric mouse livers are highly repopulated with human hepatocytes, hepatic clearance values in vivo could be used preferentially to estimate pharmacokinetic profiles for humans. 3. The second is prediction of human-specific or disproportionate metabolites. Chimeric mice reproduce human-specific metabolites of drugs under development to conform to ICH guidance M3(R2), except for compounds that were extensively eliminated by co-existing mouse hepatocytes. 4. The third is identifying metabolites with distinct pharmacokinetic profiles in humans. Slow metabolite elimination specifically in humans increases its exposure level, but if its elimination is faster in laboratory animals, the animal exposure level might not satisfy ICH guidance M3(R2). 5. Finally, two examples of reproducing acute liver toxicity in chimeric mice are introduced. Integrated pharmacokinetics, metabolism and toxicity information are expected to assist pharmaceutical scientists in selecting the best candidate compound in new drug development.
Cohen, Claudine
2010-02-01
In his 1871 book The Descent of Man, Darwin exposed the idea of sexual selection as a major principle of human evolution. His main hypothesis, which was already briefly presented in The Origin of Species, is that there exists, besides "natural selection", another form of selection, milder in its effect, but no less efficient. This selection is operated by females to mate and reproduce with some partners that are gifted with more qualities than others, and more to their taste. At more evolved stages, sexual selection was exerted by men who became able to choose the women most attractive to their taste. However, Darwin insists, sexual selection in the human species is limited by a certain number of cultural practices. If Darwin's demonstration sometimes carried the prejudices of his times regarding gender differences he was the first who took into account the importance of sexual choices in his view on evolution, and who insisted on the evolutionary role of women at the dawn of humanity. Thus, he opened the space for a rich reflection, which after him was widely developed and discussed in anthropological and gender studies. 2010. Published by Elsevier SAS.
ERIC Educational Resources Information Center
Reed, Lawrence E.; And Others
The methods and problems encountered in the development of a prototype human resources data handbook are discussed. The goal of the research was to determine whether it was feasible to consolidate, in a single comprehensive handbook, human resources data applicable to system design and development. Selected for this purpose were data on the…
Faculty Salary Equity: Issues in Regression Model Selection. AIR 1992 Annual Forum Paper.
ERIC Educational Resources Information Center
Moore, Nelle
This paper discusses the determination of college faculty salary inequity and identifies the areas in which human judgment must be used in order to conduct a statistical analysis of salary equity. In addition, it provides some informed guidelines for making those judgments. The paper provides a framework for selecting salary equity models, based…
ERIC Educational Resources Information Center
Manning, Sabine, Ed.
This document contains 13 presentations/discussion summaries and 10 supporting 'thesis' papers from a symposium on selected issues in human resources development (HRD) in Europe. The following summaries are included: "Introduction" (Sabine Manning); "Developing Flexibility in Pursuit of Competitiveness" (Nick Boreham);…
A seamless phase IIB/III adaptive outcome trial: design rationale and implementation challenges.
Chen, Y H Joshua; Gesser, Richard; Luxembourg, Alain
2015-02-01
The licensed four-valent prophylactic human papillomavirus vaccine is highly efficacious in preventing cervical, vulvar, vaginal, and anal cancers and related precancers caused by human papillomavirus types 6, 11, 16, and 18. These four types account for approximately 70% of cervical cancers. A nine-valent human papillomavirus vaccine, including the four original types (6, 11, 16, and 18) plus the next five most prevalent types in cervical cancer (31, 33, 45, 52, and 58) could provide approximately 90% overall cervical cancer coverage. To expedite the nine-valent human papillomavirus vaccine clinical development, an adaptive, seamless Phase IIB/III outcome trial with ∼ 15,000 subjects was conducted to facilitate dose formulation selection and provide pivotal evidence of safety and efficacy for regulatory registrations. We discuss the design rationale and implementation challenges of the outcome trial, focusing on the adaptive feature of the seamless Phase IIB/III design. Subjects were enrolled in two parts (Part A and Part B). Approximately 1240 women, 16-26 years of age, were enrolled in Part A for Phase IIB evaluation and equally randomized to one of three dose formulations of the nine-valent human papillomavirus vaccine or the four-valent human papillomavirus vaccine (active control). Based on an interim analysis of immunogenicity and safety, one dose formulation of the nine-valent human papillomavirus vaccine was selected for evaluation in the Phase III part of the study. Subjects enrolled in Part A who received the selected dose formulation of the nine-valent human papillomavirus vaccine or four-valent human papillomavirus vaccine continued to be followed up and contributed to the final efficacy and safety analyses. In addition, ∼ 13,400 women 16-26 years of age were enrolled in Part B, randomized to nine-valent human papillomavirus vaccine at the selected dose formulation or four-valent human papillomavirus vaccine, and followed for immunogenicity, efficacy, and safety. A seamless Phase IIB/III design was justified by the extensive pre-existing knowledge of the licensed four-valent human papillomavirus vaccine and the development objectives for the nine-valent human papillomavirus vaccine. Subjects enrolled in Part A who received either the selected nine-valent human papillomavirus formulation or four-valent human papillomavirus vaccine contributed ∼ 10% of person-years of follow-up due to its earlier start-thereby maximizing the overall efficiency of the trial. Some of the challenges encountered in the implementation of the adaptive design included practical considerations during Phase IIB formulation selection by internal and external committees, End-of-Phase II discussion with health authorities and managing changes in the assay for immunological endpoints. Application of the experience and lesson learned from this seamless adaptive design to other clinical programs may depend on case-by-case consideration. A seamless Phase IIB/III adaptive design was successfully implemented in this large outcome study. The development time of the second-generation nine-valent human papillomavirus vaccine was shortened due to improved statistical efficiency. © The Author(s) 2014.
Human evolutionary genomics: ethical and interpretive issues.
Vitti, Joseph J; Cho, Mildred K; Tishkoff, Sarah A; Sabeti, Pardis C
2012-03-01
Genome-wide computational studies can now identify targets of natural selection. The unique information about humans these studies reveal, and the media attention they attract, indicate the need for caution and precision in communicating results. This need is exacerbated by ways in which evolutionary and genetic considerations have been misapplied to support discriminatory policies, by persistent misconceptions of these fields and by the social sensitivity surrounding discussions of racial ancestry. We discuss the foundations, accomplishments and future directions of human evolutionary genomics, attending to ways in which the interpretation of good science can go awry, and offer suggestions for researchers to prevent misapplication of their work. Copyright © 2011 Elsevier Ltd. All rights reserved.
ERIC Educational Resources Information Center
Stokes, Laura
2009-01-01
In 2007, the United Animal Nations (UAN) launched the Humane Education Ambassador Readers (HEAR), an innovation that focused on mitigation of animal suffering through education. In the HEAR program, adult volunteers read carefully selected story books to children in grades 3-6 in schools or other educational settings, and hold discussions with the…
NASA Technical Reports Server (NTRS)
Haines, Richard F.
1990-01-01
As telescience systems become more and more complex, autonomous, and opaque to their operators it becomes increasingly difficult to determine whether the total system is performing as it should. Some of the complex and interrelated human performance measurement issues are addressed as they relate to total system validation. The assumption is made that human interaction with the automated system will be required well into the Space Station Freedom era. Candidate human performance measurement-validation techniques are discussed for selected ground-to-space-to-ground and space-to-space situations. Most of these measures may be used in conjunction with an information throughput model presented elsewhere (Haines, 1990). Teleoperations, teleanalysis, teleplanning, teledesign, and teledocumentation are considered, as are selected illustrative examples of space related telescience activities.
Analysis of single nucleotide polymorphisms in case-control studies.
Li, Yonghong; Shiffman, Dov; Oberbauer, Rainer
2011-01-01
Single nucleotide polymorphisms (SNPs) are the most common type of genetic variants in the human genome. SNPs are known to modify susceptibility to complex diseases. We describe and discuss methods used to identify SNPs associated with disease in case-control studies. An outline on study population selection, sample collection and genotyping platforms is presented, complemented by SNP selection, data preprocessing and analysis.
Matson, Liana M; McCarren, Hilary S; Cadieux, C Linn; Cerasoli, Douglas M; McDonough, John H
2018-01-15
Genetics likely play a role in various responses to nerve agent exposure, as genetic background plays an important role in behavioral, neurological, and physiological responses to environmental stimuli. Mouse strains or selected lines can be used to identify susceptibility based on background genetic features to nerve agent exposure. Additional genetic techniques can then be used to identify mechanisms underlying resistance and sensitivity, with the ultimate goal of developing more effective and targeted therapies. Here, we discuss the available literature on strain and selected line differences in cholinesterase activity levels and response to nerve agent-induced toxicity and seizures. We also discuss the available cholinesterase and toxicity literature across different non-human primate species. The available data suggest that robust genetic differences exist in cholinesterase activity, nerve agent-induced toxicity, and chemical-induced seizures. Available cholinesterase data suggest that acetylcholinesterase activity differs across strains, but are limited by the paucity of carboxylesterase data in strains and selected lines. Toxicity and seizures, two outcomes of nerve agent exposure, have not been fully evaluated for genetic differences, and thus further studies are required to understand baseline strain and selected line differences. Published by Elsevier B.V.
Discovery of an Oxybenzylglycine Based Peroxisome Proliferator Activated Receptor Alpha Selective
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, J.; Kennedy, L; Shi, Y
2010-01-01
An 1,3-oxybenzylglycine based compound 2 (BMS-687453) was discovered to be a potent and selective peroxisome proliferator activated receptor (PPAR) {alpha} agonist, with an EC{sub 50} of 10 nM for human PPAR{alpha} and {approx}410-fold selectivity vs human PPAR{gamma} in PPAR-GAL4 transactivation assays. Similar potencies and selectivity were also observed in the full length receptor co-transfection assays. Compound 2 has negligible cross-reactivity against a panel of human nuclear hormone receptors including PPAR{delta}. Compound 2 demonstrated an excellent pharmacological and safety profile in preclinical studies and thus was chosen as a development candidate for the treatment of atherosclerosis and dyslipidemia. The X-ray cocrystalmore » structures of the early lead compound 12 and compound 2 in complex with PPAR{alpha} ligand binding domain (LBD) were determined. The role of the crystal structure of compound 12 with PPAR{alpha} in the development of the SAR that ultimately resulted in the discovery of compound 2 is discussed.« less
Caruana, Fausto; Uithol, Sebo; Cantalupo, Gaetano; Sartori, Ivana; Lo Russo, Giorgio; Avanzini, Pietro
2014-01-01
Recent findings in monkeys suggest that action selection is based on a competition between various action options that are automatically planned by the motor system. Here we discuss data from intracranial EEG recordings in human premotor cortex (PMC) during a bimanual version of the Eriksen flankers test that suggest that the same principles apply to human action decisions. Recording sites in the dorsal PMC show an early but undifferentiated activation, a delayed response that depends on the experimental conditions and, finally, a movement related activation during action execution. Additionally, we found that the medial part of the PMC show a significant increase in response for ipsilateral trials, suggesting a role in inhibiting the wrong response. The ventral PMC seems to be involved in action execution, rather than action selection. Together these findings suggest that the human PMC is part of a network that specifies, selects, and executes actions. PMID:25206328
Binaural frequency selectivity in humans.
Verhey, Jesko L; van de Par, Steven
2018-01-23
Several behavioural studies in humans have shown that listening to sounds with two ears that is binaural hearing, provides the human auditory system with extra information on the sound source that is not available when sounds are only perceived through one ear that is monaurally. Binaural processing involves the analysis of phase and level differences between the two ear signals. As monaural cochlea processing (in each ear) precedes the neural stages responsible for binaural processing properties it is reasonable to assume that properties of the cochlea may also be observed in binaural processing. A main characteristic of cochlea processing is its frequency selectivity. In psychoacoustics, there is an ongoing discussion on the frequency selectivity of the binaural auditory system. While some psychoacoustic experiments seem to indicate poorer frequency selectivity of the binaural system than that of the monaural processing others seem to indicate the same frequency selectivity for monaural and binaural processing. This study provides an overview of these seemingly controversial results and the different explanations that were provided to account for the different results. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Human performance models for computer-aided engineering
NASA Technical Reports Server (NTRS)
Elkind, Jerome I. (Editor); Card, Stuart K. (Editor); Hochberg, Julian (Editor); Huey, Beverly Messick (Editor)
1989-01-01
This report discusses a topic important to the field of computational human factors: models of human performance and their use in computer-based engineering facilities for the design of complex systems. It focuses on a particular human factors design problem -- the design of cockpit systems for advanced helicopters -- and on a particular aspect of human performance -- vision and related cognitive functions. By focusing in this way, the authors were able to address the selected topics in some depth and develop findings and recommendations that they believe have application to many other aspects of human performance and to other design domains.
Development and human resources in the Islamic world: a study of selected countries.
Duza, M B
1987-01-01
"The present paper attempts to provide an analytical profile of development and human resources in [12] selected [Islamic] countries." The countries--Bangladesh, Somalia, Pakistan, Indonesia, Egypt, Turkey, Malaysia, Algeria, Iraq, Saudi Arabia, Kuwait, and United Arab Emirates--vary in income levels from low to high and in population size from 1 million to 159 million. Using data from the World Bank and the Population Council, comparisons are made on the basis of mortality and fertility levels, family size, income, urbanization, labor force size and growth, education, nutrition, and health. Governmental policy changes and future directions are discussed. excerpt
Dong, Dong; Ako, Roland; Hu, Ming; Wu, Baojian
2015-01-01
The UDP-glucuronosyltransferase (UGT) enzyme catalyzes the glucuronidation reaction which is a major metabolic and detoxification pathway in humans. Understanding the mechanisms for substrate recognition by UGT assumes great importance in an attempt to predict its contribution to xenobiotic/drug disposition in vivo. Spurred on by this interest, 2D/3D-quantitative structure activity relationships (QSAR) and pharmacophore models have been established in the absence of a complete mammalian UGT crystal structure. This review discusses the recent progress in modeling human UGT substrates including those with multiple sites of glucuronidation. A better understanding of UGT active site contributing to substrate selectivity (and regioselectivity) from the homologous enzymes (i.e., plant and bacterial UGTs, all belong to family 1 of glycosyltransferase (GT1)) is also highlighted, as these enzymes share a common catalytic mechanism and/or overlapping substrate selectivity. PMID:22385482
Five rules for the evolution of cooperation.
Nowak, Martin A
2006-12-08
Cooperation is needed for evolution to construct new levels of organization. Genomes, cells, multicellular organisms, social insects, and human society are all based on cooperation. Cooperation means that selfish replicators forgo some of their reproductive potential to help one another. But natural selection implies competition and therefore opposes cooperation unless a specific mechanism is at work. Here I discuss five mechanisms for the evolution of cooperation: kin selection, direct reciprocity, indirect reciprocity, network reciprocity, and group selection. For each mechanism, a simple rule is derived that specifies whether natural selection can lead to cooperation.
Five Rules for the Evolution of Cooperation
NASA Astrophysics Data System (ADS)
Nowak, Martin A.
2006-12-01
Cooperation is needed for evolution to construct new levels of organization. Genomes, cells, multicellular organisms, social insects, and human society are all based on cooperation. Cooperation means that selfish replicators forgo some of their reproductive potential to help one another. But natural selection implies competition and therefore opposes cooperation unless a specific mechanism is at work. Here I discuss five mechanisms for the evolution of cooperation: kin selection, direct reciprocity, indirect reciprocity, network reciprocity, and group selection. For each mechanism, a simple rule is derived that specifies whether natural selection can lead to cooperation.
Selection and Transmission of Antibiotic-Resistant Bacteria.
Andersson, Dan I; Hughes, Diarmaid
2017-07-01
Ever since antibiotics were introduced into human and veterinary medicine to treat and prevent bacterial infections there has been a steady selection and increase in the frequency of antibiotic resistant bacteria. To be able to reduce the rate of resistance evolution, we need to understand how various biotic and abiotic factors interact to drive the complex processes of resistance emergence and transmission. We describe several of the fundamental factors that underlay resistance evolution, including rates and niches of emergence and persistence of resistant bacteria, time- and space-gradients of various selective agents, and rates and routes of transmission of resistant bacteria between humans, animals and other environments. Furthermore, we discuss the options available to reduce the rate of resistance evolution and/ or transmission and their advantages and disadvantages.
Dietary supplements and human health: for better or for worse?
Jerome-Morais, Anita; Diamond, Alan M; Wright, Margaret E
2011-01-01
Encouraged by the potential health benefits of higher dietary intake of substances with beneficial properties, the use of supplements containing these compounds has increased steadily over recent years. The effects of several of these, many of which are antioxidants, have been supported by data obtained in vitro, in animal models, and often by human studies as well. However, as carefully controlled human supplementation trials have been conducted, questions about the efficacy and safety of these supplements have emerged. In this Educational Paper, three different supplements were selected for consideration of the benefits and risks currently associated with their intake. The selected supplements include β-carotene, selenium, and genistein. The use of each is discussed in the context of preclinical and clinical data that provide evidence for both their use in reducing disease incidence and the possible liabilities that accompany their enhanced consumption. Variables that may influence their impact, such as lifestyle habits, baseline nutritional levels, and genetic makeup are considered and the application of these issues to broader classes of supplements is discussed. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Whitehead, Lewis; Dobler, Markus R.; Radetich, Branko
2013-11-20
Herein we report the discovery of a family of novel yet simple, amino-acid derived class I HDAC inhibitors that demonstrate isoform selectivity via access to the internal acetate release channel. Isoform selectivity criteria is discussed on the basis of X-ray crystallography and molecular modeling of these novel inhibitors bound to HDAC8, potentially revealing insights into the mechanism of enzymatic function through novel structural features revealed at the atomic level.
ERIC Educational Resources Information Center
Corcos, Alain
1983-01-01
Information from scientific journals on the biology of skin color is discussed. Major areas addressed include: (1) biology of melanin, melanocytes, and melanosomes; (2) melanosome and human diversity; (3) genetics of skin color; and (4) skin color, geography, and natural selection. (JN)
NASA Astrophysics Data System (ADS)
Iwamura, Koji; Kuwahara, Shinya; Tanimizu, Yoshitaka; Sugimura, Nobuhiro
Recently, new distributed architectures of manufacturing systems are proposed, aiming at realizing more flexible control structures of the manufacturing systems. Many researches have been carried out to deal with the distributed architectures for planning and control of the manufacturing systems. However, the human operators have not yet been discussed for the autonomous components of the distributed manufacturing systems. A real-time scheduling method is proposed, in this research, to select suitable combinations of the human operators, the resources and the jobs for the manufacturing processes. The proposed scheduling method consists of following three steps. In the first step, the human operators select their favorite manufacturing processes which they will carry out in the next time period, based on their preferences. In the second step, the machine tools and the jobs select suitable combinations for the next machining processes. In the third step, the automated guided vehicles and the jobs select suitable combinations for the next transportation processes. The second and third steps are carried out by using the utility value based method and the dispatching rule-based method proposed in the previous researches. Some case studies have been carried out to verify the effectiveness of the proposed method.
Surface Support Systems for Co-Operative and Integrated Human/Robotic Lunar Exploration
NASA Technical Reports Server (NTRS)
Mueller, Robert P.
2006-01-01
Human and robotic partnerships to realize space goals can enhance space missions and provide increases in human productivity while decreasing the hazards that the humans are exposed to. For lunar exploration, the harsh environment of the moon and the repetitive nature of the tasks involved with lunar outpost construction, maintenance and operation as well as production tasks associated with in-situ resource utilization, make it highly desirable to use robotic systems in co-operation with human activity. A human lunar outpost is functionally examined and concepts for selected human/robotic tasks are discussed in the context of a lunar outpost which will enable the presence of humans on the moon for extended periods of time.
NASA Technical Reports Server (NTRS)
Davis, Robert P.; Underwood, Ian M.
1987-01-01
The use of database management systems (DBMS) and AI to minimize human involvement in the planning of optical navigation pictures for interplanetary space probes is discussed, with application to the Galileo mission. Parameters characterizing the desirability of candidate pictures, and the program generating them, are described. How these parameters automatically build picture records in a database, and the definition of the database structure, are then discussed. The various rules, priorities, and constraints used in selecting pictures are also described. An example is provided of an expert system, written in Prolog, for automatically performing the selection process.
Human Cognition and Information Display in C3I System Tasks.
1988-12-01
goes without saying that rule-based tasks are the easiest to automate, but for reasons discussed earlier, they still merit our attention . Moreover...selective attention task. Since selective attention must operate after memory retrieval, it is only when different responses are elicited that the...stimuli that is processed by impairing the memory traces of signals that originally attract less attention . Although the research reviewed above gives
Antitumor Efficacy Testing in Rodents
2008-01-01
The preclinical research and human clinical trials necessary for developing anticancer therapeutics are costly. One contributor to these costs is preclinical rodent efficacy studies, which, in addition to the costs associated with conducting them, often guide the selection of agents for clinical development. If inappropriate or inaccurate recommendations are made on the basis of these preclinical studies, then additional costs are incurred. In this commentary, I discuss the issues associated with preclinical rodent efficacy studies. These include the identification of proper preclinical efficacy models, the selection of appropriate experimental endpoints, and the correct statistical evaluation of the resulting data. I also describe important experimental design considerations, such as selecting the drug vehicle, optimizing the therapeutic treatment plan, properly powering the experiment by defining appropriate numbers of replicates in each treatment arm, and proper randomization. Improved preclinical selection criteria can aid in reducing unnecessary human studies, thus reducing the overall costs of anticancer drug development. PMID:18957675
Antonello, ZA; Nucera, C
2015-01-01
Molecular signature of advanced and metastatic thyroid carcinoma involves deregulation of multiple fundamental pathways activated in the tumor microenvironment. They include BRAFV600E and AKT that affect tumor initiation, progression and metastasis. Human thyroid cancer orthotopic mouse models are based on human cell lines that generally harbor genetic alterations found in human thyroid cancers. They can reproduce in vivo and in situ (into the thyroid) many features of aggressive and refractory human advanced thyroid carcinomas, including local invasion and metastasis. Humanized orthotopic mouse models seem to be ideal and commonly used for preclinical and translational studies of compounds and therapies not only because they may mimic key aspects of human diseases (e.g. metastasis), but also for their reproducibility. In addition, they might provide the possibility to evaluate systemic effects of treatments. So far, human thyroid cancer in vivo models were mainly used to test single compounds, non selective and selective. Despite the greater antitumor activity and lower toxicity obtained with different selective drugs in respect to non-selective ones, most of them are only able to delay disease progression, which ultimately could restart with similar aggressive behavior. Aggressive thyroid tumors (for example, anaplastic or poorly differentiated thyroid carcinoma) carry several complex genetic alterations that are likely cooperating to promote disease progression and might confer resistance to single-compound approaches. Orthotopic models of human thyroid cancer also hold the potential to be good models for testing novel combinatorial therapies. In this article, we will summarize results on preclinical testing of selective and nonselective single compounds in orthotopic mouse models based on validated human thyroid cancer cell lines harboring the BRAFV600E mutation or with wild-type BRAF. Furthermore, we will discuss the potential use of this model also for combinatorial approaches, which are expected to take place in the upcoming human thyroid cancer basic and clinical research. PMID:24362526
Five rules for the evolution of cooperation
Nowak, Martin A.
2011-01-01
Cooperation is needed for evolution to construct new levels of organization. The emergence of genomes, cells, multi-cellular organisms, social insects and human society are all based on cooperation. Cooperation means that selfish replicators forgo some of their reproductive potential to help one another. But natural selection implies competition and therefore opposes cooperation unless a specific mechanism is at work. Here I discuss five mechanisms for the evolution of cooperation: kin selection, direct reciprocity, indirect reciprocity, network reciprocity and group selection. For each mechanism, a simple rule is derived which specifies whether natural selection can lead to cooperation. PMID:17158317
DOE Office of Scientific and Technical Information (OSTI.GOV)
Li, Jun; Kennedy, Lawrence J.; Shi, Yan
2010-04-12
An 1,3-oxybenzylglycine based compound 2 (BMS-687453) was discovered to be a potent and selective peroxisome proliferator activated receptor (PPAR) {alpha} agonist, with an EC{sub 50} of 10 nM for human PPAR{alpha} and 410-fold selectivity vs human PPAR{gamma} in PPAR-GAL4 transactivation assays. Similar potencies and selectivity were also observed in the full length receptor co-transfection assays. Compound 2 has negligible cross-reactivity against a panel of human nuclear hormone receptors including PPAR{delta}. Compound 2 demonstrated an excellent pharmacological and safety profile in preclinical studies and thus was chosen as a development candidate for the treatment of atherosclerosis and dyslipidemia. The X-ray cocrystalmore » structures of the early lead compound 12 and compound 2 in complex with PPAR{alpha} ligand binding domain (LBD) were determined. The role of the crystal structure of compound 12 with PPAR{alpha} in the development of the SAR that ultimately resulted in the discovery of compound 2 is discussed.« less
Pilot interaction with automated airborne decision making systems
NASA Technical Reports Server (NTRS)
Rouse, W. B.; Hammer, J. M.; Morris, N. M.; Knaeuper, A. E.; Brown, E. N.; Lewis, C. M.; Yoon, W. C.
1984-01-01
Two project areas were pursued: the intelligent cockpit and human problem solving. The first area involves an investigation of the use of advanced software engineering methods to aid aircraft crews in procedure selection and execution. The second area is focused on human problem solving in dynamic environments, particulary in terms of identification of rule-based models land alternative approaches to training and aiding. Progress in each area is discussed.
A philosophy for CNS radiotracer design.
Van de Bittner, Genevieve C; Ricq, Emily L; Hooker, Jacob M
2014-10-21
Decades after its discovery, positron emission tomography (PET) remains the premier tool for imaging neurochemistry in living humans. Technological improvements in radiolabeling methods, camera design, and image analysis have kept PET in the forefront. In addition, the use of PET imaging has expanded because researchers have developed new radiotracers that visualize receptors, transporters, enzymes, and other molecular targets within the human brain. However, of the thousands of proteins in the central nervous system (CNS), researchers have successfully imaged fewer than 40 human proteins. To address the critical need for new radiotracers, this Account expounds on the decisions, strategies, and pitfalls of CNS radiotracer development based on our current experience in this area. We discuss the five key components of radiotracer development for human imaging: choosing a biomedical question, selection of a biological target, design of the radiotracer chemical structure, evaluation of candidate radiotracers, and analysis of preclinical imaging. It is particularly important to analyze the market of scientists or companies who might use a new radiotracer and carefully select a relevant biomedical question(s) for that audience. In the selection of a specific biological target, we emphasize how target localization and identity can constrain this process and discuss the optimal target density and affinity ratios needed for binding-based radiotracers. In addition, we discuss various PET test-retest variability requirements for monitoring changes in density, occupancy, or functionality for new radiotracers. In the synthesis of new radiotracer structures, high-throughput, modular syntheses have proved valuable, and these processes provide compounds with sites for late-stage radioisotope installation. As a result, researchers can manage the time constraints associated with the limited half-lives of isotopes. In order to evaluate brain uptake, a number of methods are available to predict bioavailability, blood-brain barrier (BBB) permeability, and the associated issues of nonspecific binding and metabolic stability. To evaluate the synthesized chemical library, researchers need to consider high-throughput affinity assays, the analysis of specific binding, and the importance of fast binding kinetics. Finally, we describe how we initially assess preclinical radiotracer imaging, using brain uptake, specific binding, and preliminary kinetic analysis to identify promising radiotracers that may be useful for human brain imaging. Although we discuss these five design components separately and linearly in this Account, in practice we develop new PET-based radiotracers using these design components nonlinearly and iteratively to develop new compounds in the most efficient way possible.
Selecting Appropriate Functionality and Technologies for EPSS.
ERIC Educational Resources Information Center
McGraw, Karen L.
1995-01-01
Presents background information that describes the major components of an embedded performance support system, compares levels of functionality, and discusses some of the required technologies. Highlights include the human-computer interface; online help; advisors; training and tutoring; hypermedia; and artificial intelligence techniques. (LRW)
What about Those Dietary Goals?
ERIC Educational Resources Information Center
Goodman, S. Jane
1980-01-01
This elaboration of the Dietary Goals for the United States, set by the U.S. Senate and Select Committee on Nutrition and Human Needs in 1977, details all seven dietary goals and includes a discussion of possible risk factors associated with certain chronic diseases. (JN)
ERIC Educational Resources Information Center
Thomson, Gareth
1998-01-01
Presents a simulation activity in which students assume the role of grizzly bears in Banff National Park. Concepts such as species diversity, fitness, natural selection, habitat loss, extinction, and population dynamics are discussed. Children learn how human activities can affect the bear's reproductive success. Lists materials, instructional…
JPL Robotics Technology Applicable to Agriculture
NASA Technical Reports Server (NTRS)
Udomkesmalee, Suraphol Gabriel; Kyte, L.
2008-01-01
This slide presentation describes several technologies that are developed for robotics that are applicable for agriculture. The technologies discussed are detection of humans to allow safe operations of autonomous vehicles, and vision guided robotic techniques for shoot selection, separation and transfer to growth media,
The sight of the peacock's tail makes me sick: the early arguments on sexual selection.
Hiraiwa-Hasegawa, M
2000-03-01
Why does a peacock have a beautiful train, while a peahen is sober without such flamboyance? Darwin proposed the theory of sexual selection to explain the differences between the sexes of the same species. Recently the study of sexual selection has been one of the most flourishing areas in evolutionary biology. However, the theory met with great resistance from biologists since the publication of the idea and the history of the theory included a lot of misunderstanding and confusion. There are several reasons for this. First, classical Darwinism failed to recognize social competition as an important selective force. Second, the good-for-the-species argument, which persisted in the days after Darwin, made the sexual selection argument more difficult to under-stand. Compared to the discussions on animals, Darwin's argument on human sex differences is not satisfactory. The reason probably lies in the debate over human racial differences which prevailed in the 19th century.
'Hurrah for the missing link!': a history of apes, ancestors and a crucial piece of evidence.
Kjaergaard, Peter C
2011-03-20
In the nineteenth century the idea of a 'missing link' connecting humans with the rest of the animal kingdom was eagerly embraced by professional scientists and popularizers. After the publication of Charles Darwin's Origin of Species in 1859, many tied the idea and subsequent search for a crucial piece of evidence to Darwin and his formulation of the theory of evolution by natural selection. This article demonstrates that the expression was widely used and that the framework for discussions about human's relation to the apes and gaps in the fossil record were well in place and widely debated long before Origin of Species became the standard reference for discussing human evolution. In the second half of the century the missing link gradually became the ultimate prize in palaeoanthropology and grew into one of the most powerful, celebrated and criticized icons of human evolution.
Can IVF influence human evolution?
Hanevik, Hans Ivar; Hessen, Dag O; Sunde, Arne; Breivik, Jarle
2016-07-01
IVF, a procedure in which pharmacological and technological manipulation is used to promote pregnancy, offers help to infertile couples by circumventing selection at the most fundamental level. Fertility is clearly one of the key fitness-promoting drivers in all forms of sexually reproducing life, and fertilization and pregnancy are fundamental evolutionary processes that involve a range of pre- and post-zygotic screening mechanisms. Here, we discuss the various selection and screening factors involved in fertilization and pregnancy and assess IVF practices in light of these factors. We then focus on the possible consequences of these differences in selection pressures, mainly at the individual but also at the population level, to evaluate whether changes in the reproducing genotype can affect human evolution. The aim of the article is not to argue for or against IVF, but to address aspects of assisted reproduction in an evolutionary context. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Serial grouping of 2D-image regions with object-based attention in humans.
Jeurissen, Danique; Self, Matthew W; Roelfsema, Pieter R
2016-06-13
After an initial stage of local analysis within the retina and early visual pathways, the human visual system creates a structured representation of the visual scene by co-selecting image elements that are part of behaviorally relevant objects. The mechanisms underlying this perceptual organization process are only partially understood. We here investigate the time-course of perceptual grouping of two-dimensional image-regions by measuring the reaction times of human participants and report that it is associated with the gradual spread of object-based attention. Attention spreads fastest over large and homogeneous areas and is slowed down at locations that require small-scale processing. We find that the time-course of the object-based selection process is well explained by a 'growth-cone' model, which selects surface elements in an incremental, scale-dependent manner. We discuss how the visual cortical hierarchy can implement this scale-dependent spread of object-based attention, leveraging the different receptive field sizes in distinct cortical areas.
The Cognitive Costs and Benefits of Automation
2003-10-01
paper discusses the cognitive costs and benefits related to the automation within the execution of all processes that lead to the course of action...selection. Among the benefits identified, the human workload and the demand of attentional resources can be significantly reduced. A major cognitive cost
Human infection with highly pathogenic H5N1 influenza virus.
Gambotto, Andrea; Barratt-Boyes, Simon M; de Jong, Menno D; Neumann, Gabriele; Kawaoka, Yoshihiro
2008-04-26
Highly pathogenic H5N1 influenza A viruses have spread relentlessly across the globe since 2003, and they are associated with widespread death in poultry, substantial economic loss to farmers, and reported infections of more than 300 people with a mortality rate of 60%. The high pathogenicity of H5N1 influenza viruses and their capacity for transmission from birds to human beings has raised worldwide concern about an impending human influenza pandemic similar to the notorious H1N1 Spanish influenza of 1918. Since many aspects of H5N1 influenza research are rapidly evolving, we aim in this Seminar to provide an up-to-date discussion on select topics of interest to influenza clinicians and researchers. We summarise the clinical features and diagnosis of infection and present therapeutic options for H5N1 infection of people. We also discuss ideas relating to virus transmission, host restriction, and pathogenesis. Finally, we discuss vaccine development in view of the probable importance of vaccination in pandemic control.
Riparian landscapes and human habitat preferences during the Hoxnian (MIS 11) Interglacial
NASA Astrophysics Data System (ADS)
Ashton, Nick; Lewis, Simon G.; Parfitt, Simon; White, Mark
2006-07-01
The archaeological, environmental and geological data from Hoxnian Interglacial (Marine Isotope Stage (MIS) 11) sites from Britain are examined to elucidate the type of habitats that humans preferred during this temperate episode. The conclusion is that humans avoided lacustrine situations, but did make use of the full range of resources that fluvial environments provide. This model is strengthened by the examination of other non-archaeological Hoxnian sites. The problem of archaeological visibility in lacustrine sediment sequences is also discussed and methods of identifying other evidence of human presence are suggested that may offset the deficiencies in the lithic record. These include presence of cut-marked bone, micro-debitage and possibly charcoal in fine-grained sediments deposited in distal settings. The reasons for human selection of fluvial situations are discussed. It is concluded that these environments provide a greater diversity of animal, plant and lithic resources, but also are major route-ways through the landscape. Patterns of human site use are identified, which seem to be triggered by local changes in hydrology and drainage, themselves possibly caused by regional changes in climate. Finally, Lower Palaeolithic sites on the interfluves are discussed. Although they lack environmental or dating evidence, it is tentatively suggested that they were used during cooler episodes, when more open conditions prevailed. Copyright
ERIC Educational Resources Information Center
Stedman, Donald J., Ed.
Six papers discuss some of the current issues in the field of mental retardation and human development. Epidemiology of mental retardation from a sociological and clinical point of view is analyzed by Jane R. Mercer, based on studies of mental retardation in the community in Pomona, California. The role of genetics and intra-uterine diagnosis of…
1981-02-01
Continue on tevetee «Id* If necemtery mid Identify br black number) Battlefield automated systems Human- computer interaction. Design criteria System...Report (this report) In-Depth Analyses of Individual Systems A. Tactical Fire Direction System (TACFIRE) (RP 81-26) B. Tactical Computer Terminal...select the design features and operating procedures of the human- computer Interface which best match the require- ments and capabilities of anticipated
Selected questions of topical interest in human bioclimatology
NASA Astrophysics Data System (ADS)
Jendritzky, G.
1991-09-01
This paper deals with the different effects of climate, and the likely impact of climatic change, on the human being, his health and well-being. Those effects follow from consideration of the human energy budget and air pollution, including photooxidants and radiation, the latter especially in the UV-range. The development of tools to produce bioclimate maps, i.e. maps expressed in physiologically significant terms, in different scales up to the high resolution necessary for the microscale urban climate, will be discussed. The most important questions in bioclimate research and its application will be considered.
Selected questions of topical interest in human bioclimatology.
Jendritzky, G
1991-11-01
This paper deals with the different effects of climate, and the likely impact of climatic change, on the human being, his health and well-being. Those effects follow from consideration of the human energy budget and air pollution, including photooxidants and radiation, the latter especially in the UV-range. The development of tools to produce bioclimate maps, i.e. maps expressed in physiologically significant terms, in different scales up to the high resolution necessary for the microscale urban climate, will be discussed. The most important questions in bioclimate research and its application will be considered.
Operational Aspects of Space Radiation
NASA Technical Reports Server (NTRS)
1997-01-01
In this session, Session FA4, the discussion focuses on the following topics: Solar Particle Events and the International Space Station; Radiation Environment on Mir and ISS Orbits During the Solar Cycle; New approach to Radiation Risk Assessment; An Industrial Method to Predict Major Solar Flares for a Better Protection of Human Beings in Space; Description of the Space Radiation Control System for the Russian Segment of ISS; Orbit Selection and Its Impact on Radiation Warning Architecture for a Human Mission to Mars; and Space Nuclear Power - Technology, Policy and Risk Considerations in Human Missions to Mars.
Demographic history, selection and functional diversity of the canine genome.
Ostrander, Elaine A; Wayne, Robert K; Freedman, Adam H; Davis, Brian W
2017-12-01
The domestic dog represents one of the most dramatic long-term evolutionary experiments undertaken by humans. From a large wolf-like progenitor, unparalleled diversity in phenotype and behaviour has developed in dogs, providing a model for understanding the developmental and genomic mechanisms of diversification. We discuss pattern and process in domestication, beginning with general findings about early domestication and problems in documenting selection at the genomic level. Furthermore, we summarize genotype-phenotype studies based first on single nucleotide polymorphism (SNP) genotyping and then with whole-genome data and show how an understanding of evolution informs topics as different as human history, adaptive and deleterious variation, morphological development, ageing, cancer and behaviour.
Neural Mechanisms of Selective Visual Attention.
Moore, Tirin; Zirnsak, Marc
2017-01-03
Selective visual attention describes the tendency of visual processing to be confined largely to stimuli that are relevant to behavior. It is among the most fundamental of cognitive functions, particularly in humans and other primates for whom vision is the dominant sense. We review recent progress in identifying the neural mechanisms of selective visual attention. We discuss evidence from studies of different varieties of selective attention and examine how these varieties alter the processing of stimuli by neurons within the visual system, current knowledge of their causal basis, and methods for assessing attentional dysfunctions. In addition, we identify some key questions that remain in identifying the neural mechanisms that give rise to the selective processing of visual information.
Weigle, David S.
1990-01-01
This discussion was selected from the weekly Grand Rounds in the Department of Medicine, University of Washington School of Medicine, Seattle. Taken from a transcription, it has been edited by Drs Paul G. Ramsey, Associate Professor of Medicine, and Philip J. Fialkow, Professor and Chair of the Department of Medicine. PMID:2244378
Opportunities and Problems in Marketing Programs.
ERIC Educational Resources Information Center
Coe, Barbara J.; Welch, Joe
1988-01-01
A description and discussion of a university market penetration plan looks at problems and opportunities related to market selection, establishment of performance objectives, timing, use of human resources, developing a promotional plan and activities, doing a market survey, garnering alumni support, using the media, and using college-community…
ERIC Educational Resources Information Center
Condon, E. C., Ed.; Freundlich, Joyce
Verbal and nonverbal patterns of communication found in the black community are discussed in this paper. They have been selected on the basis of their potential as interference factors in intergroup communication. A section on black language describes and explains the following categories: rapping, running it down, jiving, shucking, copping a…
Helle, Samuli; Lummaa, Virpi; Jokela, Jukka
2005-01-01
Evolutionary theory of senescence emphasizes the importance of intense selection on early reproduction owing to the declining force of natural selection with age that constrains lifespan. In humans, recent studies have, however, suggested that late-life mortality might be more closely related to late rather than early reproduction, although the role of late reproduction on fitness remains unclear. We examined the association between early and late reproduction with longevity in historical post-reproductive Sami women. We also estimated the strength of natural selection on early and late reproduction using path analysis, and the effect of reproductive timing on offspring survival to adulthood and maternal risk of dying at childbirth. We found that natural selection favoured both earlier start and later cessation of reproduction, and higher total fe cundity. Maternal age at childbirth was not related to offspring or maternal survival. Interestingly, females who produced their last offspring at advanced age also lived longest, while age at first reproduction and total fecundity were unrelated to female longevity. Our results thus suggest that reproductive and somatic senescence may have been coupled in these human populations, and that selection could have favoured late reproduction. We discuss alternative hypotheses for the mechanisms which might have promoted the association between late reproduction and longevity. PMID:15875567
Beatles versus Beethoven: Using Music to Introduce Cognitive Structures
ERIC Educational Resources Information Center
Herman, Andrew P.; Wyant, Christopher P.
2006-01-01
The concepts of social cognition and cognitive structures are important aspects of constructivism and human communication theory. By asking students to listen to different musical selections and fill in a simple rubric, different schemas become apparent. This creates an opportunity to discuss how cognitions relate to communication. Students who…
Cosmic Education: Linking the Human to the Universe.
ERIC Educational Resources Information Center
Gebhardt-Seele, Peter
2002-01-01
Describes cosmic education as the Montessori guide for educating 6- to 12-year-olds. Discusses practical consequences of Montessori's ideas, including the selection of the "great story," the need for physics at the elementary level to teach the laws of nature, the citizen's responsibility for the earth's survival, the importance of…
Cognitive Socialization and Competence: The Academic Development of Chicanos. Chapter 7.
ERIC Educational Resources Information Center
Laosa, Luis M.; Henderson, Ronald W.
This chapter focuses on the innermost level of Bronfenbrenner's four-level conception of the human environmental ecology, namely the microsystem, and more specifically, the child's socialization in the family. Following discussion of concepts related to socialization, competence, and environmental ecology, selected research studies are reviewed to…
HRD in Latin America. Symposium 5. [AHRD Conference, 2001].
ERIC Educational Resources Information Center
2001
This document contains three papers on human resource development (HRD) in Latin America. "Looking at the Literature on Workplace Democracy in Latin America: Factors in Favor and Against It" (Max U. Montesino) discusses selected issues related to workplace democracy in Latin America and identifies salient issues for further research,…
Dupont, Joëlle; Dequin, Sylvie; Giraud, Tatiana; Le Tacon, François; Marsit, Souhir; Ropars, Jeanne; Richard, Franck; Selosse, Marc-André
2017-06-01
In this article, we review some of the best-studied fungi used as food sources, in particular, the cheese fungi, the truffles, and the fungi used for drink fermentation such as beer, wine, and sake. We discuss their history of consumption by humans and the genomic mechanisms of adaptation during artificial selection.
Comparative Analysis of Human Communication Networks in Selected Formal Organizations.
ERIC Educational Resources Information Center
Farace, Richard V.; Johnson, Jerome David
This paper briefly describes the organization of a "data bank" containing research on communication networks, specifies the kinds of information compiled about various network properties, discusses some specific results of the work done to date, and presents some general conclusions about the overall project and its potential advantages to…
Sweeney, Mary M.; Shahan, Timothy A.
2016-01-01
Resurgence following removal of alternative reinforcement has been studied in non-human animals, children with developmental disabilities, and typically functioning adults. Adult human laboratory studies have included responses without a controlled history of reinforcement, included only two response options, or involved extensive training. Arbitrary responses allow for control over history of reinforcement. Including an inactive response never associated with reinforcement allows the conclusion that resurgence exceeds extinction-induced variability. Although procedures with extensive training produce reliable resurgence, a brief procedure with the same experimental control would allow more efficient examination of resurgence in adult humans. We tested the acceptability of a brief, single-session, three-alternative forced-choice procedure as a model of resurgence in undergraduates. Selecting a shape was the target response (reinforced in Phase I), selecting another shape was the alternative response (reinforced in Phase II), and selecting a third shape was never reinforced. Despite manipulating number of trials and probability of reinforcement, resurgence of the target response did not consistently exceed increases in the inactive response. Our findings reiterate the importance of an inactive control response and call for reexamination of resurgence studies using only two response options. We discuss potential approaches to generate an acceptable, brief human laboratory resurgence procedure. PMID:26724752
Hughes, L.; Eckstein, D.; Owen, A.M.
2008-01-01
The human capacity for voluntary action is one of the major contributors to our success as a species. In addition to choosing actions themselves, we can also voluntarily choose behavioral codes or sets of rules that can guide future responses to events. Such rules have been proposed to be superordinate to actions in a cognitive hierarchy and mediated by distinct brain regions. We used event-related functional magnetic resonance imaging to study novel tasks of rule-based and voluntary action. We show that the voluntary selection of rules to govern future responses to events is associated with activation of similar regions of prefrontal and parietal cortex as the voluntary selection of an action itself. The results are discussed in terms of hierarchical models and the adaptive coding potential of prefrontal neurons and their contribution to a global workspace for nonautomatic tasks. These tasks include the choices we make about our behavior. PMID:18234684
Olmo, Neide Regina Simões; do Nascimento Saldiva, Paulo Hilário; Braga, Alfésio Luís Ferreira; Lin, Chin An; de Paula Santos, Ubiratan; Pereira, Luiz Alberto Amador
2011-01-01
The aim of this study was to review original scientific articles describing the relationship between atmospheric pollution and damage to human health. We also aimed to determine which of these studies mentioned public policy issues. Original articles relating to atmospheric pollution and human health published between 1995 and 2009 were retrieved from the PubMed database and analyzed. This study included only articles dealing with atmospheric pollutants resulting primarily from vehicle emissions. Three researchers were involved in the final selection of the studies, and the chosen articles were approved by at least two of the three researchers. Of the 84 non-Brazilian studies analyzed, 80 showed an association between atmospheric pollution and adverse effects on human health. Moreover, 66 showed evidence of adverse effects on human health, even at levels below the permitted emission standards. Three studies mentioned public policies aimed at changing emission standards. Similarly, the 29 selected Brazilian studies reported adverse associations with human health, and 27 showed evidence of adverse effects even at levels below the legally permitted emission standards. Of these studies, 16 mentioned public policies aimed at changing emission standards. Based on the Brazilian and non-Brazilian scientific studies that have been conducted, it can be concluded that, even under conditions that are compliant with Brazilian air quality standards, the concentration of atmospheric pollutants in Brazil can negatively affect human health. However, as little discussion of this topic has been generated, this finding demonstrates the need to incorporate epidemiological evidence into decisions regarding legal regulations and to discuss the public policy implications in epidemiological studies. PMID:21655765
Gumarova, L; Cornélissen, G; Hillman, D; Halberg, F
2013-10-01
In the incidence patterns of cholera, diphtheria and croup during the past when they were of epidemic proportions, we document a set of cycles (periods), one of which was reported and discussed by A. L. Chizhevsky in the same data with emphasis on the mirroring in human disease of the ~11-year sunspot cycle. The data in this study are based on Chizhevsky’s book The Terrestrial Echo of Solar Storms and on records from the World Health Organization. For meta-analysis, we used the extended linear and nonlinear cosinor. We found a geographically selective assortment of various cycles characterizing the epidemiology of infections, which is the documented novel topic of this paper, complementing the earlier finding in the 21st century or shortly before, of a geographically selective assortment of cycles characterizing human sudden cardiac death. Solar effects, if any, interact with geophysical processes in contributing to this assortment.
A philosophy for CNS radiotracer design
Van de Bittner, Genevieve C.; Ricq, Emily L.; Hooker, Jacob M.
2014-10-01
Decades after its discovery, positron emission tomography (PET) remains the premier tool for imaging neurochemistry in living humans. Technological improvements in radiolabeling methods, camera design, and image analysis have kept PET in the forefront. In addition, the use of PET imaging has expanded because researchers have developed new radiotracers that visualize receptors, transporters, enzymes, and other molecular targets within the human brain. However, of the thousands of proteins in the central nervous system (CNS), researchers have successfully imaged fewer than 40 human proteins. To address the critical need for new radiotracers, this Account expounds on the decisions, strategies, and pitfallsmore » of CNS radiotracer development based on our current experience in this area. We discuss the five key components of radiotracer development for human imaging: choosing a biomedical question, selection of a biological target, design of the radiotracer chemical structure, evaluation of candidate radiotracers, and analysis of preclinical imaging. It is particularly important to analyze the market of scientists or companies who might use a new radiotracer and carefully select a relevant biomedical question(s) for that audience. In the selection of a specific biological target, we emphasize how target localization and identity can constrain this process and discuss the optimal target density and affinity ratios needed for binding-based radiotracers. In addition, we discuss various PET test–retest variability requirements for monitoring changes in density, occupancy, or functionality for new radiotracers. In the synthesis of new radiotracer structures, high-throughput, modular syntheses have proved valuable, and these processes provide compounds with sites for late-stage radioisotope installation. As a result, researchers can manage the time constraints associated with the limited half-lives of isotopes. In order to evaluate brain uptake, a number of methods are available to predict bioavailability, blood–brain barrier (BBB) permeability, and the associated issues of nonspecific binding and metabolic stability. To evaluate the synthesized chemical library, researchers need to consider high-throughput affinity assays, the analysis of specific binding, and the importance of fast binding kinetics. Lastly, we describe how we initially assess preclinical radiotracer imaging, using brain uptake, specific binding, and preliminary kinetic analysis to identify promising radiotracers that may be useful for human brain imaging. Although we discuss these five design components separately and linearly in this Account, in practice we develop new PET-based radiotracers using these design components nonlinearly and iteratively to develop new compounds in the most efficient way possible.« less
A Philosophy for CNS Radiotracer Design
2015-01-01
Conspectus Decades after its discovery, positron emission tomography (PET) remains the premier tool for imaging neurochemistry in living humans. Technological improvements in radiolabeling methods, camera design, and image analysis have kept PET in the forefront. In addition, the use of PET imaging has expanded because researchers have developed new radiotracers that visualize receptors, transporters, enzymes, and other molecular targets within the human brain. However, of the thousands of proteins in the central nervous system (CNS), researchers have successfully imaged fewer than 40 human proteins. To address the critical need for new radiotracers, this Account expounds on the decisions, strategies, and pitfalls of CNS radiotracer development based on our current experience in this area. We discuss the five key components of radiotracer development for human imaging: choosing a biomedical question, selection of a biological target, design of the radiotracer chemical structure, evaluation of candidate radiotracers, and analysis of preclinical imaging. It is particularly important to analyze the market of scientists or companies who might use a new radiotracer and carefully select a relevant biomedical question(s) for that audience. In the selection of a specific biological target, we emphasize how target localization and identity can constrain this process and discuss the optimal target density and affinity ratios needed for binding-based radiotracers. In addition, we discuss various PET test–retest variability requirements for monitoring changes in density, occupancy, or functionality for new radiotracers. In the synthesis of new radiotracer structures, high-throughput, modular syntheses have proved valuable, and these processes provide compounds with sites for late-stage radioisotope installation. As a result, researchers can manage the time constraints associated with the limited half-lives of isotopes. In order to evaluate brain uptake, a number of methods are available to predict bioavailability, blood–brain barrier (BBB) permeability, and the associated issues of nonspecific binding and metabolic stability. To evaluate the synthesized chemical library, researchers need to consider high-throughput affinity assays, the analysis of specific binding, and the importance of fast binding kinetics. Finally, we describe how we initially assess preclinical radiotracer imaging, using brain uptake, specific binding, and preliminary kinetic analysis to identify promising radiotracers that may be useful for human brain imaging. Although we discuss these five design components separately and linearly in this Account, in practice we develop new PET-based radiotracers using these design components nonlinearly and iteratively to develop new compounds in the most efficient way possible. PMID:25272291
Space station crew safety alternatives study. Volume 3: Safety impact of human factors
NASA Technical Reports Server (NTRS)
Rockoff, L. A.; Raasch, R. F.; Peercy, R. L., Jr.
1985-01-01
The first 15 years of accumulated space station concepts for Initial Operational Capability (IOC) during the early 1990's was considered. Twenty-five threats to the space station are identified and selected threats addressed as impacting safety criteria, escape and rescue, and human factors safety concerns. Of the 25 threats identified, eight are discussed including strategy options for threat control: fire, biological or toxic contamination, injury/illness, explosion, loss of pressurization, radiation, meteoroid penetration and debris. Of particular interest here is volume three (of five volumes) pertaining to the safety impact of human factors.
Induced pluripotent stem cells as custom therapeutics for retinal repair: progress and rationale.
Wright, Lynda S; Phillips, M Joseph; Pinilla, Isabel; Hei, Derek; Gamm, David M
2014-06-01
Human pluripotent stem cells have made a remarkable impact on science, technology and medicine by providing a potentially unlimited source of human cells for basic research and clinical applications. In recent years, knowledge gained from the study of human embryonic stem cells and mammalian somatic cell reprogramming has led to the routine production of human induced pluripotent stem cells (hiPSCs) in laboratories worldwide. hiPSCs show promise for use in transplantation, high throughput drug screening, "disease-in-a-dish" modeling, disease gene discovery, and gene therapy testing. This review will focus on the first application, beginning with a discussion of methods for producing retinal lineage cells that are lost in inherited and acquired forms of retinal degenerative disease. The selection of appropriate hiPSC-derived donor cell type(s) for transplantation will be discussed, as will the caveats and prerequisite steps to formulating a clinical Good Manufacturing Practice (cGMP) product for clinical trials. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
Induced pluripotent stem cells as custom therapeutics for retinal repair: Progress and rationale
Wright, Lynda S.; Phillips, M. Joseph; Pinilla, Isabel; Hei, Derek; Gamm, David M.
2014-01-01
Human pluripotent stem cells have made a remarkable impact on science, technology and medicine by providing a potentially unlimited source of human cells for basic research and clinical applications. In recent years, knowledge gained from the study of human embryonic stem cells and mammalian somatic cell reprogramming has led to the routine production of human induced pluripotent stem cells (hiPSCs) in laboratories worldwide. hiPSCs show promise for use in transplantation, high throughput drug screening, “disease-in-a-dish” modeling, disease gene discovery, and gene therapy testing. This review will focus on the first application, beginning with a discussion of methods for producing retinal lineage cells that are lost in inherited and acquired forms of retinal degenerative disease. The selection of appropriate hiPSC-derived donor cell type(s) for transplantation will be discussed, as will the caveats and prerequisite steps to formulating a clinical Good Manufacturing Practice (cGMP) product for clinical trials. PMID:24534198
Thomas, Elizabeth A.
2014-01-01
Histone deacetylases (HDACs) enzymes, which affect the acetylation status of histones and other important cellular proteins, have been recognized as potentially useful therapeutic targets for a broad range of human disorders. Emerging studies have demonstrated that different types of HDAC inhibitors show beneficial effects in various experimental models of neurological disorders. HDAC enzymes comprise a large family of proteins, with18 HDAC enzymes currently identified in humans. Hence, an important question for HDAC inhibitor therapeutics is which HDAC enzyme(s) is/are important for the amelioration of disease phenotypes, as it has become clear that individual HDAC enzymes play different biological roles in the brain. This review will discuss evidence supporting the involvement of HDAC1 and HDAC3 in polyglutamine disorders, including Huntington’s disease, and the use of HDAC1- and HDAC3-selective HDAC inhibitors as therapeutic intervention for these disorders. Further, while HDAC inhibitors are known alter chromatin structure resulting in changes in gene transcription, understanding the exact mechanisms responsible for the preclinical efficacy of these compounds remains a challenge. The potential chromatin-related and non-chromatin-related mechanisms of action of selective HDAC inhibitors will also be discussed. PMID:24865773
The cultural evolution of emergent group-level traits.
Smaldino, Paul E
2014-06-01
Many of the most important properties of human groups - including properties that may give one group an evolutionary advantage over another - are properly defined only at the level of group organization. Yet at present, most work on the evolution of culture has focused solely on the transmission of individual-level traits. I propose a conceptual extension of the theory of cultural evolution, particularly related to the evolutionary competition between cultural groups. The key concept in this extension is the emergent group-level trait. This type of trait is characterized by the structured organization of differentiated individuals and constitutes a unit of selection that is qualitatively different from selection on groups as defined by traditional multilevel selection (MLS) theory. As a corollary, I argue that the traditional focus on cooperation as the defining feature of human societies has missed an essential feature of cooperative groups. Traditional models of cooperation assume that interacting with one cooperator is equivalent to interacting with any other. However, human groups involve differential roles, meaning that receiving aid from one individual is often preferred to receiving aid from another. In this target article, I discuss the emergence and evolution of group-level traits and the implications for the theory of cultural evolution, including ramifications for the evolution of human cooperation, technology, and cultural institutions, and for the equivalency of multilevel selection and inclusive fitness approaches.
Serial grouping of 2D-image regions with object-based attention in humans
Jeurissen, Danique; Self, Matthew W; Roelfsema, Pieter R
2016-01-01
After an initial stage of local analysis within the retina and early visual pathways, the human visual system creates a structured representation of the visual scene by co-selecting image elements that are part of behaviorally relevant objects. The mechanisms underlying this perceptual organization process are only partially understood. We here investigate the time-course of perceptual grouping of two-dimensional image-regions by measuring the reaction times of human participants and report that it is associated with the gradual spread of object-based attention. Attention spreads fastest over large and homogeneous areas and is slowed down at locations that require small-scale processing. We find that the time-course of the object-based selection process is well explained by a 'growth-cone' model, which selects surface elements in an incremental, scale-dependent manner. We discuss how the visual cortical hierarchy can implement this scale-dependent spread of object-based attention, leveraging the different receptive field sizes in distinct cortical areas. DOI: http://dx.doi.org/10.7554/eLife.14320.001 PMID:27291188
Doolittle, Emily L; Gingras, Bruno; Endres, Dominik M; Fitch, W Tecumseh
2014-11-18
Many human musical scales, including the diatonic major scale prevalent in Western music, are built partially or entirely from intervals (ratios between adjacent frequencies) corresponding to small-integer proportions drawn from the harmonic series. Scientists have long debated the extent to which principles of scale generation in human music are biologically or culturally determined. Data from animal "song" may provide new insights into this discussion. Here, by examining pitch relationships using both a simple linear regression model and a Bayesian generative model, we show that most songs of the hermit thrush (Catharus guttatus) favor simple frequency ratios derived from the harmonic (or overtone) series. Furthermore, we show that this frequency selection results not from physical constraints governing peripheral production mechanisms but from active selection at a central level. These data provide the most rigorous empirical evidence to date of a bird song that makes use of the same mathematical principles that underlie Western and many non-Western musical scales, demonstrating surprising convergence between human and animal "song cultures." Although there is no evidence that the songs of most bird species follow the overtone series, our findings add to a small but growing body of research showing that a preference for small-integer frequency ratios is not unique to humans. These findings thus have important implications for current debates about the origins of human musical systems and may call for a reevaluation of existing theories of musical consonance based on specific human vocal characteristics.
Genome-editing technologies and their potential application in horticultural crop breeding
Xiong, Jin-Song; Ding, Jing; Li, Yi
2015-01-01
Plant breeding, one of the oldest agricultural activities, parallels human civilization. Many crops have been domesticated to satisfy human's food and aesthetical needs, including numerous specialty horticultural crops such as fruits, vegetables, ornamental flowers, shrubs, and trees. Crop varieties originated through selection during early human civilization. Other technologies, such as various forms of hybridization, mutation, and transgenics, have also been invented and applied to crop breeding over the past centuries. The progress made in these breeding technologies, especially the modern biotechnology-based breeding technologies, has had a great impact on crop breeding as well as on our lives. Here, we first review the developmental process and applications of these technologies in horticultural crop breeding. Then, we mainly describe the principles of the latest genome-editing technologies and discuss their potential applications in the genetic improvement of horticultural crops. The advantages and challenges of genome-editing technologies in horticultural crop breeding are also discussed. PMID:26504570
1981-10-02
to the point of energy imbalance and declining reproductive rates. Increased human population would also increase poaching of pronghorn in areas...reduced. Such effects, however, could be mitigated as discussed below and in ETR-38. Increased human activity, including poaching , harassment, habitat...when intense activity would be widespread in their habitat. Mortality resulting from habitat loss and poaching would decrease herd size during 4-205 4
Synthetic lipoprotein as nano-material vehicle in the targeted drug delivery.
Zhang, Xueqin; Huang, Gangliang
2017-12-01
High-density lipoprotein (HDL) and low-density lipoprotein (LDL), as human endogenous lipoprotein particles, have low toxicity, high selectivity, and good safety. They can avoid the recognition and clearance of human reticuloendothelial system. These synthetic lipoproteins (sLPs) have been attracted extensive attention as the nanovectors for tumor-targeted drug and gene delivery. Herein, recent advances in the field of anticancer based on these two lipid proteins and recombinant lipoproteins (rLPs) as target delivery vectors were analyzed and discussed.
2012-05-25
station design . These issues include: poor ergonomics ; varying data input methods; multiple inputs required to implement a single command; lack of...facing the UAS/RPA discipline. Major discussion topics included: UAS operator selection, training, control station design , manpower and scheduling...Break 1400 – 1430: Naval UAS Training LCDR Brent Olde 1430 – 1500: Control Station Design Issues Melissa Walwanis 1500 – 1600: Tour of NAMRU-D
Benton, D; Braun, H; Cobo, J C; Edmonds, C; Elmadfa, I; El-Sharkawy, A; Feehally, J; Gellert, R; Holdsworth, J; Kapsokefalou, M; Kenney, W L; Leiper, J B; Macdonald, I A; Maffeis, C; Maughan, R J; Shirreffs, S M; Toth-Heyn, P; Watson, P
2015-09-01
On April 7-8, 2014, the European Hydration Institute hosted a small group of experts at Castle Combe Manor House, United Kingdom, to discuss a range of issues related to human hydration, health, and performance. The meeting included 18 recognized experts who brought a wealth of experience and knowledge to the topics under review. Eight selected topics were addressed, with the key issues being briefly presented before an in-depth discussion. Presented here is the executive summary and conclusions from this meeting. © The Author(s) 2015. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
Abnormal Facial Emotion Recognition in Depression: Serial Testing in an Ultra-Rapid-Cycling Patient.
ERIC Educational Resources Information Center
George, Mark S.; Huggins, Teresa; McDermut, Wilson; Parekh, Priti I.; Rubinow, David; Post, Robert M.
1998-01-01
Mood disorder subjects have a selective deficit in recognizing human facial emotion. Whether the facial emotion recognition errors persist during normal mood states (i.e., are state vs. trait dependent) was studied in one male bipolar II patient. Results of five sessions are presented and discussed. (Author/EMK)
International and National Environmental Education: A Status Report - 1974.
ERIC Educational Resources Information Center
Roth, Robert E.
This report focuses on the current status of environmental education in the U.S. and a number of selected countries around the world. The scope and primary concerns of environmental education are defined, and the stimulus created by the United Nations Stockholm Conference on the Human Environment is discussed. On the international scene…
Visualization as an Aid to Problem-Solving: Examples from History.
ERIC Educational Resources Information Center
Rieber, Lloyd P.
This paper presents a historical overview of visualization as a human problem-solving tool. Visualization strategies, such as mental imagery, pervade historical accounts of scientific discovery and invention. A selected number of historical examples are presented and discussed on a wide range of topics such as physics, aviation, and the science of…
Curriculum Assessment in Social Sciences at Universiti Pendidikan Sultan Idris
ERIC Educational Resources Information Center
Saleh, Hanifah Mahat Yazid; Hashim, Mohmadisa; Yaacob, Norazlan Hadi; Kasim, Adnan Jusoh Ahmad Yunus
2015-01-01
The purpose of this paper is to discuss the effectiveness of the curriculum implementation for undergraduate programme in the Faculty of Human Sciences, UPSI producing quality and competitive educators. Curriculum implementation has to go through an assessment process that aims to determine the problem, select relevant information and collect and…
Graphics in Text: A Bibliography. Monograph No. 6.
ERIC Educational Resources Information Center
Macdonald-Ross, Michael; Smith, Eleanor
This bibliography lists books and articles discussing graphic aspects of human communication. References have been selected for their relevance to the design of self-instructional texts for the adult learner; for the most part, research on younger children, on non-text media, and on non-educational texts is not included. Items are organized into…
DOE Office of Scientific and Technical Information (OSTI.GOV)
White, M R
1985-12-01
The report discusses how climate change and vegetative response will affect selected areas of our way of life as a result of increased carbon dioxide concentrations. Needs for future research are identified. Separate abstracts have been prepared for individual chapters. (ACR)
Federal Register 2010, 2011, 2012, 2013, 2014
2010-04-27
... discussion will include the criteria for selection of the constituents, developing a proposed list of harmful... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0001... Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice. This notice announces a forthcoming...
Principal Concerns: Addressing Statewide Principal Pipelines with Data and Strategy
ERIC Educational Resources Information Center
Campbell, Christine; Gross, Bethany
2012-01-01
Discussions about human capital and school improvement typically center on teachers, not administrators, and that's a mistake. Principals, who are responsible for selecting and developing the teachers they know are so important, are a critical driver of school success. So it is imperative that states do everything they can to find, deploy, and…
The big challenges in modeling human and environmental well-being.
Tuljapurkar, Shripad
2016-01-01
This article is a selective review of quantitative research, historical and prospective, that is needed to inform sustainable development policy. I start with a simple framework to highlight how demography and productivity shape human well-being. I use that to discuss three sets of issues and corresponding challenges to modeling: first, population prehistory and early human development and their implications for the future; second, the multiple distinct dimensions of human and environmental well-being and the meaning of sustainability; and, third, inequality as a phenomenon triggered by development and models to examine changing inequality and its consequences. I conclude with a few words about other important factors: political, institutional, and cultural.
Nilsson, Lena Maria; Berner, James; Dudarev, Alexey A; Mulvad, Gert; Odland, Jon Øyvind; Parkinson, Alan; Rautio, Arja; Tikhonov, Constantine; Evengård, Birgitta
2013-01-01
In August 2012, a literature search with the aim of describing indicators on food and water security in an Arctic health context was initialized in collaboration between the Arctic Human Health Expert Group, SDWG/AHHEG and the AMAP (Arctic Monitoring and Assessment Programme within the Arctic Council) Human Health Assessment Group, AMAP/HHAG. In December 2012, workshop discussions were performed with representatives from both of these organizations, including 7 Arctic countries. The aim of this article is to describe the workshop discussions and the rational for the 12 indicators selected and the 9 rejected and to discuss the potential feasibility of these. Advantages and disadvantages of candidate indicators were listed. Informative value and costs for collecting were estimated separately on a 3-level scale: low, medium and high. Based on these reviews, the final selection of promoted and rejected indicators was performed and summarized in tables. Among 10 suggested indicators of food security, 6 were promoted: healthy weight, traditional food proportion in diet, monetary food costs, non-monetary food accessibility, food-borne diseases and food-related contaminants. Four were rejected: per-person dietary energy supply, food security modules, self-estimated food safety and healthy eating. Among 10 suggested indicators of water security, 6 were promoted: per-capita renewable water, accessibility of running water, waterborne diseases, drinking-water-related contaminants, authorized water quality assurance and water safety plans. Four were rejected: water consumption, types of water sources, periodic water shortages and household water costs.
Nilsson, Lena Maria; Berner, James; Dudarev, Alexey A.; Mulvad, Gert; Odland, Jon Øyvind; Parkinson, Alan; Rautio, Arja; Tikhonov, Constantine; Evengård, Birgitta
2013-01-01
In August 2012, a literature search with the aim of describing indicators on food and water security in an Arctic health context was initialized in collaboration between the Arctic Human Health Expert Group, SDWG/AHHEG and the AMAP (Arctic Monitoring and Assessment Programme within the Arctic Council) Human Health Assessment Group, AMAP/HHAG. In December 2012, workshop discussions were performed with representatives from both of these organizations, including 7 Arctic countries. The aim of this article is to describe the workshop discussions and the rational for the 12 indicators selected and the 9 rejected and to discuss the potential feasibility of these. Advantages and disadvantages of candidate indicators were listed. Informative value and costs for collecting were estimated separately on a 3-level scale: low, medium and high. Based on these reviews, the final selection of promoted and rejected indicators was performed and summarized in tables. Among 10 suggested indicators of food security, 6 were promoted: healthy weight, traditional food proportion in diet, monetary food costs, non-monetary food accessibility, food-borne diseases and food-related contaminants. Four were rejected: per-person dietary energy supply, food security modules, self-estimated food safety and healthy eating. Among 10 suggested indicators of water security, 6 were promoted: per-capita renewable water, accessibility of running water, waterborne diseases, drinking-water-related contaminants, authorized water quality assurance and water safety plans. Four were rejected: water consumption, types of water sources, periodic water shortages and household water costs. PMID:23940840
What changes and what endures - The capabilities and limitations of training and selection
NASA Technical Reports Server (NTRS)
Helmreich, Robert L.
1983-01-01
The contributions of psychology to aviation in the areas of selection, training, and evaluation, and the implementation of new technologies are discussed. The concept of personality traits versus modification of human behavior through principles of learning are analyzed. Particular consideration is given to achievement motivation (defined in terms of mastery, work, and competitiveness) and the differences between traits and attitudes. It is argued that personality traits are important dimensions of the self and are useful measures of individual differences. The selection of individuals with desired personality characteristics and the training of personnel to improve crew coordination, flight-deck management, and interpersonal efficacy are examined.
Whole-genome regression and prediction methods applied to plant and animal breeding.
de Los Campos, Gustavo; Hickey, John M; Pong-Wong, Ricardo; Daetwyler, Hans D; Calus, Mario P L
2013-02-01
Genomic-enabled prediction is becoming increasingly important in animal and plant breeding and is also receiving attention in human genetics. Deriving accurate predictions of complex traits requires implementing whole-genome regression (WGR) models where phenotypes are regressed on thousands of markers concurrently. Methods exist that allow implementing these large-p with small-n regressions, and genome-enabled selection (GS) is being implemented in several plant and animal breeding programs. The list of available methods is long, and the relationships between them have not been fully addressed. In this article we provide an overview of available methods for implementing parametric WGR models, discuss selected topics that emerge in applications, and present a general discussion of lessons learned from simulation and empirical data analysis in the last decade.
Whole-Genome Regression and Prediction Methods Applied to Plant and Animal Breeding
de los Campos, Gustavo; Hickey, John M.; Pong-Wong, Ricardo; Daetwyler, Hans D.; Calus, Mario P. L.
2013-01-01
Genomic-enabled prediction is becoming increasingly important in animal and plant breeding and is also receiving attention in human genetics. Deriving accurate predictions of complex traits requires implementing whole-genome regression (WGR) models where phenotypes are regressed on thousands of markers concurrently. Methods exist that allow implementing these large-p with small-n regressions, and genome-enabled selection (GS) is being implemented in several plant and animal breeding programs. The list of available methods is long, and the relationships between them have not been fully addressed. In this article we provide an overview of available methods for implementing parametric WGR models, discuss selected topics that emerge in applications, and present a general discussion of lessons learned from simulation and empirical data analysis in the last decade. PMID:22745228
B. F. Skinner's Science and Human Behavior: its antecedents and its consequences.
Catania, A Charles
2003-11-01
Skinner's Science and Human Behavior marked a transition from a treatment of behavior that took physics as its reference science to one that emphasized behavior as a fundamental part of the subject matter of biology. The book includes what may be Skinner's earliest statement about the similarity of operant selection to Darwinian natural selection in phylogeny. Other major topics discussed in the book included multiple causation, private events, the self, and social contingencies. Among the important antecedents were Skinner's own Behavior of Organisms and Keller & Schoenfeld's Pincinples of Psychology. Current developments in education, behavioral economics, and some behavior therapies can be attributed at least in part to Skinner's seminal work. The effective behavioral analysis of governmental and religious systems will probably depend on elaborations of our understanding of verbal behavior.
Lerner, Richard M.; Schwartz, Seth J; Phelps, Erin
2009-01-01
Studying human development involves describing, explaining, and optimizing intraindividual change and interindividual differences in such change and, as such, requires longitudinal research. The selection of the appropriate type of longitudinal design requires selecting the option that best addresses the theoretical questions asked about developmental process and the use of appropriate statistical procedures to best exploit data derived from theory-predicated longitudinal research. This paper focuses on several interrelated problematics involving the treatment of time and the timing of observations that developmental scientists face in creating theory-design fit and in charting in change-sensitive ways developmental processes across life. We discuss ways in which these problematics may be addressed to advance theory-predicated understanding of the role of time in processes of individual development. PMID:19554215
ERIC Educational Resources Information Center
Yue, Anthony R.
2011-01-01
Reflecting on the personal experience of teaching human resource management in the Canadian Arctic, the author explores the utility of an existentialist approach to pedagogy. The author outlines select aspects of existentialism that are pertinent to the teaching and discusses the implications of using reflexive existential thought as guidance in a…
Sawyer, Benjamin D; Hancock, P A; Deaton, John; Suedfeld, Peter
2012-01-01
A two-week mission in March and April of 2011 sent six team members to the Mars Desert Research Station (MDRS). MDRS, a research facility in the high Utah desert, provides an analogue for the harsh and unusual working conditions that will be faced by men and women who one day explore Mars. During the mission a selection of quantitative and qualitative psychological tests were administered to the international, multidisciplinary team. A selection of the results are presented along with discussion.
Phillips, Tim; Ferguson, Eamonn; Rijsdijk, Fruhling
2010-11-01
Altruistic behaviour raises major questions for psychology and biology. One hypothesis proposes that human altruistic behaviour evolved as a result of sexual selection. Mechanisms that seek to explain how sexual selection works suggest genetic influence acting on both the mate preference for the trait and the preferred trait itself. We used a twin study to estimate whether genetic effects influenced responses to psychometric scales measuring mate preference towards altruistic traits (MPAT) and the preferred trait (i.e., 'altruistic personality'). As predicted, we found significant genetic effects influencing variation in both. We also predicted that individuals expressing stronger MPAT and 'altruistic personality' would have mated at a greater frequency in ancestral populations. We found evidence for this in that 67% of the covariance in the phenotypic correlation between the two scales was associated with significant genetic effects. Both sets of findings are thus consistent with the hypothesized link between sexual selection and human altruism towards non-kin. We discuss how this study contributes to our understanding of altruistic behaviour and how further work might extend this understanding.
Engineering craniofacial structures: facing the challenge.
Zaky, S H; Cancedda, R
2009-12-01
The human innate regenerative ability is known to be limited by the intensity of the insult together with the availability of progenitor cells, which may cause certain irreparable damage. It is only recently that the paradigm of tissue engineering found its way to the treatment of irreversibly affected body structures with the challenge of reconstructing the lost part. In the current review, we underline recent trials that target engineering of human craniofacial structures, mainly bone, cartilage, and teeth. We analyze the applied engineering strategies relative to the selection of cell types to lay down a specific targeted tissue, together with their association with an escorting scaffold for a particular engineered site, and discuss their necessity to be sustained by growth factors. Challenges and expectations for facial skeletal engineering are discussed in the context of future treatment.
Doolittle, Emily L.; Gingras, Bruno; Endres, Dominik M.; Fitch, W. Tecumseh
2014-01-01
Many human musical scales, including the diatonic major scale prevalent in Western music, are built partially or entirely from intervals (ratios between adjacent frequencies) corresponding to small-integer proportions drawn from the harmonic series. Scientists have long debated the extent to which principles of scale generation in human music are biologically or culturally determined. Data from animal “song” may provide new insights into this discussion. Here, by examining pitch relationships using both a simple linear regression model and a Bayesian generative model, we show that most songs of the hermit thrush (Catharus guttatus) favor simple frequency ratios derived from the harmonic (or overtone) series. Furthermore, we show that this frequency selection results not from physical constraints governing peripheral production mechanisms but from active selection at a central level. These data provide the most rigorous empirical evidence to date of a bird song that makes use of the same mathematical principles that underlie Western and many non-Western musical scales, demonstrating surprising convergence between human and animal “song cultures.” Although there is no evidence that the songs of most bird species follow the overtone series, our findings add to a small but growing body of research showing that a preference for small-integer frequency ratios is not unique to humans. These findings thus have important implications for current debates about the origins of human musical systems and may call for a reevaluation of existing theories of musical consonance based on specific human vocal characteristics. PMID:25368163
Russell, Shirley B.; Smith, Joan C.; Huang, Minjun; Trupin, Joel S.; Williams, Scott M.
2015-01-01
Many diseases are differentially distributed among human populations. Differential selection on genetic variants in ancestral environments that coincidentally predispose to disease can be an underlying cause of these unequal prevalence patterns. Selected genes may be pleiotropic, affecting multiple phenotypes and resulting in more than one disease or trait. Patterns of pleiotropy may be helpful in understanding the underlying causes of an array of conditions in a population. For example, several fibroproliferative diseases are more prevalent and severe in populations of sub-Saharan ancestry. We propose that this disparity is due to selection for an enhanced Th2 response that confers resistance to helminthic infections, and concurrently increases susceptibility to fibrosis due to the profibrotic action of Th2 cytokines. Many studies on selection of Th2-related genes for host resistance to helminths have been reported, but the pleiotropic impact of this selection on the distribution of fibrotic disorders has not been explicitly investigated. We discuss the disproportionate occurrence of fibroproliferative diseases in individuals of African ancestry and provide evidence that adaptation of the immune system has shaped the genetic structure of these human populations in ways that alter the distribution of multiple fibroproliferative diseases. PMID:26540410
Haasl, Ryan J.; Payseur, Bret A.
2016-01-01
Genomewide scans for natural selection (GWSS) have become increasingly common over the last 15 years due to increased availability of genome-scale genetic data. Here, we report a representative survey of GWSS from 1999 to present and find that (i) between 1999 and 2009, 35 of 49 (71%) GWSS focused on human, while from 2010 to present, only 38 of 83 (46%) of GWSS focused on human, indicating increased focus on nonmodel organisms; (ii) the large majority of GWSS incorporate interpopulation or interspecific comparisons using, for example FST, cross-population extended haplotype homozygosity or the ratio of nonsynonymous to synonymous substitutions; (iii) most GWSS focus on detection of directional selection rather than other modes such as balancing selection; and (iv) in human GWSS, there is a clear shift after 2004 from microsatellite markers to dense SNP data. A survey of GWSS meant to identify loci positively selected in response to severe hypoxic conditions support an approach to GWSS in which a list of a priori candidate genes based on potential selective pressures are used to filter the list of significant hits a posteriori. We also discuss four frequently ignored determinants of genomic heterogeneity that complicate GWSS: mutation, recombination, selection and the genetic architecture of adaptive traits. We recommend that GWSS methodology should better incorporate aspects of genomewide heterogeneity using empirical estimates of relevant parameters and/or realistic, whole-chromosome simulations to improve interpretation of GWSS results. Finally, we argue that knowledge of potential selective agents improves interpretation of GWSS results and that new methods focused on correlations between environmental variables and genetic variation can help automate this approach. PMID:26224644
Haasl, Ryan J; Payseur, Bret A
2016-01-01
Genomewide scans for natural selection (GWSS) have become increasingly common over the last 15 years due to increased availability of genome-scale genetic data. Here, we report a representative survey of GWSS from 1999 to present and find that (i) between 1999 and 2009, 35 of 49 (71%) GWSS focused on human, while from 2010 to present, only 38 of 83 (46%) of GWSS focused on human, indicating increased focus on nonmodel organisms; (ii) the large majority of GWSS incorporate interpopulation or interspecific comparisons using, for example F(ST), cross-population extended haplotype homozygosity or the ratio of nonsynonymous to synonymous substitutions; (iii) most GWSS focus on detection of directional selection rather than other modes such as balancing selection; and (iv) in human GWSS, there is a clear shift after 2004 from microsatellite markers to dense SNP data. A survey of GWSS meant to identify loci positively selected in response to severe hypoxic conditions support an approach to GWSS in which a list of a priori candidate genes based on potential selective pressures are used to filter the list of significant hits a posteriori. We also discuss four frequently ignored determinants of genomic heterogeneity that complicate GWSS: mutation, recombination, selection and the genetic architecture of adaptive traits. We recommend that GWSS methodology should better incorporate aspects of genomewide heterogeneity using empirical estimates of relevant parameters and/or realistic, whole-chromosome simulations to improve interpretation of GWSS results. Finally, we argue that knowledge of potential selective agents improves interpretation of GWSS results and that new methods focused on correlations between environmental variables and genetic variation can help automate this approach. © 2015 John Wiley & Sons Ltd.
Seifert, Roland
2013-10-01
In the mid 1990s, it was assumed that a two-state model, postulating an inactive (R) state and an active (R*) state provides the molecular basis for GPCR activation. However, it became clear that this model could not accommodate many experimental observations. Accordingly, the two-state model was superseded by a multi-state model according to which any given ligand stabilizes a unique receptor conformation with distinct capabilities of activating down-stream G-proteins and β-arrestin. Much of this research was conducted with the β2-adrenoceptor in recombinant systems. At the molecular level, there is now no doubt anymore that ligand-specific receptor conformations, also referred to as functional selectivity, exist. This concept holds great potential for drug discovery in terms of developing drugs with higher selectivity for specific cells and/or cell functions and fewer side effects. A major challenge is the analysis for functional selectivity in native cells. Here, I discuss our current knowledge on functional selectivity of three representative GPCRs, the β2-adrenoceptor and the histamine H2- and H4-receptors, in recombinant systems and native human cells. Studies with human neutrophils and eosinophils support the concept of functional selectivity. A major strategy for the analysis of functional selectivity in native cells is to generate complete concentration/response curves with a large set of structurally diverse ligands for multiple parameters. Next, correlations of potencies and efficacies are analyzed, and deviations of the correlations from linearity are indicative for functional selectivity. Additionally, pharmacological inhibitors are used to dissect cell functions from each other. Copyright © 2013 Elsevier Inc. All rights reserved.
Croze, Myriam; Živković, Daniel; Stephan, Wolfgang; Hutter, Stephan
2016-08-01
Balancing selection has been widely assumed to be an important evolutionary force, yet even today little is known about its abundance and its impact on the patterns of genetic diversity. Several studies have shown examples of balancing selection in humans, plants or parasites, and many genes under balancing selection are involved in immunity. It has been proposed that host-parasite coevolution is one of the main forces driving immune genes to evolve under balancing selection. In this paper, we review the literature on balancing selection on immunity genes in several organisms, including Drosophila. Furthermore, we performed a genome scan for balancing selection in an African population of Drosophila melanogaster using coalescent simulations of a demographic model with and without selection. We find very few genes under balancing selection and only one novel candidate gene related to immunity. Finally, we discuss the possible causes of the low number of genes under balancing selection. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.
Brownstone, Robert M; Stuart, Douglas G
2011-08-29
In the preceding series of articles, the history of vertebrate motoneuron and motor unit neurobiological studies has been discussed. In this article, we select a few examples of recent advances in neuroscience and discuss their application or potential application to the study of motoneurons and the control of movement. We conclude, like Sherrington, that in order to understand normal, traumatized, and diseased human behavior, it is critical to continue to study motoneuron biology using all available and emerging tools. This article is part of a Special Issue entitled Historical Review. 2011 Elsevier B.V. All rights reserved.
People and computers--some recent highlights.
Shackel, B
2000-12-01
This paper aims to review selectively a fair proportion of the literature on human-computer interaction (HCI) over the three years since Shackel (J. Am. Soc. Inform. Sci. 48 (11) (1997) 970-986). After a brief note of history I discuss traditional input, output and workplace aspects, the web and 'E-topics', web-related aspects, virtual reality, safety-critical systems, and the need to move from HCI to human-system integration (HSI). Finally I suggest, and consider briefly, some future possibilities and issues including web consequences, embedded ubiquitous computing, and 'back to systems ergonomics?'.
Design and analysis issues in gene and environment studies
2012-01-01
Both nurture (environmental) and nature (genetic factors) play an important role in human disease etiology. Traditionally, these effects have been thought of as independent. This perspective is ill informed for non-mendelian complex disorders which result as an interaction between genetics and environment. To understand health and disease we must study how nature and nurture interact. Recent advances in human genomics and high-throughput biotechnology make it possible to study large numbers of genetic markers and gene products simultaneously to explore their interactions with environment. The purpose of this review is to discuss design and analytic issues for gene-environment interaction studies in the “-omics” era, with a focus on environmental and genetic epidemiological studies. We present an expanded environmental genomic disease paradigm. We discuss several study design issues for gene-environmental interaction studies, including confounding and selection bias, measurement of exposures and genotypes. We discuss statistical issues in studying gene-environment interactions in different study designs, such as choices of statistical models, assumptions regarding biological factors, and power and sample size considerations, especially in genome-wide gene-environment studies. Future research directions are also discussed. PMID:23253229
Design and analysis issues in gene and environment studies.
Liu, Chen-yu; Maity, Arnab; Lin, Xihong; Wright, Robert O; Christiani, David C
2012-12-19
Both nurture (environmental) and nature (genetic factors) play an important role in human disease etiology. Traditionally, these effects have been thought of as independent. This perspective is ill informed for non-mendelian complex disorders which result as an interaction between genetics and environment. To understand health and disease we must study how nature and nurture interact. Recent advances in human genomics and high-throughput biotechnology make it possible to study large numbers of genetic markers and gene products simultaneously to explore their interactions with environment. The purpose of this review is to discuss design and analytic issues for gene-environment interaction studies in the "-omics" era, with a focus on environmental and genetic epidemiological studies. We present an expanded environmental genomic disease paradigm. We discuss several study design issues for gene-environmental interaction studies, including confounding and selection bias, measurement of exposures and genotypes. We discuss statistical issues in studying gene-environment interactions in different study designs, such as choices of statistical models, assumptions regarding biological factors, and power and sample size considerations, especially in genome-wide gene-environment studies. Future research directions are also discussed.
Advancing the sensitivity of selected reaction monitoring-based targeted quantitative proteomics
Shi, Tujin; Su, Dian; Liu, Tao; Tang, Keqi; Camp, David G.; Qian, Wei-Jun; Smith, Richard D.
2012-01-01
Selected reaction monitoring (SRM)—also known as multiple reaction monitoring (MRM)—has emerged as a promising high-throughput targeted protein quantification technology for candidate biomarker verification and systems biology applications. A major bottleneck for current SRM technology, however, is insufficient sensitivity for e.g., detecting low-abundance biomarkers likely present at the low ng/mL to pg/mL range in human blood plasma or serum, or extremely low-abundance signaling proteins in cells or tissues. Herein we review recent advances in methods and technologies, including front-end immunoaffinity depletion, fractionation, selective enrichment of target proteins/peptides including posttranslational modifications (PTMs), as well as advances in MS instrumentation which have significantly enhanced the overall sensitivity of SRM assays and enabled the detection of low-abundance proteins at low to sub- ng/mL level in human blood plasma or serum. General perspectives on the potential of achieving sufficient sensitivity for detection of pg/mL level proteins in plasma are also discussed. PMID:22577010
Advancing the sensitivity of selected reaction monitoring-based targeted quantitative proteomics
DOE Office of Scientific and Technical Information (OSTI.GOV)
Shi, Tujin; Su, Dian; Liu, Tao
2012-04-01
Selected reaction monitoring (SRM)—also known as multiple reaction monitoring (MRM)—has emerged as a promising high-throughput targeted protein quantification technology for candidate biomarker verification and systems biology applications. A major bottleneck for current SRM technology, however, is insufficient sensitivity for e.g., detecting low-abundance biomarkers likely present at the pg/mL to low ng/mL range in human blood plasma or serum, or extremely low-abundance signaling proteins in the cells or tissues. Herein we review recent advances in methods and technologies, including front-end immunoaffinity depletion, fractionation, selective enrichment of target proteins/peptides or their posttranslational modifications (PTMs), as well as advances in MS instrumentation, whichmore » have significantly enhanced the overall sensitivity of SRM assays and enabled the detection of low-abundance proteins at low to sub- ng/mL level in human blood plasma or serum. General perspectives on the potential of achieving sufficient sensitivity for detection of pg/mL level proteins in plasma are also discussed.« less
Pool, Martin; de Boer, H Rudolf; Hooge, Marjolijn N Lub-de; van Vugt, Marcel A T M; de Vries, Elisabeth G E
2017-01-01
Cancer is a growing problem worldwide. The cause of death in cancer patients is often due to treatment-resistant metastatic disease. Many molecularly targeted anticancer drugs have been developed against 'oncogenic driver' pathways. However, these treatments are usually only effective in properly selected patients. Resistance to molecularly targeted drugs through selective pressure on acquired mutations or molecular rewiring can hinder their effectiveness. This review summarizes how molecular imaging techniques can potentially facilitate the optimal implementation of targeted agents. Using the human epidermal growth factor receptor (HER) family as a model in (pre)clinical studies, we illustrate how molecular imaging may be employed to characterize whole body target expression as well as monitor drug effectiveness and the emergence of tumor resistance. We further discuss how an integrative omics discovery platform could guide the selection of 'effect sensors' - new molecular imaging targets - which are dynamic markers that indicate treatment effectiveness or resistance.
The emergence of human-evolutionary medical genomics
Crespi, Bernard J
2011-01-01
In this review, I describe how evolutionary genomics is uniquely suited to spearhead advances in understanding human disease risk, owing to the privileged position of genes as fundamental causes of phenotypic variation, and the ability of population genetic and phylogenetic methods to robustly infer processes of natural selection, drift, and mutation from genetic variation at the levels of family, population, species, and clade. I first provide an overview of models for the origins and maintenance of genetically based disease risk in humans. I then discuss how analyses of genetic disease risk can be dovetailed with studies of positive and balancing selection, to evaluate the degree to which the ‘genes that make us human’ also represent the genes that mediate risk of polygenic disease. Finally, I present four basic principles for the nascent field of human evolutionary medical genomics, each of which represents a process that is nonintuitive from a proximate perspective. Joint consideration of these principles compels novel forms of interdisciplinary analyses, most notably studies that (i) analyze tradeoffs at the level of molecular genetics, and (ii) identify genetic variants that are derived in the human lineage or in specific populations, and then compare individuals with derived versus ancestral alleles. PMID:25567974
NASA Astrophysics Data System (ADS)
Saranya, Kunaparaju; John Rozario Jegaraj, J.; Ramesh Kumar, Katta; Venkateshwara Rao, Ghanta
2016-06-01
With the increased trend in automation of modern manufacturing industry, the human intervention in routine, repetitive and data specific activities of manufacturing is greatly reduced. In this paper, an attempt has been made to reduce the human intervention in selection of optimal cutting tool and process parameters for metal cutting applications, using Artificial Intelligence techniques. Generally, the selection of appropriate cutting tool and parameters in metal cutting is carried out by experienced technician/cutting tool expert based on his knowledge base or extensive search from huge cutting tool database. The present proposed approach replaces the existing practice of physical search for tools from the databooks/tool catalogues with intelligent knowledge-based selection system. This system employs artificial intelligence based techniques such as artificial neural networks, fuzzy logic and genetic algorithm for decision making and optimization. This intelligence based optimal tool selection strategy is developed using Mathworks Matlab Version 7.11.0 and implemented. The cutting tool database was obtained from the tool catalogues of different tool manufacturers. This paper discusses in detail, the methodology and strategies employed for selection of appropriate cutting tool and optimization of process parameters based on multi-objective optimization criteria considering material removal rate, tool life and tool cost.
Resource Utilization and Site Selection for a Self-Sufficient Martian Outpost
NASA Technical Reports Server (NTRS)
Barker, Donald; Chamitoff, Gregory; James, George
1998-01-01
As a planet with striking similarities to Earth, Mars is an important focus for scientific research aimed at understanding the processes of planetary evolution and the formation of our solar system. Fortunately, Mars is also a planet with abundant natural resources, including assessible materials that can be used to support human life and to sustain a self-sufficient martian outpost. Resources required include water, breathable air, food, shelter, energy, and fuel. Through a mission design based on in situ resource development, we can establish a permanent outpost on Mars beginning with the first manned mission. This paper examines the potential for supporting the first manned mission with the objective of achieving self-sufficiency through well-understood resource development and a program of rigorous scientific research aimed at extending that capability. We examine the potential for initially extracting critical resources from the martian environment, and discuss the scientific investigations required to identify additional resources in the atmosphere, on the surface, and within the subsurface. We also discuss our current state of knowledge of Mars, technical considerations of resource utilization, and using unmanned missions' data for selecting an optimal site. The primary goal of achieving self-sufficiency on Mars would accelerate the development of human colonization beyond Earth, while providing a robust and permanent martian base from which humans can explore and conduct long-term research on planetary evolution, the solar system, and life itself.
Reducing systems biology to practice in pharmaceutical company research; selected case studies.
Benson, N; Cucurull-Sanchez, L; Demin, O; Smirnov, S; van der Graaf, P
2012-01-01
Reviews of the productivity of the pharmaceutical industry have concluded that the current business model is unsustainable. Various remedies for this have been proposed, however, arguably these do not directly address the fundamental issue; namely, that it is the knowledge required to enable good decisions in the process of delivering a drug that is largely absent; in turn, this leads to a disconnect between our intuition of what the right drug target is and the reality of pharmacological intervention in a system such as a human disease state. As this system is highly complex, modelling will be required to elucidate emergent properties together with the data necessary to construct such models. Currently, however, both the models and data available are limited. The ultimate solution to the problem of pharmaceutical productivity may be the virtual human, however, it is likely to be many years, if at all, before this goal is realised. The current challenge is, therefore, whether systems modelling can contribute to improving productivity in the pharmaceutical industry in the interim and help to guide the optimal route to the virtual human. In this context, this chapter discusses the emergence of systems pharmacology in drug discovery from the interface of pharmacokinetic-pharmacodynamic modelling and systems biology. Examples of applications to the identification of optimal drug targets in given pathways, selecting drug modalities and defining biomarkers are discussed, together with future directions.
McCranor, Bryan J.; Szmacinski, Henryk; Zeng, Hui Hui; Stoddard, A.K.; Hurst, Tamiika; Fierke, Carol A.; Lakowicz, J.R.
2014-01-01
Copper is a required trace element that plays key roles in a number of human enzymes, such that copper deficiency or genetic defects in copper transport lead to serious or fatal disease. Rae, et al., had famously predicted that free copper ion levels in the cell cytoplasm were extremely low, typically too low to be observable. We recently developed a variant of human apocarbonic anhydrase II for sensing metal ions that exhibits 25-fold better selectivity for Cu(II) over Zn(II) than the wild type protein, enabling us to accurately measure Cu(II) in the presence of ordinary cellular (picomolar) concentrations of free zinc. We inserted a fluorescent labeled Cu(II)-specific variant of human apocarbonic anhydrase into PC-12 cells and found that the levels are indeed extremely low (in the femtomolar range). We imaged the free Cu(II) levels in living cells by means of frequency-domain fluorescence lifetime microscopy. Implications of this finding are discussed. PMID:24671220
Combinatorial Optimization in Project Selection Using Genetic Algorithm
NASA Astrophysics Data System (ADS)
Dewi, Sari; Sawaluddin
2018-01-01
This paper discusses the problem of project selection in the presence of two objective functions that maximize profit and minimize cost and the existence of some limitations is limited resources availability and time available so that there is need allocation of resources in each project. These resources are human resources, machine resources, raw material resources. This is treated as a consideration to not exceed the budget that has been determined. So that can be formulated mathematics for objective function (multi-objective) with boundaries that fulfilled. To assist the project selection process, a multi-objective combinatorial optimization approach is used to obtain an optimal solution for the selection of the right project. It then described a multi-objective method of genetic algorithm as one method of multi-objective combinatorial optimization approach to simplify the project selection process in a large scope.
Why human evolution should be a basic science for medicine and psychology students.
Palanza, Paola; Parmigiani, Stefano
2016-06-20
Based on our teaching experience in medicine and psychology degree programs, we examine different aspects of human evolution that can help students to understand how the human body and mind work and why they are vulnerable to certain diseases. Three main issues are discussed: 1) the necessity to consider not only the mechanisms, i.e. the "proximate causations", implicated in biological processes but also why these mechanisms have evolved, i.e. the "ultimate causations" or "adaptive significance", to understand the functioning and malfunctioning of human body and mind; 2) examples of how human vulnerabilities to disease are caused by phylogenetic constraints, evolutionary tradeoffs reflecting the combined actions of natural and sexual selection, and/or mismatch between past and present environment (i.e., evolution of the eye, teeth and diets, erect posture and their consequences); 3) human pair-bonding and parent-offspring relationships as the result of socio-sexual selection and evolutionary compromises between cooperation and conflict. These psychobiological mechanisms are interwoven with our brain developmental plasticity and the effects of culture in shaping our behavior and mind, and allow a better understanding of functional (normal) and dysfunctional (pathological) behaviors. Thus, because the study of human evolution offers a powerful framework for clinical practice and research, the curriculum studiorum of medical and psychology students should include evolutionary biology and human phylogeny.
Community perceptions of human excreta as fertilizer in peri-urban agriculture in Ghana.
Mariwah, Simon; Drangert, Jan-Olof
2011-08-01
Although human excreta contain the necessary nutrients for plant growth, local authorities in Ghana spend huge sums of money to dispose them as waste. Reusing excreta for agricultural purposes saves expenditure for chemical fertilizers, improves soil fertility, reduces poverty and ensures food security. People's attitudes and perceptions about excreta vary between cultures and even within specific cultures. This study aimed to explore attitudes and perceptions among a peri-urban agricultural community towards sanitized human excreta and its use. The study adopted an exploratory design and collected data from 154 randomly selected households using questionnaires and focus group discussions. It was found that there is a general negative attitude to fresh excreta and the handling of it. However, the residents accept that excreta can be used as fertilizer, but they are not willing to use it on their own crops or consume crops fertilized with excreta. The study recommends open discussions in the community for a successful implementation of ecological sanitation.
An adjuvant-modulated vaccine response in human whole blood
Hakimi, Jalil; Azizi, Ali; Ausar, Salvador F.; Todryk, Stephen M.; Rahman, Nausheen; Brookes, Roger H.
2017-01-01
ABSTRACT The restimulation of an immune memory response by in vitro culture of blood cells with a specific antigen has been used as a way to gauge immunity to vaccines for decades. In this commentary we discuss a less appreciated application to support vaccine process development. We report that human whole blood from pre-primed subjects can generate a profound adjuvant-modulated, antigen-specific response to several different vaccine formulations. The response is able to differentiate subtle changes in the quality of an immune memory response to vaccine formulations and can be used to select optimal conditions relating to a particular manufacture process step. While questions relating to closeness to in vivo vaccination remain, the approach is another big step nearer to the more relevant human response. It has special importance for new adjuvant development, complementing other preclinical in vivo and in vitro approaches to considerably de-risk progression of novel vaccines before and throughout early clinical development. Broader implications of the approach are discussed. PMID:28605295
Impact of human emotions on physiological characteristics
NASA Astrophysics Data System (ADS)
Partila, P.; Voznak, M.; Peterek, T.; Penhaker, M.; Novak, V.; Tovarek, J.; Mehic, Miralem; Vojtech, L.
2014-05-01
Emotional states of humans and their impact on physiological and neurological characteristics are discussed in this paper. This problem is the goal of many teams who have dealt with this topic. Nowadays, it is necessary to increase the accuracy of methods for obtaining information about correlations between emotional state and physiological changes. To be able to record these changes, we focused on two majority emotional states. Studied subjects were psychologically stimulated to neutral - calm and then to the stress state. Electrocardiography, Electroencephalography and blood pressure represented neurological and physiological samples that were collected during patient's stimulated conditions. Speech activity was recording during the patient was reading selected text. Feature extraction was calculated by speech processing operations. Classifier based on Gaussian Mixture Model was trained and tested using Mel-Frequency Cepstral Coefficients extracted from the patient's speech. All measurements were performed in a chamber with electromagnetic compatibility. The article discusses a method for determining the influence of stress emotional state on the human and his physiological and neurological changes.
NASA Technical Reports Server (NTRS)
Verigo, V. V.
1979-01-01
Simulation models were used to study theoretical problems of space biology and medicine. The reaction and adaptation of the main physiological systems to the complex effects of space flight were investigated. Mathematical models were discussed in terms of their significance in the selection of the structure and design of biological life support systems.
77 FR 31624 - Office of the Director, National Institutes of Health; Notice of Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2012-05-29
... Committee Act, as amended (5 U.S.C. App.), notice is hereby given of a meeting of the Recombinant DNA... Committee: Recombinant DNA Advisory Committee. Date: June 19, 2012. Time: 9:00 a.m. to 3:30 p.m. Agenda: The NIH Recombinant DNA Advisory Committee (RAC) will discuss selected human gene transfer protocols...
77 FR 50516 - Office of the Director, National Institutes of Health; Notice of Meeting
Federal Register 2010, 2011, 2012, 2013, 2014
2012-08-21
... Committee Act, as amended (5 U.S.C. App.), notice is hereby given of a meeting of the Recombinant DNA... Committee: Recombinant DNA Advisory Committee. Date: September 12, 2012. Time: 2:00 p.m. to 5:00 p.m. Agenda: The NIH Recombinant DNA Advisory Committee (RAC) will discuss selected human gene transfer protocols...
77 FR 8270 - Office of the Director, National Institutes of Health; Notice of Meeting
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Psychobiology and Food Perception
NASA Technical Reports Server (NTRS)
Neilson, A.
1985-01-01
Psychobiology is a scientific discipline which encompasses the phenomena known to be important as regards nutrition and food consumption in space. Specifically, it includes those areas of biology which are clearly related to behavior, human subjective experience and problems of coping and adapting to stress. Taste and odor perception; perception (knowledge gaps); perception (needs); food preference and menu selection; and choosing of acceptable diets are discussed.
The Weak Spots in Contemporary Science (and How to Fix Them)
2017-01-01
Simple Summary Several fraud cases, widespread failure to replicate or reproduce seminal findings, and pervasive error in the scientific literature have led to a crisis of confidence in the biomedical, behavioral, and social sciences. In this review, the author discusses some of the core findings that point at weak spots in contemporary science and considers the human factors that underlie them. He delves into the human tendencies that create errors and biases in data collection, analyses, and reporting of research results. He presents several solutions to deal with observer bias, publication bias, the researcher’s tendency to exploit degrees of freedom in their analysis of data, low statistical power, and errors in the reporting of results, with a focus on the specific challenges in animal welfare research. Abstract In this review, the author discusses several of the weak spots in contemporary science, including scientific misconduct, the problems of post hoc hypothesizing (HARKing), outcome switching, theoretical bloopers in formulating research questions and hypotheses, selective reading of the literature, selective citing of previous results, improper blinding and other design failures, p-hacking or researchers’ tendency to analyze data in many different ways to find positive (typically significant) results, errors and biases in the reporting of results, and publication bias. The author presents some empirical results highlighting problems that lower the trustworthiness of reported results in scientific literatures, including that of animal welfare studies. Some of the underlying causes of these biases are discussed based on the notion that researchers are only human and hence are not immune to confirmation bias, hindsight bias, and minor ethical transgressions. The author discusses solutions in the form of enhanced transparency, sharing of data and materials, (post-publication) peer review, pre-registration, registered reports, improved training, reporting guidelines, replication, dealing with publication bias, alternative inferential techniques, power, and other statistical tools. PMID:29186879
B. F. Skinner's Science and Human Behavior: its antecedents and its consequences.
Catania, A Charles
2003-01-01
Skinner's Science and Human Behavior marked a transition from a treatment of behavior that took physics as its reference science to one that emphasized behavior as a fundamental part of the subject matter of biology. The book includes what may be Skinner's earliest statement about the similarity of operant selection to Darwinian natural selection in phylogeny. Other major topics discussed in the book included multiple causation, private events, the self, and social contingencies. Among the important antecedents were Skinner's own Behavior of Organisms and Keller & Schoenfeld's Pincinples of Psychology. Current developments in education, behavioral economics, and some behavior therapies can be attributed at least in part to Skinner's seminal work. The effective behavioral analysis of governmental and religious systems will probably depend on elaborations of our understanding of verbal behavior. PMID:14964711
Humanism at heart: preserving empathy in third-year medical students.
Rosenthal, Susan; Howard, Brian; Schlussel, Yvette R; Herrigel, Dana; Smolarz, B Gabriel; Gable, Brian; Vasquez, Jennifer; Grigo, Heather; Kaufman, Margit
2011-03-01
Research suggests that medical student empathy erodes during undergraduate medical education. The authors evaluated the Jefferson Scale of Physician Empathy Medical Student Version (JSPE-MS) scores of two consecutive medical school classes to assess the impact of an educational intervention on the preservation of empathy. The authors conducted a before-and-after study of 209 Robert Wood Johnson Medical School (RWJMS) students enrolled in the classes of 2009 and 2010. Students' clerkships included a mandatory, longitudinal "Humanism and Professionalism" (H&P) component, which included blogging about clerkship experiences, debriefing after significant events, and discussing journal articles, fiction, and film. Students completed the JSPE-MS during their first and last clerkships. The results showed that (1) contrary to previous studies' findings, third-year students did not show significant decline in empathy as measured by the JSPE-MS (these students, from two consecutive RWJMS classes, experienced the H&P intervention), (2) students selected for the Gold Humanism Honor Society (GHHS) were significantly different from their peers in empathy scores as measured by JSPE-MS, and (3) knowledge of selection for the GHHS seems to positively influence students' JSPE-MS scores. Maintaining empathy during the third year of medical school is possible through educational intervention. A curriculum that includes safe, protected time for third-year students to discuss their reactions to patient care situations during clerkships may have contributed to the preservation of empathy. Programs designed to validate humanism in medicine (such as the GHHS) may reverse the decline in empathy as measured by the JSPE-MS.
Rutherford, Bret R; Hellerstein, David J
2008-01-01
To determine the degree to which the medical humanities have been integrated into the fields of internal medicine and psychiatry, the authors assessed the presence of medical humanities articles in selected psychiatry and internal medicine journals from 1950 to 2000. The journals searched were the three highest-ranking psychiatry and internal medicine journals on the Institute for Scientific Information's Impact Factor rankings that were published in English and aimed at a clinical audience. Operationalized criteria defining the medical humanities allowed the percentage of text in the selected journals constituting medical humanities to be quantified. Journals were hand searched at 10-year intervals from 1950 to 2000. Mixed effects models were used to describe the change in medical humanities over time. The percentage of text within psychiatry journals meeting the criteria for medical humanities declined from a peak of 17% in 1970 to a low of 2% in 2000, while the percentage of humanities articles in internal medicine journals roughly doubled from 5% to 11% over the same time period. A linear model increasing over time best fit the medical humanities in the internal medicine journals, while a cubic model decreasing over time best fit the psychiatry humanities data. Humanities articles in medical journals had a greater breadth and diversity than those in psychiatry journals. Medical humanities publications dramatically decreased over time in psychiatry journals while they more than doubled in internal medicine journals. These data suggest the need for further empirical research and discussion of the potential roles of the humanities in psychiatry.
Preference for human body odors is influenced by gender and sexual orientation.
Martins, Yolanda; Preti, George; Crabtree, Christina R; Runyan, Tamar; Vainius, Aldona A; Wysocki, Charles J
2005-09-01
Human body odor may contribute to selection of partners. If so, sexual orientation may influence preference for and perhaps production of human body odors. In a test of these hypotheses, heterosexual and homosexual males and females made two-alternative forced-choice preference judgments for body odors obtained from other heterosexual and homosexual males and females. Subjects chose between odors from (a) heterosexual males and gay males, (b) heterosexual males and heterosexual females, (c) heterosexual females and lesbians, and (d) gay males and lesbians. Results indicate that differences in body odor are detected and responded to on the basis of, in part, an individual's gender and sexual orientation. Possible mechanisms underlying these findings are discussed.
RESEARCH ON ENVIRONMENTAL HEALTH INTERVENTIONS: ETHICAL PROBLEMS AND SOLUTIONS
RESNIK, DAVID B.; ZELDIN, DARRYL C.; SHARP, RICHARD R.
2014-01-01
This article reviews a variety of ethical issues one must consider when conducting research on environmental health interventions on human subjects. The paper uses the Kennedy Krieger Institute lead abatement study as well as a hypothetical asthma study to discuss questions concerning benefits and risks, risk minimization, safety monitoring, the duty to warn, the duty to report, the use of control groups, informed consent, equitable subject selection, privacy, conflicts of interest, and community consultation. Research on environmental health interventions can make an important contribution to our understanding of human health and disease prevention, provided it is conducted in a manner that meets prevailing scientific, ethical, and legal standards for research on human subjects. PMID:16220621
Evolution of coalitionary killing.
Wrangham, R W
1999-01-01
Warfare has traditionally been considered unique to humans. It has, therefore, often been explained as deriving from features that are unique to humans, such as the possession of weapons or the adoption of a patriarchal ideology. Mounting evidence suggests, however, that coalitional killing of adults in neighboring groups also occurs regularly in other species, including wolves and chimpanzees. This implies that selection can favor components of intergroup aggression important to human warfare, including lethal raiding. Here I present the principal adaptive hypothesis for explaining the species distribution of intergroup coalitional killing. This is the "imbalance-of-power hypothesis," which suggests that coalitional killing is the expression of a drive for dominance over neighbors. Two conditions are proposed to be both necessary and sufficient to account for coalitional killing of neighbors: (1) a state of intergroup hostility; (2) sufficient imbalances of power between parties that one party can attack the other with impunity. Under these conditions, it is suggested, selection favors the tendency to hunt and kill rivals when the costs are sufficiently low. The imbalance-of-power hypothesis has been criticized on a variety of empirical and theoretical grounds which are discussed. To be further tested, studies of the proximate determinants of aggression are needed. However, current evidence supports the hypothesis that selection has favored a hunt-and-kill propensity in chimpanzees and humans, and that coalitional killing has a long history in the evolution of both species.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jacques V Hugo
This book chapter describes the considerations for the selection of advanced human–system interfaces (HSIs) for the new generation of nuclear power plants. The chapter discusses the technologies that will be needed to support highly automated nuclear power plants, while minimising demands for numbers of operational staff, reducing human error and improving plant efficiency and safety. Special attention is paid to the selection and deployment of advanced technologies in nuclear power plants (NPPs). The chapter closes with an examination of how technologies are likely to develop over the next 10–15 years and how this will affect design choices for the nuclearmore » industry.« less
Extraordinary intelligence and the care of infants
Piantadosi, Steven T.; Kidd, Celeste
2016-01-01
We present evidence that pressures for early childcare may have been one of the driving factors of human evolution. We show through an evolutionary model that runaway selection for high intelligence may occur when (i) altricial neonates require intelligent parents, (ii) intelligent parents must have large brains, and (iii) large brains necessitate having even more altricial offspring. We test a prediction of this account by showing across primate genera that the helplessness of infants is a particularly strong predictor of the adults’ intelligence. We discuss related implications, including this account’s ability to explain why human-level intelligence evolved specifically in mammals. This theory complements prior hypotheses that link human intelligence to social reasoning and reproductive pressures and explains how human intelligence may have become so distinctive compared with our closest evolutionary relatives. PMID:27217560
NASA Astrophysics Data System (ADS)
Cooke, R.; Frisch, B.; Saleem, A.
1991-08-01
The topic of risk to human life is addressed from different viewpoints. The question is raised whether risk assessment is good only as a tool for ranking risk sources or whether it actually yields sensible numbers for estimating the risk of events. Various measures for the quantification of risk (e.g., deaths per million, activity specific hourly mortality rate) are given and their applications are discussed. The implications of the different uses for risk numbers are explained. Known risks of several activities are used as a baseline for the discussion of the selection criteria for an achievable safety goal for manned space flight.
Epigenesis of behavioural lateralization in humans and other animals
Schaafsma, S.M.; Riedstra, B.J.; Pfannkuche, K.A.; Bouma, A.; Groothuis, T.G.G.
2008-01-01
Despite several decades of research, the epigenesis of behavioural and brain lateralization is still elusive, although its knowledge is important in understanding developmental plasticity, function and evolution of lateralization, and its relationship with developmental disorders. Over the last decades, it has become clear that behavioural lateralization is not restricted to humans, but a fundamental principle in the organization of behaviour in vertebrates. This has opened the possibility of extending descriptive studies on human lateralization with descriptive and experimental studies on other vertebrate species. In this review, we therefore explore the evidence for the role of genes and environment on behavioural lateralization in humans and other animals. First, we discuss the predominant genetic models for human handedness, and conclude that their explanatory power alone is not sufficient, leaving, together with ambiguous results from adoption studies and selection experiments in animals, ample opportunity for a role of environmental factors. Next, we discuss the potential influence of such factors, including perinatal asymmetrical perception induced by asymmetrical head position or parental care, and social modulation, both in humans and other vertebrates, presenting some evidence from our own work on the domestic chick. We conclude that both perinatal asymmetrical perception and later social modulation are likely candidates in influencing the degree or strength of lateralization in both humans and other vertebrates. However, in most cases unequivocal evidence for this is lacking and we will point out further avenues for research. PMID:19064352
[Brachycephaly in dog and cat: a "human induced" obstruction of the upper airways].
Oechtering, G U; Schlüter, C; Lippert, J P
2010-07-01
Selective breeding for exaggerated features caused in many brachycephalic dog and cat breeds virtually a loss of the nose, with serious anatomical and functional consequences. In addition to respiratory and olfactory tasks, in dogs the nose is of vital importance for thermoregulation. As obligatory nose breathers, dogs suffer far more than humans when their nasal ventilation is restricted. An open discussion in the broad public has to motivate authorities and kennel clubs to recognize extreme brachycephalic breeding as seriously affecting animal health and welfare. Copyright Georg Thieme Verlag KG Stuttgart . New York.
NON-REGULATED CONTAMINANTS EMERGING ...
Those chemical pollutants that are regulated under various international, federal, and state programs represent but a small fraction of the universe of chemicals that occur in the environment as a result of both natural processes and human influence. Although this galaxy of targeted chemicals might be minuscule compared with the universe of both known and yet-to-be identified chemicals, an implicit assumption is that these selective lists of chemicals are responsible for the most significant share of risk with respect to environmental or economic impairment or to human health. This presentation examines the less-discussed aspects of the background and assumptions that underlie society's
CENTRAL NERVOUS SYSTEM INFECTION DURING IMMUNOSUPPRESSION
Zunt, Joseph R.
2009-01-01
The central nervous system (CNS) is susceptible to bacterial, viral, and fungal infections. Suppression of the immune system by human immunodeficiency virus (HIV) infection or immunosuppressive therapy after transplantation increases susceptibility to CNS infection and modifies the presentation, diagnosis, and recommended treatment of various CNS infections. This chapter discusses how suppression of the host immune status modifies the presentation, diagnosis, and treatment of selected CNS infections. PMID:11754299
Virus and Infections 2010 - BIT's first world congress.
Garkavenko, Olga
2010-10-01
The World Congress of Virus and Infections, held in Busan, South Korea, included topics reviewing the field of zoonoses. This conference report highlights selected presentations on surveillance, epidemiology and measures for the control and prevention of zoonotic diseases. Topics discussed include human factors influencing zoonoses, the molecular epidemiology of Crimean-Congo hemorrhagic fever, the emerging Nipah virus, and the re-emergence of cowpox virus.
NASA Technical Reports Server (NTRS)
Prinzel, L.J.; Kramer, L.J.
2009-01-01
A synthetic vision system is an aircraft cockpit display technology that presents the visual environment external to the aircraft using computer-generated imagery in a manner analogous to how it would appear to the pilot if forward visibility were not restricted. The purpose of this chapter is to review the state of synthetic vision systems, and discuss selected human factors issues that should be considered when designing such displays.
The Human Factors of Sensor Fusion
2008-05-01
tool in future military operations. 23 7. References Abdi, H. Neural Networks. In M. Lewis-Beck, A . Bryman , T. Futing (Eds), Encyclopedia for... a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1...This report discusses select, cognitively based principles associated with the sensor fusion process. A review is made of the standard
Neural mechanisms of selective attention in the somatosensory system.
Gomez-Ramirez, Manuel; Hysaj, Kristjana; Niebur, Ernst
2016-09-01
Selective attention allows organisms to extract behaviorally relevant information while ignoring distracting stimuli that compete for the limited resources of their central nervous systems. Attention is highly flexible, and it can be harnessed to select information based on sensory modality, within-modality feature(s), spatial location, object identity, and/or temporal properties. In this review, we discuss the body of work devoted to understanding mechanisms of selective attention in the somatosensory system. In particular, we describe the effects of attention on tactile behavior and corresponding neural activity in somatosensory cortex. Our focus is on neural mechanisms that select tactile stimuli based on their location on the body (somatotopic-based attention) or their sensory feature (feature-based attention). We highlight parallels between selection mechanisms in touch and other sensory systems and discuss several putative neural coding schemes employed by cortical populations to signal the behavioral relevance of sensory inputs. Specifically, we contrast the advantages and disadvantages of using a gain vs. spike-spike correlation code for representing attended sensory stimuli. We favor a neural network model of tactile attention that is composed of frontal, parietal, and subcortical areas that controls somatosensory cells encoding the relevant stimulus features to enable preferential processing throughout the somatosensory hierarchy. Our review is based on data from noninvasive electrophysiological and imaging data in humans as well as single-unit recordings in nonhuman primates. Copyright © 2016 the American Physiological Society.
Neural mechanisms of selective attention in the somatosensory system
Hysaj, Kristjana; Niebur, Ernst
2016-01-01
Selective attention allows organisms to extract behaviorally relevant information while ignoring distracting stimuli that compete for the limited resources of their central nervous systems. Attention is highly flexible, and it can be harnessed to select information based on sensory modality, within-modality feature(s), spatial location, object identity, and/or temporal properties. In this review, we discuss the body of work devoted to understanding mechanisms of selective attention in the somatosensory system. In particular, we describe the effects of attention on tactile behavior and corresponding neural activity in somatosensory cortex. Our focus is on neural mechanisms that select tactile stimuli based on their location on the body (somatotopic-based attention) or their sensory feature (feature-based attention). We highlight parallels between selection mechanisms in touch and other sensory systems and discuss several putative neural coding schemes employed by cortical populations to signal the behavioral relevance of sensory inputs. Specifically, we contrast the advantages and disadvantages of using a gain vs. spike-spike correlation code for representing attended sensory stimuli. We favor a neural network model of tactile attention that is composed of frontal, parietal, and subcortical areas that controls somatosensory cells encoding the relevant stimulus features to enable preferential processing throughout the somatosensory hierarchy. Our review is based on data from noninvasive electrophysiological and imaging data in humans as well as single-unit recordings in nonhuman primates. PMID:27334956
NASA Astrophysics Data System (ADS)
Carelli, P.; Chiarello, F.; Torrioli, G.; Castellano, M. G.
2017-03-01
We present an apparatus for terahertz discrimination of materials designed to be fast, simple, compact, and economical in order to be suitable for preliminary on-field analysis. The system working principles, bio-inspired by the human vision of colors, are based on the use of an incoherent source, a room temperature detector, a series of microfabricated metamaterials selective filters, a very compact optics based on metallic ellipsoidal mirrors in air, and a treatment of the mirrors' surfaces that select the frequency band of interest. We experimentally demonstrate the operation of the apparatus in discriminating simple substances such as salt, staple foods, and grease. We present the system and the obtained results and discuss issues and possible developments.
Evaluating the efficacy of fully automated approaches for the selection of eye blink ICA components
Pontifex, Matthew B.; Miskovic, Vladimir; Laszlo, Sarah
2017-01-01
Independent component analysis (ICA) offers a powerful approach for the isolation and removal of eye blink artifacts from EEG signals. Manual identification of the eye blink ICA component by inspection of scalp map projections, however, is prone to error, particularly when non-artifactual components exhibit topographic distributions similar to the blink. The aim of the present investigation was to determine the extent to which automated approaches for selecting eye blink related ICA components could be utilized to replace manual selection. We evaluated popular blink selection methods relying on spatial features [EyeCatch()], combined stereotypical spatial and temporal features [ADJUST()], and a novel method relying on time-series features alone [icablinkmetrics()] using both simulated and real EEG data. The results of this investigation suggest that all three methods of automatic component selection are able to accurately identify eye blink related ICA components at or above the level of trained human observers. However, icablinkmetrics(), in particular, appears to provide an effective means of automating ICA artifact rejection while at the same time eliminating human errors inevitable during manual component selection and false positive component identifications common in other automated approaches. Based upon these findings, best practices for 1) identifying artifactual components via automated means and 2) reducing the accidental removal of signal-related ICA components are discussed. PMID:28191627
The evolution of music in comparative perspective.
Fitch, W Tecumseh
2005-12-01
In this paper, I briefly review some comparative data that provide an empirical basis for research on the evolution of music making in humans. First, a brief comparison of music and language leads to discussion of design features of music, suggesting a deep connection between the biology of music and language. I then selectively review data on animal "music." Examining sound production in animals, we find examples of repeated convergent evolution or analogy (the evolution of vocal learning of complex songs in birds, whales, and seals). A fascinating but overlooked potential homology to instrumental music is provided by manual percussion in African apes. Such comparative behavioral data, combined with neuroscientific and developmental data, provide an important starting point for any hypothesis about how or why human music evolved. Regarding these functional and phylogenetic questions, I discuss some previously proposed functions of music, including Pinker's "cheesecake" hypothesis; Darwin's and others' sexual selection model; Dunbar's group "grooming" hypothesis; and Trehub's caregiving model. I conclude that only the last hypothesis receives strong support from currently available data. I end with a brief synopsis of Darwin's model of a songlike musical "protolanguage," concluding that Darwin's model is consistent with much of the available evidence concerning the evolution of both music and language. There is a rich future for empirical investigations of the evolution of music, both in investigations of individual differences among humans, and in interspecific investigations of musical abilities in other animals, especially those of our ape cousins, about which we know little.
Oxytocin and social functioning
Jones, Candace; Barrera, Ingrid; Brothers, Shaun; Ring, Robert; Wahlestedt, Claes
2017-01-01
Social anxiety is a form of anxiety characterized by continuous fear of one or more social or performance situations. Although multiple treatment modalities (cognitive behavioral therapy, selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors, benzodiazepines) exist for social anxiety, they are effective for only 60% to 70% of patients. Thus, researchers have looked for other candidates for social anxiety treatment. Our review focuses on the peptide oxytocin as a potential therapeutic option for individuals with social anxiety. Animal research both in nonprimates and primates supports oxytocin's role in facilitation of prosocial behaviors and its anxiolytic effects. Human studies indicate significant associations between social anxiety and oxytocin receptor gene alleles, as well as social anxiety and oxytocin plasma levels. In addition, intranasal administration of oxytocin in humans has favorable effects on social anxiety symptomology. Other disorders, including autism, schizophrenia, and anorexia, have components of social anxiety in their pathophysiology. The therapeutic role of oxytocin for social dysfunction in these disorders is discussed. PMID:28867943
The return of the Inseminator: Eutelegenesis in past and contemporary reproductive ethics.
McMillan, John
2007-06-01
Eugenicists in the 1930s and 1940s emphasised our moral responsibilities to future generations and the importance of positively selecting traits that would benefit humanity. In 1935 Herbert Brewer recommended 'Eutelegenesis' (artificial insemination with sperm from specially selected males) so that that future generations are not only protected from hereditary disease but also become more intelligent and fraternal than us. The development of these techniques for human use and animal husbandry was the catalyst for the cross fertilization of moral ideas and the development of a critical procreative morality. While eugenicists argued for a new critical morality, religious critics argued against artificial insemination because of its potential to damage important moral institutions. The tension between critical and conservative procreative morality is a feature of the contemporary debates about reproductive technologies. This and some of the other aspects of the early and contemporary debates about artificial insemination and reproductive technologies are discussed in this article.
Oxytocin and social functioning.
Jones, Candace; Barrera, Ingrid; Brothers, Shaun; Ring, Robert; Wahlestedt, Claes
2017-06-01
Social anxiety is a form of anxiety characterized by continuous fear of one or more social or performance situations. Although multiple treatment modalities (cognitive behavioral therapy, selective serotonin reuptake inhibitors/selective norepinephrine reuptake inhibitors, benzodiazepines) exist for social anxiety, they are effective for only 60% to 70% of patients. Thus, researchers have looked for other candidates for social anxiety treatment. Our review focuses on the peptide oxytocin as a potential therapeutic option for individuals with social anxiety. Animal research both in nonprimates and primates supports oxytocin's role in facilitation of prosocial behaviors and its anxiolytic effects. Human studies indicate significant associations between social anxiety and oxytocin receptor gene alleles, as well as social anxiety and oxytocin plasma levels. In addition, intranasal administration of oxytocin in humans has favorable effects on social anxiety symptomology. Other disorders, including autism, schizophrenia, and anorexia, have components of social anxiety in their pathophysiology. The therapeutic role of oxytocin for social dysfunction in these disorders is discussed.
Facial asymmetry as an indicator of psychological, emotional, and physiological distress.
Shackelford, T K; Larsen, R J
1997-02-01
Fluctuating asymmetry (FA) is deviation from bilateral symmetry in morphological traits with asymmetry values that are normally distributed with a mean of 0. FA is produced by genetic or environmental perturbations of developmental design and may play a role in human sexual selection. K. Grammer and R. Thornhill (1994) found that facial FA negatively covaries with observer ratings of attractiveness, dominance, sexiness, and health. Using self-reports, observer ratings, daily diary reports, and psychophysiological measures, the authors assessed the relationship between facial FA and health in 2 samples of undergraduates (N = 101). Results partially replicate and extend those of K. Grammer and R. Thornhill (1994) and suggest that facial FA may signal psychological, emotional, and physiological distress. Discussion integrates the authors' findings with previous research on FA and suggests future research needed to clarify the role of FA in human sexual selection.
Invited commentary: Physical activity, mortality, and genetics.
Rankinen, Tuomo; Bouchard, Claude
2007-08-01
The importance of regular physical activity to human health has been recognized for a long time, and a physically active lifestyle is now defined as a major component of public health policies. The independent contribution of regular physical activity to lower morbidity and mortality rates is generally accepted, and the biologic mechanisms mediating these health effects are actively investigated. A few years ago, data from the Finnish Twin Registry suggested that genetic selection may account for some of the physical-activity-related benefits on mortality rates. However, results from the Swedish Twin Registry study reported by Carlsson et al. in the current issue of the Journal (Am J Epidemiol 2007;166:255-259) do not support the genetic selection hypothesis. In this commentary, the authors review the nature of the associations among physical activity level, fitness, and longevity, with special reference to the role of human genetic variation, and discuss potential reasons for different outcomes of these large twin studies.
Charles Darwin and Evolution: Illustrating Human Aspects of Science
NASA Astrophysics Data System (ADS)
Kampourakis, Kostas; McComas, William F.
2010-06-01
Recently, the nature of science (NOS) has become recognized as an important element within the K-12 science curriculum. Despite differences in the ultimate lists of recommended aspects, a consensus is emerging on what specific NOS elements should be the focus of science instruction and inform textbook writers and curriculum developers. In this article, we suggest a contextualized, explicit approach addressing one core NOS aspect: the human aspects of science that include the domains of creativity, social influences and subjectivity. To illustrate these ideas, we have focused on Charles Darwin, a scientist whose life, work and thought processes were particularly well recorded at the time and analyzed by scholars in the succeeding years. Historical facts are discussed and linked to core NOS ideas. Creativity is illustrated through the analogies between the struggle for existence in human societies and in nature, between artificial and natural selection, and between the division of labor in human societies and in nature. Social influences are represented by Darwin’s aversion of criticism of various kinds and by his response to the methodological requirements of the science of that time. Finally, subjectivity is discussed through Darwin’s development of a unique but incorrect source for the origin of variations within species.
van der Wee, Nic J A; Bilderbeck, Amy C; Cabello, Maria; Ayuso-Mateos, Jose L; Saris, Ilya M J; Giltay, Erik J; Penninx, Brenda Wjh; Arango, Celso; Post, Anke; Porcelli, Stefano
2018-06-24
Social withdrawal is one of the first and common signs of early social dysfunction in a number of important neuropsychiatric disorders, likely because of the enormous amount and complexity of brain processes required to initiate and maintain social relationships (Adolphs, 2009). The Psychiatric Ratings using Intermediate Stratified Markers (PRISM) project focusses on the shared and unique neurobiological basis of social withdrawal in schizophrenia, Alzheimer and depression. In this paper, we discuss the working definition of social withdrawal for this study and the selection of objective and subjective rating scales to assess social withdrawal chosen or adapted for this project. We also discuss the MRI and EEG paradigms selected to study the systems and neural circuitry thought to underlie social functioning and more particularly to be involved in social withdrawal in humans, such as the social perception and the social affiliation networks. A number of behavioral paradigms were selected to assess complementary aspects of social cognition. Also, a digital phenotyping method (a smartphone application) was chosen to obtain real-life data. Copyright © 2018. Published by Elsevier Ltd.
Monkey cortex through fMRI glasses
Vanduffel, Wim; Zhu, Qi; Orban, Guy A.
2015-01-01
In 1998 several groups reported the feasibility of functional magnetic resonance imaging (fMRI) experiments in monkeys, with the goal to bridge the gap between invasive nonhuman primate studies and human functional imaging. These studies yielded critical insights in the neuronal underpinnings of the BOLD signal. Furthermore, the technology has been successful in guiding electrophysiological recordings and identifying focal perturbation targets. Finally, invaluable information was obtained concerning human brain evolution. We here provide a comprehensive overview of awake monkey fMRI studies mainly confined to the visual system. We review the latest insights about the topographic organization of monkey visual cortex and discuss the spatial relationships between retinotopy and category and feature selective clusters. We briefly discuss the functional layout of parietal and frontal cortex and continue with a summary of some fascinating functional and effective connectivity studies. Finally, we review recent comparative fMRI experiments and speculate about the future of nonhuman primate imaging. PMID:25102559
NASA Technical Reports Server (NTRS)
Schenker, Paul S. (Editor)
1991-01-01
The volume on data fusion from multiple sources discusses fusing multiple views, temporal analysis and 3D motion interpretation, sensor fusion and eye-to-hand coordination, and integration in human shape perception. Attention is given to surface reconstruction, statistical methods in sensor fusion, fusing sensor data with environmental knowledge, computational models for sensor fusion, and evaluation and selection of sensor fusion techniques. Topics addressed include the structure of a scene from two and three projections, optical flow techniques for moving target detection, tactical sensor-based exploration in a robotic environment, and the fusion of human and machine skills for remote robotic operations. Also discussed are K-nearest-neighbor concepts for sensor fusion, surface reconstruction with discontinuities, a sensor-knowledge-command fusion paradigm for man-machine systems, coordinating sensing and local navigation, and terrain map matching using multisensing techniques for applications to autonomous vehicle navigation.
Current results with slow freezing and vitrification of the human oocyte.
Boldt, Jeffrey
2011-09-01
The past decade has witnessed renewed interest in human oocyte cryopreservation (OCP). This article reviews the two general methods used for OCP, slow freezing and vitrification, compares the outcomes associated with each technique and discusses the factors that might influence success with OCP (such as oocyte selection or day of transfer). Based on available data, OCP offers a reliable, reproducible method for preservation of the female gamete and will find increasing application in assisted reproductive technology. Oocyte cryopreservation can provide a number of advantages to couples undergoing assisted reproduction or to women interested in fertility preservation. Two methods, slow freezing and vitrification, have been used successfully for oocyte cryopreservation. This article reviews and compares these methods, and discusses various factors that can impact upon success of oocyte cryopreservation. Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Monkey cortex through fMRI glasses.
Vanduffel, Wim; Zhu, Qi; Orban, Guy A
2014-08-06
In 1998 several groups reported the feasibility of fMRI experiments in monkeys, with the goal to bridge the gap between invasive nonhuman primate studies and human functional imaging. These studies yielded critical insights in the neuronal underpinnings of the BOLD signal. Furthermore, the technology has been successful in guiding electrophysiological recordings and identifying focal perturbation targets. Finally, invaluable information was obtained concerning human brain evolution. We here provide a comprehensive overview of awake monkey fMRI studies mainly confined to the visual system. We review the latest insights about the topographic organization of monkey visual cortex and discuss the spatial relationships between retinotopy and category- and feature-selective clusters. We briefly discuss the functional layout of parietal and frontal cortex and continue with a summary of some fascinating functional and effective connectivity studies. Finally, we review recent comparative fMRI experiments and speculate about the future of nonhuman primate imaging. Copyright © 2014 Elsevier Inc. All rights reserved.
What have humans done for evolutionary biology? Contributions from genes to populations.
Briga, Michael; Griffin, Robert M; Berger, Vérane; Pettay, Jenni E; Lummaa, Virpi
2017-11-15
Many fundamental concepts in evolutionary biology were discovered using non-human study systems. Humans are poorly suited to key study designs used to advance this field, and are subject to cultural, technological, and medical influences often considered to restrict the pertinence of human studies to other species and general contexts. Whether studies using current and recent human populations provide insights that have broader biological relevance in evolutionary biology is, therefore, frequently questioned. We first surveyed researchers in evolutionary biology and related fields on their opinions regarding whether studies on contemporary humans can advance evolutionary biology. Almost all 442 participants agreed that humans still evolve, but fewer agreed that this occurs through natural selection. Most agreed that human studies made valuable contributions to evolutionary biology, although those less exposed to human studies expressed more negative views. With a series of examples, we discuss strengths and limitations of evolutionary studies on contemporary humans. These show that human studies provide fundamental insights into evolutionary processes, improve understanding of the biology of many other species, and will make valuable contributions to evolutionary biology in the future. © 2017 The Author(s).
What have humans done for evolutionary biology? Contributions from genes to populations
Briga, Michael; Griffin, Robert M.; Berger, Vérane; Pettay, Jenni E.
2017-01-01
Many fundamental concepts in evolutionary biology were discovered using non-human study systems. Humans are poorly suited to key study designs used to advance this field, and are subject to cultural, technological, and medical influences often considered to restrict the pertinence of human studies to other species and general contexts. Whether studies using current and recent human populations provide insights that have broader biological relevance in evolutionary biology is, therefore, frequently questioned. We first surveyed researchers in evolutionary biology and related fields on their opinions regarding whether studies on contemporary humans can advance evolutionary biology. Almost all 442 participants agreed that humans still evolve, but fewer agreed that this occurs through natural selection. Most agreed that human studies made valuable contributions to evolutionary biology, although those less exposed to human studies expressed more negative views. With a series of examples, we discuss strengths and limitations of evolutionary studies on contemporary humans. These show that human studies provide fundamental insights into evolutionary processes, improve understanding of the biology of many other species, and will make valuable contributions to evolutionary biology in the future. PMID:29118130
What should I do next? Using shared representations to solve interaction problems.
Pezzulo, Giovanni; Dindo, Haris
2011-06-01
Studies on how "the social mind" works reveal that cognitive agents engaged in joint actions actively estimate and influence another's cognitive variables and form shared representations with them. (How) do shared representations enhance coordination? In this paper, we provide a probabilistic model of joint action that emphasizes how shared representations help solving interaction problems. We focus on two aspects of the model. First, we discuss how shared representations permit to coordinate at the level of cognitive variables (beliefs, intentions, and actions) and determine a coherent unfolding of action execution and predictive processes in the brains of two agents. Second, we discuss the importance of signaling actions as part of a strategy for sharing representations and the active guidance of another's actions toward the achievement of a joint goal. Furthermore, we present data from a human-computer experiment (the Tower Game) in which two agents (human and computer) have to build together a tower made of colored blocks, but only the human knows the constellation of the tower to be built (e.g., red-blue-red-blue-…). We report evidence that humans use signaling strategies that take another's uncertainty into consideration, and that in turn our model is able to use humans' actions as cues to "align" its representations and to select complementary actions.
Quantitative bioanalysis of strontium in human serum by inductively coupled plasma-mass spectrometry
Somarouthu, Srikanth; Ohh, Jayoung; Shaked, Jonathan; Cunico, Robert L; Yakatan, Gerald; Corritori, Suzana; Tami, Joe; Foehr, Erik D
2015-01-01
Aim: A bioanalytical method using inductively-coupled plasma-mass spectrometry to measure endogenous levels of strontium in human serum was developed and validated. Results & methodology: This article details the experimental procedures used for the method development and validation thus demonstrating the application of the inductively-coupled plasma-mass spectrometry method for quantification of strontium in human serum samples. The assay was validated for specificity, linearity, accuracy, precision, recovery and stability. Significant endogenous levels of strontium are present in human serum samples ranging from 19 to 96 ng/ml with a mean of 34.6 ± 15.2 ng/ml (SD). Discussion & conclusion: Calibration procedures and sample pretreatment were simplified for high throughput analysis. The validation demonstrates that the method was sensitive, selective for quantification of strontium (88Sr) and is suitable for routine clinical testing of strontium in human serum samples. PMID:28031925
NASA Technical Reports Server (NTRS)
Graham, Robert W.
1990-01-01
The role of the middle manager in a research organization is discussed. The middle manager serves as a liaison between upper management and researchers to assure that individual research projects manifest the goals of the organization. The author draws on his long experience in this role to describe management practices that have proven successful. A general discussion is presented of the makeup of a research environment, derived from a study of a division involved in aerospace research and development (R and D). The study emphasized the importance of planning and management style in producing an attractive environment. Management practices are described, which include goal setting, planning, staffing, reviewing and evaluating, and rewarding. The importance of selecting and defining an appropriate research area is discussed. It is emphasized that in relating to the staff the middle manager must cultivate the human side of supervision, develop the art of delegating responsibility, judiciously select facilities, and provide recognition and meaningful rewards to develop a productive research staff. The development of the staff is probably the most important and challenging role of the manager.
The Weak Spots in Contemporary Science (and How to Fix Them).
Wicherts, Jelte M
2017-11-27
In this review, the author discusses several of the weak spots in contemporary science, including scientific misconduct, the problems of post hoc hypothesizing (HARKing), outcome switching, theoretical bloopers in formulating research questions and hypotheses, selective reading of the literature, selective citing of previous results, improper blinding and other design failures, p-hacking or researchers' tendency to analyze data in many different ways to find positive (typically significant) results, errors and biases in the reporting of results, and publication bias. The author presents some empirical results highlighting problems that lower the trustworthiness of reported results in scientific literatures, including that of animal welfare studies. Some of the underlying causes of these biases are discussed based on the notion that researchers are only human and hence are not immune to confirmation bias, hindsight bias, and minor ethical transgressions. The author discusses solutions in the form of enhanced transparency, sharing of data and materials, (post-publication) peer review, pre-registration, registered reports, improved training, reporting guidelines, replication, dealing with publication bias, alternative inferential techniques, power, and other statistical tools.
Present state and future perspectives of using pluripotent stem cells in toxicology research
Löser, Peter
2011-01-01
The use of novel drugs and chemicals requires reliable data on their potential toxic effects on humans. Current test systems are mainly based on animals or in vitro–cultured animal-derived cells and do not or not sufficiently mirror the situation in humans. Therefore, in vitro models based on human pluripotent stem cells (hPSCs) have become an attractive alternative. The article summarizes the characteristics of pluripotent stem cells, including embryonic carcinoma and embryonic germ cells, and discusses the potential of pluripotent stem cells for safety pharmacology and toxicology. Special attention is directed to the potential application of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) for the assessment of developmental toxicology as well as cardio- and hepatotoxicology. With respect to embryotoxicology, recent achievements of the embryonic stem cell test (EST) are described and current limitations as well as prospects of embryotoxicity studies using pluripotent stem cells are discussed. Furthermore, recent efforts to establish hPSC-based cell models for testing cardio- and hepatotoxicity are presented. In this context, methods for differentiation and selection of cardiac and hepatic cells from hPSCs are summarized, requirements and implications with respect to the use of these cells in safety pharmacology and toxicology are presented, and future challenges and perspectives of using hPSCs are discussed. PMID:21225242
Characterization of binding affinity of CJ-023,423 for human prostanoid EP4 receptor.
Murase, Akio; Nakao, Kazunari; Takada, Junji
2008-01-01
In order to characterize the receptor binding pharmacology of CJ-023,423, a potent and selective EP4 antagonist, we performed a radioligand receptor binding assay under various assay conditions. An acidic (pH 6) and hypotonic buffer is a conventional, well-known buffer for prostaglandin E2 receptor binding assays. CJ-023,423 showed moderate binding affinity for human EP4 receptor under conventional buffer conditions. However, its binding affinity was greatly increased under neutral (pH 7.4) and isotonic buffer conditions. In this report, the binding mechanism between CJ-023,423 and human EP4 receptor is discussed based on the binding affinities determined under various assay conditions. Copyright 2008 S. Karger AG, Basel.
D'Onofrio, Giuseppe; Ghosh, Tapash Chandra
2005-01-17
Fluctuations and increments of both C(3) and G(3) levels along the human coding sequences were investigated comparing two sets of Xenopus/human orthologous genes. The first set of genes shows minor differences of the GC(3) levels, the second shows considerable increments of the GC(3) levels in the human genes. In both data sets, the fluctuations of C(3) and G(3) levels along the coding sequences correlated with the secondary structures of the encoded proteins. The human genes that underwent the compositional transition showed a different increment of the C(3) and G(3) levels within and among the structural units of the proteins. The relative synonymous codon usage (RSCU) of several amino acids were also affected during the compositional transition, showing that there exists a correlation between RSCU and protein secondary structures in human genes. The importance of natural selection for the formation of isochore organization of the human genome has been discussed on the basis of these results.
Technological progress as a driver of innovation in infant foods.
Ferruzzi, Mario G; Neilson, Andrew P
2010-01-01
Advances in nutrition and food sciences are interrelated components of the innovative framework for infant formula and foods. While nutrition science continues to define the composition and functionality of human milk as a reference, food ingredient, formulation and processing technologies facilitate the design and delivery of nutritional and functional concepts to infant products. Expanding knowledge of both nutritive and non-nutritive components of human milk and their functionality guides selection and development of novel ingredient, formulation and processing methods to generate enhanced infant products targeting benefits including healthy growth, development as well as protection of health through the life cycle. In this chapter, identification and application of select novel ingredients/technologies will be discussed in the context of how these technological advancements have stimulated innovation in infant foods. Special focus will be given to advancements in protein technologies, as well as bioactive long-chain polyunsaturated fatty acids, prebiotics, probiotics that have allowed infant formula composition, and more critically functionality, to more closely align with that of human milk. Copyright © 2010 S. Karger AG, Basel.
Reconsideration of the WHO NCTB Strategy and Test Selection
Anger, W. Kent
2014-01-01
The World Health Organization-recommended Neurobehavioral Core Test Battery (NCTB) became the international standard for identifying adverse human behavioral effects due to neurotoxic chemical exposure when it was first proposed in 1983. Since then the WHO NCTB has been repeatedly cited as the basis for test selection in human neurotoxicology research. A Discussion Group was held before the International Symposium on Neurobehavioral Methods and effects in Occupational and Environmental Health to review the NCTB and reconsider it’s tests. The workshop made three consensus recommendations to the International Congress on Occupational Health (ICOH) Scientific Committee on Neurotoxicology and Psychophysiology (SCNP): a ‘screening’ battery of broadly sensitive tests is needed as guidance to the field of human neurotoxicologythe SCNP should convene a panel to reconsider the functions measured and the tests in the WHO NCTBThree disciplines should be represented in the panel recommending a revised NCTB: Neuropsychology; Experimental Psychology; Neurology This recommendation will be pursued at the next meeting of the International Congress on Occupational Health (ICOH) Scientific Committee on Neurotoxicology and Psychophysiology (SCNP). PMID:25172409
Maternal hypothyroidism: An overview of current experimental models.
Ghanbari, Mahboubeh; Ghasemi, Asghar
2017-10-15
Maternal hypothyroidism (MH) is the most common cause of transient congenital hypothyroidism. Different animal models are used for assessing developmental effects of MH in offspring. The severity and status of hypothyroidism in animal models must be a reflection of the actual conditions in humans. To obtain comparable results with different clinical conditions, which lead to MH in humans, several factors have been suggested for researchers to consider before designing the experimental models. Regarding development of fetal body systems during pregnancy, interference at different times provides different results and the appropriate time for induction of hypothyroidism should be selected based on accurate time of development of the system under assessment. Other factors that should be taken into consideration include, physiological and biochemical differences between humans and other species, thyroid hormone-independent effects of anti-thyroid drugs, circadian rhythms in TSH secretion, sex differences, physical and psychological stress. This review addresses essential guidelines for selecting and managing the optimal animal model for MH as well as discussing the pros and cons of currently used models. Copyright © 2017 Elsevier Inc. All rights reserved.
Akkina, Ramesh; Allam, Atef; Balazs, Alejandro B; Blankson, Joel N; Burnett, John C; Casares, Sofia; Garcia, J Victor; Hasenkrug, Kim J; Kashanchi, Fatah; Kitchen, Scott G; Klein, Florian; Kumar, Priti; Luster, Andrew D; Poluektova, Larisa Y; Rao, Mangala; Sanders-Beer, Brigitte E; Shultz, Leonard D; Zack, Jerome A
2016-02-01
The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and other infectious diseases has expanded rapidly over the past 8 years. Highly immunodeficient mouse strains, such as NOD/SCID/gamma chain(null) (NSG, NOG), support better human hematopoietic cell engraftment. Another improvement is the derivation of highly immunodeficient mice, transgenic with human leukocyte antigens (HLAs) and cytokines that supported development of HLA-restricted human T cells and heightened human myeloid cell engraftment. Humanized mice are also used to study the HIV reservoir using new imaging techniques. Despite these advances, there are still limitations in HIV immune responses and deficits in lymphoid structures in these models in addition to xenogeneic graft-versus-host responses. To understand and disseminate the improvements and limitations of humanized mouse models to the scientific community, the NIH sponsored and convened a meeting on April 15, 2015 to discuss the state of knowledge concerning these questions and best practices for selecting a humanized mouse model for a particular scientific investigation. This report summarizes the findings of the NIH meeting.
An Annotated Selective Bibliography on Human Performance in Fault Diagnosis Tasks
1980-01-01
and automated fault diagnosis has been omitted from this bibliography. Where possible, we used the abstract that accompanied an item. However, we...system failure, ignition system failure, drive, transmission, and rear axle trouble, and power brake and power steering failure. 98 pages Howard W. Sams...knowledge. The second section discusses some of the pedagogical issues that have emerged from the use of diagnostic models within an instructional
Nondestructive testing techniques
NASA Astrophysics Data System (ADS)
Bray, Don E.; McBride, Don
A comprehensive reference covering a broad range of techniques in nondestructive testing is presented. Based on years of extensive research and application at NASA and other government research facilities, the book provides practical guidelines for selecting the appropriate testing methods and equipment. Topics discussed include visual inspection, penetrant and chemical testing, nuclear radiation, sonic and ultrasonic, thermal and microwave, magnetic and electromagnetic techniques, and training and human factors. (No individual items are abstracted in this volume)
Cardiovascular studies in the rhesus monkey. [brain circulation during stress
NASA Technical Reports Server (NTRS)
Stone, H. L.; Sandler, H.
1977-01-01
Criteria are given for selecting the macaca mulatta as the analogue of the human in the study of cerebral circulation, particularly the control of the cerebral vascular bed during normal and stressful conditions. Topics discussed include surgical preparation of subject; responses to changes in arterial pressure, oxygen, and carbon dioxide; innervation of cerebral vessels; cerebral flow response to acceleration; and cerebral blood flow and cerebellar stimulation.
Choice Impulsivity: Definitions, Measurement Issues, and Clinical Implications
Hamilton, Kristen R.; Mitchell, Marci R.; Wing, Victoria C.; Balodis, Iris M.; Bickel, Warren K.; Fillmore, Mark; Lane, Scott D.; Lejuez, C. W.; Littlefield, Andrew K.; Luijten, Maartje; Mathias, Charles W.; Mitchell, Suzanne H.; Napier, T. Celeste; Reynolds, Brady; Schütz, Christian G.; Setlow, Barry; Sher, Kenneth J.; Swann, Alan C.; Tedford, Stephanie E.; White, Melanie J.; Winstanley, Catharine A.; Yi, Richard; Potenza, Marc N.; Moeller, F. Gerard
2015-01-01
Background Impulsivity critically relates to many psychiatric disorders. Given the multi-faceted construct that impulsivity represents, defining core aspects of impulsivity is vital for the assessment and understanding of clinical conditions. Choice impulsivity (CI), involving the preferential selection of smaller sooner rewards over larger later rewards, represents one important type of impulsivity. Method The International Society for Research on Impulsivity (InSRI) convened to discuss the definition and assessment of CI and provide recommendations regarding measurement across species. Results Commonly used preclinical and clinical CI behavioral tasks are described, and considerations for each task are provided to guide CI task selection. Differences in assessment of CI (self-report, behavioral) and calculating CI indices (e.g., area-under-the-curve, indifference point, steepness of discounting curve) are discussed along with properties of specific behavioral tasks used in preclinical and clinical settings. Conclusions The InSRI group recommends inclusion of measures of CI in human studies examining impulsivity. Animal studies examining impulsivity should also include assessments of CI and these measures should be harmonized in accordance with human studies of the disorders being modeled in the preclinical investigations. The choice of specific CI measures to be included should be based on the goals of the study and existing preclinical and clinical literature using established CI measures. PMID:25867841
Human Decision Processes: Implications for SSA Support Tools
NASA Astrophysics Data System (ADS)
Picciano, P.
2013-09-01
Despite significant advances in computing power and artificial intelligence (AI), few critical decisions are made without a human decision maker in the loop. Space Situational Awareness (SSA) missions are both critical and complex, typically adhering to the human-in-the-loop (HITL) model. The collection of human operators injects a needed diversity of expert knowledge, experience, and authority required to successfully fulfill SSA tasking. A wealth of literature on human decision making exists citing myriad empirical studies and offering a varied set of prescriptive and descriptive models of judgment and decision making (Hastie & Dawes, 2001; Baron, 2000). Many findings have been proven sufficiently robust to allow information architects or system/interface designers to take action to improve decision processes. For the purpose of discussion, these concepts are bifurcated in two groups: 1) vulnerabilities to mitigate, and 2) capabilities to augment. These vulnerabilities and capabilities refer specifically to the decision process and should not be confused with a shortcoming or skill of a specific human operator. Thus the framing of questions and orders, the automated tools with which to collaborate, priming and contextual data, and the delivery of information all play a critical role in human judgment and choice. Evaluating the merits of any decision can be elusive; in order to constrain this discussion, ‘rational choice' will tend toward the economic model characteristics such as maximizing utility and selection consistency (e.g., if A preferred to B, and B preferred to C, than A should be preferred to C). Simple decision models often encourage one to list the pros and cons of a decision, perhaps use a weighting schema, but one way or another weigh the future benefit (or harm) of making a selection. The result (sought by the rationalist models) should drive toward higher utility. Despite notable differences in researchers' theses (to be discussed in the full paper), one opinion shared is that the rational, economic, deliberate listing/evaluation of all options is NOT representative of how many decision are made. A framework gaining interest lately describes two systems predominantly at work: intuition and reasoning (Kahneman, 2003). Intuition is fast, automatic, and parallel contrasted with the more effortful, deliberative, and sequential reasoning. One of the issues of contention is that considerable research is stacked supporting both sides claiming that intuition is: • A hallmark of expertise responsible for rapid, optimal decisions in the face of adversity • A vulnerability where biases serve as decision traps leading to wrong choices Using seminal studies from a range of domains and tasking, potential solutions for SSA decision support will be offered. Important issues such as managing uncertainty, framing inquiries, and information architecture, and contextual cues will be discussed. The purpose is to provide awareness of the human limitations and capabilities in complex decision making so engineers and designers can consider such factors in their development of SSA tools.
Overview of spaceflight immunology studies
NASA Technical Reports Server (NTRS)
Taylor, G. R.
1993-01-01
The effects of spaceflight and analogues of spaceflight are discussed here and in nine accompanying articles. In this summary we present spaceflight studies with human subjects, animal subjects, and cell cultures and we review ground-based systems used to model the observed effects of spaceflight on the immune system. Human paradigms include bed rest, academic or psychological stress, physical stress, hypobaric or high altitude stress, and confinement. Animal models include antiorthostatic and orthostatic suspension, hypobarism, and confinement. The ten manuscripts in this collection were selected to provide a summary that should give the reader an overview of the various activities of spaceflight immunology researchers throughout the history of space travel. This manuscript identifies the major contributors to the study of spaceflight immunology, explains what types of studies have been conducted, and how they have changed over the years. Also presented is a discussion of the unusual limitations associated with spaceflight research and the efforts to develop appropriate ground-based surrogate model systems. Specific details, data, and mechanistic speculations will be held to a minimum, because they will be discussed in depth in the other articles in the collection.
Infectious Disease Stigmas: Maladaptive in Modern Society
Smith, Rachel A.; Hughes, David
2014-01-01
At multiple times in human history people have asked if there are good stigmas. Is there some useful function stigmas serve in the context of our evolutionary history; is stigma adaptive? This essay discusses stigmas as a group-selection strategy and the human context in which stigmas likely appeared. The next section explores how human patterns have changed in modern society and the consequences for infectious disease (ID) stigmas in the modern age. The concluding section suggests that while social-living species may be particularly apt to create and communicate ID stigmas and enact ID-related stigmatization, such stigma-related processes no longer function to protect human communities. Stigmas do not increase the ability of modern societies to survive infectious diseases, but in fact may be important drivers of problematic disease dynamics and act as catalysts for failures in protecting public health. PMID:25477728
NASA Technical Reports Server (NTRS)
Shields, W. E.; Smith, J. D.; Washburn, D. A.; Rumbaugh, D. M. (Principal Investigator)
1997-01-01
The authors asked whether animals, like humans, use an uncertain response adaptively to escape indeterminate stimulus relations. Humans and monkeys were placed in a same-different task, known to be challenging for animals. Its difficulty was increased further by reducing the size of the stimulus differences, thereby making many same and different trials difficult to tell apart. Monkeys do escape selectively from these threshold trials, even while coping with 7 absolute stimulus levels concurrently. Monkeys even adjust their response strategies on short time scales according to the local task conditions. Signal-detection and optimality analyses confirm the similarity of humans' and animals' performances. Whereas associative interpretations account poorly for these results, an intuitive uncertainty construct does so easily. The authors discuss the cognitive processes that allow uncertainty's adaptive use and recommend further comparative studies of metacognition.
Revisit of Machine Learning Supported Biological and Biomedical Studies.
Yu, Xiang-Tian; Wang, Lu; Zeng, Tao
2018-01-01
Generally, machine learning includes many in silico methods to transform the principles underlying natural phenomenon to human understanding information, which aim to save human labor, to assist human judge, and to create human knowledge. It should have wide application potential in biological and biomedical studies, especially in the era of big biological data. To look through the application of machine learning along with biological development, this review provides wide cases to introduce the selection of machine learning methods in different practice scenarios involved in the whole biological and biomedical study cycle and further discusses the machine learning strategies for analyzing omics data in some cutting-edge biological studies. Finally, the notes on new challenges for machine learning due to small-sample high-dimension are summarized from the key points of sample unbalance, white box, and causality.
The Human Cutaneous Chemokine System
McCully, Michelle L.; Moser, Bernhard
2011-01-01
Irrespective of the immune status, the vast majority of all lymphocytes reside in peripheral tissues whereas those present in blood only amount to a small fraction of the total. It has been estimated that T cells in healthy human skin outnumber those present in blood by at least a factor of two. How lymphocytes within these two compartments relate to each other is not well understood. However, mounting evidence suggest that the study of T cell subsets present in peripheral blood does not reflect the function of their counterparts at peripheral sites. This is especially true under steady-state conditions whereby long-lived memory T cells in healthy tissues, notably those in epithelial tissues at body surfaces, are thought to fulfill a critical immune surveillance function by contributing to the first line of defense against a series of local threats, including microbes, tumors, and toxins, and by participating in wound healing. The relative scarcity of information regarding peripheral T cells and the factors regulating their localization is primarily due to inherent difficulties in obtaining healthy tissue for the extraction and study of immune cells on a routine basis. This is most certainly true for humans. Here, we review our current understanding of T cell homing to human skin and compare it when possible with gut-selective homing. We also discuss candidate chemokines that may account for the tissue selectivity in this process and present a model whereby CCR8, and its ligand CCL1, selectively regulate the homeostatic migration of memory lymphocytes to skin tissue. PMID:22566823
Evolution and human sexuality.
Gray, Peter B
2013-12-01
The aim of this review is to put core features of human sexuality in an evolutionary light. Toward that end, I address five topics concerning the evolution of human sexuality. First, I address theoretical foundations, including recent critiques and developments. While much traces back to Darwin and his view of sexual selection, more recent work helps refine the theoretical bases to sex differences and life history allocations to mating effort. Second, I consider central models attempting to specify the phylogenetic details regarding how hominin sexuality might have changed, with most of those models honing in on transitions from a possible chimpanzee-like ancestor to the slightly polygynous and long-term bonded sociosexual partnerships observed among most recently studied hunter-gatherers. Third, I address recent genetic and physiological data contributing to a refined understanding of human sexuality. As examples, the availability of rapidly increasing genomic information aids comparative approaches to discern signals of selection in sexuality-related phenotypes, and neuroendocrine studies of human responses to sexual stimuli provide insight into homologous and derived mechanisms. Fourth, I consider some of the most recent, large, and rigorous studies of human sexuality. These provide insights into sexual behavior across other national samples and on the Internet. Fifth, I discuss the relevance of a life course perspective to understanding the evolution of human sexuality. Most research on the evolution of human sexuality focuses on young adults. Yet humans are sexual beings from gestation to death, albeit in different ways across the life course, and in ways that can be theoretically couched within life history theory. Copyright © 2013 Wiley Periodicals, Inc.
Synthesis of Lysine Methyltransferase Inhibitors
NASA Astrophysics Data System (ADS)
Ye, Tao; Hui, Chunngai
2015-07-01
Lysine methyltransferase which catalyze methylation of histone and nonhistone proteins, play a crucial role in diverse biological processes and has emerged as a promising target for the development of various human diseases, including cancer, inflammation, and psychiatric disorders. However, inhibiting Lysine methyltransferases selectively has presented many challenges to medicinal chemists. During the past decade, lysine methyltransferase inhibitors covering many different structural classes have been designed and developed. In this review, we describe the development of selective, small-molecule inhibitors of lysine methyltransferases with an emphasis on their discovery and chemical synthesis. We highlight the current state of lysine methyltransferase inhibitors and discuss future directions and opportunities for lysine methyltransferase inhibitor discovery.
National low-level waste management program radionuclide report series, Volume 15: Uranium-238
DOE Office of Scientific and Technical Information (OSTI.GOV)
Adams, J.P.
1995-09-01
This report, Volume 15 of the National Low-Level Waste Management Program Radionuclide Report Series, discusses the radiological and chemical characteristics of uranium-238 ({sup 238}U). The purpose of the National Low-Level Waste Management Program Radionuclide Report Series is to provide information to state representatives and developers of low-level radioactive waste disposal facilities about the radiological, chemical, and physical characteristics of selected radionuclides and their behavior in the waste disposal facility environment. This report also includes discussions about waste types and forms in which {sup 238}U can be found, and {sup 238}U behavior in the environment and in the human body.
Griff, Edwin R
2016-09-01
In the present article, a veteran lecturer of human anatomy and physiology taught several sections of the laboratory component for the first time and shares his observations and analysis from this unique perspective. The article discusses a large-enrollment, content-heavy anatomy and physiology course in relationship to published studies on learning and student self-efficacy. Changes in the laboratory component that could increase student learning are proposed. The author also points out the need for research to assess whether selective curricular changes could increase the depth of understanding and retention of learned material. Copyright © 2016 The American Physiological Society.
Corporate information systems in health organisations.
Smith, J
1997-01-01
This paper presents an overview of the nature of corporate information systems and their applications in health organisations. It emphasises the importance of financial and human resource information in the creation of a corporate data model. The paper summarises the main features of finance and human resource systems as they are used in health organisations. It looks at a series of case studies carried out in health organisations, which were selected on the basis of their representation of different aspects of service delivery. It also discusses the theoretical and practical perspectives of the systems themselves, their roles in information management, executive and decision support, and in planning and forecasting.
The data base management system alternative for computing in the human services.
Sircar, S; Schkade, L L; Schoech, D
1983-01-01
The traditional incremental approach to computerization presents substantial problems as systems develop and grow. The Data Base Management System approach to computerization was developed to overcome the problems resulting from implementing computer applications one at a time. The authors describe the applications approach and the alternative Data Base Management System (DBMS) approach through their developmental history, discuss the technology of DBMS components, and consider the implications of choosing the DBMS alternative. Human service managers need an understanding of the DBMS alternative and its applicability to their agency data processing needs. The basis for a conscious selection of computing alternatives is outlined.
NON-REGULATED WATER CONTAMINANTS: EMERGING ...
Those chemical pollutants that are regulated under various international, federal, and state programs represent but a small fraction of the universe of chemicals that occur in the environment as a result of both natural processes and human influence. Although this galaxy of targeted chemicals might be minuscule compared with the universe of both known and yet-to-be identified chemicals, an implicit assumption is that these selective lists of chemicals are responsible for the most significant share of risk with respect to environmental or economic impairment or to human health. This paper examines some of the less discussed aspects of the background and assumptions that underlie society's
Bidirectional selection between two classes in complex social networks.
Zhou, Bin; He, Zhe; Jiang, Luo-Luo; Wang, Nian-Xin; Wang, Bing-Hong
2014-12-19
The bidirectional selection between two classes widely emerges in various social lives, such as commercial trading and mate choosing. Until now, the discussions on bidirectional selection in structured human society are quite limited. We demonstrated theoretically that the rate of successfully matching is affected greatly by individuals' neighborhoods in social networks, regardless of the type of networks. Furthermore, it is found that the high average degree of networks contributes to increasing rates of successful matches. The matching performance in different types of networks has been quantitatively investigated, revealing that the small-world networks reinforces the matching rate more than scale-free networks at given average degree. In addition, our analysis is consistent with the modeling result, which provides the theoretical understanding of underlying mechanisms of matching in complex networks.
Gai, Qingqing; Qu, Feng; Zhang, Tao; Zhang, Yukui
2011-07-15
Both of the magnetic particle adsorption and aqueous two-phase extraction (ATPE) were simple, fast and low-cost method for protein separation. Selective proteins adsorption by carboxyl modified magnetic particles was investigated according to protein isoelectric point, solution pH and ionic strength. Aqueous two-phase system of PEG/sulphate exhibited selective separation and extraction for proteins before and after magnetic adsorption. The two combination ways, magnetic adsorption followed by ATPE and ATPE followed by magnetic adsorption, for the separation of proteins mixture of lysozyme, bovine serum albumin, trypsin, cytochrome C and myloglobin were discussed and compared. The way of magnetic adsorption followed by ATPE was also applied to human serum separation. Copyright © 2011 Elsevier B.V. All rights reserved.
Genotype by environment interaction and breeding for robustness in livestock
Rauw, Wendy M.; Gomez-Raya, Luis
2015-01-01
The increasing size of the human population is projected to result in an increase in meat consumption. However, at the same time, the dominant position of meat as the center of meals is on the decline. Modern objections to the consumption of meat include public concerns with animal welfare in livestock production systems. Animal breeding practices have become part of the debate since it became recognized that animals in a population that have been selected for high production efficiency are more at risk for behavioral, physiological and immunological problems. As a solution, animal breeding practices need to include selection for robustness traits, which can be implemented through the use of reaction norms analysis, or though the direct inclusion of robustness traits in the breeding objective and in the selection index. This review gives an overview of genotype × environment interactions (the influence of the environment, reaction norms, phenotypic plasticity, canalization, and genetic homeostasis), reaction norms analysis in livestock production, options for selection for increased levels of production and against environmental sensitivity, and direct inclusion of robustness traits in the selection index. Ethical considerations of breeding for improved animal welfare are discussed. The discussion on animal breeding practices has been initiated and is very alive today. This positive trend is part of the sustainable food production movement that aims at feeding 9.15 billion people not just in the near future but also beyond. PMID:26539207
Obesity-related hypertension: is there a role for selective leptin resistance?
Correia, Marcelo L G; Haynes, William G
2004-06-01
Obesity is a risk factor for cardiovascular diseases, in particular for hypertension. Serum leptin levels and sympathetic nerve activity are both increased in obesity. Leptin has been demonstrated to increase sympathetic nerve activity. Thus, leptin-dependent sympathoactivation might contribute to obesity-related hypertension. However, leptin resistance occurs in obesity. One possibility is that leptin resistance is selective to the metabolic effects of leptin, sparing its sympathoexcitatory actions. In this article, we review experimental evidence supporting the novel concept of selective leptin resistance. We also discuss the sympathetic actions of leptin that are relevant to blood pressure modulation and potential mechanisms of leptin resistance. Disruption of leptin intracellular signaling pathways and resistance of specific leptin-responsive neural networks provide theoretic models of selective leptin resistance. However, most information about leptin-sympathetic actions and leptin-resistance mechanisms derive from in vitro and animal studies. Future research in humans is widely awaited.
NASA Astrophysics Data System (ADS)
Kluiving, Sjoerd; Hamel, Arthur
2016-04-01
This research is based on a review of published examples of geoarchaeological and landscape archaeological research throughout Europe. Through environmental reconstruction we relatively date the starting points where humans a) are altering their own selective environment as an inceptive change, b) respond to a (deteriorated) selective environment in a counteractive change. It is stated that geoarchaeology and landscape archaeology make a valuable contribution to NCT studies in considering landscape gradients as focal lines. NCT phase transitions from inceptive to counteractive changes are proposed as useful alternative in the debate about the onset of the Anthropocene. While searching for a relevant approach to define this period where humans are driving the Earth, we discuss the pitfalls of the dialectic Nature/Culture and social/environmental divides and finally we prefer to approach the issue from the complex system perspective which does not opposes 'humans' with 'the rest'. In complex systems, such as Earth system, linear cause consequence relations do not exist. Therefore the response of the system is not always related in time, space or proportions with the causes. On this basis, we present an alternative definition of the Anthropocene based on the causes of the changes instead of their effects. These causes are to be found in the change in human behaviour. The Niche Construction Theory conciliates the causes and the complex system approach previous remarks: that the effects are not easily correlated with the causes of changes. This is the point of view adopted by Zeder and Smith (2013) who argue that the onset of the Anthropocene is the start of Neolithic revolution, matching the lower boundary of the Holocene. Zeder M. A. and Smith B.D. (2013). The onset of the Anthropocene. Anthropocene, 4:8-13.
NASA Astrophysics Data System (ADS)
Alford, W. A.; Kawamura, Kazuhiko; Wilkes, Don M.
1997-12-01
This paper discusses the problem of integrating human intelligence and skills into an intelligent manufacturing system. Our center has jointed the Holonic Manufacturing Systems (HMS) Project, an international consortium dedicated to developing holonic systems technologies. One of our contributions to this effort is in Work Package 6: flexible human integration. This paper focuses on one activity, namely, human integration into motion guidance and coordination. Much research on intelligent systems focuses on creating totally autonomous agents. At the Center for Intelligent Systems (CIS), we design robots that interact directly with a human user. We focus on using the natural intelligence of the user to simplify the design of a robotic system. The problem is finding ways for the user to interact with the robot that are efficient and comfortable for the user. Manufacturing applications impose the additional constraint that the manufacturing process should not be disturbed; that is, frequent interacting with the user could degrade real-time performance. Our research in human-robot interaction is based on a concept called human directed local autonomy (HuDL). Under this paradigm, the intelligent agent selects and executes a behavior or skill, based upon directions from a human user. The user interacts with the robot via speech, gestures, or other media. Our control software is based on the intelligent machine architecture (IMA), an object-oriented architecture which facilitates cooperation and communication among intelligent agents. In this paper we describe our research testbed, a dual-arm humanoid robot and human user, and the use of this testbed for a human directed sorting task. We also discuss some proposed experiments for evaluating the integration of the human into the robot system. At the time of this writing, the experiments have not been completed.
Muthukaman, Nagarajan; Deshmukh, Sanjay; Tambe, Macchindra; Pisal, Dnyandeo; Tondlekar, Shital; Shaikh, Mahamadhanif; Sarode, Neelam; Kattige, Vidya G; Sawant, Pooja; Pisat, Monali; Karande, Vikas; Honnegowda, Srinivasa; Kulkarni, Abhay; Behera, Dayanidhi; Jadhav, Satyawan B; Sangana, Ramchandra R; Gudi, Girish S; Khairatkar-Joshi, Neelima; Gharat, Laxmikant A
2018-04-15
In an effort to identify CYP and hERG clean mPGES-1 inhibitors from the dihydrofuran-fused tricyclic benzo[d]imidazole series lead 7, an extensive structure-activity relationship (SAR) studies were performed. Optimization of A, D and E-rings in 7 afforded many potent compounds with human whole blood potency in the range of 160-950 nM. Selected inhibitors 21d, 21j, 21m, 21n, 21p and 22b provided selectivity against COX-enzymes and mPGES-1 isoforms (mPGES-2 and cPGES) along with sufficient selectivity against prostanoid synthases. Most of the tested analogs demonstrated required metabolic stability in liver microsomes, low hERG and CYP liability. Oral pharmacokinetics and bioavailability of lead compounds 21j, 21m and 21p are discussed in multiple species like rat, guinea pig, dog, and cynomolgus monkey. Besides, these compounds revealed low to moderate activity against human pregnane X receptor (hPXR). The selected lead 21j further demonstrated in vivo efficacy in acute hyperalgesia (ED 50 : 39.6 mg/kg) and MIA-induced osteoarthritic pain models (ED 50 : 106 mg/kg). Copyright © 2018 Elsevier Ltd. All rights reserved.
The importance of immune gene variability (MHC) in evolutionary ecology and conservation
Sommer, Simone
2005-01-01
Genetic studies have typically inferred the effects of human impact by documenting patterns of genetic differentiation and levels of genetic diversity among potentially isolated populations using selective neutral markers such as mitochondrial control region sequences, microsatellites or single nucleotide polymorphism (SNPs). However, evolutionary relevant and adaptive processes within and between populations can only be reflected by coding genes. In vertebrates, growing evidence suggests that genetic diversity is particularly important at the level of the major histocompatibility complex (MHC). MHC variants influence many important biological traits, including immune recognition, susceptibility to infectious and autoimmune diseases, individual odours, mating preferences, kin recognition, cooperation and pregnancy outcome. These diverse functions and characteristics place genes of the MHC among the best candidates for studies of mechanisms and significance of molecular adaptation in vertebrates. MHC variability is believed to be maintained by pathogen-driven selection, mediated either through heterozygote advantage or frequency-dependent selection. Up to now, most of our knowledge has derived from studies in humans or from model organisms under experimental, laboratory conditions. Empirical support for selective mechanisms in free-ranging animal populations in their natural environment is rare. In this review, I first introduce general information about the structure and function of MHC genes, as well as current hypotheses and concepts concerning the role of selection in the maintenance of MHC polymorphism. The evolutionary forces acting on the genetic diversity in coding and non-coding markers are compared. Then, I summarise empirical support for the functional importance of MHC variability in parasite resistance with emphasis on the evidence derived from free-ranging animal populations investigated in their natural habitat. Finally, I discuss the importance of adaptive genetic variability with respect to human impact and conservation, and implications for future studies. PMID:16242022
Can Nucleoli Be Markers of Developmental Potential in Human Zygotes?
Fulka, Helena; Kyogoku, Hirohisa; Zatsepina, Olga; Langerova, Alena; Fulka, Josef
2015-11-01
In 1999, Tesarik and Greco reported that they could predict the developmental potential of human zygotes from a single static evaluation of their pronuclei. This was based on the distribution and number of specific nuclear organelles - the nucleoli. Recent studies in mice show that nucleoli play a key role in parental genome restructuring after fertilization, and that interfering with this process may lead to developmental failure. These studies thus support the Tesarik-Greco evaluation as a potentially useful method for selecting high-quality embryos in human assisted reproductive technologies. In this opinion article we discuss recent evidence linking nucleoli to parental genome reprogramming, and ask whether nucleoli can mirror or be used as representative markers of embryonic parameters such as chromosome content or DNA fragmentation. Copyright © 2015 Elsevier Ltd. All rights reserved.
The function of dog models in developing gene therapy strategies for human health.
Nowend, Keri L; Starr-Moss, Alison N; Murphy, Keith E
2011-08-01
The domestic dog is of great benefit to humankind, not only through companionship and working activities cultivated through domestication and selective breeding, but also as a model for biomedical research. Many single-gene traits have been well-characterized at the genomic level, and recent advances in whole-genome association studies will allow for better understanding of complex, multigenic hereditary diseases. Additionally, the dog serves as an invaluable large animal model for assessment of novel therapeutic agents. Thus, the dog has filled a crucial step in the translation of basic research to new treatment regimens for various human diseases. Four well-characterized diseases in canine models are discussed as they relate to other animal model availability, novel therapeutic approach, and extrapolation to human gene therapy trials.
NASA Technical Reports Server (NTRS)
Williams, Richard S.
2015-01-01
The presentation is next Sunday, May 10th. It will be to the Civil Aviation Medical Association, for 2 hours at Disney World in Orlando. It is a high level talk on space medicine, including history, the role of my office, human health risks of space flight, general aspects of space medicine practice, human health risk management (including integrated activities of medical operations and the Human Research Program, and thoughts concerning health risks for long duration exploration class space missions. No proprietary data or material will be used, all is readily available in the public sector. There is also a short (30 min) talk on Monday at the CAMA lunch. There we will describe the Visual Impairment and Intracranial Pressure syndrome, with possible etiologies and plans for research (already selected studies). Again, nothing proprietary will be discussed.
Human body burdens of chemicals used in plastic manufacture
Koch, Holger M.; Calafat, Antonia M.
2009-01-01
In the last decades, the availability of sophisticated analytical chemistry techniques has facilitated measuring trace levels of multiple environmental chemicals in human biological matrices (i.e. biomonitoring) with a high degree of accuracy and precision. As biomonitoring data have become readily available, interest in their interpretation has increased. We present an overview on the use of biomonitoring in exposure and risk assessment using phthalates and bisphenol A as examples of chemicals used in the manufacture of plastic goods. We present and review the most relevant research on biomarkers of exposure for phthalates and bisphenol A, including novel and most comprehensive biomonitoring data from Germany and the United States. We discuss several factors relevant for interpreting and understanding biomonitoring data, including selection of both biomarkers of exposure and human matrices, and toxicokinetic information. PMID:19528056
The origins of language and the evolution of music: A comparative perspective
NASA Astrophysics Data System (ADS)
Masataka, Nobuo
2009-03-01
According to Darwin [Darwin, CR. The descent of man, and selection in relation to sex. London: John Murray; 1871], the human musical faculty ‘must be ranked amongst the most mysterious with which he is endowed’. Music is a human cultural universal that serves no obvious adaptive purpose, making its evolution a puzzle for evolutionary biologists. This review examines Darwin's hypothesis of similarities between language and music indicating a shared evolutionary history. In particular, the fact that both are human universals, have phrase structure, and entail learning and cultural transmission, suggests that any theory of the evolution of language will have implications for the evolution of music, and vice versa. The argument starts by describing variable predispositional musical capabilities and the ontogeny of prosodic communication in human infants and young children, presenting comparative data regarding communication systems commonly present in living nonhuman primate species. Like language, the human music faculty is based on a suite of abilities, some of which are shared with other primates and some of which appear to be uniquely human. Each of these subcomponents may have a different evolutionary history, and should be discussed separately. After briefly considering possible functions of human music for language acquisition, the review ends by discussing the phylogenetic history of music. It concludes that many strands of evidence support Darwin's hypothesis of an intermediate stage of human evolutionary history, characterized by a communication system that resembled music more closely than language, but was identical to neither. This pre-linguistic system, which could probably referred to as “prosodic protolanguage”, provided a precursor for both modern language and music.
Human Mars Landing Site and Impacts on Mars Surface Operations
NASA Technical Reports Server (NTRS)
Bussey, Ben; Hoffman, Stephen J.
2016-01-01
NASA has begun a process to identify and discuss candidate locations where humans could land, live and work on the Martian surface. These locations are referred to as Exploration Zones (EZs). Given current mission concepts, an EZ is a collection of Regions of Interest (ROIs) that are located within approximately 100 kilometers of a centralized landing site. ROIs are areas that are relevant for scientific investigation and/or development/maturation of capabilities and resources necessary for a sustainable human presence. The EZ also contains a landing site and a habitation site that will be used by multiple human crews during missions to explore and utilize the ROIs within the EZ. These candidate EZs will be used by NASA as part of a multi-year process of determining where and how humans could explore Mars. In the near term this process includes: (a) identifying locations that would maximize the potential science return from future human exploration missions, (b) identifying locations with the potential for resources required to support humans, (c) developing concepts and engineering systems needed by future human crews to conduct operations within an EZ, and (d) identifying key characteristics of the proposed candidate EZs that cannot be evaluated using existing data sets, thus helping to define precursor measurements needed in advance of human missions. Existing and future robotic spacecraft will be tasked to gather data from specific Mars surface sites within the representative EZs to support these NASA activities. The proposed paper will describe NASA's initial steps for identifying and evaluating candidate EZs and ROIs. This includes plans for the "First Landing Site/Exploration Zone Workshop for Human Missions to the Surface of Mars" to be held in October 2015 at which proposals for EZs and ROIs will be presented and discussed. It will also include a discussion of how these considerations are (or will be) taken into account as future robotic Mars missions are defined and developed. One or more representative EZs, drawn from similar previous studies involving Mars sites, will be used in the proposed paper to illustrate the process NASA envisions for gathering additional data from robotic precursor missions to assist in making a final selection of an EZ for human crews as well as the steps likely to occur during the buildup of a habitation site. Examples of the systems and operations likely to be used by human crews, assisted by robotic vehicles, to explore the scientific ROIs as well as developing the resource ROIs within the example EZs will be discussed.
Genetic selection for temperament traits in dairy and beef cattle.
Haskell, Marie J; Simm, Geoff; Turner, Simon P
2014-01-01
Animal temperament can be defined as a response to environmental or social stimuli. There are a number of temperament traits in cattle that contribute to their welfare, including their response to handling or milking, response to challenge such as human approach or intervention at calving, and response to conspecifics. In a number of these areas, the genetic basis of the trait has been studied. Heritabilities have been estimated and in some cases quantitative trait loci (QTL) have been identified. The variation is sometimes considerable and moderate heritabilities have been found for the major handling temperament traits, making them amenable to selection. Studies have also investigated the correlations between temperament and other traits, such as productivity and meat quality. Despite this, there are relatively few examples of temperament traits being used in selection programmes. Most often, animals are screened for aggression or excessive fear during handling or milking, with extreme animals being culled, or EBVs for temperament are estimated, but these traits are not commonly included routinely in selection indices, despite there being economic, welfare and human safety drivers for their. There may be a number of constraints and barriers. For some traits and breeds, there may be difficulties in collecting behavioral data on sufficiently large populations of animals to estimate genetic parameters. Most selection indices require estimates of economic values, and it is often difficult to assign an economic value to a temperament trait. The effects of selection primarily for productivity traits on temperament and welfare are discussed. Future opportunities include automated data collection methods and the wider use of genomic information in selection.
Genetic selection for temperament traits in dairy and beef cattle
Haskell, Marie J.; Simm, Geoff; Turner, Simon P.
2014-01-01
Animal temperament can be defined as a response to environmental or social stimuli. There are a number of temperament traits in cattle that contribute to their welfare, including their response to handling or milking, response to challenge such as human approach or intervention at calving, and response to conspecifics. In a number of these areas, the genetic basis of the trait has been studied. Heritabilities have been estimated and in some cases quantitative trait loci (QTL) have been identified. The variation is sometimes considerable and moderate heritabilities have been found for the major handling temperament traits, making them amenable to selection. Studies have also investigated the correlations between temperament and other traits, such as productivity and meat quality. Despite this, there are relatively few examples of temperament traits being used in selection programmes. Most often, animals are screened for aggression or excessive fear during handling or milking, with extreme animals being culled, or EBVs for temperament are estimated, but these traits are not commonly included routinely in selection indices, despite there being economic, welfare and human safety drivers for their. There may be a number of constraints and barriers. For some traits and breeds, there may be difficulties in collecting behavioral data on sufficiently large populations of animals to estimate genetic parameters. Most selection indices require estimates of economic values, and it is often difficult to assign an economic value to a temperament trait. The effects of selection primarily for productivity traits on temperament and welfare are discussed. Future opportunities include automated data collection methods and the wider use of genomic information in selection. PMID:25374582
Detection of Nanosilver Agents in Antibacterial Textiles
NASA Astrophysics Data System (ADS)
Xu, Chengtao; Zhao, Jie; Wu, Jianjian; Nie, Jinmei; Cui, Chengmin; Xie, Weibin; Zhang, Yan
2018-01-01
The analytical techniques are needed to detect the nanosilver in textiles in direct contact with skin. In this paper, in order to discuss the extraction of nanosilver on the surface of textiles by human skin, we demonstrate the capability of constant temperature oscillation extraction method followed by Inductively Coupled Plasma Spectroscopy (ICP). The sweat and deionized water were selected as extraction solvent simulating the contact process of human skin with textiles. The SEM and TEM analysis shows the existence of nanosilver in the fabric and aqueous extract. ICP analysis shows accurately when analysing silver amounts in the range of 0.05∼1.2 mg/L with r2 values of 0.9997. The percent recoveries of all fabrics were all lower than 44 %.The results shows that the developed method of simulating of human sweat extraction was not very effective. So the nanosilver might not be transferred to human body effectively from the fabric.
Evolutionary and ecological forces that shape the bacterial communities of the human gut
Messer, Jeannette S.; Liechty, Emma R; Vogel, Olivia A.; Chang, Eugene B.
2017-01-01
Since microbes were first described in the mid-1600's, we have come to appreciate that they live all around and within us with both beneficial and detrimental effects on nearly every aspect of our lives. The human gastrointestinal tract is inhabited by a dynamic community of trillions of bacteria that constantly interact with each other and their human host. The acquisition of these bacteria is not stochastic, but determined by circumstance (environment), host rules (genetics, immune state, mucus, etc), and dynamic self-selection among microbes to form stable, resilient communities that are in balance with the host. In this review, we will discuss how these factors lead to formation of the gut bacterial community and influence its interactions with the host. We will also address how gut bacteria contribute to disease and how they could potentially be targeted to prevent and treat a variety of human ailments. PMID:28145439
NASA Technical Reports Server (NTRS)
Barbee, Brent W.; Mink, Ronald G.; Adamo, Daniel R.; Alberding, Cassandra M.
2011-01-01
Near-Earth Asteroids (NEAs) have been identified by the Administration as potential destinations for human explorers during the mid-2020s. Planning such ambitious missions requires selecting potentially accessible targets from the growing known population of 8,008 NEAs. NASA is therefore conducting the Near-Earth Object (NEO) Human Space Flight (HSF) Accessible Targets Study (NHATS), in which the trajectory opportunities to all known NEAs are being systematically evaluated with respect to a set of defined constraints. While the NHATS algorithms have identified hundreds of NEAs which satisfy purposely inclusive trajectory constraints, only a handful of them offer truly attractive mission opportunities in the time frame of greatest interest. In this paper we will describe the structure of the NHATS algorithms and the constraints utilized in the study, present current study results, and discuss various mission design considerations for future human space flight missions to NEAs.
Potential International Approaches to Ownership/Control of Human Genetic Resources.
Rhodes, Catherine
2016-09-01
In its governance activities for genetic resources, the international community has adopted various approaches to their ownership, including: free access; common heritage of mankind; intellectual property rights; and state sovereign rights. They have also created systems which combine elements of these approaches. While governance of plant and animal genetic resources is well-established internationally, there has not yet been a clear approach selected for human genetic resources. Based on assessment of the goals which international governance of human genetic resources ought to serve, and the implications for how they will be accessed and utilised, it is argued that common heritage of mankind will be the most appropriate approach to adopt to their ownership/control. It does this with the aim of stimulating discussion in this area and providing a starting point for deeper consideration of how a common heritage of mankind, or similar, regime for human genetic resources would function and be implemented.
Incorporating placental tissue in cord blood banking for stem cell transplantation.
Teofili, Luciana; Silini, Antonietta R; Bianchi, Maria; Valentini, Caterina Giovanna; Parolini, Ornella
2018-06-01
Human term placenta is comprised of various tissues from which different cell populations can be obtained, including hematopoietic stem cells and mesenchymal stem/stromal cells (MSCs). Areas covered: This review will discuss the possibility to incorporate placental tissue cells in cord blood banking. It will discuss general features of human placenta, with a brief review of the immune cells at the fetal-maternal interface and the different cell populations isolated from placenta, with a particular focus on MSCs. It will address the question as to why placenta-derived MSCs should be banked with their hematopoietic counterparts. It will discuss clinical trials which are studying safety and efficacy of placenta tissue-derived MSCs in selected diseases, and preclinical studies which have proven their therapeutic properties in other diseases. It will discuss banking of umbilical cord blood and raise several issues for improvement, and the applications of cord blood cells in non-malignant disorders. Expert Commentary: Umbilical cord blood banking saves lives worldwide. The concomitant banking of non-hematopoietic cells from placenta, which could be applied therapeutically in the future, alone or in combination to their hematopoietic counterparts, could exploit current banking processes while laying the foundation for clinical trials exploring placenta-derived cell therapies in regenerative medicine.
Modification of visual function by early visual experience.
Blakemore, C
1976-07-01
Physiological experiments, involving recording from the visual cortex in young kittens and monkeys, have given new insight into human developmental disorders. In the visual cortex of normal cats and monkeys most neurones are selectively sensitive to the orientation of moving edges and they receive very similar signals from both eyes. Even in very young kittens without visual experience, most neurones are binocularly driven and a small proportion of them are genuinely orientation selective. There is no passive maturation of the system in the absence of visual experience, but even very brief exposure to patterned images produces rapid emergence of the adult organization. These results are compared to observations on humans who have "recovered" from early blindness. Covering one eye in a kitten or a monkey, during a sensitive period early in life, produces a virtually complete loss of input from that eye in the cortex. These results can be correlated with the production of "stimulus deprivation amblyopia" in infants who have had one eye patched. Induction of a strabismus causes a loss of binocularity in the visual cortex, and in humans it leads to a loss of stereoscopic vision and binocular fusion. Exposing kittens to lines of one orientation modifies the preferred orientations of cortical cells and there is an analogous "meridional amblyopia" in astigmatic humans. The existence of a sensitive period in human vision is discussed, as well as the possibility of designing remedial and preventive treatments for human developmental disorders.
Should the scope of human mixture risk assessment span legislative/regulatory silos for chemicals?
Evans, Richard M; Martin, Olwenn V; Faust, Michael; Kortenkamp, Andreas
2016-02-01
Current chemicals regulation operates almost exclusively on a chemical-by-chemical basis, however there is concern that this approach may not be sufficiently protective if two or more chemicals have the same toxic effect. Humans are indisputably exposed to more than one chemical at a time, for example to the multiple chemicals found in food, air and drinking water, and in household and consumer products, and in cosmetics. Assessment of cumulative risk to human health and/or the environment from multiple chemicals and routes can be done in a mixture risk assessment (MRA). Whilst there is a broad consensus on the basic science of mixture toxicology, the path to regulatory implementation of MRA within chemical risk assessment is less clear. In this discussion piece we pose an open question: should the scope of human MRA cross legislative remits or 'silos'? We define silos as, for instance, legislation that defines risk assessment practice for a subset of chemicals, usually on the basis of substance/product, media or process orientation. Currently any form of legal mandate for human MRA in the EU is limited to only a few pieces of legislation. We describe two lines of evidence, illustrated with selected examples, that are particularly pertinent to this question: 1) evidence that mixture effects have been shown for chemicals regulated in different silos and 2) evidence that humans are co-exposed to chemicals from different silos. We substantiate the position that, because there is no reason why chemicals allocated to specific regulatory silos would have non-overlapping risk profiles, then there is also no reason to expect that MRA limited only to chemicals within one silo can fully capture the risk that may be present to human consumers. Finally, we discuss possible options for implementation of MRA and we hope to prompt wider discussion of this issue. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
Rosen, Baruch; Tepper, Yotam; Bar-Oz, Guy
2018-01-01
Metric data of 6th century CE pigeons from the Negev Desert, Israel, are employed to test competing hypotheses on flock management strategies: that directed selection for size or shape took place under intensive management; or, alternatively, that stabilizing selection was a stronger determinant of size and shape under extensive management conditions. The results of the analysis support the second hypothesis by demonstrating that the Byzantine Negev pigeons were like wild pigeon (Columba livia) in shape, albeit small-sized. The inferred extensive management system is then discussed in the context of pigeon domestication and human micro-ecologies in marginal regions. PMID:29561880
Multiple Export Mechanisms for mRNAs
Delaleau, Mildred; Borden, Katherine L. B.
2015-01-01
Nuclear mRNA export plays an important role in gene expression. We describe the mechanisms of mRNA export including the importance of mRNP assembly, docking with the nuclear basket of the nuclear pore complex (NPC), transit through the central channel of the NPC and cytoplasmic release. We describe multiple mechanisms of mRNA export including NXF1 and CRM1 mediated pathways. Selective groups of mRNAs can be preferentially transported in order to respond to cellular stimuli. RNAs can be selected based on the presence of specific cis-acting RNA elements and binding of specific adaptor proteins. The role that dysregulation of this process plays in human disease is also discussed. PMID:26343730
Thermal infrared imaging in psychophysiology: Potentialities and limits
Ioannou, Stephanos; Gallese, Vittorio; Merla, Arcangelo
2014-01-01
Functional infrared thermal imaging (fITI) is considered an upcoming, promising methodology in the emotional arena. Driven by sympathetic nerves, observations of affective nature derive from muscular activity subcutaneous blood flow as well as perspiration patterns in specific body parts. A review of 23 experimental procedures that employed fITI for investigations of affective nature is provided, along with the adopted experimental protocol and the thermal changes that took place on selected regions of interest in human and nonhuman subjects. Discussion is provided regarding the selection of an appropriate baseline, the autonomic nature of the thermal print, the experimental setup, methodological issues, limitations, and considerations, as well as future directions. PMID:24961292
Attention-like processes in insects
2016-01-01
Attention is fundamentally important for sensory systems to focus on behaviourally relevant stimuli. It has therefore been an important field of study in human psychology and neuroscience. Primates, however, are not the only animals that might benefit from attention-like processes. Other animals, including insects, also have to use their senses and select one among many stimuli to forage, avoid predators and find mates. They have evolved different mechanisms to reduce the information processed by their brains to focus on only relevant stimuli. What are the mechanisms used by insects to selectively attend to visual and auditory stimuli? Do these attention-like mechanisms achieve the same functions as they do in primates? To investigate these questions, I use an established framework for investigating attention in non-human animals that proposes four fundamental components of attention: salience filters, competitive selection, top-down sensitivity control and working memory. I discuss evidence for each of these component processes in insects and compare the characteristics of these processes in insects to what we know from primates. Finally, I highlight important outstanding questions about insect attention that need to be addressed for us to understand the differences and similarities between vertebrate and insect attention. PMID:27852803
Attention-like processes in insects.
Nityananda, Vivek
2016-11-16
Attention is fundamentally important for sensory systems to focus on behaviourally relevant stimuli. It has therefore been an important field of study in human psychology and neuroscience. Primates, however, are not the only animals that might benefit from attention-like processes. Other animals, including insects, also have to use their senses and select one among many stimuli to forage, avoid predators and find mates. They have evolved different mechanisms to reduce the information processed by their brains to focus on only relevant stimuli. What are the mechanisms used by insects to selectively attend to visual and auditory stimuli? Do these attention-like mechanisms achieve the same functions as they do in primates? To investigate these questions, I use an established framework for investigating attention in non-human animals that proposes four fundamental components of attention: salience filters, competitive selection, top-down sensitivity control and working memory. I discuss evidence for each of these component processes in insects and compare the characteristics of these processes in insects to what we know from primates. Finally, I highlight important outstanding questions about insect attention that need to be addressed for us to understand the differences and similarities between vertebrate and insect attention. © 2016 The Author(s).
Akkina, Ramesh; Allam, Atef; Balazs, Alejandro B.; Blankson, Joel N.; Burnett, John C.; Casares, Sofia; Garcia, J. Victor; Hasenkrug, Kim J.; Kitchen, Scott G.; Klein, Florian; Kumar, Priti; Luster, Andrew D.; Poluektova, Larisa Y.; Rao, Mangala; Shultz, Leonard D.; Zack, Jerome A.
2016-01-01
Abstract The number of humanized mouse models for the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) and other infectious diseases has expanded rapidly over the past 8 years. Highly immunodeficient mouse strains, such as NOD/SCID/gamma chainnull (NSG, NOG), support better human hematopoietic cell engraftment. Another improvement is the derivation of highly immunodeficient mice, transgenic with human leukocyte antigens (HLAs) and cytokines that supported development of HLA-restricted human T cells and heightened human myeloid cell engraftment. Humanized mice are also used to study the HIV reservoir using new imaging techniques. Despite these advances, there are still limitations in HIV immune responses and deficits in lymphoid structures in these models in addition to xenogeneic graft-versus-host responses. To understand and disseminate the improvements and limitations of humanized mouse models to the scientific community, the NIH sponsored and convened a meeting on April 15, 2015 to discuss the state of knowledge concerning these questions and best practices for selecting a humanized mouse model for a particular scientific investigation. This report summarizes the findings of the NIH meeting. PMID:26670361
The effects of advertisement location and familiarity on selective attention.
Jessen, Tanja Lund; Rodway, Paul
2010-06-01
This study comprised two experiments to examine the distracting effects of advertisement familiarity, location, and onset on the performance of a selective attention task. In Exp. 1, familiar advertisements presented in peripheral vision disrupted selective attention when the attention task was more demanding, suggesting that the distracting effect of advertisements is a product of task demands and advertisement familiarity and location. In Exp. 2, the onset of the advertisement shortly before, or after, the attention task captured attention and disrupted attentional performance. The onset of the advertisement before the attention task reduced target response time without an increase in errors and therefore facilitated performance. Despite being instructed to ignore the advertisements, the participants were able to recall a substantial proportion of the familiar advertisements. Implications for the presentation of advertisements during human-computer interaction were discussed.
Toward a Systematic Approach for Selection of NASA Technology Portfolios
NASA Technical Reports Server (NTRS)
Weisbin, Charles R.; Rodriguez, Guillermo; Alberto, Elfes; Smith, Jeffrey H.
2004-01-01
There is an important need for a consistent analytical foundation supporting the selection and monitoring of R&D tasks that support new system concepts that enable future NASA missions. This capability should be applicable at various degrees of abstraction, depending upon whether one is interested in formulation, development, or operations. It should also be applicable to a single project, a program comprised of a group of projects, an enterprise typically including multiple programs, and the overall agency itself. Emphasis here is on technology selection and new initiatives, but the same approach can be generalized to other applications, dealing, for example, with new system architectures, risk reduction, and task allocation among humans and machines. The purpose of this paper is to describe one such approach, which is in its early stages of implementation within NASA programs, and to discuss several illustrative examples.
Challenges in measuring and valuing productivity costs, and their relevance in mood disorders
Lensberg, Benedikte R; Drummond, Michael F; Danchenko, Natalya; Despiégel, Nicolas; François, Clément
2013-01-01
Lost productivity is often excluded from economic evaluations, which may lead to an underestimation of the societal benefits of treatment. However, there are multiple challenges in reliably estimating and reporting productivity losses. This article explores the main challenges, ie, selecting an appropriate valuation method (ie, human capital, friction cost, or multiplier), avoiding double counting, and accounting for equity. It also discusses the use of presenteeism instruments and their application in clinical trials, with a specific focus on their relevance in individuals with mood disorders. Further research and discussion is required on the development of reliable techniques for measuring and valuing productivity changes due to presenteeism. PMID:24273412
Ebolavirus Evolution: Past and Present.
de La Vega, Marc-Antoine; Stein, Derek; Kobinger, Gary P
2015-01-01
The past year has marked the most devastating Ebola outbreak the world has ever witnessed, with over 28,000 cases and over 11,000 deaths. Ebola virus (EBOV) has now been around for almost 50 years. In this review, we discuss past and present outbreaks of EBOV and how those variants evolved over time. We explore and discuss selective pressures that drive the evolution of different Ebola variants, and how they may modify the efficacy of therapeutic treatments and vaccines currently being developed. Finally, given the unprecedented size and spread of the outbreak, as well as the extended period of replication in human hosts, specific attention is given to the 2014-2015 West African outbreak variant (Makona).
Ebolavirus Evolution: Past and Present
de La Vega, Marc-Antoine; Stein, Derek; Kobinger, Gary P
2015-01-01
The past year has marked the most devastating Ebola outbreak the world has ever witnessed, with over 28,000 cases and over 11,000 deaths. Ebola virus (EBOV) has now been around for almost 50 years. In this review, we discuss past and present outbreaks of EBOV and how those variants evolved over time. We explore and discuss selective pressures that drive the evolution of different Ebola variants, and how they may modify the efficacy of therapeutic treatments and vaccines currently being developed. Finally, given the unprecedented size and spread of the outbreak, as well as the extended period of replication in human hosts, specific attention is given to the 2014–2015 West African outbreak variant (Makona). PMID:26562671
Space Station crew safety alternatives study. Volume 2: Threat development
NASA Technical Reports Server (NTRS)
Raasch, R. F.; Peercy, R. L., Jr.; Rockoff, L. A.
1985-01-01
The first 15 years of accumulated space station concepts for initial operational capability (IOC) during the early 1990's were considered. Twenty-five threats to the space station are identified and selected threats addressed as impacting safety criteria, escape and rescue, and human factors safety concerns. Of the 25 threats identified, eight are discussed including strategy options for threat control: fire, biological or toxic contamination, injury/illness, explosion, loss of pressurization, radiation, meteoroid penetration, and debris.
Space station crew safety alternatives study, volume 1
NASA Technical Reports Server (NTRS)
Peercy, R. L., Jr.; Raasch, R. F.; Rockoff, L. A.
1985-01-01
The first 15 years of accumulated space station concepts for initial operational capability (IOC) during the early 1990's were considered. Twenty-five threats to the space station are identified and selected threats addressed as impacting safety criteria, escape and rescue, and human factors safety concerns. Of the 25 threats identified, eight are discussed including strategy options for threat control: fire, biological or toxic contamination, injury/illness, explosion, loss of pressurization, radiation, meteoroid penetration and debris.
Multifractal analysis of real and imaginary movements: EEG study
NASA Astrophysics Data System (ADS)
Pavlov, Alexey N.; Maksimenko, Vladimir A.; Runnova, Anastasiya E.; Khramova, Marina V.; Pisarchik, Alexander N.
2018-04-01
We study abilities of the wavelet-based multifractal analysis in recognition specific dynamics of electrical brain activity associated with real and imaginary movements. Based on the singularity spectra we analyze electroencephalograms (EEGs) acquired in untrained humans (operators) during imagination of hands movements, and show a possibility to distinguish between the related EEG patterns and the recordings performed during real movements or the background electrical brain activity. We discuss how such recognition depends on the selected brain region.
Encountering science education's capacity to affect and be affected
NASA Astrophysics Data System (ADS)
Alsop, Steve
2016-09-01
What might science education learn from the recent affective turn in the humanities and social sciences? Framed as a response to Michalinos Zembylas's article, this essay draws from selected theorizing in affect theory, science education and science and technology studies, in pursuit of diverse and productive ways to talk of affect within science education. These discussions are framed by desires to transcend traditional epistemic boundaries and practices. The article concludes offering some associated ambiguities and tensions involved.
Health concerns and hazardous waste
DOE Office of Scientific and Technical Information (OSTI.GOV)
Yassi, A.; Weeks, J.; Kraut, A.
1990-01-01
This report discusses health effects of hazardous waste and emphasizes human health concerns related to establishing a hazardous waste management facility. The study reviewed world epidemiological and public health literature to identify cases of suspected or substantiated claims of public health impacts associated with hazardous waste management facilities and potential products or emissions from such facilities, and placed them into perspective, including possible routes and consequences of exposure, risk assessment, and the toxicity of selected organic and inorganic compounds.
Some Impacts of Risk-Centric Certification Requirements for UAS
NASA Technical Reports Server (NTRS)
Neogi, Natasha A. (Inventor); Hayhurst, Kelly J.; Maddalon, Jeffrey M.; Verstynen, Harry A.
2016-01-01
This paper discusses results from a recent study that investigates certification requirements for an unmanned rotorcraft performing agricultural application operations. The process of determining appropriate requirements using a risk-centric approach revealed a number of challenges that could impact larger UAS standardization efforts. Fundamental challenges include selecting the correct level of abstraction for requirements to permit design flexibility, transforming human-centric operational requirements to aircraft airworthiness requirements, and assessing all hazards associated with the operation.
Groen, Iris I A; Silson, Edward H; Baker, Chris I
2017-02-19
Visual scene analysis in humans has been characterized by the presence of regions in extrastriate cortex that are selectively responsive to scenes compared with objects or faces. While these regions have often been interpreted as representing high-level properties of scenes (e.g. category), they also exhibit substantial sensitivity to low-level (e.g. spatial frequency) and mid-level (e.g. spatial layout) properties, and it is unclear how these disparate findings can be united in a single framework. In this opinion piece, we suggest that this problem can be resolved by questioning the utility of the classical low- to high-level framework of visual perception for scene processing, and discuss why low- and mid-level properties may be particularly diagnostic for the behavioural goals specific to scene perception as compared to object recognition. In particular, we highlight the contributions of low-level vision to scene representation by reviewing (i) retinotopic biases and receptive field properties of scene-selective regions and (ii) the temporal dynamics of scene perception that demonstrate overlap of low- and mid-level feature representations with those of scene category. We discuss the relevance of these findings for scene perception and suggest a more expansive framework for visual scene analysis.This article is part of the themed issue 'Auditory and visual scene analysis'. © 2017 The Author(s).
2017-01-01
Visual scene analysis in humans has been characterized by the presence of regions in extrastriate cortex that are selectively responsive to scenes compared with objects or faces. While these regions have often been interpreted as representing high-level properties of scenes (e.g. category), they also exhibit substantial sensitivity to low-level (e.g. spatial frequency) and mid-level (e.g. spatial layout) properties, and it is unclear how these disparate findings can be united in a single framework. In this opinion piece, we suggest that this problem can be resolved by questioning the utility of the classical low- to high-level framework of visual perception for scene processing, and discuss why low- and mid-level properties may be particularly diagnostic for the behavioural goals specific to scene perception as compared to object recognition. In particular, we highlight the contributions of low-level vision to scene representation by reviewing (i) retinotopic biases and receptive field properties of scene-selective regions and (ii) the temporal dynamics of scene perception that demonstrate overlap of low- and mid-level feature representations with those of scene category. We discuss the relevance of these findings for scene perception and suggest a more expansive framework for visual scene analysis. This article is part of the themed issue ‘Auditory and visual scene analysis’. PMID:28044013
NASA Technical Reports Server (NTRS)
Jeanneret, P. R.
1988-01-01
The development and use of a menu of performance tests that can be self-administered on a portable microcomputer are investigated. In order to identify, develop, or otherwise select the relevant human capabilities/attributes to measure and hence include in the performance battery, it is essential that an analysis be conducted of the jobs or functions that will be performed throughout a space shuttle mission. The primary job analysis instrument, the Position Analysis Questionnaire (PAQ), is discussed in detail so the reader will have sufficient background for understanding the application of the instrument to the various work activities included within the scope of the study, and the derivation of the human requirements (abilities/attributes) from the PAQ analyses. The research methodology is described and includes the procedures used for gathering the PAQ data. The results are presented in detail with specific emphasis on identifying critical requirements that can be measured with a portable computerized assessment battery. A discussion of the results is given with implications for future research.
Game, cloud architecture and outreach for The BIG Bell Test
NASA Astrophysics Data System (ADS)
Abellan, Carlos; Tura, Jordi; Garcia, Marta; Beduini, Federica; Hirschmann, Alina; Pruneri, Valerio; Acin, Antonio; Marti, Maria; Mitchell, Morgan
The BIG Bell test uses the input from the Bellsters, self-selected human participants introducing zeros and ones through an online videogame, to perform a suite of quantum physics experiments. In this talk, we will explore the videogame, the data infrastructure and the outreach efforts of the BIG Bell test collaboration. First, we will discuss how the game was designed so as to eliminate possible feedback mechanisms that could influence people's behavior. Second, we will discuss the cloud architecture design for scalability as well as explain how we sent each individual bit from the users to the labs. Also, and using all the bits collected via the BIG Bell test interface, we will show a data analysis on human randomness, e.g. are younger Bellsters more random than older Bellsters? Finally, we will talk about the outreach and communication efforts of the BIG Bell test collaboration, exploring both the social media campaigns as well as the close interaction with teachers and educators to bring the project into classrooms.
Photochemical oxidants: state of the science.
Kley, D; Kleinmann, M; Sanderman, H; Krupa, S
1999-01-01
Atmospheric photochemical processes resulting in the production of tropospheric ozone (O(3)) and other oxidants are described. The spatial and temporal variabilities in the occurrence of surface level oxidants and their relationships to air pollution meteorology are discussed. Models of photooxidant formation are reviewed in the context of control strategies and comparisons are provided of the air concentrations of O(3) at select geographic locations around the world. This overall oxidant (O(3)) climatology is coupled to human health and ecological effects. The discussion of the effects includes both acute and chronic responses, mechanisms of action, human epidemiological and plant population studies and briefly, efforts to establish cause-effect relationships through numerical modeling. A short synopsis is provided of the interactive effects of O(3) with other abiotic and biotic factors. The overall emphasis of the paper is on identifying the current uncertainties and gaps in our understanding of the state of the science and some suggestions as to how they may be addressed.
Evenly spaced Detrended Fluctuation Analysis: Selecting the number of points for the diffusion plot
NASA Astrophysics Data System (ADS)
Liddy, Joshua J.; Haddad, Jeffrey M.
2018-02-01
Detrended Fluctuation Analysis (DFA) has become a widely-used tool to examine the correlation structure of a time series and provided insights into neuromuscular health and disease states. As the popularity of utilizing DFA in the human behavioral sciences has grown, understanding its limitations and how to properly determine parameters is becoming increasingly important. DFA examines the correlation structure of variability in a time series by computing α, the slope of the log SD- log n diffusion plot. When using the traditional DFA algorithm, the timescales, n, are often selected as a set of integers between a minimum and maximum length based on the number of data points in the time series. This produces non-uniformly distributed values of n in logarithmic scale, which influences the estimation of α due to a disproportionate weighting of the long-timescale regions of the diffusion plot. Recently, the evenly spaced DFA and evenly spaced average DFA algorithms were introduced. Both algorithms compute α by selecting k points for the diffusion plot based on the minimum and maximum timescales of interest and improve the consistency of α estimates for simulated fractional Gaussian noise and fractional Brownian motion time series. Two issues that remain unaddressed are (1) how to select k and (2) whether the evenly-spaced DFA algorithms show similar benefits when assessing human behavioral data. We manipulated k and examined its effects on the accuracy, consistency, and confidence limits of α in simulated and experimental time series. We demonstrate that the accuracy and consistency of α are relatively unaffected by the selection of k. However, the confidence limits of α narrow as k increases, dramatically reducing measurement uncertainty for single trials. We provide guidelines for selecting k and discuss potential uses of the evenly spaced DFA algorithms when assessing human behavioral data.
Human and team performance in extreme environments: Antarctica
NASA Technical Reports Server (NTRS)
Stuster, J.
1998-01-01
Analogous experience is often instructive when attempting to understand human behavior in extreme environments. The current paper refers to the experiences of polar explorers and remote duty personnel to help identify the factors that influence individual and team performance when small groups are isolated and confined for long durations. The principal factors discussed include organizational structure, intracrew communications, interpersonal relations, leadership style, personnel selection, and training. Behavioral implications also are addressed for the design of procedures and equipment to facilitate sustained individual and group performance under conditions of isolation and confinement. To be consistent with the theme of the symposium, this paper emphasizes the crew requirements for an international expedition to Mars.
2009 Epigenetics Gordon Research Conference (August 9 - 14, 2009)
DOE Office of Scientific and Technical Information (OSTI.GOV)
Jeanie Lee
Epigenetics refers to the study of heritable changes in genome function that occur without a change in primary DNA sequence. The 2009 Gordon Conference in Epigenetics will feature discussion of various epigenetic phenomena, emerging understanding of their underlying mechanisms, and the growing appreciation that human, animal, and plant health all depend on proper epigenetic control. Special emphasis will be placed on genome-environment interactions particularly as they relate to human disease. Towards improving knowledge of molecular mechanisms, the conference will feature international leaders studying the roles of higher order chromatin structure, noncoding RNA, repeat elements, nuclear organization, and morphogenic evolution. Traditionalmore » and new model organisms are selected from plants, fungi, and metazoans.« less
Rusch, Hannes
2014-01-01
Drawing on an idea proposed by Darwin, it has recently been hypothesized that violent intergroup conflict might have played a substantial role in the evolution of human cooperativeness and altruism. The central notion of this argument, dubbed ‘parochial altruism’, is that the two genetic or cultural traits, aggressiveness against the out-groups and cooperativeness towards the in-group, including self-sacrificial altruistic behaviour, might have coevolved in humans. This review assesses the explanatory power of current theories of ‘parochial altruism’. After a brief synopsis of the existing literature, two pitfalls in the interpretation of the most widely used models are discussed: potential direct benefits and high relatedness between group members implicitly induced by assumptions about conflict structure and frequency. Then, a number of simplifying assumptions made in the construction of these models are pointed out which currently limit their explanatory power. Next, relevant empirical evidence from several disciplines which could guide future theoretical extensions is reviewed. Finally, selected alternative accounts of evolutionary links between intergroup conflict and intragroup cooperation are briefly discussed which could be integrated with parochial altruism in the future. PMID:25253457
Designer human tissue: coming to a lab near you.
Hay, David C; O'Farrelly, Cliona
2018-07-05
Human pluripotent stem cells (PSCs) offer a scalable alternative to primary and transformed human tissue. PSCs include human embryonic stem cells, derived from the inner cell mass of blastocysts unsuitable for human implantation; and induced PSCs, generated by the reprogramming of somatic cells. Both cell types display the ability to self-renew and retain pluripotency, promising an unlimited supply of human somatic cells for biomedical application. A distinct advantage of using PSCs is the ability to select for genetic background, promising personalized modelling of human biology 'in a dish' or immune-matched cell-based therapies for the clinic. This special issue will guide the reader through stem cell self-renewal, pluripotency and differentiation. The first articles focus on improving cell fidelity, understanding the innate immune system and the importance of materials chemistry, biofabrication and bioengineering. These are followed by articles that focus on industrial application, commercialization and label-free assessment of tissue formation. The special issue concludes with an article discussing human liver cell-based therapies past, present and future.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'. © 2018 The Authors.
Human Mars Mission Overview and Dust Storm Impacts on Site Selection
NASA Technical Reports Server (NTRS)
Hoffman, S. J.
2017-01-01
NASA has begun a process to identify and discuss candidate locations where humans could land, live and work on the martian surface. This process is being carried out as a cooperative effort by NASA's Human Exploration and Operations Mission Directorate (HEOMD), responsible for future human mission preparations, and the Science Mission Directorate (SMD), responsible for the on-going Mars Exploration Program of robotic vehicles in orbit and on the surface of Mars. Both of these Directorates have a significant interest in this process, as these candidate locations will be used by NASA as part of a multi-year effort to determine where and how humans could explore Mars. In the near term this process includes: (a) identifying locations that would maximize the potential science return from future human exploration missions, (b) identifying locations with the potential for resources required to support humans, (c) developing concepts and engineering systems needed by future human crews to conduct operations within a candidate location, and (d) identifying key characteristics of the proposed candidate locations that cannot be evaluated using existing data sets, thus helping to define precursor measurements needed in advance of human missions.
Investigation of human biomarkers in exhaled breath by laser photoacoustic spectroscopy
NASA Astrophysics Data System (ADS)
Dumitras, D. C.; Giubileo, G.; Puiu, A.
2005-06-01
The paper underlines the importance of breath tests in medicine and the potential of laser techniques to measure in-vivo and in real time human biomarkers. The presence of trace amounts of gases or the metabolites of a precursor in exhaled air could be linked to kidney or liver malfunction, asthma, diabetes, cancer, ulcers or neurological disorders. The measurement of some human biomarkers (ethylene, ammonia), based on laser photoacoustic spectroscopy methods, insure very high sensitivity and selectivity. The technical characteristics of this instrument were measured to determine the detection limits (sub-ppb for ethylene). The results of ethylene release following lipid peroxidation initiated by X-ray irradiation or ingestion of radioactive compounds are presented. The possibility to extend this technique for measurement of breath ammonia levels in patients with end-stage renal disease while they are undergoing hemodialysis is discussed.
NASA Technical Reports Server (NTRS)
1981-01-01
The impact of modern technology on the role, responsibility, authority, and performance of human operators in modern aircraft and ATC systems was examined in terms of principles defined by Paul Fitts. Research into human factors in aircraft operations and the use of human factors engineering for aircraft safety improvements were discussed, and features of the man-machine interface in computerized cockpit warning systems are examined. The design and operational features of computerized avionics displays and HUDs are described, along with results of investigations into pilot decision-making behavior, aircrew procedural compliance, and aircrew judgment training programs. Experiments in vision and visual perception are detailed, as are behavioral studies of crew workload, coordination, and complement. The effectiveness of pilot selection, screening, and training techniques are assessed, as are methods for evaluating pilot performance.
Petersson, K M; Nichols, T E; Poline, J B; Holmes, A P
1999-01-01
Functional neuroimaging (FNI) provides experimental access to the intact living brain making it possible to study higher cognitive functions in humans. In this review and in a companion paper in this issue, we discuss some common methods used to analyse FNI data. The emphasis in both papers is on assumptions and limitations of the methods reviewed. There are several methods available to analyse FNI data indicating that none is optimal for all purposes. In order to make optimal use of the methods available it is important to know the limits of applicability. For the interpretation of FNI results it is also important to take into account the assumptions, approximations and inherent limitations of the methods used. This paper gives a brief overview over some non-inferential descriptive methods and common statistical models used in FNI. Issues relating to the complex problem of model selection are discussed. In general, proper model selection is a necessary prerequisite for the validity of the subsequent statistical inference. The non-inferential section describes methods that, combined with inspection of parameter estimates and other simple measures, can aid in the process of model selection and verification of assumptions. The section on statistical models covers approaches to global normalization and some aspects of univariate, multivariate, and Bayesian models. Finally, approaches to functional connectivity and effective connectivity are discussed. In the companion paper we review issues related to signal detection and statistical inference. PMID:10466149
Schoen, Mary E; Xue, Xiaobo; Wood, Alison; Hawkins, Troy R; Garland, Jay; Ashbolt, Nicholas J
2017-02-01
We compared water and sanitation system options for a coastal community across selected sustainability metrics, including environmental impact (i.e., life cycle eutrophication potential, energy consumption, and global warming potential), equivalent annual cost, and local human health impact. We computed normalized metric scores, which we used to discuss the options' strengths and weaknesses, and conducted sensitivity analysis of the scores to changes in variable and uncertain input parameters. The alternative systems, which combined centralized drinking water with sanitation services based on the concepts of energy and nutrient recovery as well as on-site water reuse, had reduced environmental and local human health impacts and costs than the conventional, centralized option. Of the selected sustainability metrics, the greatest advantages of the alternative community water systems (compared to the conventional system) were in terms of local human health impact and eutrophication potential, despite large, outstanding uncertainties. Of the alternative options, the systems with on-site water reuse and energy recovery technologies had the least local human health impact; however, the cost of these options was highly variable and the energy consumption was comparable to on-site alternatives without water reuse or energy recovery, due to on-site reuse treatment. Future work should aim to reduce the uncertainty in the energy recovery process and explore the health risks associated with less costly, on-site water treatment options. Copyright © 2016 Elsevier Ltd. All rights reserved.
Quantitative studies of mRNA recruitment to the eukaryotic ribosome.
Fraser, Christopher S
2015-07-01
The process of peptide bond synthesis by ribosomes is conserved between species, but the initiation step differs greatly between the three kingdoms of life. This is illustrated by the evolution of roughly an order of magnitude more initiation factor mass found in humans compared with bacteria. Eukaryotic initiation of translation is comprised of a number of sub-steps: (i) recruitment of an mRNA and initiator methionyl-tRNA to the 40S ribosomal subunit; (ii) migration of the 40S subunit along the 5' UTR to locate the initiation codon; and (iii) recruitment of the 60S subunit to form the 80S initiation complex. Although the mechanism and regulation of initiation has been studied for decades, many aspects of the pathway remain unclear. In this review, I will focus discussion on what is known about the mechanism of mRNA selection and its recruitment to the 40S subunit. I will summarize how the 43S preinitiation complex (PIC) is formed and stabilized by interactions between its components. I will discuss what is known about the mechanism of mRNA selection by the eukaryotic initiation factor 4F (eIF4F) complex and how the selected mRNA is recruited to the 43S PIC. The regulation of this process by secondary structure located in the 5' UTR of an mRNA will also be discussed. Finally, I present a possible kinetic model with which to explain the process of mRNA selection and recruitment to the eukaryotic ribosome. Copyright © 2015 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.
Space Station crew safety alternatives study. Volume 4: Appendices
NASA Technical Reports Server (NTRS)
Peercy, R. L., Jr.; Raasch, R. F.; Rockoff, L. A.
1985-01-01
The scope of this study considered the first 15 years of accumulated space station concepts for Initial Operational Capability (10C) during the early 1990's. Twenty-five threats to the space station are identified and selected threats addressed as impacting safety criteria, escape and rescue, and human factors safety concerns. Of the 25 threats identified, eight are discussed including strategy options for threat control: fire, biological or toxic contamination, injury/illness, explosion, loss of pressurization, radiation, meteoroid penetration and debris.
Level 1 remedial investigation work plan, 300 Area Process Ponds
DOE Office of Scientific and Technical Information (OSTI.GOV)
Not Available
This report discusses the objectives of the site characterization for the 300 Area Process Ponds which are to identify and quantify contamination at the ponds and to estimate their potential impact on human health and the environment. The results of the site characterization will be used to identify any future actions related to contamination at the site and to identify any additional data requirements needed to support selection of a remedial action. 9 refs., 12 figs., 8 tabs.
2013-06-01
Much of Progress and Promise discusses and reviews the Pro - gram’s activities, accomplishments, and impacts. The DDR&E report also spurred activity...recommendations of that report (hereafter referred to as the SPG report), which pro - vided a vital impetus for the next six years of Department of Defense (DoD...selection to allow more time for planning. It draws on historical data about the players and their standard operating pro - cedures, commander’s preference
Adolescents' sexual media diets.
Brown, J D
2000-08-01
A model of how adolescents choose, interpret, and interact with the mass media is discussed in the context of sexual development. The Media Practice Model suggests that adolescents select and react to sexual media diets that speak to an emerging sense of themselves as sexual human beings. Relatively little is known about how the sexual content adolescents attend to in the media is interpreted or incorporated into their lives. Entertainment-education and media literacy are two strategies for increasing the possibility of healthy outcomes from adolescents' use of sexual media.
ERIC Educational Resources Information Center
Congress of the U.S., Washington, DC. House Committee on the Budget.
In observance of National Children's Day, this House of Representatives' joint hearing was concerned with children's health, education, and welfare issues. Its purpose was to discuss the first National Children's Day Report Card, which provides information about changes that need to be made in government spending and in the treatment of children…
Zion Golumbic, Elana M.; Poeppel, David; Schroeder, Charles E.
2012-01-01
The human capacity for processing speech is remarkable, especially given that information in speech unfolds over multiple time scales concurrently. Similarly notable is our ability to filter out of extraneous sounds and focus our attention on one conversation, epitomized by the ‘Cocktail Party’ effect. Yet, the neural mechanisms underlying on-line speech decoding and attentional stream selection are not well understood. We review findings from behavioral and neurophysiological investigations that underscore the importance of the temporal structure of speech for achieving these perceptual feats. We discuss the hypothesis that entrainment of ambient neuronal oscillations to speech’s temporal structure, across multiple time-scales, serves to facilitate its decoding and underlies the selection of an attended speech stream over other competing input. In this regard, speech decoding and attentional stream selection are examples of ‘active sensing’, emphasizing an interaction between proactive and predictive top-down modulation of neuronal dynamics and bottom-up sensory input. PMID:22285024
Searching for patterns in remote sensing image databases using neural networks
NASA Technical Reports Server (NTRS)
Paola, Justin D.; Schowengerdt, Robert A.
1995-01-01
We have investigated a method, based on a successful neural network multispectral image classification system, of searching for single patterns in remote sensing databases. While defining the pattern to search for and the feature to be used for that search (spectral, spatial, temporal, etc.) is challenging, a more difficult task is selecting competing patterns to train against the desired pattern. Schemes for competing pattern selection, including random selection and human interpreted selection, are discussed in the context of an example detection of dense urban areas in Landsat Thematic Mapper imagery. When applying the search to multiple images, a simple normalization method can alleviate the problem of inconsistent image calibration. Another potential problem, that of highly compressed data, was found to have a minimal effect on the ability to detect the desired pattern. The neural network algorithm has been implemented using the PVM (Parallel Virtual Machine) library and nearly-optimal speedups have been obtained that help alleviate the long process of searching through imagery.
Natural Selection in Large Populations
NASA Astrophysics Data System (ADS)
Desai, Michael
2011-03-01
I will discuss theoretical and experimental approaches to the evolutionary dynamics and population genetics of natural selection in large populations. In these populations, many mutations are often present simultaneously, and because recombination is limited, selection cannot act on them all independently. Rather, it can only affect whole combinations of mutations linked together on the same chromosome. Methods common in theoretical population genetics have been of limited utility in analyzing this coupling between the fates of different mutations. In the past few years it has become increasingly clear that this is a crucial gap in our understanding, as sequence data has begun to show that selection appears to act pervasively on many linked sites in a wide range of populations, including viruses, microbes, Drosophila, and humans. I will describe approaches that combine analytical tools drawn from statistical physics and dynamical systems with traditional methods in theoretical population genetics to address this problem, and describe how experiments in budding yeast can help us directly observe these evolutionary dynamics.
Why humans might help strangers
Raihani, Nichola J.; Bshary, Redouan
2015-01-01
Humans regularly help strangers, even when interactions are apparently unobserved and unlikely to be repeated. Such situations have been simulated in the laboratory using anonymous one-shot games (e.g., prisoner’s dilemma) where the payoff matrices used make helping biologically altruistic. As in real-life, participants often cooperate in the lab in these one-shot games with non-relatives, despite that fact that helping is under negative selection under these circumstances. Two broad explanations for such behavior prevail. The “big mistake” or “mismatch” theorists argue that behavior is constrained by psychological mechanisms that evolved predominantly in the context of repeated interactions with known individuals. In contrast, the cultural group selection theorists posit that humans have been selected to cooperate in anonymous one-shot interactions due to strong between-group competition, which creates interdependence among in-group members. We present these two hypotheses before discussing alternative routes by which humans could increase their direct fitness by cooperating with strangers under natural conditions. In doing so, we explain why the standard lab games do not capture real-life in various important aspects. First, asymmetries in the cost of perceptual errors regarding the context of the interaction (one-shot vs. repeated; anonymous vs. public) might have selected for strategies that minimize the chance of making costly behavioral errors. Second, helping strangers might be a successful strategy for identifying other cooperative individuals in the population, where partner choice can turn strangers into interaction partners. Third, in contrast to the assumptions of the prisoner’s dilemma model, it is possible that benefits of cooperation follow a non-linear function of investment. Non-linear benefits result in negative frequency dependence even in one-shot games. Finally, in many real-world situations individuals are able to parcel investments such that a one-shot interaction is turned into a repeated game of many decisions. PMID:25750619
Monzillo, Eloise; Gronowicz, Gloria
2011-01-01
Our purpose is to discuss the study design and innovative approaches that led to finding significant effects of one energy medicine therapy, Therapeutic Touch (TT), on cells. In the original published studies, TT was shown to significantly increase human osteoblast DNA synthesis, differentiation, and mineralization; increase in a dose-dependent manner the growth of other human cell types; and decrease the differentiation and mineralization of a human osteosarcoma-derived cell line. A unique feature of the study's methodology and design that contributed to the success of the findings was that a basic level of skill and maturity of the TT practitioner was quantified for producing observable and replicable outcomes in a test administered to all TT practitioners. Only those practitioners that passed the test were selected for the study. (2) The practitioners were required to keep a journal, which appeared to promote their ability to stay centered and replicate their treatments over months of cell experimentation. (3) The origin of the cells that the practitioners were treating was explained to them, although they were blinded to cell type during the experiments. (4) Only early passage cells were used to maintain a stable cell phenotype. (5) Standard protocols for performing TT in the room were followed to ensure reproducible conditions. (6) Placebo controls and untreated controls were used for each experiment. (7) The principal investigator and technicians performing the assays were blinded as to the experimental groups, and all assays and procedures were well established in the laboratory prior to the start of the TT experiments. The absence of studies on the human biofield from mainstream scientific literature is also discussed by describing the difficulties encountered in publishing. These roadblocks contribute to our lack of understanding of the human biofield and energy medicine modalities in science. In conclusion, this report seeks to encourage well-designed, evidence-based studies on the human biofield and the therapeutic potential of the human biofield. Copyright © 2011 Elsevier Inc. All rights reserved.
An OMIC biomarker detection algorithm TriVote and its application in methylomic biomarker detection.
Xu, Cheng; Liu, Jiamei; Yang, Weifeng; Shu, Yayun; Wei, Zhipeng; Zheng, Weiwei; Feng, Xin; Zhou, Fengfeng
2018-04-01
Transcriptomic and methylomic patterns represent two major OMIC data sources impacted by both inheritable genetic information and environmental factors, and have been widely used as disease diagnosis and prognosis biomarkers. Modern transcriptomic and methylomic profiling technologies detect the status of tens of thousands or even millions of probing residues in the human genome, and introduce a major computational challenge for the existing feature selection algorithms. This study proposes a three-step feature selection algorithm, TriVote, to detect a subset of transcriptomic or methylomic residues with highly accurate binary classification performance. TriVote outperforms both filter and wrapper feature selection algorithms with both higher classification accuracy and smaller feature number on 17 transcriptomes and two methylomes. Biological functions of the methylome biomarkers detected by TriVote were discussed for their disease associations. An easy-to-use Python package is also released to facilitate the further applications.
Sun, Zhifu; Cunningham, Julie; Slager, Susan; Kocher, Jean-Pierre
2015-01-01
Bisulfite treatment-based methylation microarray (mainly Illumina 450K Infinium array) and next-generation sequencing (reduced representation bisulfite sequencing, Agilent SureSelect Human Methyl-Seq, NimbleGen SeqCap Epi CpGiant or whole-genome bisulfite sequencing) are commonly used for base resolution DNA methylome research. Although multiple tools and methods have been developed and used for the data preprocessing and analysis, confusions remains for these platforms including how and whether the 450k array should be normalized; which platform should be used to better fit researchers’ needs; and which statistical models would be more appropriate for differential methylation analysis. This review presents the commonly used platforms and compares the pros and cons of each in methylome profiling. We then discuss approaches to study design, data normalization, bias correction and model selection for differentially methylated individual CpGs and regions. PMID:26366945
Eto, K; Yasutake, A; Kuwana, T; Korogi, Y; Akima, M; Shimozeki, T; Tokunaga, H; Kaneko, Y
2001-01-01
Neuropathological lesions found in chronic human Minamata disease tend to be localized in the calcarine cortex of occipital lobes, the pre- and postcentral lobuli, and the temporal gyri. The mechanism for the selective vulnerability is still not clear, though several hypotheses have been proposed. One hypothesis is vascular and postulates that the lesions are the result of ischemia secondary to compression of sulcal arteries from methylmercury-induced cerebral edema. To test this hypothesis, we studied common marmosets because the cerebrum of marmosets has 2 distinct deep sulci, the calcarine and Sylvian fissures. MRI analysis, mercury assays of tissue specimens, histologic and histochemical studies of the brain are reported and discussed. Brains sacrificed early after exposure to methylmercury showed high contents of methylmercury and edema of the cerebral white matter. These results may explain the selective cortical degeneration along the deep cerebral fissures or sulci.
Artificial Intelligence in Cardiology.
Johnson, Kipp W; Torres Soto, Jessica; Glicksberg, Benjamin S; Shameer, Khader; Miotto, Riccardo; Ali, Mohsin; Ashley, Euan; Dudley, Joel T
2018-06-12
Artificial intelligence and machine learning are poised to influence nearly every aspect of the human condition, and cardiology is not an exception to this trend. This paper provides a guide for clinicians on relevant aspects of artificial intelligence and machine learning, reviews selected applications of these methods in cardiology to date, and identifies how cardiovascular medicine could incorporate artificial intelligence in the future. In particular, the paper first reviews predictive modeling concepts relevant to cardiology such as feature selection and frequent pitfalls such as improper dichotomization. Second, it discusses common algorithms used in supervised learning and reviews selected applications in cardiology and related disciplines. Third, it describes the advent of deep learning and related methods collectively called unsupervised learning, provides contextual examples both in general medicine and in cardiovascular medicine, and then explains how these methods could be applied to enable precision cardiology and improve patient outcomes. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Mathias, Patricia I.; B’Hymer, Clayton
2016-01-01
This review describes recent selected HPLC/MS methods for the determination of urinary mercapturates that are useful as non-invasive biomarkers in characterizing human exposure to electrophilic industrial chemicals in occupational and environmental studies. High performance liquid chromatography/mass spectrometry is a sensitive and specific method for analysis of small molecules found in biological fluids. In this review, recent selected mercapturate quantification methods are summarized and specific cases are presented. The biological formation of mercapturates is introduced and their use indicators of metabolic processing of reactive toxicants is discussed, as well as future trends and limitations in this area of research. PMID:26900903
Horváth, Gergő; Bencsura, Ákos; Simon, Ágnes; Tochtrop, Gregory P; DeKoster, Gregory T; Covey, Douglas F; Cistola, David P; Toke, Orsolya
2016-02-01
Besides aiding digestion, bile salts are important signal molecules exhibiting a regulatory role in metabolic processes. Human ileal bile acid binding protein (I-BABP) is an intracellular carrier of bile salts in the epithelial cells of the distal small intestine and has a key role in the enterohepatic circulation of bile salts. Positive binding cooperativity combined with site selectivity of glycocholate and glycochenodeoxycholate, the two most abundant bile salts in the human body, make human I-BABP a unique member of the family of intracellular lipid binding proteins. Solution NMR structure of the ternary complex of human I-BABP with glycocholate and glycochenodeoxycholate reveals an extensive network of hydrogen bonds and hydrophobic interactions stabilizing the bound bile salts. Conformational changes accompanying bile salt binding affects four major regions in the protein including the C/D, E/F and G/H loops as well as the helical segment. Most of these protein regions coincide with a previously described network of millisecond time scale fluctuations in the apo protein, a motion absent in the bound state. Comparison of the heterotypic doubly ligated complex with the unligated form provides further evidence of a conformation selection mechanism of ligand entry. Structural and dynamic aspects of human I-BABP-bile salt interaction are discussed and compared with characteristics of ligand binding in other members of the intracellular lipid binding protein family. The coordinates of the 10 lowest energy structures of the human I-BABP : GCDA : GCA complex as well as the distance restraints used to calculate the final ensemble have been deposited in the Brookhaven Protein Data Bank with accession number 2MM3. © 2015 FEBS.
Contextual specificity in perception and action
NASA Technical Reports Server (NTRS)
Proffitt, Dennis R.
1991-01-01
The visually guided control of helicopter flight is a human achievement, and, thus, understanding this skill is, in part, a psychological problem. The abilities of skilled pilots are impressive, and yet it is of concern that pilots' performance is less than ideal: they suffer from workload constraints, make occasional errors, and are subject to such debilities as simulator sickness. Remedying such deficiencies is both an engineering and a psychological problem. When studying the psychological aspects of this problem, it is desirable to simplify the problem as much as possible, and thereby, sidestep as many intractable psychological issues as possible. Simply stated, we do not want to have to resolve such polemics as the mind-body problem in order to contribute to the design of more effective helicopter systems. On the other hand, the study of human behavior is a psychological endeavor and certain problems cannot be evaded. Four related issues that are of psychological significance in understanding the visually guided control of helicopter flight are discussed. First, a selected discussion of the nature of descriptive levels in analyzing human perception and performance is presented. It is argued that the appropriate level of description for perception is kinematical, and for performance, it is procedural. Second, it is argued that investigations into pilot performance cannot ignore the nature of pilots' phenomenal experience. The conscious control of actions is not based upon environmental states of affairs, nor upon the optical information that specifies them. Actions are coupled to perceptions. Third, the acquisition of skilled actions in the context of inherent misperceptions is discussed. Such skills may be error prone in some situations, but not in others. Finally, I discuss the contextual relativity of human errors. Each of these four issues relates to a common theme: the control of action is mediated by phenomenal experience, the veracity of which is context specific.
NASA Technical Reports Server (NTRS)
Winget, C. M.; Deroshia, C. W.; Markley, C. L.; Holley, D. C.
1984-01-01
This review discusses the effects, in the aerospace environment, of alterations in approximately 24-h periodicities (circadian rhythms) upon physiological and psychological functions and possible therapies for desynchronosis induced by such alterations. The consequences of circadian rhythm alteration resulting from shift work, transmeridian flight, or altered day lengths are known as desynchronosis, dysrhythmia, dyschrony, jet lag, or jet syndrome. Considerable attention is focused on the ability to operate jet aircraft and manned space vehicles. The importance of environmental cues, such as light-dark cycles, which influence physiological and psychological rhythms is discussed. A section on mathematical models is presented to enable selection and verification of appropriate preventive and corrective measures and to better understand the problem of dysrhythmia.
NASA Technical Reports Server (NTRS)
Grigor'ev, A. I. (Editor); Klein, K. E. (Editor); Nicogossian, A. (Editor)
1991-01-01
The present conference on findings from space life science investigations relevant to long-term earth orbit and planetary exploration missions, as well as considerations for future research projects on these issues, discusses the cardiovascular system and countermeasures against its deterioration in the microgravity environment, cerebral and sensorimotor functions, findings to date in endocrinology and immunology, the musculoskeletal system, and health maintenance and medical care. Also discussed are radiation hazards and protective systems, life-support and habitability factors, and such methodologies and equipment for long space mission research as the use of animal models, novel noninvasive techniques for space crew health monitoring, and an integrated international aerospace medical information system.
Space technology test facilities at the NASA Ames Research Center
NASA Technical Reports Server (NTRS)
Gross, Anthony R.; Rodrigues, Annette T.
1990-01-01
The major space research and technology test facilities at the NASA Ames Research Center are divided into five categories: General Purpose, Life Support, Computer-Based Simulation, High Energy, and the Space Exploraton Test Facilities. The paper discusses selected facilities within each of the five categories and discusses some of the major programs in which these facilities have been involved. Special attention is given to the 20-G Man-Rated Centrifuge, the Human Research Facility, the Plant Crop Growth Facility, the Numerical Aerodynamic Simulation Facility, the Arc-Jet Complex and Hypersonic Test Facility, the Infrared Detector and Cryogenic Test Facility, and the Mars Wind Tunnel. Each facility is described along with its objectives, test parameter ranges, and major current programs and applications.
Passive and active mechanical properties of biotemplated ceramics revisited.
Van Opdenbosch, Daniel; Fritz-Popovski, Gerhard; Plank, Johann; Zollfrank, Cordt; Paris, Oskar
2016-10-13
Living nature and human technology apply different principles to create hard, strong and tough materials. In this review, we compare and discuss prominent aspects of these alternative strategies, and demonstrate for selected examples that nanoscale-precision biotemplating is able to produce uncommon mechanical properties as well as actuating behavior, resembling to some extent the properties of the original natural templates. We present and discuss mechanical testing data showing for the first time that nanometer-precision biotemplating can lead to porous ceramic materials with deformation characteristics commonly associated with either biological or highly advanced technical materials. We also review recent findings on the relation between hierarchical structuring and humidity-induced directional motion. Finally, we discuss to which extent the observed behavior is in agreement with previous results and theories on the mechanical properties of multiscale hierarchical materials, as well as studies of highly disperse technical materials, together with an outlook for further lines of investigation.
Corona, Erik; Wang, Liuyang; Ko, Dennis; Patel, Chirag J
2018-01-01
Infectious disease has shaped the natural genetic diversity of humans throughout the world. A new approach to capture positive selection driven by pathogens would provide information regarding pathogen exposure in distinct human populations and the constantly evolving arms race between host and disease-causing agents. We created a human pathogen interaction database and used the integrated haplotype score (iHS) to detect recent positive selection in genes that interact with proteins from 26 different pathogens. We used the Human Genome Diversity Panel to identify specific populations harboring pathogen-interacting genes that have undergone positive selection. We found that human genes that interact with 9 pathogen species show evidence of recent positive selection. These pathogens are Yersenia pestis, human immunodeficiency virus (HIV) 1, Zaire ebolavirus, Francisella tularensis, dengue virus, human respiratory syncytial virus, measles virus, Rubella virus, and Bacillus anthracis. For HIV-1, GWAS demonstrate that some naturally selected variants in the host-pathogen protein interaction networks continue to have functional consequences for susceptibility to these pathogens. We show that selected human genes were enriched for HIV susceptibility variants (identified through GWAS), providing further support for the hypothesis that ancient humans were exposed to lentivirus pandemics. Human genes in the Italian, Miao, and Biaka Pygmy populations that interact with Y. pestis show significant signs of selection. These results reveal some of the genetic footprints created by pathogens in the human genome that may have left lasting marks on susceptibility to infectious disease.
The acute effects of cannabinoids on memory in humans: a review.
Ranganathan, Mohini; D'Souza, Deepak Cyril
2006-11-01
Cannabis is one of the most frequently used substances. Cannabis and its constituent cannabinoids are known to impair several aspects of cognitive function, with the most robust effects on short-term episodic and working memory in humans. A large body of the work in this area occurred in the 1970s before the discovery of cannabinoid receptors. Recent advances in the knowledge of cannabinoid receptors' function have rekindled interest in examining effects of exogenous cannabinoids on memory and in understanding the mechanism of these effects. The literature about the acute effects of cannabinoids on memory tasks in humans is reviewed. The limitations of the human literature including issues of dose, route of administration, small sample sizes, sample selection, effects of other drug use, tolerance and dependence to cannabinoids, and the timing and sensitivity of psychological tests are discussed. Finally, the human literature is discussed against the backdrop of preclinical findings. Acute administration of Delta-9-THC transiently impairs immediate and delayed free recall of information presented after, but not before, drug administration in a dose- and delay-dependent manner. In particular, cannabinoids increase intrusion errors. These effects are more robust with the inhaled and intravenous route and correspond to peak drug levels. This profile of effects suggests that cannabinoids impair all stages of memory including encoding, consolidation, and retrieval. Several mechanisms, including effects on long-term potentiation and long-term depression and the inhibition of neurotransmitter (GABA, glutamate, acetyl choline, dopamine) release, have been implicated in the amnestic effects of cannabinoids. Future research in humans is necessary to characterize the neuroanatomical and neurochemical basis of the memory impairing effects of cannabinoids, to dissect out their effects on the various stages of memory and to bridge the expanding gap between the humans and preclinical literature.
Physiological markers of motor inhibition during human behavior
Duque, Julie; Greenhouse, Ian; Labruna, Ludovica; Ivry, Richard B.
2017-01-01
Transcranial magnetic stimulation (TMS) studies in humans have shown that many behaviors engage processes that suppress excitability within the corticospinal tract. Inhibition of the motor output pathway has been extensively studied in the context of action stopping, where a planned movement needs to be abruptly aborted. Recent TMS work has also revealed markers of motor inhibition during the preparation of movement. Here, we review the evidence for motor inhibition during action stopping and action preparation, focusing on studies that have used TMS to monitor changes in the excitability of the corticospinal pathway. We discuss how these physiological results have motivated theoretical models of how the brain selects actions, regulates movement initiation and execution, and switches from one state to another. PMID:28341235
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.
NASA Technical Reports Server (NTRS)
Ghista, D. N.; Rasmussen, D. N.; Linebarger, R. N.; Sandler, H.
1971-01-01
Interdisciplinary engineering research effort in studying the intact human left ventricle has been employed to physiologically monitor the heart and to obtain its 'state-of-health' characteristics. The left ventricle was selected for this purpose because it plays a key role in supplying energy to the body cells. The techniques for measurement of the left ventricular geometry are described; the geometry is effectively displayed to bring out the abnormalities in cardiac function. Methods of mathematical modeling, which make it possible to determine the performance of the intact left ventricular muscle, are also described. Finally, features of a control system for the left ventricle for predicting the effect of certain physiological stress situations on the ventricle performance are discussed.
PROBING HUMAN AND MONKEY ANTERIOR CINGULATE CORTEX IN VARIABLE ENVIRONMENTS
Walton, Mark E.; Mars, Rogier B.
2008-01-01
Previous research has identified the anterior cingulate cortex (ACC) as an important node in the neural network underlying decision making in primates. Decision making can, however, be studied under large variety of circumstances, ranging from the standard well-controlled lab situation to more natural, stochastic settings during which multiple agents interact. Here, we illustrate how these different varieties of decision making studied can influence theories of ACC function in monkeys. Converging evidence from unit recordings and lesions studies now suggest that the ACC is important for interpreting outcome information according to the current task context to guide future action selection. We then apply this framework to the study of human ACC function and discuss its potential implications. PMID:18189014
Innate lymphoid cells in the initiation, regulation and resolution of inflammation
Sonnenberg, Gregory F.; Artis, David
2016-01-01
A previously unappreciated cell type of the innate immune system, termed innate lymphoid cells (ILCs), has been characterized in mice and humans, and found to profoundly influence the induction, regulation and resolution of inflammation. ILCs play an important role in these processes in murine models of infection, inflammatory disease and tissue repair. Further, disease association studies in defined patient populations have identified significant alterations in ILC responses, suggesting a potential role for these cell populations in human health and disease. In this review, we discuss the emerging family of ILCs, the role of ILCs in inflammation, and how current or novel therapeutic strategies could be employed to selectively modulate ILC responses and limit chronic inflammatory diseases in patients. PMID:26121198
Immunologic "vaccination" for the prevention of autoimmune diabetes (type 1A).
Simone, E A; Wegmann, D R; Eisenbarth, G S
1999-03-01
Diabetes type 1A is an autoimmune condition characterized by lymphocytic infiltration of islets and selective destruction of insulin-secreting beta-cells. Numerous investigators have prevented diabetes in animal models with a variety of antigens and routes of administration. It is also now possible to identify high-risk individuals even before the appearance of autoantibodies. These advances have created the opportunity to design and begin human prevention trials. This review focuses on a variety of immunomodulatory approaches (including administration of adjuvants, autoantigens, T-cells, T-cell receptors, and DNA) that we have collectively termed immunologic "vaccination." In addition, we discuss the potential benefits and dangers of these approaches and issues relating to the design of human trials.
NASA Astrophysics Data System (ADS)
Golikov, S. Yu; Petukhov, V. I.; Maiorov, I. S.
2017-11-01
The features of artificial landscapes’ spatial systems created for the optimization of industry facilities and settlements (as well as forest and agricultural crops taking into account the optimality of the existing microclimate and the possibilities for its improvement) are discussed in the paper. They improve the population health (through the optimization of the environment of settlements), the health of farm animals, the state of crops (through optimization of the climate), watercourses and forests reducing catastrophes on the shores and slopes by the proper selection and placement of species for artificial planting. They are achieved by revegetation, greening, garden and landscape design. In general, their purpose is to optimize the human environment.
Automation literature: A brief review and analysis
NASA Technical Reports Server (NTRS)
Smith, D.; Dieterly, D. L.
1980-01-01
Current thought and research positions which may allow for an improved capability to understand the impact of introducing automation to an existing system are established. The orientation was toward the type of studies which may provide some general insight into automation; specifically, the impact of automation in human performance and the resulting system performance. While an extensive number of articles were reviewed, only those that addressed the issue of automation and human performance were selected to be discussed. The literature is organized along two dimensions: time, Pre-1970, Post-1970; and type of approach, Engineering or Behavioral Science. The conclusions reached are not definitive, but do provide the initial stepping stones in an attempt to begin to bridge the concept of automation in a systematic progression.
Hrycay, E G; Bandiera, S M
2009-12-01
The present review focuses on the expression, function and regulation of mouse cytochrome P450 (Cyp) enzymes. Information compiled for mouse Cyp enzymes is compared with data collected for human CYP enzymes. To date, approximately 40 pairs of orthologous mouse-human CYP genes have been identified that encode enzymes performing similar metabolic functions. Recent knowledge concerning the tissue expression of mouse Cyp enzymes from families 1 to 51 is summarized. The catalytic activities of microsomal, mitochondrial and recombinant mouse Cyp enzymes are discussed and their involvement in the metabolism of exogenous and endogenous compounds is highlighted. The role of nuclear receptors, such as the aryl hydrocarbon receptor, constitutive androstane receptor and pregnane X receptor, in regulating the expression of mouse Cyp enzymes is examined. Targeted disruption of selected Cyp genes has generated numerous Cyp null mouse lines used to decipher the role of Cyp enzymes in metabolic, toxicological and biological processes. In conclusion, the laboratory mouse is an indispensable model for exploring human CYP-mediated activities.
How Genetically Engineered Mouse Tumor Models Provide Insights Into Human Cancers
Politi, Katerina; Pao, William
2011-01-01
Genetically engineered mouse models (GEMMs) of human cancer were first created nearly 30 years ago. These early transgenic models demonstrated that mouse cells could be transformed in vivo by expression of an oncogene. A new field emerged, dedicated to generating and using mouse models of human cancer to address a wide variety of questions in cancer biology. The aim of this review is to highlight the contributions of mouse models to the diagnosis and treatment of human cancers. Because of the breadth of the topic, we have selected representative examples of how GEMMs are clinically relevant rather than provided an exhaustive list of experiments. Today, as detailed here, sophisticated mouse models are being created to study many aspects of cancer biology, including but not limited to mechanisms of sensitivity and resistance to drug treatment, oncogene cooperation, early detection, and metastasis. Alternatives to GEMMs, such as chemically induced or spontaneous tumor models, are not discussed in this review. PMID:21263096
Scanpath-based analysis of objects conspicuity in context of human vision physiology.
Augustyniak, Piotr
2007-01-01
This paper discusses principal aspects of objects conspicuity investigated with use of an eye tracker and interpreted on the background of human vision physiology. Proper management of objects conspicuity is fundamental in several leading edge applications in the information society like advertisement, web design, man-machine interfacing and ergonomics. Although some common rules of human perception are applied since centuries in the art, the interest of human perception process is motivated today by the need of gather and maintain the recipient attention by putting selected messages in front of the others. Our research uses the visual tasks methodology and series of progressively modified natural images. The modifying details were attributed by their size, color and position while the scanpath-derived gaze points confirmed or not the act of perception. The statistical analysis yielded the probability of detail perception and correlations with the attributes. This probability conforms to the knowledge about the retina anatomy and perception physiology, although we use noninvasive methods only.
Precone, Vincenza; Del Monaco, Valentina; Esposito, Maria Valeria; De Palma, Fatima Domenica Elisa; Ruocco, Anna; D'Argenio, Valeria
2015-01-01
Next-generation sequencing (NGS) technologies have greatly impacted on every field of molecular research mainly because they reduce costs and increase throughput of DNA sequencing. These features, together with the technology's flexibility, have opened the way to a variety of applications including the study of the molecular basis of human diseases. Several analytical approaches have been developed to selectively enrich regions of interest from the whole genome in order to identify germinal and/or somatic sequence variants and to study DNA methylation. These approaches are now widely used in research, and they are already being used in routine molecular diagnostics. However, some issues are still controversial, namely, standardization of methods, data analysis and storage, and ethical aspects. Besides providing an overview of the NGS-based approaches most frequently used to study the molecular basis of human diseases at DNA level, we discuss the principal challenges and applications of NGS in the field of human genomics. PMID:26665001
Fernando, Ruani N; Chaudhari, Umesh; Escher, Sylvia E; Hengstler, Jan G; Hescheler, Jürgen; Jennings, Paul; Keun, Hector C; Kleinjans, Jos C S; Kolde, Raivo; Kollipara, Laxmikanth; Kopp-Schneider, Annette; Limonciel, Alice; Nemade, Harshal; Nguemo, Filomain; Peterson, Hedi; Prieto, Pilar; Rodrigues, Robim M; Sachinidis, Agapios; Schäfer, Christoph; Sickmann, Albert; Spitkovsky, Dimitry; Stöber, Regina; van Breda, Simone G J; van de Water, Bob; Vivier, Manon; Zahedi, René P; Vinken, Mathieu; Rogiers, Vera
2016-06-01
SEURAT-1 is a joint research initiative between the European Commission and Cosmetics Europe aiming to develop in vitro- and in silico-based methods to replace the in vivo repeated dose systemic toxicity test used for the assessment of human safety. As one of the building blocks of SEURAT-1, the DETECTIVE project focused on a key element on which in vitro toxicity testing relies: the development of robust and reliable, sensitive and specific in vitro biomarkers and surrogate endpoints that can be used for safety assessments of chronically acting toxicants, relevant for humans. The work conducted by the DETECTIVE consortium partners has established a screening pipeline of functional and "-omics" technologies, including high-content and high-throughput screening platforms, to develop and investigate human biomarkers for repeated dose toxicity in cellular in vitro models. Identification and statistical selection of highly predictive biomarkers in a pathway- and evidence-based approach constitute a major step in an integrated approach towards the replacement of animal testing in human safety assessment. To discuss the final outcomes and achievements of the consortium, a meeting was organized in Brussels. This meeting brought together data-producing and supporting consortium partners. The presentations focused on the current state of ongoing and concluding projects and the strategies employed to identify new relevant biomarkers of toxicity. The outcomes and deliverables, including the dissemination of results in data-rich "-omics" databases, were discussed as were the future perspectives of the work completed under the DETECTIVE project. Although some projects were still in progress and required continued data analysis, this report summarizes the presentations, discussions and the outcomes of the project.
Fernando, Ruani N.; Chaudhari, Umesh; Escher, Sylvia E.; Hengstler, Jan G.; Hescheler, Jürgen; Jennings, Paul; Keun, Hector C.; Kleinjans, Jos C. S.; Kolde, Raivo; Kollipara, Laxmikanth; Kopp-Schneider, Annette; Limonciel, Alice; Nemade, Harshal; Nguemo, Filomain; Peterson, Hedi; Prieto, Pilar; Rodrigues, Robim M.; Sachinidis, Agapios; Schäfer, Christoph; Sickmann, Albert; Spitkovsky, Dimitry; Stöber, Regina; van Breda, Simone G.J.; van de Water, Bob; Vivier, Manon; Zahedi, René P.
2017-01-01
SEURAT-1 is a joint research initiative between the European Commission and Cosmetics Europe aiming to develop in vitro and in silico based methods to replace the in vivo repeated dose systemic toxicity test used for the assessment of human safety. As one of the building blocks of SEURAT-1, the DETECTIVE project focused on a key element on which in vitro toxicity testing relies: the development of robust and reliable, sensitive and specific in vitro biomarkers and surrogate endpoints that can be used for safety assessments of chronically acting toxicants, relevant for humans. The work conducted by the DETECTIVE consortium partners has established a screening pipeline of functional and “-omics” technologies, including high-content and high-throughput screening platforms, to develop and investigate human biomarkers for repeated dose toxicity in cellular in vitro models. Identification and statistical selection of highly predictive biomarkers in a pathway- and evidence-based approach constitutes a major step in an integrated approach towards the replacement of animal testing in human safety assessment. To discuss the final outcomes and achievements of the consortium, a meeting was organized in Brussels. This meeting brought together data-producing and supporting consortium partners. The presentations focused on the current state of ongoing and concluding projects and the strategies employed to identify new relevant biomarkers of toxicity. The outcomes and deliverables, including the dissemination of results in data-rich “-omics” databases, were discussed as were the future perspectives of the work completed under the DETECTIVE project. Although some projects were still in progress and required continued data analysis, this report summarizes the presentations, discussions and the outcomes of the project. PMID:27129694
Talati, Jamsheer Jehangir
2016-05-01
Most surgeons are ethical. Increasingly, however, a variety of unprofessional behaviors are surfacing. Awareness of these behaviors and their causation is required to plan their eradication. To (i) identify the prevalent causes of unprofessional behaviors amongst surgeons; and (ii) suggest corrective interventions. Literature was searched and models constructed to interpret interrelationships between causes. Unprofessional behaviors extend beyond those frequently discussed, necessitating the term 'dysprofessionalism'. Causal influences arise from (i) an overpowering society; (ii) limited education and (iii) the underdeveloped state of human nature at birth. Societies corrupt by role-modeling avarice and encouraging industry-despite consequent pollution. Society brooks no interference. Surgeons are loath to oppose, resulting in an unprofessional silence. Surgical education based on best evidence is an indoctrination, with little opportunity to deploy alternatives. Evidence based guidelines increasingly risk errors, as publication fraud increases. Effective interaction with government/legislation is not taught. Human nature and our brain remain arrested in a stage of strongly stabilized evolutionary selection. Humans are born with larval brains requiring intense educational interventions. Genetic modification holds promise as it can circumvent birth in undeveloped states, and facilitate trans-generational transfer of knowledge. CRISPR/Cas-9 techniques make this possible, necessitating ethical discussion-an urgent issue. Reforming society would otherwise be an impossible task as behaviors cannot be taught in classrooms. Instances of dysprofessionalism are unlikely to diminish using current approaches. Discussion of the ethics of genetically modifying embryos is urgently needed, as this could provide a possible shortcut to positive changes in human behavior, but risks unwanted changes and misuse. Copyright © 2016 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.
Chemical Exchange Saturation Transfer (CEST): what is in a name and what isn’t?
van Zijl, Peter C.M.; Yadav, Nirbhay N.
2011-01-01
Chemical exchange saturation transfer (CEST) imaging is a relatively new MRI contrast approach in which exogenous or endogenous compounds containing either exchangeable protons or exchangeable molecules are selectively saturated and, after transfer of this saturation, detected indirectly through the water signal with enhanced sensitivity. The focus of this review is on basic MR principles underlying CEST and similarities to and differences with conventional magnetization transfer contrast (MTC). In CEST MRI, transfer of magnetization is studied in mobile compounds instead of semisolids. Similar to MTC, CEST has contributions of both chemical exchange and dipolar cross-relaxation, but the latter can often be neglected if exchange is fast. Contrary to MTC, CEST imaging requires sufficiently slow exchange on the MR time scale to allow selective irradiation of the protons of interest. As a consequence, magnetic labeling is not limited to radio-frequency saturation but can be expanded with slower frequency-selective approaches such as inversion, gradient dephasing and frequency labeling. The basic theory, design criteria, and experimental issues for exchange transfer imaging are discussed. A new classification for CEST agents based on exchange type is proposed. The potential of this young field is discussed, especially with respect to in vivo application and translation to humans. PMID:21337419
The eco-evolutionary impacts of domestication and agricultural practices on wild species.
Turcotte, Martin M; Araki, Hitoshi; Karp, Daniel S; Poveda, Katja; Whitehead, Susan R
2017-01-19
Agriculture is a dominant evolutionary force that drives the evolution of both domesticated and wild species. However, the various mechanisms of agriculture-induced evolution and their socio-ecological consequences are not often synthetically discussed. Here, we explore how agricultural practices and evolutionary changes in domesticated species cause evolution in wild species. We do so by examining three processes by which agriculture drives evolution. First, differences in the traits of domesticated species, compared with their wild ancestors, alter the selective environment and create opportunities for wild species to specialize. Second, selection caused by agricultural practices, including both those meant to maximize productivity and those meant to control pest species, can lead to pest adaptation. Third, agriculture can cause non-selective changes in patterns of gene flow in wild species. We review evidence for these processes and then discuss their ecological and sociological impacts. We finish by identifying important knowledge gaps and future directions related to the eco-evolutionary impacts of agriculture including their extent, how to prevent the detrimental evolution of wild species, and finally, how to use evolution to minimize the ecological impacts of agriculture.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Author(s).
The eco-evolutionary impacts of domestication and agricultural practices on wild species
Araki, Hitoshi; Karp, Daniel S.; Poveda, Katja
2017-01-01
Agriculture is a dominant evolutionary force that drives the evolution of both domesticated and wild species. However, the various mechanisms of agriculture-induced evolution and their socio-ecological consequences are not often synthetically discussed. Here, we explore how agricultural practices and evolutionary changes in domesticated species cause evolution in wild species. We do so by examining three processes by which agriculture drives evolution. First, differences in the traits of domesticated species, compared with their wild ancestors, alter the selective environment and create opportunities for wild species to specialize. Second, selection caused by agricultural practices, including both those meant to maximize productivity and those meant to control pest species, can lead to pest adaptation. Third, agriculture can cause non-selective changes in patterns of gene flow in wild species. We review evidence for these processes and then discuss their ecological and sociological impacts. We finish by identifying important knowledge gaps and future directions related to the eco-evolutionary impacts of agriculture including their extent, how to prevent the detrimental evolution of wild species, and finally, how to use evolution to minimize the ecological impacts of agriculture. This article is part of the themed issue ‘Human influences on evolution, and the ecological and societal consequences’. PMID:27920378
Chemical ecology of animal and human pathogen vectors in a changing global climate.
Pickett, John A; Birkett, Michael A; Dewhirst, Sarah Y; Logan, James G; Omolo, Maurice O; Torto, Baldwyn; Pelletier, Julien; Syed, Zainulabeuddin; Leal, Walter S
2010-01-01
Infectious diseases affecting livestock and human health that involve vector-borne pathogens are a global problem, unrestricted by borders or boundaries, which may be exacerbated by changing global climate. Thus, the availability of effective tools for control of pathogen vectors is of the utmost importance. The aim of this article is to review, selectively, current knowledge of the chemical ecology of pathogen vectors that affect livestock and human health in the developed and developing world, based on key note lectures presented in a symposium on "The Chemical Ecology of Disease Vectors" at the 25th Annual ISCE meeting in Neuchatel, Switzerland. The focus is on the deployment of semiochemicals for monitoring and control strategies, and discusses briefly future directions that such research should proceed along, bearing in mind the environmental challenges associated with climate change that we will face during the 21st century.
Exploring Effective Decision Making through Human-Centered and Computational Intelligence Methods
DOE Office of Scientific and Technical Information (OSTI.GOV)
Han, Kyungsik; Cook, Kristin A.; Shih, Patrick C.
Decision-making has long been studied to understand a psychological, cognitive, and social process of selecting an effective choice from alternative options. Its studies have been extended from a personal level to a group and collaborative level, and many computer-aided decision-making systems have been developed to help people make right decisions. There has been significant research growth in computational aspects of decision-making systems, yet comparatively little effort has existed in identifying and articulating user needs and requirements in assessing system outputs and the extent to which human judgments could be utilized for making accurate and reliable decisions. Our research focus ismore » decision-making through human-centered and computational intelligence methods in a collaborative environment, and the objectives of this position paper are to bring our research ideas to the workshop, and share and discuss ideas.« less
Chemical Probes for Visualizing Intact Animal and Human Brain Tissue.
Lai, Hei Ming; Ng, Wai-Lung; Gentleman, Steve M; Wu, Wutian
2017-06-22
Newly developed tissue clearing techniques can be used to render intact tissues transparent. When combined with fluorescent labeling technologies and optical sectioning microscopy, this allows visualization of fine structure in three dimensions. Gene-transfection techniques have proved very useful in visualizing cellular structures in animal models, but they are not applicable to human brain tissue. Here, we discuss the characteristics of an ideal chemical fluorescent probe for use in brain and other cleared tissues, and offer a comprehensive overview of currently available chemical probes. We describe their working principles and compare their performance with the goal of simplifying probe selection for neuropathologists and stimulating probe development by chemists. We propose several approaches for the development of innovative chemical labeling methods which, when combined with tissue clearing, have the potential to revolutionize how we study the structure and function of the human brain. Copyright © 2017 Elsevier Ltd. All rights reserved.
Interdisciplinary education approach to the human science
NASA Astrophysics Data System (ADS)
Szu, Harold; Zheng, Yufeng; Zhang, Nian
2012-06-01
We introduced human sciences as components, and integrated them together as an interdisciplinary endeavor over decades. This year, we built a website to maintain systematically the educational research service. We captured the human sciences in various components in the SPIE proceedings over the last decades, which included: (i) ears & eyes like adaptive wavelets, (ii) brain-like unsupervised learning independent component analysis (ICA); (iii) compressive sampling spatiotemporal sparse information processing, (iv) nanoengineering approach to sensing components, (v) systems biology measurements, and (vi) biomedical wellness applications. In order to serve the interdisciplinary community better, our system approach is based on that the former recipients invited the next recipients to deliver their review talks and panel discussions. Since only the former recipients of each component can lead the nomination committees and make the final selections, we also create a leadership award which may be nominated by any conference attendance, to be approved by the conference organization committee.
Safety and Clinical Usage of Newcastle Disease Virus in Cancer Therapy
Lam, Han Yuen; Yeap, Swee Keong; Rasoli, Mehdi; Omar, Abdul Rahman; Yusoff, Khatijah; Suraini, Abd Aziz; Banu Alitheen, Noorjahan
2011-01-01
Newcastle disease virus (NDV) is an avian virus that causes deadly infection to over 250 species of birds, including domestic and wild-type, thus resulting in substantial losses to the poultry industry worldwide. Many reports have demonstrated the oncolytic effect of NDV towards human tumor cells. The interesting aspect of NDV is its ability to selectively replicate in cancer cells. Some of the studies have undergone human clinical trials, and favorable results were obtained. Therefore, NDV strains can be the potential therapeutic agent in cancer therapy. However, investigation on the therapeutic perspectives of NDV, especially human immunological effects, is still ongoing. This paper provides an overview of the current studies on the cytotoxic and anticancer effect of NDV via direct oncolysis effects or immune stimulation. Safety of NDV strains applied for cancer immunotherapy is also discussed in this paper. PMID:22131816
Enhanced Oceanic Operations Human-In-The-Loop In-Trail Procedure Validation Simulation Study
NASA Technical Reports Server (NTRS)
Murdoch, Jennifer L.; Bussink, Frank J. L.; Chamberlain, James P.; Chartrand, Ryan C.; Palmer, Michael T.; Palmer, Susan O.
2008-01-01
The Enhanced Oceanic Operations Human-In-The-Loop In-Trail Procedure (ITP) Validation Simulation Study investigated the viability of an ITP designed to enable oceanic flight level changes that would not otherwise be possible. Twelve commercial airline pilots with current oceanic experience flew a series of simulated scenarios involving either standard or ITP flight level change maneuvers and provided subjective workload ratings, assessments of ITP validity and acceptability, and objective performance measures associated with the appropriate selection, request, and execution of ITP flight level change maneuvers. In the majority of scenarios, subject pilots correctly assessed the traffic situation, selected an appropriate response (i.e., either a standard flight level change request, an ITP request, or no request), and executed their selected flight level change procedure, if any, without error. Workload ratings for ITP maneuvers were acceptable and not substantially higher than for standard flight level change maneuvers, and, for the majority of scenarios and subject pilots, subjective acceptability ratings and comments for ITP were generally high and positive. Qualitatively, the ITP was found to be valid and acceptable. However, the error rates for ITP maneuvers were higher than for standard flight level changes, and these errors may have design implications for both the ITP and the study's prototype traffic display. These errors and their implications are discussed.
Pisani, Anthony R; Wyman, Peter A; Mohr, David C; Perrino, Tatiana; Gallo, Carlos; Villamar, Juan; Kendziora, Kimberly; Howe, George W; Sloboda, Zili; Brown, C Hendricks
2016-08-01
Internet-connected devices are changing the way people live, work, and relate to one another. For prevention scientists, technological advances create opportunities to promote the welfare of human subjects and society. The challenge is to obtain the benefits while minimizing risks. In this article, we use the guiding principles for ethical human subjects research and proposed changes to the Common Rule regulations, as a basis for discussing selected opportunities and challenges that new technologies present for prevention science. The benefits of conducting research with new populations, and at new levels of integration into participants' daily lives, are presented along with five challenges along with technological and other solutions to strengthen the protections that we provide: (1) achieving adequate informed consent with procedures that are acceptable to participants in a digital age; (2) balancing opportunities for rapid development and broad reach, with gaining adequate understanding of population needs; (3) integrating data collection and intervention into participants' lives while minimizing intrusiveness and fatigue; (4) setting appropriate expectations for responding to safety and suicide concerns; and (5) safeguarding newly available streams of sensitive data. Our goal is to promote collaboration between prevention scientists, institutional review boards, and community members to safely and ethically harness advancing technologies to strengthen impact of prevention science.
Mathias, Patricia I; B'Hymer, Clayton
2014-08-01
High-performance liquid chromatography/mass spectrometry (HPLC/MS) is sensitive and specific for targeted quantitative analysis and is readily utilized for small molecules from biological matrices. This brief review describes recent selected HPLC/MS methods for the determination of urinary mercapturic acids (mercapturates) which are useful as biomarkers in characterizing human exposure to electrophilic industrial chemicals in occupational and environmental studies. Electrophilic compounds owing to their reactivity are used in chemical and industrial processes. They are present in industrial emissions, are combustion products of fossil fuels, and are components in tobacco smoke. Their presence in both the industrial and general environments are of concern for human and environmental health. Urinary mercapturates which are the products of metabolic detoxification of reactive chemicals provide a non-invasive tool to investigate human exposure to electrophilic toxicants. Selected recent mercapturate quantification methods are summarized and specific cases are presented. The biological formation of mercapturates is introduced and their use as biomarkers of metabolic processing of electrophilic compounds is discussed. Also, the use of liquid chromatography/tandem mass spectrometry in simultaneous determinations of the mercapturates of multiple parent compounds in a single determination is considered, as well as future trends and limitations in this area of research. Published by Elsevier B.V.
Evolutionary consequences of human disturbance in a rainforest bird species from Central Africa.
Smith, Thomas B; Milá, Borja; Grether, Gregory F; Slabbekoorn, Hans; Sepil, Irem; Buermann, Wolfgang; Saatchi, Sassan; Pollinger, John P
2008-01-01
Relatively little attention has been directed towards understanding the impacts of human disturbance on evolutionary processes that produce and maintain biodiversity. Here, we examine the influence of anthropogenic habitat changes on traits typically associated with natural and sexual selection in the little greenbul (Andropadus virens), an African rainforest bird species. Using satellite remote-sensing and field survey data, we classified habitats into nonhuman-altered mature and human-altered secondary forest. Mature rainforest consisted of pristine rainforest, with little or no human influence, and secondary forest was characterized by plantations of coffee and cacao and high human impacts. Andropadus virens abundance was higher in secondary forest, and populations inhabiting mature rainforest were significantly larger in wing and tarsus length and bill size; characters often correlated with fitness. To assess the extent to which characters important in sexual section and mate choice might be influenced by habitat change, we also examined differences in plumage colour and song. Plumage colour and the variance in plumage luminance were found to differ between forest types, and song duration was found to be significantly longer in mature forest. The possible adaptive significance of these differences in traits is discussed. Despite relatively high levels of gene flow across habitats, amplified fragment length polymorphism analysis revealed that a small proportion of high-F(ST) loci differentiated mature from secondary forest populations. These loci were significant outliers against neutral expectations in a simulation analysis, suggesting a role for divergent selection in differentiation across habitats. A distance-based redundancy analysis further showed that forest type as defined by remote-sensing variables was significantly associated with genetic dissimilarities between habitats, even when controlling for distance. The observed shifts in morphology, plumage and song were consistent with divergent selection on heritable variation, but a role for plasticity cannot be ruled out. Results suggest that anthropogenic habitat changes may have evolutionary consequences, with implications for conservation and restoration.
Evolutionary Perspectives on Genetic and Environmental Risk Factors for Psychiatric Disorders.
Keller, Matthew C
2018-05-07
Evolutionary medicine uses evolutionary theory to help elucidate why humans are vulnerable to disease and disorders. I discuss two different types of evolutionary explanations that have been used to help understand human psychiatric disorders. First, a consistent finding is that psychiatric disorders are moderately to highly heritable, and many, such as schizophrenia, are also highly disabling and appear to decrease Darwinian fitness. Models used in evolutionary genetics to understand why genetic variation exists in fitness-related traits can be used to understand why risk alleles for psychiatric disorders persist in the population. The usual explanation for species-typical adaptations-natural selection-is less useful for understanding individual differences in genetic risk to disorders. Rather, two other types of models, mutation-selection-drift and balancing selection, offer frameworks for understanding why genetic variation in risk to psychiatric (and other) disorders exists, and each makes predictions that are now testable using whole-genome data. Second, species-typical capacities to mount reactions to negative events are likely to have been crafted by natural selection to minimize fitness loss. The pain reaction to tissue damage is almost certainly such an example, but it has been argued that the capacity to experience depressive symptoms such as sadness, anhedonia, crying, and fatigue in the face of adverse life situations may have been crafted by natural selection as well. I review the rationale and strength of evidence for this hypothesis. Evolutionary hypotheses of psychiatric disorders are important not only for offering explanations for why psychiatric disorders exist, but also for generating new, testable hypotheses and understanding how best to design studies and analyze data.
Recurrent DNA inversion rearrangements in the human genome
Flores, Margarita; Morales, Lucía; Gonzaga-Jauregui, Claudia; Domínguez-Vidaña, Rocío; Zepeda, Cinthya; Yañez, Omar; Gutiérrez, María; Lemus, Tzitziki; Valle, David; Avila, Ma. Carmen; Blanco, Daniel; Medina-Ruiz, Sofía; Meza, Karla; Ayala, Erandi; García, Delfino; Bustos, Patricia; González, Víctor; Girard, Lourdes; Tusie-Luna, Teresa; Dávila, Guillermo; Palacios, Rafael
2007-01-01
Several lines of evidence suggest that reiterated sequences in the human genome are targets for nonallelic homologous recombination (NAHR), which facilitates genomic rearrangements. We have used a PCR-based approach to identify breakpoint regions of rearranged structures in the human genome. In particular, we have identified intrachromosomal identical repeats that are located in reverse orientation, which may lead to chromosomal inversions. A bioinformatic workflow pathway to select appropriate regions for analysis was developed. Three such regions overlapping with known human genes, located on chromosomes 3, 15, and 19, were analyzed. The relative proportion of wild-type to rearranged structures was determined in DNA samples from blood obtained from different, unrelated individuals. The results obtained indicate that recurrent genomic rearrangements occur at relatively high frequency in somatic cells. Interestingly, the rearrangements studied were significantly more abundant in adults than in newborn individuals, suggesting that such DNA rearrangements might start to appear during embryogenesis or fetal life and continue to accumulate after birth. The relevance of our results in regard to human genomic variation is discussed. PMID:17389356
Martlé, Valentine; Van Ham, Luc; Raedt, Robrecht; Vonck, Kristl; Boon, Paul; Bhatti, Sofie
2014-03-01
Refractory epilepsy is a common disorder both in humans and dogs and treatment protocols are difficult to optimise. In humans, different non-pharmacological treatment modalities currently available include surgery, the ketogenic diet and neurostimulation. Surgery leads to freedom from seizures in 50-75% of patients, but requires strict patient selection. The ketogenic diet is indicated in severe childhood epilepsies, but efficacy is limited and long-term compliance can be problematic. In the past decade, various types of neurostimulation have emerged as promising treatment modalities for humans with refractory epilepsy. Currently, none of these treatment options are used in routine daily clinical practice to treat dogs with the condition. Since many dogs with poorly controlled seizures do not survive, the search for alternative treatment options for canine refractory epilepsy should be prioritised. This review provides an overview of non-pharmacological treatment options for human refractory epilepsy. The current knowledge and limitations of these treatments in canine refractory epilepsy is also discussed. Copyright © 2013 Elsevier Ltd. All rights reserved.
Sparrow, Robert
2014-11-01
A series of recent scientific results suggest that, in the not-too-distant future, it will be possible to create viable human gametes from human stem cells. This paper discusses the potential of this technology to make possible what I call 'in vitro eugenics': the deliberate breeding of human beings in vitro by fusing sperm and egg derived from different stem-cell lines to create an embryo and then deriving new gametes from stem cells derived from that embryo. Repeated iterations of this process would allow scientists to proceed through multiple human generations in the laboratory. In vitro eugenics might be used to study the heredity of genetic disorders and to produce cell lines of a desired character for medical applications. More controversially, it might also function as a powerful technology of 'human enhancement' by allowing researchers to use all the techniques of selective breeding to produce individuals with a desired genotype. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Cinema in the training of psychiatry residents: focus on helping relationships
2013-01-01
Background Medical schools are currently charged with a lack of education as far as empathic/relational skills and the meaning of being a health-care provider are concerned, thus leading to increased interest in medical humanities. Discussion Medical humanities can offer an insight into human illness and in a broader outlook into human condition, understanding of one self, responsibility. An empathic relation to patients might be fostered by a matching approach to humanities and sciences, which should be considered as subjects of equal relevance, complementary to one another. Recently, movies have been used in medical – especially psychiatric - trainees education, but mainly within the limits of teaching a variety of disorders. A different approach dealing with the use of cinema in the training of psychiatry residents is proposed, based on Jung and Hillman’s considerations about the relation between images and archetypes, archetypal experience and learning. Summary Selected full-length movies or clips can offer a priceless opportunity to face with the meaning of being involved in a care-providing, helping profession. PMID:23800186
Transcranial Magnetic Stimulation: Decomposing the Processes Underlying Action Preparation.
Bestmann, Sven; Duque, Julie
2016-08-01
Preparing actions requires the operation of several cognitive control processes that influence the state of the motor system to ensure that the appropriate behavior is ultimately selected and executed. For example, some form of competition resolution ensures that the right action is chosen among alternatives, often in the presence of conflict; at the same time, impulse control ought to be deployed to prevent premature responses. Here we review how state-changes in the human motor system during action preparation can be studied through motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation over the contralateral primary motor cortex (M1). We discuss how the physiological fingerprints afforded by MEPs have helped to decompose some of the dynamic and effector-specific influences on the motor system during action preparation. We focus on competition resolution, conflict and impulse control, as well as on the influence of higher cognitive decision-related variables. The selected examples demonstrate the usefulness of MEPs as physiological readouts for decomposing the influence of distinct, but often overlapping, control processes on the human motor system during action preparation. © The Author(s) 2015.
NASA Astrophysics Data System (ADS)
Andoni, Heri; Wonorahardjo, Surjamanto
2018-05-01
Urban Heat Island (UHI) has many harm impacts to urban and human life, the examples are increased building and energy consumption, increased air pollutants emissions, compromised human comfort and health, and many more. Despite UHI phenomenon and those impacts has been realized long enough by the experts along with development of major cities in the world, but its mitigation technology has not been well developed. This paper discusses few mitigation technologies for UHI phenomenon that have been developed by experts. Some mitigation technologies such as double skin façade, shading strategies, and many more are discussed in this study, include the strengths and the weaknesses of each strategy. The focus of the study is mainly on the potential of building skin engineering in which thermal conductivity, infrared emissivity, and specific heat factors. The selected case discussed are buildings made of heavy weight materials. The result in this study reveals a potential map where thermal insulation is one potential strategy to reduce the intensity of UHI through the reduction of heat emissions of heavy building materials components. By this study, improvement of the urban life in its relation to UHI are expected to occur, especially in housing and settlements area.
Rusch, Hannes
2014-11-07
Drawing on an idea proposed by Darwin, it has recently been hypothesized that violent intergroup conflict might have played a substantial role in the evolution of human cooperativeness and altruism. The central notion of this argument, dubbed 'parochial altruism', is that the two genetic or cultural traits, aggressiveness against the out-groups and cooperativeness towards the in-group, including self-sacrificial altruistic behaviour, might have coevolved in humans. This review assesses the explanatory power of current theories of 'parochial altruism'. After a brief synopsis of the existing literature, two pitfalls in the interpretation of the most widely used models are discussed: potential direct benefits and high relatedness between group members implicitly induced by assumptions about conflict structure and frequency. Then, a number of simplifying assumptions made in the construction of these models are pointed out which currently limit their explanatory power. Next, relevant empirical evidence from several disciplines which could guide future theoretical extensions is reviewed. Finally, selected alternative accounts of evolutionary links between intergroup conflict and intragroup cooperation are briefly discussed which could be integrated with parochial altruism in the future. © 2014 The Author(s) Published by the Royal Society. All rights reserved.
Love, David C.; Davis, Meghan F.; Bassett, Anna; Gunther, Andrew; Nachman, Keeve E.
2011-01-01
Background Industrial food animal production employs many of the same antibiotics or classes of antibiotics that are used in human medicine. These drugs can be administered to food animals in the form of free-choice medicated feeds (FCMF), where animals choose how much feed to consume. Routine administration of these drugs to livestock selects for microorganisms that are resistant to medications critical to the treatment of clinical infections in humans. Objectives In this commentary, we discuss the history of medicated feeds, the nature of FCMF use with regard to dose delivery, and U.S. policies that address antimicrobial drug use in food animals. Discussion FCMF makes delivering a predictable, accurate, and intended dose difficult. Overdosing can lead to animal toxicity; underdosing or inconsistent dosing can result in a failure to resolve animal diseases and in the development of antimicrobial-resistant microorganisms. Conclusions The delivery of antibiotics to food animals for reasons other than the treatment of clinically diagnosed disease, especially via free-choice feeding methods, should be reconsidered. PMID:21030337
A candid conversation about men, sexual health, and diabetes.
Jack, Leonard
2005-01-01
While the profound relationship between human sexuality and diabetes can affect quality of life for both men and women, male sexual health issues in the published literature have primarily focused on physical aspects of erectile dysfunction. The purpose of this article is to move this important discussion regarding aspects of human sexuality and diabetes further to consider the absence of and need for more male-focused research. Attention is given to define and discuss how male perceptions of control and masculinity shape male views on male sex roles. The author offers 4 published explanations to explain factors that influence whether men, regardless of age, nationality, or ethnic group, initiate help-seeking behaviors for sexual health concerns. These explanations can help health care professionals have candid, consistent, and nonjudgmental conversations with their patients and each other. This article concludes with strong recommendations that health care providers engage patients in timely conversations, jointly select and implement tailored treatment options, and, when necessary, link patients with social support systems to maximize improvements in both physical and psychological aspects of sexual health.
Tripolar mitosis in human cells and embryos: occurrence, pathophysiology and medical implications.
Kalatova, Beata; Jesenska, Renata; Hlinka, Daniel; Dudas, Marek
2015-01-01
Tripolar mitosis is a specific case of cell division driven by typical molecular mechanisms of mitosis, but resulting in three daughter cells instead of the usual count of two. Other variants of multipolar mitosis show even more mitotic poles and are relatively rare. In nature, this phenomenon was frequently observed or suspected in multiple common cancers, infected cells, the placenta, and in early human embryos with impaired pregnancy-yielding potential. Artificial causes include radiation and various toxins. Here we combine several pieces of the most recent evidence for the existence of different types of multipolar mitosis in preimplantation embryos together with a detailed review of the literature. The related molecular and cellular mechanisms are discussed, including the regulation of centriole duplication, mitotic spindle biology, centromere functions, cell cycle checkpoints, mitotic autocorrection mechanisms, and the related complicating factors in healthy and affected cells, including post-mitotic cell-cell fusion often associated with multipolar cell division. Clinical relevance for oncology and embryo selection in assisted reproduction is also briefly discussed in this context. Copyright © 2014 Elsevier GmbH. All rights reserved.
Neuronal adaptation, novelty detection and regularity encoding in audition
Malmierca, Manuel S.; Sanchez-Vives, Maria V.; Escera, Carles; Bendixen, Alexandra
2014-01-01
The ability to detect unexpected stimuli in the acoustic environment and determine their behavioral relevance to plan an appropriate reaction is critical for survival. This perspective article brings together several viewpoints and discusses current advances in understanding the mechanisms the auditory system implements to extract relevant information from incoming inputs and to identify unexpected events. This extraordinary sensitivity relies on the capacity to codify acoustic regularities, and is based on encoding properties that are present as early as the auditory midbrain. We review state-of-the-art studies on the processing of stimulus changes using non-invasive methods to record the summed electrical potentials in humans, and those that examine single-neuron responses in animal models. Human data will be based on mismatch negativity (MMN) and enhanced middle latency responses (MLR). Animal data will be based on the activity of single neurons at the cortical and subcortical levels, relating selective responses to novel stimuli to the MMN and to stimulus-specific neural adaptation (SSA). Theoretical models of the neural mechanisms that could create SSA and novelty responses will also be discussed. PMID:25009474
Kurosawa, Gene; Kondo, Mariko; Kurosawa, Yoshikazu
2016-11-04
When the technology for constructing human antibody (Ab) libraries using a phage-display system was developed, many researchers in Ab-related fields anticipated that it would be widely applied to the development of pharmaceutical drugs against various diseases, including cancers. However, successful examples of such applications are very limited. Moreover, researchers who utilize phage-display technology now show divergent ways of thinking about phage Ab libraries. For example, there is debate about what should be the source of V H and V L genes for the construction of libraries to cover the whole repertoire of Abs present in the human body. In the immune system, the introduction of mutations into V genes followed by selection based on binding activity, termed Ab maturation, is required for the production of Abs exhibiting high affinity to the antigen (Ag). Therefore, introduction of mutations and selection are required for isolation of Abs with high affinity after isolation of clones from phage Ab libraries. We constructed a large human Ab library termed AIMS, developed a screening method termed ICOS, and succeeded in isolating many human monoclonal Abs (mAbs) that specifically and strongly bind to various tumor-associated Ags. Eight anti-EGFR mAbs were included, which we characterized. These mAbs showed various different activities against EGFR-expressing cancer cells. In this paper, we describe these data and discuss the possibility and necessity that the mAbs isolated from the AIMS library might be developed as therapeutic drugs against cancers without introduction of mutations. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
Project Explorer - Student experiments aboard the Space Shuttle
NASA Technical Reports Server (NTRS)
Buckbee, E.; Dannenberg, K.; Driggers, G.; Orillion, A.
1979-01-01
Project Explorer, a program of high school student experiments in space in a Space Shuttle self-contained payload unit (Getaway Special), sponsored by the Alabama Space and Rocket Center (ASRC) in cooperation with four Alabama universities is presented. Organizations aspects of the project, which is intended to promote public awareness of the space program and encourage space research, are considered, and the proposal selection procedure is outlined. The projects selected for inclusion in the self-contained payload canister purchased in 1977 and expected to be flown on an early shuttle mission include experiments on alloy solidification, electric plating, whisker growth, chick embryo development and human blood freezing, and an amateur radio experiment. Integration support activities planned and underway are summarized, and possible uses for a second payload canister purchased by ASRC are discussed.
Age and motives for volunteering: testing hypotheses derived from socioemotional selectivity theory.
Okun, Morris A; Schultz, Amy
2003-06-01
Following a meta-analysis of the relations between age and volunteer motives (career, understanding, enhancement, protective, making friends, social, and values), the authors tested hypotheses derived from socioemotional selectivity theory regarding the effects of age on these volunteer motives. The Volunteer Functions Inventory was completed by 523 volunteers from 2 affiliates of the International Habitat for Humanity. Multiple regression analyses revealed, as predicted, that as age increases, career and understanding volunteer motivation decrease and social volunteer motivation increases. Contrary to expectations, age did not contribute to the prediction of enhancement, protective, and values volunteer motivations and the relation between age and making friends volunteer motivation was nonlinear. The results were discussed in the context of age-differential and age-similarity perspectives on volunteer motivation.
Interventions to Slow Aging in Humans: Are We Ready?
Longo, Valter D; Antebi, Adam; Bartke, Andrzej; Barzilai, Nir; Brown-Borg, Holly M; Caruso, Calogero; Curiel, Tyler J; de Cabo, Rafael; Franceschi, Claudio; Gems, David; Ingram, Donald K; Johnson, Thomas E; Kennedy, Brian K; Kenyon, Cynthia; Klein, Samuel; Kopchick, John J; Lepperdinger, Guenter; Madeo, Frank; Mirisola, Mario G; Mitchell, James R; Passarino, Giuseppe; Rudolph, Karl L; Sedivy, John M; Shadel, Gerald S; Sinclair, David A; Spindler, Stephen R; Suh, Yousin; Vijg, Jan; Vinciguerra, Manlio; Fontana, Luigi
2015-01-01
The workshop entitled ‘Interventions to Slow Aging in Humans: Are We Ready?’ was held in Erice, Italy, on October 8–13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR–S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting. PMID:25902704
Merchant, Hugo; Honing, Henkjan
2013-01-01
We propose a decomposition of the neurocognitive mechanisms that might underlie interval-based timing and rhythmic entrainment. Next to reviewing the concepts central to the definition of rhythmic entrainment, we discuss recent studies that suggest rhythmic entrainment to be specific to humans and a selected group of bird species, but, surprisingly, is not obvious in non-human primates. On the basis of these studies we propose the gradual audiomotor evolution hypothesis that suggests that humans fully share interval-based timing with other primates, but only partially share the ability of rhythmic entrainment (or beat-based timing). This hypothesis accommodates the fact that non-human primates (i.e., macaques) performance is comparable to humans in single interval tasks (such as interval reproduction, categorization, and interception), but show differences in multiple interval tasks (such as rhythmic entrainment, synchronization, and continuation). Furthermore, it is in line with the observation that macaques can, apparently, synchronize in the visual domain, but show less sensitivity in the auditory domain. And finally, while macaques are sensitive to interval-based timing and rhythmic grouping, the absence of a strong coupling between the auditory and motor system of non-human primates might be the reason why macaques cannot rhythmically entrain in the way humans do.
NASA Astrophysics Data System (ADS)
Dey, Pankaj; Mishra, Ashok
2017-05-01
Climate change and human activity are two major drivers that alter hydrological cycle processes and cause change in spatio-temporal distribution of water availability. Streamflow, the most important component of hydrological cycle undergoes variation which is expected to be influenced by climate change as well as human activities. Since these two affecting conditions are time dependent, having unequal influence, identification of the change point in natural flow regime is of utmost important to separate the individual impact of climate change and human activities on streamflow variability. Subsequently, it is important as well for framing adaptation strategies and policies for regional water resources planning and management. In this paper, a comprehensive review of different approaches used by research community to isolate the impacts of climate change and human activities on streamflow are presented. The important issues pertaining to different approaches, to make rational use of methodology, are discussed so that researcher and policymaker can understand the importance of individual methodology and its use in water resources management. A new approach has also been suggested to select a representative change point under different scenarios of human activities with incorporation of climate variability/change.
Natural pedagogy as evolutionary adaptation.
Csibra, Gergely; Gergely, György
2011-04-12
We propose that the cognitive mechanisms that enable the transmission of cultural knowledge by communication between individuals constitute a system of 'natural pedagogy' in humans, and represent an evolutionary adaptation along the hominin lineage. We discuss three kinds of arguments that support this hypothesis. First, natural pedagogy is likely to be human-specific: while social learning and communication are both widespread in non-human animals, we know of no example of social learning by communication in any other species apart from humans. Second, natural pedagogy is universal: despite the huge variability in child-rearing practices, all human cultures rely on communication to transmit to novices a variety of different types of cultural knowledge, including information about artefact kinds, conventional behaviours, arbitrary referential symbols, cognitively opaque skills and know-how embedded in means-end actions. Third, the data available on early hominin technological culture are more compatible with the assumption that natural pedagogy was an independently selected adaptive cognitive system than considering it as a by-product of some other human-specific adaptation, such as language. By providing a qualitatively new type of social learning mechanism, natural pedagogy is not only the product but also one of the sources of the rich cultural heritage of our species.
Natural pedagogy as evolutionary adaptation
Csibra, Gergely; Gergely, György
2011-01-01
We propose that the cognitive mechanisms that enable the transmission of cultural knowledge by communication between individuals constitute a system of ‘natural pedagogy’ in humans, and represent an evolutionary adaptation along the hominin lineage. We discuss three kinds of arguments that support this hypothesis. First, natural pedagogy is likely to be human-specific: while social learning and communication are both widespread in non-human animals, we know of no example of social learning by communication in any other species apart from humans. Second, natural pedagogy is universal: despite the huge variability in child-rearing practices, all human cultures rely on communication to transmit to novices a variety of different types of cultural knowledge, including information about artefact kinds, conventional behaviours, arbitrary referential symbols, cognitively opaque skills and know-how embedded in means-end actions. Third, the data available on early hominin technological culture are more compatible with the assumption that natural pedagogy was an independently selected adaptive cognitive system than considering it as a by-product of some other human-specific adaptation, such as language. By providing a qualitatively new type of social learning mechanism, natural pedagogy is not only the product but also one of the sources of the rich cultural heritage of our species. PMID:21357237
Persson, Johanna
2017-01-01
This article reviews literature about simulation systems for training in healthcare regarding the prevalence of human-centered approaches in the design and development of these systems, motivated by a tradition in this field of working technology-centered. The results show that the focus on human needs and context of use is limited. It is argued that a reduction of the focus on technical advancements in favor of the needs of the users and the healthcare community, underpinned by human factors and ergonomics theory, is favorable. Due to the low number of identified articles describing or discussing human-centered approaches it is furthermore concluded that the publication culture promotes technical descriptions and summative evaluations rather than descriptions and reflections regarding the design and development processes. Shifting the focus from a technology-centered approach to a human-centered one can aid in the process of creating simulation systems for training in healthcare that are: 1) relevant to the learning objectives, 2) adapted to the needs of users, context and task, and 3) not selected based on technical or fidelity criteria. Copyright © 2016 Elsevier Ltd. All rights reserved.
Acceptability of risk from radiation: Application to human space flight
DOE Office of Scientific and Technical Information (OSTI.GOV)
NONE
This one of NASA`s sponsored activities of the NCRP. In 1983, NASA asked NCRP to examine radiation risks in space and to make recommendations about career radiation limits for astronauts (with cancer considered as the principal risk). In conjunction with that effort, NCRP was asked to convene this symposium; objective is to examine the technical, strategic, and philosophical issues pertaining to acceptable risk and radiation in space. Nine papers are included together with panel discussions and a summary. Selected papers are indexed separately for inclusion in the Energy Science and Technology Database.
An infrared illuminator for a healing bed
NASA Astrophysics Data System (ADS)
Acharekar, Madhu A.; Crowley, Edward
2011-05-01
Bio-stimulation by a light is called the Light Therapy (LT) and an Infrared Illuminator (IRI) provides the human sleeping in a Healing Bed (HB) continuously a dose of the IR radiation. General specifications for the IRI given below and its data are discussed in the paper. (1) Use of 60" wide by 80" long queen size bed. (2) A LED providing 1.5 mw at 1550 nm is selected. (3) 60 LED are mounted in series and parallel on a chip and this chip is mounted on top of the HB.
The Genetics of Canine Skull Shape Variation
Schoenebeck, Jeffrey J.; Ostrander, Elaine A.
2013-01-01
A dog’s craniofacial diversity is the result of continual human intervention in natural selection, a process that began tens of thousands of years ago. To date, we know little of the genetic underpinnings and developmental mechanisms that make dog skulls so morphologically plastic. In this Perspectives, we discuss the origins of dog skull shapes in terms of history and biology and highlight recent advances in understanding the genetics of canine skull shapes. Of particular interest are those molecular genetic changes that are associated with the development of distinct breeds. PMID:23396475
A view on sphingolipids and disease.
Kolter, Thomas
2011-09-01
Sphingolipid and glycosphingolipid levels and expression of sphingolipid metabolizing enzymes are altered in a variety of diseases or in response to drug treatment. Inherited defects of enzymes and other proteins required for the lysosomal degradation of these lipids lead to human sphingolipidoses. Also genetic defects that affect sphingolipid biosynthesis are known. Although the molecular details are often far from clear, (glyco)sphingolipids have been implicated to play a role in atherosclerosis, insulin resistance, cancer, and infections by pathogens. More general aspects of selected diseases are discussed. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
Imaging empathy and prosocial emotions.
Lamm, Claus; Rütgen, Markus; Wagner, Isabella C
2017-06-29
Empathy is a multi-faceted construct with important implications for social behavior. Based on a selective review of the neuroscientific evidence collected in humans, the present paper discusses the neural representations underlying affect sharing, its relation to mentalizing, the importance of self-other distinction, the distinction between empathy, sympathy and compassion, and how these phenomena are linked to prosocial behavior. Apart from reviewing the literature, we also highlight open questions and how they might be addressed by a research approach that tries to integrate across these diverse constructs. Copyright © 2017 Elsevier B.V. All rights reserved.
Błaszkowska, Joanna; Wójcik, Anna
2012-01-01
Current issues concerning Parasitology and Mycology with regard to diseases of the skin and its appendages are presented. Aspects of diagnostics, clinical picture and therapy of skin and nail mycoses, as well as difficulties in the diagnosis and treatment of both native parasitoses (toxoplasmosis) and imported human tropical parasitoses (malaria, filariosis) have been emphasised. The clinical importance of environmental mould fungi in nosocomial infections and fungal meningitis, as well as selected properties of fungi isolated from patients with head and neck neoplasms treated by radiotherapy are discussed. Other mycological topics include the characteristics of newly-synthesized thiosemicarbazides and thiadiazoles as potential drugs against toxoplasmosis and their biological activity against Toxoplasma gondii tachyzoites, selected molecular mechanisms of resistance to azoles, Candida albicans strains and a new tool (barcoding DNA) for describing the biodiversity of potential allergenic molds. The importance of environmental factors in pathogenesis of mycoses and parasitoses is noted. The characteristics of pathogenic fungi isolated from natural ponds in Bialystok and potentially pathogenic yeast-like fungi isolated from children's recreation areas in Lodz are presented. The ongoing problem of anthropozoonoses is considered, as are the roles of stray cats and dogs in contaminating soil with the developing forms of intestinal parasites. The characteristics of the human microbiome, including population composition, activity and their importance in normal human physiology, are presented, as are the major goals of the Human Microbiome Project initiated by National Institutes of Health (NIH).
Exploring Assessment Tools for Research and Evaluation in Astronomy Education and Outreach
NASA Astrophysics Data System (ADS)
Buxner, S. R.; Wenger, M. C.; Dokter, E. F. C.
2011-09-01
The ability to effectively measure knowledge, attitudes, and skills in formal and informal educational settings is an important aspect of astronomy education research and evaluation. Assessments may take the form of interviews, observations, surveys, exams, or other probes to help unpack people's understandings or beliefs. In this workshop, we discussed characteristics of a variety of tools that exist to assess understandings of different concepts in astronomy as well as attitudes towards science and science teaching; these include concept inventories, surveys, interview protocols, observation protocols, card sorting, reflection videos, and other methods currently being used in astronomy education research and EPO program evaluations. In addition, we discussed common questions in the selection of assessment tools including issues of reliability and validity, time to administer, format of implementation, analysis, and human subject concerns.
Design and control of active vision based mechanisms for intelligent robots
NASA Technical Reports Server (NTRS)
Wu, Liwei; Marefat, Michael M.
1994-01-01
In this paper, we propose a design of an active vision system for intelligent robot application purposes. The system has the degrees of freedom of pan, tilt, vergence, camera height adjustment, and baseline adjustment with a hierarchical control system structure. Based on this vision system, we discuss two problems involved in the binocular gaze stabilization process: fixation point selection and vergence disparity extraction. A hierarchical approach to determining point of fixation from potential gaze targets using evaluation function representing human visual behavior to outside stimuli is suggested. We also characterize different visual tasks in two cameras for vergence control purposes, and a phase-based method based on binarized images to extract vergence disparity for vergence control is presented. A control algorithm for vergence control is discussed.
Physiological Markers of Motor Inhibition during Human Behavior.
Duque, Julie; Greenhouse, Ian; Labruna, Ludovica; Ivry, Richard B
2017-04-01
Transcranial magnetic stimulation (TMS) studies in humans have shown that many behaviors engage processes that suppress excitability within the corticospinal tract. Inhibition of the motor output pathway has been extensively studied in the context of action stopping, where a planned movement needs to be abruptly aborted. Recent TMS work has also revealed markers of motor inhibition during the preparation of movement. Here, we review the evidence for motor inhibition during action stopping and action preparation, focusing on studies that have used TMS to monitor changes in the excitability of the corticospinal pathway. We discuss how these physiological results have motivated theoretical models of how the brain selects actions, regulates movement initiation and execution, and switches from one state to another. Copyright © 2017 Elsevier Ltd. All rights reserved.
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
Glutamate Dysregulation and Glutamatergic Therapeutics for PTSD: Evidence from Human Studies
Averill, Lynnette A.; Purohit, Prerana; Averill, Christopher L.; Boesl, Markus A.; Krystal, John H.; Abdallah, Chadi G.
2017-01-01
Posttraumatic stress disorder (PTSD) is a chronic and debilitating psychiatric disorder afflicting millions of individuals across the world. While the availability of robust pharmacologic interventions is quite lacking, our understanding of the putative neurobiological underpinnings of PTSD has significantly increased over the past two decades. Accumulating evidence demonstrates aberrant glutamatergic function in mood, anxiety, and trauma-related disorders and dysfunction in glutamate neurotransmission is increasingly considered a cardinal feature of stress-related psychiatric disorders including PTSD. As part of a PTSD Special Issue, this mini-review provides a concise discussion of (1) evidence of glutamatergic abnormalities in PTSD, with emphasis on human subjects data; (2) glutamate-modulating agents as potential alternative pharmacologic treatments for PTSD; and (3) selected gaps in the literature and related future directions. PMID:27916636
Motion, identity and the bias toward agency
Fields, Chris
2014-01-01
The well-documented human bias toward agency as a cause and therefore an explanation of observed events is typically attributed to evolutionary selection for a “social brain”. Based on a review of developmental and adult behavioral and neurocognitive data, it is argued that the bias toward agency is a result of the default human solution, developed during infancy, to the computational requirements of object re-identification over gaps in observation of more than a few seconds. If this model is correct, overriding the bias toward agency to construct mechanistic explanations of observed events requires structure-mapping inferences, implemented by the pre-motor action planning system, that replace agents with mechanisms as causes of unobserved changes in contextual or featural properties of objects. Experiments that would test this model are discussed. PMID:25191245
Recent Progress in Technologies for Tactile Sensors.
Chi, Cheng; Sun, Xuguang; Xue, Ning; Li, Tong; Liu, Chang
2018-03-22
Over the last two decades, considerable scientific and technological efforts have been devoted to developing tactile sensing based on a variety of transducing mechanisms, with prospective applications in many fields such as human-machine interaction, intelligent robot tactile control and feedback, and tactile sensorized minimally invasive surgery. This paper starts with an introduction of human tactile systems, followed by a presentation of the basic demands of tactile sensors. State-of-the-art tactile sensors are reviewed in terms of their diverse sensing mechanisms, design consideration, and material selection. Subsequently, typical performances of the sensors, along with their advantages and disadvantages, are compared and analyzed. Two major potential applications of tactile sensing systems are discussed in detail. Lastly, we propose prospective research directions and market trends of tactile sensing systems.
Gordon, Erynn S; Gordish Dressman, Heather A; Hoffman, Eric P
2005-10-01
Much of the vast diversity we see in animals and people is governed by genetic loci that have quantitative effects of phenotype (quantitative trait loci; QTLs). Here we review the current knowledge of the genetics of atrophy and hypertrophy in both animal husbandry (meat quantity and quality), and humans (muscle size and performance). The selective breeding of animals for meat has apparently led to a few genetic loci with strong effects, with different loci in different animals. In humans, muscle quantitative trait loci (QTLs) appear to be more complex, with few "major" loci identified to date, although this is likely to change in the near future. We describe how the same phenotypic traits we see as positive, greater lean muscle mass in cattle or a better exercise results in humans, can also have negative "side effects" given specific environmental challenges. We also discuss the strength and limitations of single nucleotide polymorphisms (SNP) association studies; what the reader should look for and expect in a published study. Lastly we discuss the ethical and societal implications of this genetic information. As more and more research into the genetic loci that dictate phenotypic traits become available, the ethical implications of testing for these loci become increasingly important. As a society, most accept testing for genetic diseases or susceptibility, but do we as easily accept testing to determine one's athletic potential to be an Olympic endurance runner, or quarterback on the high school football team.
Construction of human antibody gene libraries and selection of antibodies by phage display.
Schirrmann, Thomas; Hust, Michael
2010-01-01
Recombinant antibodies as therapeutics offer new opportunities for the treatment of many tumor diseases. To date, 18 antibody-based drugs are approved for cancer treatment and hundreds of anti-tumor antibodies are under development. The first clinically approved antibodies were of murine origin or human-mouse chimeric. However, since murine antibody domains are immunogenic in human patients and could result in human anti-mouse antibody (HAMA) responses, currently mainly humanized and fully human antibodies are developed for therapeutic applications.Here, in vitro antibody selection technologies directly allow the selection of human antibodies and the corresponding genes from human antibody gene libraries. Antibody phage display is the most common way to generate human antibodies and has already yielded thousands of recombinant antibodies for research, diagnostics and therapy. Here, we describe methods for the construction of human scFv gene libraries and the antibody selection.
Models of Cultural Niche Construction with Selection and Assortative Mating
Feldman, Marcus W.
2012-01-01
Niche construction is a process through which organisms modify their environment and, as a result, alter the selection pressures on themselves and other species. In cultural niche construction, one or more cultural traits can influence the evolution of other cultural or biological traits by affecting the social environment in which the latter traits may evolve. Cultural niche construction may include either gene-culture or culture-culture interactions. Here we develop a model of this process and suggest some applications of this model. We examine the interactions between cultural transmission, selection, and assorting, paying particular attention to the complexities that arise when selection and assorting are both present, in which case stable polymorphisms of all cultural phenotypes are possible. We compare our model to a recent model for the joint evolution of religion and fertility and discuss other potential applications of cultural niche construction theory, including the evolution and maintenance of large-scale human conflict and the relationship between sex ratio bias and marriage customs. The evolutionary framework we introduce begins to address complexities that arise in the quantitative analysis of multiple interacting cultural traits. PMID:22905167
Directed evolution: tailoring biocatalysts for industrial applications.
Kumar, Ashwani; Singh, Suren
2013-12-01
Current challenges and promises of white biotechnology encourage protein engineers to use a directed evolution approach to generate novel and useful biocatalysts for various sets of applications. Different methods of enzyme engineering have been used in the past in an attempt to produce enzymes with improved functions and properties. Recent advancement in the field of random mutagenesis, screening, selection and computational design increased the versatility and the rapid development of enzymes under strong selection pressure with directed evolution experiments. Techniques of directed evolution improve enzymes fitness without understanding them in great detail and clearly demonstrate its future role in adapting enzymes for use in industry. Despite significant advances to date regarding biocatalyst improvement, there still remains a need to improve mutagenesis strategies and development of easy screening and selection tools without significant human intervention. This review covers fundamental and major development of directed evolution techniques, and highlights the advances in mutagenesis, screening and selection methods with examples of enzymes developed by using these approaches. Several commonly used methods for creating molecular diversity with their advantages and disadvantages including some recently used strategies are also discussed.
Animal evolution during domestication: the domesticated fox as a model.
Trut, Lyudmila; Oskina, Irina; Kharlamova, Anastasiya
2009-03-01
We review the evolution of domestic animals, emphasizing the effect of the earliest steps of domestication on its course. Using the first domesticated species, the dog (Canis familiaris), for illustration, we describe the evolutionary peculiarities during the historical domestication, such as the high level and wide range of diversity. We suggest that the process of earliest domestication via unconscious and later conscious selection of human-defined behavioral traits may accelerate phenotypic variations. The review is based on the results of a long-term experiment designed to reproduce early mammalian domestication in the silver fox (Vulpes vulpes) selected for tameability or amenability to domestication. We describe changes in behavior, morphology and physiology that appeared in the fox during its selection for tameability, which were similar to those observed in the domestic dog. Based on the data of the fox experiment and survey of relevant data, we discuss the developmental, genetic and possible molecular genetic mechanisms underlying these changes. We ascribe the causative role in evolutionary transformation of domestic animals to the selection for behavior and to the neurospecific regulatory genes it affects.
Utsunomiya, Yuri T.; Pérez O'Brien, Ana M.; Sonstegard, Tad S.; Sölkner, Johann; Garcia, José F.
2015-01-01
The bovine species have witnessed and played a major role in the drastic socio-economical changes that shaped our culture over the last 10,000 years. During this journey, cattle “hitchhiked” on human development and colonized the world, facing strong selective pressures such as dramatic environmental changes and disease challenge. Consequently, hundreds of specialized cattle breeds emerged and spread around the globe, making up a rich spectrum of genomic resources. Their DNA still carry the scars left from adapting to this wide range of conditions, and we are now empowered with data and analytical tools to track the milestones of past selection in their genomes. In this review paper, we provide a summary of the reconstructed demographic events that shaped cattle diversity, offer a critical synthesis of popular methodologies applied to the search for signatures of selection (SS) in genomic data, and give examples of recent SS studies in cattle. Then, we outline the potential and challenges of the application of SS analysis in cattle, and discuss the future directions in this field. PMID:25713583
Ledesma, Mark C; Jung-Hynes, Brittney; Schmit, Travis L; Kumar, Raj; Mukhtar, Hasan; Ahmad, Nihal
2011-01-01
Various formulations of selenium and vitamin E, both essential human dietary components, have been shown to possess a therapeutic and preventive effect against prostate cancer. Fortuitous results of clinical trials also implied a risk-reduction effect of selenium and vitamin E supplements. The Selenium and Vitamin E Cancer Prevention Trial (SELECT), using oral selenium and vitamin E supplementation in disease-free volunteers, was designed to test a prostate cancer chemoprevention hypothesis. SELECT was terminated early because of both safety concerns and negative data for the formulations and doses given. Here, we review and discuss the studies done before and since the inception of SELECT, as well as the parameters of the trial itself. We believe that there is a lack of appropriate in vivo preclinical studies on selenium and vitamin E despite many promising in vitro studies on these agents. It seems that the most effective doses and formulations of these agents for prostate cancer chemoprevention have yet to be tested. Also, improved understanding of selenium and vitamin E biology may facilitate the discovery of these doses and formulations. PMID:20882260
Animal evolution during domestication: the domesticated fox as a model
Trut, Lyudmila; Oskina, Irina; Kharlamova, Anastasiya
2009-01-01
Summary We review the evolution of domestic animals, emphasizing the effect of the earliest steps of domestication on its course. Using the first domesticated species, the dog (Canis familiaris) as an illustration, we describe the evolutionary specificities of the historical domestication, such as the high level and wide range of diversity. We suggest that the process of earliest domestication via unconscious and later conscious selection of human-defined behavioral traits may accelerate phenotypic variations. The review is based on the results of the long-term experiment designed to reproduce early mammalian domestication in the silver fox (Vulpes vulpes) selected for tameability, or amenability to domestication. We describe changes in behavior, morphology and physiology that appeared in the fox during its selection for tameability and that were similar to those observed in the domestic dog. Based on the experimental fox data and survey of relevant data, we discuss the developmental, genetic and possible molecular-genetic mechanisms of these changes. We assign the causative role in evolutionary transformation of domestic animals to selection for behavior and to the neurospecific regulatory genes it affects. PMID:19260016
Human platelet lysate: Replacing fetal bovine serum as a gold standard for human cell propagation?
Burnouf, Thierry; Strunk, Dirk; Koh, Mickey B C; Schallmoser, Katharina
2016-01-01
The essential physiological role of platelets in wound healing and tissue repair builds the rationale for the use of human platelet derivatives in regenerative medicine. Abundant growth factors and cytokines stored in platelet granules can be naturally released by thrombin activation and clotting or artificially by freeze/thaw-mediated platelet lysis, sonication or chemical treatment. Human platelet lysate prepared by the various release strategies has been established as a suitable alternative to fetal bovine serum as culture medium supplement, enabling efficient propagation of human cells under animal serum-free conditions for a multiplicity of applications in advanced somatic cell therapy and tissue engineering. The rapidly increasing number of studies using platelet derived products for inducing human cell proliferation and differentiation has also uncovered a considerable variability of human platelet lysate preparations which limits comparability of results. The main variations discussed herein encompass aspects of donor selection, preparation of the starting material, the possibility for pooling in plasma or additive solution, the implementation of pathogen inactivation and consideration of ABO blood groups, all of which can influence applicability. This review outlines the current knowledge about human platelet lysate as a powerful additive for human cell propagation and highlights its role as a prevailing supplement for human cell culture capable to replace animal serum in a growing spectrum of applications. Copyright © 2015 Elsevier Ltd. All rights reserved.
A Dimeric Mutant of Human Pancreatic Ribonuclease with Selective Cytotoxicity toward Malignant Cells
NASA Astrophysics Data System (ADS)
Piccoli, Renata; di Gaetano, Sonia; de Lorenzo, Claudia; Grauso, Michela; Monaco, Carmen; Spalletti-Cernia, Daniela; Laccetti, Paolo; Cinatl, Jaroslav; Matousek, Josef; D'Alessio, Giuseppe
1999-07-01
Monomeric human pancreatic RNase, devoid of any biological activity other than its RNA degrading ability, was engineered into a dimeric protein with a cytotoxic action on mouse and human tumor cells, but lacking any appreciable toxicity on mouse and human normal cells. This dimeric variant of human pancreas RNase selectively sensitizes to apoptotic death cells derived from a human thyroid tumor. Because of its selectivity for tumor cells, and because of its human origin, this protein represents a potentially very attractive, novel tool for anticancer therapy.
Pragmatic Frames for Teaching and Learning in Human-Robot Interaction: Review and Challenges.
Vollmer, Anna-Lisa; Wrede, Britta; Rohlfing, Katharina J; Oudeyer, Pierre-Yves
2016-01-01
One of the big challenges in robotics today is to learn from human users that are inexperienced in interacting with robots but yet are often used to teach skills flexibly to other humans and to children in particular. A potential route toward natural and efficient learning and teaching in Human-Robot Interaction (HRI) is to leverage the social competences of humans and the underlying interactional mechanisms. In this perspective, this article discusses the importance of pragmatic frames as flexible interaction protocols that provide important contextual cues to enable learners to infer new action or language skills and teachers to convey these cues. After defining and discussing the concept of pragmatic frames, grounded in decades of research in developmental psychology, we study a selection of HRI work in the literature which has focused on learning-teaching interaction and analyze the interactional and learning mechanisms that were used in the light of pragmatic frames. This allows us to show that many of the works have already used in practice, but not always explicitly, basic elements of the pragmatic frames machinery. However, we also show that pragmatic frames have so far been used in a very restricted way as compared to how they are used in human-human interaction and argue that this has been an obstacle preventing robust natural multi-task learning and teaching in HRI. In particular, we explain that two central features of human pragmatic frames, mostly absent of existing HRI studies, are that (1) social peers use rich repertoires of frames, potentially combined together, to convey and infer multiple kinds of cues; (2) new frames can be learnt continually, building on existing ones, and guiding the interaction toward higher levels of complexity and expressivity. To conclude, we give an outlook on the future research direction describing the relevant key challenges that need to be solved for leveraging pragmatic frames for robot learning and teaching.
Microfluidics for mammalian embryo culture and selection: where do we stand now?
Le Gac, Séverine; Nordhoff, Verena
2017-04-01
The optimization of in-vitro culture conditions and the selection of the embryo(s) with the highest developmental competence are essential components in an ART program. Culture conditions are manifold and they underlie not always evidence-based research but also trends entering the IVF laboratory. At the moment, the idea of using sequential media according to the embryo requirements has been given up in favor of the use of single step media in an uninterrupted manner due to practical issues such as time-lapse incubators. The selection of the best embryo is performed using morphological and, recently, also morphokinetic criteria. In this review, we aim to demonstrate how the ART field may benefit from the use of microfluidic technology, with a particular focus on specific steps, namely the embryo in-vitro culture, embryo scoring and selection, and embryo cryopreservation. We first provide an overview of microfluidic and microfabricated devices, which have been developed for embryo culture, characterization of pre-implantation embryos (or in some instances a combination of both steps) and embryo cryopreservation. Building upon these existing platforms and the various capabilities offered by microfluidics, we discuss how this technology could provide integrated and automated systems, not only for real-time and multi-parametric monitoring of embryo development, but also for performing the entire ART procedure. Although microfluidic technology has been around for a couple of decades already, it has still not made its way into the clinics and IVF laboratories, which we discuss in terms of: (i) a lack of user-friendliness and automation of the microfluidic platforms, (ii) a lack of robust and convincing validation using human embryos and (iii) some psychological threshold for embryologists and practitioners to test and use microfluidic technology. In spite of these limitations, we envision that microfluidics is likely to have a significant impact in the field of ART, for fundamental research in the near future and, in the longer term, for providing a novel generation of clinical tools. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.For Permissions, please email: journals.permissions@oup.com.
Heidbreder, Christian A.; Newman, Amy H.
2011-01-01
Repeated exposure to drugs of abuse produces long-term molecular and neurochemical changes that may explain the core features of addiction, such as the compulsive seeking and taking of the drug, as well as the risk of relapse. A growing number of new molecular and cellular targets of addictive drugs have been identified, and rapid advances are being made in relating those targets to specific behavioral phenotypes in animal models of addiction. In this context, the pattern of expression of the dopamine (DA) D3 receptor in the rodent and human brain and changes in this pattern in response to drugs of abuse have contributed primarily to direct research efforts toward the development of selective DA D3 receptor antagonists. Growing preclinical evidence indicates that these compounds may actually regulate the motivation to self-administer drugs and disrupt drug-associated cue-induced craving. This report will be divided into three parts. First, preclinical evidence in support of the efficacy of selective DA D3 receptor antagonists in animal models of drug addiction will be reviewed. The effects of mixed DA D2/D3 receptor antagonists will not be discussed here because most of these compounds have low selectivity at the D3 versus D2 receptor, and their efficacy profile is related primarily to functional antagonism at D2 receptors and possibly interactions with other neurotransmitter systems. Second, major advances in medicinal chemistry for the identification and optimization of selective DA D3 receptor antagonists and partial agonists will be analyzed. Third, translational research from preclinical efficacy studies to so-called proof-of-concept studies for drug addiction indications will be discussed. PMID:20201845
Heidbreder, Christian A; Newman, Amy H
2010-02-01
Repeated exposure to drugs of abuse produces long-term molecular and neurochemical changes that may explain the core features of addiction, such as the compulsive seeking and taking of the drug, as well as the risk of relapse. A growing number of new molecular and cellular targets of addictive drugs have been identified, and rapid advances are being made in relating those targets to specific behavioral phenotypes in animal models of addiction. In this context, the pattern of expression of the dopamine (DA) D(3) receptor in the rodent and human brain and changes in this pattern in response to drugs of abuse have contributed primarily to direct research efforts toward the development of selective DA D(3) receptor antagonists. Growing preclinical evidence indicates that these compounds may actually regulate the motivation to self-administer drugs and disrupt drug-associated cue-induced craving. This report will be divided into three parts. First, preclinical evidence in support of the efficacy of selective DA D(3) receptor antagonists in animal models of drug addiction will be reviewed. The effects of mixed DA D(2)/D(3) receptor antagonists will not be discussed here because most of these compounds have low selectivity at the D(3) versus D(2) receptor, and their efficacy profile is related primarily to functional antagonism at D(2) receptors and possibly interactions with other neurotransmitter systems. Second, major advances in medicinal chemistry for the identification and optimization of selective DA D(3) receptor antagonists and partial agonists will be analyzed. Third, translational research from preclinical efficacy studies to so-called proof-of-concept studies for drug addiction indications will be discussed.
Perception of Human-Derived Risk Influences Choice at Top of the Food Chain
Cristescu, Bogdan; Stenhouse, Gordon B.; Boyce, Mark S.
2013-01-01
On human-used landscapes, animal behavior is a trade-off between maximizing fitness and minimizing human-derived risk. Understanding risk perception in wildlife can allow mitigation of anthropogenic risk, with benefits to long-term animal fitness. Areas where animals choose to rest should minimize risk from predators, which for large carnivores typically equate to humans. We hypothesize that high human activity leads to selection for habitat security, whereas low activity enables trading security for forage. We investigated selection of resting (bedding) sites by GPS radiocollared adult grizzly bears (n = 10) in a low density population on a multiple-use landscape in Canada. We compared security and foods at resting and random locations while accounting for land use, season, and time of day. On reclaimed mines with low human access, bears selected high horizontal cover far from trails, but did not avoid open (herbaceous) areas, resting primarily at night. In protected areas bears also bedded at night, in areas with berry shrubs and Hedysarum spp., with horizontal cover selected in the summer, during high human access. On public lands with substantial human recreation, bears bedded at day, selected resting sites with high horizontal cover in the summer and habitat edges, with bedding associated with herbaceous foods. These spatial and temporal patterns of selection suggest that bears perceive human-related risk differentially in relation to human activity level, season and time of day, and employ a security-food trade-off strategy. Although grizzly bears are presently not hunted in Alberta, their perceived risks associated with humans influence resting-site selection. PMID:24367549
Recent advances in understanding the role of nutrition in human genome evolution.
Ye, Kaixiong; Gu, Zhenglong
2011-11-01
Dietary transitions in human history have been suggested to play important roles in the evolution of mankind. Genetic variations caused by adaptation to diet during human evolution could have important health consequences in current society. The advance of sequencing technologies and the rapid accumulation of genome information provide an unprecedented opportunity to comprehensively characterize genetic variations in human populations and unravel the genetic basis of human evolution. Series of selection detection methods, based on various theoretical models and exploiting different aspects of selection signatures, have been developed. Their applications at the species and population levels have respectively led to the identification of human specific selection events that distinguish human from nonhuman primates and local adaptation events that contribute to human diversity. Scrutiny of candidate genes has revealed paradigms of adaptations to specific nutritional components and genome-wide selection scans have verified the prevalence of diet-related selection events and provided many more candidates awaiting further investigation. Understanding the role of diet in human evolution is fundamental for the development of evidence-based, genome-informed nutritional practices in the era of personal genomics.
Sumboja, Afriyanti; Liu, Jiawei; Zheng, Wesley Guangyuan; Zong, Yun; Zhang, Hua; Liu, Zhaolin
2018-06-27
Compatible energy storage devices that are able to withstand various mechanical deformations, while delivering their intended functions, are required in wearable technologies. This imposes constraints on the structural designs, materials selection, and miniaturization of the cells. To date, extensive efforts have been dedicated towards developing electrochemical energy storage devices for wearables, with a focus on incorporation of shape-conformable materials into mechanically robust designs that can be worn on the human body. In this review, we highlight the quantified performances of reported wearable electrochemical energy storage devices, as well as their micro-sized counterparts under specific mechanical deformations, which can be used as the benchmark for future studies in this field. A general introduction to the wearable technology, the development of the selection and synthesis of active materials, cell design approaches and device fabrications are discussed. It is followed by challenges and outlook toward the practical use of electrochemical energy storage devices for wearable applications.
DEMOGRAPHIC OPPORTUNITY AND THE MATE SELECTION PROCESS IN INDIA
South, Scott J.; Trent, Katherine; Bose, Sunita
2016-01-01
We merged individual-level data from the 2004–2005 India Human Development Survey with district-level data derived from the 1991 and 2001 Indian population censuses to examine how the numerical supply of men to which married women were exposed during late adolescence is associated with women’s agency in the mate selection process and the duration of courtships. Multilevel models that control for an array of both individual and contextual factors showed that exposure to a relative surplus of potential mates is associated with a higher likelihood that women will have little or no say in the selection of their husband and an increased probability that women will meet their husband for the first time on their wedding day. Women’s educational attainment, birth cohort, religion, caste, and region of residence also emerged as significant correlates of women’s marital agency and courtship duration. The implications of these findings for India’s growing sex ratio imbalance are discussed. PMID:27616798
The "SWOT" of BRAF inhibition in melanoma: RAF inhibitors, MEK inhibitors or both?
Nissan, Moriah H; Solit, David B
2011-12-01
Activating mutations in the BRAF gene are among the most prevalent kinase mutations in human cancer. BRAF mutations are most frequent in patients with melanoma where they occur in approximately 50% of patients with advanced disease. Remarkable clinical activity has recently been reported with highly selective RAF inhibitors in melanoma patients whose tumors harbor V600E BRAF mutations. The response rates of RAF inhibitors in patients with BRAF-mutant melanomas far exceed the activity level of any prior therapy studied in this disease. The results suggest that we have entered an era of personalized therapy for patients with metastatic melanoma in which treatment selection will be guided by BRAF mutational status. This review will discuss the strengths, weaknesses, opportunities and threats ("SWOT") of developing RAF and MEK selective inhibitors as anti-cancer therapies, recent insights into the mechanisms of intrinsic and acquired resistance to these agents, and current efforts to develop mechanism-based combination therapies.
Recent Developments of C-Aryl Glucoside SGLT2 Inhibitors.
Zhang, Yang; Liu, Zhao-Peng
2016-01-01
Sodium-glucose cotransporter 2 (SGLT2) is almost exclusively expressed in the proximal renal tubules. It is responsible for about 90% of the glucose reabsorption from tubular fluid. Selective inhibition of SGLT2 is expected to favor in the normalization of plasma glucose levels in T2DM patients through the prevention of renal glucose reabsorption and the promotion of glucose excretion from urine. Selective SGLT2 inhibitors have the merits to minimize the gastrointestinal side effects associated with SGLT1 inhibition, and selective SGLT2 inhibition may have a low risk of hypoglycemia. Since the C-aryl glucosides are metabolically more stable than the O-glucosides, numerous efforts have been made in the development of potent and selective C-aryl glucoside SGLT2 inhibitors, and a number of them are now used as anti-diabetes drugs in clinic or at various stages of clinical developments. Based on their structural features, in this review, these SGLT2 inhibitors are classified as three types: the phenyl/arylmethylphenyl C-glucosides, with an emphasis on the modifications on the proximal and/or the distal phenyl ring, and the spacer; the heteroarylmethylphenyl Cglucosides, with a replacement of the distal phenyl ring by a heterocycle like pyridazine, pyrimidine, thiophene and benzothiophene, thiazole, 1,3,4-thiadiazole, and triazolopyridinone; and the glucose-modified Caryl glucosides, including the glucose C-1 derived O-spiroketals, C-4 gem-difluoro analogues, C-5 and C-6 modified derivatives, dioxa-bicyclo[3.2.1]octane bridged ketals, the thioglucosides, and carbasugars. The structure-activity relationships (SARs) of each type along with their inhibitory potency against human SGLT2 and selectivity over human SGLT1 are discussed.
Biofortification in China: policy and practice
Campos-Bowers, Monica H; Wittenmyer, Brian F
2007-01-01
Micronutrient deficiency undernutrition, due to insufficient levels of vitamins and minerals in the diet, remains one of the most prevalent and preventable nutritional problems in the world today. Micronutrient undernutrition is the most common form of malnutrition. Compared to the 180 million children with protein-energy malnutrition, 3.5–5 billion persons are iron-deficient, and 140–250 million persons are vitamin A-deficient. Micronutrient deficiencies diminish physical, cognitive, and reproductive development. Undernutrition is both a cause and a result of poor human health and achievement. Middle-income nations, such as China, also suffer from micronutrient undernutrition's effects. In China's poor western provinces, despite supplementation and fortification efforts, stunting and underweight (symptoms of micronutrient undernutrition) remain common. In recent decades, nutritional adequacy, in terms of available food energy, improved immensely, as the government made food security a top priority. A potential next step for China could be to address specifically micronutrient undernutrition. The paper aims to provide a discussion of policy issues relevant to biofortification, if China were to consider the implementation of this intervention in its rural provinces. Traditional nutritional interventions currently employ four main strategies: dietary modification, supplementation, commercial fortification, and biofortification. Biofortification, a relatively new technique, involves selectively breeding staple plant varieties to increase specific nutrient levels in plant tissues. Biofortification has the potential to provide benefits to humans, plants, and livestock; nourish nutrient-depleted soils; and help increase crop yields per acre. Biofortification methods include selective breeding, reducing levels of anti-nutrients, and increasing levels of substances that promote nutrient absorption. If China were to implement biofortification programs, with help from government agencies and international organizations, several policy questions would need to be addressed. The paper discusses several policy questions that pertain to the relationship between biofortified and genetically modified crops, human health and safety concerns, labeling of biofortified crops for consumers, consumer rights, potential environmental impacts, intellectual property rights, seed disbursement, government investment, private-sector research, and additional agricultural and commercial regulations. Biofortification has the potential to help alleviate the suffering, death, disability, and failure to achieve full human potential that results from micronutrient undernutrition-related diseases. PMID:17897456
Human influences on evolution, and the ecological and societal consequences
Hendry, Andrew P.; Svensson, Erik I.
2017-01-01
Humans have dramatic, diverse and far-reaching influences on the evolution of other organisms. Numerous examples of this human-induced contemporary evolution have been reported in a number of ‘contexts’, including hunting, harvesting, fishing, agriculture, medicine, climate change, pollution, eutrophication, urbanization, habitat fragmentation, biological invasions and emerging/disappearing diseases. Although numerous papers, journal special issues and books have addressed each of these contexts individually, the time has come to consider them together and thereby seek important similarities and differences. The goal of this special issue, and this introductory paper, is to promote and expand this nascent integration. We first develop predictions as to which human contexts might cause the strongest and most consistent directional selection, the greatest changes in evolutionary potential, the greatest genetic (as opposed to plastic) changes and the greatest effects on evolutionary diversification. We then develop predictions as to the contexts where human-induced evolutionary changes might have the strongest effects on the population dynamics of the focal evolving species, the structure of their communities, the functions of their ecosystems and the benefits and costs for human societies. These qualitative predictions are intended as a rallying point for broader and more detailed future discussions of how human influences shape evolution, and how that evolution then influences species traits, biodiversity, ecosystems and humans. This article is part of the themed issue ‘Human influences on evolution, and the ecological and societal consequences’. PMID:27920373
Filippi, Piera; Gogoleva, Svetlana S; Volodina, Elena V; Volodin, Ilya A; de Boer, Bart
2017-08-01
The ability to identify emotional arousal in heterospecific vocalizations may facilitate behaviors that increase survival opportunities. Crucially, this ability may orient inter-species interactions, particularly between humans and other species. Research shows that humans identify emotional arousal in vocalizations across multiple species, such as cats, dogs, and piglets. However, no previous study has addressed humans' ability to identify emotional arousal in silver foxes. Here, we adopted low- and high-arousal calls emitted by three strains of silver fox-Tame, Aggressive, and Unselected-in response to human approach. Tame and Aggressive foxes are genetically selected for friendly and attacking behaviors toward humans, respectively. Unselected foxes show aggressive and fearful behaviors toward humans. These three strains show similar levels of emotional arousal, but different levels of emotional valence in relation to humans. This emotional information is reflected in the acoustic features of the calls. Our data suggest that humans can identify high-arousal calls of Aggressive and Unselected foxes, but not of Tame foxes. Further analyses revealed that, although within each strain different acoustic parameters affect human accuracy in identifying high-arousal calls, spectral center of gravity, harmonic-to-noise ratio, and F0 best predict humans' ability to discriminate high-arousal calls across all strains. Furthermore, we identified in spectral center of gravity and F0 the best predictors for humans' absolute ratings of arousal in each call. Implications for research on the adaptive value of inter-specific eavesdropping are discussed.
Microbial Ecology along the Gastrointestinal Tract
Hillman, Ethan T.; Lu, Hang; Yao, Tianming; Nakatsu, Cindy H.
2017-01-01
The ecosystem of the human gastrointestinal (GI) tract traverses a number of environmental, chemical, and physical conditions because it runs from the oral cavity to the anus. These differences in conditions along with food or other ingested substrates affect the composition and density of the microbiota as well as their functional roles by selecting those that are the most suitable for that environment. Previous studies have mostly focused on Bacteria, with the number of studies conducted on Archaea, Eukarya, and Viruses being limited despite their important roles in this ecosystem. Furthermore, due to the challenges associated with collecting samples directly from the inside of humans, many studies are still exploratory, with a primary focus on the composition of microbiomes. Thus, mechanistic studies to investigate functions are conducted using animal models. However, differences in physiology and microbiomes need to be clarified in order to aid in the translation of animal model findings into the context of humans. This review will highlight Bacteria, Archaea, Fungi, and Viruses, discuss differences along the GI tract of healthy humans, and perform comparisons with three common animal models: rats, mice, and pigs. PMID:29129876
Automation in the graphic arts
NASA Astrophysics Data System (ADS)
Truszkowski, Walt
1995-04-01
The CHIMES (Computer-Human Interaction Models) tool was designed to help solve a simply-stated but important problem, i.e., the problem of generating a user interface to a system that complies with established human factors standards and guidelines. Though designed for use in a fairly restricted user domain, i.e., spacecraft mission operations, the CHIMES system is essentially domain independent and applicable wherever graphical user interfaces of displays are to be encountered. The CHIMES philosophy and operating strategy are quite simple. Instead of requiring a human designer to actively maintain in his or her head the now encyclopedic knowledge that human factors and user interface specialists have evolved, CHIMES incorporates this information in its knowledge bases. When directed to evaluated a design, CHIMES determines and accesses the appropriate knowledge, performs an evaluation of the design against that information, determines whether the design is compliant with the selected guidelines and suggests corrective actions if deviations from guidelines are discovered. This paper will provide an overview of the capabilities of the current CHIMES tool and discuss the potential integration of CHIMES-like technology in automated graphic arts systems.
Sizing up human health through remote sensing: uses and misuses.
Herbreteau, V; Salem, G; Souris, M; Hugot, J P; Gonzalez, J P
2005-03-01
Following the launch of new satellites, remote sensing (RS) has been increasingly implicated in human health research for thirty years, providing a growing availability of images with higher resolution and spectral ranges. However, the scope of applications, beyond theoretical large potentialities, appears limited both by their technical nature and the models developed. An exhaustive review of RS applications in human health highlights the real implication thus far regarding the diversity and range of health issues, remotely sensed data, processes and interpretations. The place of RS is far under its expected potential, revealing fundamental barriers in its implementation for health applications. The selection of images is done by practical considerations as trivial as price and availability, which are often not relevant to addressing health questions requiring suitable resolutions and spatio-temporal range. The relationships of environmental variables from RS, geospatial data from other sources for health investigations are poorly addressed and usually simplified. A discussion covering the potential of RS for human health is developed here to assist health scientists deal with spatial and temporal dynamics of health, by finding the most relevant data and analysis procedures.
Factors Shaping the Human Exposome in the Built Environment: Opportunities for Engineering Control.
Dai, Dongjuan; Prussin, Aaron J; Marr, Linsey C; Vikesland, Peter J; Edwards, Marc A; Pruden, Amy
2017-07-18
The "exposome" is a term describing the summation of one's lifetime exposure to microbes and chemicals. Such exposures are now recognized as major drivers of human health and disease. Because humans spend ∼90% of their time indoors, the built environment exposome merits particular attention. Herein we utilize an engineering perspective to advance understanding of the factors that shape the built environment exposome and its influence on human wellness and disease, while simultaneously informing development of a framework for intentionally controlling the exposome to protect public health. Historically, engineers have been focused on controlling chemical and physical contaminants and on eradicating microbes; however, there is a growing awareness of the role of "beneficial" microbes. Here we consider the potential to selectively control the materials and chemistry of the built environment to positively influence the microbial and chemical components of the indoor exposome. Finally, we discuss research gaps that must be addressed to enable intentional engineering design, including the need to define a "healthy" built environment exposome and how to control it.
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
Keim, Mark E
2008-11-01
Global climate change will increase the probability of extreme weather events, including heatwaves, drought, wildfire, cyclones, and heavy precipitation that could cause floods and landslides. Such events create significant public health needs that can exceed local capacity to respond, resulting in excess morbidity or mortality and in the declaration of disasters. Human vulnerability to any disaster is a complex phenomenon with social, economic, health, and cultural dimensions. Vulnerability to natural disasters has two sides: the degree of exposure to dangerous hazards (susceptibility) and the capacity to cope with or recover from disaster consequences (resilience). Vulnerability reduction programs reduce susceptibility and increase resilience. Susceptibility to disasters is reduced largely by prevention and mitigation of emergencies. Emergency preparedness and response and recovery activities--including those that address climate change--increase disaster resilience. Because adaptation must occur at the community level, local public health agencies are uniquely placed to build human resilience to climate-related disasters. This article discusses the role of public health in reducing human vulnerability to climate change within the context of select examples for emergency preparedness and response.
Tele-rehabilitation using in-house wearable ankle rehabilitation robot.
Jamwal, Prashant K; Hussain, Shahid; Mir-Nasiri, Nazim; Ghayesh, Mergen H; Xie, Sheng Q
2018-01-01
This article explores wide-ranging potential of the wearable ankle robot for in-house rehabilitation. The presented robot has been conceptualized following a brief analysis of the existing technologies, systems, and solutions for in-house physical ankle rehabilitation. Configuration design analysis and component selection for ankle robot have been discussed as part of the conceptual design. The complexities of human robot interaction are closely encountered while maneuvering a rehabilitation robot. We present a fuzzy logic-based controller to perform the required robot-assisted ankle rehabilitation treatment. Designs of visual haptic interfaces have also been discussed, which will make the treatment interesting, and the subject will be motivated to exert more and regain lost functions rapidly. The complex nature of web-based communication between user and remotely sitting physiotherapy staff has also been discussed. A high-level software architecture appended with robot ensures user-friendly operations. This software is made up of three important components: patient-related database, graphical user interface (GUI), and a library of exercises creating virtual reality-specifically developed for ankle rehabilitation.
Overview of the Orion Thermal Protection System
NASA Technical Reports Server (NTRS)
Kowal, T. John
2010-01-01
The Orion spacecraft is being developed as part of the Constellation Exploration Program and will serve as the United States crewed transportation system to the International Space Station after the retirement of the Space Shuttle in 2010 and as the eventual means to return U.S. astronauts to the Moon. Therefore, Orion is being designed for reentry missions from both low Earth orbit and from Lunar-return trajectories. This presentation will provide an overview of the development of the Orion TPS, a critical component in the development of the spacecraft. The thermal protection system (TPS) that protects the crew module from the extreme environments associated with Earth atmospheric reentry consists of a forward heatshield and an aft backshell. The requirements that drive the design of the TPS will be discussed, including several key requirements that establish a precedent for U.S. human-rated spacecraft. For the first time in U.S. human spaceflight, a vehicle s TPS is being designed with a specific, derived requirement for reliability. Also, due to the increased presence of spacecraft in Earth s orbit in recent decades, requirements for micro-meteoroid/orbital debris damage tolerance are also a driving requirement that has affected the selection of portions of the TPS. The efforts to select materials and to define a preliminary design for both the heatshield and the backshell will be described. This will include a discussion of the design challenges presented by the numerous penetrations on both the backshell and the heatshield. Finally, the verification and validation plan which is currently under development to certify the TPS for human-rated missions will be outlined. To support the execution of this plan, a ground test campaign for both thermal and structural performance is being designed. This test campaign will directly support thermal and thermal/structural analyses that also are fundamental to the certification effort.
Development of lightweight graphite/polyimide honeycomb. Phase 1: Materials selection
NASA Technical Reports Server (NTRS)
Poesch, J. G.
1971-01-01
The materials selected for the production of extremely lightweight honeycomb sandwich panels are discussed. The resin selected for the first core and face sheet fabrication was Monsanto RS6234 polyimide. The fiber selected for core manufacture was Hercules HT-S, and for face sheets, Hercules HM-S; these selections are discussed.
Charbonnel, Nathalie; Pagès, Marie; Sironen, Tarja; Henttonen, Heikki; Vapalahti, Olli; Mustonen, Jukka; Vaheri, Antti
2014-01-01
We reviewed the associations of immunity-related genes with susceptibility of humans and rodents to hantaviruses, and with severity of hantaviral diseases in humans. Several class I and class II HLA haplotypes were linked with severe or benign hantavirus infections, and these haplotypes varied among localities and hantaviruses. The polymorphism of other immunity-related genes including the C4A gene and a high-producing genotype of TNF gene associated with severe PUUV infection. Additional genes that may contribute to disease or to PUUV infection severity include non-carriage of the interleukin-1 receptor antagonist (IL-1RA) allele 2 and IL-1β (-511) allele 2, polymorphisms of plasminogen activator inhibitor (PAI-1) and platelet GP1a. In addition, immunogenetic studies have been conducted to identify mechanisms that could be linked with the persistence/clearance of hantaviruses in reservoirs. Persistence was associated during experimental infections with an upregulation of anti-inflammatory responses. Using natural rodent population samples, polymorphisms and/or expression levels of several genes have been analyzed. These genes were selected based on the literature of rodent or human/hantavirus interactions (some Mhc class II genes, Tnf promoter, and genes encoding the proteins TLR4, TLR7, Mx2 and β3 integrin). The comparison of genetic differentiation estimated between bank vole populations sampled over Europe, at neutral and candidate genes, has allowed to evidence signatures of selection for Tnf, Mx2 and the Drb Mhc class II genes. Altogether, these results corroborated the hypothesis of an evolution of tolerance strategies in rodents. We finally discuss the importance of these results from the medical and epidemiological perspectives. PMID:24859344
Air and Water System (AWS) Design and Technology Selection for the Vision for Space Exploration
NASA Technical Reports Server (NTRS)
Jones, Harry; Kliss, Mark
2005-01-01
This paper considers technology selection for the crew air and water recycling systems to be used in long duration human space exploration. The specific objectives are to identify the most probable air and water technologies for the vision for space exploration and to identify the alternate technologies that might be developed. The approach is to conduct a preliminary first cut systems engineering analysis, beginning with the Air and Water System (AWS) requirements and the system mass balance, and then define the functional architecture, review the International Space Station (ISS) technologies, and discuss alternate technologies. The life support requirements for air and water are well known. The results of the mass flow and mass balance analysis help define the system architectural concept. The AWS includes five subsystems: Oxygen Supply, Condensate Purification, Urine Purification, Hygiene Water Purification, and Clothes Wash Purification. AWS technologies have been evaluated in the life support design for ISS node 3, and in earlier space station design studies, in proposals for the upgrade or evolution of the space station, and in studies of potential lunar or Mars missions. The leading candidate technologies for the vision for space exploration are those planned for Node 3 of the ISS. The ISS life support was designed to utilize Space Station Freedom (SSF) hardware to the maximum extent possible. The SSF final technology selection process, criteria, and results are discussed. Would it be cost-effective for the vision for space exploration to develop alternate technology? This paper will examine this and other questions associated with AWS design and technology selection.
Analysis of dietary intake of selected metals in the NHEXAS-Maryland investigation.
Ryan, P B; Scanlon, K A; MacIntosh, D L
2001-01-01
As part of a large pilot investigation of multimedia exposure to several classes of environmental contaminants, the National Human Exposure Assessment Survey (NHEXAS)-Maryland study, we collected 388 semiquantitative food checklists and duplicate diet solid food samples, analyzed for arsenic, cadmium, chromium, and lead concentrations, from 80 individuals in Maryland in 1995-1996 in a repeated measures design. Here we explore several methods to infer foods most strongly associated with concentrations of these metals observed in the duplicate diet in our data set. We employed two techniques in which logarithmically transformed metal concentrations in the duplicate diet were regressed on individual food item consumption using algorithms designed to identify the foods most associated with the observed duplicate diet concentrations. We also employed an alternative strategy in which foods to be used as independent variables in regression were selected using data collected in national food consumption and residue surveys, with regression procedures proceeding with the selected foods in a similar manner. The concordance of foods selected as major predictors among these three techniques is noteworthy and is discussed. Finally, the Dietary Exposure Potential Model (DEPM) was used with the Dietary Checklist data to predict duplicate diet concentrations within our sample. A comparison between the predicted values and those observed gave R(2) values of 0.180, 0.206, and 0.076 for As, Cd, and Pb, respectively (p < 0.0001 in all cases). We discuss the significance of these observations and the implications for dietary-exposure-based risk analysis and dietary intake epidemiology. PMID:11266320
Pathogen security-help or hindrance?
Morse, Stephen A
2014-01-01
Events over the past 15 years have resulted in the promulgation of regulations in the United States to enhance biosecurity by restricting the access to pathogens and toxins (i.e., biological select agents and toxins [BSATs]), which pose a severe threat to human being, animal, or plant health or to animal or plant products, to qualified institutions, laboratories, and scientists. These regulations also reduce biosafety concerns by imposing specific requirements on laboratories working with BSATs. Furthermore, they provide a legal framework for prosecuting someone who possesses a BSAT illegally. With the implementation of these regulations has come discussion in the scientific community about the potential of these regulations to affect the cost of doing BSAT research, hamper research and international collaborations, or whether it would stop someone with a microbiological background from isolating many of the select agents from nature.
Iida, T; Momose, T; Chang, F C; Goto, J; Nambara, T
1989-12-01
The 4 beta-hydroxylated derivatives of lithocholic, deoxycholic, chenodeoxycholic, and cholic acids were synthesized from their respective parent compounds. The principal reactions employed were 1) beta-face cis-dihydroxylation of delta 3 intermediates with osmium tetroxide-N-methylmorpholine N-oxide, 2) selective cathylation of vicinal 3 beta,4 beta-diols followed by oxidation of the resulting 4 beta-monocathylates, or direct selective oxidation at C-3 of 3 beta,4 beta-diols with pyridinium chlorochromate, and 3) stereoselective reduction of the 3-oxo compounds with tert-butylamine-borane complex. The results of analysis of the prepared 4 beta-hydroxylated bile acids with a diequatorial trans-glycol structure and their 3 beta-epimers by proton and carbon-13 nuclear magnetic resonance spectroscopies are briefly discussed along with the mass spectrometric properties.
The application of mixed methods designs to trauma research.
Creswell, John W; Zhang, Wanqing
2009-12-01
Despite the use of quantitative and qualitative data in trauma research and therapy, mixed methods studies in this field have not been analyzed to help researchers designing investigations. This discussion begins by reviewing four core characteristics of mixed methods research in the social and human sciences. Combining these characteristics, the authors focus on four select mixed methods designs that are applicable in trauma research. These designs are defined and their essential elements noted. Applying these designs to trauma research, a search was conducted to locate mixed methods trauma studies. From this search, one sample study was selected, and its characteristics of mixed methods procedures noted. Finally, drawing on other mixed methods designs available, several follow-up mixed methods studies were described for this sample study, enabling trauma researchers to view design options for applying mixed methods research in trauma investigations.
A design study of the energy selection system for carbon-ion therapy
NASA Astrophysics Data System (ADS)
Hahn, Garam; An, Dong Hyun; Hong, Bong Hwan; Kim, Geun Beom; Yim, Heejoong; Chang, Hong Seok; Jung, In Su; Kang, Kun Uk; Nam, Sang Hoon; Park, Inkyu
2015-02-01
KHIMA, a research project to construct a carbon radio-therapy facility in Korea, has been developing a superconducting cyclotron named KIRAMS-430 as a carbon(12 C 6+) particle accelerator. Due to the fixed beam energy of the cyclotron, an energy selection system (ESS) is required for treatment of tumors located at various depths in the human body. In the present paper, two design stages of the ESS are discussed. First, the beam tracks behind the degrader block and the statistical twiss parameters for the entire energy range were calculated by using the GEANT4 simulation toolkit. Analysis of the beam transmission and the contamination ratios were performed. In the second stage, the beam optics was designed to support the same phase profile at the end regardless of the variations in all of input twiss parameters and the emittance.
Pathogen Security-Help or Hindrance?
Morse, Stephen A.
2015-01-01
Events over the past 15 years have resulted in the promulgation of regulations in the United States to enhance biosecurity by restricting the access to pathogens and toxins (i.e., biological select agents and toxins [BSATs]), which pose a severe threat to human being, animal, or plant health or to animal or plant products, to qualified institutions, laboratories, and scientists. These regulations also reduce biosafety concerns by imposing specific requirements on laboratories working with BSATs. Furthermore, they provide a legal framework for prosecuting someone who possesses a BSAT illegally. With the implementation of these regulations has come discussion in the scientific community about the potential of these regulations to affect the cost of doing BSAT research, hamper research and international collaborations, or whether it would stop someone with a microbiological background from isolating many of the select agents from nature. PMID:25610829
Nozeret, Karine; Loll, François; Cardoso, Gildas Mouta; Escudé, Christophe; Boutorine, Alexandre S
2018-06-01
Pericentromeric heterochromatin plays important roles in controlling gene expression and cellular differentiation. Fluorescent pyrrole-imidazole polyamides targeting murine pericentromeric DNA (major satellites) can be used for the visualization of pericentromeric heterochromatin foci in live mouse cells. New derivatives targeting human repeated DNA sequences (α-satellites) were synthesized and their interaction with target DNA was characterized. The possibility to use major satellite and α -satellite binding polyamides as tools for staining pericentromeric heterochromatin was further investigated in fixed and living mouse and human cells. The staining that was previously observed using the mouse model was further characterized and optimized, but remained limited regarding the fluorophores that can be used. The promising results regarding the staining in the mouse model could not be extended to the human model. Experiments performed in human cells showed chromosomal DNA staining without selectivity. Factors limiting the use of fluorescent polyamides, in particular probe aggregation in the cytoplasm, were investigated. Results are discussed with regards to structure and affinity of probes, density of target sites and chromatin accessibility in both models. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.
Adaptation of human skin color in various populations.
Deng, Lian; Xu, Shuhua
2018-01-01
Skin color is a well-recognized adaptive trait and has been studied extensively in humans. Understanding the genetic basis of adaptation of skin color in various populations has many implications in human evolution and medicine. Impressive progress has been made recently to identify genes associated with skin color variation in a wide range of geographical and temporal populations. In this review, we discuss what is currently known about the genetics of skin color variation. We enumerated several cases of skin color adaptation in global modern humans and archaic hominins, and illustrated why, when, and how skin color adaptation occurred in different populations. Finally, we provided a summary of the candidate loci associated with pigmentation, which could be a valuable reference for further evolutionary and medical studies. Previous studies generally indicated a complex genetic mechanism underlying the skin color variation, expanding our understanding of the role of population demographic history and natural selection in shaping genetic and phenotypic diversity in humans. Future work is needed to dissect the genetic architecture of skin color adaptation in numerous ethnic minority groups around the world, which remains relatively obscure compared with that of major continental groups, and to unravel the exact genetic basis of skin color adaptation.
Contributions of basic immunology to human health.
Albright, J F; Oppenheim, J J
1991-03-01
The sixth symposium in the series "Contemporary Topics in Immunology" was held in New Orleans on June 3, 1990, at the joint meeting of The American Association of Immunologists and the American Society of Biochemistry and Molecular Biology. The symposium was sponsored jointly by The American Association of Immunologists, the Clinical Immunology Society, and and the National Institute of Allergy and Infectious Diseases, and was titled "The Contributions of Basic Immunology to Human Health." Five speakers, whose research has clear relevance to the treatment and prevention of major human diseases, discussed topics of great current interest: hematopoietic stem cells, cell adhesion and lymphocyte homing; the complexities of autoimmunity and approaches to diverting or depressing autoaggressive immunity; structure and functions of the interferons and the construction of designer and chimeric interferons; the varied functions of transforming growth factors and molecular events that regulate the synthesis of TGF beta; and the roles of cytokines in the expression of human immunodeficiency virus and the prospects for controlling HIV infections by regulating selected cytokines. This symposium will be remembered for the exceptional clarity with which each speaker illustrated how fundamental knowledge in immunology fuels advances in the treatment and prevention of those human disorders that involve the immune system.
Repurposing drugs to treat l-DOPA-induced dyskinesia in Parkinson's disease.
Johnston, Tom H; Lacoste, Alix M B; Visanji, Naomi P; Lang, Anthony E; Fox, Susan H; Brotchie, Jonathan M
2018-06-01
In this review, we discuss the opportunity for repurposing drugs for use in l-DOPA-induced dyskinesia (LID) in Parkinson's disease. LID is a particularly suitable indication for drug repurposing given its pharmacological diversity, translatability of animal-models, availability of Phase II proof-of-concept (PoC) methodologies and the indication-specific regulatory environment. A compound fit for repurposing is defined as one with appropriate human safety-data as well as animal safety, toxicology and pharmacokinetic data as found in an Investigational New Drug (IND) package for another indication. We first focus on how such repurposing candidates can be identified and then discuss development strategies that might progress such a candidate towards a Phase II clinical PoC. We discuss traditional means for identifying repurposing candidates and contrast these with newer approaches, especially focussing on the use of computational and artificial intelligence (AI) platforms. We discuss strategies that can be categorised broadly as: in vivo phenotypic screening in a hypothesis-free manner; in vivo phenotypic screening based on analogy to a related disorder; hypothesis-driven evaluation of candidates in vivo and in silico screening with a hypothesis-agnostic component to the selection. To highlight the power of AI approaches, we describe a case study using IBM Watson where a training set of compounds, with demonstrated ability to reduce LID, were employed to identify novel repurposing candidates. Using the approaches discussed, many diverse candidates for repurposing in LID, originally envisaged for other indications, will be described that have already been evaluated for efficacy in non-human primate models of LID and/or clinically. Copyright © 2018 Elsevier Ltd. All rights reserved.
Evaluating Models of Human Performance: Safety-Critical Systems Applications
NASA Technical Reports Server (NTRS)
Feary, Michael S.
2012-01-01
This presentation is part of panel discussion on Evaluating Models of Human Performance. The purpose of this panel is to discuss the increasing use of models in the world today and specifically focus on how to describe and evaluate models of human performance. My presentation will focus on discussions of generating distributions of performance, and the evaluation of different strategies for humans performing tasks with mixed initiative (Human-Automation) systems. I will also discuss issues with how to provide Human Performance modeling data to support decisions on acceptability and tradeoffs in the design of safety critical systems. I will conclude with challenges for the future.
Oxidative damage to macromolecules in human Parkinson’s disease and the rotenone model
Sanders, Laurie H.; Greenamyre, J. Timothy
2013-01-01
Parkinson’s disease (PD), the most common neurodegenerative movement disorder, is associated with selective degeneration of nigrostriatal dopamine neurons. While the underlying mechanisms contributing to neurodegeneration in PD appear to be multifactorial, mitochondrial impairment and oxidative stress are widely considered to be central to many forms of the disease. Whether oxidative stress is a cause or consequence of dopaminergic death, there is substantial evidence for oxidative stress in both human PD patients and in animal models of PD, especially using rotenone, a complex I inhibitor. There are many indices of oxidative stress, but this review covers the recent evidence for oxidative damage to nucleic acids, lipids and proteins in both the brain and peripheral tissues in human PD and in the rotenone model. Limitations of the existing literature and future perspectives are discussed. Understanding how each particular macromolecule is damaged by oxidative stress and the interplay of secondary damage to other biomolecules may help design better targets for treatment of PD. PMID:23328732
Clinical chemistry and hematology values in a Caribbean population of African green monkeys.
Liddie, Shervin; Goody, Robin J; Valles, Rodrigo; Lawrence, Matthew S
2010-12-01
Hematology and clinical chemistry (HCC) reference values are critical in veterinary practice and in vivo pre-clinical research, enabling detection of health abnormalities, response to therapeutic intervention or adverse toxicological effects, as well as monitoring of clinical management. In this report, reference ranges for 46 HCC parameters were characterized in 331 wild-caught and colony-bred African green monkeys. Effects of sex, weight and duration of captivity were determined by one-way analysis of variance. Significant sex differences were observed for several HCC parameters. Significant differences were also observed for select HCC variables between newly caught animals and those held in captivity for 1-12 months or longer. Comparison of this data with other non-human primate species and humans highlights similarities and disparities between species. Potential causes of interpopulation variability and relevance to the use of the African green monkey as a non-human primate model are discussed. © 2010 John Wiley & Sons A/S.
European bats as carriers of viruses with zoonotic potential.
Kohl, Claudia; Kurth, Andreas
2014-08-13
Bats are being increasingly recognized as reservoir hosts of highly pathogenic and zoonotic emerging viruses (Marburg virus, Nipah virus, Hendra virus, Rabies virus, and coronaviruses). While numerous studies have focused on the mentioned highly human-pathogenic bat viruses in tropical regions, little is known on similar human-pathogenic viruses that may be present in European bats. Although novel viruses are being detected, their zoonotic potential remains unclear unless further studies are conducted. At present, it is assumed that the risk posed by bats to the general public is rather low. In this review, selected viruses detected and isolated in Europe are discussed from our point of view in regard to their human-pathogenic potential. All European bat species and their roosts are legally protected and some European species are even endangered. Nevertheless, the increasing public fear of bats and their viruses is an obstacle to their protection. Educating the public regarding bat lyssaviruses might result in reduced threats to both the public and the bats.
Heterogeneity of Human CD4(+) T Cells Against Microbes.
Sallusto, Federica
2016-05-20
CD4(+) T helper (Th) cells play a central role in the adaptive immune response by providing help to B cells and cytotoxic T cells and by releasing different types of cytokines in tissues to mediate protection against a wide range of pathogenic microorganisms. These functions are performed by different types of Th cells endowed with distinct migratory capacities and effector functions. Here we discuss how studies of the human T cell response to microbes have advanced our understanding of Th cell functional heterogeneity, in particular with the discovery of a distinct Th1 subset involved in the response to Mycobacteria and the characterization of two types of Th17 cells specific for extracellular bacteria or fungi. We also review new approaches to dissect at the clonal level the human CD4(+) T cell response induced by pathogens or vaccines that have revealed an unexpected degree of intraclonal diversification and propose a progressive and selective model of CD4(+) T cell differentiation.
Explosive genetic evidence for explosive human population growth
Gao, Feng; Keinan, Alon
2016-01-01
The advent of next-generation sequencing technology has allowed the collection of vast amounts of genetic variation data. A recurring discovery from studying larger and larger samples of individuals had been the extreme, previously unexpected, excess of very rare genetic variants, which has been shown to be mostly due to the recent explosive growth of human populations. Here, we review recent literature that inferred recent changes in population size in different human populations and with different methodologies, with many pointing to recent explosive growth, especially in European populations for which more data has been available. We also review the state-of-the-art methods and software for the inference of historical population size changes that lead to these discoveries. Finally, we discuss the implications of recent population growth on personalized genomics, on purifying selection in the non-equilibrium state it entails and, as a consequence, on the genetic architecture underlying complex disease and the performance of mapping methods in discovering rare variants that contribute to complex disease risk. PMID:27710906
Summary of the 9th annual meeting of the Italian Society for Virology.
Salata, Cristiano; Calistri, Arianna; Parolin, Cristina; Palù, Giorgio
2011-01-01
The 9th annual meeting of the Italian Society for Virology (SIV) comprised seven plenary sessions focused on: General virology and viral genetics; Virus-Host interaction and pathogenesis; Viral oncology; Emerging viruses and zoonotic, foodborne, and environmental pathways of transmission; Viral immunology and vaccines; Medical virology and antiviral therapy; Viral biotechnologies and gene therapy. Moreover, four hot topics were discussed in special lectures: the Pioneer in human virology lecture regarding the control of viral epidemics with particular emphasis on the human immunodeficiency virus (HIV), the Pioneer in plant virology lecture focused on cell responses to plant virus infection, a Keynote lecture on the epidemiology and genetic diversity of Crimea-Congo Hemorrhagic Fever virus, and the G.B. Rossi lecture on the molecular basis and clinical implications of human cytomegalovirus tropism for endothelial/epithelial cells. The meeting had an attendance of about 160 virologists. A summary of the plenary lectures and oral selected presentations is reported.
Single-cell recordings in the human medial temporal lobe
Rey, Hernan G; Ison, Matias J; Pedreira, Carlos; Valentin, Antonio; Alarcon, Gonzalo; Selway, Richard; Richardson, Mark P; Quian Quiroga, Rodrigo
2015-01-01
Recordings from individual neurons in patients who are implanted with depth electrodes for clinical reasons have opened the possibility to narrow down the gap between neurophysiological studies in animals and non-invasive (e.g. functional magnetic resonance imaging, electroencephalogram, magnetoencephalography) investigations in humans. Here we provide a description of the main procedures for electrode implantation and recordings, the experimental paradigms used and the main steps for processing the data. We also present key characteristics of the so-called ‘concept cells’, neurons in the human medial temporal lobe with selective and invariant responses that represent the meaning of the stimulus, and discuss their proposed role in declarative memory. Finally, we present novel results dealing with the stability of the representation given by these neurons, by studying the effect of stimulus repetition in the strength of the responses. In particular, we show that, after an initial decay, the response strength reaches an asymptotic value after approximately 15 presentations that remains above baseline for the whole duration of the experiment. PMID:25163775
Rift Valley Fever: An Emerging Mosquito-Borne Disease.
Linthicum, Kenneth J; Britch, Seth C; Anyamba, Assaf
2016-01-01
Rift Valley fever (RVF), an emerging mosquito-borne zoonotic infectious viral disease caused by the RVF virus (RVFV) (Bunyaviridae: Phlebovirus), presents significant threats to global public health and agriculture in Africa and the Middle East. RVFV is listed as a select agent with significant potential for international spread and use in bioterrorism. RVFV has caused large, devastating periodic epizootics and epidemics in Africa over the past ∼60 years, with severe economic and nutritional impacts on humans from illness and livestock loss. In the past 15 years alone, RVFV caused tens of thousands of human cases, hundreds of human deaths, and more than 100,000 domestic animal deaths. Cattle, sheep, goats, and camels are particularly susceptible to RVF and serve as amplifying hosts for the virus. This review highlights recent research on RVF, focusing on vectors and their ecology, transmission dynamics, and use of environmental and climate data to predict disease outbreaks. Important directions for future research are also discussed.
NASA Technical Reports Server (NTRS)
Andringa, Jason M.; Gray, Andrew A.
2005-01-01
A pre-phase A idea-generation team at the Jet Propulsion Laboratory (JPL), has conducted a study to rank all locations in the solar system based on attractiveness for human exploration. The process used to perform the study was composed of the following primary steps: determination of criteria (including value, cost, and risk criteria) upon which to rate sites in the solar system; weighting of the criteria based upon importance to eventual human exploration; selection of sites to consider and assignment of team members to the task of advocating the benefits of particular sites; rating the sites in both the short- and longterm based on team member presentations and team discussions; compilation of a score based on criteria weights and individual ratings. Finally a comparison of the total scores of different sites was completed to determine a ranking of all the bodies and sites in the solar system. Sensitivity analysis was also performed to determine how weightings affect the rankings.
Microbiome Therapeutics – Advances and Challenges
Mimee, Mark; Citorik, Robert J.; Lu, Timothy K.
2016-01-01
The microbial community that lives on and in the human body exerts a major impact on human health, from metabolism to immunity. In order to leverage the close associations between microbes and their host, development of therapeutics targeting the microbiota has surged in recent years. Here, we discuss current additive and subtractive strategies to manipulate the microbiota, focusing on bacteria engineered to produce therapeutic payloads, consortia of natural organisms and selective antimicrobials. Further, we present challenges faced by the community in the development of microbiome therapeutics, including designing microbial therapies that are adapted for specific geographies in the body, stable colonization with microbial therapies, discovery of clinically relevant biosensors, robustness of engineered synthetic gene circuits and addressing safety and biocontainment concerns. Moving forward, collaboration between basic and applied researchers and clinicians to address these challenges will poise the field to herald an age of next-generation, cellular therapies that draw on novel findings in basic research to inform directed augmentation of the human microbiota. PMID:27158095
Microbiome therapeutics - Advances and challenges.
Mimee, Mark; Citorik, Robert J; Lu, Timothy K
2016-10-01
The microbial community that lives on and in the human body exerts a major impact on human health, from metabolism to immunity. In order to leverage the close associations between microbes and their host, development of therapeutics targeting the microbiota has surged in recent years. Here, we discuss current additive and subtractive strategies to manipulate the microbiota, focusing on bacteria engineered to produce therapeutic payloads, consortia of natural organisms and selective antimicrobials. Further, we present challenges faced by the community in the development of microbiome therapeutics, including designing microbial therapies that are adapted for specific geographies in the body, stable colonization with microbial therapies, discovery of clinically relevant biosensors, robustness of engineered synthetic gene circuits and addressing safety and biocontainment concerns. Moving forward, collaboration between basic and applied researchers and clinicians to address these challenges will poise the field to herald an age of next-generation, cellular therapies that draw on novel findings in basic research to inform directed augmentation of the human microbiota. Copyright © 2016. Published by Elsevier B.V.
Properties of different selection signature statistics and a new strategy for combining them.
Ma, Y; Ding, X; Qanbari, S; Weigend, S; Zhang, Q; Simianer, H
2015-11-01
Identifying signatures of recent or ongoing selection is of high relevance in livestock population genomics. From a statistical perspective, determining a proper testing procedure and combining various test statistics is challenging. On the basis of extensive simulations in this study, we discuss the statistical properties of eight different established selection signature statistics. In the considered scenario, we show that a reasonable power to detect selection signatures is achieved with high marker density (>1 SNP/kb) as obtained from sequencing, while rather small sample sizes (~15 diploid individuals) appear to be sufficient. Most selection signature statistics such as composite likelihood ratio and cross population extended haplotype homozogysity have the highest power when fixation of the selected allele is reached, while integrated haplotype score has the highest power when selection is ongoing. We suggest a novel strategy, called de-correlated composite of multiple signals (DCMS) to combine different statistics for detecting selection signatures while accounting for the correlation between the different selection signature statistics. When examined with simulated data, DCMS consistently has a higher power than most of the single statistics and shows a reliable positional resolution. We illustrate the new statistic to the established selective sweep around the lactase gene in human HapMap data providing further evidence of the reliability of this new statistic. Then, we apply it to scan selection signatures in two chicken samples with diverse skin color. Our analysis suggests that a set of well-known genes such as BCO2, MC1R, ASIP and TYR were involved in the divergent selection for this trait.
Pan, Sheng; Rush, John; Peskind, Elaine R; Galasko, Douglas; Chung, Kathryn; Quinn, Joseph; Jankovic, Joseph; Leverenz, James B; Zabetian, Cyrus; Pan, Catherine; Wang, Yan; Oh, Jung Hun; Gao, Jean; Zhang, Jianpeng; Montine, Thomas; Zhang, Jing
2008-02-01
Targeted quantitative proteomics by mass spectrometry aims to selectively detect one or a panel of peptides/proteins in a complex sample and is particularly appealing for novel biomarker verification/validation because it does not require specific antibodies. Here, we demonstrated the application of targeted quantitative proteomics in searching, identifying, and quantifying selected peptides in human cerebrospinal spinal fluid (CSF) using a matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (MALDI TOF/TOF)-based platform. The approach involved two major components: the use of isotopic-labeled synthetic peptides as references for targeted identification and quantification and a highly selective mass spectrometric analysis based on the unique characteristics of the MALDI instrument. The platform provides high confidence for targeted peptide detection in a complex system and can potentially be developed into a high-throughput system. Using the liquid chromatography (LC) MALDI TOF/TOF platform and the complementary identification strategy, we were able to selectively identify and quantify a panel of targeted peptides in the whole proteome of CSF without prior depletion of abundant proteins. The effectiveness and robustness of the approach associated with different sample complexity, sample preparation strategies, as well as mass spectrometric quantification were evaluated. Other issues related to chromatography separation and the feasibility for high-throughput analysis were also discussed. Finally, we applied targeted quantitative proteomics to analyze a subset of previously identified candidate markers in CSF samples of patients with Parkinson's disease (PD) at different stages and Alzheimer's disease (AD) along with normal controls.
A comparison of biological and cultural evolution.
Portin, Petter
2015-03-01
This review begins with a definition of biological evolution and a description of its general principles. This is followed by a presentation of the biological basis of culture, specifically the concept of social selection. Further, conditions for cultural evolution are proposed, including a suggestion for language being the cultural replicator corresponding to the concept of the gene in biological evolution. Principles of cultural evolution are put forward and compared to the principles of biological evolution. Special emphasis is laid on the principle of selection in cultural evolution, including presentation of the concept of cultural fitness. The importance of language as a necessary condition for cultural evolution is stressed. Subsequently, prime differences between biological and cultural evolution are presented, followed by a discussion on interaction of our genome and our culture. The review aims at contributing to the present discussion concerning the modern development of the general theory of evolution, for example by giving a tentative formulation of the necessary and sufficient conditions for cultural evolution, and proposing that human creativity and mind reading or theory of mind are motors specific for it. The paper ends with the notion of the still ongoing coevolution of genes and culture.
New Challenges for Intervertebral Disc Treatment Using Regenerative Medicine
Masuda, Koichi
2010-01-01
The development of tissue engineering therapies for the intervertebral disc is challenging due to ambiguities of disease and pain mechanisms in patients, and lack of consensus on preclinical models for safety and efficacy testing. Although the issues associated with model selection for studying orthopedic diseases or treatments have been discussed often, the multifaceted challenges associated with developing intervertebral disc tissue engineering therapies require special discussion. This review covers topics relevant to the clinical translation of tissue-engineered technologies: (1) the unmet clinical need, (2) appropriate models for safety and efficacy testing, (3) the need for standardized model systems, and (4) the translational pathways leading to a clinical trial. For preclinical evaluation of new therapies, we recommend establishing biologic plausibility of efficacy and safety using models of increasing complexity, starting with cell culture, small animals (rats and rabbits), and then large animals (goat and minipig) that more closely mimic nutritional, biomechanical, and surgical realities of human application. The use of standardized and reproducible experimental procedures and outcome measures is critical for judging relative efficacy. Finally, success will hinge on carefully designed clinical trials with well-defined patient selection criteria, gold-standard controls, and objective outcome metrics to assess performance in the early postoperative period. PMID:19903086
Are Evolution and the Intracellular Innate Immune System Key Determinants in HIV Transmission?
Sumner, Rebecca P.; Thorne, Lucy G.; Fink, Doug L.; Khan, Hataf; Milne, Richard S.; Towers, Greg J.
2017-01-01
HIV-1 is the single most important sexually transmitted disease in humans from a global health perspective. Among human lentiviruses, HIV-1 M group has uniquely achieved pandemic levels of human-to-human transmission. The requirement to transmit between hosts likely provides the strongest selective forces on a virus, as without transmission, there can be no new infections within a host population. Our perspective is that evolution of all of the virus–host interactions, which are inherited and perpetuated from host-to-host, must be consistent with transmission. For example, CXCR4 use, which often evolves late in infection, does not favor transmission and is therefore lost when a virus transmits to a new host. Thus, transmission inevitably influences all aspects of virus biology, including interactions with the innate immune system, and dictates the biological niche in which the virus exists in the host. A viable viral niche typically does not select features that disfavor transmission. The innate immune response represents a significant selective pressure during the transmission process. In fact, all viruses must antagonize and/or evade the mechanisms of the host innate and adaptive immune systems that they encounter. We believe that viewing host–virus interactions from a transmission perspective helps us understand the mechanistic details of antiviral immunity and viral escape. This is particularly true for the innate immune system, which typically acts from the very earliest stages of the host–virus interaction, and must be bypassed to achieve successful infection. With this in mind, here we review the innate sensing of HIV, the consequent downstream signaling cascades and the viral restriction that results. The centrality of these mechanisms to host defense is illustrated by the array of countermeasures that HIV deploys to escape them, despite the coding constraint of a 10 kb genome. We consider evasion strategies in detail, in particular the role of the HIV capsid and the viral accessory proteins highlighting important unanswered questions and discussing future perspectives. PMID:29056936
Directional and balancing selection in human beta-defensins.
Hollox, Edward J; Armour, John A L
2008-04-16
In primates, infection is an important force driving gene evolution, and this is reflected in the importance of infectious disease in human morbidity today. The beta-defensins are key components of the innate immune system, with antimicrobial and cell signalling roles, but also reproductive functions. Here we examine evolution of beta-defensins in catarrhine primates and variation within different human populations. We show that five beta-defensin genes that do not show copy number variation in humans show evidence of positive selection in catarrhine primates, and identify specific codons that have been under selective pressure. Direct haplotyping of DEFB127 in humans suggests long-term balancing selection: there are two highly diverged haplotype clades carrying different variants of a codon that, in primates, is positively selected. For DEFB132, we show that extensive diversity, including a four-state amino acid polymorphism (valine, isoleucine, alanine and threonine at position 93), is present in hunter-gatherer populations, both African and non-African, but not found in samples from agricultural populations. Some, but not all, beta-defensin genes show positive selection in catarrhine primates. There is suggestive evidence of different selective pressures on these genes in humans, but the nature of the selective pressure remains unclear and is likely to differ between populations.
Roudi, Raheleh; Syn, Nicholas L; Roudbary, Maryam
2017-01-01
Antimicrobial peptides (AMPs) are a pervasive and evolutionarily ancient component of innate host defense which is present in virtually all classes of life. In recent years, evidence has accumulated that parallel or de novo mechanisms by which AMPs curb infectious pathologies are also effective at restraining cancer cell proliferation and dissemination, and have consequently stimulated significant interest in their deployment as novel biologic and immunotherapeutic agents against human malignancies. In this review, we explicate the biochemical underpinnings of their tumor-selectivity, and discuss results of recent clinical trials (outside of oncologic indications) which substantiate their safety and tolerability profiles. Next, we present evidence for their preclinical antitumor activity, systematically organized by the major and minor classes of natural AMPs. Finally, we discuss the barriers to their clinical implementation and envision directions for further development.
Early childhood development: putting knowledge into action.
2000-11-01
As part of its continuing mission to serve trustees and staff of health foundations and corporate giving programs, Grantmakers In Health (GIH) convened a select group of grantmakers and national experts who have made a major commitment to improve the health and well being of young children. The roundtable explored the latest research examining early childhood development, as well as public and private programs serving families with young children. The discussion ultimately centered upon the importance of grantmaker involvement to improve early childhood development, including the services delivered to young children and their families, training for professionals, and continued research and evaluation. This report brings together key points from the day's discussion with factual information on demographic, health and human services, and public policy trends drawn from a background paper prepared for the meeting. When available, recent findings, facts, and figures have been incorporated.
Exploiting genomics and natural genetic variation to decode macrophage enhancers
Romanoski, Casey E.; Link, Verena M.; Heinz, Sven; Glass, Christopher K.
2015-01-01
The mammalian genome contains on the order of a million enhancer-like regions that are required to establish the identities and functions of specific cell types. Here, we review recent studies in immune cells that have provided insight into the mechanisms that selectively activate certain enhancers in response to cell lineage and environmental signals. We describe a working model wherein distinct classes of transcription factors define the repertoire of active enhancers in macrophages through collaborative and hierarchical interactions, and discuss important challenges to this model, specifically providing examples from T cells. We conclude by discussing the use of natural genetic variation as a powerful approach for decoding transcription factor combinations that play dominant roles in establishing the enhancer landscapes, and the potential that these insights have for advancing our understanding of the molecular causes of human disease. PMID:26298065
Cancer Chemoprevention by Phytochemicals: Nature's Healing Touch.
Zubair, Haseeb; Azim, Shafquat; Ahmad, Aamir; Khan, Mohammad Aslam; Patel, Girijesh Kumar; Singh, Seema; Singh, Ajay Pratap
2017-03-03
Phytochemicals are an important part of traditional medicine and have been investigated in detail for possible inclusion in modern medicine as well. These compounds often serve as the backbone for the synthesis of novel therapeutic agents. For many years, phytochemicals have demonstrated encouraging activity against various human cancer models in pre-clinical assays. Here, we discuss select phytochemicals-curcumin, epigallocatechin-3-gallate (EGCG), resveratrol, plumbagin and honokiol-in the context of their reported effects on the processes of inflammation and oxidative stress, which play a key role in tumorigenesis. We also discuss the emerging evidence on modulation of tumor microenvironment by these phytochemicals which can possibly define their cancer-specific action. Finally, we provide recent updates on how low bioavailability, a major concern with phytochemicals, is being circumvented and the general efficacy being improved, by synthesis of novel chemical analogs and nanoformulations.
2017-01-01
Does the progress in understanding evolutionary theory depend on the species that is doing the investigation? This question is difficult to answer scientifically, as we are dealing with an n = 1 scenario: every individual who has ever written about evolution is a human being. I will discuss, first, whether we get the correct answer to questions if we begin with ourselves and expand outwards, and second, whether we might fail to ask all the interesting questions unless we combat our tendencies to favour taxa that are close to us. As a whole, the human tendency to understand general biological phenomena via ‘putting oneself in another organism's shoes’ has upsides and downsides. As an upside, our intuitive ability to rethink strategies if the situation changes can lead to ready generation of adaptive hypotheses. Downsides occur if we trust this intuition too much, and particular danger zones exist for traits where humans are an unusual species. I argue that the levels of selection debate might have proceeded differently if human cooperation patterns were not so unique, as this brings about unique challenges in biology teaching; and that theoretical insights regarding inbreeding avoidance versus tolerance could have spread faster if we were not extrapolating our emotional reactions to incest disproportionately depending on whether we study animals or plants. I also discuss patterns such as taxonomic chauvinism, i.e. less attention being paid to species that differ more from human-like life histories. Textbooks on evolution reinforce such biases insofar as they present, as a default case, systems that resemble ours in terms of life cycles and other features (e.g. gonochorism). Additionally, societal norms may have led to incorrect null hypotheses such as females not mating multiply. PMID:29142112
Walsh, Kyle P.; Pasanen, Edward G.; McFadden, Dennis
2014-01-01
Human subjects performed in several behavioral conditions requiring, or not requiring, selective attention to visual stimuli. Specifically, the attentional task was to recognize strings of digits that had been presented visually. A nonlinear version of the stimulus-frequency otoacoustic emission (SFOAE), called the nSFOAE, was collected during the visual presentation of the digits. The segment of the physiological response discussed here occurred during brief silent periods immediately following the SFOAE-evoking stimuli. For all subjects tested, the physiological-noise magnitudes were substantially weaker (less noisy) during the tasks requiring the most visual attention. Effect sizes for the differences were >2.0. Our interpretation is that cortico-olivo influences adjusted the magnitude of efferent activation during the SFOAE-evoking stimulation depending upon the attention task in effect, and then that magnitude of efferent activation persisted throughout the silent period where it also modulated the physiological noise present. Because the results were highly similar to those obtained when the behavioral conditions involved auditory attention, similar mechanisms appear to operate both across modalities and within modalities. Supplementary measurements revealed that the efferent activation was spectrally global, as it was for auditory attention. PMID:24732070
Elia, I E
2013-09-01
Within 20 years, experimental selection of quantified "not too aggressive, not too fearful" behavior to human approach was shown in silver foxes (Vulpes vulpes) to produce a neotenic package of traits in adults: ability to seek, induce, and sustain contact (called friendly or rapport behavior); relatively short limbs and foreshortened skull/face; and light pigmentation areas. Earlier sexual maturation, prolonged receptivity, and larger litters were also noted. The increased estradiol supporting these changes was apparently also responsible for faster skeletal maturation, including earlier fusion of the basicranium causing tooth crowding, but also paedomorphic craniofacial proportions that we find attractive in our own and other species. In this paper, these important findings of the farm fox experiment are juxtaposed with insights from social psychology, physical anthropology, and neuroscience about facial beauty and reaction to it. Since many unrelated species show some or all of the neotenic package or domestication profile when they have achieved rapport past the juvenile stage, craniofacial proportions considered attractive are discussed as genetically and hormonally linked to the evolution of rapport--social contact, trust, and cooperation--whether by natural, intuitive, intentional, or mixed paths of selection.
Therapeutic Antibodies by Phage Display.
Shim, Hyunbo
2016-01-01
Antibody phage display is a major technological platform for the generation of fully human antibodies for therapeutic purposes. The in vitro binder selection by phage display allows researchers to have more extensive control over binding parameters and facilitates the isolation of clinical candidate antibodies with desired binding and/or functional profiles. Since the invention of antibody phage display in late 1980s, significant technological advancements in the design, construction, and selection of the antibody libraries have been made, and several fully human antibodies generated by phage display are currently approved or in various clinical development stages. In this review, the background and details of antibody phage display technology, and representative antibody libraries with natural or synthetic sequence diversity and different construction strategies are described. The generation, optimization, functional and biophysical properties, and preclinical and clinical developments of some of the phage display-derived therapeutic antibodies approved for use in patients or in late-stage clinical trials are also discussed. With evolving novel disease targets and therapeutic strategies, antibody phage display is expected to continue to play a central role in the development of the next generation of therapeutic antibodies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
García-Barreno, B; Palomo, C; Peñas, C; Delgado, T; Perez-Breña, P; Melero, J A
1989-01-01
Monoclonal antibodies directed against the glycoproteins of human respiratory syncytial virus were used in competitive enzyme-linked immunosorbent assays for topological mapping of epitopes. Whereas epitopes of the F glycoprotein could be ascribed to five nonoverlapping antigenic sites, anti-G antibodies recognized unique epitopes, many of whose competition profiles overlapped extensively. Variant viruses selected with a neutralizing (47F) anti-F antibody lost the binding for only 47F and 49F antibodies, which mapped in the same antigenic area. In contrast, viruses selected with an anti-G antibody lost the capacity to bind most of the anti-G antibodies, and their G protein was not recognized by an anti-virus antiserum, indicating major changes in the antigenic structure of the G molecule. Finally, we found great antigenic variation of the G protein among viral isolates. This occurred even within viruses of the same subtype with only limited divergence of amino acid sequence between strains. All of these data indicate marked differences in the antigenic organization of the G and F glycoproteins of respiratory syncytial virus; we discuss these differences in terms of the chemical structure of the glycoproteins. Images PMID:2463385
ERIC Educational Resources Information Center
Yoshida, Aya
2017-01-01
The aim of this paper is to analyse the actions of various actors involved in "global human resource development" and to clarify whether discussions on global human resources are based on local perspectives. The results of the analysis are as follows: 1) after the year 2000 began, industry started discussions on global human resources in…
Visual Attention and Applications in Multimedia Technologies
Le Callet, Patrick; Niebur, Ernst
2013-01-01
Making technological advances in the field of human-machine interactions requires that the capabilities and limitations of the human perceptual system are taken into account. The focus of this report is an important mechanism of perception, visual selective attention, which is becoming more and more important for multimedia applications. We introduce the concept of visual attention and describe its underlying mechanisms. In particular, we introduce the concepts of overt and covert visual attention, and of bottom-up and top-down processing. Challenges related to modeling visual attention and their validation using ad hoc ground truth are also discussed. Examples of the usage of visual attention models in image and video processing are presented. We emphasize multimedia delivery, retargeting and quality assessment of image and video, medical imaging, and the field of stereoscopic 3D images applications. PMID:24489403
Brazilian and Mexican experiences in the study of incipient domestication.
Lins Neto, Ernani Machado de Freitas; Peroni, Nivaldo; Casas, Alejandro; Parra, Fabiola; Aguirre, Xitlali; Guillén, Susana; Albuquerque, Ulysses Paulino
2014-04-02
Studies of domestication enables a better understanding of human cultures, landscape changes according to peoples' purposes, and evolutionary consequences of human actions on biodiversity. This review aimed at discussing concepts, hypotheses, and current trends in studies of domestication of plants, using examples of cases studied in regions of Mesoamerica and Brazil. We analyzed trends of ethnobiological studies contributing to document processes of domestication and to establish criteria for biodiversity conservation based on traditional ecological knowledge. Based on reviewing our own and other authors' studies we analyzed management patterns and evolutionary trends associated to domestication occurring at plant populations and landscape levels. Particularly, we systematized information documenting: ethnobotanical aspects about plant management and artificial selection mechanisms, morphological consequences of plant management, population genetics of wild and managed plant populations, trends of change in reproduction systems of plants associated to management, and other ecological and physiological aspects influenced by management and domestication. Based on the analysis of study cases of 20 native species of herbs, shrubs and trees we identified similar criteria of artificial selection in different cultural contexts of Mexico and Brazil. Similar evolutionary trends were also identified in morphology (selection in favor of gigantism of useful and correlated parts); organoleptic characteristics such as taste, toxicity, color, texture; reproductive biology, mainly breeding system, phenological changes, and population genetics aspects, maintenance or increasing of genetic diversity in managed populations, high gene flow with wild relatives and low structure maintained by artificial selection. Our review is a first attempt to unify research methods for analyzing a high diversity of processes. Further research should emphasize deeper analyses of contrasting and diverse cultural and ecological contexts for a better understanding of evolution under incipient processes of domestication. Higher research effort is particularly required in Brazil, where studies on this topic are scarcer than in Mexico but where diversity of human cultures managing their also high plant resources diversity offer high potential for documenting the diversity of mechanisms of artificial selection and evolutionary trends. Comparisons and evaluations of incipient domestication in the regions studied as well as the Andean area would significantly contribute to understanding origins and diffusion of the experience of managing and domesticating plants.
TU-CD-213-04: Panel Discussion
DOE Office of Scientific and Technical Information (OSTI.GOV)
Johnson, J.
As part of the AAPM’s Scope of Practice, medical physicists are expected to collaborate effectively with practioners and allied health care providers. Interpersonal skills such as communication, negotiation and persuasion are vital for successful collaboration to achieve shared goals. This session will provide some theoretical background of these interpersonal skills as well as specific techniques and practical tools to influence others. Applications of these interpersonal skills for administrative and human resource management purposes vital to medical physicists will be shared. Session attendees will gain knowledge and tools to help them effectively collaborate with administrative and physician leaders in areas suchmore » as capital and human resource selection, prioritization, and implementation. Participants will hear methods of how to articulate their goals and to understand the goals of administration, helping ensure alignment of purpose. Session speakers will present one of the topics: equipment selection, budget creation, contracts, and program-related policy development. Specifics may include designing a business case in language that administrators understand, calculating the prioritization of budget requests, and influencing policies for safe and effective care. Human resource topics may include staffing justification, recruitment for fit, employment contracts, and benefits. Speakers will provide examples in both radiation therapy and diagnostic imaging departments and will share experiences and outcomes of their approaches for better results. Learning Objectives: After this course attendees will be better able to Understand the shared goal between administrative and physicist leadership. Articulate the “why” of the technical or human resource need. Utilize communication, negotiation and persuasion tools to improve collaboration.« less
Couesnon, Aurélie; Aráoz, Rómulo; Iorga, Bogdan I.; Benoit, Evelyne; Reynaud, Morgane; Servent, Denis; Molgó, Jordi
2016-01-01
The cyclic imine toxin 20-methyl spirolide G (20-meSPX-G), produced by the toxigenic dinoflagellate Alexandrium ostenfeldii/Alexandrium peruvianum, has been previously reported to contaminate shellfish in various European coastal locations, as revealed by mouse toxicity bioassay. The aim of the present study was to determine its toxicological profile and its molecular target selectivity. 20-meSPX-G blocked nerve-evoked isometric contractions in isolated mouse neuromuscular preparations, while it had no action on contractions elicited by direct electrical stimulation, and reduced reversibly nerve-evoked compound muscle action potential amplitudes in anesthetized mice. Voltage-clamp recordings in Xenopus oocytes revealed that 20-meSPX-G potently inhibited currents evoked by ACh on Torpedo muscle-type and human α7 nicotinic acetylcholine receptors (nAChR), whereas lower potency was observed in human α4β2 nAChR. Competition-binding assays showed that 20-meSPX-G fully displaced [3H]epibatidine binding to HEK-293 cells expressing the human α3β2 (Ki = 0.040 nM), whereas a 90-fold lower affinity was detected in human α4β2 nAChR. The spirolide displaced [125I]α-bungarotoxin binding to Torpedo membranes (Ki = 0.028 nM) and in HEK-293 cells expressing chick chimeric α7-5HT3 nAChR (Ki = 0.11 nM). In conclusion, this is the first study to demonstrate that 20-meSPX-G is a potent antagonist of nAChRs, and its subtype selectivity is discussed on the basis of molecular docking models. PMID:27563924
McCloskey, Rebecca J; Karandikar, Sharvari
2018-04-01
Human milk sharing between peers is a common and growing practice. Although human milk has been unequivocally established as the ideal food source for infants, much stigma surrounds the practice of human milk sharing. Furthermore, there is little research examining peer-to-peer human milk sharing. Research Aim: We used the liberation health social work model to examine the experiences of mothers who have received donated human milk from a peer. Research questions were as follows: (a) What challenges do recipient mothers experience in peer-to-peer human milk sharing? (b) What supports do recipient mothers identify in peer-to-peer human milk sharing? Researchers conducted in-depth interviews with mothers ( N = 20) in the United States and Canada who were recipients of peer-to-peer human milk sharing. Researchers independently reviewed transcripts and completed open, axial, and selective coding. The authors discussed conflicts in theme identification until agreement was reached. Challenges to peer-to-peer human milk sharing were (a) substantial effort required to secure human milk; (b) institutional barriers; (c) milk bank specific barriers; and (d) lack of societal awareness and acceptance of human milk sharing. Facilitators included (a) informed decision making and transparency and (b) support from healthcare professionals. Despite risks and barriers, participants continued to pursue peer-to-peer human milk sharing. Informed by a liberation health framework, healthcare professionals-rather than universally discouraging human milk sharing between peers-should facilitate open dialogue with parents about the pros and cons of this practice and about screening recommendations to promote safety and mitigate risk.
Cultural Diversity in Nursing Education: Perils, Pitfalls, and Pearls
Bednarz, Hedi; Schim, Stephanie; Doorenbos, Ardith
2010-01-01
Increasing diversity in the classroom challenges nursing educators to identify issues that complicate teaching (perils), analyze barriers for themselves and their students (pitfalls), and select new strategies for working with nontraditional students (pearls). This article identifies concerns arising from attitudes and values within nursing and common approaches to diversity education, and then discusses key issues in nursing education that relate to human nature, culture, faculty workload, and student demographics. Finally, some strategies are proposed for increasing the effectiveness of professional preparation with diverse students through a focus on culturally congruent education and development of faculty cultural competence. PMID:20143759
Cultural diversity in nursing education: perils, pitfalls, and pearls.
Bednarz, Hedi; Schim, Stephanie; Doorenbos, Ardith
2010-05-01
Increasing diversity in the classroom challenges nursing educators to identify issues that complicate teaching (perils), analyze barriers for themselves and their students (pitfalls), and select new strategies for working with nontraditional students (pearls). This article identifies concerns arising from attitudes and values within nursing and common approaches to diversity education, and then discusses key issues in nursing education that relate to human nature, culture, faculty workload, and student demographics. Finally, some strategies are proposed for increasing the effectiveness of professional preparation with diverse students through a focus on culturally congruent education and development of faculty cultural competence.
Notable Images of the 2017 Total Solar Eclipse
NASA Astrophysics Data System (ADS)
Wilson, Teresa; Dahiwale, Aishwarya; Nemiroff, Robert; Bonnell, Jerry
2018-01-01
The "Great American Eclipse" – the total solar eclipse visible across the USA on 21 August 2017 – resulted in some notable eclipse images and videos high in educational and scientific value. Some of the images that were selected to appear on the Astronomy Picture of the Day (APOD) website are shown in high resolution accompanied by educational descriptions. The questions of whether this eclipse was the most viewed and the most photographed event of any type in human history will be discussed. People are invited to come by and share their own eclipse images and stories.
Review of the GAS3 Family of Proteins and their Relevance to Cancer
Ashki, Negin; Gordon, Lynn; Wadehra, Madhuri
2017-01-01
The GAS3 family of tetraspan proteins has recently been implicated in the progression of cancer. Currently, six members of the GAS3 family have been identified in humans and mice, and while their expressions in disease vary, data suggest that they play a role in epithelial cell structure and function. In this review, we highlight the studies implicating four of the members in disease pathogenesis as well as probe the structural similarities between the family members. Finally, the impact of targeting select members of the family such as PMP22 and EMP2 is discussed. PMID:27279240
Review of the GAS3 Family of Proteins and their Relevance to Cancer.
Ashki, Negin; Gordon, Lynn; Wadehra, Madhuri
2015-01-01
The GAS3 family of tetraspan proteins has recently been implicated in the progression of cancer. Currently, six members of the GAS3 family have been identified in humans and mice, and while their expressions in disease vary, data suggest that they play a role in epithelial cell structure and function. In this review, we highlight the studies implicating four of the members in disease pathogenesis as well as probe the structural similarities between the family members. Finally, the impact of targeting select members of the family such as PMP22 and EMP2 is discussed.
Public Health Threat of New, Reemerging, and Neglected Zoonoses in the Industrialized World
Cutler, Sally J.; Fooks, Anthony R.
2010-01-01
Microbiologic infections acquired from animals, known as zoonoses, pose a risk to public health. An estimated 60% of emerging human pathogens are zoonotic. Of these pathogens, >71% have wildlife origins. These pathogens can switch hosts by acquiring new genetic combinations that have altered pathogenic potential or by changes in behavior or socioeconomic, environmental, or ecologic characteristics of the hosts. We discuss causal factors that influence the dynamics associated with emergence or reemergence of zoonoses, particularly in the industrialized world, and highlight selected examples to provide a comprehensive view of their range and diversity. PMID:20031035
ERIC Educational Resources Information Center
Congress of the U.S., Washington, DC. Senate Committee on Labor and Human Resources.
This document presents testimony regarding the impact of violence on children. The opening statement of Senator Dodd discusses the exposure of American children to violence and notes the Senator's introduction of the "Child and Family Services and Law Enforcement Partnership Act," an act proposed to provide children exposed to violence…
The inflammatory protein Pentraxin 3 in cardiovascular disease.
Fornai, Francesco; Carrizzo, Albino; Forte, Maurizio; Ambrosio, Mariateresa; Damato, Antonio; Ferrucci, Michela; Biagioni, Francesca; Busceti, Carla; Puca, Annibale A; Vecchione, Carmine
2016-01-01
The acute phase protein Pentraxin 3 (PTX3) plays a non-redundant role as a soluble pattern recognition receptor for selected pathogens and it represents a rapid biomarker for primary local activation of innate immunity and inflammation. Recent evidence indicates that PTX3 exerts an important role in modulating the cardiovascular system in humans and experimental models. In particular, there are conflicting points concerning the effects of PTX3 in cardiovascular diseases (CVD) since several observations indicate a cardiovascular protective effect of PTX3 while others speculate that the increased plasma levels of PTX3 in subjects with CVD correlate with disease severity and with poor prognosis in elderly patients. In the present review, we discuss the multifaceted effects of PTX3 on the cardiovascular system focusing on its involvement in atherosclerosis, endothelial function, hypertension, myocardial infarction and angiogenesis. This may help to explain how the specific modulation of PTX3 such as the use of different dosing, time, and target organs could help to contain different vascular diseases. These opposite actions of PTX3 will be emphasized concerning the modulation of cardiovascular system where potential therapeutic implications of PTX3 in humans are discussed.
Drangert, Jan-Olof; Nawab, Bahadar
2011-01-01
The sanitation issue is entering the development discussion and the UN proclaimed 2008 the year of sanitation. The study aims to understand the cultural-spatial dimension among Muslim communities of excreting and recirculating human excreta in North West Frontier Province in Pakistan. Information on local perceptions and cultural understanding was collected through interviews, group discussions and observations in four selected villages. The study identifies a diversity of excreting practices among age groups and sexes, and varied adherence to expressed cultural norms. Interviewees express less resentment towards urine compared to faeces, however, their negative attitude subsides when faecal matter is mixed with water since this changes appearance, odour-and cultural meaning. Religious dictums about excreta and sewage accommodate contradicting routine behaviours to cater for needs of residents and farmers. For example, when mothers pray wearing soiled clothing, and in the use of wastewater as fertiliser for food production. The excreta-related practices are compatible with good hygienic behaviour as outlined by WHO Guidelines, except for children who are allowed to defecate anywhere. Copyright © 2010 Elsevier Ltd. All rights reserved.
Rai, Amit; Aboumanei, Mohamed H.; Verma, Suraj P.; Kumar, Sachidanand; Raj, Vinit
2017-01-01
Introduction: Ebola Virus Disease (EVD) is caused by Ebola virus, which is often accompanied by fatal hemorrhagic fever upon infection in humans. This virus has caused the majority of deaths in human. There are no proper vaccinations and medications available for EVD. It is pivoting the attraction of scientist to develop the potent vaccination or novel lead to inhibit Ebola virus. Methods & Materials: In the present study, we developed 3D-QSAR and the pharmacophoric model from the previous reported potent compounds for the Ebola virus. Results & Discussion: Results & Discussion: The pharmacophoric model AAAP.116 was generated with better survival value and selectivity. Moreover, the 3D-QSAR model also showed the best r2 value 0.99 using PLS factor. Thereby, we found the higher F value, which demonstrated the statistical significance of both the models. Furthermore, homological modeling and molecular docking study were performed to analyze the affinity of the potent lead. This showed the best binding energy and bond formation with targeted protein. Conclusion: Finally, all the results of this study concluded that 3D-QSAR and Pharmacophore models may be helpful to search potent lead for EVD treatment in future. PMID:29387271
Genomic and metagenomic technologies to explore the antibiotic resistance mobilome.
Martínez, José L; Coque, Teresa M; Lanza, Val F; de la Cruz, Fernando; Baquero, Fernando
2017-01-01
Antibiotic resistance is a relevant problem for human health that requires global approaches to establish a deep understanding of the processes of acquisition, stabilization, and spread of resistance among human bacterial pathogens. Since natural (nonclinical) ecosystems are reservoirs of resistance genes, a health-integrated study of the epidemiology of antibiotic resistance requires the exploration of such ecosystems with the aim of determining the role they may play in the selection, evolution, and spread of antibiotic resistance genes, involving the so-called resistance mobilome. High-throughput sequencing techniques allow an unprecedented opportunity to describe the genetic composition of a given microbiome without the need to subculture the organisms present inside. However, bioinformatic methods for analyzing this bulk of data, mainly with respect to binning each resistance gene with the organism hosting it, are still in their infancy. Here, we discuss how current genomic methodologies can serve to analyze the resistance mobilome and its linkage with different bacterial genomes and metagenomes. In addition, we describe the drawbacks of current methodologies for analyzing the resistance mobilome, mainly in cases of complex microbiotas, and discuss the possibility of implementing novel tools to improve our current metagenomic toolbox. © 2016 New York Academy of Sciences.
The human brain—from cells to society
Hoogland, Eva; Patten, Iain; Berghmans, Stephane
2013-01-01
In December 2011, the European Science Foundation (ESF) brought together experts from a wide range of disciplines to discuss the issues that will influence the development of a healthier, more brain-aware European society. This perspective summarizes the main outcomes of that discussion and highlights important considerations to support improved mental health in Europe, including: The development of integrated neuropsychotherapeutic approaches to the treatment of psychiatric disorders.The development of more valid disease models for research into psychiatric disorders.An improved understanding of the relationship between biology and environment, particularly in relation to developmental plasticity and emerging pathology.More comparative studies to explore how scientific concepts relating to the human brain are received and understood in different sociocultural contexts.Research into the legal and ethical implications of recent developments in the brain sciences, including behavioral screening and manipulation, and emerging neurotechnologies. The broad geographical spread of the consulted experts across the whole of Europe, along with the wide range of disciplines they represent, gives these conclusions a strong scientific and pan-European endorsement. The next step will be to look closely into these five selected topics, in terms of research strategy, science policy, societal implications, and legal and ethical frameworks. PMID:23966920
Lipidomics of human brain aging and Alzheimer's disease pathology.
Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald
2015-01-01
Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.
Genome-wide scans for loci under selection in humans
2005-01-01
Natural selection, which can be defined as the differential contribution of genetic variants to future generations, is the driving force of Darwinian evolution. Identifying regions of the human genome that have been targets of natural selection is an important step in clarifying human evolutionary history and understanding how genetic variation results in phenotypic diversity, it may also facilitate the search for complex disease genes. Technological advances in high-throughput DNA sequencing and single nucleotide polymorphism genotyping have enabled several genome-wide scans of natural selection to be undertaken. Here, some of the observations that are beginning to emerge from these studies will be reviewed, including evidence for geographically restricted selective pressures (ie local adaptation) and a relationship between genes subject to natural selection and human disease. In addition, the paper will highlight several important problems that need to be addressed in future genome-wide studies of natural selection. PMID:16004726
The role of metals in mammalian olfaction of low molecular weight organosulfur compounds
Block, Eric; Batista, Victor S.; Matsunami, Hiroaki; Zhuang, Hanyi; Ahmed, Lucky
2017-01-01
While suggestions concerning the possible role of metals in olfaction and taste date back 50 years, only recently has it been possible to confirm these proposals with experiments involving individual olfactory receptors (ORs). A detailed discussion of recent experimental results demonstrating the key role of metals in enhancing the response of human and other vertebrate ORs to specific odorants is presented against the backdrop of our knowledge of how the sense of smell functions both at the molecular and whole animal levels. This review emphasizes the role of metals in the detection of low molecular weight thiols, sulfides, and other organosulfur compounds, including those found in strong-smelling animal excretions and plant volatiles, and those used in gas odorization. Alternative theories of olfaction are described, with evidence favoring the modified “shape” theory. The use of quantum mechanical/molecular modeling (QM/MM), site-directed mutagenesis and saturation-transfer-difference (STD) NMR is discussed, providing support for biological studies of mouse and human receptors, MOR244-3 and OR OR2T11, respectively. Copper is bound at the active site of MOR244-3 by cysteine and histidine, while cysteine, histidine and methionine are involved with OR2T11. The binding pockets of these two receptors are found in different locations in the three-dimensional seven transmembrane models. Another recently deorphaned human olfactory receptor, OR2M3, highly selective for a thiol from onions, and a broadly-tuned thiol receptor, OR1A1, are also discussed. Other topics covered include the effects of nanoparticles and heavy metal toxicants on vertebrate and fish ORs, intranasal zinc products and the loss of smell (anosmia). PMID:28471462
Pinsk, Mark A; Arcaro, Michael; Weiner, Kevin S; Kalkus, Jan F; Inati, Souheil J; Gross, Charles G; Kastner, Sabine
2009-05-01
Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part-selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part-selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between the two species and provide an initial step toward establishing functionally homologous category-selective areas.
Neural Representations of Faces and Body Parts in Macaque and Human Cortex: A Comparative fMRI Study
Pinsk, Mark A.; Arcaro, Michael; Weiner, Kevin S.; Kalkus, Jan F.; Inati, Souheil J.; Gross, Charles G.; Kastner, Sabine
2009-01-01
Single-cell studies in the macaque have reported selective neural responses evoked by visual presentations of faces and bodies. Consistent with these findings, functional magnetic resonance imaging studies in humans and monkeys indicate that regions in temporal cortex respond preferentially to faces and bodies. However, it is not clear how these areas correspond across the two species. Here, we directly compared category-selective areas in macaques and humans using virtually identical techniques. In the macaque, several face- and body part–selective areas were found located along the superior temporal sulcus (STS) and middle temporal gyrus (MTG). In the human, similar to previous studies, face-selective areas were found in ventral occipital and temporal cortex and an additional face-selective area was found in the anterior temporal cortex. Face-selective areas were also found in lateral temporal cortex, including the previously reported posterior STS area. Body part–selective areas were identified in the human fusiform gyrus and lateral occipitotemporal cortex. In a first experiment, both monkey and human subjects were presented with pictures of faces, body parts, foods, scenes, and man-made objects, to examine the response profiles of each category-selective area to the five stimulus types. In a second experiment, face processing was examined by presenting upright and inverted faces. By comparing the responses and spatial relationships of the areas, we propose potential correspondences across species. Adjacent and overlapping areas in the macaque anterior STS/MTG responded strongly to both faces and body parts, similar to areas in the human fusiform gyrus and posterior STS. Furthermore, face-selective areas on the ventral bank of the STS/MTG discriminated both upright and inverted faces from objects, similar to areas in the human ventral temporal cortex. Overall, our findings demonstrate commonalities and differences in the wide-scale brain organization between the two species and provide an initial step toward establishing functionally homologous category-selective areas. PMID:19225169
Selection of antigenically advanced variants of seasonal influenza viruses.
Li, Chengjun; Hatta, Masato; Burke, David F; Ping, Jihui; Zhang, Ying; Ozawa, Makoto; Taft, Andrew S; Das, Subash C; Hanson, Anthony P; Song, Jiasheng; Imai, Masaki; Wilker, Peter R; Watanabe, Tokiko; Watanabe, Shinji; Ito, Mutsumi; Iwatsuki-Horimoto, Kiyoko; Russell, Colin A; James, Sarah L; Skepner, Eugene; Maher, Eileen A; Neumann, Gabriele; Klimov, Alexander I; Kelso, Anne; McCauley, John; Wang, Dayan; Shu, Yuelong; Odagiri, Takato; Tashiro, Masato; Xu, Xiyan; Wentworth, David E; Katz, Jacqueline M; Cox, Nancy J; Smith, Derek J; Kawaoka, Yoshihiro
2016-05-23
Influenza viruses mutate frequently, necessitating constant updates of vaccine viruses. To establish experimental approaches that may complement the current vaccine strain selection process, we selected antigenic variants from human H1N1 and H3N2 influenza virus libraries possessing random mutations in the globular head of the haemagglutinin protein (which includes the antigenic sites) by incubating them with human and/or ferret convalescent sera to human H1N1 and H3N2 viruses. We also selected antigenic escape variants from human viruses treated with convalescent sera and from mice that had been previously immunized against human influenza viruses. Our pilot studies with past influenza viruses identified escape mutants that were antigenically similar to variants that emerged in nature, establishing the feasibility of our approach. Our studies with contemporary human influenza viruses identified escape mutants before they caused an epidemic in 2014-2015. This approach may aid in the prediction of potential antigenic escape variants and the selection of future vaccine candidates before they become widespread in nature.
ERIC Educational Resources Information Center
Case, Beau David
2000-01-01
Library literature from the late 19th century to the present offers numerous guides to materials selection. Yet, collection development policies and lists of selection criteria are inadequate for humanities electronic texts. Libraries, humanities disciplines, and electronic texts are too complex for any rigid approach to acquisition. To meet goals…
Jagoda, Evelyn; Lawson, Daniel J; Wall, Jeffrey D; Lambert, David; Muller, Craig; Westaway, Michael; Leavesley, Matthew; Capellini, Terence D; Mirazón Lahr, Marta; Gerbault, Pascale; Thomas, Mark G; Migliano, Andrea Bamberg; Willerslev, Eske; Metspalu, Mait; Pagani, Luca
2018-01-01
Abstract Recent studies have reported evidence suggesting that portions of contemporary human genomes introgressed from archaic hominin populations went to high frequencies due to positive selection. However, no study to date has specifically addressed the postintrogression population dynamics of these putative cases of adaptive introgression. Here, for the first time, we specifically define cases of immediate adaptive introgression (iAI) in which archaic haplotypes rose to high frequencies in humans as a result of a selective sweep that occurred shortly after the introgression event. We define these cases as distinct from instances of selection on standing introgressed variation (SI), in which an introgressed haplotype initially segregated neutrally and subsequently underwent positive selection. Using a geographically diverse data set, we report novel cases of selection on introgressed variation in living humans and shortlist among these cases those whose selective sweeps are more consistent with having been the product of iAI rather than SI. Many of these novel inferred iAI haplotypes have potential biological relevance, including three that contain immune-related genes in West Siberians, South Asians, and West Eurasians. Overall, our results suggest that iAI may not represent the full picture of positive selection on archaically introgressed haplotypes in humans and that more work needs to be done to analyze the role of SI in the archaic introgression landscape of living humans. PMID:29220488
The genomics of selection in dogs and the parallel evolution between dogs and humans.
Wang, Guo-dong; Zhai, Weiwei; Yang, He-chuan; Fan, Ruo-xi; Cao, Xue; Zhong, Li; Wang, Lu; Liu, Fei; Wu, Hong; Cheng, Lu-guang; Poyarkov, Andrei D; Poyarkov, Nikolai A; Tang, Shu-sheng; Zhao, Wen-ming; Gao, Yun; Lv, Xue-mei; Irwin, David M; Savolainen, Peter; Wu, Chung-I; Zhang, Ya-ping
2013-01-01
The genetic bases of demographic changes and artificial selection underlying domestication are of great interest in evolutionary biology. Here we perform whole-genome sequencing of multiple grey wolves, Chinese indigenous dogs and dogs of diverse breeds. Demographic analysis show that the split between wolves and Chinese indigenous dogs occurred 32,000 years ago and that the subsequent bottlenecks were mild. Therefore, dogs may have been under human selection over a much longer time than previously concluded, based on molecular data, perhaps by initially scavenging with humans. Population genetic analysis identifies a list of genes under positive selection during domestication, which overlaps extensively with the corresponding list of positively selected genes in humans. Parallel evolution is most apparent in genes for digestion and metabolism, neurological process and cancer. Our study, for the first time, draws together humans and dogs in their recent genomic evolution.
Human Mars Landing Site and Impacts on Mars Surface Operations
NASA Technical Reports Server (NTRS)
Bussey, Ben; Hoffman, Stephen J.
2016-01-01
This paper describes NASA's initial steps for identifying and evaluating candidate Exploration Zones (EZs) and Regions of Interests (ROIs) for the first human crews that will explore the surface of Mars. NASA's current effort to define the exploration of this planet by human crews, known as the Evolvable Mars Campaign (EMC), provides the context in which these EZs and ROIs are being considered. The EMC spans all aspects of a human Mars mission including launch from Earth, transit to and from Mars, and operations on the surface of Mars. Studies related to Mars surface operations and related system capabilities have led to the current definition of an EZ as well as ROIs. An EZ is a collection of ROIs that are located within approximately 100 kilometers of a centralized landing site. ROIs are areas that are relevant for scientific investigation and/or development/maturation of capabilities and resources necessary for a sustainable human presence. The EZ also contains one or more landing sites and a habitation site that will be used by multiple human crews during missions to explore and utilize the ROIs within the EZ. With the EMC as a conceptual basis, the EZ model has been refined to a point where specific site selection criteria for scientific exploration and in situ resource utilization can be defined. In 2015 these criteria were distributed to the planetary sciences community and the in situ resource utilization and civil engineering communities as part of a call for EZ proposals. The resulting "First Landing Site/Exploration Zone Workshop for Human Missions to the Surface of Mars" was held in October 2015 during which 47 proposals for EZs and ROIs were presented and discussed. Proposed locations spanned all longitudes and all allowable latitudes (+/- 50 degrees). Proposed justification for selecting one of these EZs also spanned a significant portion of the scientific and resource criteria provided to the community. Workshop results will be used to prepare for follow-on workshops to refine our understanding of proposed EZs and ultimately select a single location to be explored and utilized by human crews. Another significant workshop outcome was a recognition that new data will be needed to refine our understanding of the value of proposed EZs. These new data will come in part from existing spacecraft at Mars and may come from future robotic Mars missions as appropriate consideration is given to these new data needs during mission definition and development.
Interactions of attention, emotion and motivation.
Raymond, Jane
2009-01-01
Although successful visually guided action begins with sensory processes and ends with motor control, the intervening processes related to the appropriate selection of information for processing are especially critical because of the brain's limited capacity to handle information. Three important mechanisms--attention, emotion and motivation--contribute to the prioritization and selection of information. In this chapter, the interplay between these systems is discussed with emphasis placed on interactions between attention (or immediate task relevance of stimuli) and emotion (or affective evaluation of stimuli), and between attention and motivation (or the predicted value of stimuli). Although numerous studies have shown that emotional stimuli modulate mechanisms of selective attention in humans, little work has been directed at exploring whether such interactions can be reciprocal, that is, whether attention can influence emotional response. Recent work on this question (showing that distracting information is typically devalued upon later encounters) is reviewed in the first half of the chapter. In the second half, some recent experiments exploring how prior value-prediction learning (i.e., learning to associate potential outcomes, good or bad, with specific stimuli) plays a role in visual selection and conscious perception. The results indicate that some aspects of motivation act on selection independently of traditionally defined attention and other aspects interact with it.
The good, the bad, and the timely: how temporal order and moral judgment influence causal selection
Reuter, Kevin; Kirfel, Lara; van Riel, Raphael; Barlassina, Luca
2014-01-01
Causal selection is the cognitive process through which one or more elements in a complex causal structure are singled out as actual causes of a certain effect. In this paper, we report on an experiment in which we investigated the role of moral and temporal factors in causal selection. Our results are as follows. First, when presented with a temporal chain in which two human agents perform the same action one after the other, subjects tend to judge the later agent to be the actual cause. Second, the impact of temporal location on causal selection is almost canceled out if the later agent did not violate a norm while the former did. We argue that this is due to the impact that judgments of norm violation have on causal selection—even if the violated norm has nothing to do with the obtaining effect. Third, moral judgments about the effect influence causal selection even in the case in which agents could not have foreseen the effect and did not intend to bring it about. We discuss our findings in connection to recent theories of the role of moral judgment in causal reasoning, on the one hand, and to probabilistic models of temporal location, on the other. PMID:25477851
Human Rights and Education. Comparative & International Education Series, Volume 3.
ERIC Educational Resources Information Center
Tarrow, Norma Bernstein, Ed.
This book discusses the relationship between human rights and education. Education is discussed both within the context of human rights, and as the ultimate sanction and guarantee of all human rights. Part 1, "Education as a Human Right," is comprised of the following chapters: (1) "Human Rights and Education: An Overview" (D.…
Bastien, Dominic; Ebert, Maximilian C C J C; Forge, Delphine; Toulouse, Jacynthe; Kadnikova, Natalia; Perron, Florent; Mayence, Annie; Huang, Tien L; Vanden Eynde, Jean Jacques; Pelletier, Joelle N
2012-04-12
The continuously increasing use of trimethoprim as a common antibiotic for medical use and for prophylactic application in terrestrial and aquatic animal farming has increased its prevalence in the environment. This has been accompanied by increased drug resistance, generally in the form of alterations in the drug target, dihydrofolate reductase (DHFR). The most highly resistant variants of DHFR are known as type II DHFR, among which R67 DHFR is the most broadly studied variant. We report the first attempt at designing specific inhibitors to this emerging drug target by fragment-based design. The detection of inhibition in R67 DHFR was accompanied by parallel monitoring of the human DHFR, as an assessment of compound selectivity. By those means, small aromatic molecules of 150-250 g/mol (fragments) inhibiting R67 DHFR selectively in the low millimolar range were identified. More complex, symmetrical bis-benzimidazoles and a bis-carboxyphenyl were then assayed as fragment-based leads, which procured selective inhibition of the target in the low micromolar range (K(i) = 2-4 μM). The putative mode of inhibition is discussed according to molecular modeling supported by in vitro tests. © 2012 American Chemical Society
Optimizing Experimental Design for Comparing Models of Brain Function
Daunizeau, Jean; Preuschoff, Kerstin; Friston, Karl; Stephan, Klaas
2011-01-01
This article presents the first attempt to formalize the optimization of experimental design with the aim of comparing models of brain function based on neuroimaging data. We demonstrate our approach in the context of Dynamic Causal Modelling (DCM), which relates experimental manipulations to observed network dynamics (via hidden neuronal states) and provides an inference framework for selecting among candidate models. Here, we show how to optimize the sensitivity of model selection by choosing among experimental designs according to their respective model selection accuracy. Using Bayesian decision theory, we (i) derive the Laplace-Chernoff risk for model selection, (ii) disclose its relationship with classical design optimality criteria and (iii) assess its sensitivity to basic modelling assumptions. We then evaluate the approach when identifying brain networks using DCM. Monte-Carlo simulations and empirical analyses of fMRI data from a simple bimanual motor task in humans serve to demonstrate the relationship between network identification and the optimal experimental design. For example, we show that deciding whether there is a feedback connection requires shorter epoch durations, relative to asking whether there is experimentally induced change in a connection that is known to be present. Finally, we discuss limitations and potential extensions of this work. PMID:22125485
Parasites and fungi as risk factors for human and animal health.
Góralska, Katarzyna; Błaszkowska, Joanna
2015-01-01
Recent literature data suggests that parasitic and fungal diseases, which pose a threat to both human and animal health, remain a clinical, diagnostic and therapeutic problem. Attention is increasingly paid to the role played by natural microbiota in maintaining homeostasis in humans. A particular emphasis is placed on the possibility of manipulating the human microbiota (permanent, transient, pathogenic) and macrobiota (e.g., Trichuris suis) to support the treatment of selected diseases such as Crohn's disease, obesity, diabetes and cancer. Emphasis is placed on important medical species whose infections not only impair health but can also be life threatening, such as Plasmodium falciparum, Echinococcus multilocularis and Baylisascaris procyonis, which expand into areas which have so far been uninhabited. This article also presents the epidemiology, diagnosis and treatment of opportunistic parasitoses imported from the tropics, which spread across large groups of people through human-to-human transmission (Enterobius vermicularis, Sarcoptes scabiei). It also discusses the problem of environmentally-conditioned parasitoses, particularly their etiological factors associated with food contaminated with invasive forms (Trichinella sp., Toxoplasma gondii). The analysis also concerns the presence of developmental forms of geohelminths (Toxocara sp.) and ectoparasites (ticks), which are vectors of serious human diseases (Lyme borreliosis, anaplasmosis, babesiosis), in the environment. Mycological topics contains rare cases of mycoses environmentally conditioned (CNS aspergillosis) and transmissions of these pathogens in a population of hospitalized individuals, as well as seeking new methods used to treat mycoses.
Søe, Martin Jensen; Nejsum, Peter; Fredensborg, Brian Lund; Kapel, Christian Moliin Outzen
2015-02-01
Ancient parasite eggs were recovered from environmental samples collected at a Viking-age settlement in Viborg, Denmark, dated 1018-1030 A.D. Morphological examination identified Ascaris sp., Trichuris sp., and Fasciola sp. eggs, but size and shape did not allow species identification. By carefully selecting genetic markers, PCR amplification and sequencing of ancient DNA (aDNA) isolates resulted in identification of: the human whipworm, Trichuris trichiura , using SSUrRNA sequence homology; Ascaris sp. with 100% homology to cox1 haplotype 07; and Fasciola hepatica using ITS1 sequence homology. The identification of T. trichiura eggs indicates that human fecal material is present and, hence, that the Ascaris sp. haplotype 07 was most likely a human variant in Viking-age Denmark. The location of the F. hepatica finding suggests that sheep or cattle are the most likely hosts. Further, we sequenced the Ascaris sp. 18S rRNA gene in recent isolates from humans and pigs of global distribution and show that this is not a suited marker for species-specific identification. Finally, we discuss ancient parasitism in Denmark and the implementation of aDNA analysis methods in paleoparasitological studies. We argue that when employing species-specific identification, soil samples offer excellent opportunities for studies of human parasite infections and of human and animal interactions of the past.
Human influences on evolution, and the ecological and societal consequences.
Hendry, Andrew P; Gotanda, Kiyoko M; Svensson, Erik I
2017-01-19
Humans have dramatic, diverse and far-reaching influences on the evolution of other organisms. Numerous examples of this human-induced contemporary evolution have been reported in a number of 'contexts', including hunting, harvesting, fishing, agriculture, medicine, climate change, pollution, eutrophication, urbanization, habitat fragmentation, biological invasions and emerging/disappearing diseases. Although numerous papers, journal special issues and books have addressed each of these contexts individually, the time has come to consider them together and thereby seek important similarities and differences. The goal of this special issue, and this introductory paper, is to promote and expand this nascent integration. We first develop predictions as to which human contexts might cause the strongest and most consistent directional selection, the greatest changes in evolutionary potential, the greatest genetic (as opposed to plastic) changes and the greatest effects on evolutionary diversification We then develop predictions as to the contexts where human-induced evolutionary changes might have the strongest effects on the population dynamics of the focal evolving species, the structure of their communities, the functions of their ecosystems and the benefits and costs for human societies. These qualitative predictions are intended as a rallying point for broader and more detailed future discussions of how human influences shape evolution, and how that evolution then influences species traits, biodiversity, ecosystems and humans.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'. © 2016 The Author(s).
Radiosynthesis and evaluation of novel acetylcholine receptor radioligands
NASA Astrophysics Data System (ADS)
Pimlott, Sally L.
Neuroreceptor single photon emission computed tomography (SPECT) imaging provides a powerful tool for the evaluation of the function of a neurotransmitter system in normal and or disease states in the living human brain. The cholinergic system is involved in the control of a variety of complex functions including learning, memory and modulation of behaviour. Deficits in the cholinergic system have been found in a number of neurological diseases, such as Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease and Epilepsy. Acetylcholine receptors (AChRs) are divided into two classes, muscarinic and nicotinic. The aim of this project was to develop two novel SPECT AChR ligands: (R,R)[123I]I-QNB, a M1 subtype selective muscarinic acetylcholine receptor (mAChR) ligand, and 5-[123I]-A-85380, a alpha4beta2 subtype selective nicotinic receptor (nAChR) ligand, for use in human SPECT imaging studies. The calculation of the binding potential of a ligand can be used to obtain quantitative information from a SPECT scan, enabling comparisons to be made between studies. Methodological issues involved in the calculation of binding potential are therefore crucial for the accuracy of results. A particularly important parameter is the amount of authentic radioligand available to cross the blood brain barrier. This was characterised in the research performed for this thesis. The radiosynthesis of two novel neuroreceptor radioligands has been optimised for use in humans. (R, R)[123I]I-QNB has been used in human studies to provide useful information on the human mAChR function in disease. Pre-clinical evaluation of 5-[123I]-A-85380 provided useful information for in vivo human studies. Both radioligands are concluded to successfully provide novel information on the function of the acetylcholine system. Methodological issues involved in the blood metabolite analysis and measurement of plasma protein binding have been investigated and discussed, with particular reference made to the factors that must be taken into account when designing these experiments. (Abstract shortened by ProQuest.).
Taste perception, associated hormonal modulation, and nutrient intake
Loper, Hillary B.; La Sala, Michael; Dotson, Cedrick
2015-01-01
It is well known that taste perception influences food intake. After ingestion, gustatory receptors relay sensory signals to the brain, which segregates, evaluates, and distinguishes the stimuli, leading to the experience known as “flavor.” It is well accepted that five taste qualities – sweet, salty, bitter, sour, and umami – can be perceived by animals. In this review, the anatomy and physiology of human taste buds, the hormonal modulation of taste function, the importance of genetic chemosensory variation, and the influence of gustatory functioning on macronutrient selection and eating behavior are discussed. Individual genotypic variation results in specific phenotypes of food preference and nutrient intake. Understanding the role of taste in food selection and ingestive behavior is important for expanding our understanding of the factors involved in body weight maintenance and the risk of chronic diseases including obesity, atherosclerosis, cancer, diabetes, liver disease, and hypertension. PMID:26024495
Sampling designs for HIV molecular epidemiology with application to Honduras.
Shepherd, Bryan E; Rossini, Anthony J; Soto, Ramon Jeremias; De Rivera, Ivette Lorenzana; Mullins, James I
2005-11-01
Proper sampling is essential to characterize the molecular epidemiology of human immunodeficiency virus (HIV). HIV sampling frames are difficult to identify, so most studies use convenience samples. We discuss statistically valid and feasible sampling techniques that overcome some of the potential for bias due to convenience sampling and ensure better representation of the study population. We employ a sampling design called stratified cluster sampling. This first divides the population into geographical and/or social strata. Within each stratum, a population of clusters is chosen from groups, locations, or facilities where HIV-positive individuals might be found. Some clusters are randomly selected within strata and individuals are randomly selected within clusters. Variation and cost help determine the number of clusters and the number of individuals within clusters that are to be sampled. We illustrate the approach through a study designed to survey the heterogeneity of subtype B strains in Honduras.
Cancer: A disease at the crossroads of trade-offs.
Jacqueline, Camille; Biro, Peter A; Beckmann, Christa; Moller, Anders Pape; Renaud, François; Sorci, Gabriele; Tasiemski, Aurélie; Ujvari, Beata; Thomas, Frédéric
2017-03-01
Central to evolutionary theory is the idea that living organisms face phenotypic and/or genetic trade-offs when allocating resources to competing life-history demands, such as growth, survival, and reproduction. These trade-offs are increasingly considered to be crucial to further our understanding of cancer. First, evidences suggest that neoplastic cells, as any living entities subject to natural selection, are governed by trade-offs such as between survival and proliferation. Second, selection might also have shaped trade-offs at the organismal level, especially regarding protective mechanisms against cancer. Cancer can also emerge as a consequence of additional trade-offs in organisms (e.g., eco-immunological trade-offs). Here, we review the wide range of trade-offs that occur at different scales and their relevance for understanding cancer dynamics. We also discuss how acknowledging these phenomena, in light of human evolutionary history, may suggest new guidelines for preventive and therapeutic strategies.
Würth, Roberto; Barbieri, Federica; Florio, Tullio
2014-01-01
Despite relevant progress obtained by multimodal treatment, glioblastoma (GBM), the most aggressive primary brain tumor, is still incurable. The most encouraging advancement of GBM drug research derives from the identification of cancer stem cells (CSCs), since these cells appear to represent the determinants of resistance to current standard therapies. The goal of most ongoing studies is to identify drugs able to affect CSCs biology, either inducing selective toxicity or differentiating this tumor cell population into nontumorigenic cells. Moreover, the therapeutic approach for GBM could be improved interfering with chemo- or radioresistance mechanisms, microenvironment signals, and the neoangiogenic process. During the last years, molecular targeted compounds such as sorafenib and old drugs, like metformin, displayed interesting efficacy in preclinical studies towards several tumors, including GBM, preferentially affecting CSC viability. In this review, the latest experimental results, controversies, and prospective application concerning these promising anticancer drugs will be discussed.
Monitoring technologies for ocean disposal of radioactive waste
NASA Astrophysics Data System (ADS)
Triplett, M. B.; Solomon, K. A.; Bishop, C. B.; Tyce, R. C.
1982-01-01
The feasibility of using carefully selected subseabed locations to permanently isolate high level radioactive wastes at ocean depths greater than 4000 meters is discussed. Disposal at several candidate subseabed areas is being studied because of the long term geologic stability of the sediments, remoteness from human activity, and lack of useful natural resources. While the deep sea environment is remote, it also poses some significant challenges for the technology required to survey and monitor these sites, to identify and pinpoint container leakage should it occur, and to provide the environmental information and data base essential to determining the probable impacts of any such occurrence. Objectives and technical approaches to aid in the selective development of advanced technologies for the future monitoring of nuclear low level and high level waste disposal in the deep seabed are presented. Detailed recommendations for measurement and sampling technology development needed for deep seabed nuclear waste monitoring are also presented.
Sylvetsky, Allison C.; Blau, Jenny E.; Rother, Kristina I.
2016-01-01
Consumption of foods, beverages, and packets containing low-calorie sweeteners (LCS) has increased markedly across gender, age, race/ethnicity, weight status, and socioeconomic subgroups. However, well-controlled intervention studies rigorously evaluating the health effects of LCS in humans are limited. One of the key questions is whether LCS are indeed a beneficial strategy for weight management and prevention of obesity. The current review discusses several methodological considerations in the design and interpretation of these studies. Specifically, we focus on the selection of study participants, inclusion of an appropriate control, importance of considering habitual LCS exposure, selection of specific LCS, dose and route of LCS administration, choice of study outcomes, and the context and generalizability of the study findings. These critical considerations will guide the design of future studies and thus assist in understanding the health effects of LCS. PMID:26936185
Sylvetsky, Allison C; Blau, Jenny E; Rother, Kristina I
2016-06-01
Consumption of foods, beverages, and packets containing low-calorie sweeteners (LCS) has increased markedly across gender, age, race/ethnicity, weight status, and socio-economic subgroups. However, well-controlled intervention studies rigorously evaluating the health effects of LCS in humans are limited. One of the key questions is whether LCS are indeed a beneficial strategy for weight management and prevention of obesity. The current review discusses several methodological considerations in the design and interpretation of these studies. Specifically, we focus on the selection of study participants, inclusion of an appropriate control, importance of considering habitual LCS exposure, selection of specific LCS, dose and route of LCS administration, choice of study outcomes, and the context and generalizability of the study findings. These critical considerations will guide the design of future studies and thus assist in understanding the health effects of LCS.
Moore, Holly; Geyer, Mark A; Carter, Cameron S; Barch, Deanna M
2013-11-01
Over the past two decades, the awareness of the disabling and treatment-refractory effects of impaired cognition in schizophrenia has increased dramatically. In response to this still unmet need in the treatment of schizophrenia, the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative was developed. The goal of CNTRICS is to harness cognitive neuroscience to develop a brain-based set of tools for measuring cognition in schizophrenia and to test new treatments. CNTRICS meetings focused on development of tasks with cognitive construct validity for use in both human and animal model studies. This special issue presents papers discussing the cognitive testing paradigms selected by CNTRICS for animal model systems. These paradigms are designed to measure cognitive constructs within the domains of perception, attention, executive function, working memory, object/relational long-term memory, and social/affective processes. Copyright © 2013. Published by Elsevier Ltd.
Bartrolí, J; Martin, M J; Rigola, M
2001-10-16
The great complexity of the nitrogen cycle, including anthropogenic contributions, makes it necessary to carry out local studies, which allow us to identify the specific cause-effect links in a particular society. Models of local societies that are based on methods such as Substance Flow Analysis (SFA), which study and characterise the performance of metabolic exchanges between human society and the environment, are a useful tools for directing local policy towards sustainable management of the nitrogen cycle. In this paper, the selection of geographical boundaries for SFA application is discussed. Data availability and accuracy, and the possibility of linking the results with instructions for decision making, are critical aspects for proper scale selection. The experience obtained in the construction of the model for Catalonia is used to draw attention to the difficulties found in regional studies.
USSR Space Life Sciences Digest, issue 7
NASA Technical Reports Server (NTRS)
Hooke, L. R. (Editor); Teeter, R. (Editor); Teeter, R. (Editor); Teeter, R. (Editor); Teeter, R. (Editor); Teeter, R. (Editor)
1986-01-01
This is the seventh issue of NASA's USSR Space Life Sciences Digest. It contains abstracts of 29 papers recently published in Russian language periodicals and bound collections and of 8 new Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. Additional features include two interviews with the Soviet Union's cosmonaut physicians and others knowledgable of the Soviet space program. The topics discussed at a Soviet conference on problems in space psychology are summarized. Information about English translations of Soviet materials available to readers is provided. The topics covered in this issue have been identified as relevant to 29 areas of aerospace medicine and space biology. These areas are adaptation, biospherics, body fluids, botany, cardiovascular and respiratory systems, developmental biology, endocrinology, enzymology, exobiology, genetics, habitability and environment effects, hematology, human performance, immunology, life support systems, mathematical modeling, metabolism, microbiology, morphology and cytology, musculoskeletal system, neurophysiology, nutrition, perception, personnel selection, psychology, radiobiology, and space medicine.
Dent, Kevin; Lestou, Vaia; Humphreys, Glyn W
2010-02-01
It has been argued that area hMT+/V5 in humans acts as a motion filter, enabling targets defined by a conjunction of motion and form to be efficiently selected. We present data indicating that (a) damage to parietal cortex leads to a selective problem in processing motion-form conjunctions, and (b) that the presence of a structurally and functional intact hMT+/V5 is not sufficient for efficient search for motion-form conjunctions. We suggest that, in addition to motion-processing areas (e.g., hMT+/V5), the posterior parietal cortex is necessary for efficient search with motion-form conjunctions, so that damage to either brain region may bring about deficits in search. We discuss the results in terms of the involvement of the posterior parietal cortex in the top-down guidance of search or in the binding of motion and form information.
Resting cerebral blood flow, attention, and aging.
Bertsch, Katja; Hagemann, Dirk; Hermes, Michael; Walter, Christof; Khan, Robina; Naumann, Ewald
2009-04-24
Aging is accompanied by a decline of fluid cognitive functions, e.g., a slowing of information processing, working memory, and division of attention. This is at least partly due to structural and functional changes in the aging brain. Although a decrement of resting cerebral blood flow (CBF) has been positively associated with cognitive functions in patients with brain diseases, studies with healthy participants have revealed inconsistent results. Therefore, we investigated the relation between resting cerebral blood flow and cognitive functions (tonic and phasic alertness, selective and divided attention) in two samples of healthy young and older participants. We found higher resting CBF and better cognitive performances in the young than in the older sample. In addition, resting CBF was inversely correlated with selective attention in the young and with tonic alertness in the elderly participants. This finding is discussed with regard to the neural efficiency hypothesis of human intelligence.
Moore, Holly; Geyer, Mark A.; Carter, Cameron S.; Barch, Deanna M.
2014-01-01
Over the past two decades, the awareness of the disabling and treatment-refractory effects of impaired cognition in schizophrenia has increased dramatically. In response to this still unmet need in the treatment of schizophrenia, the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative was developed. The goal of CNTRICS is to harness cognitive neuroscience to develop a brain-based set of tools for measuring cognition in schizophrenia and to test new treatments. CNTRICS meetings focused on development of tasks with cognitive construct validity for use in both human and animal model studies. This special issue presents papers discussing the cognitive testing paradigms selected by CNTRICS for animal model systems. These paradigms are designed to measure cognitive constructs within the domains of perception, attention, executive function, working memory, object/relational long-term memory, and social/affective processes. PMID:24090823
Coates, M D; Tekin, I; Vrana, K E; Mawe, G M
2017-09-01
Serotonin (5-hydroxytryptamine, 5-HT) is an important mediator of every major gut-related function. Recent investigations also suggest that 5-HT can influence the development and severity of inflammation within the gut, particularly in the setting of inflammatory bowel disease (IBD). To review the roles that the intestinal serotonin signalling system plays in gut function, with a specific focus on IBD. We reviewed manuscripts from 1952 to 2017 that investigated and discussed roles for 5-HT signalling in gastrointestinal function and IBD, as well as the influence of inflammation on 5-HT signalling elements within the gut. Inflammation appears to affect every major element of intestinal 5-HT signalling, including 5-HT synthesis, release, receptor expression and reuptake capacity. Importantly, many studies (most utilising animal models) also demonstrate that modulation of selective serotonergic receptors (via agonism of 5-HT 4 R and antagonism of 5-HT 3 R) or 5-HT signal termination (via serotonin reuptake inhibitors) can alter the likelihood and severity of intestinal inflammation and/or its complicating symptoms. However, there are few human studies that have studied these relationships in a targeted manner. Insights discussed in this review have strong potential to lead to new diagnostic and therapeutic tools to improve the management of IBD and other related disorders. Specifically, strategies that focus on modifying the activity of selective serotonin receptors and reuptake transporters in the gut could be effective for controlling disease activity and/or its associated symptoms. Further studies in humans are required, however, to more completely understand the pathophysiological mechanisms underlying the roles of 5-HT in this setting. © 2017 John Wiley & Sons Ltd.
Lewis, Jada; Dickson, Dennis W
2016-01-01
Tau is a microtubule-associated protein and a key regulator of microtubule stabilization as well as the main component of neurofibrillary tangles-a principle neuropathological hallmark of Alzheimer's disease (AD)-as well as pleomorphic neuronal and glial inclusions in neurodegenerative tauopathies. Cross-sectional studies of neurofibrillary pathology in AD reveal a stereotypic spatiotemporal pattern of neuronal vulnerability that correlates with disease severity; however, the relationship of this pattern to disease progression is less certain and exceptions to the typical pattern have been described in a subset of AD patients. The basis for the selective vulnerability of specific populations of neurons to tau pathology and cell death is largely unknown, although there have been a number of hypotheses based upon shared properties of vulnerable neurons (e.g., degree of axonal myelination or synaptic plasticity). A recent hypothesis for selective vulnerability takes into account the emerging science of functional connectivity based upon resting state functional magnetic resonance imaging, where subsets of neurons that fire synchronously define patterns of degeneration similar to specific neurodegenerative disorders, including various tauopathies. In the past 6 years, the concept of tau propagation has emerged from numerous studies in cell and animal models suggesting that tau moves from cell-to-cell and that this may trigger aggregation and region-to-region spread of tau pathology within the brain. How the spread of tau pathology relates to functional connectivity is an area of active investigation. Observations of templated folding and propagation of tau have prompted comparisons of tau to prions, the pathogenic proteins in transmissible spongiform encephalopathies. In this review, we discuss the most compelling studies in the field, discuss their shortcomings and consider their implications with respect to human tauopathies as well as the controversy that tauopathies may be prion-like disorders.
Genomic signatures of positive selection in humans and the limits of outlier approaches.
Kelley, Joanna L; Madeoy, Jennifer; Calhoun, John C; Swanson, Willie; Akey, Joshua M
2006-08-01
Identifying regions of the human genome that have been targets of positive selection will provide important insights into recent human evolutionary history and may facilitate the search for complex disease genes. However, the confounding effects of population demographic history and selection on patterns of genetic variation complicate inferences of selection when a small number of loci are studied. To this end, identifying outlier loci from empirical genome-wide distributions of genetic variation is a promising strategy to detect targets of selection. Here, we evaluate the power and efficiency of a simple outlier approach and describe a genome-wide scan for positive selection using a dense catalog of 1.58 million SNPs that were genotyped in three human populations. In total, we analyzed 14,589 genes, 385 of which possess patterns of genetic variation consistent with the hypothesis of positive selection. Furthermore, several extended genomic regions were found, spanning >500 kb, that contained multiple contiguous candidate selection genes. More generally, these data provide important practical insights into the limits of outlier approaches in genome-wide scans for selection, provide strong candidate selection genes to study in greater detail, and may have important implications for disease related research.
Genomics of local adaptation with gene flow.
Tigano, Anna; Friesen, Vicki L
2016-05-01
Gene flow is a fundamental evolutionary force in adaptation that is especially important to understand as humans are rapidly changing both the natural environment and natural levels of gene flow. Theory proposes a multifaceted role for gene flow in adaptation, but it focuses mainly on the disruptive effect that gene flow has on adaptation when selection is not strong enough to prevent the loss of locally adapted alleles. The role of gene flow in adaptation is now better understood due to the recent development of both genomic models of adaptive evolution and genomic techniques, which both point to the importance of genetic architecture in the origin and maintenance of adaptation with gene flow. In this review, we discuss three main topics on the genomics of adaptation with gene flow. First, we investigate selection on migration and gene flow. Second, we discuss the three potential sources of adaptive variation in relation to the role of gene flow in the origin of adaptation. Third, we explain how local adaptation is maintained despite gene flow: we provide a synthesis of recent genomic models of adaptation, discuss the genomic mechanisms and review empirical studies on the genomics of adaptation with gene flow. Despite predictions on the disruptive effect of gene flow in adaptation, an increasing number of studies show that gene flow can promote adaptation, that local adaptations can be maintained despite high gene flow, and that genetic architecture plays a fundamental role in the origin and maintenance of local adaptation with gene flow. © 2016 John Wiley & Sons Ltd.
Speech-associated gestures, Broca’s area, and the human mirror system
Skipper, Jeremy I.; Goldin-Meadow, Susan; Nusbaum, Howard C.; Small, Steven L
2009-01-01
Speech-associated gestures are hand and arm movements that not only convey semantic information to listeners but are themselves actions. Broca’s area has been assumed to play an important role both in semantic retrieval or selection (as part of a language comprehension system) and in action recognition (as part of a “mirror” or “observation–execution matching” system). We asked whether the role that Broca’s area plays in processing speech-associated gestures is consistent with the semantic retrieval/selection account (predicting relatively weak interactions between Broca’s area and other cortical areas because the meaningful information that speech-associated gestures convey reduces semantic ambiguity and thus reduces the need for semantic retrieval/selection) or the action recognition account (predicting strong interactions between Broca’s area and other cortical areas because speech-associated gestures are goal-direct actions that are “mirrored”). We compared the functional connectivity of Broca’s area with other cortical areas when participants listened to stories while watching meaningful speech-associated gestures, speech-irrelevant self-grooming hand movements, or no hand movements. A network analysis of neuroimaging data showed that interactions involving Broca’s area and other cortical areas were weakest when spoken language was accompanied by meaningful speech-associated gestures, and strongest when spoken language was accompanied by self-grooming hand movements or by no hand movements at all. Results are discussed with respect to the role that the human mirror system plays in processing speech-associated movements. PMID:17533001