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Sample records for human cardiovascular-respiratory model

  1. Flipped classroom model improves graduate student performance in cardiovascular, respiratory, and renal physiology.

    PubMed

    Tune, Johnathan D; Sturek, Michael; Basile, David P

    2013-12-01

    The purpose of this study was to assess the effectiveness of a traditional lecture-based curriculum versus a modified "flipped classroom" curriculum of cardiovascular, respiratory, and renal physiology delivered to first-year graduate students. Students in both courses were provided the same notes and recorded lectures. Students in the modified flipped classroom were required to watch the prerecorded lectures before class and then attend class, where they received a quiz or homework covering material in each lecture (valued at 25% of the final grade) followed by a question and answer/problem-solving period. In the traditional curriculum, attending lectures was optional and there were no quizzes. Evaluation of effectiveness and student performance was achieved by having students in both courses take the same multiple-choice exams. Within a comparable group of graduate students, participants in the flipped course scored significantly higher (P ≤ 0.05) on the cardiovascular, respiratory, and weighted cumulative sections by an average of >12 percentage points. Exam averages for students in the flipped course also tended to be higher on the renal section by ∼11 percentage points (P = 0.06). Based on our experience and responses obtained in blinded student surveys, we propose that the use of homework and in-class quizzes were critical motivating factors that likely contributed to the increase in student exam performance. Taken together, our findings support that the flipped classroom model is a highly effective means in which to disseminate key physiological concepts to graduate students.

  2. Flipped Classroom Model Improves Graduate Student Performance in Cardiovascular, Respiratory, and Renal Physiology

    ERIC Educational Resources Information Center

    Tune, Johnathan D.; Sturek, Michael; Basile, David P.

    2013-01-01

    The purpose of this study was to assess the effectiveness of a traditional lecture-based curriculum versus a modified "flipped classroom" curriculum of cardiovascular, respiratory, and renal physiology delivered to first-year graduate students. Students in both courses were provided the same notes and recorded lectures. Students in the…

  3. Cardiovascular, respiratory, and total mortality attributed to PM2.5 in Mashhad, Iran.

    PubMed

    Bonyadi, Ziaeddin; Ehrampoush, Mohammad Hasan; Ghaneian, Mohammad Taghi; Mokhtari, Mehdi; Sadeghi, Abbas

    2016-10-01

    Poor air quality is one of the most important environmental problems in many large cities of the world, which can cause a wide range of acute and chronic health effects, including partial physiological disorders and cardiac death due to respiratory and cardiovascular diseases. According to the latest edition of the national standard for air quality, maximum contamination level is 15 μg/m(3) per year and 35 μg/m(3) per day. The aim of this study was to evaluate cardiovascular, respiratory, and total mortality attributed to PM2.5 in the city of Mashhad during 2013. To this end, the Air Q model was used to assess health impacts of PM2.5 and human exposure to it. In this model, the attributable proportion of health outcome, annual number of excess cases of mortality for all causes, and cardiovascular and respiratory diseases were estimated. The results showed that the number of excess cases of mortality for all causes and cardiovascular and respiratory diseases attributable to PM2.5 was 32, 263, and 332 μg/m(3), respectively. Moreover, the annual average of PM2.5 in Mashhad was obtained to be 37.85 μg/m(3). This study demonstrated that a high percentage of mortality resulting from this pollutant could be due to the high average concentration of PM2.5 in the city during 2013. In this case, using the particle control methods, such as optimal use of fuel, management of air quality in urban areas, technical inspection of vehicles, faster development of public transport, and use of industrial technology can be effective in reducing air pollution in cities and turning existing situations into preferred ones.

  4. Cardiovascular, respiratory, and total mortality attributed to PM2.5 in Mashhad, Iran.

    PubMed

    Bonyadi, Ziaeddin; Ehrampoush, Mohammad Hasan; Ghaneian, Mohammad Taghi; Mokhtari, Mehdi; Sadeghi, Abbas

    2016-10-01

    Poor air quality is one of the most important environmental problems in many large cities of the world, which can cause a wide range of acute and chronic health effects, including partial physiological disorders and cardiac death due to respiratory and cardiovascular diseases. According to the latest edition of the national standard for air quality, maximum contamination level is 15 μg/m(3) per year and 35 μg/m(3) per day. The aim of this study was to evaluate cardiovascular, respiratory, and total mortality attributed to PM2.5 in the city of Mashhad during 2013. To this end, the Air Q model was used to assess health impacts of PM2.5 and human exposure to it. In this model, the attributable proportion of health outcome, annual number of excess cases of mortality for all causes, and cardiovascular and respiratory diseases were estimated. The results showed that the number of excess cases of mortality for all causes and cardiovascular and respiratory diseases attributable to PM2.5 was 32, 263, and 332 μg/m(3), respectively. Moreover, the annual average of PM2.5 in Mashhad was obtained to be 37.85 μg/m(3). This study demonstrated that a high percentage of mortality resulting from this pollutant could be due to the high average concentration of PM2.5 in the city during 2013. In this case, using the particle control methods, such as optimal use of fuel, management of air quality in urban areas, technical inspection of vehicles, faster development of public transport, and use of industrial technology can be effective in reducing air pollution in cities and turning existing situations into preferred ones. PMID:27640165

  5. Impact of breath holding on cardiovascular respiratory and cerebrovascular health.

    PubMed

    Dujic, Zeljko; Breskovic, Toni

    2012-06-01

    Human underwater breath-hold diving is a fascinating example of applied environmental physiology. In combination with swimming, it is one of the most popular forms of summer outdoor physical activities. It is performed by a variety of individuals ranging from elite breath-hold divers, underwater hockey and rugby players, synchronized and sprint swimmers, spear fishermen, sponge harvesters and up to recreational swimmers. Very few data currently exist concerning the influence of regular breath holding on possible health risks such as cerebrovascular, cardiovascular and respiratory diseases. A literature search of the PubMed electronic search engine using keywords 'breath-hold diving' and 'apnoea diving' was performed. This review focuses on recent advances in knowledge regarding possibly harmful physiological changes and/or potential health risks associated with breath-hold diving. Available evidence indicates that deep breath-hold dives can be very dangerous and can cause serious acute health problems such a collapse of the lungs, barotrauma at descent and ascent, pulmonary oedema and alveolar haemorrhage, cardiac arrest, blackouts, nitrogen narcosis, decompression sickness and death. Moreover, even shallow apnoea dives, which are far more frequent, can present a significant health risk. The state of affairs is disturbing as athletes, as well as recreational individuals, practice voluntary apnoea on a regular basis. Long-term health risks of frequent maximal breath holds are at present unknown, but should be addressed in future research. Clearly, further studies are needed to better understand the mechanisms related to the possible development or worsening of different clinical disorders in recreational or competitive breath holding and to determine the potential changes in training/competition regimens in order to prevent these adverse events.

  6. Assessment of the Possible Association of Air Pollutants PM10, O3, NO2 With an Increase in Cardiovascular, Respiratory, and Diabetes Mortality in Panama City

    PubMed Central

    Zúñiga, Julio; Tarajia, Musharaf; Herrera, Víctor; Urriola, Wilfredo; Gómez, Beatriz; Motta, Jorge

    2016-01-01

    Abstract In recent years, Panama has experienced a marked economic growth, and this, in turn, has been associated with rapid urban development and degradation of air quality. This study is the first evaluation done in Panama on the association between air pollution and mortality. Our objective was to assess the possible association between monthly levels of PM10, O3, and NO2, and cardiovascular, respiratory, and diabetes mortality, as well as the seasonal variation of mortality in Panama City, Panama. The study was conducted in Panama City, using air pollution data from January 2003 to December 2013. We utilized a Poisson regression model based on generalized linear models, to evaluate the association between PM10, NO2, and O3 exposure and mortality from diabetes, cardiovascular, and respiratory diseases. The sample size for PM10, NO2, and O2 was 132, 132, and 108 monthly averages, respectively. We found that levels of PM10, O3, and NO2 were associated with increases in cardiovascular, respiratory, and diabetes mortality. For PM10 levels ≥ 40 μg/m3, we found an increase in cardiovascular mortality of 9.7% (CI 5.8–13.6%), and an increase of 12.6% (CI 0.2–24.2%) in respiratory mortality. For O3 levels ≥ 20 μg/m3 we found an increase of 32.4% (IC 14.6–52.9) in respiratory mortality, after a 2-month lag period following exposure in the 65 to <74 year-old age group. For NO2 levels ≥20 μg/m3 we found an increase in respiratory mortality of 11.2% (IC 1.9–21.3), after a 2-month lag period following exposure among those aged between 65 and <74 years. There could be an association between the air pollution in Panama City and an increase in cardiovascular, respiratory, and diabetes mortality. This study confirms the urgent need to improve the measurement frequency of air pollutants in Panama. PMID:26765444

  7. Ambient temperature enhanced acute cardiovascular-respiratory mortality effects of PM2.5 in Beijing, China

    NASA Astrophysics Data System (ADS)

    Li, Yi; Ma, Zhiqiang; Zheng, Canjun; Shang, Yu

    2015-12-01

    Studies have shown that temperature could modify the effect of ambient fine particles on mortality risk. In assessing air pollution effects, temperature is usually considered as a confounder. However, ambient temperature can alter people's physiological response to air pollution and might "modify" the impact of air pollution on health outcomes. This study investigated the interaction between daily PM2.5 and daily mean temperature in Beijing, China, using data for the period 2005-2009. Bivariate PM2.5-temperature response surfaces and temperature-stratified generalized additive model (GAM) were applied to study the effect of PM2.5 on cardiovascular, respiratory mortality, and total non-accidental mortality across different temperature levels. We found that low temperature could significantly enhance the effect of PM2.5 on cardiovascular mortality. For an increase of 10 μg/m3 in PM2.5 concentration in the lowest temperature range (-9.7˜2.6 °C), the relative risk (RR) of cardiovascular mortality increased 1.27 % (95 % CI 0.38˜2.17 %), which was higher than that of the whole temperature range (0.59 %, 95 % CI 0.22-1.16 %). The largest effect of PM2.5 on respiratory mortality appeared in the high temperature range. For an increase of 10 μg/m3 in PM2.5 concentration, RR of respiratory mortality increased 1.70 % (95 % CI 0.92˜3.33 %) in the highest level (23.50˜31.80 °C). For the total non-accidental mortality, significant associations appeared only in low temperature levels (-9.7˜2.6 °C): for an increase of 10 μg/m3 in current day PM2.5 concentration, RR increased 1.27 % (95 % CI 0.46˜2.00 %) in the lowest temperature level. No lag effect was observed. The results suggest that in air pollution mortality time series studies, the possibility of an interaction between air pollution and temperature should be considered.

  8. Ambient temperature enhanced acute cardiovascular-respiratory mortality effects of PM2.5 in Beijing, China.

    PubMed

    Li, Yi; Ma, Zhiqiang; Zheng, Canjun; Shang, Yu

    2015-12-01

    Studies have shown that temperature could modify the effect of ambient fine particles on mortality risk. In assessing air pollution effects, temperature is usually considered as a confounder. However, ambient temperature can alter people's physiological response to air pollution and might "modify" the impact of air pollution on health outcomes. This study investigated the interaction between daily PM2.5 and daily mean temperature in Beijing, China, using data for the period 2005-2009. Bivariate PM2.5-temperature response surfaces and temperature-stratified generalized additive model (GAM) were applied to study the effect of PM2.5 on cardiovascular, respiratory mortality, and total non-accidental mortality across different temperature levels. We found that low temperature could significantly enhance the effect of PM2.5 on cardiovascular mortality. For an increase of 10 μg/m(3) in PM2.5 concentration in the lowest temperature range (-9.7∼2.6 °C), the relative risk (RR) of cardiovascular mortality increased 1.27 % (95 % CI 0.38∼2.17 %), which was higher than that of the whole temperature range (0.59 %, 95 % CI 0.22-1.16 %). The largest effect of PM2.5 on respiratory mortality appeared in the high temperature range. For an increase of 10 μg/m(3) in PM2.5 concentration, RR of respiratory mortality increased 1.70 % (95 % CI 0.92∼3.33 %) in the highest level (23.50∼31.80 °C). For the total non-accidental mortality, significant associations appeared only in low temperature levels (-9.7∼2.6 °C): for an increase of 10 μg/m(3) in current day PM2.5 concentration, RR increased 1.27 % (95 % CI 0.46∼2.00 %) in the lowest temperature level. No lag effect was observed. The results suggest that in air pollution mortality time series studies, the possibility of an interaction between air pollution and temperature should be considered.

  9. Assessment of the Possible Association of Air Pollutants PM10, O3, NO2 With an Increase in Cardiovascular, Respiratory, and Diabetes Mortality in Panama City: A 2003 to 2013 Data Analysis.

    PubMed

    Zúñiga, Julio; Tarajia, Musharaf; Herrera, Víctor; Urriola, Wilfredo; Gómez, Beatriz; Motta, Jorge

    2016-01-01

    In recent years, Panama has experienced a marked economic growth, and this, in turn, has been associated with rapid urban development and degradation of air quality. This study is the first evaluation done in Panama on the association between air pollution and mortality. Our objective was to assess the possible association between monthly levels of PM10, O3, and NO2, and cardiovascular, respiratory, and diabetes mortality, as well as the seasonal variation of mortality in Panama City, Panama.The study was conducted in Panama City, using air pollution data from January 2003 to December 2013. We utilized a Poisson regression model based on generalized linear models, to evaluate the association between PM10, NO2, and O3 exposure and mortality from diabetes, cardiovascular, and respiratory diseases. The sample size for PM10, NO2, and O2 was 132, 132, and 108 monthly averages, respectively.We found that levels of PM10, O3, and NO2 were associated with increases in cardiovascular, respiratory, and diabetes mortality. For PM10 levels ≥ 40 μg/m3, we found an increase in cardiovascular mortality of 9.7% (CI 5.8-13.6%), and an increase of 12.6% (CI 0.2-24.2%) in respiratory mortality. For O3 levels ≥ 20 μg/m3 we found an increase of 32.4% (IC 14.6-52.9) in respiratory mortality, after a 2-month lag period following exposure in the 65 to <74 year-old age group. For NO2 levels ≥20 μg/m3 we found an increase in respiratory mortality of 11.2% (IC 1.9-21.3), after a 2-month lag period following exposure among those aged between 65 and <74 years.There could be an association between the air pollution in Panama City and an increase in cardiovascular, respiratory, and diabetes mortality. This study confirms the urgent need to improve the measurement frequency of air pollutants in Panama. PMID:26765444

  10. HumMod: A Modeling Environment for the Simulation of Integrative Human Physiology

    PubMed Central

    Hester, Robert L.; Brown, Alison J.; Husband, Leland; Iliescu, Radu; Pruett, Drew; Summers, Richard; Coleman, Thomas G.

    2011-01-01

    Mathematical models and simulations are important tools in discovering key causal relationships governing physiological processes. Simulations guide and improve outcomes of medical interventions involving complex physiology. We developed HumMod, a Windows-based model of integrative human physiology. HumMod consists of 5000 variables describing cardiovascular, respiratory, renal, neural, endocrine, skeletal muscle, and metabolic physiology. The model is constructed from empirical data obtained from peer-reviewed physiological literature. All model details, including variables, parameters, and quantitative relationships, are described in Extensible Markup Language (XML) files. The executable (HumMod.exe) parses the XML and displays the results of the physiological simulations. The XML description of physiology in HumMod's modeling environment allows investigators to add detailed descriptions of human physiology to test new concepts. Additional or revised XML content is parsed and incorporated into the model. The model accurately predicts both qualitative and quantitative changes in clinical and experimental responses. The model is useful in understanding proposed physiological mechanisms and physiological interactions that are not evident, allowing one to observe higher level emergent properties of the complex physiological systems. HumMod has many uses, for instance, analysis of renal control of blood pressure, central role of the liver in creating and maintaining insulin resistance, and mechanisms causing orthostatic hypotension in astronauts. Users simulate different physiological and pathophysiological situations by interactively altering numerical parameters and viewing time-dependent responses. HumMod provides a modeling environment to understand the complex interactions of integrative physiology. HumMod can be downloaded at http://hummod.org PMID:21647209

  11. Human Factors Model

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Jack is an advanced human factors software package that provides a three dimensional model for predicting how a human will interact with a given system or environment. It can be used for a broad range of computer-aided design applications. Jack was developed by the computer Graphics Research Laboratory of the University of Pennsylvania with assistance from NASA's Johnson Space Center, Ames Research Center and the Army. It is the University's first commercial product. Jack is still used for academic purposes at the University of Pennsylvania. Commercial rights were given to Transom Technologies, Inc.

  12. Perspectives on human performance modelling

    SciTech Connect

    Pew, R.W.; Baron, S.

    1983-11-01

    A combination of psychologically-based and control-theoretic approaches to human performance modelling results in other models which have the potential for unifying related works in psychology, artificial intelligence, and system-oriented supervisory control. 33 references.

  13. Integrated Environmental Modelling: human decisions, human challenges

    USGS Publications Warehouse

    Glynn, Pierre D.

    2015-01-01

    Integrated Environmental Modelling (IEM) is an invaluable tool for understanding the complex, dynamic ecosystems that house our natural resources and control our environments. Human behaviour affects the ways in which the science of IEM is assembled and used for meaningful societal applications. In particular, human biases and heuristics reflect adaptation and experiential learning to issues with frequent, sharply distinguished, feedbacks. Unfortunately, human behaviour is not adapted to the more diffusely experienced problems that IEM typically seeks to address. Twelve biases are identified that affect IEM (and science in general). These biases are supported by personal observations and by the findings of behavioural scientists. A process for critical analysis is proposed that addresses some human challenges of IEM and solicits explicit description of (1) represented processes and information, (2) unrepresented processes and information, and (3) accounting for, and cognizance of, potential human biases. Several other suggestions are also made that generally complement maintaining attitudes of watchful humility, open-mindedness, honesty and transparent accountability. These suggestions include (1) creating a new area of study in the behavioural biogeosciences, (2) using structured processes for engaging the modelling and stakeholder communities in IEM, and (3) using ‘red teams’ to increase resilience of IEM constructs and use.

  14. Multimodal signature modeling of humans

    NASA Astrophysics Data System (ADS)

    Cathcart, J. Michael; Kocher, Brian; Prussing, Keith; Lane, Sarah; Thomas, Alan

    2010-04-01

    Georgia Tech been investigating method for the detection of covert personnel in traditionally difficult environments (e.g., urban, caves). This program focuses on a detailed phenomenological analysis of human physiology and signatures with the subsequent identification and characterization of potential observables. Both aspects are needed to support the development of personnel detection and tracking algorithms. The difficult nature of these personnel-related problems dictates a multimodal sensing approach. Human signature data of sufficient and accurate quality and quantity do not exist, thus the development of an accurate signature model for a human is needed. This model should also simulate various human activities to allow motion-based observables to be exploited. This paper will describe a multimodal signature modeling approach that incorporates human physiological aspects, thermoregulation, and dynamics into the signature calculation. This approach permits both passive and active signatures to be modeled. The focus of the current effort involved the computation of signatures in urban environments. This paper will discuss the development of a human motion model for use in simulating both electro-optical signatures and radar-based signatures. Video sequences of humans in a simulated urban environment will also be presented; results using these sequences for personnel tracking will be presented.

  15. Mouse models of human disease

    PubMed Central

    Perlman, Robert L.

    2016-01-01

    The use of mice as model organisms to study human biology is predicated on the genetic and physiological similarities between the species. Nonetheless, mice and humans have evolved in and become adapted to different environments and so, despite their phylogenetic relatedness, they have become very different organisms. Mice often respond to experimental interventions in ways that differ strikingly from humans. Mice are invaluable for studying biological processes that have been conserved during the evolution of the rodent and primate lineages and for investigating the developmental mechanisms by which the conserved mammalian genome gives rise to a variety of different species. Mice are less reliable as models of human disease, however, because the networks linking genes to disease are likely to differ between the two species. The use of mice in biomedical research needs to take account of the evolved differences as well as the similarities between mice and humans. PMID:27121451

  16. Stochastic Models of Human Growth.

    ERIC Educational Resources Information Center

    Goodrich, Robert L.

    Stochastic difference equations of the Box-Jenkins form provide an adequate family of models on which to base the stochastic theory of human growth processes, but conventional time series identification methods do not apply to available data sets. A method to identify structure and parameters of stochastic difference equation models of human…

  17. Human Modeling for Ground Processing Human Factors Engineering Analysis

    NASA Technical Reports Server (NTRS)

    Stambolian, Damon B.; Lawrence, Brad A.; Stelges, Katrine S.; Steady, Marie-Jeanne O.; Ridgwell, Lora C.; Mills, Robert E.; Henderson, Gena; Tran, Donald; Barth, Tim

    2011-01-01

    There have been many advancements and accomplishments over the last few years using human modeling for human factors engineering analysis for design of spacecraft. The key methods used for this are motion capture and computer generated human models. The focus of this paper is to explain the human modeling currently used at Kennedy Space Center (KSC), and to explain the future plans for human modeling for future spacecraft designs

  18. Animal models for human diseases.

    PubMed

    Rust, J H

    1982-01-01

    The use of animal models for the study of human disease is, for the most part, a recent development. This discussion of the use of animal models for human diseases directs attention to the sterile period, early advances, some personal experiences, the human as the model, biological oddities among common laboratory animals, malignancies in laboratory animals, problems created by federal regulations, cancer tests with animals, and what the future holds in terms of the use of animal models as an aid to understanding human disease. In terms of early use of animal models, there was a school of rabbis, some of whom were also physicians, in Babylon who studied and wrote extensively on ritual slaughter and the suitability of birds and beasts for food. Considerable detailed information on animal pathology, physiology, anatomy, and medicine in general can be found in the Soncino Babylonian Talmudic Translations. The 1906 edition of the "Jewish Encyclopedia," has been a rich resource. Although it has not been possible to establish what diseases of animals were studied and their relationship to the diseases of humans, there are fascinating clues to pursue, despite the fact that these were sterile years for research in medicine. The quotation from the Talmud is of interest: "The medical knowledge of the Talmudist was based upon tradition, the dissection of human bodies, observation of disease and experiments upon animals." A bright light in the lackluster years of medical research was provided by Galen, considered the originator of research in physiology and anatomy. His dissection of animals and work on apes and other lower animals were models for human anatomy and physiology and the bases for many treatises. Yet, Galen never seemed to suggest that animals could serve as models for human diseases. Most early physicians who can be considered to have been students of disease developed their medical knowledge by observing the sick under their care. 1 early medical investigator

  19. Mouse Models of Human Phenylketonuria

    PubMed Central

    Shedlovsky, A.; McDonald, J. D.; Symula, D.; Dove, W. F.

    1993-01-01

    Phenylketonuria (PKU) results from a deficiency in phenylalanine hydroxylase, the enzyme catalyzing the conversion of phenylalanine (PHE) to tyrosine. Although this inborn error of metabolism was among the first in humans to be understood biochemically and genetically, little is known of the mechanism(s) involved in the pathology of PKU. We have combined mouse germline mutagenesis with screens for hyperphenylalaninemia to isolate three mutants deficient in phenylalanine hydroxylase (PAH) activity and cross-reactive protein. Two of these have reduced PAH mRNA and display characteristics of untreated human PKU patients. A low PHE diet partially reverses these abnormalities. Our success in using high frequency random germline point mutagenesis to obtain appropriate disease models illustrates how such mutagenesis can complement the emergent power of targeted mutagenesis in the mouse. The mutants now can be used as models in studying both maternal PKU and somatic gene therapy. PMID:8375656

  20. Human jaw and muscle modelling.

    PubMed

    Peck, Christopher C; Hannam, Alan G

    2007-04-01

    Dynamic mathematical modelling is an invaluable method to help understand the biomechanics of the anatomically and functionally complex masticatory system. It provides insight into variables which are impossible to measure directly such as joint loads and individual muscle tensions, and into physical relationships between jaw structure and function. Individual parameters can be modified easily to understand their influence on function. Our models are constructed with best available structural and functional data, and evaluated against human jaw behaviour. Image data provide hard and soft tissue morphology and the jaw's inertial properties. The drive to the system is provided by actuators which simulate active and passive jaw muscle properties. In whole-jaw modelling, muscle models which behave plausibly rather than mimic the ultra-structural cross-bridge interactions are common since they are computationally feasible. Whole-jaw models have recently incorporated flexible finite-elements to explore tissue distortion in the temporomandibular joint and tongue movements. Furthermore, the jaw has been integrated with laryngeal models to explore complex tasks such as swallowing. These dynamic models have helped better understand joint loading, movement constraints and muscle activation strategies. Future directions will include further incorporation of rigid and flexible model dynamics and the creation of subject-specific models to better understand the functional implications of pathology.

  1. Network model of human language

    NASA Astrophysics Data System (ADS)

    Markošová, Mária

    2008-01-01

    The phenomenon of human language is widely studied from various points of view. It is interesting not only for social scientists, antropologists or philosophers, but also for those, interested in the network dynamics. In several recent papers word web, or language as a graph has been investigated [R.F. Cancho, R. Solé, The small world of human language, Proc. R. Soc. London B 268 (2001) 2261-2265; A.E. Motter, P.S. de Moura, Lai Ying-Cheng, P. Dasgupta, Topology of the conceptual network of language, Phys. Rev. E 65 (2002) R 065102; M. Steyvers, J.B. Tenenbaum, The large-scale structure of semantic networks: Statistical analysis and a model of semantic growth, Cogn. Sci. 29 (2005) 41-78]. In this paper I revise recent studies of syntactical word web [R.F. Cancho, R. Solé, The small world of human language, Proc. R. Soc. London B 268 (2001) 2261-2265; S.N. Dorogovtsev, J.F.F. Mendes, Language as an evolving word web, Proc. R. Soc. London B 268 (2001) 2603-2606]. I present a model of growing network in which such processes as node addition, edge rewiring and new link creation are taken into account. I argue, that this model is a satisfactory minimal model explaining measured data [R.F. Cancho, R. Solé, The small world of human language, Proc. R. Soc. London B 268 (2001) 2261-2265; M. Markošová, P. Náther, Language as a graph, in: V. Kvasnička, P. Trebatický, J. Pospíchal (Eds.), Mind, Intelligence and Life, Kelemen, STU Bratislava, 2007, pp. 298-307 (in Slovak)].

  2. Modeling skewness in human transcriptomes.

    PubMed

    Casellas, Joaquim; Varona, Luis

    2012-01-01

    Gene expression data are influenced by multiple biological and technological factors leading to a wide range of dispersion scenarios, although skewed patterns are not commonly addressed in microarray analyses. In this study, the distribution pattern of several human transcriptomes has been studied on free-access microarray gene expression data. Our results showed that, even in previously normalized gene expression data, probe and differential expression within probe effects suffer from substantial departures from the commonly assumed symmetric gaussian distribution. We developed a flexible mixed model for non-competitive microarray data analysis that accounted for asymmetric and heavy-tailed (Student's t distribution) dispersion processes. Random effects for gene expression data were modeled under asymmetric Student's t distributions where the asymmetry parameter (λ) took values from perfect symmetry (λ = 0) to right- (λ>0) or left-side (λ>0) over-expression patterns. This approach was applied to four free-access human data sets and revealed clearly better model performance when comparing with standard approaches accounting for traditional symmetric gaussian distribution patterns. Our analyses on human gene expression data revealed a substantial degree of right-hand asymmetry for probe effects, whereas differential gene expression addressed both symmetric and left-hand asymmetric patterns. Although these results cannot be extrapolated to all microarray experiments, they highlighted the incidence of skew dispersion patterns in human transcriptome; moreover, we provided a new analytical approach to appropriately address this biological phenomenon. The source code of the program accommodating these analytical developments and additional information about practical aspects on running the program are freely available by request to the corresponding author of this article. PMID:22701729

  3. Human Thermal Model Evaluation Using the JSC Human Thermal Database

    NASA Technical Reports Server (NTRS)

    Bue, Grant; Makinen, Janice; Cognata, Thomas

    2012-01-01

    Human thermal modeling has considerable long term utility to human space flight. Such models provide a tool to predict crew survivability in support of vehicle design and to evaluate crew response in untested space environments. It is to the benefit of any such model not only to collect relevant experimental data to correlate it against, but also to maintain an experimental standard or benchmark for future development in a readily and rapidly searchable and software accessible format. The Human thermal database project is intended to do just so; to collect relevant data from literature and experimentation and to store the data in a database structure for immediate and future use as a benchmark to judge human thermal models against, in identifying model strengths and weakness, to support model development and improve correlation, and to statistically quantify a model s predictive quality. The human thermal database developed at the Johnson Space Center (JSC) is intended to evaluate a set of widely used human thermal models. This set includes the Wissler human thermal model, a model that has been widely used to predict the human thermoregulatory response to a variety of cold and hot environments. These models are statistically compared to the current database, which contains experiments of human subjects primarily in air from a literature survey ranging between 1953 and 2004 and from a suited experiment recently performed by the authors, for a quantitative study of relative strength and predictive quality of the models.

  4. Modeling Forces on the Human Body.

    ERIC Educational Resources Information Center

    Pagonis, Vasilis; Drake, Russel; Morgan, Michael; Peters, Todd; Riddle, Chris; Rollins, Karen

    1999-01-01

    Presents five models of the human body as a mechanical system which can be used in introductory physics courses: human arms as levers, humans falling from small heights, a model of the human back, collisions during football, and the rotating gymnast. Gives ideas for discussions and activities, including Interactive Physics (TM) simulations. (WRM)

  5. Creating Simulated Microgravity Patient Models

    NASA Technical Reports Server (NTRS)

    Hurst, Victor; Doerr, Harold K.; Bacal, Kira

    2004-01-01

    The Medical Operational Support Team (MOST) has been tasked by the Space and Life Sciences Directorate (SLSD) at the NASA Johnson Space Center (JSC) to integrate medical simulation into 1) medical training for ground and flight crews and into 2) evaluations of medical procedures and equipment for the International Space Station (ISS). To do this, the MOST requires patient models that represent the physiological changes observed during spaceflight. Despite the presence of physiological data collected during spaceflight, there is no defined set of parameters that illustrate or mimic a 'space normal' patient. Methods: The MOST culled space-relevant medical literature and data from clinical studies performed in microgravity environments. The areas of focus for data collection were in the fields of cardiovascular, respiratory and renal physiology. Results: The MOST developed evidence-based patient models that mimic the physiology believed to be induced by human exposure to a microgravity environment. These models have been integrated into space-relevant scenarios using a human patient simulator and ISS medical resources. Discussion: Despite the lack of a set of physiological parameters representing 'space normal,' the MOST developed space-relevant patient models that mimic microgravity-induced changes in terrestrial physiology. These models are used in clinical scenarios that will medically train flight surgeons, biomedical flight controllers (biomedical engineers; BME) and, eventually, astronaut-crew medical officers (CMO).

  6. Deformable human body model development

    SciTech Connect

    Wray, W.O.; Aida, T.

    1998-11-01

    This is the final report of a three-year, Laboratory Directed Research and Development (LDRD) project at the Los Alamos National Laboratory (LANL). A Deformable Human Body Model (DHBM) capable of simulating a wide variety of deformation interactions between man and his environment has been developed. The model was intended to have applications in automobile safety analysis, soldier survivability studies and assistive technology development for the disabled. To date, we have demonstrated the utility of the DHBM in automobile safety analysis and are currently engaged in discussions with the U.S. military involving two additional applications. More specifically, the DHBM has been incorporated into a Virtual Safety Lab (VSL) for automobile design under contract to General Motors Corporation. Furthermore, we have won $1.8M in funding from the U.S. Army Medical Research and Material Command for development of a noninvasive intracranial pressure measurement system. The proposed research makes use of the detailed head model that is a component of the DHBM; the project duration is three years. In addition, we have been contacted by the Air Force Armstrong Aerospace Medical Research Laboratory concerning possible use of the DHBM in analyzing the loads and injury potential to pilots upon ejection from military aircraft. Current discussions with Armstrong involve possible LANL participation in a comparison between DHBM and the Air Force Articulated Total Body (ATB) model that is the current military standard.

  7. Generation of improved humanized mouse models for human infectious diseases

    PubMed Central

    Brehm, Michael A.; Wiles, Michael V.; Greiner, Dale L.; Shultz, Leonard D.

    2014-01-01

    The study of human-specific infectious agents has been hindered by the lack of optimal small animal models. More recently development of novel strains of immunodeficient mice has begun to provide the opportunity to utilize small animal models for the study of many human-specific infectious agents. The introduction of a targeted mutation in the IL2 receptor common gamma chain gene (IL2rgnull) in mice already deficient in T and B cells led to a breakthrough in the ability to engraft hematopoietic stem cells, as well as functional human lymphoid cells and tissues, effectively creating human immune systems in immunodeficient mice. These humanized mice are becoming increasingly important as pre-clinical models for the study of human immunodeficiency virus-1 (HIV-1) and other human-specific infectious agents. However, there remain a number of opportunities to further improve humanized mouse models for the study of human-specific infectious agents. This is being done by the implementation of innovative technologies, which collectively will accelerate the development of new models of genetically modified mice, including; i) modifications of the host to reduce innate immunity, which impedes human cell engraftment; ii) genetic modification to provide human-specific growth factors and cytokines required for optimal human cell growth and function; iii) and new cell and tissue engraftment protocols. The development of “next generation” humanized mouse models continues to provide exciting opportunities for the establishment of robust small animal models to study the pathogenesis of human-specific infectious agents, as well as for testing the efficacy of therapeutic agents and experimental vaccines. PMID:24607601

  8. Human Thermal Model Evaluation Using the JSC Human Thermal Database

    NASA Technical Reports Server (NTRS)

    Cognata, T.; Bue, G.; Makinen, J.

    2011-01-01

    The human thermal database developed at the Johnson Space Center (JSC) is used to evaluate a set of widely used human thermal models. This database will facilitate a more accurate evaluation of human thermoregulatory response using in a variety of situations, including those situations that might otherwise prove too dangerous for actual testing--such as extreme hot or cold splashdown conditions. This set includes the Wissler human thermal model, a model that has been widely used to predict the human thermoregulatory response to a variety of cold and hot environments. These models are statistically compared to the current database, which contains experiments of human subjects primarily in air from a literature survey ranging between 1953 and 2004 and from a suited experiment recently performed by the authors, for a quantitative study of relative strength and predictive quality of the models. Human thermal modeling has considerable long term utility to human space flight. Such models provide a tool to predict crew survivability in support of vehicle design and to evaluate crew response in untested environments. It is to the benefit of any such model not only to collect relevant experimental data to correlate it against, but also to maintain an experimental standard or benchmark for future development in a readily and rapidly searchable and software accessible format. The Human thermal database project is intended to do just so; to collect relevant data from literature and experimentation and to store the data in a database structure for immediate and future use as a benchmark to judge human thermal models against, in identifying model strengths and weakness, to support model development and improve correlation, and to statistically quantify a model s predictive quality.

  9. Mental models and human reasoning

    PubMed Central

    Johnson-Laird, Philip N.

    2010-01-01

    To be rational is to be able to reason. Thirty years ago psychologists believed that human reasoning depended on formal rules of inference akin to those of a logical calculus. This hypothesis ran into difficulties, which led to an alternative view: reasoning depends on envisaging the possibilities consistent with the starting point—a perception of the world, a set of assertions, a memory, or some mixture of them. We construct mental models of each distinct possibility and derive a conclusion from them. The theory predicts systematic errors in our reasoning, and the evidence corroborates this prediction. Yet, our ability to use counterexamples to refute invalid inferences provides a foundation for rationality. On this account, reasoning is a simulation of the world fleshed out with our knowledge, not a formal rearrangement of the logical skeletons of sentences. PMID:20956326

  10. Human Performance Modeling for Dynamic Human Reliability Analysis

    SciTech Connect

    Boring, Ronald Laurids; Joe, Jeffrey Clark; Mandelli, Diego

    2015-08-01

    Part of the U.S. Department of Energy’s (DOE’s) Light Water Reac- tor Sustainability (LWRS) Program, the Risk-Informed Safety Margin Charac- terization (RISMC) Pathway develops approaches to estimating and managing safety margins. RISMC simulations pair deterministic plant physics models with probabilistic risk models. As human interactions are an essential element of plant risk, it is necessary to integrate human actions into the RISMC risk framework. In this paper, we review simulation based and non simulation based human reliability analysis (HRA) methods. This paper summarizes the founda- tional information needed to develop a feasible approach to modeling human in- teractions in RISMC simulations.

  11. Computer modeling of human decision making

    NASA Technical Reports Server (NTRS)

    Gevarter, William B.

    1991-01-01

    Models of human decision making are reviewed. Models which treat just the cognitive aspects of human behavior are included as well as models which include motivation. Both models which have associated computer programs, and those that do not, are considered. Since flow diagrams, that assist in constructing computer simulation of such models, were not generally available, such diagrams were constructed and are presented. The result provides a rich source of information, which can aid in construction of more realistic future simulations of human decision making.

  12. Human systems dynamics: Toward a computational model

    NASA Astrophysics Data System (ADS)

    Eoyang, Glenda H.

    2012-09-01

    A robust and reliable computational model of complex human systems dynamics could support advancements in theory and practice for social systems at all levels, from intrapersonal experience to global politics and economics. Models of human interactions have evolved from traditional, Newtonian systems assumptions, which served a variety of practical and theoretical needs of the past. Another class of models has been inspired and informed by models and methods from nonlinear dynamics, chaos, and complexity science. None of the existing models, however, is able to represent the open, high dimension, and nonlinear self-organizing dynamics of social systems. An effective model will represent interactions at multiple levels to generate emergent patterns of social and political life of individuals and groups. Existing models and modeling methods are considered and assessed against characteristic pattern-forming processes in observed and experienced phenomena of human systems. A conceptual model, CDE Model, based on the conditions for self-organizing in human systems, is explored as an alternative to existing models and methods. While the new model overcomes the limitations of previous models, it also provides an explanatory base and foundation for prospective analysis to inform real-time meaning making and action taking in response to complex conditions in the real world. An invitation is extended to readers to engage in developing a computational model that incorporates the assumptions, meta-variables, and relationships of this open, high dimension, and nonlinear conceptual model of the complex dynamics of human systems.

  13. Rabbit Models for Studying Human Infectious Diseases

    PubMed Central

    Peng, Xuwen; Knouse, John A; Hernon, Krista M

    2015-01-01

    Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia–lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described. PMID:26678367

  14. Rabbit Models for Studying Human Infectious Diseases.

    PubMed

    Peng, Xuwen; Knouse, John A; Hernon, Krista M

    2015-12-01

    Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia-lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described. PMID:26678367

  15. Human Performance Models of Pilot Behavior

    NASA Technical Reports Server (NTRS)

    Foyle, David C.; Hooey, Becky L.; Byrne, Michael D.; Deutsch, Stephen; Lebiere, Christian; Leiden, Ken; Wickens, Christopher D.; Corker, Kevin M.

    2005-01-01

    Five modeling teams from industry and academia were chosen by the NASA Aviation Safety and Security Program to develop human performance models (HPM) of pilots performing taxi operations and runway instrument approaches with and without advanced displays. One representative from each team will serve as a panelist to discuss their team s model architecture, augmentations and advancements to HPMs, and aviation-safety related lessons learned. Panelists will discuss how modeling results are influenced by a model s architecture and structure, the role of the external environment, specific modeling advances and future directions and challenges for human performance modeling in aviation.

  16. Hooked! Modeling human disease in zebrafish.

    PubMed

    Santoriello, Cristina; Zon, Leonard I

    2012-07-01

    Zebrafish have been widely used as a model system for studying developmental processes, but in the last decade, they have also emerged as a valuable system for modeling human disease. The development and function of zebrafish organs are strikingly similar to those of humans, and the ease of creating mutant or transgenic fish has facilitated the generation of disease models. Here, we highlight the use of zebrafish for defining disease pathways and for discovering new therapies. PMID:22751109

  17. Human Centered Hardware Modeling and Collaboration

    NASA Technical Reports Server (NTRS)

    Stambolian Damon; Lawrence, Brad; Stelges, Katrine; Henderson, Gena

    2013-01-01

    In order to collaborate engineering designs among NASA Centers and customers, to in clude hardware and human activities from multiple remote locations, live human-centered modeling and collaboration across several sites has been successfully facilitated by Kennedy Space Center. The focus of this paper includes innovative a pproaches to engineering design analyses and training, along with research being conducted to apply new technologies for tracking, immersing, and evaluating humans as well as rocket, vehic le, component, or faci lity hardware utilizing high resolution cameras, motion tracking, ergonomic analysis, biomedical monitoring, wor k instruction integration, head-mounted displays, and other innovative human-system integration modeling, simulation, and collaboration applications.

  18. Genetically Engineered Pig Models for Human Diseases

    PubMed Central

    Prather, Randall S.; Lorson, Monique; Ross, Jason W.; Whyte, Jeffrey J.; Walters, Eric

    2015-01-01

    Although pigs are used widely as models of human disease, their utility as models has been enhanced by genetic engineering. Initially, transgenes were added randomly to the genome, but with the application of homologous recombination, zinc finger nucleases, and transcription activator-like effector nuclease (TALEN) technologies, now most any genetic change that can be envisioned can be completed. To date these genetic modifications have resulted in animals that have the potential to provide new insights into human diseases for which a good animal model did not exist previously. These new animal models should provide the preclinical data for treatments that are developed for diseases such as Alzheimer's disease, cystic fibrosis, retinitis pigmentosa, spinal muscular atrophy, diabetes, and organ failure. These new models will help to uncover aspects and treatments of these diseases that were otherwise unattainable. The focus of this review is to describe genetically engineered pigs that have resulted in models of human diseases. PMID:25387017

  19. Flows In Model Human Femoral Arteries

    NASA Technical Reports Server (NTRS)

    Back, Lloyd H.; Kwack, Eug Y.; Crawford, Donald W.

    1990-01-01

    Flow is visualized with dye traces, and pressure measurements made. Report describes experimental study of flow in models of human femoral artery. Conducted to examine effect of slight curvature of artery on flow paths and distribution of pressure.

  20. Rethinking animal models and human obesity.

    PubMed

    Joyner, Michael J

    2014-11-01

    Human obesity is a complex phenomenon where economic, cultural, behavioral, and biological factors intersect in the physiological space. Developing animal models that capture several elements of the many potential interactions between these factors will only increase their translational value.

  1. Murine models of human wound healing.

    PubMed

    Chen, Jerry S; Longaker, Michael T; Gurtner, Geoffrey C

    2013-01-01

    In vivo wound healing experiments remain the most predictive models for studying human wound healing, allowing an accurate representation of the complete wound healing environment including various cell types, environmental cues, and paracrine interactions. Small animals are economical, easy to maintain, and allow researchers to take advantage of the numerous transgenic strains that have been developed to investigate the specific mechanisms involved in wound healing and regeneration. Here we describe three reproducible murine wound healing models that recapitulate the human wound healing process.

  2. Humanized Mouse Models of HIV Infection

    PubMed Central

    Denton, Paul W.; Garcia, J. Victor

    2013-01-01

    Because of the limited tropism of HIV, in vivo modeling of this virus has been almost exclusively limited to other lentiviruses such as SIV that reproduce many important characteristics of HIV infection. However, there are significant genetic and biological differences among lentiviruses and some HIV-specific interventions are not effective against other lentiviruses in non-human hosts. For these reasons much emphasis has recently been placed on developing alternative animal models that support HIV replication and recapitulate key aspects of HIV infection and pathogenesis in humans. Humanized mice, CD34+ hematopoietic progenitor cell transplanted immunodeficient mice and in particular mice also implanted with human thymic/liver tissue (BLT mice) that develop a functional human immune system, have been the focus of a great deal of attention as possible models to study virtually all aspects of HIV biology and pathogenesis. Humanized mice are systemically reconstituted with human lymphoid cells offering rapid, reliable and reproducible experimental systems for HIV research. Peripheral blood of humanized mice can be readily sampled longitudinally to assess reconstitution with human cells and to monitor HIV replication permitting the evaluation of multiple parameters of HIV infection such as viral load levels, CD4+ T cell depletion, immune activation, as well as the effects of therapeutic interventions. Of high relevance to HIV transmission is the extensive characterization and validation of the reconstitution with human lymphoid cells of the female reproductive tract and of the gastrointestinal tract of humanized BLT mice that renders them susceptible to both vaginal and rectal HIV infection. Other important attributes of all types of humanized mice include: 1) their small size and cost that make them broadly accessible; 2) multiple cohorts of humanized mice can be made from multiple human donors and each cohort has identical human cells, permitting control of

  3. [Experimental models of human skin aging].

    PubMed

    Nikolakis, G; Zoschke, C; Makrantonaki, E; Hausmann, C; Schäfer-Korting, M; Zouboulis, C C

    2016-02-01

    The skin is a representative model for the study of human aging. Despite the high regenerative capacity of the skin, skin physiology changes over the course of life. Medical and cosmetic research is trying to prevent aging, to slow, to stop, or to reverse it. Effects of age-related DNA damage and of changing skin structure on pharmacological parameters are largely unknown. This review article summarizes the state of scientific knowledge in the field of experimental models of human skin aging and shows approaches to improve organotypic skin models, to develop predictive models of aging, and improve aging research.

  4. [Experimental models of human skin aging].

    PubMed

    Nikolakis, G; Zoschke, C; Makrantonaki, E; Hausmann, C; Schäfer-Korting, M; Zouboulis, C C

    2016-02-01

    The skin is a representative model for the study of human aging. Despite the high regenerative capacity of the skin, skin physiology changes over the course of life. Medical and cosmetic research is trying to prevent aging, to slow, to stop, or to reverse it. Effects of age-related DNA damage and of changing skin structure on pharmacological parameters are largely unknown. This review article summarizes the state of scientific knowledge in the field of experimental models of human skin aging and shows approaches to improve organotypic skin models, to develop predictive models of aging, and improve aging research. PMID:26743051

  5. Animal models of human response to dioxins.

    PubMed Central

    Grassman, J A; Masten, S A; Walker, N J; Lucier, G W

    1998-01-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent member of a class of chlorinated hydrocarbons that interact with the aryl hydrocarbon receptor (AhR). TCDD and dioxinlike compounds are environmentally and biologically stable and as a result, human exposure is chronic and widespread. Studies of highly exposed human populations show that dioxins produce developmental effects, chloracne, and an increase in all cancers and suggest that they may also alter immune and endocrine function. In contrast, the health effects of low-level environmental exposure have not been established. Experimental animal models can enhance the understanding of the effects of low-level dioxin exposure, particularly when there is evidence that humans respond similarly to the animal models. Although there are species differences in pharmacokinetics, experimental animal models demonstrate AhR-dependent health effects that are similar to those found in exposed human populations. Comparisons of biochemical changes show that humans and animal models have similar degrees of sensitivity to dioxin-induced effects. The information gained from animal models is important for developing mechanistic models of dioxin toxicity and critical for assessing the risks to human populations under different circumstances of exposure. PMID:9599728

  6. Modeling human brain development with cerebral organoids.

    PubMed

    Muzio, Luca; Consalez, G Giacomo

    2013-01-01

    The recent discovery of a new three-dimensional culture system for the derivation of cerebral organoids from human induced pluripotent stem cells provides developmental neurobiologists with the first example of a three-dimensional framework for the study of human brain development. This innovative approach permits the in vitro assembly of a human embryonic brain rudiment that recapitulates the developing human cerebrum. Organoids contain progenitor populations that develop to yield mature cortical neuron subtypes, potentially allowing investigators to study complex brain diseases that lack appropriate animal models. PMID:24367992

  7. Finite element modeling of the human pelvis

    SciTech Connect

    Carlson, B.

    1995-11-01

    A finite element model of the human pelvis was created using a commercial wire frame image as a template. To test the final mesh, the model`s mechanical behavior was analyzed through finite element analysis and the results were displayed graphically as stress concentrations. In the future, this grid of the pelvis will be integrated with a full leg model and used in side-impact car collision simulations.

  8. Simplified experimental human dermatophytosis model.

    PubMed

    Aly, R; Maibach, H I; Ho, I; Abrams, B B

    1992-02-01

    The authors have improved and simplified previous methods for producing localized mycotic skin infections in an attempt to compare topical antifungal agents for their bioequivalency. Healthy human volunteers who had negative results for commercial, purified Trichophyton antigen (Trichophytin) were inoculated with Trichophyton mentagrophytes on two sites on each forearm in a randomized study designed to compare the antifungal activities of two ciclopirox olamine formulations. The lesions, easily induced by the authors' method, were localized and did not spread under the occlusive dressings. Infections established at the four sites on 26 subjects were treated twice daily for 14 days with the two active drug formulations and their vehicles. There were no significant differences in culture-documented cure rates or alleviation of clinical signs and symptoms between ciclopirox olamine lotion and cream. Each drug was significantly better than its vehicle. The authors' method seems to be effective and suitable for therapeutic studies.

  9. Animal models of human disease: inflammation.

    PubMed

    Webb, David R

    2014-01-01

    Animals have been used as models to study inflammation and autoimmunity for more than 80 years. During that time it has been understood that although the use of such models is an important and necessary part of understanding human disease, they inevitably display significant differences from the human disease state. Since our understanding of human inflammation and autoimmunity is necessarily incomplete, it may be concluded that the animal models will also be reflective of the state of knowledge regarding such diseases. Nevertheless, animal models of rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis have been successfully used to enhance the understanding of the human disease and have made significant contributions to the development of powerful new therapies. However, there are exceptions. One of the most persistent has been the study of sepsis where the animal models have been woefully inadequate in uncovering targets for drug discovery and have led to repeated clinical failures. As will be explained, only by using newly developed genomics tools has it been possible to uncover the differences between sepsis in mice and sepsis in man. It is concluded that approaches using the newer genomic and proteomic data derived from human tissues, will make possible the development of animal models with more predictive power as aids to drug discovery.

  10. Mathematical model for predicting human vertebral fracture

    NASA Technical Reports Server (NTRS)

    Benedict, J. V.

    1973-01-01

    Mathematical model has been constructed to predict dynamic response of tapered, curved beam columns in as much as human spine closely resembles this form. Model takes into consideration effects of impact force, mass distribution, and material properties. Solutions were verified by dynamic tests on curved, tapered, elastic polyethylene beam.

  11. A Model of the Human Eye

    ERIC Educational Resources Information Center

    Colicchia, G.; Wiesner, H.; Waltner, C.; Zollman, D.

    2008-01-01

    We describe a model of the human eye that incorporates a variable converging lens. The model can be easily constructed by students with low-cost materials. It shows in a comprehensible way the functionality of the eye's optical system. Images of near and far objects can be focused. Also, the defects of near and farsighted eyes can be demonstrated.

  12. Toward a Model of Human Leadership.

    ERIC Educational Resources Information Center

    Jenkins, Mercilee M.

    The literature on sex-related differences in leadership behavior was reviewed in order to explore underlying factors. Currently there exist several models of male leadership in small groups, but no models of human leadership which represent the experiences of women in same sex and mixed sex groups. Key considerations for constructing such a model…

  13. Interior Design Research: A Human Ecosystem Model.

    ERIC Educational Resources Information Center

    Guerin, Denise A.

    1992-01-01

    The interior ecosystems model illustrates effects on the human organism of the interaction of the natural, behavioral, and built environment. Examples of interior lighting and household energy consumption show the model's flexibility for organizing study variables in interior design research. (SK)

  14. DEVELOPING MEANINGFUL COHORTS FOR HUMAN EXPOSURE MODELS

    EPA Science Inventory

    This paper summarizes numerous statistical analyses focused on the U.S. Environmental Protection Agency's Consolidated Human Activity Database (CHAD), used by many exposure modelers as the basis for data on what people do and where they spend their time. In doing so, modelers ...

  15. Advances in Computationally Modeling Human Oral Bioavailability

    PubMed Central

    Wang, Junmei; Hou, Tingjun

    2015-01-01

    Although significant progress has been made in experimental high throughput screening (HTS) of ADME (absorption, distribution, metabolism, excretion) and pharmacokinetic properties, the ADME and Toxicity (ADME-Tox) in silico modeling is still indispensable in drug discovery as it can guide us to wisely select drug candidates prior to expensive ADME screenings and clinical trials. Compared to other ADME-Tox properties, human oral bioavailability (HOBA) is particularly important but extremely difficult to predict. In this paper, the advances in human oral bioavailability modeling will be reviewed. Moreover, our deep insight on how to construct more accurate and reliable HOBA QSAR and classification models will also discussed. PMID:25582307

  16. Mathematical models of human african trypanosomiasis epidemiology.

    PubMed

    Rock, Kat S; Stone, Chris M; Hastings, Ian M; Keeling, Matt J; Torr, Steve J; Chitnis, Nakul

    2015-03-01

    Human African trypanosomiasis (HAT), commonly called sleeping sickness, is caused by Trypanosoma spp. and transmitted by tsetse flies (Glossina spp.). HAT is usually fatal if untreated and transmission occurs in foci across sub-Saharan Africa. Mathematical modelling of HAT began in the 1980s with extensions of the Ross-Macdonald malaria model and has since consisted, with a few exceptions, of similar deterministic compartmental models. These models have captured the main features of HAT epidemiology and provided insight on the effectiveness of the two main control interventions (treatment of humans and tsetse fly control) in eliminating transmission. However, most existing models have overestimated prevalence of infection and ignored transient dynamics. There is a need for properly validated models, evolving with improved data collection, that can provide quantitative predictions to help guide control and elimination strategies for HAT.

  17. Optimal estimator model for human spatial orientation

    NASA Technical Reports Server (NTRS)

    Borah, J.; Young, L. R.; Curry, R. E.

    1979-01-01

    A model is being developed to predict pilot dynamic spatial orientation in response to multisensory stimuli. Motion stimuli are first processed by dynamic models of the visual, vestibular, tactile, and proprioceptive sensors. Central nervous system function is then modeled as a steady-state Kalman filter which blends information from the various sensors to form an estimate of spatial orientation. Where necessary, this linear central estimator has been augmented with nonlinear elements to reflect more accurately some highly nonlinear human response characteristics. Computer implementation of the model has shown agreement with several important qualitative characteristics of human spatial orientation, and it is felt that with further modification and additional experimental data the model can be improved and extended. Possible means are described for extending the model to better represent the active pilot with varying skill and work load levels.

  18. Mathematical modeling of the human knee joint

    SciTech Connect

    Ricafort, Juliet

    1996-05-01

    A model was developed to determine the forces exerted by several flexor and extensor muscles of the human knee under static conditions. The following muscles were studied: the gastrocnemius, biceps femoris, semitendinosus, semimembranosus, and the set of quadricep muscles. The tibia and fibula were each modeled as rigid bodies; muscles were modeled by their functional lines of action in space. Assumptions based on previous data were used to resolve the indeterminacy.

  19. NASA: Model development for human factors interfacing

    NASA Technical Reports Server (NTRS)

    Smith, L. L.

    1984-01-01

    The results of an intensive literature review in the general topics of human error analysis, stress and job performance, and accident and safety analysis revealed no usable techniques or approaches for analyzing human error in ground or space operations tasks. A task review model is described and proposed to be developed in order to reduce the degree of labor intensiveness in ground and space operations tasks. An extensive number of annotated references are provided.

  20. Immune-competent human skin disease models.

    PubMed

    Bergers, Lambert I J C; Reijnders, Christianne M A; van den Broek, Lenie J; Spiekstra, Sander W; de Gruijl, Tanja D; Weijers, Ester M; Gibbs, Susan

    2016-09-01

    All skin diseases have an underlying immune component. Owing to differences in animal and human immunology, the majority of drugs fail in the preclinical or clinical testing phases. Therefore animal alternative methods that incorporate human immunology into in vitro skin disease models are required to move the field forward. This review summarizes the progress, using examples from fibrosis, autoimmune diseases, psoriasis, cancer and contact allergy. The emphasis is on co-cultures and 3D organotypic models. Our conclusion is that current models are inadequate and future developments with immune-competent skin-on-chip models based on induced pluripotent stem cells could provide a next generation of skin models for drug discovery and testing.

  1. Three dimensional model of the human mandible.

    PubMed

    Muftić, O; Milcić, D; Saucha, J; Carek, V

    2000-07-01

    A new biomechanical three-dimensional (3D) model for the human mandible is proposed. A simple two-dimensional model cannot explain the biomechanics of the human mandible, where muscular forces through occlusion and condylar surfaces are in a state of dynamical 3D equilibrium. All forces are resolved into components according to a selected coordinate system. The muscular forces, which during clenching act on the jaw, along with the necessary force level for chewing, also act as some kind of stabilizers of the mandibular condyles preventing dislocation and loading of nonarticular tissues.

  2. Generative models of the human connectome

    PubMed Central

    Betzel, Richard F.; Avena-Koenigsberger, Andrea; Goñi, Joaquín; He, Ye; de Reus, Marcel A.; Griffa, Alessandra; Vértes, Petra E.; Mišic, Bratislav; Thiran, Jean-Philippe; Hagmann, Patric; van den Heuvel, Martijn; Zuo, Xi-Nian; Bullmore, Edward T.; Sporns, Olaf

    2016-01-01

    The human connectome represents a network map of the brain's wiring diagram and the pattern into which its connections are organized is thought to play an important role in cognitive function. The generative rules that shape the topology of the human connectome remain incompletely understood. Earlier work in model organisms has suggested that wiring rules based on geometric relationships (distance) can account for many but likely not all topological features. Here we systematically explore a family of generative models of the human connectome that yield synthetic networks designed according to different wiring rules combining geometric and a broad range of topological factors. We find that a combination of geometric constraints with a homophilic attachment mechanism can create synthetic networks that closely match many topological characteristics of individual human connectomes, including features that were not included in the optimization of the generative model itself. We use these models to investigate a lifespan dataset and show that, with age, the model parameters undergo progressive changes, suggesting a rebalancing of the generative factors underlying the connectome across the lifespan. PMID:26427642

  3. Generative models of the human connectome.

    PubMed

    Betzel, Richard F; Avena-Koenigsberger, Andrea; Goñi, Joaquín; He, Ye; de Reus, Marcel A; Griffa, Alessandra; Vértes, Petra E; Mišic, Bratislav; Thiran, Jean-Philippe; Hagmann, Patric; van den Heuvel, Martijn; Zuo, Xi-Nian; Bullmore, Edward T; Sporns, Olaf

    2016-01-01

    The human connectome represents a network map of the brain's wiring diagram and the pattern into which its connections are organized is thought to play an important role in cognitive function. The generative rules that shape the topology of the human connectome remain incompletely understood. Earlier work in model organisms has suggested that wiring rules based on geometric relationships (distance) can account for many but likely not all topological features. Here we systematically explore a family of generative models of the human connectome that yield synthetic networks designed according to different wiring rules combining geometric and a broad range of topological factors. We find that a combination of geometric constraints with a homophilic attachment mechanism can create synthetic networks that closely match many topological characteristics of individual human connectomes, including features that were not included in the optimization of the generative model itself. We use these models to investigate a lifespan dataset and show that, with age, the model parameters undergo progressive changes, suggesting a rebalancing of the generative factors underlying the connectome across the lifespan. PMID:26427642

  4. A stochastic model of human gait dynamics

    NASA Astrophysics Data System (ADS)

    Ashkenazy, Yosef; M. Hausdorff, Jeffrey; Ch. Ivanov, Plamen; Eugene Stanley, H.

    2002-12-01

    We present a stochastic model of gait rhythm dynamics, based on transitions between different “neural centers”, that reproduces distinctive statistical properties of normal human walking. By tuning one model parameter, the transition (hopping) range, the model can describe alterations in gait dynamics from childhood to adulthood-including a decrease in the correlation and volatility exponents with maturation. The model also generates time series with multifractal spectra whose broadness depends only on this parameter. Moreover, we find that the volatility exponent increases monotonically as a function of the width of the multifractal spectrum, suggesting the possibility of a change in multifractality with maturation.

  5. Engineering large animal models of human disease.

    PubMed

    Whitelaw, C Bruce A; Sheets, Timothy P; Lillico, Simon G; Telugu, Bhanu P

    2016-01-01

    The recent development of gene editing tools and methodology for use in livestock enables the production of new animal disease models. These tools facilitate site-specific mutation of the genome, allowing animals carrying known human disease mutations to be produced. In this review, we describe the various gene editing tools and how they can be used for a range of large animal models of diseases. This genomic technology is in its infancy but the expectation is that through the use of gene editing tools we will see a dramatic increase in animal model resources available for both the study of human disease and the translation of this knowledge into the clinic. Comparative pathology will be central to the productive use of these animal models and the successful translation of new therapeutic strategies.

  6. Airflow patterns in a human nasal model

    SciTech Connect

    Hornung, D.E.; Leopold, D.A.; Youngentob, S.L.; Sheehe, P.R.; Gagne, G.M.; Thomas, F.D.; Mozell, M.M.

    1987-02-01

    Nasal airflow patterns were studied by using xenon 133 gas to image the course taken by air as it flowed through a plastic model of the human nasal cavity. The model was produced from the head of a human cadaver, and was anatomically correct. A needle catheter was used to infuse the radioactive xenon into a continuous flow of room air maintained through the model by a variable vacuum source connected to the nasopharynx. The radioactive gas was infused at one of five release sites in the nostril, and the distribution of the radioactivity was imaged in the sagittal plane with a scintillation camera. The data were organized to show the activity in six contiguous regions of the midnose. For each catheter, release site activity patterns were determined for three flow rates. The results of this experiment showed that both catheter position and flow rate had significant and reproducible effects on the distribution of radioactivity within the model.

  7. Bayesian Modeling of a Human MMORPG Player

    NASA Astrophysics Data System (ADS)

    Synnaeve, Gabriel; Bessière, Pierre

    2011-03-01

    This paper describes an application of Bayesian programming to the control of an autonomous avatar in a multiplayer role-playing game (the example is based on World of Warcraft). We model a particular task, which consists of choosing what to do and to select which target in a situation where allies and foes are present. We explain the model in Bayesian programming and show how we could learn the conditional probabilities from data gathered during human-played sessions.

  8. Modelling dengue epidemic spreading with human mobility

    NASA Astrophysics Data System (ADS)

    Barmak, D. H.; Dorso, C. O.; Otero, M.

    2016-04-01

    We explored the effect of human mobility on the spatio-temporal dynamics of Dengue with a stochastic model that takes into account the epidemiological dynamics of the infected mosquitoes and humans, with different mobility patterns of the human population. We observed that human mobility strongly affects the spread of infection by increasing the final size and by changing the morphology of the epidemic outbreaks. When the spreading of the disease is driven only by mosquito dispersal (flight), a main central focus expands diffusively. On the contrary, when human mobility is taken into account, multiple foci appear throughout the evolution of the outbreaks. These secondary foci generated throughout the outbreaks could be of little importance according to their mass or size compared with the largest main focus. However, the coalescence of these foci with the main one generates an effect, through which the latter develops a size greater than the one obtained in the case driven only by mosquito dispersal. This increase in growth rate due to human mobility and the coalescence of the foci are particularly relevant in temperate cities such as the city of Buenos Aires, since they give more possibilities to the outbreak to grow before the arrival of the low-temperature season. The findings of this work indicate that human mobility could be the main driving force in the dynamics of vector epidemics.

  9. Are animal models predictive for humans?

    PubMed Central

    2009-01-01

    It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes. Whether animals can be used to predict human response to drugs and other chemicals is apparently a contentious issue. However, when one empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is not surprising considering what we have learned from fields such evolutionary and developmental biology, gene regulation and expression, epigenetics, complexity theory, and comparative genomics. PMID:19146696

  10. Cholestasis: human disease and experimental animal models.

    PubMed

    Rodríguez-Garay, Emilio Alberto

    2003-01-01

    Cholestasis may result from a failure in bile secretion in hepatocytes or ductular cells, or from a blockade to the free bile flow. Human cholestasis may be induced by many drugs, being antibiotics the more common. Other types of cholestasis seen in humans are a group of familial cholestatic disorders, obstructive cholestasis, primary biliary cirrhosis, extrahepatic biliary atresia, primary sclerosing cholangitis, cholestasis of pregnancy, oral contraceptive-induced cholestasis, and sepsis-induced cholestasis. Experimental animal models allow the understanding of pathophysiological mechanisms involved and their clinical correlates. The most common experimental models of intrahepatic cholestasis are estrogen-induced, endotoxin-induced and drug-induced cholestasis. A well known model of extrahepatic biliary obstruction is common bile duct ligation. Drug-induced cholestasis were described using different drugs. On this regard, alpha naphthylisothiocyanate treatment has been extensively used, permitting to describe not only cholestatic alterations but also compensatory mechanisms. Congenital defficiency of transport proteins also were studied in natural rat models of cholestasis. The experimental animal models allow to define down-regulated alterations of hepatocyte transport proteins, and up-regulated ones acting as compensatory mechanisms. In conclusion, animal model and transport protein studies are necessary for the progressive understanding of congenital and acquired human cholestasis, and regulatory mechanisms that operate on liver cells.

  11. Canine models of human rare disorders

    PubMed Central

    Hytönen, Marjo K.

    2016-01-01

    ABSTRACT Millions of children worldwide are born with rare and debilitating developmental disorders each year. Although an increasing number of these conditions are being recognized at the molecular level, the characterization of the underlying pathophysiology remains a grand challenge. This is often due to the lack of appropriate patient material or relevant animal models. Dogs are coming to the rescue as physiologically relevant large animal models. Hundreds of spontaneous genetic conditions have been described in dogs, most with close counterparts to human rare disorders. Our recent examples include the canine models of human Caffey (SLC37A2), van den Ende-Gupta (SCARF2) and Raine (FAM20C) syndromes. These studies demonstrate the pathophysiological similarity of human and canine syndromes, and suggest that joint efforts to characterize both human and canine rare diseases could provide additional benefits to the advancement of the field of rare diseases. Besides revealing new candidate genes, canine models allow access to experimental resources such as cells, tissues and even live animals for research and intervention purposes. PMID:27803843

  12. Human driven transitions in complex model ecosystems

    NASA Astrophysics Data System (ADS)

    Harfoot, Mike; Newbold, Tim; Tittinsor, Derek; Purves, Drew

    2015-04-01

    Human activities have been observed to be impacting ecosystems across the globe, leading to reduced ecosystem functioning, altered trophic and biomass structure and ultimately ecosystem collapse. Previous attempts to understand global human impacts on ecosystems have usually relied on statistical models, which do not explicitly model the processes underlying the functioning of ecosystems, represent only a small proportion of organisms and do not adequately capture complex non-linear and dynamic responses of ecosystems to perturbations. We use a mechanistic ecosystem model (1), which simulates the underlying processes structuring ecosystems and can thus capture complex and dynamic interactions, to investigate boundaries of complex ecosystems to human perturbation. We explore several drivers including human appropriation of net primary production and harvesting of animal biomass. We also present an analysis of the key interactions between biotic, societal and abiotic earth system components, considering why and how we might think about these couplings. References: M. B. J. Harfoot et al., Emergent global patterns of ecosystem structure and function from a mechanistic general ecosystem model., PLoS Biol. 12, e1001841 (2014).

  13. Virtual human hand: model and kinematics.

    PubMed

    Peña-Pitarch, Esteban; Falguera, Neus Ticó; Yang, Jingzhou James

    2014-04-01

    The human hand plays an important role in daily life. It is the interface between the human and the exterior world by positioning, orienting, touching and grasping objects. The human hand has multiple degrees of freedom (DOFs) to enable mobility and dexterity. A virtual human hand model can be inserted into CAD (Computer Aided Design) models to assess the manipulation capabilities in the early design stage to reduce design time and cost. Joystick assessment is one of the important design cases. This study is a first step towards a comprehensive hand simulation tool to simulate the manipulation and grasping of objects. This paper presents a novel 25 DOFs' hand skeletal model based on hand anatomy and hand kinematics: (1) joint range of motion, (2) Denavit-Hartenberg method to define the joint relationship and (3) finger workspace determination. Novelty for this hand model includes arching the palm with the four DOFs added in the carpometacarpal and wrist joints for the ring and small fingers.

  14. Constructing predictive models of human running.

    PubMed

    Maus, Horst-Moritz; Revzen, Shai; Guckenheimer, John; Ludwig, Christian; Reger, Johann; Seyfarth, Andre

    2015-02-01

    Running is an essential mode of human locomotion, during which ballistic aerial phases alternate with phases when a single foot contacts the ground. The spring-loaded inverted pendulum (SLIP) provides a starting point for modelling running, and generates ground reaction forces that resemble those of the centre of mass (CoM) of a human runner. Here, we show that while SLIP reproduces within-step kinematics of the CoM in three dimensions, it fails to reproduce stability and predict future motions. We construct SLIP control models using data-driven Floquet analysis, and show how these models may be used to obtain predictive models of human running with six additional states comprising the position and velocity of the swing-leg ankle. Our methods are general, and may be applied to any rhythmic physical system. We provide an approach for identifying an event-driven linear controller that approximates an observed stabilization strategy, and for producing a reduced-state model which closely recovers the observed dynamics.

  15. Animal models of human granulocyte diseases.

    PubMed

    Schäffer, Alejandro A; Klein, Christoph

    2013-02-01

    In vivo animal models have proven very useful to the understanding of basic biologic pathways of the immune system, a prerequisite for the development of innovate therapies. This article addresses currently available models for defined human monogenetic defects of neutrophil granulocytes, including murine, zebrafish, and larger mammalian species. Strengths and weaknesses of each system are summarized, and clinical investigators may thus be inspired to develop further lines of research to improve diagnosis and therapy by use of the appropriate animal model system. PMID:23351993

  16. Modeling human influenza infection in the laboratory

    PubMed Central

    Radigan, Kathryn A; Misharin, Alexander V; Chi, Monica; Budinger, GR Scott

    2015-01-01

    Influenza is the leading cause of death from an infectious cause. Because of its clinical importance, many investigators use animal models to understand the biologic mechanisms of influenza A virus replication, the immune response to the virus, and the efficacy of novel therapies. This review will focus on the biosafety, biosecurity, and ethical concerns that must be considered in pursuing influenza research, in addition to focusing on the two animal models – mice and ferrets – most frequently used by researchers as models of human influenza infection. PMID:26357484

  17. Space Station crew safety - Human factors model

    NASA Technical Reports Server (NTRS)

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

    1984-01-01

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

  18. Multistage integration model for human egomotion perception.

    PubMed

    Zacharias, G L; Miao, A X; Warren, R

    1995-01-01

    Human computational vision models that attempt to account for the dynamic perception of egomotion and relative depth typically assume a common three-stage process: first, compute the optical flow field based on the dynamically changing image; second, estimate the egomotion states based on the flow; and third, estimate the relative depth/shape based on the egomotion states and possibly on a model of the viewed surface. We propose a model more in line with recent work in human vision, employing multistage integration. Here the dynamic image is first processed to generate spatial and temporal image gradients that drive a mutually interconnected state estimator and depth/shape estimator. The state estimator uses the image gradient information in combination with a depth/shape estimate of the viewed surface and an assumed model of the viewer's dynamics to generate current state estimates; in tandem, the depth/shape estimator uses the image gradient information in combination with the viewer's state estimate and assumed shape model to generate current depth/shape estimates. In this paper, we describe the model and compare model predictions with empirical data.

  19. Development of a realistic human airway model.

    PubMed

    Lizal, Frantisek; Elcner, Jakub; Hopke, Philip K; Jedelsky, Jan; Jicha, Miroslav

    2012-03-01

    Numerous models of human lungs with various levels of idealization have been reported in the literature; consequently, results acquired using these models are difficult to compare to in vivo measurements. We have developed a set of model components based on realistic geometries, which permits the analysis of the effects of subsequent model simplification. A realistic digital upper airway geometry except for the lack of an oral cavity has been created which proved suitable both for computational fluid dynamics (CFD) simulations and for the fabrication of physical models. Subsequently, an oral cavity was added to the tracheobronchial geometry. The airway geometry including the oral cavity was adjusted to enable fabrication of a semi-realistic model. Five physical models were created based on these three digital geometries. Two optically transparent models, one with and one without the oral cavity, were constructed for flow velocity measurements, two realistic segmented models, one with and one without the oral cavity, were constructed for particle deposition measurements, and a semi-realistic model with glass cylindrical airways was developed for optical measurements of flow velocity and in situ particle size measurements. One-dimensional phase doppler anemometry measurements were made and compared to the CFD calculations for this model and good agreement was obtained. PMID:22558834

  20. Modeling the Human Knee for Assistive Technologies

    PubMed Central

    Sartori, Massimo; Reggiani, Monica; Pagello, Enrico; Lloyd, David G.

    2013-01-01

    In this paper, we use motion capture technology together with an EMG-driven musculoskeletal model of the knee joint to predict muscle behavior during human dynamic movements. We propose a muscle model based on infinitely stiff tendons and show this allows speeding up 250 times the computation of muscle force and the resulting joint moment calculation with no loss of accuracy with respect to the previously developed elastictendon model. We then integrate our previously developed method for the estimation of 3-D musculotendon kinematics in the proposed EMG-driven model. This new code enabled the creation of a standalone EMG-driven model that was implemented and run on an embedded system for applications in assistive technologies such as myoelectrically controlled prostheses and orthoses. PMID:22911539

  1. Modeling Operations Costs for Human Exploration Architectures

    NASA Technical Reports Server (NTRS)

    Shishko, Robert

    2013-01-01

    Operations and support (O&S) costs for human spaceflight have not received the same attention in the cost estimating community as have development costs. This is unfortunate as O&S costs typically comprise a majority of life-cycle costs (LCC) in such programs as the International Space Station (ISS) and the now-cancelled Constellation Program. Recognizing this, the Constellation Program and NASA HQs supported the development of an O&S cost model specifically for human spaceflight. This model, known as the Exploration Architectures Operations Cost Model (ExAOCM), provided the operations cost estimates for a variety of alternative human missions to the moon, Mars, and Near-Earth Objects (NEOs) in architectural studies. ExAOCM is philosophically based on the DoD Architecture Framework (DoDAF) concepts of operational nodes, systems, operational functions, and milestones. This paper presents some of the historical background surrounding the development of the model, and discusses the underlying structure, its unusual user interface, and lastly, previous examples of its use in the aforementioned architectural studies.

  2. Nonlinear dynamical model of human gait.

    PubMed

    West, Bruce J; Scafetta, Nicola

    2003-05-01

    We present a nonlinear dynamical model of the human gait control system in a variety of gait regimes. The stride-interval time series in normal human gait is characterized by slightly multifractal fluctuations. The fractal nature of the fluctuations becomes more pronounced under both an increase and decrease in the average gait. Moreover, the long-range memory in these fluctuations is lost when the gait is keyed on a metronome. Human locomotion is controlled by a network of neurons capable of producing a correlated syncopated output. The central nervous system is coupled to the motocontrol system, and together they control the locomotion of the gait cycle itself. The metronomic gait is simulated by a forced nonlinear oscillator with a periodic external force associated with the conscious act of walking in a particular way. PMID:12786188

  3. Nonlinear dynamical model of human gait

    NASA Astrophysics Data System (ADS)

    West, Bruce J.; Scafetta, Nicola

    2003-05-01

    We present a nonlinear dynamical model of the human gait control system in a variety of gait regimes. The stride-interval time series in normal human gait is characterized by slightly multifractal fluctuations. The fractal nature of the fluctuations becomes more pronounced under both an increase and decrease in the average gait. Moreover, the long-range memory in these fluctuations is lost when the gait is keyed on a metronome. Human locomotion is controlled by a network of neurons capable of producing a correlated syncopated output. The central nervous system is coupled to the motocontrol system, and together they control the locomotion of the gait cycle itself. The metronomic gait is simulated by a forced nonlinear oscillator with a periodic external force associated with the conscious act of walking in a particular way.

  4. Recent trends in digital human modeling and the concurrent issues that face human modeling approach

    NASA Technical Reports Server (NTRS)

    Rajulu, Sudhakar; Gonzalez, L. Javier; Margerum, Sarah; Clowers, Kurt; Moreny, Richard; Abercomby, Andrew; Velasquez, Luis

    2006-01-01

    Tremendous strides have been made in the recent years to digitally represent human beings in computer simulation models ranging from assembly plant maintenance operations to occupants getting in and out of vehicles to action movie scenarios. While some of these tools are being actively pursued by the engineering communities, there is still a lot of work that remains to be done for the newly planned planetary exploration missions. For example, certain unique and several common challenges are seen in developing computer generated suited human models for designing the next generation space vehicle. The purpose of this presentation is to discuss NASA s potential needs for better human models and to show also many of the inherent yet not too obvious pitfalls that still are left unresolved in this new arena of digital human modeling. As part of NASA s Habitability and Human Factors Branch, the Anthropometry and Biomechanics Facility has been engaged in studying the various facets of computer generated human physical performance models; for instance, it has been engaged in utilizing three-dimensional laser scan data along with three dimensional video based motion and reach data to gather suited anthropometric and shape and size information that are not available yet in the form of computer mannequins. Our goal is to bring in new approaches to deal with heavily clothed humans (such as, suited astronauts) and to overcome the current limitations of wrongly identifying humans (either real or virtual) as univariate percentiles. We are looking at whole-body posture based anthropometric models as a means to identify humans of significantly different shapes and sizes to arrive at mathematically sound computer models for analytical purposes.

  5. Modeling fear‐conditioned bradycardia in humans

    PubMed Central

    Tzovara, Athina; Staib, Matthias; Paulus, Philipp C.; Hofer, Nicolas; Bach, Dominik R.

    2016-01-01

    Abstract Across species, cued fear conditioning is a common experimental paradigm to investigate aversive Pavlovian learning. While fear‐conditioned stimuli (CS+) elicit overt behavior in many mammals, this is not the case in humans. Typically, autonomic nervous system activity is used to quantify fear memory in humans, measured by skin conductance responses (SCR). Here, we investigate whether heart period responses (HPR) evoked by the CS, often observed in humans and small mammals, are suitable to complement SCR as an index of fear memory in humans. We analyze four datasets involving delay and trace conditioning, in which heart beats are identified via electrocardiogram or pulse oximetry, to show that fear‐conditioned heart rate deceleration (bradycardia) is elicited and robustly distinguishes CS+ from CS−. We then develop a psychophysiological model (PsPM) of fear‐conditioned HPR. This PsPM is inverted to yield estimates of autonomic input into the heart. We show that the sensitivity to distinguish CS+ and CS− (predictive validity) is higher for model‐based estimates than peak‐scoring analysis, and compare this with SCR. Our work provides a novel tool to investigate fear memory in humans that allows direct comparison between species. PMID:26950648

  6. Understanding human functioning using graphical models

    PubMed Central

    2010-01-01

    Background Functioning and disability are universal human experiences. However, our current understanding of functioning from a comprehensive perspective is limited. The development of the International Classification of Functioning, Disability and Health (ICF) on the one hand and recent developments in graphical modeling on the other hand might be combined and open the door to a more comprehensive understanding of human functioning. The objective of our paper therefore is to explore how graphical models can be used in the study of ICF data for a range of applications. Methods We show the applicability of graphical models on ICF data for different tasks: Visualization of the dependence structure of the data set, dimension reduction and comparison of subpopulations. Moreover, we further developed and applied recent findings in causal inference using graphical models to estimate bounds on intervention effects in an observational study with many variables and without knowing the underlying causal structure. Results In each field, graphical models could be applied giving results of high face-validity. In particular, graphical models could be used for visualization of functioning in patients with spinal cord injury. The resulting graph consisted of several connected components which can be used for dimension reduction. Moreover, we found that the differences in the dependence structures between subpopulations were relevant and could be systematically analyzed using graphical models. Finally, when estimating bounds on causal effects of ICF categories on general health perceptions among patients with chronic health conditions, we found that the five ICF categories that showed the strongest effect were plausible. Conclusions Graphical Models are a flexible tool and lend themselves for a wide range of applications. In particular, studies involving ICF data seem to be suited for analysis using graphical models. PMID:20149230

  7. Human Plague Risk: Spatial-Temporal Models

    NASA Technical Reports Server (NTRS)

    Pinzon, Jorge E.

    2010-01-01

    This chpater reviews the use of spatial-temporal models in identifying potential risks of plague outbreaks into the human population. Using earth observations by satellites remote sensing there has been a systematic analysis and mapping of the close coupling between the vectors of the disease and climate variability. The overall result is that incidence of plague is correlated to positive El Nino/Southem Oscillation (ENSO).

  8. Computational models of human vision with applications

    NASA Technical Reports Server (NTRS)

    Wandell, B. A.

    1985-01-01

    Perceptual problems in aeronautics were studied. The mechanism by which color constancy is achieved in human vision was examined. A computable algorithm was developed to model the arrangement of retinal cones in spatial vision. The spatial frequency spectra are similar to the spectra of actual cone mosaics. The Hartley transform as a tool of image processing was evaluated and it is suggested that it could be used in signal processing applications, GR image processing.

  9. MODELING HUMAN RELIABILITY ANALYSIS USING MIDAS

    SciTech Connect

    Ronald L. Boring; Donald D. Dudenhoeffer; Bruce P. Hallbert; Brian F. Gore

    2006-05-01

    This paper summarizes an emerging collaboration between Idaho National Laboratory and NASA Ames Research Center regarding the utilization of high-fidelity MIDAS simulations for modeling control room crew performance at nuclear power plants. The key envisioned uses for MIDAS-based control room simulations are: (i) the estimation of human error with novel control room equipment and configurations, (ii) the investigative determination of risk significance in recreating past event scenarios involving control room operating crews, and (iii) the certification of novel staffing levels in control rooms. It is proposed that MIDAS serves as a key component for the effective modeling of risk in next generation control rooms.

  10. Human responses to augmented virtual scaffolding models.

    PubMed

    Hsiao, Hongwei; Simeonov, Peter; Dotson, Brian; Ammons, Douglas; Kau, Tsui-Ying; Chiou, Sharon

    2005-08-15

    This study investigated the effect of adding real planks, in virtual scaffolding models of elevation, on human performance in a surround-screen virtual reality (SSVR) system. Twenty-four construction workers and 24 inexperienced controls performed walking tasks on real and virtual planks at three virtual heights (0, 6 m, 12 m) and two scaffolding-platform-width conditions (30, 60 cm). Gait patterns, walking instability measurements and cardiovascular reactivity were assessed. The results showed differences in human responses to real vs. virtual planks in walking patterns, instability score and heart-rate inter-beat intervals; it appeared that adding real planks in the SSVR virtual scaffolding model enhanced the quality of SSVR as a human - environment interface research tool. In addition, there were significant differences in performance between construction workers and the control group. The inexperienced participants were more unstable as compared to construction workers. Both groups increased their stride length with repetitions of the task, indicating a possibly confidence- or habit-related learning effect. The practical implications of this study are in the adoption of augmented virtual models of elevated construction environments for injury prevention research, and the development of programme for balance-control training to reduce the risk of falls at elevation before workers enter a construction job. PMID:16253942

  11. Modeling Oxygen Transport in the Human Placenta

    NASA Astrophysics Data System (ADS)

    Serov, Alexander; Filoche, Marcel; Salafia, Carolyn; Grebenkov, Denis

    Efficient functioning of the human placenta is crucial for the favorable pregnancy outcome. We construct a 3D model of oxygen transport in the placenta based on its histological cross-sections. The model accounts for both diffusion and convention of oxygen in the intervillous space and allows one to estimate oxygen uptake of a placentone. We demonstrate the existence of an optimal villi density maximizing the uptake and explain it as a trade-off between the incoming oxygen flow and the absorbing villous surface. Calculations performed for arbitrary shapes of fetal villi show that only two geometrical characteristics - villi density and the effective villi radius - are required to predict fetal oxygen uptake. Two combinations of physiological parameters that determine oxygen uptake are also identified: maximal oxygen inflow of a placentone and the Damköhler number. An automatic image analysis method is developed and applied to 22 healthy placental cross-sections demonstrating that villi density of a healthy human placenta lies within 10% of the optimal value, while overall geometry efficiency is rather low (around 30-40%). In a perspective, the model can constitute the base of a reliable tool of post partum oxygen exchange efficiency assessment in the human placenta. Also affiliated with Department of Chemistry and Biochemistry, UCLA, Los Angeles, CA 90095, USA.

  12. Human responses to augmented virtual scaffolding models.

    PubMed

    Hsiao, Hongwei; Simeonov, Peter; Dotson, Brian; Ammons, Douglas; Kau, Tsui-Ying; Chiou, Sharon

    2005-08-15

    This study investigated the effect of adding real planks, in virtual scaffolding models of elevation, on human performance in a surround-screen virtual reality (SSVR) system. Twenty-four construction workers and 24 inexperienced controls performed walking tasks on real and virtual planks at three virtual heights (0, 6 m, 12 m) and two scaffolding-platform-width conditions (30, 60 cm). Gait patterns, walking instability measurements and cardiovascular reactivity were assessed. The results showed differences in human responses to real vs. virtual planks in walking patterns, instability score and heart-rate inter-beat intervals; it appeared that adding real planks in the SSVR virtual scaffolding model enhanced the quality of SSVR as a human - environment interface research tool. In addition, there were significant differences in performance between construction workers and the control group. The inexperienced participants were more unstable as compared to construction workers. Both groups increased their stride length with repetitions of the task, indicating a possibly confidence- or habit-related learning effect. The practical implications of this study are in the adoption of augmented virtual models of elevated construction environments for injury prevention research, and the development of programme for balance-control training to reduce the risk of falls at elevation before workers enter a construction job.

  13. Biomedical Simulation Models of Human Auditory Processes

    NASA Technical Reports Server (NTRS)

    Bicak, Mehmet M. A.

    2012-01-01

    Detailed acoustic engineering models that explore noise propagation mechanisms associated with noise attenuation and transmission paths created when using hearing protectors such as earplugs and headsets in high noise environments. Biomedical finite element (FE) models are developed based on volume Computed Tomography scan data which provides explicit external ear, ear canal, middle ear ossicular bones and cochlea geometry. Results from these studies have enabled a greater understanding of hearing protector to flesh dynamics as well as prioritizing noise propagation mechanisms. Prioritization of noise mechanisms can form an essential framework for exploration of new design principles and methods in both earplug and earcup applications. These models are currently being used in development of a novel hearing protection evaluation system that can provide experimentally correlated psychoacoustic noise attenuation. Moreover, these FE models can be used to simulate the effects of blast related impulse noise on human auditory mechanisms and brain tissue.

  14. Models of human core transcriptional regulatory circuitries

    PubMed Central

    Saint-André, Violaine; Federation, Alexander J.; Lin, Charles Y.; Abraham, Brian J.; Reddy, Jessica; Lee, Tong Ihn; Bradner, James E.; Young, Richard A.

    2016-01-01

    A small set of core transcription factors (TFs) dominates control of the gene expression program in embryonic stem cells and other well-studied cellular models. These core TFs collectively regulate their own gene expression, thus forming an interconnected auto-regulatory loop that can be considered the core transcriptional regulatory circuitry (CRC) for that cell type. There is limited knowledge of core TFs, and thus models of core regulatory circuitry, for most cell types. We recently discovered that genes encoding known core TFs forming CRCs are driven by super-enhancers, which provides an opportunity to systematically predict CRCs in poorly studied cell types through super-enhancer mapping. Here, we use super-enhancer maps to generate CRC models for 75 human cell and tissue types. These core circuitry models should prove valuable for further investigating cell-type–specific transcriptional regulation in healthy and diseased cells. PMID:26843070

  15. A dynamic model of human physiology

    NASA Astrophysics Data System (ADS)

    Green, Melissa; Kaplan, Carolyn; Oran, Elaine; Boris, Jay

    2010-11-01

    To study the systems-level transport in the human body, we develop the Computational Man (CMAN): a set of one-dimensional unsteady elastic flow simulations created to model a variety of coupled physiological systems including the circulatory, respiratory, excretory, and lymphatic systems. The model systems are collapsed from three spatial dimensions and time to one spatial dimension and time by assuming axisymmetric vessel geometry and a parabolic velocity profile across the cylindrical vessels. To model the actions of a beating heart or expanding lungs, the flow is driven by user-defined changes to the equilibrium areas of the elastic vessels. The equations are then iteratively solved for pressure, area, and average velocity. The model is augmented with valves and contractions to resemble the biological structure of the different systems. CMAN will be used to track material transport throughout the human body for diagnostic and predictive purposes. Parameters will be adjustable to match those of individual patients. Validation of CMAN has used both higher-dimensional simulations of similar geometries and benchmark measurement from medical literature.

  16. Testing Bayesian models of human coincidence timing.

    PubMed

    Miyazaki, Makoto; Nozaki, Daichi; Nakajima, Yasoichi

    2005-07-01

    A sensorimotor control task often requires an accurate estimation of the timing of the arrival of an external target (e.g., when hitting a pitched ball). Conventional studies of human timing processes have ignored the stochastic features of target timing: e.g., the speed of the pitched ball is not generally constant, but is variable. Interestingly, based on Bayesian theory, it has been recently shown that the human sensorimotor system achieves the optimal estimation by integrating sensory information with prior knowledge of the probabilistic structure of the target variation. In this study, we tested whether Bayesian integration is also implemented while performing a coincidence-timing type of sensorimotor task by manipulating the trial-by-trial variability (i.e., the prior distribution) of the target timing. As a result, within several hundred trials of learning, subjects were able to generate systematic timing behavior according to the width of the prior distribution, as predicted by the optimal Bayesian model. Considering the previous studies showing that the human sensorimotor system uses Bayesian integration in spacing and force-grading tasks, our result indicates that Bayesian integration is fundamental to all aspects of human sensorimotor control. Moreover, it was noteworthy that the subjects could adjust their behavior both when the prior distribution was switched from wide to narrow and vice versa, although the adjustment was slower in the former case. Based on a comparison with observations in a previous study, we discuss the flexibility and adaptability of Bayesian sensorimotor learning.

  17. Modeling human reliability analysis using MIDAS

    SciTech Connect

    Boring, R. L.

    2006-07-01

    This paper documents current efforts to infuse human reliability analysis (HRA) into human performance simulation. The Idaho National Laboratory is teamed with NASA Ames Research Center to bridge the SPAR-H HRA method with NASA's Man-machine Integration Design and Analysis System (MIDAS) for use in simulating and modeling the human contribution to risk in nuclear power plant control room operations. It is anticipated that the union of MIDAS and SPAR-H will pave the path for cost-effective, timely, and valid simulated control room operators for studying current and next generation control room configurations. This paper highlights considerations for creating the dynamic HRA framework necessary for simulation, including event dependency and granularity. This paper also highlights how the SPAR-H performance shaping factors can be modeled in MIDAS across static, dynamic, and initiator conditions common to control room scenarios. This paper concludes with a discussion of the relationship of the workload factors currently in MIDAS and the performance shaping factors in SPAR-H. (authors)

  18. Modeling Breast Tumor Development with a Humanized Mouse Model.

    PubMed

    Arendt, Lisa M

    2016-01-01

    The tumor microenvironment plays a critical role in breast cancer growth and progression to metastasis. Here, we describe a method to examine stromal-epithelial interactions during tumor formation and progression utilizing human-derived mammary epithelial cells and breast stromal cells. This method outlines the isolation of each cell type from reduction mammoplasty tissue, the culture and genetic modification of both epithelial and stromal cells using lentiviral technology, and the method of humanizing and implantation of transformed epithelial cells into the cleared mammary fat pads of immunocompromised mice. This model system may be a useful tool to dissect signaling interactions that contribute to invasive tumor behavior and therapeutic resistance. PMID:27581027

  19. Insights from mouse models into human retinoblastoma

    PubMed Central

    MacPherson, David

    2008-01-01

    Novel murine models of retinoblastoma based on Rb gene deletion in concert with inactivation of Rb family members have recently been developed. These new Rb knockout models of retinoblastoma provide excellent tools for pre-clinical studies and for the exploration of the genetics of tumorigenesis driven by RB inactivation. This review focuses on the developmental consequences of Rb deletion in the retina and the genetic interactions between Rb and the two other members of the pocket protein family, p107 (Rbl1) and p130 (Rbl2). There is increasing appreciation that homozygous RB mutations are insufficient for human retinoblastoma. Identifying and understanding secondary gene alterations that cooperate with RB inactivation in tumorigenesis may be facilitated by mouse models. Recent investigation of the p53 pathway in retinoblastoma, and evidence of spatial topology to early murine retinoblastoma are also discussed in this review. PMID:18489754

  20. Zebrafish Models for Human Acute Organophosphorus Poisoning.

    PubMed

    Faria, Melissa; Garcia-Reyero, Natàlia; Padrós, Francesc; Babin, Patrick J; Sebastián, David; Cachot, Jérôme; Prats, Eva; Arick Ii, Mark; Rial, Eduardo; Knoll-Gellida, Anja; Mathieu, Guilaine; Le Bihanic, Florane; Escalon, B Lynn; Zorzano, Antonio; Soares, Amadeu M V M; Raldúa, Demetrio

    2015-10-22

    Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning.

  1. Zebrafish Models for Human Acute Organophosphorus Poisoning.

    PubMed

    Faria, Melissa; Garcia-Reyero, Natàlia; Padrós, Francesc; Babin, Patrick J; Sebastián, David; Cachot, Jérôme; Prats, Eva; Arick Ii, Mark; Rial, Eduardo; Knoll-Gellida, Anja; Mathieu, Guilaine; Le Bihanic, Florane; Escalon, B Lynn; Zorzano, Antonio; Soares, Amadeu M V M; Raldúa, Demetrio

    2015-01-01

    Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning. PMID:26489395

  2. Zebrafish Models for Human Acute Organophosphorus Poisoning

    PubMed Central

    Faria, Melissa; Garcia-Reyero, Natàlia; Padrós, Francesc; Babin, Patrick J.; Sebastián, David; Cachot, Jérôme; Prats, Eva; Arick II, Mark; Rial, Eduardo; Knoll-Gellida, Anja; Mathieu, Guilaine; Le Bihanic, Florane; Escalon, B. Lynn; Zorzano, Antonio; Soares, Amadeu M.V.M; Raldúa, Demetrio

    2015-01-01

    Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning. PMID:26489395

  3. The quantitative modelling of human spatial habitability

    NASA Technical Reports Server (NTRS)

    Wise, J. A.

    1985-01-01

    A model for the quantitative assessment of human spatial habitability is presented in the space station context. The visual aspect assesses how interior spaces appear to the inhabitants. This aspect concerns criteria such as sensed spaciousness and the affective (emotional) connotations of settings' appearances. The kinesthetic aspect evaluates the available space in terms of its suitability to accommodate human movement patterns, as well as the postural and anthrometric changes due to microgravity. Finally, social logic concerns how the volume and geometry of available space either affirms or contravenes established social and organizational expectations for spatial arrangements. Here, the criteria include privacy, status, social power, and proxemics (the uses of space as a medium of social communication).

  4. Humanized animal exercise model for clinical implication.

    PubMed

    Seo, Dae Yun; Lee, Sung Ryul; Kim, Nari; Ko, Kyung Soo; Rhee, Byoung Doo; Han, Jin

    2014-09-01

    Exercise and physical activity function as a patho-physiological process that can prevent, manage, and regulate numerous chronic conditions, including metabolic syndrome and age-related sarcopenia. Because of research ethics and technical difficulties in humans, exercise models using animals are requisite for the future development of exercise mimetics to treat such abnormalities. Moreover, the beneficial or adverse outcomes of a new regime or exercise intervention in the treatment of a specific condition should be tested prior to implementation in a clinical setting. In rodents, treadmill running (or swimming) and ladder climbing are widely used as aerobic and anaerobic exercise models, respectively. However, exercise models are not limited to these types. Indeed, there are no golden standard exercise modes or protocols for managing or improving health status since the types (aerobic vs. anaerobic), time (morning vs. evening), and duration (continuous vs. acute bouts) of exercise are the critical determinants for achieving expected beneficial effects. To provide insight into the understanding of exercise and exercise physiology, we have summarized current animal exercise models largely based on aerobic and anaerobic criteria. Additionally, specialized exercise models that have been developed for testing the effect of exercise on specific physiological conditions are presented. Finally, we provide suggestions and/or considerations for developing a new regime for an exercise model.

  5. HLA-Modeler: Automated Homology Modeling of Human Leukocyte Antigens.

    PubMed

    Amari, Shinji; Kataoka, Ryoichi; Ikegami, Takashi; Hirayama, Noriaki

    2013-01-01

    The three-dimensional (3D) structures of human leukocyte antigen (HLA) molecules are indispensable for the studies on the functions at molecular level. We have developed a homology modeling system named HLA-modeler specialized in the HLA molecules. Segment matching algorithm is employed for modeling and the optimization of the model is carried out by use of the PFROSST force field considering the implicit solvent model. In order to efficiently construct the homology models, HLA-modeler uses a local database of the 3D structures of HLA molecules. The structure of the antigenic peptide-binding site is important for the function and the 3D structure is highly conserved between various alleles. HLA-modeler optimizes the use of this structural motif. The leave-one-out cross-validation using the crystal structures of class I and class II HLA molecules has demonstrated that the rmsds of nonhydrogen atoms of the sites between homology models and crystal structures are less than 1.0 Å in most cases. The results have indicated that the 3D structures of the antigenic peptide-binding sites can be reproduced by HLA-modeler at the level almost corresponding to the crystal structures.

  6. Modelling human eye under blast loading.

    PubMed

    Esposito, L; Clemente, C; Bonora, N; Rossi, T

    2015-01-01

    Primary blast injury (PBI) is the general term that refers to injuries resulting from the mere interaction of a blast wave with the body. Although few instances of primary ocular blast injury, without a concomitant secondary blast injury from debris, are documented, some experimental studies demonstrate its occurrence. In order to investigate PBI to the eye, a finite element model of the human eye using simple constitutive models was developed. The material parameters were calibrated by a multi-objective optimisation performed on available eye impact test data. The behaviour of the human eye and the dynamics of mechanisms occurring under PBI loading conditions were modelled. For the generation of the blast waves, different combinations of explosive (trinitrotoluene) mass charge and distance from the eye were analysed. An interpretation of the resulting pressure, based on the propagation and reflection of the waves inside the eye bulb and orbit, is proposed. The peculiar geometry of the bony orbit (similar to a frustum cone) can induce a resonance cavity effect and generate a pressure standing wave potentially hurtful for eye tissues.

  7. Modelling human eye under blast loading.

    PubMed

    Esposito, L; Clemente, C; Bonora, N; Rossi, T

    2015-01-01

    Primary blast injury (PBI) is the general term that refers to injuries resulting from the mere interaction of a blast wave with the body. Although few instances of primary ocular blast injury, without a concomitant secondary blast injury from debris, are documented, some experimental studies demonstrate its occurrence. In order to investigate PBI to the eye, a finite element model of the human eye using simple constitutive models was developed. The material parameters were calibrated by a multi-objective optimisation performed on available eye impact test data. The behaviour of the human eye and the dynamics of mechanisms occurring under PBI loading conditions were modelled. For the generation of the blast waves, different combinations of explosive (trinitrotoluene) mass charge and distance from the eye were analysed. An interpretation of the resulting pressure, based on the propagation and reflection of the waves inside the eye bulb and orbit, is proposed. The peculiar geometry of the bony orbit (similar to a frustum cone) can induce a resonance cavity effect and generate a pressure standing wave potentially hurtful for eye tissues. PMID:23521031

  8. The quantitative modelling of human spatial habitability

    NASA Technical Reports Server (NTRS)

    Wise, James A.

    1988-01-01

    A theoretical model for evaluating human spatial habitability (HuSH) in the proposed U.S. Space Station is developed. Optimizing the fitness of the space station environment for human occupancy will help reduce environmental stress due to long-term isolation and confinement in its small habitable volume. The development of tools that operationalize the behavioral bases of spatial volume for visual kinesthetic, and social logic considerations is suggested. This report further calls for systematic scientific investigations of how much real and how much perceived volume people need in order to function normally and with minimal stress in space-based settings. The theoretical model presented in this report can be applied to any size or shape interior, at any scale of consideration, for the Space Station as a whole to an individual enclosure or work station. Using as a point of departure the Isovist model developed by Dr. Michael Benedikt of the U. of Texas, the report suggests that spatial habitability can become as amenable to careful assessment as engineering and life support concerns.

  9. Adaptive human behavior in epidemiological models.

    PubMed

    Fenichel, Eli P; Castillo-Chavez, Carlos; Ceddia, M G; Chowell, Gerardo; Parra, Paula A Gonzalez; Hickling, Graham J; Holloway, Garth; Horan, Richard; Morin, Benjamin; Perrings, Charles; Springborn, Michael; Velazquez, Leticia; Villalobos, Cristina

    2011-04-12

    The science and management of infectious disease are entering a new stage. Increasingly public policy to manage epidemics focuses on motivating people, through social distancing policies, to alter their behavior to reduce contacts and reduce public disease risk. Person-to-person contacts drive human disease dynamics. People value such contacts and are willing to accept some disease risk to gain contact-related benefits. The cost-benefit trade-offs that shape contact behavior, and hence the course of epidemics, are often only implicitly incorporated in epidemiological models. This approach creates difficulty in parsing out the effects of adaptive behavior. We use an epidemiological-economic model of disease dynamics to explicitly model the trade-offs that drive person-to-person contact decisions. Results indicate that including adaptive human behavior significantly changes the predicted course of epidemics and that this inclusion has implications for parameter estimation and interpretation and for the development of social distancing policies. Acknowledging adaptive behavior requires a shift in thinking about epidemiological processes and parameters.

  10. Stem Cell Models of Human Brain Development.

    PubMed

    Kelava, Iva; Lancaster, Madeline A

    2016-06-01

    Recent breakthroughs in pluripotent stem cell technologies have enabled a new class of in vitro systems for functional modeling of human brain development. These advances, in combination with improvements in neural differentiation methods, allow the generation of in vitro systems that reproduce many in vivo features of the brain with remarkable similarity. Here, we describe advances in the development of these methods, focusing on neural rosette and organoid approaches, and compare their relative capabilities and limitations. We also discuss current technical hurdles for recreating the cell-type complexity and spatial architecture of the brain in culture and offer potential solutions.

  11. Virtual pharmacokinetic model of human eye.

    PubMed

    Kotha, Sreevani; Murtomäki, Lasse

    2014-07-01

    A virtual pharmacokinetic 3D model of the human eye is built using Comsol Multiphysics® software, which is based on the Finite Element Method (FEM). The model considers drug release from a polymer patch placed on sclera. The model concentrates on the posterior part of the eye, retina being the target tissue, and comprises the choroidal blood flow, partitioning of the drug between different tissues and active transport at the retina pigment epithelium (RPE)-choroid boundary. Although most straightforward, in order to check the mass balance, no protein binding or metabolism is yet included. It appeared that the most important issue in obtaining reliable simulation results is the finite element mesh, while time stepping has hardly any significance. Simulations were extended to 100,000 s. The concentration of a drug is shown as a function of time at various points of retina, as well as its average value, varying several parameters in the model. This work demonstrates how anybody with basic knowledge of calculus is able to build physically meaningful models of quite complex biological systems.

  12. Molecular modeling of human alkaline sphingomyelinase.

    PubMed

    Suresh, Panneer Selvam; Olubiyi, Olujide; Thirunavukkarasu, Chinnasamy; Strodel, Birgit; Kumar, Muthuvel Suresh

    2011-01-01

    Alkaline sphingomyelinase, which is expressed in the human intestine and hydrolyses sphingomyelin, is a component of the plasma and the lysosomal membranes. Hydrolase of sphingomyelin generates ceramide, sphingosine, and sphingosine 1-phosphate that have regulatory effects on vital cellular functions such as proliferation, differentiation, and apoptosis. The enzyme belongs to the Nucleotide Pyrophosphatase/Phosphodiesterase family and it differs in structural similarity with acidic and neutral sphingomyelinase. In the present study we modeled alkaline sphingomyelinase using homology modeling based on the structure of Nucleotide Pyrophosphatase/Phosphodiesterase from Xanthomonas axonopodis with which it shares 34% identity. Homology modeling was performed using Modeller9v7. We found that Cys78 and Cys394 form a disulphide bond. Further analysis shows that Ser76 may be important for the function of this enzyme, which is supported by the findings of Wu et al. (2005), that S76F abolishes the activity completely. We found that the residues bound to Zn(2+) are conserved and geometrically similar with the template. Molecular Dynamics simulations were carried out for the modeled protein to observe the effect of Zinc metal ions. It was observed that the metal ion has little effect with regard to the stability but induces increased fluctuations in the protein. These analyses showed that Zinc ions play an important role in stabilizing the secondary structure and in maintaining the compactness of the active site. PMID:21544170

  13. Virtual pharmacokinetic model of human eye.

    PubMed

    Kotha, Sreevani; Murtomäki, Lasse

    2014-07-01

    A virtual pharmacokinetic 3D model of the human eye is built using Comsol Multiphysics® software, which is based on the Finite Element Method (FEM). The model considers drug release from a polymer patch placed on sclera. The model concentrates on the posterior part of the eye, retina being the target tissue, and comprises the choroidal blood flow, partitioning of the drug between different tissues and active transport at the retina pigment epithelium (RPE)-choroid boundary. Although most straightforward, in order to check the mass balance, no protein binding or metabolism is yet included. It appeared that the most important issue in obtaining reliable simulation results is the finite element mesh, while time stepping has hardly any significance. Simulations were extended to 100,000 s. The concentration of a drug is shown as a function of time at various points of retina, as well as its average value, varying several parameters in the model. This work demonstrates how anybody with basic knowledge of calculus is able to build physically meaningful models of quite complex biological systems. PMID:24721554

  14. Homology modelling of human P-glycoprotein.

    PubMed

    Domicevica, Laura; Biggin, Philip C

    2015-10-01

    P-glycoprotein (P-gp) is an ATP-binding cassette transporter that exports a huge range of compounds out of cells and is thus one of the key proteins in conferring multi-drug resistance in cancer. Understanding how it achieves such a broad specificity and the series of conformational changes that allow export to occur form major, on-going, research objectives around the world. Much of our knowledge to date has been derived from mutagenesis and assay data. However, in recent years, there has also been great progress in structural biology and although the structure of human P-gp has not yet been solved, there are now a handful of related structures on which homology models can be built to aid in the interpretation of the vast amount of experimental data that currently exists. Many models for P-gp have been built with this aim, but the situation is complicated by the apparent flexibility of the system and by the fact that although many potential templates exist, there is large variation in the conformational state in which they have been crystallized. In this review, we summarize how homology modelling has been used in the past, how models are typically selected and finally illustrate how MD simulations can be used as a means to give more confidence about models that have been generated via this approach.

  15. A three-dimensional human walking model

    NASA Astrophysics Data System (ADS)

    Yang, Q. S.; Qin, J. W.; Law, S. S.

    2015-11-01

    A three-dimensional human bipedal walking model with compliant legs is presented in this paper. The legs are modeled with time-variant dampers, and the model is able to characterize the gait pattern of an individual using a minimal set of parameters. Feedback control, for both the forward and lateral movements, is implemented to regulate the walking performance of the pedestrian. The model provides an improvement over classic invert pendulum models. Numerical studies were undertaken to investigate the effects of leg stiffness and attack angle. Simulation results show that when walking at a given speed, increasing the leg stiffness with a constant attack angle results in a longer step length, a higher step frequency, a faster walking speed and an increase in both the peak vertical and lateral ground reaction forces. Increasing the attack angle with a constant leg stiffness results in a higher step frequency, a decrease in the step length, an increase in the total energy of the system and a decrease in both the peak vertical and lateral ground reaction forces.

  16. Human factors engineering program review model

    SciTech Connect

    Not Available

    1994-07-01

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

  17. A human neurodevelopmental model for Williams syndrome.

    PubMed

    Chailangkarn, Thanathom; Trujillo, Cleber A; Freitas, Beatriz C; Hrvoj-Mihic, Branka; Herai, Roberto H; Yu, Diana X; Brown, Timothy T; Marchetto, Maria C; Bardy, Cedric; McHenry, Lauren; Stefanacci, Lisa; Järvinen, Anna; Searcy, Yvonne M; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Ard, M Colin; Hanson, Kari L; Romero, Sarah; Jacobs, Bob; Dale, Anders M; Dai, Li; Korenberg, Julie R; Gage, Fred H; Bellugi, Ursula; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R

    2016-08-18

    Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain. PMID:27509850

  18. Conditional Lineage Ablation to Model Human Diseases

    NASA Astrophysics Data System (ADS)

    Lee, Paul; Morley, Gregory; Huang, Qian; Fischer, Avi; Seiler, Stephanie; Horner, James W.; Factor, Stephen; Vaidya, Dhananjay; Jalife, Jose; Fishman, Glenn I.

    1998-09-01

    Cell loss contributes to the pathogenesis of many inherited and acquired human diseases. We have developed a system to conditionally ablate cells of any lineage and developmental stage in the mouse by regulated expression of the diphtheria toxin A (DTA) gene by using tetracycline-responsive promoters. As an example of this approach, we targeted expression of DTA to the hearts of adult mice to model structural abnormalities commonly observed in human cardiomyopathies. Induction of DTA expression resulted in cell loss, fibrosis, and chamber dilatation. As in many human cardiomyopathies, transgenic mice developed spontaneous arrhythmias in vivo, and programmed electrical stimulation of isolated-perfused transgenic hearts demonstrated a strikingly high incidence of spontaneous and inducible ventricular tachycardia. Affected mice showed marked perturbations of cardiac gap junction channel expression and localization, including a subset with disorganized epicardial activation patterns as revealed by optical action potential mapping. These studies provide important insights into mechanisms of arrhythmogenesis and suggest that conditional lineage ablation may have wide applicability for studies of disease pathogenesis.

  19. A human neurodevelopmental model for Williams syndrome.

    PubMed

    Chailangkarn, Thanathom; Trujillo, Cleber A; Freitas, Beatriz C; Hrvoj-Mihic, Branka; Herai, Roberto H; Yu, Diana X; Brown, Timothy T; Marchetto, Maria C; Bardy, Cedric; McHenry, Lauren; Stefanacci, Lisa; Järvinen, Anna; Searcy, Yvonne M; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Ard, M Colin; Hanson, Kari L; Romero, Sarah; Jacobs, Bob; Dale, Anders M; Dai, Li; Korenberg, Julie R; Gage, Fred H; Bellugi, Ursula; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R

    2016-08-18

    Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.

  20. Mouse models for human otitis media

    PubMed Central

    Trune, Dennis R.; Zheng, Qing Yin

    2010-01-01

    Otitis media (OM) remains the most common childhood disease and its annual costs exceed $5 billion. Its potential for permanent hearing impairment also emphasizes the need to better understand and manage this disease. The pathogenesis of OM is multifactorial and includes infectious pathogens, anatomy, immunologic status, genetic predisposition, and environment. Recent progress in mouse model development is helping to elucidate the respective roles of these factors and to significantly contribute toward efforts of OM prevention and control. Genetic predisposition is recognized as an important factor in OM and increasing numbers of mouse models are helping to uncover the potential genetic bases for human OM. Furthermore, the completion of the mouse genome sequence has offered a powerful set of tools for investigating gene function and is generating a rich resource of mouse mutants for studying the genetic factors underlying OM. PMID:19272362

  1. A biorobotic model of the human larynx.

    PubMed

    Manti, M; Cianchetti, M; Nacci, A; Ursino, F; Laschi, C

    2015-08-01

    This work focuses on a physical model of the human larynx that replicates its main components and functions. The prototype reproduces the multilayer vocal folds and the ab/adduction movements. In particular, the vocal folds prototype is made with soft materials whose mechanical properties have been obtained to be similar to the natural tissue in terms of viscoelasticity. A computational model was used to study fluid-structure interaction between vocal folds and the airflow. This tool allowed us to make a comparison between theoretical and experimental results. Measurements were performed with this prototype in an experimental platform comprising a controlled air flow, pressure sensors and a high-speed camera for measuring vocal fold vibrations. Data included oscillation frequency at the onset pressure and glottal width. Results show that the combination between vocal fold geometry, mechanical properties and dimensions exhibits an oscillation frequency close to that of the human vocal fold. Moreover, computational results show a high correlation with the experimental one.

  2. A synergetic model for human gait transitions

    NASA Astrophysics Data System (ADS)

    Abdolvahab, Mohammad

    2015-09-01

    Gait transitions have been considered as bifurcations between states (e.g. walking or running modes) of a nonlinear dynamical system. A top-down synergetic approach to model gait transitions has been adapted from Frank et al. (2009) and applied to two sets of empirical observations. In this approach, it is assumed that the amplitudes of the spatio-temporal modes of locomotion satisfy a generic form of evolution equations that are known to hold for animate and inanimate self-organizing systems. The presented experimental results focus on hysteresis in human walk-to-run and run-to-walk transitions on a treadmill as a function of treadmill inclination and acceleration, the rate at which speed was increased or decreased during experimental trials. The bi-stability in the synergetic model is assumed to account for the hysteretic transitions. Accordingly, the relevant parameters of the model were estimated from the empirical data and the model's efficacy in predicting the observed hysteresis effects was evaluated.

  3. Simple models of human brain functional networks.

    PubMed

    Vértes, Petra E; Alexander-Bloch, Aaron F; Gogtay, Nitin; Giedd, Jay N; Rapoport, Judith L; Bullmore, Edward T

    2012-04-10

    Human brain functional networks are embedded in anatomical space and have topological properties--small-worldness, modularity, fat-tailed degree distributions--that are comparable to many other complex networks. Although a sophisticated set of measures is available to describe the topology of brain networks, the selection pressures that drive their formation remain largely unknown. Here we consider generative models for the probability of a functional connection (an edge) between two cortical regions (nodes) separated by some Euclidean distance in anatomical space. In particular, we propose a model in which the embedded topology of brain networks emerges from two competing factors: a distance penalty based on the cost of maintaining long-range connections; and a topological term that favors links between regions sharing similar input. We show that, together, these two biologically plausible factors are sufficient to capture an impressive range of topological properties of functional brain networks. Model parameters estimated in one set of functional MRI (fMRI) data on normal volunteers provided a good fit to networks estimated in a second independent sample of fMRI data. Furthermore, slightly detuned model parameters also generated a reasonable simulation of the abnormal properties of brain functional networks in people with schizophrenia. We therefore anticipate that many aspects of brain network organization, in health and disease, may be parsimoniously explained by an economical clustering rule for the probability of functional connectivity between different brain areas.

  4. Monitoring and modeling human interactions with ecosystems

    NASA Astrophysics Data System (ADS)

    Milesi, Cristina

    With rapidly increasing consumption rates and global population, there is a growing interest in understanding how to balance human activities with the other components of the Earth system. Humans alter ecosystem functioning with land cover changes, greenhouse gas emissions and overexploitation of natural resources. On the other side, climate and its inherent interannual variability drive global Net Primary Productivity (NPP), the base of energy for all trophic levels, shaping humans' distribution on the land surface and their sensitivity to natural and accelerated patterns of variation in ecosystem processes. In this thesis, I analyzed anthropogenic influences on ecosystems and ecosystems impacts on humans through a multi-scale approach. Anthropogenic influences were analyzed with a special focus on urban ecosystems, the living environment of nearly half of the global population and almost 90% of the population in the industrialized countries. A poorly quantified aspect of urban ecosystems is the biogeochemistry of urban vegetation, intensively managed through fertilization and irrigation. In chapter 1, adapting the ecosystem model Biome-BGC, I simulated the growth of turf grasses across the United States, and estimated their potential impact on the continental water and carbon budget. Using a remote sensing-based approach, I also developed a methodology to estimate the impact of land cover changes due to urbanization on the regional photosynthetic capacity (chapter 2), finding that low-density urbanization can retain high levels of net primary productivity, although at the expense of inefficient sprawl. One of the feedbacks of urbanization is the urban heat island effect, which I analyzed in conjunction with a remote sensing based estimate of fractional impervious surface area, showing how this is related to increases in land surface temperatures, independently from geographic location and population density (chapter 3). Finally, in chapter 4, I described the

  5. Mouse Genetic Models of Human Brain Disorders.

    PubMed

    Leung, Celeste; Jia, Zhengping

    2016-01-01

    Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome. We will then explore psychiatric disorders such as schizophrenia and lastly, neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. We will outline the creation of these mouse models that range from single gene deletions, subtle point mutations to multi-gene manipulations, and discuss the key behavioral phenotypes of these mice. Ultimately, the analysis of the models outlined in this review will enhance our understanding of the in vivo role and underlying mechanisms of disease-related genes in both normal brain function and brain disorders, and provide potential therapeutic targets and strategies to prevent and treat these diseases. PMID:27047540

  6. Mouse Genetic Models of Human Brain Disorders

    PubMed Central

    Leung, Celeste; Jia, Zhengping

    2016-01-01

    Over the past three decades, genetic manipulations in mice have been used in neuroscience as a major approach to investigate the in vivo function of genes and their alterations. In particular, gene targeting techniques using embryonic stem cells have revolutionized the field of mammalian genetics and have been at the forefront in the generation of numerous mouse models of human brain disorders. In this review, we will first examine childhood developmental disorders such as autism, intellectual disability, Fragile X syndrome, and Williams-Beuren syndrome. We will then explore psychiatric disorders such as schizophrenia and lastly, neurodegenerative disorders including Alzheimer’s disease and Parkinson’s disease. We will outline the creation of these mouse models that range from single gene deletions, subtle point mutations to multi-gene manipulations, and discuss the key behavioral phenotypes of these mice. Ultimately, the analysis of the models outlined in this review will enhance our understanding of the in vivo role and underlying mechanisms of disease-related genes in both normal brain function and brain disorders, and provide potential therapeutic targets and strategies to prevent and treat these diseases. PMID:27047540

  7. Modeling the human prothrombinase complex components

    NASA Astrophysics Data System (ADS)

    Orban, Tivadar

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

  8. Updating the ICRP human respiratory tract model.

    PubMed

    Bailey, M R; Ansoborlo, E; Guilmette, R A; Paquet, F

    2007-01-01

    The ICRP Task Group on Internal Dosimetry is developing new Occupational Intakes of Radionuclides (OIR) documents. Application of the Human Respiratory Tract Model (HRTM) requires a review of the lung-to-blood absorption characteristics of inhaled compounds of importance in radiological protection. Where appropriate, material-specific absorption parameter values will be given, and for other compounds, assignments to default Types will be made on current information. Publication of the OIR provides an opportunity for updating the HRTM in the light of experience and new information. The main possibilities under consideration relate to the two main clearance pathways. Recent studies provide important new data on rates of particle transport from the nasal passages, bronchial tree (slow phase) and alveolar region. The review of absorption rates provides a database of parameter values from which consideration can be given to deriving typical values for default Types F, M and S materials, and element-specific rapid dissolution rates. PMID:18192668

  9. Three mouse models of human thalassemia.

    PubMed Central

    Martinell, J; Whitney, J B; Popp, R A; Russell, L B; Anderson, W F

    1981-01-01

    Three types of mice with globin gene mutations, called 352HB, 27HB, and Hbath-J, appear to be true animal models of human thalassemia. Expression of the alpha-globin genes in three stocks of mice, each one heterozygous for one of the alpha-globin mutations, was examined at the polypeptide, RNA, and DNA levels. alpha-Globin polypeptide chains, relative to beta-globin chains in heterozygous thalassemic mice, are present at approximately 80% of normal. The ratios of alpha-globin to beta-globin RNA sequences are also 75-80% of normal, exactly reflecting the alpha-globin to beta-globin chain ratios. In the case of mutant 352HB, at least one alpha-globin gene is deleted. Thalassemic mouse erythroid cells appear to compensate partially for the loss of half of their alpha-globin genes. Images PMID:6946454

  10. Neurocysticercosis: A natural human model of epileptogenesis

    PubMed Central

    Nash, T.E.; Mahanty, S.; Loeb, J.A.; Theodore, W.H.; Friedman, A.; Sander, J.W.; Singh, E. G.; Cavalheiro, E.; Del Brutto, O.H.; Takayanagui, O.; Fleury, A.; Verastegui, M.; Preux, PM.; Montano, E.J.S.; Pretell, E.J.; White, A.C.; Gonzales, A. E.; Gilman, R.H.; Garcia, H.H.

    2014-01-01

    Objective To develop a better understanding on mechanisms of seizures and long-term epileptogenesis caused by neurocysticercosis. Methods A workshop was held bringing together experts in epilepsy and epileptogenesis and neurocysticercosis Results Human neurocysticercosis and parallel animal models offer a unique opportunity to understand basic mechanisms of seizures. Inflammatory responses to degenerating forms and in later stage calcified parasite granulomas are associated with seizures and epilepsy. Other mechanisms may also be involved in epileptogenesis as well. Conclusions Naturally occurring brain infections with neurocysticercosis offer a unique opportunity to develop treatments for one of the world’s most common causes of epilepsy and for the development of more general anti-epileptogenic treatments. Key advantages stem from the time course where an acute seizure heralds a start of the epileptogenic process and radiographic changes of calcification and perilesional edema provide biomarkers of a chronic epileptic state. PMID:25534640

  11. 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.

  12. Human visual performance model for crewstation design

    NASA Astrophysics Data System (ADS)

    Larimer, James O.; Prevost, Michael P.; Arditi, Aries R.; Azueta, Steven; Bergen, James R.; Lubin, Jeffrey

    1991-08-01

    In a cockpit, the crewstation of an airplane, the ability of the pilot to unambiguously perceive rapidly changing information both internal and external to the crewstation is critical. To assess the impact of crewstation design decisions on the pilot''s ability to perceive information, the designer needs a means of evaluating the trade-offs that result from different designs. The Visibility Modeling Tool (VMT) provides the designer with a CAD tool for assessing these trade-offs. It combines the technologies of computer graphics, computational geometry, human performance modeling and equipment modeling into a computer-based interactive design tool. Through a simple interactive interface, a designer can manipulate design parameters such as the geometry of the cockpit, environmental factors such as ambient lighting, pilot parameters such as point of regard and adaptation state, and equipment parameters such as the location of displays, their size and the contrast of displayed symbology. VMT provides an end-to-end analysis that answers questions such as ''Will the pilot be able to read the display?'' Performance data can be projected, in the form of 3D contours, into the crewstation graphic model, providing the designer with a footprint of the operator''s visual capabilities, defining, for example, the regions in which fonts of a particular type, size and contrast can be read without error. Geometrical data such as the pilot''s volume field of view, occlusions caused by facial geometry, helmet margins, and objects in the crewstation can also be projected into the crewstation graphic model with respect to the coordinates of the aviator''s eyes and fixation point. The intersections of the projections with objects in the crewstation, delineate the area of coverage, masking, or occlusion associated with the objects. Objects in the crewstation space can be projected onto models of the operator''s retinas. These projections can be used to provide the designer with the

  13. Integrated Human Futures Modeling in Egypt

    SciTech Connect

    Passell, Howard D.; Aamir, Munaf Syed; Bernard, Michael Lewis; Beyeler, Walter E.; Fellner, Karen Marie; Hayden, Nancy Kay; Jeffers, Robert Fredric; Keller, Elizabeth James Kistin; Malczynski, Leonard A.; Mitchell, Michael David; Silver, Emily; Tidwell, Vincent C.; Villa, Daniel; Vugrin, Eric D.; Engelke, Peter; Burrow, Mat; Keith, Bruce

    2016-01-01

    The Integrated Human Futures Project provides a set of analytical and quantitative modeling and simulation tools that help explore the links among human social, economic, and ecological conditions, human resilience, conflict, and peace, and allows users to simulate tradeoffs and consequences associated with different future development and mitigation scenarios. In the current study, we integrate five distinct modeling platforms to simulate the potential risk of social unrest in Egypt resulting from the Grand Ethiopian Renaissance Dam (GERD) on the Blue Nile in Ethiopia. The five platforms simulate hydrology, agriculture, economy, human ecology, and human psychology/behavior, and show how impacts derived from development initiatives in one sector (e.g., hydrology) might ripple through to affect other sectors and how development and security concerns may be triggered across the region. This approach evaluates potential consequences, intended and unintended, associated with strategic policy actions that span the development-security nexus at the national, regional, and international levels. Model results are not intended to provide explicit predictions, but rather to provide system-level insight for policy makers into the dynamics among these interacting sectors, and to demonstrate an approach to evaluating short- and long-term policy trade-offs across different policy domains and stakeholders. The GERD project is critical to government-planned development efforts in Ethiopia but is expected to reduce downstream freshwater availability in the Nile Basin, fueling fears of negative social and economic impacts that could threaten stability and security in Egypt. We tested these hypotheses and came to the following preliminary conclusions. First, the GERD will have an important short-term impact on water availability, food production, and hydropower production in Egypt, depending on the short- term reservoir fill rate. Second, the GERD will have a very small impact on

  14. Modeling the Human Genome Maintenance network

    NASA Astrophysics Data System (ADS)

    Simão, Éder M.; Cabral, Heleno B.; Castro, Mauro A. A.; Sinigaglia, Marialva; Mombach, José C. M.; Librelotto, Giovani R.

    2010-10-01

    We present the Ontocancro Database ( www.ontocancro.org) illustrated with applications to network modeling and pathway functional analysis. The database compiles information on gene pathways involved in Human Genome Maintenance Mechanisms (GMM) whose dysfunction accounts for cancer and several genetic syndromes. Ontocancro is the most complete, manually curated information resource available providing genomics and interatomics data on 120 GMM pathways (comprising a total of 1435 genes) obtained from curated databases and the literature. It was developed to facilitate the GMM network and functional modeling for the integration of genomic, transcriptomic and interatomic data. The database’s main contribution is the Ontocancro pathways that are expanded versions of standard GMM pathways for including additional genes with evidences of functional involvement in GMM. Using these pathways we find the largest cluster of interacting proteins involving GMM and on it we project a microarray study of adenoma to identify the regions of the network that are highly altered. In the last application we present the dynamical alterations of the pathways in a study of the effect of Cadmium, a known carcinogenic substance, on prostate cells to find that it produces a strong decrease of the pathway activity.

  15. Mouse models for human hereditary deafness.

    PubMed

    Leibovici, Michel; Safieddine, Saaid; Petit, Christine

    2008-01-01

    Hearing impairment is a frequent condition in humans. Identification of the causative genes for the early onset forms of isolated deafness began 15 years ago and has been very fruitful. To date, approximately 50 causative genes have been identified. Yet, limited information regarding the underlying pathogenic mechanisms can be derived from hearing tests in deaf patients. This chapter describes the success of mouse models in the elucidation of some pathophysiological processes in the auditory sensory organ, the cochlea. These models have revealed a variety of defective structures and functions at the origin of deafness genetic forms. This is illustrated by three different examples: (1) the DFNB9 deafness form, a synaptopathy of the cochlear sensory cells where otoferlin is defective; (2) the Usher syndrome, in which deafness is related to abnormal development of the hair bundle, the mechanoreceptive structure of the sensory cells to sound; (3) the DFNB1 deafness form, which is the most common form of inherited deafness in Caucasian populations, mainly caused by connexin-26 defects that alter gap junction communication between nonsensory cochlear cells. PMID:19186249

  16. PROBABILISTIC MODELING FOR ADVANCED HUMAN EXPOSURE ASSESSMENT

    EPA Science Inventory

    Human exposures to environmental pollutants widely vary depending on the emission patterns that result in microenvironmental pollutant concentrations, as well as behavioral factors that determine the extent of an individual's contact with these pollutants. Probabilistic human exp...

  17. Genomic responses in mouse models poorly mimic human inflammatory diseases

    PubMed Central

    Seok, Junhee; Warren, H. Shaw; Cuenca, Alex G.; Mindrinos, Michael N.; Baker, Henry V.; Xu, Weihong; Richards, Daniel R.; McDonald-Smith, Grace P.; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C.; López, Cecilia M.; Honari, Shari; Moore, Ernest E.; Minei, Joseph P.; Cuschieri, Joseph; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Jeschke, Marc G.; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Brownstein, Bernard H.; Miller-Graziano, Carol; Calvano, Steve E.; Mason, Philip H.; Cobb, J. Perren; Rahme, Laurence G.; Lowry, Stephen F.; Maier, Ronald V.; Moldawer, Lyle L.; Herndon, David N.; Davis, Ronald W.; Xiao, Wenzhong; Tompkins, Ronald G.; Abouhamze, Amer; Balis, Ulysses G. J.; Camp, David G.; De, Asit K.; Harbrecht, Brian G.; Hayden, Douglas L.; Kaushal, Amit; O’Keefe, Grant E.; Kotz, Kenneth T.; Qian, Weijun; Schoenfeld, David A.; Shapiro, Michael B.; Silver, Geoffrey M.; Smith, Richard D.; Storey, John D.; Tibshirani, Robert; Toner, Mehmet; Wilhelmy, Julie; Wispelwey, Bram; Wong, Wing H

    2013-01-01

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases. PMID:23401516

  18. Dynamic Modeling of Molybdenum Metabolism in Humans

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Molybdenum is an essential nutrient in the human diet and is a cofactor for several enzymes. While intakes can vary widely with geographical region, both deficiency and toxicity in humans are rare. To determine if humans have adaptive mechanisms for maintaining molybdenum status under varying inta...

  19. A long term model of circulation. [human body

    NASA Technical Reports Server (NTRS)

    White, R. J.

    1974-01-01

    A quantitative approach to modeling human physiological function, with a view toward ultimate application to long duration space flight experiments, was undertaken. Data was obtained on the effect of weightlessness on certain aspects of human physiological function during 1-3 month periods. Modifications in the Guyton model are reviewed. Design considerations for bilateral interface models are discussed. Construction of a functioning whole body model was studied, as well as the testing of the model versus available data.

  20. Modeling human response errors in synthetic flight simulator domain

    NASA Technical Reports Server (NTRS)

    Ntuen, Celestine A.

    1992-01-01

    This paper presents a control theoretic approach to modeling human response errors (HRE) in the flight simulation domain. The human pilot is modeled as a supervisor of a highly automated system. The synthesis uses the theory of optimal control pilot modeling for integrating the pilot's observation error and the error due to the simulation model (experimental error). Methods for solving the HRE problem are suggested. Experimental verification of the models will be tested in a flight quality handling simulation.

  1. Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature

    PubMed Central

    Melican, Keira; Aubey, Flore; Duménil, Guillaume

    2014-01-01

    Neisseria meningitidis causes a severe, frequently fatal sepsis when it enters the human blood stream. Infection leads to extensive damage of the blood vessels resulting in vascular leak, the development of purpuric rashes and eventual tissue necrosis. Studying the pathogenesis of this infection was previously limited by the human specificity of the bacteria, which makes in vivo models difficult. In this protocol, we describe a humanized model for this infection in which human skin, containing dermal microvessels, is grafted onto immunocompromised mice. These vessels anastomose with the mouse circulation while maintaining their human characteristics. Once introduced into this model, N. meningitidis adhere exclusively to the human vessels, resulting in extensive vascular damage, inflammation and in some cases the development of purpuric rash. This protocol describes the grafting, infection and evaluation steps of this model in the context of N. meningitidis infection. The technique may be applied to numerous human specific pathogens that infect the blood stream. PMID:24747976

  2. Competency Modeling in Extension Education: Integrating an Academic Extension Education Model with an Extension Human Resource Management Model

    ERIC Educational Resources Information Center

    Scheer, Scott D.; Cochran, Graham R.; Harder, Amy; Place, Nick T.

    2011-01-01

    The purpose of this study was to compare and contrast an academic extension education model with an Extension human resource management model. The academic model of 19 competencies was similar across the 22 competencies of the Extension human resource management model. There were seven unique competencies for the human resource management model.…

  3. Models of Human Behavior: An Interdisciplinary Instructional Focus.

    ERIC Educational Resources Information Center

    Hymel, Glenn M.

    An undergraduate psychology course (Models of Human Behavior) that is taught at New Orleans's Loyola University is described. The survey-type course emphasizes an interdisciplinary approach to understanding human behavior and spans several major orientations in Western intellectual thought regarding human behavior. The course is intended to…

  4. Modelling Human Emotions for Tactical Decision-Making Games

    ERIC Educational Resources Information Center

    Visschedijk, Gillian C.; Lazonder, Ard W.; van der Hulst, Anja; Vink, Nathalie; Leemkuil, Henny

    2013-01-01

    The training of tactical decision making increasingly occurs through serious computer games. A challenging aspect of designing such games is the modelling of human emotions. Two studies were performed to investigate the relation between fidelity and human emotion recognition in virtual human characters. Study 1 compared five versions of a virtual…

  5. Minimizing Human Risk: Human Performance Models in the Space Human Factors and Habitability and Behavioral Health and Performance Elements

    NASA Technical Reports Server (NTRS)

    Gore, Brian F.

    2016-01-01

    Human space exploration has never been more exciting than it is today. Human presence to outer worlds is becoming a reality as humans are leveraging much of our prior knowledge to the new mission of going to Mars. Exploring the solar system at greater distances from Earth than ever before will possess some unique challenges, which can be overcome thanks to the advances in modeling and simulation technologies. The National Aeronautics and Space Administration (NASA) is at the forefront of exploring our solar system. NASA's Human Research Program (HRP) focuses on discovering the best methods and technologies that support safe and productive human space travel in the extreme and harsh space environment. HRP uses various methods and approaches to answer questions about the impact of long duration missions on the human in space including: gravity's impact on the human body, isolation and confinement on the human, hostile environments impact on the human, space radiation, and how the distance is likely to impact the human. Predictive models are included in the HRP research portfolio as these models provide valuable insights into human-system operations. This paper will provide an overview of NASA's HRP and will present a number of projects that have used modeling and simulation to provide insights into human-system issues (e.g. automation, habitat design, schedules) in anticipation of space exploration.

  6. A human motor control perspective to multiple manipulator modelling.

    PubMed

    Kambhampati, C; Rajasekharan, S

    2003-10-01

    This paper describes the aspects involved in modelling a multi-robot system from a human motor control perspective. The human motor control system has a hierarchical and decentralised structure, and building a control system for a multi-robot system that attains human features would require a decomposable model. Decomposition of a complex robotic system is difficult due to the interactions between the subsystems, so these have to be first separated before the system is modelled. The proposed method of separating the interconnections is applied with the aid of fuzzy modelling to derive a fully decomposable model of two manipulator robots handling a common object.

  7. Predicting human walking gaits with a simple planar model.

    PubMed

    Martin, Anne E; Schmiedeler, James P

    2014-04-11

    Models of human walking with moderate complexity have the potential to accurately capture both joint kinematics and whole body energetics, thereby offering more simultaneous information than very simple models and less computational cost than very complex models. This work examines four- and six-link planar biped models with knees and rigid circular feet. The two differ in that the six-link model includes ankle joints. Stable periodic walking gaits are generated for both models using a hybrid zero dynamics-based control approach. To establish a baseline of how well the models can approximate normal human walking, gaits were optimized to match experimental human walking data, ranging in speed from very slow to very fast. The six-link model well matched the experimental step length, speed, and mean absolute power, while the four-link model did not, indicating that ankle work is a critical element in human walking models of this type. Beyond simply matching human data, the six-link model can be used in an optimization framework to predict normal human walking using a torque-squared objective function. The model well predicted experimental step length, joint motions, and mean absolute power over the full range of speeds.

  8. On the rat model of human osteopenias and osteoporoses

    NASA Technical Reports Server (NTRS)

    Frost, Harold M.; Jee, Webster S. S.

    1992-01-01

    The idea that rats cannot model human osteopenias errs. The same mechanisms control gains in bone mass (longitudinal bone growth and modeling drifts) and losses (BMU-based remodeling), in young and aged rats and humans. Furthermore, they respond similarly in rats and man to mechanical influences, hormones, drugs and other agents.

  9. An integrated model of human-wildlife interdependence

    USGS Publications Warehouse

    John, Kun H.; Walsh, Richard G.; Johnson, R. L.

    1994-01-01

    This paper attempts to integrate wildlife-related ecologic and economic variables into an econometric model. The model reveals empirical evidence of the presumed interdependence of human-wildlife and the holistic nature of humanity's relationship to the ecosystem. Human use of biologic resources varies not only with income, education, and population, but also with sustainability of humankind's action relative to the quality and quantity of the supporting ecological base.

  10. Three-Dimensional Human Tissue Models of Wounded Skin

    PubMed Central

    Egles, Christophe; Garlick, Jonathan A.; Shamis, Yulia

    2010-01-01

    Human skin equivalents (HSEs) are in vitro tissues in which a fully differentiated, stratified squamous epithelium is grown at an air–liquid interface on a Type I collagen gel harboring human dermal fibroblasts. HSEs now provide experimental human tissue models to study factors that direct re-epithelialization and epithelial–mesenchymal cross-talk following wounding. This chapter describes the fabrication of HSEs from human keratinocytes and fibroblasts and how HSEs can be modified to characterize the response of the human epithelium during wound repair. The protocols outlined first describe techniques for the generation of human tissues that closely approximate the architectural features, differentiation, and growth of human skin. This will be followed by a description of a protocol that enables HSEs to be adapted to monitor their response following wounding. These engineered human tissues provide powerful tools to study biological process in tissues that mimic the healing of human skin and of the epithelial tissue. PMID:19908015

  11. HUMAN EXPOSURE MODELING: CONCEPTS, METHODS, AND TOOLS

    EPA Science Inventory

    Understanding human exposure is critical when estimating the occurrence of deleterious effects that could follow contact with environmental contaminants. For many pollutants, the intensity, duration, frequency, route, and timing of exposure is highly variable, particularly whe...

  12. Mucocele: a human model for lymphangiogenesis.

    PubMed

    Castro, Eumenia Costa da Cunha; Galambos, Csaba

    2009-01-01

    lymphatic vessel regression were observed during mucocele evolution. The abundant newly formed ectatic lymphatic vessels seen in the intermediate phase may play a role in the clearance of extravasated material (mucin, edema, and lymph fluid) and in the initiation of the young fibroblast-rich granulation tissue. Mucocele appears to be an excellent human model for studying the factors that play a role in new lymphangiogenesis and regression. PMID:18937525

  13. Context in Models of Human-Machine Systems

    NASA Technical Reports Server (NTRS)

    Callantine, Todd J.; Null, Cynthia H. (Technical Monitor)

    1998-01-01

    All human-machine systems models represent context. This paper proposes a theory of context through which models may be usefully related and integrated for design. The paper presents examples of context representation in various models, describes an application to developing models for the Crew Activity Tracking System (CATS), and advances context as a foundation for integrated design of complex dynamic systems.

  14. Drosophila as a model for human neurodegenerative disease.

    PubMed

    Bilen, Julide; Bonini, Nancy M

    2005-01-01

    Among many achievements in the neurodegeneration field in the past decade, two require special attention due to the huge impact on our understanding of molecular and cellular pathogenesis of human neurodegenerative diseases. First is defining specific mutations in familial neurodegenerative diseases and second is modeling these diseases in easily manipulable model organisms including the fruit fly, nematode, and yeast. The power of these genetic systems has revealed many genetic factors involved in the various pathways affected, as well as provided potential drug targets for therapeutics. This review focuses on fruit fly models of human neurodegenerative diseases, with emphasis on how fly models have provided new insights into various aspects of human diseases.

  15. OPTICAL EYE MODEL: Human eye aberrations: 2. Development of a dynamic model of the human eye based on measurements

    NASA Astrophysics Data System (ADS)

    Galetskii, S. O.; Cherezova, T. Yu; Kudryashov, A. V.

    2008-11-01

    A human eye model based on a flexible semipassive bimorph mirror is proposed and experimentally realised. The model can be used for the real-time reproduction of human eye aberrations and their fluctuations. The accuracy of the reproduction of individual Zernike polynomials and of total eye aberrations of inspected patients is discussed.

  16. Human surrogate models of neuropathic pain: validity and limitations.

    PubMed

    Binder, Andreas

    2016-02-01

    Human surrogate models of neuropathic pain in healthy subjects are used to study symptoms, signs, and the hypothesized underlying mechanisms. Although different models are available, different spontaneous and evoked symptoms and signs are inducible; 2 key questions need to be answered: are human surrogate models conceptually valid, ie, do they share the sensory phenotype of neuropathic pain states, and are they sufficiently reliable to allow consistent translational research?

  17. Synthetic vision and memory model for virtual human - biomed 2010.

    PubMed

    Zhao, Yue; Kang, Jinsheng; Wright, David

    2010-01-01

    This paper describes the methods and case studies of a novel synthetic vision and memory model for virtual human. The synthetic vision module simulates the biological / optical abilities and limitations of the human vision. The module is based on a series of collision detection between the boundary of virtual humans field of vision (FOV) volume and the surface of objects in a recreated 3D environment. The memory module simulates a short-term memory capability by employing a simplified memory structure (first-in-first-out stack). The synthetic vision and memory model has been integrated into a virtual human modelling project, Intelligent Virtual Modelling. The project aimed to improve the realism and autonomy of virtual humans. PMID:20467105

  18. Canine tumors: a spontaneous animal model of human carcinogenesis.

    PubMed

    Pinho, Salomé S; Carvalho, Sandra; Cabral, Joana; Reis, Celso A; Gärtner, Fátima

    2012-03-01

    The enormous biologic complexity of human cancer has stimulated the development of more appropriate experimental models that could resemble in a natural and spontaneous manner the physiopathologic aspects of cancer biology. Companion animals have many desired characteristics that fill the gap between in vitro and in vivo studies, and these characteristics have proven to be important in understanding many complex molecular aspects of human cancer. Spontaneous tumors in dogs share a wide variety of epidemiologic, biologic, and clinical features with human cancer, which makes this animal model both attractive and underused in oncology research. In this review, we summarize the importance of naturally occurring canine tumors as valuable tools for studying numerous aspects of human cancer as well as the potential use of this animal model for the development of new cancer treatments. We address specifically the use of canine mammary tumors as an increasingly powerful model to study human breast cancer. PMID:22340765

  19. Mouse models for understanding human developmental anomalies

    SciTech Connect

    Generoso, W.M.

    1989-01-01

    The mouse experimental system presents an opportunity for studying the nature of the underlying mutagenic damage and the molecular pathogenesis of this class of anomalies by virtue of the accessibility of the zygote and its descendant blastomeres. Such studies could contribute to the understanding of the etiology of certain sporadic but common human malformations. The vulnerability of the zygotes to mutagens as demonstrated in the studies described in this report should be a major consideration in chemical safety evaluation. It raises questions regarding the danger to human zygotes when the mother is exposed to drugs and environmental chemicals.

  20. 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.

  1. Modeling forces on the human body

    NASA Astrophysics Data System (ADS)

    Pagonis, Vasilis; Drake, Russel; Morgan, Michael; Peters, Todd; Riddle, Chris; Rollins, Karen

    1999-11-01

    Several simulations involving the human body, using the simulation software Interactive Physics™, are used to analyze the forces during both static situations and dynamic collisions. The connection of the simulations with the biological sciences and with sports activities should make them appealing to both high school and college-level physics students.

  2. HUMAN--A Comprehensive Physiological Model.

    ERIC Educational Resources Information Center

    Coleman, Thomas G.; Randall, James E.

    1983-01-01

    Describes computer program (HUMAN) used to simulate physiological experiments on patient pathology. Program (available from authors, including versions for microcomputers) consists of dynamic interactions of over 150 physiological variables and integrating approximations of cardiovascular, renal, lung, temperature regulation, and some hormone…

  3. New Metacognitive Model for Human Performance Technology

    ERIC Educational Resources Information Center

    Turner, John R.

    2011-01-01

    Addressing metacognitive functions has been shown to improve performance at the individual, team, group, and organizational levels. Metacognition is beginning to surface as an added cognate discipline for the field of human performance technology (HPT). Advances from research in the fields of cognition and metacognition offer a place for HPT to…

  4. Homology modeling of human muscarinic acetylcholine receptors.

    PubMed

    Thomas, Trayder; McLean, Kimberley C; McRobb, Fiona M; Manallack, David T; Chalmers, David K; Yuriev, Elizabeth

    2014-01-27

    We have developed homology models of the acetylcholine muscarinic receptors M₁R-M₅R, based on the β₂-adrenergic receptor crystal as the template. This is the first report of homology modeling of all five subtypes of acetylcholine muscarinic receptors with binding sites optimized for ligand binding. The models were evaluated for their ability to discriminate between muscarinic antagonists and decoy compounds using virtual screening using enrichment factors, area under the ROC curve (AUC), and an early enrichment measure, LogAUC. The models produce rational binding modes of docked ligands as well as good enrichment capacity when tested against property-matched decoy libraries, which demonstrates their unbiased predictive ability. To test the relative effects of homology model template selection and the binding site optimization procedure, we generated and evaluated a naïve M₂R model, using the M₃R crystal structure as a template. Our results confirm previous findings that binding site optimization using ligand(s) active at a particular receptor, i.e. including functional knowledge into the model building process, has a more pronounced effect on model quality than target-template sequence similarity. The optimized M₁R-M₅R homology models are made available as part of the Supporting Information to allow researchers to use these structures, compare them to their own results, and thus advance the development of better modeling approaches.

  5. A dual-loop model of the human controller

    NASA Technical Reports Server (NTRS)

    Hess, R. A.

    1977-01-01

    A representative model of the human controller in single-axis compensatory tracking tasks that exhibits an internal feedback loop which is not evident in single-loop models now in common use is presented. This hypothetical inner-loop involves a neuromuscular command signal derived from the time rate of change of controlled element output which is due to control activity. It is not contended that the single-loop human controller models now in use are incorrect, but that they contain an implicit but important internal loop closure, which, if explicitly considered, can account for a good deal of the adaptive nature of the human controller in a systematic manner.

  6. A Perspective on Computational Human Performance Models as Design Tools

    NASA Technical Reports Server (NTRS)

    Jones, Patricia M.

    2010-01-01

    The design of interactive systems, including levels of automation, displays, and controls, is usually based on design guidelines and iterative empirical prototyping. A complementary approach is to use computational human performance models to evaluate designs. An integrated strategy of model-based and empirical test and evaluation activities is particularly attractive as a methodology for verification and validation of human-rated systems for commercial space. This talk will review several computational human performance modeling approaches and their applicability to design of display and control requirements.

  7. A Computational Model of Human Table Tennis for Robot Application

    NASA Astrophysics Data System (ADS)

    Mülling, Katharina; Peters, Jan

    Table tennis is a difficult motor skill which requires all basic components of a general motor skill learning system. In order to get a step closer to such a generic approach to the automatic acquisition and refinement of table tennis, we study table tennis from a human motor control point of view. We make use of the basic models of discrete human movement phases, virtual hitting points, and the operational timing hypothesis. Using these components, we create a computational model which is aimed at reproducing human-like behavior. We verify the functionality of this model in a physically realistic simulation of a Barrett WAM.

  8. Human performance modeling for system of systems analytics.

    SciTech Connect

    Dixon, Kevin R.; Lawton, Craig R.; Basilico, Justin Derrick; Longsine, Dennis E.; Forsythe, James Chris; Gauthier, John Henry; Le, Hai D.

    2008-10-01

    A Laboratory-Directed Research and Development project was initiated in 2005 to investigate Human Performance Modeling in a System of Systems analytic environment. SAND2006-6569 and SAND2006-7911 document interim results from this effort; this report documents the final results. The problem is difficult because of the number of humans involved in a System of Systems environment and the generally poorly defined nature of the tasks that each human must perform. A two-pronged strategy was followed: one prong was to develop human models using a probability-based method similar to that first developed for relatively well-understood probability based performance modeling; another prong was to investigate more state-of-art human cognition models. The probability-based modeling resulted in a comprehensive addition of human-modeling capability to the existing SoSAT computer program. The cognitive modeling resulted in an increased understanding of what is necessary to incorporate cognition-based models to a System of Systems analytic environment.

  9. A Human View Model for Socio-Technical Interactions

    NASA Technical Reports Server (NTRS)

    Handley, Holly A.; Tolk, Andreas

    2012-01-01

    The Human View was developed as an additional architectural viewpoint to focus on the human part of a system. The Human View can be used to collect and organize data in order to understand how human operators interact and impact the other elements of a system. This framework can also be used to develop a model to describe how humans interact with each other in network enabled systems. These socio-technical interactions form the foundation of the emerging area of Human Interoperability. Human Interoperability strives to understand the relationships required between human operators that impact collaboration across networked environments, including the effect of belonging to different organizations. By applying organizational relationship concepts from network theory to the Human View elements, and aligning these relationships with a model developed to identify layers of coalition interoperability, the conditions for different levels for Human Interoperability for network enabled systems can be identified. These requirements can then be captured in the Human View products to improve the overall network enabled system.

  10. Understanding What We Do: Emerging Models for Human Rights Education

    NASA Astrophysics Data System (ADS)

    Tibbitts, Felisa

    2002-07-01

    The author presents three approaches to contemporary human rights education practice: the Values and Awareness Model, the Accountability Model and the Transformational Model. Each model is associated with particular target groups, contents and strategies. The author suggests that these models can lend themselves to theory development and research in what might be considered an emerging educational field. Human rights education can be further strengthened through the appropriate use oflearning theory, as well as through the setting of standards for trainer preparation and program content, and through evaluating the impact of programs in terms of reaching learner goals (knowledge, values and skills) and contributing to social change.

  11. Biostereometric Data Processing In ERGODATA: Choice Of Human Body Models

    NASA Astrophysics Data System (ADS)

    Pineau, J. C.; Mollard, R.; Sauvignon, M.; Amphoux, M.

    1983-07-01

    The definition of human body models was elaborated with anthropometric data from ERGODATA. The first model reduces the human body into a series of points and lines. The second model is well adapted to represent volumes of each segmentary element. The third is an original model built from the conventional anatomical points. Each segment is defined in space by a tri-angular plane located with its 3-D coordinates. This new model can answer all the processing possibilities in the field of computer-aided design (C.A.D.) in ergonomy but also biomechanics and orthopaedics.

  12. Compact continuum brain model for human electroencephalogram

    NASA Astrophysics Data System (ADS)

    Kim, J. W.; Shin, H.-B.; Robinson, P. A.

    2007-12-01

    A low-dimensional, compact brain model has recently been developed based on physiologically based mean-field continuum formulation of electric activity of the brain. The essential feature of the new compact model is a second order time-delayed differential equation that has physiologically plausible terms, such as rapid corticocortical feedback and delayed feedback via extracortical pathways. Due to its compact form, the model facilitates insight into complex brain dynamics via standard linear and nonlinear techniques. The model successfully reproduces many features of previous models and experiments. For example, experimentally observed typical rhythms of electroencephalogram (EEG) signals are reproduced in a physiologically plausible parameter region. In the nonlinear regime, onsets of seizures, which often develop into limit cycles, are illustrated by modulating model parameters. It is also shown that a hysteresis can occur when the system has multiple attractors. As a further illustration of this approach, power spectra of the model are fitted to those of sleep EEGs of two subjects (one with apnea, the other with narcolepsy). The model parameters obtained from the fittings show good matches with previous literature. Our results suggest that the compact model can provide a theoretical basis for analyzing complex EEG signals.

  13. Modelling mutational landscapes of human cancers in vitro

    NASA Astrophysics Data System (ADS)

    Olivier, Magali; Weninger, Annette; Ardin, Maude; Huskova, Hana; Castells, Xavier; Vallée, Maxime P.; McKay, James; Nedelko, Tatiana; Muehlbauer, Karl-Rudolf; Marusawa, Hiroyuki; Alexander, John; Hazelwood, Lee; Byrnes, Graham; Hollstein, Monica; Zavadil, Jiri

    2014-03-01

    Experimental models that recapitulate mutational landscapes of human cancers are needed to decipher the rapidly expanding data on human somatic mutations. We demonstrate that mutation patterns in immortalised cell lines derived from primary murine embryonic fibroblasts (MEFs) exposed in vitro to carcinogens recapitulate key features of mutational signatures observed in human cancers. In experiments with several cancer-causing agents we obtained high genome-wide concordance between human tumour mutation data and in vitro data with respect to predominant substitution types, strand bias and sequence context. Moreover, we found signature mutations in well-studied human cancer driver genes. To explore endogenous mutagenesis, we used MEFs ectopically expressing activation-induced cytidine deaminase (AID) and observed an excess of AID signature mutations in immortalised cell lines compared to their non-transgenic counterparts. MEF immortalisation is thus a simple and powerful strategy for modelling cancer mutation landscapes that facilitates the interpretation of human tumour genome-wide sequencing data.

  14. Synthetic vision and emotion calculation in intelligent virtual human modeling.

    PubMed

    Zhao, Y; Kang, J; Wright, D K

    2007-01-01

    The virtual human technique can already provide vivid and believable human behaviour in more and more scenarios. Virtual humans are expected to replace real humans in hazardous situations to undertake tests and feed back valuable information. This paper will introduce a virtual human with a novel collision-based synthetic vision, short-term memory model and a capability to implement emotion calculation and decision making. The virtual character based on this model can 'see' what is in its field of view (FOV) and remember those objects. After that, a group of affective computing equations have been introduced. These equations have been implemented into a proposed emotion calculation process to enlighten emotion for virtual intelligent humans. PMID:17487108

  15. A framework for modeling human evolution.

    PubMed

    Gintis, Herbert

    2016-01-01

    Culture-led gene-culture coevolution is a framework within which substantive explanations of human evolution must be located. It is not itself an explanation. Explanations depend on such concrete historical evolutionary factors such as the control of fire, collective child-rearing, lethal weapon technology, altruistic cooperation and punishment, and the mastery of complex collaboration protocols leading to an effective division of social labor. PMID:27561218

  16. Dynamical Analysis in the Mathematical Modelling of Human Blood Glucose

    ERIC Educational Resources Information Center

    Bae, Saebyok; Kang, Byungmin

    2012-01-01

    We want to apply the geometrical method to a dynamical system of human blood glucose. Due to the educational importance of model building, we show a relatively general modelling process using observational facts. Next, two models of some concrete forms are analysed in the phase plane by means of linear stability, phase portrait and vector…

  17. In vitro comparative models for canine and human breast cancers.

    PubMed

    Visan, Simona; Balacescu, Ovidiu; Berindan-Neagoe, Ioana; Catoi, Cornel

    2016-01-01

    During the past four decades, an increased number of similarities between canine mammary tumors and human breast cancer have been reported: molecular, histological, morphological, clinical and epidemiological, which lead to comparative oncological studies. One of the most important goals in human and veterinary oncology is to discover potential molecular biomarkers that could detect breast cancer in an early stage and to develop new effective therapies. Recently, cancer cell lines have successfully been used as an in vitro model to study the biology of cancer, to investigate molecular pathways and to test the efficiency of anticancer drugs. Moreover, establishment of an experimental animal model for the study of human breast cancer will improve testing potential anti-cancer therapies and the discovery of effective therapeutic schemes suitable for human clinical trials. In this review, we collected data from previous studies that strengthen the value of canine mammary cancer cell lines as an in vitro model for the study of human breast cancer. PMID:27004024

  18. Cerebral organoids model human brain development and microcephaly.

    PubMed

    Lancaster, Madeline A; Renner, Magdalena; Martin, Carol-Anne; Wenzel, Daniel; Bicknell, Louise S; Hurles, Matthew E; Homfray, Tessa; Penninger, Josef M; Jackson, Andrew P; Knoblich, Juergen A

    2013-09-19

    The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue.

  19. Cerebral organoids model human brain development and microcephaly

    PubMed Central

    Lancaster, Madeline A.; Renner, Magdalena; Martin, Carol-Anne; Wenzel, Daniel; Bicknell, Louise S.; Hurles, Matthew E.; Homfray, Tessa; Penninger, Josef M.; Jackson, Andrew P.; Knoblich, Juergen A.

    2013-01-01

    The complexity of the human brain has made it difficult to study many brain disorders in model organisms, and highlights the need for an in vitro model of human brain development. We have developed a human pluripotent stem cell-derived 3D organoid culture system, termed cerebral organoid, which develops various discrete though interdependent brain regions. These include cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNAi and patient-specific iPS cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could explain the disease phenotype. Our data demonstrate that 3D organoids can recapitulate development and disease of even this most complex human tissue. PMID:23995685

  20. In vitro comparative models for canine and human breast cancers

    PubMed Central

    VISAN, SIMONA; BALACESCU, OVIDIU; BERINDAN-NEAGOE, IOANA; CATOI, CORNEL

    2016-01-01

    During the past four decades, an increased number of similarities between canine mammary tumors and human breast cancer have been reported: molecular, histological, morphological, clinical and epidemiological, which lead to comparative oncological studies. One of the most important goals in human and veterinary oncology is to discover potential molecular biomarkers that could detect breast cancer in an early stage and to develop new effective therapies. Recently, cancer cell lines have successfully been used as an in vitro model to study the biology of cancer, to investigate molecular pathways and to test the efficiency of anticancer drugs. Moreover, establishment of an experimental animal model for the study of human breast cancer will improve testing potential anti-cancer therapies and the discovery of effective therapeutic schemes suitable for human clinical trials. In this review, we collected data from previous studies that strengthen the value of canine mammary cancer cell lines as an in vitro model for the study of human breast cancer. PMID:27004024

  1. Phase transitions in models of human cooperation

    NASA Astrophysics Data System (ADS)

    Perc, Matjaž

    2016-08-01

    If only the fittest survive, why should one cooperate? Why should one sacrifice personal benefits for the common good? Recent research indicates that a comprehensive answer to such questions requires that we look beyond the individual and focus on the collective behavior that emerges as a result of the interactions among individuals, groups, and societies. Although undoubtedly driven also by culture and cognition, human cooperation is just as well an emergent, collective phenomenon in a complex system. Nonequilibrium statistical physics, in particular the collective behavior of interacting particles near phase transitions, has already been recognized as very valuable for understanding counterintuitive evolutionary outcomes. However, unlike pairwise interactions among particles that typically govern solid-state physics systems, interactions among humans often involve group interactions, and they also involve a larger number of possible states even for the most simplified description of reality. Here we briefly review research done in the realm of the public goods game, and we outline future research directions with an emphasis on merging the most recent advances in the social sciences with methods of nonequilibrium statistical physics. By having a firm theoretical grip on human cooperation, we can hope to engineer better social systems and develop more efficient policies for a sustainable and better future.

  2. TGN1412 Induces Lymphopenia and Human Cytokine Release in a Humanized Mouse Model.

    PubMed

    Weißmüller, Sabrina; Kronhart, Stefanie; Kreuz, Dorothea; Schnierle, Barbara; Kalinke, Ulrich; Kirberg, Jörg; Hanschmann, Kay-Martin; Waibler, Zoe

    2016-01-01

    Therapeutic monoclonal antibodies (mAbs) such as the superagonistic, CD28-specific antibody TGN1412, or OKT3, an anti-CD3 mAb, can cause severe adverse events including cytokine release syndrome. A predictive model for mAb-mediated adverse effects, for which no previous knowledge on severe adverse events to be expected or on molecular mechanisms underlying is prerequisite, is not available yet. We used a humanized mouse model of human peripheral blood mononuclear cell-reconstituted NOD-RAG1-/-Aβ-/-HLADQ(tg+ or tg-)IL-2Rγc-/- mice to evaluate its predictive value for preclinical testing of mAbs. 2-6 hours after TGN1412 treatment, mice showed a loss of human CD45+ cells from the peripheral blood and loss of only human T cells after OKT3 injection, reminiscent of effects observed in mAb-treated humans. Moreover, upon OKT3 injection we detected selective CD3 downmodulation on T cells, a typical effect of OKT3. Importantly, we detected release of human cytokines in humanized mice upon both OKT3 and TGN1412 application. Finally, humanized mice showed severe signs of illness, a rapid drop of body temperature, and succumbed to antibody application 2-6 hours after administration. Hence, the humanized mouse model used here reproduces several effects and adverse events induced in humans upon application of the therapeutic mAbs OKT3 and TGN1412. PMID:26959227

  3. Human Engineering Modeling and Performance Lab Study Project

    NASA Technical Reports Server (NTRS)

    Oliva-Buisson, Yvette J.

    2014-01-01

    The HEMAP (Human Engineering Modeling and Performance) Lab is a joint effort between the Industrial and Human Engineering group and the KAVE (Kennedy Advanced Visualiations Environment) group. The lab consists of sixteen camera system that is used to capture human motions and operational tasks, through te use of a Velcro suit equipped with sensors, and then simulate these tasks in an ergonomic software package know as Jac, The Jack software is able to identify the potential risk hazards.

  4. A model for dengue disease with variable human population.

    PubMed

    Esteva, L; Vargas, C

    1999-03-01

    A model for the transmission of dengue fever with variable human population size is analyzed. We find three threshold parameters which govern the existence of the endemic proportion equilibrium, the increase of the human population size, and the behaviour of the total number of human infectives. We prove the global asymptotic stability of the equilibrium points using the theory of competitive systems, compound matrices, and the center manifold theorem.

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

    NASA Technical Reports Server (NTRS)

    Hess, Ronald A.

    1987-01-01

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

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

    NASA Technical Reports Server (NTRS)

    Hess, Ronald A.

    1987-01-01

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

  7. Agency, Values, and Well-Being: A Human Development Model

    ERIC Educational Resources Information Center

    Welzel, Christian; Inglehart, Ronald

    2010-01-01

    This paper argues that feelings of agency are linked to human well-being through a sequence of adaptive mechanisms that promote human development, once existential conditions become permissive. In the first part, we elaborate on the evolutionary logic of this model and outline why an evolutionary perspective is helpful to understand changes in…

  8. Relevance of animal models to human tardive dyskinesia

    PubMed Central

    2012-01-01

    Tardive dyskinesia remains an elusive and significant clinical entity that can possibly be understood via experimentation with animal models. We conducted a literature review on tardive dyskinesia modeling. Subchronic antipsychotic drug exposure is a standard approach to model tardive dyskinesia in rodents. Vacuous chewing movements constitute the most common pattern of expression of purposeless oral movements and represent an impermanent response, with individual and strain susceptibility differences. Transgenic mice are also used to address the contribution of adaptive and maladaptive signals induced during antipsychotic drug exposure. An emphasis on non-human primate modeling is proposed, and past experimental observations reviewed in various monkey species. Rodent and primate models are complementary, but the non-human primate model appears more convincingly similar to the human condition and better suited to address therapeutic issues against tardive dyskinesia. PMID:22404856

  9. Improving digital human modelling for proactive ergonomics in design.

    PubMed

    Chaffin, D B

    2005-04-15

    This paper presents the need to improve existing digital human models (DHMs) so they are better able to serve as effective ergonomics analysis and design tools. Existing DHMs are meant to be used by a designer early in a product development process when attempting to improve the physical design of vehicle interiors and manufacturing workplaces. The emphasis in this paper is placed on developing future DHMs that include valid posture and motion prediction models for various populations. It is argued that existing posture and motion prediction models now used in DHMs must be changed to become based on real motion data to assure validity for complex dynamic task simulations. It is further speculated that if valid human posture and motion prediction models are developed and used, these can be combined with psychophysical and biomechanical models to provide a much greater understanding of dynamic human performance and population specific limitations and that these new DHM models will ultimately provide a powerful ergonomics design tool.

  10. Dynamic Human Body Modeling Using a Single RGB Camera

    PubMed Central

    Zhu, Haiyu; Yu, Yao; Zhou, Yu; Du, Sidan

    2016-01-01

    In this paper, we present a novel automatic pipeline to build personalized parametric models of dynamic people using a single RGB camera. Compared to previous approaches that use monocular RGB images, our system can model a 3D human body automatically and incrementally, taking advantage of human motion. Based on coarse 2D and 3D poses estimated from image sequences, we first perform a kinematic classification of human body parts to refine the poses and obtain reconstructed body parts. Next, a personalized parametric human model is generated by driving a general template to fit the body parts and calculating the non-rigid deformation. Experimental results show that our shape estimation method achieves comparable accuracy with reconstructed models using depth cameras, yet requires neither user interaction nor any dedicated devices, leading to the feasibility of using this method on widely available smart phones. PMID:26999159

  11. Dynamic Human Body Modeling Using a Single RGB Camera.

    PubMed

    Zhu, Haiyu; Yu, Yao; Zhou, Yu; Du, Sidan

    2016-01-01

    In this paper, we present a novel automatic pipeline to build personalized parametric models of dynamic people using a single RGB camera. Compared to previous approaches that use monocular RGB images, our system can model a 3D human body automatically and incrementally, taking advantage of human motion. Based on coarse 2D and 3D poses estimated from image sequences, we first perform a kinematic classification of human body parts to refine the poses and obtain reconstructed body parts. Next, a personalized parametric human model is generated by driving a general template to fit the body parts and calculating the non-rigid deformation. Experimental results show that our shape estimation method achieves comparable accuracy with reconstructed models using depth cameras, yet requires neither user interaction nor any dedicated devices, leading to the feasibility of using this method on widely available smart phones. PMID:26999159

  12. Dynamic Human Body Modeling Using a Single RGB Camera.

    PubMed

    Zhu, Haiyu; Yu, Yao; Zhou, Yu; Du, Sidan

    2016-03-18

    In this paper, we present a novel automatic pipeline to build personalized parametric models of dynamic people using a single RGB camera. Compared to previous approaches that use monocular RGB images, our system can model a 3D human body automatically and incrementally, taking advantage of human motion. Based on coarse 2D and 3D poses estimated from image sequences, we first perform a kinematic classification of human body parts to refine the poses and obtain reconstructed body parts. Next, a personalized parametric human model is generated by driving a general template to fit the body parts and calculating the non-rigid deformation. Experimental results show that our shape estimation method achieves comparable accuracy with reconstructed models using depth cameras, yet requires neither user interaction nor any dedicated devices, leading to the feasibility of using this method on widely available smart phones.

  13. Systemic modelling of human bioenergetics and blood circulation.

    PubMed

    Lim, K M; Yang, S-H; Shim, E B

    2012-10-01

    This work reviews the main aspects of human bioenergetics and the dynamics of the cardiovascular system, with emphasis on modelling their physiological characteristics. The methods used to study human bioenergetics and circulation dynamics, including the use of mathematical models, are summarised. The main characteristics of human bioenergetics, including mitochondrial metabolism and global energy balance, are first described, and the systemic aspects of blood circulation and related physiological issues are introduced. The authors also discuss the present status of studies of human bioenergetics and blood circulation. Then, the limitations of the existing studies are described in an effort to identify directions for future research towards integrated and comprehensive modelling. This review emphasises that a multi-scale and multi-physical approach to bioenergetics and blood circulation that considers multiple scales and physiological factors are necessary for the appropriate clinical application of computational models.

  14. Generating Phenotypical Erroneous Human Behavior to Evaluate Human-automation Interaction Using Model Checking

    PubMed Central

    Bolton, Matthew L.; Bass, Ellen J.; Siminiceanu, Radu I.

    2012-01-01

    Breakdowns in complex systems often occur as a result of system elements interacting in unanticipated ways. In systems with human operators, human-automation interaction associated with both normative and erroneous human behavior can contribute to such failures. Model-driven design and analysis techniques provide engineers with formal methods tools and techniques capable of evaluating how human behavior can contribute to system failures. This paper presents a novel method for automatically generating task analytic models encompassing both normative and erroneous human behavior from normative task models. The generated erroneous behavior is capable of replicating Hollnagel’s zero-order phenotypes of erroneous action for omissions, jumps, repetitions, and intrusions. Multiple phenotypical acts can occur in sequence, thus allowing for the generation of higher order phenotypes. The task behavior model pattern capable of generating erroneous behavior can be integrated into a formal system model so that system safety properties can be formally verified with a model checker. This allows analysts to prove that a human-automation interactive system (as represented by the model) will or will not satisfy safety properties with both normative and generated erroneous human behavior. We present benchmarks related to the size of the statespace and verification time of models to show how the erroneous human behavior generation process scales. We demonstrate the method with a case study: the operation of a radiation therapy machine. A potential problem resulting from a generated erroneous human action is discovered. A design intervention is presented which prevents this problem from occurring. We discuss how our method could be used to evaluate larger applications and recommend future paths of development. PMID:23105914

  15. Human Communication--A New Model.

    ERIC Educational Resources Information Center

    McLeish, John

    1978-01-01

    Pavlov's organism-in-the-environment model was adapted to a functional analysis of communication, expecially abstract and symbolic activities. A classification of discrimination response and reinforcement patterns was given. (CP)

  16. Testing modern human out-of-Africa dispersal models and implications for modern human origins.

    PubMed

    Reyes-Centeno, Hugo; Hubbe, Mark; Hanihara, Tsunehiko; Stringer, Chris; Harvati, Katerina

    2015-10-01

    The modern human expansion process out of Africa has important implications for understanding the genetic and phenotypic structure of extant populations. While intensely debated, the primary hypotheses focus on either a single dispersal or multiple dispersals out of the continent. Here, we use the human fossil record from Africa and the Levant, as well as an exceptionally large dataset of Holocene human crania sampled from Asia, to model ancestor-descendant relationships along hypothetical dispersal routes. We test the spatial and temporal predictions of competing out-of-Africa models by assessing the correlation of geographical distances between populations and measures of population differentiation derived from quantitative cranial phenotype data. Our results support a model in which extant Australo-Melanesians are descendants of an initial dispersal out of Africa by early anatomically modern humans, while all other populations are descendants of a later migration wave. Our results have implications for understanding the complexity of modern human origins and diversity.

  17. Testing modern human out-of-Africa dispersal models and implications for modern human origins.

    PubMed

    Reyes-Centeno, Hugo; Hubbe, Mark; Hanihara, Tsunehiko; Stringer, Chris; Harvati, Katerina

    2015-10-01

    The modern human expansion process out of Africa has important implications for understanding the genetic and phenotypic structure of extant populations. While intensely debated, the primary hypotheses focus on either a single dispersal or multiple dispersals out of the continent. Here, we use the human fossil record from Africa and the Levant, as well as an exceptionally large dataset of Holocene human crania sampled from Asia, to model ancestor-descendant relationships along hypothetical dispersal routes. We test the spatial and temporal predictions of competing out-of-Africa models by assessing the correlation of geographical distances between populations and measures of population differentiation derived from quantitative cranial phenotype data. Our results support a model in which extant Australo-Melanesians are descendants of an initial dispersal out of Africa by early anatomically modern humans, while all other populations are descendants of a later migration wave. Our results have implications for understanding the complexity of modern human origins and diversity. PMID:26164107

  18. Computational models of human vision with applications

    NASA Technical Reports Server (NTRS)

    Wandell, Brian A.

    1987-01-01

    The research program supported by this grant was initiated in l977 by the Joint Institute for Aeronautics and Acoustics of the Department of Aeronautics and Astronautics at Stanford University. The purpose of the research was to study human performance with the goal of improving the design of flight instrumentation. By mutual agreement between the scientists at NASA-Ames and Stanford, all research activities in this area were consolidated into a single funding mechanism, NCC 2-307 (Center of Excellence Grant, 7/1/84 - present). This is the final report on this research grant.

  19. Application of postured human model for SAR measurements

    NASA Astrophysics Data System (ADS)

    Vuchkovikj, M.; Munteanu, I.; Weiland, T.

    2013-07-01

    In the last two decades, the increasing number of electronic devices used in day-to-day life led to a growing interest in the study of the electromagnetic field interaction with biological tissues. The design of medical devices and wireless communication devices such as mobile phones benefits a lot from the bio-electromagnetic simulations in which digital human models are used. The digital human models currently available have an upright position which limits the research activities in realistic scenarios, where postured human bodies must be considered. For this reason, a software application called "BodyFlex for CST STUDIO SUITE" was developed. In its current version, this application can deform the voxel-based human model named HUGO (Dipp GmbH, 2010) to allow the generation of common postures that people use in normal life, ensuring the continuity of tissues and conserving the mass to an acceptable level. This paper describes the enhancement of the "BodyFlex" application, which is related to the movements of the forearm and the wrist of a digital human model. One of the electromagnetic applications in which the forearm and the wrist movement of a voxel based human model has a significant meaning is the measurement of the specific absorption rate (SAR) when a model is exposed to a radio frequency electromagnetic field produced by a mobile phone. Current SAR measurements of the exposure from mobile phones are performed with the SAM (Specific Anthropomorphic Mannequin) phantom which is filled with a dispersive but homogeneous material. We are interested what happens with the SAR values if a realistic inhomogeneous human model is used. To this aim, two human models, a homogeneous and an inhomogeneous one, in two simulation scenarios are used, in order to examine and observe the differences in the results for the SAR values.

  20. Human casualties in earthquakes: modelling and mitigation

    USGS Publications Warehouse

    Spence, R.J.S.; So, E.K.M.

    2011-01-01

    Earthquake risk modelling is needed for the planning of post-event emergency operations, for the development of insurance schemes, for the planning of mitigation measures in the existing building stock, and for the development of appropriate building regulations; in all of these applications estimates of casualty numbers are essential. But there are many questions about casualty estimation which are still poorly understood. These questions relate to the causes and nature of the injuries and deaths, and the extent to which they can be quantified. This paper looks at the evidence on these questions from recent studies. It then reviews casualty estimation models available, and finally compares the performance of some casualty models in making rapid post-event casualty estimates in recent earthquakes.

  1. Modelling human locomotion: applications to cycling.

    PubMed

    Olds, T

    2001-01-01

    Mathematical models of performance in locomotor sports are reducible to functions of the sort y = f(x) where y is some performance variable, such as time, distance or speed, and x is a combination of predictor variables which may include expressions for power (or energy) supply and/or demand. The most valid and useful models are first-principles models that equate expressions for power supply and power demand. Power demand in cycling is the sum of the power required to overcome air resistance and rolling resistance, the power required to change the kinetic energy of the system, and the power required to ride up or down a grade. Power supply is drawn from aerobic and anaerobic sources, and modellers must consider not only the rate but also the kinetics and pattern of power supply. The relative contributions of air resistance to total demand, and of aerobic energy to total supply, increase curvilinearly with performance time, while the importance of other factors decreases. Factors such as crosswinds, aerodynamic accessories and drafting can modify the power demand in cycling, while body configuration/orientation and altitude will affect both power demand and power supply, often in opposite directions. Mathematical models have been used to solve specific problems in cycling, such as the chance of success of a breakaway, the optimal altitude for performance, creating a 'level playing field' to compare performances for selection purposes, and to quantify, in the common currency of minutes and seconds, the effects on performance of changes in physiological, environmental and equipment variables. The development of crank dynamometers and portable gas-analysis systems, combined with a modelling approach, will in the future provide valuable information on the effect of changes in equipment, configuration and environment on both supply and demand-side variables. PMID:11428687

  2. Human visual performance model for crewstation design

    NASA Technical Reports Server (NTRS)

    Larimer, James; Prevost, Michael; Arditi, Aries; Azueta, Steven; Bergen, James; Lubin, Jeffrey

    1991-01-01

    An account is given of a Visibility Modeling Tool (VMT) which furnishes a crew-station designer with the means to assess configurational tradeoffs, with a view to the impact of various options on the unambiguous access of information to the pilot. The interactive interface of the VMT allows the manipulation of cockpit geometry, ambient lighting, pilot ergonomics, and the displayed symbology. Performance data can be displayed in the form of 3D contours into the crewstation graphic model, thereby yielding an indication of the operator's visual capabilities.

  3. Human intelligence: the model is the message.

    PubMed

    Sternberg, R J

    1985-12-01

    Theories of intelligence, and some of the research testing them, are designed to answer three basic questions about intelligence: (i) What is the relation of intelligence to the internal world of the individual? (ii) What is the relation of intelligence to the external world of the individual? (iii) What is the relation of intelligence to experience? Various models of the mind underlying the theories have been proposed; the strengths and limitations of these models are assessed. A theory that addresses all three questions simultaneously is the triarchic theory. PMID:17739108

  4. Building a Shared Definitional Model of Long Duration Human Spaceflight

    NASA Technical Reports Server (NTRS)

    Arias, Diana; Orr, Martin; Whitmire, Alexandra; Leveton, Lauren; Sandoval, Luis

    2012-01-01

    Objective: To establish the need for a shared definitional model of long duration human spaceflight, that would provide a framework and vision to facilitate communication, research and practice In 1956, on the eve of human space travel, Hubertus Strughold first proposed a "simple classification of the present and future stages of manned flight" that identified key factors, risks and developmental stages for the evolutionary journey ahead. As we look to new destinations, we need a current shared working definitional model of long duration human space flight to help guide our path. Here we describe our preliminary findings and outline potential approaches for the future development of a definition and broader classification system

  5. Dynamic inverse models in human-cyber-physical systems

    NASA Astrophysics Data System (ADS)

    Robinson, Ryan M.; Scobee, Dexter R. R.; Burden, Samuel A.; Sastry, S. Shankar

    2016-05-01

    Human interaction with the physical world is increasingly mediated by automation. This interaction is characterized by dynamic coupling between robotic (i.e. cyber) and neuromechanical (i.e. human) decision-making agents. Guaranteeing performance of such human-cyber-physical systems will require predictive mathematical models of this dynamic coupling. Toward this end, we propose a rapprochement between robotics and neuromechanics premised on the existence of internal forward and inverse models in the human agent. We hypothesize that, in tele-robotic applications of interest, a human operator learns to invert automation dynamics, directly translating from desired task to required control input. By formulating the model inversion problem in the context of a tracking task for a nonlinear control system in control-a_ne form, we derive criteria for exponential tracking and show that the resulting dynamic inverse model generally renders a portion of the physical system state (i.e., the internal dynamics) unobservable from the human operator's perspective. Under stability conditions, we show that the human can achieve exponential tracking without formulating an estimate of the system's state so long as they possess an accurate model of the system's dynamics. These theoretical results are illustrated using a planar quadrotor example. We then demonstrate that the automation can intervene to improve performance of the tracking task by solving an optimal control problem. Performance is guaranteed to improve under the assumption that the human learns and inverts the dynamic model of the altered system. We conclude with a discussion of practical limitations that may hinder exact dynamic model inversion.

  6. Modeling human development in 3D culture.

    PubMed

    Ader, Marius; Tanaka, Elly M

    2014-12-01

    Recently human embryonic stem cell research has taken on a new dimension - the third dimension. Capitalizing on increasing knowledge on directing pluripotent cells along different lineages, combined with ECM supported three-dimensional culture conditions, it has become possible to generate highly organized tissues of the central nervous system, gut, liver and kidney. Each system has been used to study different aspects of organogenesis and function including physical forces underlying optic cup morphogenesis, the function of disease related genes in progenitor cell control, as well as interaction of the generated tissues with host tissue upon transplantation. Pluripotent stem cell derived organoids represent powerful systems for the study of how cells self-organize to generate tissues with a given shape, pattern and form. PMID:25033469

  7. Animal model of human disease: lymphocytic gastritis.

    PubMed

    Rubio, C A; Jarlnäs, M; Johnson, L

    1993-01-01

    Gastric specimens from 102 belonging to 11 different species were reviewed. Of the 11 species, only the gastric mucosa of pigs contained a large number of lymphocytes in the surface and in the foveolar epithelium (mean 82 lymphocytes/1000 epithelial cells, range 62-128 lymphocytes. The gastric specimens of the remaining 10 species revealed none or occasional lymphocytes in the surface or the foveolar epithelium. The occurrence of intraepithelial lymphocytes in the gastric mucosa of pigs mimics the human disease known as "lymphocytic gastritis". Since the etiology of this disease remains unknown, the apparently endemic nature of lymphocytic gastritis in pigs offer an alternative to investigate the possible cause(s), as well as the mechanism of, this disease.

  8. Paralysis recovery in humans and model systems

    NASA Technical Reports Server (NTRS)

    Edgerton, V. Reggie; Roy, Roland R.

    2002-01-01

    Considerable evidence now demonstrates that extensive functional and anatomical reorganization following spinal cord injury occurs in centers of the brain that have some input into spinal motor pools. This is very encouraging, given the accumulating evidence that new connections formed across spinal lesions may not be initially functionally useful. The second area of advancement in the field of paralysis recovery is in the development of effective interventions to counter axonal growth inhibition. A third area of significant progress is the development of robotic devices to quantify the performance level of motor tasks following spinal cord injury and to 'teach' the spinal cord to step and stand. Advances are being made with robotic devices for mice, rats and humans.

  9. Using Human Induced Pluripotent Stem Cells to Model Skeletal Diseases.

    PubMed

    Barruet, Emilie; Hsiao, Edward C

    2016-01-01

    Musculoskeletal disorders affecting the bones and joints are major health problems among children and adults. Major challenges such as the genetic origins or poor diagnostics of severe skeletal disease hinder our understanding of human skeletal diseases. The recent advent of human induced pluripotent stem cells (human iPS cells) provides an unparalleled opportunity to create human-specific models of human skeletal diseases. iPS cells have the ability to self-renew, allowing us to obtain large amounts of starting material, and have the potential to differentiate into any cell types in the body. In addition, they can carry one or more mutations responsible for the disease of interest or be genetically corrected to create isogenic controls. Our work has focused on modeling rare musculoskeletal disorders including fibrodysplasia ossificans progressive (FOP), a congenital disease of increased heterotopic ossification. In this review, we will discuss our experiences and protocols differentiating human iPS cells toward the osteogenic lineage and their application to model skeletal diseases. A number of critical challenges and exciting new approaches are also discussed, which will allow the skeletal biology field to harness the potential of human iPS cells as a critical model system for understanding diseases of abnormal skeletal formation and bone regeneration.

  10. Human Intelligence: The Model Is the Message.

    ERIC Educational Resources Information Center

    Sternberg, Robert J.

    1985-01-01

    Examines the relationship of intelligence to the internal and external world of the individual and to the experience of the individual. Also examines competing models and metaphors that have motivated questions about these relationships. Indicates that a theory that addressed all three areas simultaneously is the triarchic theory. (JN)

  11. Recapitulating Human Gastric Cancer Pathogenesis: Experimental Models of Gastric Cancer.

    PubMed

    Ding, Lin; El Zaatari, Mohamad; Merchant, Juanita L

    2016-01-01

    This review focuses on the various experimental models to study gastric cancer pathogenesis, with the role of genetically engineered mouse models (GEMMs) used as the major examples. We review differences in human stomach anatomy compared to the stomachs of the experimental models, including the mouse and invertebrate models such as Drosophila and C. elegans. The contribution of major signaling pathways, e.g., Notch, Hedgehog, AKT/PI3K is discussed in the context of their potential contribution to foregut tumorigenesis. We critically examine the rationale behind specific GEMMs, chemical carcinogens, dietary promoters, Helicobacter infection, and direct mutagenesis of relevant oncogenes and tumor suppressor that have been developed to study gastric cancer pathogenesis. Despite species differences, more efficient and effective models to test specific genes and pathways disrupted in human gastric carcinogenesis have yet to emerge. As we better understand these species differences, "humanized" versions of mouse models will more closely approximate human gastric cancer pathogenesis. Towards that end, epigenetic marks on chromatin, the gut microbiota, and ways of manipulating the immune system will likely move center stage, permitting greater overlap between rodent and human cancer phenotypes thus providing a unified progression model. PMID:27573785

  12. Lumped parametric model of the human ear for sound transmission.

    PubMed

    Feng, Bin; Gan, Rong Z

    2004-09-01

    A lumped parametric model of the human auditoria peripherals consisting of six masses suspended with six springs and ten dashpots was proposed. This model will provide the quantitative basis for the construction of a physical model of the human middle ear. The lumped model parameters were first identified using published anatomical data, and then determined through a parameter optimization process. The transfer function of the middle ear obtained from human temporal bone experiments with laser Doppler interferometers was used for creating the target function during the optimization process. It was found that, among 14 spring and dashpot parameters, there were five parameters which had pronounced effects on the dynamic behaviors of the model. The detailed discussion on the sensitivity of those parameters was provided with appropriate applications for sound transmission in the ear. We expect that the methods for characterizing the lumped model of the human ear and the model parameters will be useful for theoretical modeling of the ear function and construction of the ear physical model. PMID:15300453

  13. Lumped parametric model of the human ear for sound transmission.

    PubMed

    Feng, Bin; Gan, Rong Z

    2004-09-01

    A lumped parametric model of the human auditoria peripherals consisting of six masses suspended with six springs and ten dashpots was proposed. This model will provide the quantitative basis for the construction of a physical model of the human middle ear. The lumped model parameters were first identified using published anatomical data, and then determined through a parameter optimization process. The transfer function of the middle ear obtained from human temporal bone experiments with laser Doppler interferometers was used for creating the target function during the optimization process. It was found that, among 14 spring and dashpot parameters, there were five parameters which had pronounced effects on the dynamic behaviors of the model. The detailed discussion on the sensitivity of those parameters was provided with appropriate applications for sound transmission in the ear. We expect that the methods for characterizing the lumped model of the human ear and the model parameters will be useful for theoretical modeling of the ear function and construction of the ear physical model.

  14. Modeling and remote sensing of human induced water cycle change

    NASA Astrophysics Data System (ADS)

    Pokhrel, Yadu N.

    2016-04-01

    The global water cycle has been profoundly affected by human land-water management especially during the last century. Since the changes in water cycle can affect the functioning of a wide range of biophysical and biogeochemical processes of the Earth system, it is essential to account for human land-water management in land surface models (LSMs) which are used for water resources assessment and to simulate the land surface hydrologic processes within Earth system models (ESMs). During the last two decades, noteworthy progress has been made in modeling human impacts on the water cycle but sufficient advancements have not yet been made, especially in representing human factors in large-scale LSMs toward integrating them into ESMs. In this study, an integrated modeling framework of continental-scale water cycle, with explicit representation of climate and human induced forces (e.g., irrigation, groundwater pumping) is developed and used to reconstruct the observed water cycle changes in the past and to attribute the observed changes to climatic and human factors. The new model builds upon two different previously developed models: a global LSM called the Human Impacts and GroundWater in the MATSIRO (HiGW-MAT) and a high-resolution regional groundwater model called the LEAF-Hydro-Flood. The model is used to retro-simulate the hydrologic stores and fluxes in close dialogue with in-situ and GRACE satellite based observations at a wide range of river basin scales around the world, with a particular focus on the changes in groundwater dynamics in northwest India, Pakistan, and the High Plains and Central Valley aquifers in the US.

  15. Theoretical model of infrared radiation of dressed human body indoors

    NASA Astrophysics Data System (ADS)

    Xiong, Zonglong; Yang, Kuntao

    2008-02-01

    The human body detecting by infrared thermography plays an important role in the field of medical treatment, scout and rescuing work after disaster occuring. The infrared image theoretical model is a foundation for a human body detecting because it can improve the ability and efficiency. The essence and significance of the information on the temperature field of the human body in indoor environment is systematically discussed on the basis of physical structure and thermoregulation system. The various factors that influence the body temperature are analyzed, then the method for the calculation of temperature distribution of the surface temperature is introduced. On the basis of the infrared radiation theory, a theoretical model is proposed to calculate the radiant flux intensity of the human body. This model can be applied to many fields.

  16. Modeling aspects of human memory for scientific study.

    SciTech Connect

    Caudell, Thomas P.; Watson, Patrick; McDaniel, Mark A.; Eichenbaum, Howard B.; Cohen, Neal J.; Vineyard, Craig Michael; Taylor, Shawn Ellis; Bernard, Michael Lewis; Morrow, James Dan; Verzi, Stephen J.

    2009-10-01

    Working with leading experts in the field of cognitive neuroscience and computational intelligence, SNL has developed a computational architecture that represents neurocognitive mechanisms associated with how humans remember experiences in their past. The architecture represents how knowledge is organized and updated through information from individual experiences (episodes) via the cortical-hippocampal declarative memory system. We compared the simulated behavioral characteristics with those of humans measured under well established experimental standards, controlling for unmodeled aspects of human processing, such as perception. We used this knowledge to create robust simulations of & human memory behaviors that should help move the scientific community closer to understanding how humans remember information. These behaviors were experimentally validated against actual human subjects, which was published. An important outcome of the validation process will be the joining of specific experimental testing procedures from the field of neuroscience with computational representations from the field of cognitive modeling and simulation.

  17. Generation and use of human 3D-CAD models

    NASA Astrophysics Data System (ADS)

    Grotepass, Juergen; Speyer, Hartmut; Kaiser, Ralf

    2002-05-01

    Individualized Products are one of the ten mega trends of the 21st Century with human modeling as the key issue for tomorrow's design and product development. The use of human modeling software for computer based ergonomic simulations within the production process increases quality while reducing costs by 30- 50 percent and shortening production time. This presentation focuses on the use of human 3D-CAD models for both, the ergonomic design of working environments and made to measure garment production. Today, the entire production chain can be designed, individualized models generated and analyzed in 3D computer environments. Anthropometric design for ergonomics is matched to human needs, thus preserving health. Ergonomic simulation includes topics as human vision, reachability, kinematics, force and comfort analysis and international design capabilities. In German more than 17 billions of Mark are moved to other industries, because clothes do not fit. Individual clothing tailored to the customer's preference means surplus value, pleasure and perfect fit. The body scanning technology is the key to generation and use of human 3D-CAD models for both, the ergonomic design of working environments and made to measure garment production.

  18. A novel polar-based human face recognition computational model.

    PubMed

    Zana, Y; Mena-Chalco, J P; Cesar, R M

    2009-07-01

    Motivated by a recently proposed biologically inspired face recognition approach, we investigated the relation between human behavior and a computational model based on Fourier-Bessel (FB) spatial patterns. We measured human recognition performance of FB filtered face images using an 8-alternative forced-choice method. Test stimuli were generated by converting the images from the spatial to the FB domain, filtering the resulting coefficients with a band-pass filter, and finally taking the inverse FB transformation of the filtered coefficients. The performance of the computational models was tested using a simulation of the psychophysical experiment. In the FB model, face images were first filtered by simulated V1- type neurons and later analyzed globally for their content of FB components. In general, there was a higher human contrast sensitivity to radially than to angularly filtered images, but both functions peaked at the 11.3-16 frequency interval. The FB-based model presented similar behavior with regard to peak position and relative sensitivity, but had a wider frequency band width and a narrower response range. The response pattern of two alternative models, based on local FB analysis and on raw luminance, strongly diverged from the human behavior patterns. These results suggest that human performance can be constrained by the type of information conveyed by polar patterns, and consequently that humans might use FB-like spatial patterns in face processing. PMID:19578643

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

    SciTech Connect

    R. L. Boring

    2007-06-01

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

  20. Mathematical modeling of human brain physiological data

    NASA Astrophysics Data System (ADS)

    Böhm, Matthias; Faltermeier, Rupert; Brawanski, Alexander; Lang, Elmar W.

    2013-12-01

    Recently, a mathematical model of the basic physiological processes regulating the cerebral perfusion and oxygen supply was introduced [Jung , J. Math. Biol.JMBLAJ0303-681210.1007/s00285-005-0343-5 51, 491 (2005)]. Although this model correctly describes the interdependence of arterial blood pressure (ABP) and intracranial pressure (ICP), it fails badly when it comes to explaining certain abnormal correlations seen in about 80% of the recordings of ABP together with ICP and the partial oxygen pressure (TiPO2) of the neuronal tissue, taken at an intensive care unit during neuromonitoring of patients with a severe brain trauma. Such recordings occasionally show segments, where the mean arterial blood pressure is correlated with the partial oxygen pressure in tissue but anticorrelated with the intracranial pressure. The origin of such abnormal correlations has not been fully understood yet. Here, two extensions to the previous approach are proposed which can reproduce such abnormal correlations in simulations quantitatively. Furthermore, as the simulations are based on a mathematical model, additional insight into the physiological mechanisms from which such abnormal correlations originate can be gained.

  1. Modelling human disease with pluripotent stem cells

    PubMed Central

    Park, In-Hyun; Sullivan, Gareth J.

    2013-01-01

    Recent progress in the field of cellular reprogramming has opened up the doors to a new era of disease modelling, as pluripotent stem cells representing a myriad of genetic diseases can now be produced from patient tissue. These cells can be expanded and differentiated to produce a potentially limitless supply of the affected cell type, which can then be used as a tool to improve understanding of disease mechanisms and test therapeutic interventions. This process requires high levels of scrutiny and validation at every stage, but international standards for the characterisation of pluripotent cells and their progeny have yet to be established. Here we discuss the current state of the art with regard to modelling diseases affecting the ectodermal, mesodermal and endodermal lineages, focussing on studies which have demonstrated a disease phenotype in the tissue of interest. We also discuss the utility of pluripotent cell technology for the modelling of cancer and infectious disease. Finally, we spell out the technical and scientific challenges which must be addressed if the field is to deliver on its potential and produce improved patient outcomes in the clinic. PMID:23444871

  2. Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.

    PubMed

    Bird, Brian H; Spengler, Jessica R; Chakrabarti, Ayan K; Khristova, Marina L; Sealy, Tara K; Coleman-McCray, JoAnn D; Martin, Brock E; Dodd, Kimberly A; Goldsmith, Cynthia S; Sanders, Jeanine; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

    2016-03-01

    Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening.

  3. Development of humanized mouse models to study human malaria parasite infection

    PubMed Central

    Vaughan, Ashley M; Kappe, Stefan HI; Ploss, Alexander; Mikolajczak, Sebastian A

    2013-01-01

    Malaria is a disease caused by infection with Plasmodium parasites that are transmitted by mosquito bite. Five different species of Plasmodium infect humans with severe disease, but human malaria is primarily caused by Plasmodium falciparum. The burden of malaria on the developing world is enormous, and a fully protective vaccine is still elusive. One of the biggest challenges in the quest for the development of new antimalarial drugs and vaccines is the lack of accessible animal models to study P. falciparum infection because the parasite is restricted to the great apes and human hosts. Here, we review the current state of research in this field and provide an outlook of the development of humanized small animal models to study P. falciparum infection that will accelerate fundamental research into human parasite biology and could accelerate drug and vaccine design in the future. PMID:22568719

  4. Animal models are reliably mimicking human diseases? A morphological study that compares animal with human NAFLD.

    PubMed

    Solinas, Paola; Isola, Michela; Lilliu, Maria Alberta; Conti, Gabriele; Civolani, Alberto; Demelia, Luigi; Loy, Francesco; Isola, Raffaella

    2014-10-01

    Non-alcoholic fatty liver disease (NAFLD) is a clinical-pathological syndrome that includes a wide spectrum of morphological alterations. In research, animal models are crucial in evaluating not only the pathogenesis of NAFLD and its progression, but also the therapeutic effects of various agents. Investigations on the ultrastructural features of NAFLD in humans are not copious, due to the difficulty to obtain human samples and to the long time of NAFLD to evolve. Translational comparative studies on the reliability of animal models in representing the histopathologic picture as seen in humans are missing. To overcome this lack of investigations, we compared the ultrastructural NAFLD features of an animal model versus human. Sprague-Dawley rats were fed with a high fat diet (HFD) for 1-4 weeks, while control rats were fed with a standard diet. Human specimens were collected from patients with diagnosed fatty liver disease, undergoing liver biopsies or surgery. Rat and human samples were examined by light microscopy and by transmission and high resolution scanning electron microscopy. The present work demonstrated that NAFLD in animal model and in human, share overlapping ultrastructural features. In conclusion, animal HFD represent an appropriate tool in studying the pathogenesis of NAFLD.

  5. Applications of the human p53 knock-in (Hupki) mouse model for human carcinogen testing.

    PubMed

    Besaratinia, Ahmad; Pfeifer, Gerd P

    2010-08-01

    Tumor-driving mutations in the TP53 gene occur frequently in human cancers. These inactivating mutations arise predominantly from a single-point mutation in the DNA-binding domain of this tumor suppressor gene (i.e., exons 4-9). The human p53 knock-in (Hupki) mouse model was constructed using gene-targeting technology to create a mouse strain that harbors human wild-type TP53 DNA sequences in both copies of the mouse TP53 gene. Replacement of exons 4-9 of the endogenous mouse TP53 alleles in the Hupki mouse with the homologous normal human TP53 gene sequences has offered a humanized replica of the TP53 gene in a murine genetic environment. The Hupki mouse model system has proven to be an invaluable research tool for studying the underlying mechanisms of human TP53 mutagenesis. The utility of the Hupki mouse model system for exploring carcinogen-induced TP53 mutagenesis has been demonstrated in both in vivo animal experiments and in vitro cell culture experiments. Here, we highlight applications of the Hupki mouse model system for investigating mutagenesis induced by a variety of environmental carcinogens, including sunlight ultraviolet radiation, benzo[a]pyrene (a tobacco smoke-derived carcinogen), 3-nitrobenzanthrone (an urban air pollutant), aristolochic acid (a component of Chinese herbal medicine), and aflatoxin B1 (a food contaminant). We summarize the salient findings of the respective studies and discuss their relevance to human cancer etiology.

  6. Pharmacokinetic model-predicted anticancer drug concentrations in human tumors.

    PubMed

    Gallo, James M; Vicini, Paolo; Orlansky, Amy; Li, Shaolan; Zhou, Feng; Ma, Jianguo; Pulfer, Sharon; Bookman, Michel A; Guo, Ping

    2004-12-01

    In an era when molecular and targeted anticancer therapeutics is a major focus and when understanding drug dynamics in tumor is critical, it seems advantageous to be able to relate drug concentrations in tumors to corresponding biological end points. To that end, a novel method, based on physiologically based hybrid pharmacokinetic models, is presented to predict human tumor drug concentrations. Such models consist of a forcing function, describing the plasma drug concentration-time profile, which is linked to a model describing drug disposition in tumors. The hybrid models are originally derived from preclinical data and then scaled to humans. Integral to the scale-up procedure is the ability to derive human forcing functions directly from clinical pharmacokinetic data. Three examples of this approach are presented based on preclinical investigations with carboplatin, topotecan, and temozolomide. Translation of these preclinical hybrid models to humans used a Monte Carlo simulation technique that accounted for intrasubject and intersubject variability. Different pharmacokinetic end points, such as the AUC tumor, were extracted from the simulated human tumor drug concentrations to show how the predicted drug concentrations might be used to select drug-dosing regimens. It is believed that this modeling strategy can be used as an aid in the drug development process by providing key insights into drug disposition in tumors and by offering a foundation to optimize drug regimen design. PMID:15585640

  7. Tissue-engineered models of human tumors for cancer research

    PubMed Central

    Villasante, Aranzazu; Vunjak-Novakovic, Gordana

    2015-01-01

    Introduction Drug toxicity often goes undetected until clinical trials, which are the most costly and dangerous phase of drug development. Both the cultures of human cells and animal studies have limitations that cannot be overcome by incremental improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. An area that could greatly benefit from these models is cancer research. Areas covered In this review, the authors first describe the engineered tumor systems, using Ewing's sarcoma as an example of human tumor that cannot be predictably studied in cell culture and animal models. Then, they discuss the importance of the tissue context for cancer progression and outline the biomimetic principles for engineering human tumors. Finally, they discuss the utility of bioengineered tumor models for cancer research and address the challenges in modeling human tumors for use in drug discovery and testing. Expert opinion While tissue models are just emerging as a new tool for cancer drug discovery, they are already demonstrating potential for recapitulating, in vitro, the native behavior of human tumors. Still, numerous challenges need to be addressed before we can have platforms with a predictive power appropriate for the pharmaceutical industry. Some of the key needs include the incorporation of the vascular compartment, immune system components, and mechanical signals that regulate tumor development and function. PMID:25662589

  8. Pharmacokinetic modeling of trichloroethylene and trichloroacetic acid in humans.

    PubMed

    Allen, B C; Fisher, J W

    1993-02-01

    The development and application of appropriate physiologically based pharmacokinetic (PBPK) models of chemical contaminants will provide a rational basis for risk assessment extrapolation. Trichloroethylene (TCE) is a widespread contaminant found in soil, groundwater, and the atmosphere. Exposures to TCE and its metabolites have been found to be carcinogenic in rodents. In this study, a PBPK model for TCE and its major metabolite, trichloroacetic acid (TCA), is developed for humans. The model parameters, estimated from the relevant published literature on human exposures to TCE and its metabolites, are described. Key parameters describing the metabolism of TCE and the kinetics of TCA were estimated by optimization. The optimization was accomplished by simultaneously matching model predictions to observations of TCE concentrations in blood and exhaled breath, TCA plasma concentrations, and urinary TCA excretion from five published studies. The optimized human PBPK model provides an excellent description of TCE and TCA kinetics. The predictions were especially good for TCA plasma concentrations following repeated TCE inhalation, an exposure scenario similar to that occurring in the workplace. The human PBPK model can be used to estimate dose metrics resulting from TCE exposures and is therefore useful when considering the estimation of human health risks associated with such exposures.

  9. A Systemic Cause Analysis Model for Human Performance Technicians

    ERIC Educational Resources Information Center

    Sostrin, Jesse

    2011-01-01

    This article presents a systemic, research-based cause analysis model for use in the field of human performance technology (HPT). The model organizes the most prominent barriers to workplace learning and performance into a conceptual framework that explains and illuminates the architecture of these barriers that exist within the fabric of everyday…

  10. Computational 3-D Model of the Human Respiratory System

    EPA Science Inventory

    We are developing a comprehensive, morphologically-realistic computational model of the human respiratory system that can be used to study the inhalation, deposition, and clearance of contaminants, while being adaptable for age, race, gender, and health/disease status. The model ...

  11. New Models and Metaphors for Human Resource Development.

    ERIC Educational Resources Information Center

    1999

    This document contains two reports from a poster session on new ideas and models in human resource development (HRD). The first presentation, "Two-way Customer-Service Provider Cycle" (Harriet V. Lawrence, Albert K. Wiswell), discusses a two-way supply cycle model that illustrates relational issues in customer service, including needs and wants,…

  12. The Various Roles of Animal Models in Understanding Human Development

    ERIC Educational Resources Information Center

    Gottlieb, Gilbert; Lickliter, Robert

    2004-01-01

    In this article, the authors take a very conservative view of the contribution of animal models to an understanding of human development. We do not think that homologies can be readily documented with even our most closely related relatives' behavior and psychological functioning. The major contribution of animal models is their provision of food…

  13. Energy expenditure during human gait. I - An optimized model.

    PubMed

    Rodrigo, Silvia; Garcia, Isabel; Franco, Marian; Alonso-Vazquez, Ana; Ambrosio, Jorge

    2010-01-01

    Within the framework of multibody dynamics, a 3D large scale neuromusculoskeletal model of the human body is presented. To characterize the dynamics of skeletal muscle, a phenomenological model of energy expenditure was developed for estimating energy consumption during normal locomotion. Such model is able for predicting thermal and mechanical energy liberation under submaximal activation, muscle fiber type, and varying contractile conditions, typically observed in human motion. Future formulations of the indeterminate biomechanical problem, solved through the physiological criteria of minimization of metabolical cost of transport during gait, should consider the role of muscle groups in coordinating multijoint motion. Such an approach is presented in part II of the paper.

  14. Evaluation of the human nickel retention model with workplace data.

    PubMed

    Yu, C P; Hsieh, T H; Oller, A R; Oberdörster, G

    2001-04-01

    A previously developed dosimetry model of inhaled Ni compounds in the human lung has been expanded by incorporating three additional factors: (1) inhalability, (2) mixed breathing mode, and (3) clearance rate coefficient of a Ni compounds' mixture. Predicted lung burdens of Ni compounds from the expanded model for workers at different departments in a Ni refinery plant compared favorably with the reported data. Although many uncertainties remain, the present model represents a first step toward developing a more meaningful risk assessment tool that will allow for more accurate extrapolation of animal data to humans. PMID:11350199

  15. Combined Hand Gesture — Speech Model for Human Action Recognition

    PubMed Central

    Cheng, Sheng-Tzong; Hsu, Chih-Wei; Li, Jian-Pan

    2013-01-01

    This study proposes a dynamic hand gesture detection technology to effectively detect dynamic hand gesture areas, and a hand gesture recognition technology to improve the dynamic hand gesture recognition rate. Meanwhile, the corresponding relationship between state sequences in hand gesture and speech models is considered by integrating speech recognition technology with a multimodal model, thus improving the accuracy of human behavior recognition. The experimental results proved that the proposed method can effectively improve human behavior recognition accuracy and the feasibility of system applications. Experimental results verified that the multimodal gesture-speech model provided superior accuracy when compared to the single modal versions. PMID:24351628

  16. Applications of the human p53 knock-in (Hupki) mouse model for human carcinogen testing

    PubMed Central

    Besaratinia, Ahmad; Pfeifer, Gerd P.

    2010-01-01

    Tumor-driving mutations in the TP53 gene occur frequently in human cancers. These inactivating mutations arise predominantly from a single-point mutation in the DNA-binding domain of this tumor suppressor gene (i.e., exons 4–9). The human p53 knock-in (Hupki) mouse model was constructed using gene-targeting technology to create a mouse strain that harbors human wild-type TP53 DNA sequences in both copies of the mouse TP53 gene. Replacement of exons 4–9 of the endogenous mouse TP53 alleles in the Hupki mouse with the homologous normal human TP53 gene sequences has offered a humanized replica of the TP53 gene in a murine genetic environment. The Hupki mouse model system has proven to be an invaluable research tool for studying the underlying mechanisms of human TP53 mutagenesis. The utility of the Hupki mouse model system for exploring carcinogen-induced TP53 mutagenesis has been demonstrated in both in vivo animal experiments and in vitro cell culture experiments. Here, we highlight applications of the Hupki mouse model system for investigating mutagenesis induced by a variety of environmental carcinogens, including sunlight ultraviolet radiation, benzo[a]pyrene (a tobacco smoke-derived carcinogen), 3-nitrobenzanthrone (an urban air pollutant), aristolochic acid (a component of Chinese herbal medicine), and aflatoxin B1 (a food contaminant). We summarize the salient findings of the respective studies and discuss their relevance to human cancer etiology.—Besaratinia, A., Pfeifer, G. P. Applications of the human p53 knock-in (Hupki) mouse model for human carcinogen testing. PMID:20371617

  17. Modelling human decision-making in coupled human and natural systems

    NASA Astrophysics Data System (ADS)

    Feola, G.

    2012-12-01

    A solid understanding of human decision-making is essential to analyze the complexity of coupled human and natural systems (CHANS) and inform policies to promote resilience in the face of environmental change. Human decisions drive and/or mediate the interactions and feedbacks, and contribute to the heterogeneity and non-linearity that characterize CHANS. However, human decision-making is usually over-simplistically modeled, whereby human agents are represented deterministically either as dumb or clairvoyant decision-makers. Decision-making models fall short in the integration of both environmental and human behavioral drivers, and concerning the latter, tend to focus on only one category, e.g. economic, cultural, or psychological. Furthermore, these models render a linear decision-making process and therefore fail to account for the recursive co-evolutionary dynamics in CHANS. As a result, these models constitute only a weak basis for policy-making. There is therefore scope and an urgent need for better approaches to human decision-making, to produce the knowledge that can inform vulnerability reduction policies in the face of environmental change. This presentation synthesizes the current state-of-the-art of modelling human decision-making in CHANS, with particular reference to agricultural systems, and delineates how the above mentioned shortcomings can be overcome. Through examples from research on pesticide use and adaptation to climate change, both based on the integrative agent-centered framework (Feola and Binder, 2010), the approach for an improved understanding of human agents in CHANS are illustrated. This entails: integrative approach, focus on behavioral dynamics more than states, feedbacks between individual and system levels, and openness to heterogeneity.

  18. Human surrogate models of histaminergic and non-histaminergic itch.

    PubMed

    Andersen, Hjalte H; Elberling, Jesper; Arendt-Nielsen, Lars

    2015-09-01

    Within the last decade understanding of the mechanistic basis of itch has improved significantly, resulting in the development of several human surrogate models of itch and related dysesthetic states. Well-characterized somatosensory models are useful in basic studies in healthy volunteers, in clinical studies for diagnostic and segmentation purposes, and in pharmacological studies to evaluate the antipruritic efficacy of existing and novel compounds. This review outlines recently introduced histamine-independent human models of itch, their mechanisms, their ability to induce clinically relevant phenomena, such as alloknesis, and the results obtained through their use. The article also introduces recent advances in the understanding of itch and provides an overview of the methods to assess experimentally-induced itch and associated manifestations. Major improvements are warranted in the treatment of chronic pruritus, and reliable human surrogate models are a valuable tool in achieving them, both for basic researchers and for clinicians.

  19. Modeling cognition and disease using human glial chimeric mice.

    PubMed

    Goldman, Steven A; Nedergaard, Maiken; Windrem, Martha S

    2015-08-01

    As new methods for producing and isolating human glial progenitor cells (hGPCs) have been developed, the disorders of myelin have become especially compelling targets for cell-based therapy. Yet as animal modeling of glial progenitor cell-based therapies has progressed, it has become clear that transplanted hGPCs not only engraft and expand within murine hosts, but dynamically outcompete the resident progenitors so as to ultimately dominate the host brain. The engrafted human progenitor cells proceed to generate parenchymal astrocytes, and when faced with a hypomyelinated environment, oligodendrocytes as well. As a result, the recipient brains may become inexorably humanized with regards to their resident glial populations, yielding human glial chimeric mouse brains. These brains provide us a fundamentally new tool by which to assess the species-specific attributes of glia in modulating human cognition and information processing. In addition, the cellular humanization of these brains permits their use in studying glial infectious and inflammatory disorders unique to humans, and the effects of those disorders on the glial contributions to cognition. Perhaps most intriguingly, by pairing our ability to construct human glial chimeras with the production of patient-specific hGPCs derived from pluripotential stem cells, we may now establish mice in which a substantial proportion of resident glia are both human and disease-derived. These mice in particular may provide us new opportunities for studying the human-specific contributions of glia to psychopathology, as well as to higher cognition. As such, the assessment of human glial chimeric mice may provide us new insight into the species-specific contributions of glia to human cognitive evolution, as well as to the pathogenesis of human neurological and neuropsychiatric disease.

  20. Modeling and simulating human teamwork behaviors using intelligent agents

    NASA Astrophysics Data System (ADS)

    Fan, Xiaocong; Yen, John

    2004-12-01

    Among researchers in multi-agent systems there has been growing interest in using intelligent agents to model and simulate human teamwork behaviors. Teamwork modeling is important for training humans in gaining collaborative skills, for supporting humans in making critical decisions by proactively gathering, fusing, and sharing information, and for building coherent teams with both humans and agents working effectively on intelligence-intensive problems. Teamwork modeling is also challenging because the research has spanned diverse disciplines from business management to cognitive science, human discourse, and distributed artificial intelligence. This article presents an extensive, but not exhaustive, list of work in the field, where the taxonomy is organized along two main dimensions: team social structure and social behaviors. Along the dimension of social structure, we consider agent-only teams and mixed human-agent teams. Along the dimension of social behaviors, we consider collaborative behaviors, communicative behaviors, helping behaviors, and the underpinning of effective teamwork-shared mental models. The contribution of this article is that it presents an organizational framework for analyzing a variety of teamwork simulation systems and for further studying simulated teamwork behaviors.

  1. Animal models of human placentation--a review.

    PubMed

    Carter, A M

    2007-04-01

    This review examines the strengths and weaknesses of animal models of human placentation and pays particular attention to the mouse and non-human primates. Analogies can be drawn between mouse and human in placental cell types and genes controlling placental development. There are, however, substantive differences, including a different mode of implantation, a prominent yolk sac placenta, and fewer placental hormones in the mouse. Crucially, trophoblast invasion is very limited in the mouse and transformation of uterine arteries depends on maternal factors. The mouse also has a short gestation and delivers poorly developed young. Guinea pig is a good alternative rodent model and among the few species known to develop pregnancy toxaemia. The sheep is well established as a model in fetal physiology but is of limited value for placental research. The ovine placenta is epitheliochorial, there is no trophoblast invasion of uterine vessels, and the immunology of pregnancy may be quite different. We conclude that continued research on non-human primates is needed to clarify embryonic-endometrial interactions. The interstitial implantation of human is unusual, but the initial interaction between trophoblast and endometrium is similar in macaques and baboons, as is the subsequent lacunar stage. The absence of interstitial trophoblast cells in the monkey is an important difference from human placentation. However, there is a strong resemblance in the way spiral arteries are invaded and transformed in the macaque, baboon and human. Non-human primates are therefore important models for understanding the dysfunction that has been linked to pre-eclampsia and fetal growth restriction. Models that are likely to be established in the wake of comparative genomics include the marmoset, tree shrew, hedgehog tenrec and nine-banded armadillo.

  2. MODELING ENERGY EXPENDITURE AND OXYGEN CONSUMPTION IN HUMAN EXPOSURE MODELS: ACCOUNTING FOR FATIGUE AND EPOC

    EPA Science Inventory

    Human exposure and dose models often require a quantification of oxygen consumption for a simulated individual. Oxygen consumption is dependent on the modeled Individual's physical activity level as described in an activity diary. Activity level is quantified via standardized val...

  3. The GOURD model of human-computer interaction

    SciTech Connect

    Goldbogen, G.

    1996-12-31

    This paper presents a model, the GOURD model, that can be used to measure the goodness of {open_quotes}interactivity{close_quotes} of an interface design and qualifies how to improve the design. The GOURD model describes what happens to the computer and to the human during a human-computer interaction. Since the interaction is generally repeated, the traversal of the model repeatedly is similar to a loop programming structure. Because the model measures interaction over part or all of the application, it can also be used as a classifier of the part or the whole application. But primarily, the model is used as a design guide and a predictor of effectiveness.

  4. Modeling Human Behavior to Anticipate Insider Attacks

    SciTech Connect

    Greitzer, Frank L.; Hohimer, Ryan E.

    2011-06-09

    The insider threat ranks among the most pressing cybersecurity challenges that threaten government and industry information infrastructures. To date, no systematic methods have been developed that provide a complete and effective approach to prevent data leakage, espionage and sabotage. Current practice is forensic in nature, relegating to the analyst the bulk of the responsibility to monitor, analyze, and correlate an overwhelming amount of data. We describe a predictive modeling framework that integrates a diverse set of data sources from the cyber domain as well as inferred psychological/motivational factors that may underlie malicious insider exploits. This comprehensive threat assessment approach provides automated support for the detection of high-risk behavioral “triggers” to help focus the analyst’s attention and inform the analysis. Designed to be domain independent, the system may be applied to many different threat and warning analysis/sensemaking problems.

  5. A human experimental model of episodic pain.

    PubMed

    Petrini, Laura; Hennings, Kristian; Li, Xi; Negro, Francesco; Arendt-Nielsen, Lars

    2014-12-01

    An experimental model of daily episodic pain was developed to investigate peripheral sensitization and cortical reorganization in healthy individuals. Two experiments (A and B) were conducted. Experiments A and B consisted of one and five consecutive days, respectively, in which the participants were subjected to 45 min of intense painful cutaneous electrical stimulation (episodic pain session), using a stimulus paradigm that in animals has been shown to induce long-term potentiation. These electrical stimulations produced a verbal pain rating of approximately 85 on a 0-100 verbal rating scale (VRS). Physiological (blood flow and axon flare reflex), psychophysical (perception threshold and verbal pain ratings) and electrophysiological (128 channels recorded somatosensory evoked potential (SEP)) measurements were recorded. The stimulation evoked a visible axon flare reflex and caused significantly increased cutaneous blood flow around the site of the stimulation. Axon flare reflex and blood flow reached a plateau on day one in all the subjects and no significant changes between the days were observed. The results showed that the effect of the electrical stimulations changed over the five days; pain potentiation was induced on the first day (significant increase in the verbal pain ratings during the 45 min stimulation) but not on any of the subsequent days. After five days of subsequent pain induction, the global field power showed a significant reduction in P2 amplitude in the late stage (200-370 ms, in the central-parietal area). In conclusion, the results suggest that in healthy individuals this model of episodic pain produces a rapid adaptation after day one and that generates significant SEP changes at day five.

  6. DigitalHuman (DH): An Integrative Mathematical Model ofHuman Physiology

    NASA Technical Reports Server (NTRS)

    Hester, Robert L.; Summers, Richard L.; lIescu, Radu; Esters, Joyee; Coleman, Thomas G.

    2010-01-01

    Mathematical models and simulation are important tools in discovering the key causal relationships governing physiological processes and improving medical intervention when physiological complexity is a central issue. We have developed a model of integrative human physiology called DigitalHuman (DH) consisting of -5000 variables modeling human physiology describing cardiovascular, renal, respiratory, endocrine, neural and metabolic physiology. Users can view time-dependent solutions and interactively introduce perturbations by altering numerical parameters to investigate new hypotheses. The variables, parameters and quantitative relationships as well as all other model details are described in XML text files. All aspects of the model, including the mathematical equations describing the physiological processes are written in XML open source, text-readable files. Model structure is based upon empirical data of physiological responses documented within the peer-reviewed literature. The model can be used to understand proposed physiological mechanisms and physiological interactions that may not be otherwise intUitively evident. Some of the current uses of this model include the analyses of renal control of blood pressure, the central role of the liver in creating and maintaining insulin resistance, and the mechanisms causing orthostatic hypotension in astronauts. Additionally the open source aspect of the modeling environment allows any investigator to add detailed descriptions of human physiology to test new concepts. The model accurately predicts both qualitative and more importantly quantitative changes in clinically and experimentally observed responses. DigitalHuman provides scientists a modeling environment to understand the complex interactions of integrative physiology. This research was supported by.NIH HL 51971, NSF EPSCoR, and NASA

  7. A model of the human in a cognitive prediction task.

    NASA Technical Reports Server (NTRS)

    Rouse, W. B.

    1973-01-01

    The human decision maker's behavior when predicting future states of discrete linear dynamic systems driven by zero-mean Gaussian processes is modeled. The task is on a slow enough time scale that physiological constraints are insignificant compared with cognitive limitations. The model is basically a linear regression system identifier with a limited memory and noisy observations. Experimental data are presented and compared to the model.

  8. Genetically engineered humanized mouse models for preclinical antibody studies.

    PubMed

    Proetzel, Gabriele; Wiles, Michael V; Roopenian, Derry C

    2014-04-01

    The use of genetic engineering has vastly improved our capabilities to create animal models relevant in preclinical research. With the recent advances in gene-editing technologies, it is now possible to very rapidly create highly tunable mouse models as needs arise. Here, we provide an overview of genetic engineering methods, as well as the development of humanized neonatal Fc receptor (FcRn) models and their use for monoclonal antibody in vivo studies.

  9. Microscopic Modelling Circadian and Bursty Pattern of Human Activities

    PubMed Central

    Kim, Jinhong; Lee, Deokjae; Kahng, Byungnam

    2013-01-01

    Recent studies for a wide range of human activities such as email communication, Web browsing, and library visiting, have revealed the bursty nature of human activities. The distribution of inter-event times (IETs) between two consecutive human activities exhibits a heavy-tailed decay behavior and the oscillating pattern with a one-day period, reflective of the circadian pattern of human life. Even though a priority-based queueing model was successful as a basic model for understanding the heavy-tailed behavior, it ignored important ingredients, such as the diversity of individual activities and the circadian pattern of human life. Here, we collect a large scale of dataset which contains individuals’ time stamps when articles are posted on blog posts, and based on which we construct a theoretical model which can take into account of both ignored ingredients. Once we identify active and inactive time intervals of individuals and remove the inactive time interval, thereby constructing an ad hoc continuous time domain. Therein, the priority-based queueing model is applied by adjusting the arrival and the execution rates of tasks by comparing them with the activity data of individuals. Then, the obtained results are transferred back to the real-time domain, which produces the oscillating and heavy-tailed IET distribution. This microscopic model enables us to develop theoretical understanding towards more empirical results. PMID:23505479

  10. Human Modeling Evaluations in Microgravity Workstation and Restraint Development

    NASA Technical Reports Server (NTRS)

    Whitmore, Mihriban; Chmielewski, Cynthia; Wheaton, Aneice; Hancock, Lorraine; Beierle, Jason; Bond, Robert L. (Technical Monitor)

    1999-01-01

    The International Space Station (ISS) will provide long-term missions which will enable the astronauts to live and work, as well as, conduct research in a microgravity environment. The dominant factor in space affecting the crew is "weightlessness" which creates a challenge for establishing workstation microgravity design requirements. The crewmembers will work at various workstations such as Human Research Facility (HRF), Microgravity Sciences Glovebox (MSG) and Life Sciences Glovebox (LSG). Since the crew will spend considerable amount of time at these workstations, it is critical that ergonomic design requirements are integral part of design and development effort. In order to achieve this goal, the Space Human Factors Laboratory in the Johnson Space Center Flight Crew Support Division has been tasked to conduct integrated evaluations of workstations and associated crew restraints. Thus, a two-phase approach was used: 1) ground and microgravity evaluations of the physical dimensions and layout of the workstation components, and 2) human modeling analyses of the user interface. Computer-based human modeling evaluations were an important part of the approach throughout the design and development process. Human modeling during the conceptual design phase included crew reach and accessibility of individual equipment, as well as, crew restraint needs. During later design phases, human modeling has been used in conjunction with ground reviews and microgravity evaluations of the mock-ups in order to verify the human factors requirements. (Specific examples will be discussed.) This two-phase approach was the most efficient method to determine ergonomic design characteristics for workstations and restraints. The real-time evaluations provided a hands-on implementation in a microgravity environment. On the other hand, only a limited number of participants could be tested. The human modeling evaluations provided a more detailed analysis of the setup. The issues identified

  11. Are animal models relevant to key aspects of human parturition?

    PubMed

    Mitchell, Bryan F; Taggart, Michael J

    2009-09-01

    Preterm birth remains the most serious complication of pregnancy and is associated with increased rates of infant death or permanent neurodevelopmental disability. Our understanding of the regulation of parturition remains inadequate. The scientific literature, largely derived from rodent animal models, suggests two major mechanisms regulating the timing of parturition: the withdrawal of the steroid hormone progesterone and a proinflammatory response by the immune system. However, available evidence strongly suggests that parturition in the human has significantly different regulators and mediators from those in most of the animal models. Our objectives are to critically review the data and concepts that have arisen from use of animal models for parturition and to rationalize the use of a new model. Many animal models have contributed to advances in our understanding of the regulation of parturition. However, we suggest that those animals dependent on progesterone withdrawal to initiate parturition clearly have a limitation to their translation to the human. In such models, a linear sequence of events (e.g., luteolysis, progesterone withdrawal, uterine activation, parturition) gives rise to the concept of a "trigger" mechanism. Conversely, we propose that human parturition may arise from the concomitant maturation of several systems in parallel. We have termed this novel concept "modular accumulation of physiological systems" (MAPS). We also emphasize the urgency to determine the precise role of the immune system in the process of parturition in situations other than intrauterine infection. Finally, we accentuate the need to develop a nonprimate animal model whose physiology is more relevant to human parturition. We suggest that the guinea pig displays several key physiological characteristics of gestation that more closely resemble human pregnancy than do currently favored animal models. We conclude that the application of novel concepts and new models are

  12. Thermodynamic Modeling and Analysis of Human Stress Response

    NASA Technical Reports Server (NTRS)

    Boregowda, S. C.; Tiwari, S. N.

    1999-01-01

    A novel approach based on the second law of thermodynamics is developed to investigate the psychophysiology and quantify human stress level. Two types of stresses (thermal and mental) are examined. A Unified Stress Response Theory (USRT) is developed under the new proposed field of study called Engineering Psychophysiology. The USRT is used to investigate both thermal and mental stresses from a holistic (human body as a whole) and thermodynamic viewpoint. The original concepts and definitions are established as postulates which form the basis for thermodynamic approach to quantify human stress level. An Objective Thermal Stress Index (OTSI) is developed by applying the second law of thermodynamics to the human thermal system to quantify thermal stress or dis- comfort in the human body. The human thermal model based on finite element method is implemented. It is utilized as a "Computational Environmental Chamber" to conduct series of simulations to examine the human thermal stress responses under different environmental conditions. An innovative hybrid technique is developed to analyze human thermal behavior based on series of human-environment interaction simulations. Continuous monitoring of thermal stress is demonstrated with the help of OTSI. It is well established that the human thermal system obeys the second law of thermodynamics. Further, the OTSI is validated against the experimental data. Regarding mental stress, an Objective Mental Stress Index (OMSI) is developed by applying the Maxwell relations of thermodynamics to the combined thermal and cardiovascular system in the human body. The OMSI is utilized to demonstrate the technique of monitoring mental stress continuously and is validated with the help of series of experimental studies. Although the OMSI indicates the level of mental stress, it provides a strong thermodynamic and mathematical relationship between activities of thermal and cardiovascular systems of the human body.

  13. MODELING HUMAN EXPOSURES AND DOSE USING A 2-DIMENSIONAL MONTE-CARLO MODEL (SHEDS)

    EPA Science Inventory

    Since 1998, US EPA's National Exposure Research Laboratory (NERL) has been developing the Stochastic Human Exposure and Dose Simulation (SHEDS) model for various classes of pollutants. SHEDS is a physically-based probabilistic model intended for improving estimates of human ex...

  14. Contemporary Animal Models For Human Gene Therapy Applications.

    PubMed

    Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Remington Nelson, Everette Jacob

    2015-01-01

    Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial. PMID:26415576

  15. Contemporary Animal Models For Human Gene Therapy Applications.

    PubMed

    Gopinath, Chitra; Nathar, Trupti Job; Ghosh, Arkasubhra; Hickstein, Dennis Durand; Remington Nelson, Everette Jacob

    2015-01-01

    Over the past three decades, gene therapy has been making considerable progress as an alternative strategy in the treatment of many diseases. Since 2009, several studies have been reported in humans on the successful treatment of various diseases. Animal models mimicking human disease conditions are very essential at the preclinical stage before embarking on a clinical trial. In gene therapy, for instance, they are useful in the assessment of variables related to the use of viral vectors such as safety, efficacy, dosage and localization of transgene expression. However, choosing a suitable disease-specific model is of paramount importance for successful clinical translation. This review focuses on the animal models that are most commonly used in gene therapy studies, such as murine, canine, non-human primates, rabbits, porcine, and a more recently developed humanized mice. Though small and large animals both have their own pros and cons as disease-specific models, the choice is made largely based on the type and length of study performed. While small animals with a shorter life span could be well-suited for degenerative/aging studies, large animals with longer life span could suit longitudinal studies and also help with dosage adjustments to maximize therapeutic benefit. Recently, humanized mice or mouse-human chimaeras have gained interest in the study of human tissues or cells, thereby providing a more reliable understanding of therapeutic interventions. Thus, animal models are of great importance with regard to testing new vector technologies in vivo for assessing safety and efficacy prior to a gene therapy clinical trial.

  16. Human performance modeling for system of systems analytics :soldier fatigue.

    SciTech Connect

    Lawton, Craig R.; Campbell, James E.; Miller, Dwight Peter

    2005-10-01

    The military has identified Human Performance Modeling (HPM) as a significant requirement and challenge of future systems modeling and analysis initiatives as can be seen in the Department of Defense's (DoD) Defense Modeling and Simulation Office's (DMSO) Master Plan (DoD 5000.59-P 1995). To this goal, the military is currently spending millions of dollars on programs devoted to HPM in various military contexts. Examples include the Human Performance Modeling Integration (HPMI) program within the Air Force Research Laboratory, which focuses on integrating HPMs with constructive models of systems (e.g. cockpit simulations) and the Navy's Human Performance Center (HPC) established in September 2003. Nearly all of these initiatives focus on the interface between humans and a single system. This is insufficient in the era of highly complex network centric SoS. This report presents research and development in the area of HPM in a system-of-systems (SoS). Specifically, this report addresses modeling soldier fatigue and the potential impacts soldier fatigue can have on SoS performance.

  17. Chimeric animal models in human stem cell biology.

    PubMed

    Glover, Joel C; Boulland, Jean-Luc; Halasi, Gabor; Kasumacic, Nedim

    2009-01-01

    The clinical use of stem cells for regenerative medicine is critically dependent on preclinical studies in animal models. In this review we examine some of the key issues and challenges in the use of animal models to study human stem cell biology-experimental standardization, body size, immunological barriers, cell survival factors, fusion of host and donor cells, and in vivo imaging and tracking. We focus particular attention on the various imaging modalities that can be used to track cells in living animals, comparing their strengths and weaknesses and describing technical developments that are likely to lead to new opportunities for the dynamic assessment of stem cell behavior in vivo. We then provide an overview of some of the most commonly used animal models, their advantages and disadvantages, and examples of their use for xenotypic transplantation of human stem cells, with separate reviews of models involving rodents, ungulates, nonhuman primates, and the chicken embryo. As the use of human somatic, embryonic, and induced pluripotent stem cells increases, so too will the range of applications for these animal models. It is likely that increasingly sophisticated uses of human/animal chimeric models will be developed through advances in genetic manipulation, cell delivery, and in vivo imaging.

  18. Think Small: Zebrafish as a Model System of Human Pathology

    PubMed Central

    Goldsmith, J. R.; Jobin, Christian

    2012-01-01

    Although human pathologies have mostly been modeled using higher mammal systems such as mice, the lower vertebrate zebrafish has gained tremendous attention as a model system. The advantages of zebrafish over classical vertebrate models are multifactorial and include high genetic and organ system homology to humans, high fecundity, external fertilization, ease of genetic manipulation, and transparency through early adulthood that enables powerful imaging modalities. This paper focuses on four areas of human pathology that were developed and/or advanced significantly in zebrafish in the last decade. These areas are (1) wound healing/restitution, (2) gastrointestinal diseases, (3) microbe-host interactions, and (4) genetic diseases and drug screens. Important biological processes and pathologies explored include wound-healing responses, pancreatic cancer, inflammatory bowel diseases, nonalcoholic fatty liver disease, and mycobacterium infection. The utility of zebrafish in screening for novel genes important in various pathologies such as polycystic kidney disease is also discussed. PMID:22701308

  19. Modeling Human Dynamics of Face-to-Face Interaction Networks

    NASA Astrophysics Data System (ADS)

    Starnini, Michele; Baronchelli, Andrea; Pastor-Satorras, Romualdo

    2013-04-01

    Face-to-face interaction networks describe social interactions in human gatherings, and are the substrate for processes such as epidemic spreading and gossip propagation. The bursty nature of human behavior characterizes many aspects of empirical data, such as the distribution of conversation lengths, of conversations per person, or of interconversation times. Despite several recent attempts, a general theoretical understanding of the global picture emerging from data is still lacking. Here we present a simple model that reproduces quantitatively most of the relevant features of empirical face-to-face interaction networks. The model describes agents that perform a random walk in a two-dimensional space and are characterized by an attractiveness whose effect is to slow down the motion of people around them. The proposed framework sheds light on the dynamics of human interactions and can improve the modeling of dynamical processes taking place on the ensuing dynamical social networks.

  20. Engineering Large Animal Species to Model Human Diseases.

    PubMed

    Rogers, Christopher S

    2016-07-01

    Animal models are an important resource for studying human diseases. Genetically engineered mice are the most commonly used species and have made significant contributions to our understanding of basic biology, disease mechanisms, and drug development. However, they often fail to recreate important aspects of human diseases and thus can have limited utility as translational research tools. Developing disease models in species more similar to humans may provide a better setting in which to study disease pathogenesis and test new treatments. This unit provides an overview of the history of genetically engineered large animals and the techniques that have made their development possible. Factors to consider when planning a large animal model, including choice of species, type of modification and methodology, characterization, production methods, and regulatory compliance, are also covered. © 2016 by John Wiley & Sons, Inc.

  1. Prostaglandin ethanolamides attenuate damage in a human explant colitis model.

    PubMed

    Nicotra, Lauren L; Vu, Megan; Harvey, Benjamin S; Smid, Scott D

    2013-01-01

    Endocannabinoids are protective in animal colitis models. As endocannabinoids also form novel prostaglandin ethanolamides (prostamides) via COX-2, we investigated the effects of prostamides and other COX-2 mediators on tissue damage in an ex vivo human mucosal explant colitis model. Healthy human colonic mucosae were incubated with pro-inflammatory cytokines TNF-α and IL-1β to elicit colitis-like tissue damage. The PGF-ethanolamide analogue, bimatoprost decreased colitis scores which were reversed by a prostamide-specific antagonist AGN 211334, but not the FP receptor antagonist AL-8810. PGF-ethanolamide and PGE-ethanolamide also reduced cytokine-evoked epithelial damage. Anandamide was protective in the explant colitis model; however COX-2 inhibition did not alter its effects, associated with a lack of COX-2 induction in explant mucosal tissue. These findings support an anti-inflammatory role for prostamides and endocannabinoids in the human colon. PMID:23380599

  2. Engineering Large Animal Species to Model Human Diseases.

    PubMed

    Rogers, Christopher S

    2016-01-01

    Animal models are an important resource for studying human diseases. Genetically engineered mice are the most commonly used species and have made significant contributions to our understanding of basic biology, disease mechanisms, and drug development. However, they often fail to recreate important aspects of human diseases and thus can have limited utility as translational research tools. Developing disease models in species more similar to humans may provide a better setting in which to study disease pathogenesis and test new treatments. This unit provides an overview of the history of genetically engineered large animals and the techniques that have made their development possible. Factors to consider when planning a large animal model, including choice of species, type of modification and methodology, characterization, production methods, and regulatory compliance, are also covered. © 2016 by John Wiley & Sons, Inc. PMID:27367161

  3. Modeling the human as a controller in a multitask environment

    NASA Technical Reports Server (NTRS)

    Govindaraj, T.; Rouse, W. B.

    1978-01-01

    Modeling the human as a controller of slowly responding systems with preview is considered. Along with control tasks, discrete noncontrol tasks occur at irregular intervals. In multitask situations such as these, it has been observed that humans tend to apply piecewise constant controls. It is believed that the magnitude of controls and the durations for which they remain constant are dependent directly on the system bandwidth, preview distance, complexity of the trajectory to be followed, and nature of the noncontrol tasks. A simple heuristic model of human control behavior in this situation is presented. The results of a simulation study, whose purpose was determination of the sensitivity of the model to its parameters, are discussed.

  4. Multibody model of the human upper extremity for fracture simulation

    PubMed Central

    Milanowicz, Marcin; Kędzior, Krzysztof

    2016-01-01

    About 3.8 million people are injured in accidents at work in Europe every year. The resulting high costs are incurred by the victims themselves, their families, employers and society. We have used a numerical simulation to reconstruct accidents at work for several years. To reconstruct these accidents MADYMO R7.5 with a numerical human model (pedestrian model) is used. However, this model is dedicated to the analysis of car-to-pedestrian accidents and thus cannot be fully used for reconstructing accidents at work. Therefore, we started working on the development of a numerical model of the human body for the purpose of simulating accidents at work. Developing a new numerical model which gives an opportunity to simulate fractures of the upper extremity bones is a stage of that work. PMID:26651896

  5. A control-theory model for human decision-making

    NASA Technical Reports Server (NTRS)

    Levison, W. H.; Tanner, R. B.

    1971-01-01

    A model for human decision making is an adaptation of an optimal control model for pilot/vehicle systems. The models for decision and control both contain concepts of time delay, observation noise, optimal prediction, and optimal estimation. The decision making model was intended for situations in which the human bases his decision on his estimate of the state of a linear plant. Experiments are described for the following task situations: (a) single decision tasks, (b) two-decision tasks, and (c) simultaneous manual control and decision making. Using fixed values for model parameters, single-task and two-task decision performance can be predicted to within an accuracy of 10 percent. Agreement is less good for the simultaneous decision and control situation.

  6. A structural model of the adaptive human pilot

    NASA Technical Reports Server (NTRS)

    Hess, R. A.

    1979-01-01

    A compensatory tracking model of the human pilot is offered which attempts to provide a more realistic representation of the human's signal processing structure than that which is exhibited by pilot models currently in use. Two features of the model distinguish it from other representations of the human pilot. First, proprioceptive information from the control stick or manipulator constitutes one of the major feedback paths in the model, providing feedback of vehicle output rate due to control activity. Implicit in this feedback loop is a model of the vehicle dynamics which is valid in and beyond the region of crossover. Second, error-rate information is continuously derived and independently but intermittently controlled. An output injected remnant model is offered and qualitatively justified on the basis of providing a measure of the effect of inaccuracies such as time variations in the pilot's internal model of the controlled element dynamics. The data from experimental tracking tasks involving five different controlled element dynamics and one nonideal viewing condition were matched with model generated describing functions and remnant power spectral densities.

  7. Large animal models of rare genetic disorders: sheep as phenotypically relevant models of human genetic disease.

    PubMed

    Pinnapureddy, Ashish R; Stayner, Cherie; McEwan, John; Baddeley, Olivia; Forman, John; Eccles, Michael R

    2015-09-02

    Animals that accurately model human disease are invaluable in medical research, allowing a critical understanding of disease mechanisms, and the opportunity to evaluate the effect of therapeutic compounds in pre-clinical studies. Many types of animal models are used world-wide, with the most common being small laboratory animals, such as mice. However, rodents often do not faithfully replicate human disease, despite their predominant use in research. This discordancy is due in part to physiological differences, such as body size and longevity. In contrast, large animal models, including sheep, provide an alternative to mice for biomedical research due to their greater physiological parallels with humans. Completion of the full genome sequences of many species, and the advent of Next Generation Sequencing (NGS) technologies, means it is now feasible to screen large populations of domesticated animals for genetic variants that resemble human genetic diseases, and generate models that more accurately model rare human pathologies. In this review, we discuss the notion of using sheep as large animal models, and their advantages in modelling human genetic disease. We exemplify several existing naturally occurring ovine variants in genes that are orthologous to human disease genes, such as the Cln6 sheep model for Batten disease. These, and other sheep models, have contributed significantly to our understanding of the relevant human disease process, in addition to providing opportunities to trial new therapies in animals with similar body and organ size to humans. Therefore sheep are a significant species with respect to the modelling of rare genetic human disease, which we summarize in this review.

  8. Anatomically based modelling of the human skull and jaw.

    PubMed

    van Essen, N L; Anderson, I A; Hunter, P J; Carman, J; Clarke, R D; Pullan, A J

    2005-01-01

    We present here an anatomically based model of the human masticatory system that provides a framework for simulating the complex chewing process. The initial motivation for creating this model was the desire to have a computational model of the human jaw that can be used to simulate the action of simple bites, and to calculate the stresses and forces on the teeth that are involved. The model created also provides a platform that can be used to investigate other features of the masticatory system. To construct this global model, individual models of the bones of the skull and jaw were created from generic data sets. Geometric models of the muscles of mastication were also created and attached to the appropriate bones. To complete this initial model, representations of the crowns of the teeth were created and a basic model of the temporomandibular joint (TMJ) was included. The finite element method was used to solve for the stresses and strains created by the loading conditions during a clenching simulation involving the mandible bone. The model presented here is also discussed in relation to a model of the entire musculo-skeletal system being developed as part of the Physiome Project.

  9. A stereo model based upon mechanisms of human binocular vision

    NASA Technical Reports Server (NTRS)

    Griswold, N. C.; Yeh, C. P.

    1986-01-01

    A model for stereo vision, which is based on the human-binocular vision system, is proposed. Data collected from studies of neurophysiology of the human binocular system are discussed. An algorithm for the implementation of this stereo vision model is derived. The algorithm is tested on computer-generated and real scene images. Examples of a computer-generated image and a grey-level image are presented. It is noted that the proposed method is computationally efficient for depth perception, and the results indicate accuracies that are noise tolerant.

  10. Modelling human balance using switched systems with linear feedback control.

    PubMed

    Kowalczyk, Piotr; Glendinning, Paul; Brown, Martin; Medrano-Cerda, Gustavo; Dallali, Houman; Shapiro, Jonathan

    2012-02-01

    We are interested in understanding the mechanisms behind and the character of the sway motion of healthy human subjects during quiet standing. We assume that a human body can be modelled as a single-link inverted pendulum, and the balance is achieved using linear feedback control. Using these assumptions, we derive a switched model which we then investigate. Stable periodic motions (limit cycles) about an upright position are found. The existence of these limit cycles is studied as a function of system parameters. The exploration of the parameter space leads to the detection of multi-stability and homoclinic bifurcations. PMID:21697168

  11. Modeling human decision making behavior in supervisory control

    NASA Technical Reports Server (NTRS)

    Tulga, M. K.; Sheridan, T. B.

    1977-01-01

    An optimal decision control model was developed, which is based primarily on a dynamic programming algorithm which looks at all the available task possibilities, charts an optimal trajectory, and commits itself to do the first step (i.e., follow the optimal trajectory during the next time period), and then iterates the calculation. A Bayesian estimator was included which estimates the tasks which might occur in the immediate future and provides this information to the dynamic programming routine. Preliminary trials comparing the human subject's performance to that of the optimal model show a great similarity, but indicate that the human skips certain movements which require quick change in strategy.

  12. Modelling human balance using switched systems with linear feedback control.

    PubMed

    Kowalczyk, Piotr; Glendinning, Paul; Brown, Martin; Medrano-Cerda, Gustavo; Dallali, Houman; Shapiro, Jonathan

    2012-02-01

    We are interested in understanding the mechanisms behind and the character of the sway motion of healthy human subjects during quiet standing. We assume that a human body can be modelled as a single-link inverted pendulum, and the balance is achieved using linear feedback control. Using these assumptions, we derive a switched model which we then investigate. Stable periodic motions (limit cycles) about an upright position are found. The existence of these limit cycles is studied as a function of system parameters. The exploration of the parameter space leads to the detection of multi-stability and homoclinic bifurcations.

  13. Elucidation of Xenobiotic Metabolism Pathways in Human Skin and Human Skin Models by Proteomic Profiling

    PubMed Central

    van Eijl, Sven; Zhu, Zheying; Cupitt, John; Gierula, Magdalena; Götz, Christine; Fritsche, Ellen; Edwards, Robert J.

    2012-01-01

    Background Human skin has the capacity to metabolise foreign chemicals (xenobiotics), but knowledge of the various enzymes involved is incomplete. A broad-based unbiased proteomics approach was used to describe the profile of xenobiotic metabolising enzymes present in human skin and hence indicate principal routes of metabolism of xenobiotic compounds. Several in vitro models of human skin have been developed for the purpose of safety assessment of chemicals. The suitability of these epidermal models for studies involving biotransformation was assessed by comparing their profiles of xenobiotic metabolising enzymes with those of human skin. Methodology/Principal Findings Label-free proteomic analysis of whole human skin (10 donors) was applied and analysed using custom-built PROTSIFT software. The results showed the presence of enzymes with a capacity for the metabolism of alcohols through dehydrogenation, aldehydes through dehydrogenation and oxidation, amines through oxidation, carbonyls through reduction, epoxides and carboxylesters through hydrolysis and, of many compounds, by conjugation to glutathione. Whereas protein levels of these enzymes in skin were mostly just 4–10 fold lower than those in liver and sufficient to support metabolism, the levels of cytochrome P450 enzymes were at least 300-fold lower indicating they play no significant role. Four epidermal models of human skin had profiles very similar to one another and these overlapped substantially with that of whole skin. Conclusions/Significance The proteomics profiling approach was successful in producing a comprehensive analysis of the biotransformation characteristics of whole human skin and various in vitro skin models. The results show that skin contains a range of defined enzymes capable of metabolising different classes of chemicals. The degree of similarity of the profiles of the in vitro models indicates their suitability for epidermal toxicity testing. Overall, these results provide a

  14. An Illumination Modeling System for Human Factors Analyses

    NASA Technical Reports Server (NTRS)

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

    2002-01-01

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

  15. Making Organisms Model Human Behavior: Situated Models in North-American Alcohol Research, 1950-onwards

    PubMed Central

    Leonelli, Sabina; Ankeny, Rachel A.; Nelson, Nicole C.; Ramsden, Edmund

    2014-01-01

    Argument We examine the criteria used to validate the use of nonhuman organisms in North-American alcohol addiction research from the 1950s to the present day. We argue that this field, where the similarities between behaviors in humans and non-humans are particularly difficult to assess, has addressed questions of model validity by transforming the situatedness of non-human organisms into an experimental tool. We demonstrate that model validity does not hinge on the standardization of one type of organism in isolation, as often the case with genetic model organisms. Rather, organisms are viewed as necessarily situated: they cannot be understood as a model for human behavior in isolation from their environmental conditions. Hence the environment itself is standardized as part of the modeling process; and model validity is assessed with reference to the environmental conditions under which organisms are studied. PMID:25233743

  16. Modeling Neuronal Current MRI Signal with Human Neuron

    PubMed Central

    Luo, Qingfei; Jiang, Xia; Chen, Bin; Zhu, Yi; Gao, Jia-Hong

    2010-01-01

    Up to date, no consensus has been achieved regarding the possibility of detecting neuronal currents by MRI (ncMRI) in human brain. To evaluate the detectability of ncMRI, an effective way is to simulate ncMRI signal with the realistic neuronal geometry and electrophysiological processes. Unfortunately, previous realistic ncMRI models are based on rat and monkey neurons. The species difference in neuronal morphology and physiology would prevent these models from simulating the ncMRI signal accurately in human subjects. The aim of the present study is to bridge this gap by establishing a realistic ncMRI model specifically for human cerebral cortex. In this model, the ncMRI signal was simulated using anatomically reconstructed human pyramidal neurons and their biophysical properties. The modeling results showed that the amplitude of ncMRI signal significantly depends on the density of synchronously firing neurons and imaging conditions such as position of imaging voxel, direction of main magnetic field (B0) relative to the cortical surface and echo time. The results indicated that physiologically-evoked ncMRI signal is too weak to be detected (magnitude/phase change ≤ -1.4×10−6/0.02°), but the phase signal induced by spontaneous activity may reach a detectable level (up to 0.2°) in favorable conditions. PMID:21254209

  17. Development of a hydraulic model of the human systemic circulation

    NASA Technical Reports Server (NTRS)

    Sharp, M. K.; Dharmalingham, R. K.

    1999-01-01

    Physical and numeric models of the human circulation are constructed for a number of objectives, including studies and training in physiologic control, interpretation of clinical observations, and testing of prosthetic cardiovascular devices. For many of these purposes it is important to quantitatively validate the dynamic response of the models in terms of the input impedance (Z = oscillatory pressure/oscillatory flow). To address this need, the authors developed an improved physical model. Using a computer study, the authors first identified the configuration of lumped parameter elements in a model of the systemic circulation; the result was a good match with human aortic input impedance with a minimum number of elements. Design, construction, and testing of a hydraulic model analogous to the computer model followed. Numeric results showed that a three element model with two resistors and one compliance produced reasonable matching without undue complication. The subsequent analogous hydraulic model included adjustable resistors incorporating a sliding plate to vary the flow area through a porous material and an adjustable compliance consisting of a variable-volume air chamber. The response of the hydraulic model compared favorably with other circulation models.

  18. Coupling of the Models of Human Physiology and Thermal Comfort

    NASA Astrophysics Data System (ADS)

    Pokorny, J.; Jicha, M.

    2013-04-01

    A coupled model of human physiology and thermal comfort was developed in Dymola/Modelica. A coupling combines a modified Tanabe model of human physiology and thermal comfort model developed by Zhang. The Coupled model allows predicting the thermal sensation and comfort of both local and overall from local boundary conditions representing ambient and personal factors. The aim of this study was to compare prediction of the Coupled model with the Fiala model prediction and experimental data. Validation data were taken from the literature, mainly from the validation manual of software Theseus-FE [1]. In the paper validation of the model for very light physical activities (1 met) indoor environment with temperatures from 12 °C up to 48 °C is presented. The Coupled model predicts mean skin temperature for cold, neutral and warm environment well. However prediction of core temperature in cold environment is inaccurate and very affected by ambient temperature. Evaluation of thermal comfort in warm environment is supplemented by skin wettedness prediction. The Coupled model is designed for non-uniform and transient environmental conditions; it is also suitable simulation of thermal comfort in vehicles cabins. The usage of the model is limited for very light physical activities up to 1.2 met only.

  19. More-Realistic Digital Modeling of a Human Body

    NASA Technical Reports Server (NTRS)

    Rogge, Renee

    2010-01-01

    A MATLAB computer program has been written to enable improved (relative to an older program) modeling of a human body for purposes of designing space suits and other hardware with which an astronaut must interact. The older program implements a kinematic model based on traditional anthropometric measurements that do provide important volume and surface information. The present program generates a three-dimensional (3D) whole-body model from 3D body-scan data. The program utilizes thin-plate spline theory to reposition the model without need for additional scans.

  20. Modeling static and dynamic detection of humans in rural terrain

    NASA Astrophysics Data System (ADS)

    Flug, Eric

    2014-05-01

    Historically, the focus of detection experiments and modeling at the Night Vision and Electronic Sensors Directorate (NVESD) has been on detecting military vehicles in rural terrains. A gap remains in understanding the detection of human targets in rural terrains and how it might differ from detection of vehicles. There are also improvements that can be made in how to quantify the effect of human movement on detectability. Two experiments were developed to look at probability of detection and time to detect fully exposed human targets in a low to moderate clutter environment in the infrared waveband. The first test uses static images of standing humans while the second test uses videos of humans walking across the scene at various ranges and speeds. Various definitions of target and background areas are explored to calculated contrast and target size. Ultimately, task difficulty parameters (V50s) are calculated to calibrate NVESD sensor performance models, specifically NVThermIP and NV-IPM, for the human detection task. The focus of the analysis in this paper is primarily on the static detection task since the analysis for the dynamic detection experiment is still in the early stages. Results will be presented as well as a plan for future work in this area.

  1. A Multiscale Survival Process for Modeling Human Activity Patterns

    PubMed Central

    Zhang, Tianyang; Cui, Peng; Song, Chaoming; Zhu, Wenwu; Yang, Shiqiang

    2016-01-01

    Human activity plays a central role in understanding large-scale social dynamics. It is well documented that individual activity pattern follows bursty dynamics characterized by heavy-tailed interevent time distributions. Here we study a large-scale online chatting dataset consisting of 5,549,570 users, finding that individual activity pattern varies with timescales whereas existing models only approximate empirical observations within a limited timescale. We propose a novel approach that models the intensity rate of an individual triggering an activity. We demonstrate that the model precisely captures corresponding human dynamics across multiple timescales over five orders of magnitudes. Our model also allows extracting the population heterogeneity of activity patterns, characterized by a set of individual-specific ingredients. Integrating our approach with social interactions leads to a wide range of implications. PMID:27023682

  2. A kinematic model for Bayesian tracking of cyclic human motion

    NASA Astrophysics Data System (ADS)

    Greif, Thomas; Lienhart, Rainer

    2010-01-01

    We introduce a two-dimensional kinematic model for cyclic motions of humans, which is suitable for the use as temporal prior in any Bayesian tracking framework. This human motion model is solely based on simple kinematic properties: the joint accelerations. Distributions of joint accelerations subject to the cycle progress are learned from training data. We present results obtained by applying the introduced model to the cyclic motion of backstroke swimming in a Kalman filter framework that represents the posterior distribution by a Gaussian. We experimentally evaluate the sensitivity of the motion model with respect to the frequency and noise level of assumed appearance-based pose measurements by simulating various fidelities of the pose measurements using ground truth data.

  3. Sensitivity analysis techniques for models of human behavior.

    SciTech Connect

    Bier, Asmeret Brooke

    2010-09-01

    Human and social modeling has emerged as an important research area at Sandia National Laboratories due to its potential to improve national defense-related decision-making in the presence of uncertainty. To learn about which sensitivity analysis techniques are most suitable for models of human behavior, different promising methods were applied to an example model, tested, and compared. The example model simulates cognitive, behavioral, and social processes and interactions, and involves substantial nonlinearity, uncertainty, and variability. Results showed that some sensitivity analysis methods create similar results, and can thus be considered redundant. However, other methods, such as global methods that consider interactions between inputs, can generate insight not gained from traditional methods.

  4. Cerebral organoids model human brain development and microcephaly.

    PubMed

    Lancaster, Madeline A; Renner, Magdalena; Martin, Carol-Anne; Wenzel, Daniel; Bicknell, Louise S; Hurles, Matthew E; Homfray, Tessa; Penninger, Josef M; Jackson, Andrew P; Knoblich, Juergen A

    2013-09-19

    The complexity of the human brain has made it difficult to study many brain disorders in model organisms, highlighting the need for an in vitro model of human brain development. Here we have developed a human pluripotent stem cell-derived three-dimensional organoid culture system, termed cerebral organoids, that develop various discrete, although interdependent, brain regions. These include a cerebral cortex containing progenitor populations that organize and produce mature cortical neuron subtypes. Furthermore, cerebral organoids are shown to recapitulate features of human cortical development, namely characteristic progenitor zone organization with abundant outer radial glial stem cells. Finally, we use RNA interference and patient-specific induced pluripotent stem cells to model microcephaly, a disorder that has been difficult to recapitulate in mice. We demonstrate premature neuronal differentiation in patient organoids, a defect that could help to explain the disease phenotype. Together, these data show that three-dimensional organoids can recapitulate development and disease even in this most complex human tissue. PMID:23995685

  5. Coupled Dynamic Modeling to Assess Human Impact on Watershed Hydrology

    NASA Astrophysics Data System (ADS)

    Mohammed, I. N.; Tsai, Y.; Turnbull, S.; Bomblies, A.; Zia, A.

    2014-12-01

    Humans are intrinsic to the hydrologic system, both as agents of change and as beneficiaries of ecosystem services. This connection has been underappreciated in hydrology. We present a modeling linkage framework of an agent-based land use change model with a physical-based watershed model. The coupled model framework presented constitutes part of an integrated assessment model that is being developed to study human-ecosystem interaction in Missisquoi Bay, spanning Vermont and Québec, which is experiencing high concentrations of nutrients from the Missisquoi River watershed. The integrated assessment approach proposed is comprised of linking two simulation models: the Interactive Land-Use Transition Agent-Based Model (ILUTABM) and a physically based process model, the Regional Hydro-Ecological Simulation System (RHESSys). The ILUTABM treats both landscape and landowners as agents and simulates annual land-use patterns resulting from landowners annual land-use decisions and Best Management Practices (BMPs) adaptations to landowners utilities, land productivity and perceived impacts of floods. The Missisquoi River at Swanton watershed RHESSys model (drainage area of 2,200 km2) driven by climate data was first calibrated to daily streamflows and water quality sensor data at the watershed outlet. Simulated land-use patterns were then processed to drive the calibrated RHESSys model to obtain streamflow nutrient loading realizations. Nutrients loading realizations are then examined and routed back to the ILUTAB model to obtain public polices needed to manage the Missisquoi watershed as well as the Lake Champlain in general. We infer that the applicability of this approach can be generalized to other similar watersheds. Index Terms: 0402: Agricultural systems; 1800: Hydrology; 1803: Anthropogenic effects; 1834 Human impacts; 6344: System operation and management; 6334: Regional Planning

  6. A validation study of a stochastic model of human interaction

    NASA Astrophysics Data System (ADS)

    Burchfield, Mitchel Talmadge

    The purpose of this dissertation is to validate a stochastic model of human interactions which is part of a developmentalism paradigm. Incorporating elements of ancient and contemporary philosophy and science, developmentalism defines human development as a progression of increasing competence and utilizes compatible theories of developmental psychology, cognitive psychology, educational psychology, social psychology, curriculum development, neurology, psychophysics, and physics. To validate a stochastic model of human interactions, the study addressed four research questions: (a) Does attitude vary over time? (b) What are the distributional assumptions underlying attitudes? (c) Does the stochastic model, {-}N{intlimitssbsp{-infty}{infty}}varphi(chi,tau)\\ Psi(tau)dtau, have utility for the study of attitudinal distributions and dynamics? (d) Are the Maxwell-Boltzmann, Fermi-Dirac, and Bose-Einstein theories applicable to human groups? Approximately 25,000 attitude observations were made using the Semantic Differential Scale. Positions of individuals varied over time and the logistic model predicted observed distributions with correlations between 0.98 and 1.0, with estimated standard errors significantly less than the magnitudes of the parameters. The results bring into question the applicability of Fisherian research designs (Fisher, 1922, 1928, 1938) for behavioral research based on the apparent failure of two fundamental assumptions-the noninteractive nature of the objects being studied and normal distribution of attributes. The findings indicate that individual belief structures are representable in terms of a psychological space which has the same or similar properties as physical space. The psychological space not only has dimension, but individuals interact by force equations similar to those described in theoretical physics models. Nonlinear regression techniques were used to estimate Fermi-Dirac parameters from the data. The model explained a high degree

  7. 3D active workspace of human hand anatomical model

    PubMed Central

    Dragulescu, Doina; Perdereau, Véronique; Drouin, Michel; Ungureanu, Loredana; Menyhardt, Karoly

    2007-01-01

    Background If the model of the human hand is created with accuracy by respecting the type of motion provided by each articulation and the dimensions of articulated bones, it can function as the real organ providing the same motions. Unfortunately, the human hand is hard to model due to its kinematical chains submitted to motion constraints. On the other hand, if an application does not impose a fine manipulation it is not necessary to create a model as complex as the human hand is. But always the hand model has to perform a certain space of motions in imposed workspace architecture no matter what the practical application does. Methods Based on Denavit-Hartenberg convention, we conceived the kinematical model of the human hand, having in mind the structure and the behavior of the natural model. We obtained the kinematical equations describing the motion of every fingertip with respect to the general coordinate system, placed on the wrist. For every joint variable, a range of motion was established. Dividing these joint variables to an appropriate number of intervals and connecting them, the complex surface bordering the active hand model workspace was obtained. Results Using MATLAB 7.0, the complex surface described by fingertips, when hand articulations are all simultaneously moving, was obtained. It can be seen that any point on surface has its own coordinates smaller than the maximum length of the middle finger in static position. Therefore, a sphere having the centre in the origin of the general coordinate system and the radius which equals this length covers the represented complex surface. Conclusion We propose a human hand model that represents a new solution compared to the existing ones. This model is capable to make special movements like power grip and dexterous manipulations. During them, the fingertips do not exceed the active workspace encapsulated by determined surfaces. The proposed kinematical model can help to choose which model joints could be

  8. Network effects in a human capital based economic growth model

    NASA Astrophysics Data System (ADS)

    Vaz Martins, Teresa; Araújo, Tanya; Augusta Santos, Maria; St Aubyn, Miguel

    2009-06-01

    We revisit a recently introduced agent model [ACS, 11, 99 (2008)], where economic growth is a consequence of education (human capital formation) and innovation, and investigate the influence of the agents’ social network, both on an agent’s decision to pursue education and on the output of new ideas. Regular and random networks are considered. The results are compared with the predictions of a mean field (representative agent) model.

  9. Validation of Human Physiologically Based Pharmacokinetic Model for Vinyl Acetate Against Human Nasal Dosimetry Data

    SciTech Connect

    Hinderliter, Paul M.; Thrall, Karla D.; Corley, Rick A.; Bloemen, Louis J.; Bogdanffy, M S.

    2005-05-01

    Vinyl acetate has been shown to induce nasal lesions in rodents in inhalation bioassays. A physiologically based pharmacokinetic (PBPK) model for vinyl acetate has been used in human risk assessment, but previous in vivo validation was conducted only in rats. Controlled human exposures to vinyl acetate were conducted to provide validation data for the application of the model in humans. Five volunteers were exposed to 1, 5, and 10 ppm 13 C1 , 13 C2 vinyl acetate via inhalation. A probe inserted into thenasopharyngeal region sampled both 13 C1 , 13 C2 vinyl acetate and the major metabolite 13 C1 , 13 C2 acetaldehyde during rest and light exercise. Nasopharyngeal air concentrations were analyzed in real time by ion trap mass spectrometry (MS/MS). Experimental concentrations of both vinyl acetate and acetaldehyde were then compared to predicted concentrations calculated from the previously published human model. Model predictions of vinyl acetate nasal extraction compared favorably with measured values of vinyl acetate, as did predictions of nasopharyngeal acetaldehyde when compared to measured acetaldehyde. The results showed that the current PBPK model structure and parameterization are appropriate for vinyl acetate. These analyses were conducted from 1 to 10 ppm vinyl acetate, a range relevant to workplace exposure standards but which would not be expected to saturate vinyl acetate metabolism. Risk assessment based on this model further concluded that 24 h per day exposures up to 1 ppm do not present concern regarding cancer or non-cancer toxicity. Validation of the vinyl acetate human PBPK model provides support for these conclusions.

  10. Science-Based Simulation Model of Human Performance for Human Reliability Analysis

    SciTech Connect

    Dana L. Kelly; Ronald L. Boring; Ali Mosleh; Carol Smidts

    2011-10-01

    Human reliability analysis (HRA), a component of an integrated probabilistic risk assessment (PRA), is the means by which the human contribution to risk is assessed, both qualitatively and quantitatively. However, among the literally dozens of HRA methods that have been developed, most cannot fully model and quantify the types of errors that occurred at Three Mile Island. Furthermore, all of the methods lack a solid empirical basis, relying heavily on expert judgment or empirical results derived in non-reactor domains. Finally, all of the methods are essentially static, and are thus unable to capture the dynamics of an accident in progress. The objective of this work is to begin exploring a dynamic simulation approach to HRA, one whose models have a basis in psychological theories of human performance, and whose quantitative estimates have an empirical basis. This paper highlights a plan to formalize collaboration among the Idaho National Laboratory (INL), the University of Maryland, and The Ohio State University (OSU) to continue development of a simulation model initially formulated at the University of Maryland. Initial work will focus on enhancing the underlying human performance models with the most recent psychological research, and on planning follow-on studies to establish an empirical basis for the model, based on simulator experiments to be carried out at the INL and at the OSU.

  11. Fractional calculus model of electrical impedance applied to human skin.

    PubMed

    Vosika, Zoran B; Lazovic, Goran M; Misevic, Gradimir N; Simic-Krstic, Jovana B

    2013-01-01

    Fractional calculus is a mathematical approach dealing with derivatives and integrals of arbitrary and complex orders. Therefore, it adds a new dimension to understand and describe basic nature and behavior of complex systems in an improved way. Here we use the fractional calculus for modeling electrical properties of biological systems. We derived a new class of generalized models for electrical impedance and applied them to human skin by experimental data fitting. The primary model introduces new generalizations of: 1) Weyl fractional derivative operator, 2) Cole equation, and 3) Constant Phase Element (CPE). These generalizations were described by the novel equation which presented parameter [Formula: see text] related to remnant memory and corrected four essential parameters [Formula: see text] We further generalized single generalized element by introducing specific partial sum of Maclaurin series determined by parameters [Formula: see text] We defined individual primary model elements and their serial combination models by the appropriate equations and electrical schemes. Cole equation is a special case of our generalized class of models for[Formula: see text] Previous bioimpedance data analyses of living systems using basic Cole and serial Cole models show significant imprecisions. Our new class of models considerably improves the quality of fitting, evaluated by mean square errors, for bioimpedance data obtained from human skin. Our models with new parameters presented in specific partial sum of Maclaurin series also extend representation, understanding and description of complex systems electrical properties in terms of remnant memory effects. PMID:23577065

  12. Human task animation from performance models and natural language input

    NASA Technical Reports Server (NTRS)

    Esakov, Jeffrey; Badler, Norman I.; Jung, Moon

    1989-01-01

    Graphical manipulation of human figures is essential for certain types of human factors analyses such as reach, clearance, fit, and view. In many situations, however, the animation of simulated people performing various tasks may be based on more complicated functions involving multiple simultaneous reaches, critical timing, resource availability, and human performance capabilities. One rather effective means for creating such a simulation is through a natural language description of the tasks to be carried out. Given an anthropometrically-sized figure and a geometric workplace environment, various simple actions such as reach, turn, and view can be effectively controlled from language commands or standard NASA checklist procedures. The commands may also be generated by external simulation tools. Task timing is determined from actual performance models, if available, such as strength models or Fitts' Law. The resulting action specification are animated on a Silicon Graphics Iris workstation in real-time.

  13. Induced pluripotent stem cells for modelling human diseases

    PubMed Central

    Unternaehrer, Juli J.; Daley, George Q.

    2011-01-01

    Research into the pathophysiological mechanisms of human disease and the development of targeted therapies have been hindered by a lack of predictive disease models that can be experimentally manipulated in vitro. This review describes the current state of modelling human diseases with the use of human induced pluripotent stem (iPS) cell lines. To date, a variety of neurodegenerative diseases, haematopoietic disorders, metabolic conditions and cardiovascular pathologies have been captured in a Petri dish through reprogramming of patient cells into iPS cells followed by directed differentiation of disease-relevant cells and tissues. However, realizing the true promise of iPS cells for advancing our basic understanding of disease and ultimately providing novel cell-based therapies will require more refined protocols for generating the highly specialized cells affected by disease, coupled with strategies for drug discovery and cell transplantation. PMID:21727133

  14. Human Factors Research for Space Exploration: Measurement, Modeling, and Mitigation

    NASA Technical Reports Server (NTRS)

    Kaiser, Mary K.; Allen, Christopher S.; Barshi, Immanuel; Billman, Dorrit; Holden, Kritina L.

    2010-01-01

    As part of NASA's Human Research Program, the Space Human Factors Engineering Project serves as the bridge between Human Factors research and Human Spaceflight applications. Our goal is to be responsive to the operational community while addressing issues at a sufficient level of abstraction to ensure that our tools and solutions generalize beyond the point design. In this panel, representatives from four of our research domains will discuss the challenges they face in solving current problems while also enabling future capabilities. Historically, engineering-dominated organizations have tended to view good Human Factors (HF) as a desire rather than a requirement in system design and development. Our field has made significant gains in the past decade, however; the Department of Defense, for example, now recognizes Human-System Integration (HSI), of which HF is a component, as an integral part of their divisions hardware acquisition processes. And our own agency was far more accepting of HF/HSI requirements during the most recent vehicle systems definition than in any prior cycle. Nonetheless, HF subject matter experts at NASA often find themselves in catch up mode... coping with legacy systems (hardware and software) and procedures that were designed with little regard for the human element, and too often with an attitude of we can deal with any operator issues during training. Our challenge, then, is to segregate the true knowledge gaps in Space Human Factors from the prior failures to incorporate best (or even good) HF design principles. Further, we strive to extract the overarching core HF issues from the point-design-specific concerns that capture the operators (and managers) attention. Generally, our approach embraces a 3M approach to Human Factors: Measurement, Modeling, and Mitigation. Our first step is to measure human performance, to move from subjective anecdotes to objective, quantified data. Next we model the phenomenon, using appropriate methods in

  15. Human nonindependent mate choice: is model female attractiveness everything?

    PubMed

    Vakirtzis, Antonios; Roberts, S Craig

    2012-05-06

    Following two decades of research on non-human animals, there has recently been increased interest in human nonindependent mate choice, namely the ways in which choosing women incorporate information about a man's past or present romantic partners ('model females') into their own assessment of the male. Experimental studies using static facial images have generally found that men receive higher desirability ratings from female raters when presented with attractive (compared to unattractive) model females. This phenomenon has a straightforward evolutionary explanation: the fact that female mate value is more dependent on physical attractiveness compared to male mate value. Furthermore, due to assortative mating for attractiveness, men who are paired with attractive women are more likely to be of high mate value themselves. Here, we also examine the possible relevance of model female cues other than attractiveness (personality and behavioral traits) by presenting video recordings of model females to a set of female raters. The results confirm that the model female's attractiveness is the primary cue. Contrary to some earlier findings in the human and nonhuman literature, we found no evidence that female raters prefer partners of slightly older model females. We conclude by suggesting some promising variations on the present experimental design.

  16. New Frontiers: Moving the Humanities Model of Curricular Development.

    ERIC Educational Resources Information Center

    Grady, Elizabeth

    1995-01-01

    The American Council of Learned Societies (ACLS) humanities model in the Cambridge (Massachusetts) public schools has significantly affected curricular reform and teacher development. The endeavor is in its third year at the Pilot School, a program within the Cambridge Rindge and Latin School. The article describes progressive reform experiences…

  17. RECONSTRUCTION OF HUMAN LUNG MORPHOLOGY MODELS FROM MAGNETIC RESONANCE IMAGES

    EPA Science Inventory


    Reconstruction of Human Lung Morphology Models from Magnetic Resonance Images
    T. B. Martonen (Experimental Toxicology Division, U.S. EPA, Research Triangle Park, NC 27709) and K. K. Isaacs (School of Public Health, University of North Carolina, Chapel Hill, NC 27514)

  18. The Teacher/Writer: Model, Learner, Human Being.

    ERIC Educational Resources Information Center

    Susi, Geraldine Lee

    1984-01-01

    Describes observations of classrooms in which the teachers participated with the students in writing exercises. Discusses the three teacher/writer roles that emerged during the class--teacher/writer as model, teacher/writer as learner, and teacher/writer as human being--and the bond of understanding that developed as the teachers as students…

  19. A Competency-Based Model for Developing Human Resource Professionals

    ERIC Educational Resources Information Center

    McEvoy, Glenn M.; Hayton, James C.; Warnick, Alan P.; Mumford, Troy V.; Hanks, Steven H.; Blahna, Mary Jo

    2005-01-01

    This article describes a framework for the design and implementation of a competency-based curriculum for graduate management education. The article also outlines how this model has been implemented at one university in the context of a graduate degree in human resource management. Among the significant challenges discussed are the identification…

  20. Mathematical model of the human lungs during phonation

    NASA Astrophysics Data System (ADS)

    Meshcheryakov, R. V.

    2012-08-01

    Modeling of the human lungs during phonation is considered. The main relationships during physiological phonation process and air passage through vocal folds are established. Results of investigation are presented for statements of various types corresponding to different intonation patterns of the statement.

  1. Being human: The role of pluripotent stem cells in regenerative medicine and humanizing Alzheimer's disease models.

    PubMed

    Sproul, Andrew A

    2015-01-01

    Human pluripotent stem cells (PSCs) have the capacity to revolutionize medicine by allowing the generation of functional cell types such as neurons for cell replacement therapy. However, the more immediate impact of PSCs on treatment of Alzheimer's disease (AD) will be through improved human AD model systems for mechanistic studies and therapeutic screening. This review will first briefly discuss different types of PSCs and genome-editing techniques that can be used to modify PSCs for disease modeling or for personalized medicine. This will be followed by a more in depth analysis of current AD iPSC models and a discussion of the need for more complex multicellular models, including cell types such as microglia. It will finish with a discussion on current clinical trials using PSC-derived cells and the long-term potential of such strategies for treating AD.

  2. A Circuit Model of Real Time Human Body Hydration.

    PubMed

    Asogwa, Clement Ogugua; Teshome, Assefa K; Collins, Stephen F; Lai, Daniel T H

    2016-06-01

    Changes in human body hydration leading to excess fluid losses or overload affects the body fluid's ability to provide the necessary support for healthy living. We propose a time-dependent circuit model of real-time human body hydration, which models the human body tissue as a signal transmission medium. The circuit model predicts the attenuation of a propagating electrical signal. Hydration rates are modeled by a time constant τ, which characterizes the individual specific metabolic function of the body part measured. We define a surrogate human body anthropometric parameter θ by the muscle-fat ratio and comparing it with the body mass index (BMI), we find theoretically, the rate of hydration varying from 1.73 dB/min, for high θ and low τ to 0.05 dB/min for low θ and high τ. We compare these theoretical values with empirical measurements and show that real-time changes in human body hydration can be observed by measuring signal attenuation. We took empirical measurements using a vector network analyzer and obtained different hydration rates for various BMI, ranging from 0.6 dB/min for 22.7 [Formula: see text] down to 0.04 dB/min for 41.2 [Formula: see text]. We conclude that the galvanic coupling circuit model can predict changes in the volume of the body fluid, which are essential in diagnosing and monitoring treatment of body fluid disorder. Individuals with high BMI would have higher time-dependent biological characteristic, lower metabolic rate, and lower rate of hydration. PMID:26485354

  3. A Circuit Model of Real Time Human Body Hydration.

    PubMed

    Asogwa, Clement Ogugua; Teshome, Assefa K; Collins, Stephen F; Lai, Daniel T H

    2016-06-01

    Changes in human body hydration leading to excess fluid losses or overload affects the body fluid's ability to provide the necessary support for healthy living. We propose a time-dependent circuit model of real-time human body hydration, which models the human body tissue as a signal transmission medium. The circuit model predicts the attenuation of a propagating electrical signal. Hydration rates are modeled by a time constant τ, which characterizes the individual specific metabolic function of the body part measured. We define a surrogate human body anthropometric parameter θ by the muscle-fat ratio and comparing it with the body mass index (BMI), we find theoretically, the rate of hydration varying from 1.73 dB/min, for high θ and low τ to 0.05 dB/min for low θ and high τ. We compare these theoretical values with empirical measurements and show that real-time changes in human body hydration can be observed by measuring signal attenuation. We took empirical measurements using a vector network analyzer and obtained different hydration rates for various BMI, ranging from 0.6 dB/min for 22.7 [Formula: see text] down to 0.04 dB/min for 41.2 [Formula: see text]. We conclude that the galvanic coupling circuit model can predict changes in the volume of the body fluid, which are essential in diagnosing and monitoring treatment of body fluid disorder. Individuals with high BMI would have higher time-dependent biological characteristic, lower metabolic rate, and lower rate of hydration.

  4. Biological Analysis of Human CML Stem Cells; Xenograft Model of Chronic Phase Human Chronic Myeloid Leukemia.

    PubMed

    Abraham, Sheela A

    2016-01-01

    Xenograft mouse models have been instrumental in expanding our knowledge of hematopoiesis and can provide a functional description of stem cells that possess engrafting potential. Here we describe methodology outlining one way of analyzing human malignant cells that are able to engraft immune compromised mice. Using models such as these will allow researchers to gain valuable insight into the primitive leukemic subtypes that evade current therapy regimes and are critical to understand, in order to eradicate malignancy. PMID:27581148

  5. Age and gender specific biokinetic model for strontium in humans.

    PubMed

    Shagina, N B; Tolstykh, E I; Degteva, M O; Anspaugh, L R; Napier, B A

    2015-03-01

    A biokinetic model for strontium in humans is necessary for quantification of internal doses due to strontium radioisotopes. The ICRP-recommended biokinetic model for strontium has limitations for use in a population study, because it is not gender specific and does not cover all age ranges. The extensive Techa River data set on (90)Sr in humans (tens of thousands of measurements) is a unique source of data on long-term strontium retention for men and women of all ages at intake. These, as well as published data, were used for evaluation of age- and gender-specific parameters for a new compartment biokinetic model for strontium (Sr-AGe model). The Sr-AGe model has a similar structure to the ICRP model for the alkaline earth elements. The following parameters were mainly re-evaluated: gastrointestinal absorption and parameters related to the processes of bone formation and resorption defining calcium and strontium transfers in skeletal compartments. The Sr-AGe model satisfactorily describes available data sets on strontium retention for different kinds of intake (dietary and intravenous) at different ages (0-80 years old) and demonstrates good agreement with data sets for different ethnic groups. The Sr-AGe model can be used for dose assessment in epidemiological studies of general populations exposed to ingested strontium radioisotopes.

  6. Age and gender specific biokinetic model for strontium in humans

    SciTech Connect

    Shagina, N. B.; Tolstykh, E. I.; Degteva, M. O.; Anspaugh, L. R.; Napier, Bruce A.

    2015-03-01

    A biokinetic model for strontium in humans is necessary for quantification of internal doses due to strontium radioisotopes. The ICRP-recommended biokinetic model for strontium has limitation for use in a population study, because it is not gender specific and does not cover all age ranges. The extensive Techa River data set on 90Sr in humans (tens of thousands of measurements) is a unique source of data on long-term strontium retention for men and women of all ages at intake. These, as well as published data, were used for evaluation of age- and gender-specific parameters for a new compartment biokinetic model for strontium (Sr-AGe model). The Sr-AGe model has similar structure as the ICRP model for the alkaline earth elements. The following parameters were mainly reevaluated: gastro-intestinal absorption and parameters related to the processes of bone formation and resorption defining calcium and strontium transfers in skeletal compartments. The Sr-AGe model satisfactorily describes available data sets on strontium retention for different kinds of intake (dietary and intravenous) at different ages (0–80 years old) and demonstrates good agreement with data sets for different ethnic groups. The Sr-AGe model can be used for dose assessment in epidemiological studies of general population exposed to ingested strontium radioisotopes.

  7. Reduced-order models for vertical human-structure interaction

    NASA Astrophysics Data System (ADS)

    Van Nimmen, Katrien; Lombaert, Geert; De Roeck, Guido; Van den Broeck, Peter

    2016-09-01

    For slender and lightweight structures, the vibration serviceability under crowd- induced loading is often critical in design. Currently, designers rely on equivalent load models, upscaled from single-person force measurements. Furthermore, it is important to consider the mechanical interaction with the human body as this can significantly reduce the structural response. To account for these interaction effects, the contact force between the pedestrian and the structure can be modelled as the superposition of the force induced by the pedestrian on a rigid floor and the force resulting from the mechanical interaction between the structure and the human body. For the case of large crowds, however, this approach leads to models with a very high system order. In the present contribution, two equivalent reduced-order models are proposed to approximate the dynamic behaviour of the full-order coupled crowd-structure system. A numerical study is performed to evaluate the impact of the modelling assumptions on the structural response to pedestrian excitation. The results show that the full-order moving crowd model can be well approximated by a reduced-order model whereby the interaction with the pedestrians in the crowd is modelled using a single (equivalent) SDOF system.

  8. Discrete-time pilot model. [human dynamics and digital simulation

    NASA Technical Reports Server (NTRS)

    Cavalli, D.

    1978-01-01

    Pilot behavior is considered as a discrete-time process where the decision making has a sequential nature. This model differs from both the quasilinear model which follows from classical control theory and from the optimal control model which considers the human operator as a Kalman estimator-predictor. An additional factor considered is that the pilot's objective may not be adequately formulated as a quadratic cost functional to be minimized, but rather as a more fuzzy measure of the closeness with which the aircraft follows a reference trajectory. All model parameters, in the digital program simulating the pilot's behavior, were successfully compared in terms of standard-deviation and performance with those of professional pilots in IFR configuration. The first practical application of the model was in the study of its performance degradation when the aircraft model static margin decreases.

  9. Computational model of soft tissues in the human upper airway.

    PubMed

    Pelteret, J-P V; Reddy, B D

    2012-01-01

    This paper presents a three-dimensional finite element model of the tongue and surrounding soft tissues with potential application to the study of sleep apnoea and of linguistics and speech therapy. The anatomical data was obtained from the Visible Human Project, and the underlying histological data was also extracted and incorporated into the model. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus. PMID:25830209

  10. Computational model of soft tissues in the human upper airway.

    PubMed

    Pelteret, J-P V; Reddy, B D

    2012-01-01

    This paper presents a three-dimensional finite element model of the tongue and surrounding soft tissues with potential application to the study of sleep apnoea and of linguistics and speech therapy. The anatomical data was obtained from the Visible Human Project, and the underlying histological data was also extracted and incorporated into the model. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus.

  11. A network model of human aging: Limits, errors, and information

    NASA Astrophysics Data System (ADS)

    Farrell, Spencer; Mitnitski, Arnold; Rockwood, Kenneth; Rutenberg, Andrew

    The Frailty Index (FI) quantifies human aging using the fraction of accumulated age-related deficits. The FI correlates strongly with mortality and accumulates non-linearly and stochastically with age. Clinical data shows a nearly universal limit of FI <= 0 . 7 . We computationally model an aging population using a network model of interacting deficits. Deficits damage and repair at rates that depend upon the average damage of connected nodes. The model is parametrized to fit clinical data. We find that attribution errors, especially false negative, allow the model to recover the frailty limit. Mutual information allows us to assess how well the FI can predict mortality. Mutual information provides a non-parametric measure of how the FI predicts mortality. We find that attribution errors have a small effect on the mutual information when many deficits are included in the model. The mutual information of our model and of the clinical data are comparable.

  12. A transparent model of the human scala tympani cavity.

    PubMed

    Rebscher, S J; Talbot, N; Bruszewski, W; Heilmann, M; Brasell, J; Merzenich, M M

    1996-01-01

    A dimensionally accurate clear model of the human scala tympani has been produced to evaluate the insertion and position of clinically applied intracochlear electrodes for electrical stimulation. Replicates of the human scala tympani were made from low melting point metal alloy (LMA) and from polymethylmeth-acrylate (PMMA) resin. The LMA metal casts were embedded in blocks of epoxy and in clear silicone rubber. After removal of the metal alloy, a cavity was produced that accurately models the human scala tympani. Investment casting molds were made from the PMMA scala tympani casts to enable production of multiple LMA casts from which identical models were fabricated. Total dimensional distortion of the LMA casting process was less than 1% in length and 2% in diameter. The models have been successfully integrated into the design process for the iterative development of advanced intracochlear electrode arrays at UCSF. These fabrication techniques are applicable to a wide range of biomedical design problems that require modelling of visually obscured cavities.

  13. Development of an innervated model of human skin.

    PubMed

    Khammo, Nancy; Ogilvie, Jane; Clothier, Richard H

    2007-10-01

    Neuronal cell responses and interactions with the epithelial and fibroblastic cells of the skin are a key factor in the production in vivo of the irritation/inflammatory response. Currently, few in vitro models are available that contain dermal, epidermal and the relevant neuronal components. The primary objective of this study was to produce and maintain a 3-D in vitro model of human skin containing these elements. The relevant neuronal component was supplied by adding sensory neurons derived from the dorsal root ganglion (DRG). Since adult neuronal cells do not grow significantly in vivo or in vitro, and since it is very difficult to obtain such cells from humans, it was necessary to employ embryonic rat DRG cells. The ultimate purpose of this model is to improve prediction of the in vivo skin irritancy potential of chemicals and formulations, without the need to use animal models. In addition, this approach has also been applied to the in vitro human eye and bronchial 3-D models being developed in the FRAME Alternatives Laboratory.

  14. A Culture-Behavior-Brain Loop Model of Human Development.

    PubMed

    Han, Shihui; Ma, Yina

    2015-11-01

    Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model.

  15. Model-based hierarchical reinforcement learning and human action control.

    PubMed

    Botvinick, Matthew; Weinstein, Ari

    2014-11-01

    Recent work has reawakened interest in goal-directed or 'model-based' choice, where decisions are based on prospective evaluation of potential action outcomes. Concurrently, there has been growing attention to the role of hierarchy in decision-making and action control. We focus here on the intersection between these two areas of interest, considering the topic of hierarchical model-based control. To characterize this form of action control, we draw on the computational framework of hierarchical reinforcement learning, using this to interpret recent empirical findings. The resulting picture reveals how hierarchical model-based mechanisms might play a special and pivotal role in human decision-making, dramatically extending the scope and complexity of human behaviour.

  16. Model-based hierarchical reinforcement learning and human action control

    PubMed Central

    Botvinick, Matthew; Weinstein, Ari

    2014-01-01

    Recent work has reawakened interest in goal-directed or ‘model-based’ choice, where decisions are based on prospective evaluation of potential action outcomes. Concurrently, there has been growing attention to the role of hierarchy in decision-making and action control. We focus here on the intersection between these two areas of interest, considering the topic of hierarchical model-based control. To characterize this form of action control, we draw on the computational framework of hierarchical reinforcement learning, using this to interpret recent empirical findings. The resulting picture reveals how hierarchical model-based mechanisms might play a special and pivotal role in human decision-making, dramatically extending the scope and complexity of human behaviour. PMID:25267822

  17. A microphysiological model of the human placental barrier.

    PubMed

    Blundell, Cassidy; Tess, Emily R; Schanzer, Ariana S R; Coutifaris, Christos; Su, Emily J; Parry, Samuel; Huh, Dongeun

    2016-08-01

    During human pregnancy, the fetal circulation is separated from maternal blood in the placenta by two cell layers - the fetal capillary endothelium and placental trophoblast. This placental barrier plays an essential role in fetal development and health by tightly regulating the exchange of endogenous and exogenous materials between the mother and the fetus. Here we present a microengineered device that provides a novel platform to mimic the structural and functional complexity of this specialized tissue in vitro. Our model is created in a multilayered microfluidic system that enables co-culture of human trophoblast cells and human fetal endothelial cells in a physiologically relevant spatial arrangement to replicate the characteristic architecture of the human placental barrier. We have engineered this co-culture model to induce progressive fusion of trophoblast cells and to form a syncytialized epithelium that resembles the syncytiotrophoblast in vivo. Our system also allows the cultured trophoblasts to form dense microvilli under dynamic flow conditions and to reconstitute expression and physiological localization of membrane transport proteins, such as glucose transporters (GLUTs), critical to the barrier function of the placenta. To provide a proof-of-principle for using this microdevice to recapitulate native function of the placental barrier, we demonstrated physiological transport of glucose across the microengineered maternal-fetal interface. Importantly, the rate of maternal-to-fetal glucose transfer in this system closely approximated that measured in ex vivo perfused human placentas. Our "placenta-on-a-chip" platform represents an important advance in the development of new technologies to model and study the physiological complexity of the human placenta for a wide variety of applications. PMID:27229450

  18. Modeling the human invader in the United States

    NASA Astrophysics Data System (ADS)

    Stohlgren, Thomas J.; Jarnevich, Catherine S.; Giri, Chandra P.

    2010-02-01

    Modern biogeographers recognize that humans are seen as constituents of ecosystems, drivers of significant change, and perhaps, the most invasive species on earth. We found it instructive to model humans as invasive organisms with the same environmental factors. We present a preliminary model of the spread of modern humans in the conterminous United States between 1992 and 2001 based on a subset of National Land Cover Data (NLCD), a time series LANDSAT product. We relied on the commonly used Maxent model, a species-environmental matching model, to map urbanization. Results: Urban areas represented 5.1% of the lower 48 states in 2001, an increase of 7.5% (18,112 km2) in the nine year period. At this rate, an area the size of Massachusetts is converted to urban land use every ten years. We used accepted models commonly used for mapping plant and animal distributions and found that climatic and environmental factors can strongly predict our spread (i.e., the conversion of forests, shrub/grass, and wetland areas into urban areas), with a 92.5% success rate (Area Under the Curve). Adding a roads layer in the model improved predictions to a 95.5% success rate. 8.8% of the 1-km2 cells in the conterminous U.S. now have a major road in them. In 2001, 0.8% of 1-km2 cells in the U.S. had an urbanness value of > 800, (>89% of a 1-km2 cell is urban), while we predict that 24.5% of 1-km2 cells in the conterminous U.S. will be > 800 eventually. Main conclusion: Humans have a highly predictable pattern of urbanization based on climatic and topographic variables. Conservation strategies may benefit from that predictability.

  19. Designers' models of the human-computer interface

    NASA Technical Reports Server (NTRS)

    Gillan, Douglas J.; Breedin, Sarah D.

    1993-01-01

    Understanding design models of the human-computer interface (HCI) may produce two types of benefits. First, interface development often requires input from two different types of experts: human factors specialists and software developers. Given the differences in their backgrounds and roles, human factors specialists and software developers may have different cognitive models of the HCI. Yet, they have to communicate about the interface as part of the design process. If they have different models, their interactions are likely to involve a certain amount of miscommunication. Second, the design process in general is likely to be guided by designers' cognitive models of the HCI, as well as by their knowledge of the user, tasks, and system. Designers do not start with a blank slate; rather they begin with a general model of the object they are designing. The author's approach to a design model of the HCI was to have three groups make judgments of categorical similarity about the components of an interface: human factors specialists with HCI design experience, software developers with HCI design experience, and a baseline group of computer users with no experience in HCI design. The components of the user interface included both display components such as windows, text, and graphics, and user interaction concepts, such as command language, editing, and help. The judgments of the three groups were analyzed using hierarchical cluster analysis and Pathfinder. These methods indicated, respectively, how the groups categorized the concepts, and network representations of the concepts for each group. The Pathfinder analysis provides greater information about local, pairwise relations among concepts, whereas the cluster analysis shows global, categorical relations to a greater extent.

  20. Modeling the human invader in the United States

    USGS Publications Warehouse

    Stohlgren, Thomas J.; Jarnevich, Catherine S.; Giri, Chandra P.

    2010-01-01

    Modern biogeographers recognize that humans are seen as constituents of ecosystems, drivers of significant change, and perhaps, the most invasive species on earth. We found it instructive to model humans as invasive organisms with the same environmental factors. We present a preliminary model of the spread of modern humans in the conterminous United States between 1992 and 2001 based on a subset of National Land Cover Data (NLCD), a time series LANDSAT product. We relied on the commonly used Maxent model, a species-environmental matching model, to map urbanization. Results: Urban areas represented 5.1% of the lower 48 states in 2001, an increase of 7.5% (18,112 km2) in the nine year period. At this rate, an area the size of Massachusetts is converted to urban land use every ten years. We used accepted models commonly used for mapping plant and animal distributions and found that climatic and environmental factors can strongly predict our spread (i.e., the conversion of forests, shrub/grass, and wetland areas into urban areas), with a 92.5% success rate (Area Under the Curve). Adding a roads layer in the model improved predictions to a 95.5% success rate. 8.8% of the 1-km2> cells in the conterminous U.S. now have a major road in them. In 2001, 0.8% of 1-km2 > cells in the U.S. had an urbanness value of > 800, (>89% of a 1-km2> cell is urban), while we predict that 24.5% of 1-km2> cells in the conterminous U.S. will be > 800 eventually. Main conclusion: Humans have a highly predictable pattern of urbanization based on climatic and topographic variables. Conservation strategies may benefit from that predictability.

  1. Mouse models of human AML accurately predict chemotherapy response

    PubMed Central

    Zuber, Johannes; Radtke, Ina; Pardee, Timothy S.; Zhao, Zhen; Rappaport, Amy R.; Luo, Weijun; McCurrach, Mila E.; Yang, Miao-Miao; Dolan, M. Eileen; Kogan, Scott C.; Downing, James R.; Lowe, Scott W.

    2009-01-01

    The genetic heterogeneity of cancer influences the trajectory of tumor progression and may underlie clinical variation in therapy response. To model such heterogeneity, we produced genetically and pathologically accurate mouse models of common forms of human acute myeloid leukemia (AML) and developed methods to mimic standard induction chemotherapy and efficiently monitor therapy response. We see that murine AMLs harboring two common human AML genotypes show remarkably diverse responses to conventional therapy that mirror clinical experience. Specifically, murine leukemias expressing the AML1/ETO fusion oncoprotein, associated with a favorable prognosis in patients, show a dramatic response to induction chemotherapy owing to robust activation of the p53 tumor suppressor network. Conversely, murine leukemias expressing MLL fusion proteins, associated with a dismal prognosis in patients, are drug-resistant due to an attenuated p53 response. Our studies highlight the importance of genetic information in guiding the treatment of human AML, functionally establish the p53 network as a central determinant of chemotherapy response in AML, and demonstrate that genetically engineered mouse models of human cancer can accurately predict therapy response in patients. PMID:19339691

  2. Space station crew safety: Human factors interaction model

    NASA Technical Reports Server (NTRS)

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

    1985-01-01

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

  3. A human fetal prostate xenograft model of developmental estrogenization

    PubMed Central

    Saffarini, Camelia M.; McDonnell-Clark, Elizabeth V.; Amin, Ali; Boekelheide, Kim

    2015-01-01

    Prostate cancer is a common disease in older men. Rodent models have demonstrated that an early and later-life exposure to estrogen can lead to cancerous lesions, and implicated hormonal dysregulation as an avenue for developing future prostate neoplasia. This study utilizes a human fetal prostate xenograft model to study the role of estrogen in the progression of human disease. Histopathological lesions were assessed in 7, 30, 90, 200, and 400-day human prostate xenografts. Gene expression for cell cycle, tumor suppressors, and apoptosis-related genes (i.e. CDKN1A, CASP9, ESR2, PTEN, and TP53) were performed for 200-day estrogen-treated xenografts. Glandular hyperplasia was observed in xenografts given both an initial and secondary exposure to estradiol in both 200 and 400-day xenografts. Persistent estrogenic effects were verified using immunohistochemical markers for cytokeratin 10, p63, and estrogen receptor-α. This model provides data on the histopathological state of the human prostate following estrogenic treatment, which can be utilized in understanding the complicated pathology associated with prostatic disease and early- and later-life estrogenic exposures. PMID:25633637

  4. Personalized medicine for cystic fibrosis: establishing human model systems.

    PubMed

    Mou, Hongmei; Brazauskas, Karissa; Rajagopal, Jayaraj

    2015-10-01

    With over 1,500 identifiable mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that result in distinct functional and phenotypical abnormalities, it is virtually impossible to perform randomized clinical trials to identify the best therapeutics for all patients. Therefore, a personalized medicine approach is essential. The only way to realistically accomplish this is through the development of improved in vitro human model systems. The lack of a readily available and infinite supply of human CFTR-expressing airway epithelial cells is a key bottleneck. We propose that a concerted two-pronged approach is necessary for patient-specific cystic fibrosis research to continue to prosper and realize its potential: (1) more effective culture and differentiation conditions for growing primary human airway and nasal epithelial cells and (2) the development of collective protocols for efficiently differentiating disease- and patient-specific induced pluripotent stem cells (iPSC) into pure populations of adult epithelial cells. Ultimately, we need a personalized human model system for cystic fibrosis with the capacity for uncomplicated bankability, widespread availability, and universal applicability for patient-specific disease modeling, novel pharmacotherapy investigation and screening, and readily executable genetic modification.

  5. Culture models of human mammary epithelial cell transformation

    SciTech Connect

    Stampfer, Martha R.; Yaswen, Paul

    2000-11-10

    Human pre-malignant breast diseases, particularly ductal carcinoma in situ (DCIS)3 already display several of the aberrant phenotypes found in primary breast cancers, including chromosomal abnormalities, telomerase activity, inactivation of the p53 gene and overexpression of some oncogenes. Efforts to model early breast carcinogenesis in human cell cultures have largely involved studies in vitro transformation of normal finite lifespan human mammary epithelial cells (HMEC) to immortality and malignancy. We present a model of HMEC immortal transformation consistent with the know in vivo data. This model includes a recently described, presumably epigenetic process, termed conversion, which occurs in cells that have overcome stringent replicative senescence and are thus able to maintain proliferation with critically short telomeres. The conversion process involves reactivation of telomerase activity, and acquisition of good uniform growth in the absence and presence of TFGB. We propose th at overcoming the proliferative constraints set by senescence, and undergoing conversion, represent key rate-limiting steps in human breast carcinogenesis, and occur during early stage breast cancer progression.

  6. Modeling neurodevelopmental disorders using human pluripotent stem cells.

    PubMed

    Telias, Michael; Ben-Yosef, Dalit

    2014-08-01

    Neurodevelopmental disorders (NDs) are impairments that affect the development and growth of the brain and the central nervous system during embryonic and early postnatal life. Genetically manipulated animals have contributed greatly to the advancement of ND research, but many of them differ considerably from the human phenotype. Cellular in vitro models are also valuable, but the availability of human neuronal cells is limited and their lifespan in culture is short. Human pluripotent stem cells (hPSCs), including embryonic stem cells and induced pluripotent stem cells, comprise a powerful tool for studying developmentally regulated diseases, including NDs. We reviewed all recent studies in which hPSCs were used as in vitro models for diseases and syndromes characterized by impairment of neurogenesis or synaptogenesis leading to intellectual disability and delayed neurodevelopment. We analyzed their methodology and results, focusing on the data obtained following in vitro neural differentiation and gene expression and profiling of the derived neurons. Electrophysiological recording of action potentials, synaptic currents and response to neurotransmitters is pivotal for validation of the neuronal fate as well as for assessing phenotypic dysfunctions linked to the disease in question. We therefore focused on the studies which included electrophysiological recordings on the in vitro-derived neurons. Finally, we addressed specific issues that are critical for the advancement of this area of research, specifically in providing a reliable human pre-clinical research model and drug screening platform. PMID:24728983

  7. Modeling of Radiation Risks for Human Space Missions

    NASA Technical Reports Server (NTRS)

    Fletcher, Graham

    2004-01-01

    Prior to any human space flight, calculations of radiation risks are used to determine the acceptable scope of astronaut activity. Using the supercomputing facilities at NASA Ames Research Center, Ames researchers have determined the damage probabilities of DNA functional groups by space radiation. The data supercede those used in the current Monte Carlo model for risk assessment. One example is the reaction of DNA with hydroxyl radical produced by the interaction of highly energetic particles from space radiation with water molecules in the human body. This reaction is considered an important cause of DNA mutations, although its mechanism is not well understood.

  8. Modeling human diseases: an education in interactions and interdisciplinary approaches.

    PubMed

    Zon, Leonard

    2016-06-01

    Traditionally, most investigators in the biomedical arena exploit one model system in the course of their careers. Occasionally, an investigator will switch models. The selection of a suitable model system is a crucial step in research design. Factors to consider include the accuracy of the model as a reflection of the human disease under investigation, the numbers of animals needed and ease of husbandry, its physiology and developmental biology, and the ability to apply genetics and harness the model for drug discovery. In my lab, we have primarily used the zebrafish but combined it with other animal models and provided a framework for others to consider the application of developmental biology for therapeutic discovery. Our interdisciplinary approach has led to many insights into human diseases and to the advancement of candidate drugs to clinical trials. Here, I draw on my experiences to highlight the importance of combining multiple models, establishing infrastructure and genetic tools, forming collaborations, and interfacing with the medical community for successful translation of basic findings to the clinic.

  9. Modeling human diseases: an education in interactions and interdisciplinary approaches.

    PubMed

    Zon, Leonard

    2016-06-01

    Traditionally, most investigators in the biomedical arena exploit one model system in the course of their careers. Occasionally, an investigator will switch models. The selection of a suitable model system is a crucial step in research design. Factors to consider include the accuracy of the model as a reflection of the human disease under investigation, the numbers of animals needed and ease of husbandry, its physiology and developmental biology, and the ability to apply genetics and harness the model for drug discovery. In my lab, we have primarily used the zebrafish but combined it with other animal models and provided a framework for others to consider the application of developmental biology for therapeutic discovery. Our interdisciplinary approach has led to many insights into human diseases and to the advancement of candidate drugs to clinical trials. Here, I draw on my experiences to highlight the importance of combining multiple models, establishing infrastructure and genetic tools, forming collaborations, and interfacing with the medical community for successful translation of basic findings to the clinic. PMID:27483497

  10. Modeling human diseases: an education in interactions and interdisciplinary approaches

    PubMed Central

    2016-01-01

    ABSTRACT Traditionally, most investigators in the biomedical arena exploit one model system in the course of their careers. Occasionally, an investigator will switch models. The selection of a suitable model system is a crucial step in research design. Factors to consider include the accuracy of the model as a reflection of the human disease under investigation, the numbers of animals needed and ease of husbandry, its physiology and developmental biology, and the ability to apply genetics and harness the model for drug discovery. In my lab, we have primarily used the zebrafish but combined it with other animal models and provided a framework for others to consider the application of developmental biology for therapeutic discovery. Our interdisciplinary approach has led to many insights into human diseases and to the advancement of candidate drugs to clinical trials. Here, I draw on my experiences to highlight the importance of combining multiple models, establishing infrastructure and genetic tools, forming collaborations, and interfacing with the medical community for successful translation of basic findings to the clinic. PMID:27483497

  11. Pedigree models for complex human traits involving the mitochrondrial genome

    SciTech Connect

    Schork, N.J.; Guo, S.W. )

    1993-12-01

    Recent biochemical and molecular-genetic discoveries concerning variations in human mtDNA have suggested a role for mtDNA mutations in a number of human traits and disorders. Although the importance of these discoveries cannot be emphasized enough, the complex natures of mitochondrial biogenesis, mutant mtDNA phenotype expression, and the maternal inheritance pattern exhibited by mtDNA transmission make it difficult to develop models that can be used routinely in pedigree analyses to quantify and test hypotheses about the role of mtDNA in the expression of a trait. In the present paper, the authors describe complexities inherent in mitochondrial biogenesis and genetic transmission and show how these complexities can be incorporated into appropriate mathematical models. The authors offer a variety of likelihood-based models which account for the complexities discussed. The derivation of the models is meant to stimulate the construction of statistical tests for putative mtDNA contribution to a trait. Results of simulation studies which make use of the proposed models are described. The results of the simulation studies suggest that, although pedigree models of mtDNA effects can be reliable, success in mapping chromosomal determinants of a trait does not preclude the possibility that mtDNA determinants exist for the trait as well. Shortcomings inherent in the proposed models are described in an effort to expose areas in need of additional research. 58 refs., 5 figs., 2 tabs.

  12. Cognition and procedure representational requirements for predictive human performance models

    NASA Technical Reports Server (NTRS)

    Corker, K.

    1992-01-01

    Models and modeling environments for human performance are becoming significant contributors to early system design and analysis procedures. Issues of levels of automation, physical environment, informational environment, and manning requirements are being addressed by such man/machine analysis systems. The research reported here investigates the close interaction between models of human cognition and models that described procedural performance. We describe a methodology for the decomposition of aircrew procedures that supports interaction with models of cognition on the basis of procedures observed; that serves to identify cockpit/avionics information sources and crew information requirements; and that provides the structure to support methods for function allocation among crew and aiding systems. Our approach is to develop an object-oriented, modular, executable software representation of the aircrew, the aircraft, and the procedures necessary to satisfy flight-phase goals. We then encode in a time-based language, taxonomies of the conceptual, relational, and procedural constraints among the cockpit avionics and control system and the aircrew. We have designed and implemented a goals/procedures hierarchic representation sufficient to describe procedural flow in the cockpit. We then execute the procedural representation in simulation software and calculate the values of the flight instruments, aircraft state variables and crew resources using the constraints available from the relationship taxonomies. The system provides a flexible, extensible, manipulative and executable representation of aircrew and procedures that is generally applicable to crew/procedure task-analysis. The representation supports developed methods of intent inference, and is extensible to include issues of information requirements and functional allocation. We are attempting to link the procedural representation to models of cognitive functions to establish several intent inference methods

  13. Models of Human Information Requirements: "When Reasonable Aiding Systems Disagree"

    NASA Technical Reports Server (NTRS)

    Corker, Kevin; Pisanich, Gregory; Shafto, Michael (Technical Monitor)

    1994-01-01

    Aircraft flight management and Air Traffic Control (ATC) automation are under development to maximize the economy of flight and to increase the capacity of the terminal area airspace while maintaining levels of flight safety equal to or better than current system performance. These goals are being realized by the introduction of flight management automation aiding and operations support systems on the flight deck and by new developments of ATC aiding systems that seek to optimize scheduling of aircraft while potentially reducing required separation and accounting for weather and wake vortex turbulence. Aiding systems on both the flight deck and the ground operate through algorithmic functions on models of the aircraft and of the airspace. These models may differ from each other as a result of variations in their models of the immediate environment. The resultant flight operations or ATC commands may differ in their response requirements (e.g. different preferred descent speeds or descent initiation points). The human operators in the system must then interact with the automation to reconcile differences and resolve conflicts. We have developed a model of human performance including cognitive functions (decision-making, rule-based reasoning, procedural interruption recovery and forgetting) that supports analysis of the information requirements for resolution of flight aiding and ATC conflicts. The model represents multiple individuals in the flight crew and in ATC. The model is supported in simulation on a Silicon Graphics' workstation using Allegro Lisp. Design guidelines for aviation automation aiding systems have been developed using the model's specification of information and team procedural requirements. Empirical data on flight deck operations from full-mission flight simulation are provided to support the model's predictions. The paper describes the model, its development and implementation, the simulation test of the model predictions, and the empirical

  14. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis.

    PubMed

    Takasato, Minoru; Er, Pei X; Chiu, Han S; Maier, Barbara; Baillie, Gregory J; Ferguson, Charles; Parton, Robert G; Wolvetang, Ernst J; Roost, Matthias S; Chuva de Sousa Lopes, Susana M; Little, Melissa H

    2015-10-22

    The human kidney contains up to 2 million epithelial nephrons responsible for blood filtration. Regenerating the kidney requires the induction of the more than 20 distinct cell types required for excretion and the regulation of pH, and electrolyte and fluid balance. We have previously described the simultaneous induction of progenitors for both collecting duct and nephrons via the directed differentiation of human pluripotent stem cells. Paradoxically, although both are of intermediate mesoderm in origin, collecting duct and nephrons have distinct temporospatial origins. Here we identify the developmental mechanism regulating the preferential induction of collecting duct versus kidney mesenchyme progenitors. Using this knowledge, we have generated kidney organoids that contain nephrons associated with a collecting duct network surrounded by renal interstitium and endothelial cells. Within these organoids, individual nephrons segment into distal and proximal tubules, early loops of Henle, and glomeruli containing podocytes elaborating foot processes and undergoing vascularization. When transcription profiles of kidney organoids were compared to human fetal tissues, they showed highest congruence with first trimester human kidney. Furthermore, the proximal tubules endocytose dextran and differentially apoptose in response to cisplatin, a nephrotoxicant. Such kidney organoids represent powerful models of the human organ for future applications, including nephrotoxicity screening, disease modelling and as a source of cells for therapy.

  15. Modeling Humans as Reinforcement Learners: How to Predict Human Behavior in Multi-Stage Games

    NASA Technical Reports Server (NTRS)

    Lee, Ritchie; Wolpert, David H.; Backhaus, Scott; Bent, Russell; Bono, James; Tracey, Brendan

    2011-01-01

    This paper introduces a novel framework for modeling interacting humans in a multi-stage game environment by combining concepts from game theory and reinforcement learning. The proposed model has the following desirable characteristics: (1) Bounded rational players, (2) strategic (i.e., players account for one anothers reward functions), and (3) is computationally feasible even on moderately large real-world systems. To do this we extend level-K reasoning to policy space to, for the first time, be able to handle multiple time steps. This allows us to decompose the problem into a series of smaller ones where we can apply standard reinforcement learning algorithms. We investigate these ideas in a cyber-battle scenario over a smart power grid and discuss the relationship between the behavior predicted by our model and what one might expect of real human defenders and attackers.

  16. Rich-and-Poor Model for Human and Nature Interaction

    NASA Astrophysics Data System (ADS)

    Motesharrei, S.; Kalnay, E.; Rivas, J.; Rich-n-Poor

    2011-12-01

    Historical evidence shows collapse of several civilizations in different regions of the world. Jared Diamond presents an account of such societal failures in his 2005 book "Collapse: How Societies Choose to Fail or Succeed." As a precursor to building a complex model for interaction of human and environment, we developed a "thought-experiment" model based on Lotka-Volterra equations for the interaction of two species, known as the Predator-Prey model. We constructed a fairly simple rich-and-poor model that includes only four state variables (or stocks): Rich Population, Poor Population, Nature, and Rich Savings. We observed several scenarios for growth of societies by varying the model's parameter values, including scenarios that resemble the catastrophic fall of ancient civilizations such as the Maya and Anasazi.

  17. Human supervisory approach to modeling industrial scenes using geometric primitives

    SciTech Connect

    Luck, J.P.; Little, C.Q.; Roberts, R.S.

    1997-11-19

    A three-dimensional world model is crucial for many robotic tasks. Modeling techniques tend to be either fully manual or autonomous. Manual methods are extremely time consuming but also highly accurate and flexible. Autonomous techniques are fast but inflexible and, with real-world data, often inaccurate. The method presented in this paper combines the two, yielding a highly efficient, flexible, and accurate mapping tool. The segmentation and modeling algorithms that compose the method are specifically designed for industrial environments, and are described in detail. A mapping system based on these algorithms has been designed. It enables a human supervisor to quickly construct a fully defined world model from unfiltered and unsegmented real-world range imagery. Examples of how industrial scenes are modeled with the mapping system are provided.

  18. A computational model of the human hand 93-ERI-053

    SciTech Connect

    Hollerbach, K.; Axelrod, T.

    1996-03-01

    The objectives of the Computational Hand Modeling project were to prove the feasibility of the Laboratory`s NIKE3D finite element code to orthopaedic problems. Because of the great complexity of anatomical structures and the nonlinearity of their behavior, we have focused on a subset of joints of the hand and lower extremity and have developed algorithms to model their behavior. The algorithms developed here solve fundamental problems in computational biomechanics and can be expanded to describe any other joints of the human body. This kind of computational modeling has never successfully been attempted before, due in part to a lack of biomaterials data and a lack of computational resources. With the computational resources available at the National Laboratories and the collaborative relationships we have established with experimental and other modeling laboratories, we have been in a position to pursue our innovative approach to biomechanical and orthopedic modeling.

  19. Translating the MAM Model of Psychosis to Humans

    PubMed Central

    Modinos, Gemma; Allen, Paul; Grace, Anthony A.; McGuire, Philip

    2015-01-01

    Elevated dopamine function and alterations in the medial temporal lobe structure and function (MTL) are two of the most robust findings in schizophrenia, but how interactions between these abnormalities underlie the onset of psychosis is unclear. Although several preclinical models of psychosis have been proposed, the methylazoxymethanol acetate (MAM) rodent model provides a mechanistic account linking these two clinical observations. The model proposes that psychosis develops as a result of a perturbation of MTL function, leading to elevated striatal dopamine dysfunction. We review a number of recent neuroimaging studies that examine components of the putative model in people with an ultra high risk (UHR) of psychosis. Whilst data from these studies are broadly consistent with the MAM model, that the potential for comparing various kinds of neurobiological data across animal and human studies imposes some limitations on what can be inferred from these data. Going forward, longitudinal studies are needed to explicitly test the model’s predictions in UHR populations. PMID:25554679

  20. Animal models of human respiratory syncytial virus disease

    PubMed Central

    Domachowske, Joseph B.; Rosenberg, Helene F.

    2011-01-01

    Infection with the human pneumovirus pathogen, respiratory syncytial virus (hRSV), causes a wide spectrum of respiratory disease, notably among infants and the elderly. Laboratory animal studies permit detailed experimental modeling of hRSV disease and are therefore indispensable in the search for novel therapies and preventative strategies. Present animal models include several target species for hRSV, including chimpanzees, cattle, sheep, cotton rats, and mice, as well as alternative animal pneumovirus models, such as bovine RSV and pneumonia virus of mice. These diverse animal models reproduce different features of hRSV disease, and their utilization should therefore be based on the scientific hypothesis under investigation. The purpose of this review is to summarize the strengths and limitations of each of these animal models. Our intent is to provide a resource for investigators and an impetus for future research. PMID:21571908

  1. Proteomics in farm animals models of human diseases.

    PubMed

    Ceciliani, Fabrizio; Restelli, Laura; Lecchi, Cristina

    2014-10-01

    The need to provide in vivo complex environments to understand human diseases strongly relies on the use of animal models, which traditionally include small rodents and rabbits. It is becoming increasingly evident that the few species utilised to date cannot be regarded as universal. There is a great need for new animal species that are naturally endowed with specific features relevant to human diseases. Farm animals, including pigs, cows, sheep and horses, represent a valid alternative to commonly utilised rodent models. There is an ample scope for the application of proteomic techniques in farm animals, and the establishment of several proteomic maps of plasma and tissue has clearly demonstrated that farm animals provide a disease environment that closely resembles that of human diseases. The present review offers a snapshot of how proteomic techniques have been applied to farm animals to improve their use as biomedical models. Focus will be on specific topics of biomedical research in which farm animal models have been characterised through the application of proteomic techniques.

  2. The non-human primate experimental glaucoma model.

    PubMed

    Burgoyne, Claude F

    2015-12-01

    The purpose of this report is to summarize the current strengths and weaknesses of the non-human primate (NHP) experimental glaucoma (EG) model through sections devoted to its history, methods, important findings, alternative optic neuropathy models and future directions. NHP EG has become well established for studying human glaucoma in part because the NHP optic nerve head (ONH) shares a close anatomic association with the human ONH and because it provides the only means of systematically studying the very earliest visual system responses to chronic intraocular pressure (IOP) elevation, i.e. the conversion from ocular hypertension to glaucomatous damage. However, NHPs are impractical for studies that require large animal numbers, demonstrate spontaneous glaucoma only rarely, do not currently provide a model of the neuropathy at normal levels of IOP, and cannot easily be genetically manipulated, except through tissue-specific, viral vectors. The goal of this summary is to direct NHP EG and non-NHP EG investigators to the previous, current and future accomplishment of clinically relevant knowledge in this model.

  3. Hologram QSAR model for the prediction of human oral bioavailability.

    PubMed

    Moda, Tiago L; Montanari, Carlos A; Andricopulo, Adriano D

    2007-12-15

    A drug intended for use in humans should have an ideal balance of pharmacokinetics and safety, as well as potency and selectivity. Unfavorable pharmacokinetics can negatively affect the clinical development of many otherwise promising drug candidates. A variety of in silico ADME (absorption, distribution, metabolism, and excretion) models are receiving increased attention due to a better appreciation that pharmacokinetic properties should be considered in early phases of the drug discovery process. Human oral bioavailability is an important pharmacokinetic property, which is directly related to the amount of drug available in the systemic circulation to exert pharmacological and therapeutic effects. In the present work, hologram quantitative structure-activity relationships (HQSAR) were performed on a training set of 250 structurally diverse molecules with known human oral bioavailability. The most significant HQSAR model (q(2)=0.70, r(2)=0.93) was obtained using atoms, bond, connection, and chirality as fragment distinction. The predictive ability of the model was evaluated by an external test set containing 52 molecules not included in the training set, and the predicted values were in good agreement with the experimental values. The HQSAR model should be useful for the design of new drug candidates having increased bioavailability as well as in the process of chemical library design, virtual screening, and high-throughput screening.

  4. Modelling large scale human activity in San Francisco

    NASA Astrophysics Data System (ADS)

    Gonzalez, Marta

    2010-03-01

    Diverse group of people with a wide variety of schedules, activities and travel needs compose our cities nowadays. This represents a big challenge for modeling travel behaviors in urban environments; those models are of crucial interest for a wide variety of applications such as traffic forecasting, spreading of viruses, or measuring human exposure to air pollutants. The traditional means to obtain knowledge about travel behavior is limited to surveys on travel journeys. The obtained information is based in questionnaires that are usually costly to implement and with intrinsic limitations to cover large number of individuals and some problems of reliability. Using mobile phone data, we explore the basic characteristics of a model of human travel: The distribution of agents is proportional to the population density of a given region, and each agent has a characteristic trajectory size contain information on frequency of visits to different locations. Additionally we use a complementary data set given by smart subway fare cards offering us information about the exact time of each passenger getting in or getting out of the subway station and the coordinates of it. This allows us to uncover the temporal aspects of the mobility. Since we have the actual time and place of individual's origin and destination we can understand the temporal patterns in each visited location with further details. Integrating two described data set we provide a dynamical model of human travels that incorporates different aspects observed empirically.

  5. Patient-Specific Computational Modeling of Human Phonation

    NASA Astrophysics Data System (ADS)

    Xue, Qian; Zheng, Xudong; University of Maine Team

    2013-11-01

    Phonation is a common biological process resulted from the complex nonlinear coupling between glottal aerodynamics and vocal fold vibrations. In the past, the simplified symmetric straight geometric models were commonly employed for experimental and computational studies. The shape of larynx lumen and vocal folds are highly three-dimensional indeed and the complex realistic geometry produces profound impacts on both glottal flow and vocal fold vibrations. To elucidate the effect of geometric complexity on voice production and improve the fundamental understanding of human phonation, a full flow-structure interaction simulation is carried out on a patient-specific larynx model. To the best of our knowledge, this is the first patient-specific flow-structure interaction study of human phonation. The simulation results are well compared to the established human data. The effects of realistic geometry on glottal flow and vocal fold dynamics are investigated. It is found that both glottal flow and vocal fold dynamics present a high level of difference from the previous simplified model. This study also paved the important step toward the development of computer model for voice disease diagnosis and surgical planning. The project described was supported by Grant Number ROlDC007125 from the National Institute on Deafness and Other Communication Disorders (NIDCD).

  6. System parameters for erythropoiesis control model: Comparison of normal values in human and mouse model

    NASA Technical Reports Server (NTRS)

    1979-01-01

    The computer model for erythropoietic control was adapted to the mouse system by altering system parameters originally given for the human to those which more realistically represent the mouse. Parameter values were obtained from a variety of literature sources. Using the mouse model, the mouse was studied as a potential experimental model for spaceflight. Simulation studies of dehydration and hypoxia were performed. A comparison of system parameters for the mouse and human models is presented. Aside from the obvious differences expected in fluid volumes, blood flows and metabolic rates, larger differences were observed in the following: erythrocyte life span, erythropoietin half-life, and normal arterial pO2.

  7. Human Intestinal Enteroids: a New Model To Study Human Rotavirus Infection, Host Restriction, and Pathophysiology

    PubMed Central

    Saxena, Kapil; Blutt, Sarah E.; Ettayebi, Khalil; Zeng, Xi-Lei; Broughman, James R.; Crawford, Sue E.; Karandikar, Umesh C.; Sastri, Narayan P.; Conner, Margaret E.; Opekun, Antone R.; Graham, David Y.; Qureshi, Waqar; Sherman, Vadim; Foulke-Abel, Jennifer; In, Julie; Kovbasnjuk, Olga; Zachos, Nicholas C.; Donowitz, Mark

    2015-01-01

    ABSTRACT Human gastrointestinal tract research is limited by the paucity of in vitro intestinal cell models that recapitulate the cellular diversity and complex functions of human physiology and disease pathology. Human intestinal enteroid (HIE) cultures contain multiple intestinal epithelial cell types that comprise the intestinal epithelium (enterocytes and goblet, enteroendocrine, and Paneth cells) and are physiologically active based on responses to agonists. We evaluated these nontransformed, three-dimensional HIE cultures as models for pathogenic infections in the small intestine by examining whether HIEs from different regions of the small intestine from different patients are susceptible to human rotavirus (HRV) infection. Little is known about HRVs, as they generally replicate poorly in transformed cell lines, and host range restriction prevents their replication in many animal models, whereas many animal rotaviruses (ARVs) exhibit a broader host range and replicate in mice. Using HRVs, including the Rotarix RV1 vaccine strain, and ARVs, we evaluated host susceptibility, virus production, and cellular responses of HIEs. HRVs infect at higher rates and grow to higher titers than do ARVs. HRVs infect differentiated enterocytes and enteroendocrine cells, and viroplasms and lipid droplets are induced. Heterogeneity in replication was seen in HIEs from different patients. HRV infection and RV enterotoxin treatment of HIEs caused physiological lumenal expansion detected by time-lapse microscopy, recapitulating one of the hallmarks of rotavirus-induced diarrhea. These results demonstrate that HIEs are a novel pathophysiological model that will allow the study of HRV biology, including host restriction, cell type restriction, and virus-induced fluid secretion. IMPORTANCE Our research establishes HIEs as nontransformed cell culture models to understand human intestinal physiology and pathophysiology and the epithelial response, including host restriction of

  8. Naturally occurring animal models of human hepatitis E virus infection.

    PubMed

    Yugo, Danielle M; Cossaboom, Caitlin M; Meng, Xiang-Jin

    2014-01-01

    Hepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus in the family Hepeviridae. Hepatitis E caused by HEV is a clinically important global disease. There are currently four well-characterized genotypes of HEV in mammalian species, although numerous novel strains of HEV likely belonging to either new genotypes or species have recently been identified from several other animal species. HEV genotypes 1 and 2 are limited to infection in humans, whereas genotypes 3 and 4 infect an expanding host range of animal species and are zoonotic to humans. Historical animal models include various species of nonhuman primates, which have been indispensable for the discovery of human HEV and for understanding its pathogenesis and course of infection. With the genetic identification and characterization of animal strains of HEV, a number of naturally occurring animal models such as swine, chicken, and rabbit have recently been developed for various aspects of HEV research, including vaccine trials, pathogenicity, cross-species infection, mechanism of virus replication, and molecular biology studies. Unfortunately, the current available animal models for HEV are still inadequate for certain aspects of HEV research. For instance, an animal model is still lacking to study the underlying mechanism of severe and fulminant hepatitis E during pregnancy. Also, an animal model that can mimic chronic HEV infection is critically needed to study the mechanism leading to chronicity in immunocompromised individuals. Genetic identification of additional novel animal strains of HEV may lead to the development of better naturally occurring animal models for HEV. This article reviews the current understanding of animal models of HEV infection in both natural and experimental infection settings and identifies key research needs and limitations.

  9. Modeling of Chronic Myeloid Leukemia: An Overview of In Vivo Murine and Human Xenograft Models.

    PubMed

    Sontakke, Pallavi; Jaques, Jenny; Vellenga, Edo; Schuringa, Jan Jacob

    2016-01-01

    Over the past years, a wide variety of in vivo mouse models have been generated in order to unravel the molecular pathology of Chronic Myeloid Leukemia (CML) and to develop and improve therapeutic approaches. These models range from (conditional) transgenic models, knock-in models, and murine bone marrow retroviral transduction models followed by transplantation. With the advancement of immunodeficient xenograft models, it has become possible to use human stem/progenitor cells for in vivo studies as well as cells directly derived from CML patients. These models not only mimic CML but also have been instrumental in uncovering various fundamental mechanisms of CML disease progression and tyrosine kinase inhibitor (TKI) resistance. With the availability of iPSC technology, it has become feasible to derive, maintain, and expand CML subclones that are at least genetically identical to those in patients. The following review provides an overview of all murine as well as human xenograft models for CML established till date. PMID:27642303

  10. Modeling of Chronic Myeloid Leukemia: An Overview of In Vivo Murine and Human Xenograft Models

    PubMed Central

    Vellenga, Edo

    2016-01-01

    Over the past years, a wide variety of in vivo mouse models have been generated in order to unravel the molecular pathology of Chronic Myeloid Leukemia (CML) and to develop and improve therapeutic approaches. These models range from (conditional) transgenic models, knock-in models, and murine bone marrow retroviral transduction models followed by transplantation. With the advancement of immunodeficient xenograft models, it has become possible to use human stem/progenitor cells for in vivo studies as well as cells directly derived from CML patients. These models not only mimic CML but also have been instrumental in uncovering various fundamental mechanisms of CML disease progression and tyrosine kinase inhibitor (TKI) resistance. With the availability of iPSC technology, it has become feasible to derive, maintain, and expand CML subclones that are at least genetically identical to those in patients. The following review provides an overview of all murine as well as human xenograft models for CML established till date.

  11. Modeling of Chronic Myeloid Leukemia: An Overview of In Vivo Murine and Human Xenograft Models

    PubMed Central

    Vellenga, Edo

    2016-01-01

    Over the past years, a wide variety of in vivo mouse models have been generated in order to unravel the molecular pathology of Chronic Myeloid Leukemia (CML) and to develop and improve therapeutic approaches. These models range from (conditional) transgenic models, knock-in models, and murine bone marrow retroviral transduction models followed by transplantation. With the advancement of immunodeficient xenograft models, it has become possible to use human stem/progenitor cells for in vivo studies as well as cells directly derived from CML patients. These models not only mimic CML but also have been instrumental in uncovering various fundamental mechanisms of CML disease progression and tyrosine kinase inhibitor (TKI) resistance. With the availability of iPSC technology, it has become feasible to derive, maintain, and expand CML subclones that are at least genetically identical to those in patients. The following review provides an overview of all murine as well as human xenograft models for CML established till date. PMID:27642303

  12. A dengue model incorporating saturation incidence and human migration

    NASA Astrophysics Data System (ADS)

    Gakkhar, S.; Mishra, A.

    2015-03-01

    In this paper, a non-linear model has been proposed to investigate the effects of human migration on dengue dynamics. Human migration has been considered between two patches having different dengue strains. Due to migration secondary infection is possible. Further, the secondary infection is considered in patch-2 only as strain-2 in patch-2 is considered to be more severe than that of strain-1 in patch-1. The saturation incidence rate has been considered to incorporate the behavioral changes towards epidemic in human population. The basic reproduction number has been computed. Four Equilibrium states have been found and analyzed. Increasing saturation rate decreases the threshold thereby enhancing the stability of disease-free state in both the patches. Control on migration may lead to change in infection level of patches.

  13. Modelling human mobility patterns using photographic data shared online.

    PubMed

    Barchiesi, Daniele; Preis, Tobias; Bishop, Steven; Moat, Helen Susannah

    2015-08-01

    Humans are inherently mobile creatures. The way we move around our environment has consequences for a wide range of problems, including the design of efficient transportation systems and the planning of urban areas. Here, we gather data about the position in space and time of about 16 000 individuals who uploaded geo-tagged images from locations within the UK to the Flickr photo-sharing website. Inspired by the theory of Lévy flights, which has previously been used to describe the statistical properties of human mobility, we design a machine learning algorithm to infer the probability of finding people in geographical locations and the probability of movement between pairs of locations. Our findings are in general agreement with official figures in the UK and on travel flows between pairs of major cities, suggesting that online data sources may be used to quantify and model large-scale human mobility patterns.

  14. Modelling human mobility patterns using photographic data shared online

    PubMed Central

    Barchiesi, Daniele; Preis, Tobias; Bishop, Steven; Moat, Helen Susannah

    2015-01-01

    Humans are inherently mobile creatures. The way we move around our environment has consequences for a wide range of problems, including the design of efficient transportation systems and the planning of urban areas. Here, we gather data about the position in space and time of about 16 000 individuals who uploaded geo-tagged images from locations within the UK to the Flickr photo-sharing website. Inspired by the theory of Lévy flights, which has previously been used to describe the statistical properties of human mobility, we design a machine learning algorithm to infer the probability of finding people in geographical locations and the probability of movement between pairs of locations. Our findings are in general agreement with official figures in the UK and on travel flows between pairs of major cities, suggesting that online data sources may be used to quantify and model large-scale human mobility patterns. PMID:26361545

  15. A Model of Representational Spaces in Human Cortex.

    PubMed

    Guntupalli, J Swaroop; Hanke, Michael; Halchenko, Yaroslav O; Connolly, Andrew C; Ramadge, Peter J; Haxby, James V

    2016-06-01

    Current models of the functional architecture of human cortex emphasize areas that capture coarse-scale features of cortical topography but provide no account for population responses that encode information in fine-scale patterns of activity. Here, we present a linear model of shared representational spaces in human cortex that captures fine-scale distinctions among population responses with response-tuning basis functions that are common across brains and models cortical patterns of neural responses with individual-specific topographic basis functions. We derive a common model space for the whole cortex using a new algorithm, searchlight hyperalignment, and complex, dynamic stimuli that provide a broad sampling of visual, auditory, and social percepts. The model aligns representations across brains in occipital, temporal, parietal, and prefrontal cortices, as shown by between-subject multivariate pattern classification and intersubject correlation of representational geometry, indicating that structural principles for shared neural representations apply across widely divergent domains of information. The model provides a rigorous account for individual variability of well-known coarse-scale topographies, such as retinotopy and category selectivity, and goes further to account for fine-scale patterns that are multiplexed with coarse-scale topographies and carry finer distinctions.

  16. Malarial birds: modeling infectious human disease in animals.

    PubMed

    Slater, Leo B

    2005-01-01

    Through the examination of avian malarias as models of infectious human disease, this paper reveals the kinds of claims that scientists and physicians made on the basis of animal models-biological systems in the laboratory and the field-and what characteristics made for congruence between these models and human malaria. The focus is on the period between 1895 and 1945, and on the genesis and trajectory of certain animal models of malaria within specific locations, such as the Johns Hopkins School of Hygiene and Public Health in Baltimore and Bayer (I. G. Farben) in Elberfeld. These exemplars illustrate a diversity of approaches to malaria-as-disease, and the difficulties of framing aspects of this disease complex within an animal or laboratory system. The diversity and nearness to wild types of the birds, protozoan parasites, and mosquitoes that made up these malaria models contributed a great deal to the complexity of the models. Avian malarias, adopted with enthusiasm, were essential to the success of the U.S. antimalarial program during World War II.

  17. A Model of Representational Spaces in Human Cortex

    PubMed Central

    Guntupalli, J. Swaroop; Hanke, Michael; Halchenko, Yaroslav O.; Connolly, Andrew C.; Ramadge, Peter J.; Haxby, James V.

    2016-01-01

    Current models of the functional architecture of human cortex emphasize areas that capture coarse-scale features of cortical topography but provide no account for population responses that encode information in fine-scale patterns of activity. Here, we present a linear model of shared representational spaces in human cortex that captures fine-scale distinctions among population responses with response-tuning basis functions that are common across brains and models cortical patterns of neural responses with individual-specific topographic basis functions. We derive a common model space for the whole cortex using a new algorithm, searchlight hyperalignment, and complex, dynamic stimuli that provide a broad sampling of visual, auditory, and social percepts. The model aligns representations across brains in occipital, temporal, parietal, and prefrontal cortices, as shown by between-subject multivariate pattern classification and intersubject correlation of representational geometry, indicating that structural principles for shared neural representations apply across widely divergent domains of information. The model provides a rigorous account for individual variability of well-known coarse-scale topographies, such as retinotopy and category selectivity, and goes further to account for fine-scale patterns that are multiplexed with coarse-scale topographies and carry finer distinctions. PMID:26980615

  18. Human models of pain for the prediction of clinical analgesia.

    PubMed

    Lötsch, Jörn; Oertel, Bruno G; Ultsch, Alfred

    2014-10-01

    Human experimental pain models are widely used to study drug effects under controlled conditions. However, efforts to improve both animal and human experimental model selection, on the basis of increased understanding of the underlying pathophysiological pain mechanisms, have been disappointing, with poor translation of results to clinical analgesia. We have developed an alternative approach to the selection of suitable pain models that can correctly predict drug efficacy in particular clinical settings. This is based on the analysis of successful or unsuccessful empirical prediction of clinical analgesia using experimental pain models. We analyzed statistically the distribution of published mutual agreements or disagreements between drug efficacy in experimental and clinical pain settings. Significance limits were derived by random permutations of agreements. We found that a limited subset of pain models predicts a large number of clinically relevant pain settings, including efficacy against neuropathic pain for which novel analgesics are particularly needed. Thus, based on empirical evidence of agreement between drugs for their efficacy in experimental and clinical pain settings, it is possible to identify pain models that reliably predict clinical analgesic drug efficacy in cost-effective experimental settings.

  19. Development and implication of a human-volcano system model

    NASA Astrophysics Data System (ADS)

    Bachri, Syamsul; Stötter, Johann; Monreal, Matthias; Sartohadi, Junun

    2014-05-01

    In an attempt to understand the complexity of human-environment systems, models help to define, quantify, describe, or simulate complex interactions. With regards to the human-volcano system, we develop a conceptual model in order to assist analysis of its two basic elements, the physical and the social environment. A field survey of the human environment interaction of two of the most active volcanic areas in Indonesia (Mt. Merapi and Mt. Bromo) and a corresponding literature review from other case studies was carried out. A differentiated understanding of human interaction with hazard potential elements within the human-volcano system is the main focus of the model development. We classified volcanic processes and effects as three pairs of dichotomies: positive or negative impacts, on society or environment in an indirect or direct way. Each volcanically induced process or effect characterized accordingly leads to eight distinct process/effect classes. They are positive direct effects on society (PDS); positive direct effects on natural resources (PDN); positive indirect effects on society (PIS); positive indirect effects on natural resources (PIN); negative direct effects on society (NDS); negative direct effects on natural resources (NDN); negative indirect effects on society (NIS) and lastly negative indirect effects on natural resources (NIN). Such differentiated view of volcanic process/effects bears several advantages. First, whereas volcanic processes have hitherto been viewed as hazards only, it becomes possible now to describe a particular process/effect in a particular context as negative or positive. Secondly, such a categorization makes it possible to account for processes of the human-volcano system that do not have a direct physical expression but are of socio-cultural relevance. Thirdly, the greater degree of differentiation that is made possible when evaluating volcanic processes has significant repercussions on the way volcanic risk must be

  20. All-human microphysical model of metastasis therapy.

    PubMed

    Wheeler, Sarah E; Borenstein, Jeffrey T; Clark, Amanda M; Ebrahimkhani, Mohammad R; Fox, Ira J; Griffith, Linda; Inman, Walker; Lauffenburger, Douglas; Nguyen, Transon; Pillai, Venkateswaran C; Prantil-Baun, Rachelle; Stolz, Donna B; Taylor, Donald; Ulrich, Theresa; Venkataramanan, Raman; Wells, Alan; Young, Carissa

    2013-01-01

    The vast majority of cancer mortalities result from distant metastases. The metastatic microenvironment provides unique protection to ectopic tumors as the primary tumors often respond to specific agents. Although significant interventional progress has been made on primary tumors, the lack of relevant accessible model in vitro systems in which to study metastases has plagued metastatic therapeutic development--particularly among micrometastases. A real-time, all-human model of metastatic seeding and cancer cells that recapitulate metastatic growth and can be probed in real time by a variety of measures and challenges would provide a critical window into the pathophysiology of metastasis and pharmacology of metastatic tumor resistance. To achieve this we are advancing our microscale bioreactor that incorporates human hepatocytes, human nonparenchymal liver cells, and human breast cancer cells to mimic the hepatic niche in three dimensions with functional tissue. This bioreactor is instrumented with oxygen sensors, micropumps capable of generating diurnally varying profiles of nutrients and hormones, while enabling real-time sampling. Since the liver is a major metastatic site for a wide variety of carcinomas and other tumors, this bioreactor uniquely allows us to more accurately recreate the human metastatic microenvironment and probe the paracrine effects between the liver parenchyma and metastatic cells. Further, as the liver is the principal site of xenobiotic metabolism, this reactor will help us investigate the chemotherapeutic response within a metabolically challenged liver microenvironment. This model is anticipated to yield markers of metastatic behavior and pharmacologic metabolism that will enable better clinical monitoring, and will guide the design of clinical studies to understand drug efficacy and safety in cancer therapeutics. This highly instrumented bioreactor format, hosting a growing tumor within a microenvironment and monitoring its responses

  1. Marmosets: A Neuroscientific Model of Human Social Behavior.

    PubMed

    Miller, Cory T; Freiwald, Winrich A; Leopold, David A; Mitchell, Jude F; Silva, Afonso C; Wang, Xiaoqin

    2016-04-20

    The common marmoset (Callithrix jacchus) has garnered interest recently as a powerful model for the future of neuroscience research. Much of this excitement has centered on the species' reproductive biology and compatibility with gene editing techniques, which together have provided a path for transgenic marmosets to contribute to the study of disease as well as basic brain mechanisms. In step with technical advances is the need to establish experimental paradigms that optimally tap into the marmosets' behavioral and cognitive capacities. While conditioned task performance of a marmoset can compare unfavorably with rhesus monkey performance on conventional testing paradigms, marmosets' social behavior and cognition are more similar to that of humans. For example, marmosets are among only a handful of primates that, like humans, routinely pair bond and care cooperatively for their young. They are also notably pro-social and exhibit social cognitive abilities, such as imitation, that are rare outside of the Apes. In this Primer, we describe key facets of marmoset natural social behavior and demonstrate that emerging behavioral paradigms are well suited to isolate components of marmoset cognition that are highly relevant to humans. These approaches generally embrace natural behavior, which has been rare in conventional primate testing, and thus allow for a new consideration of neural mechanisms underlying primate social cognition and signaling. We anticipate that through parallel technical and paradigmatic advances, marmosets will become an essential model of human social behavior, including its dysfunction in neuropsychiatric disorders.

  2. Learning atomic human actions using variable-length Markov models.

    PubMed

    Liang, Yu-Ming; Shih, Sheng-Wen; Shih, Arthur Chun-Chieh; Liao, Hong-Yuan Mark; Lin, Cheng-Chung

    2009-02-01

    Visual analysis of human behavior has generated considerable interest in the field of computer vision because of its wide spectrum of potential applications. Human behavior can be segmented into atomic actions, each of which indicates a basic and complete movement. Learning and recognizing atomic human actions are essential to human behavior analysis. In this paper, we propose a framework for handling this task using variable-length Markov models (VLMMs). The framework is comprised of the following two modules: a posture labeling module and a VLMM atomic action learning and recognition module. First, a posture template selection algorithm, based on a modified shape context matching technique, is developed. The selected posture templates form a codebook that is used to convert input posture sequences into discrete symbol sequences for subsequent processing. Then, the VLMM technique is applied to learn the training symbol sequences of atomic actions. Finally, the constructed VLMMs are transformed into hidden Markov models (HMMs) for recognizing input atomic actions. This approach combines the advantages of the excellent learning function of a VLMM and the fault-tolerant recognition ability of an HMM. Experiments on realistic data demonstrate the efficacy of the proposed system.

  3. Marmosets: A Neuroscientific Model of Human Social Behavior.

    PubMed

    Miller, Cory T; Freiwald, Winrich A; Leopold, David A; Mitchell, Jude F; Silva, Afonso C; Wang, Xiaoqin

    2016-04-20

    The common marmoset (Callithrix jacchus) has garnered interest recently as a powerful model for the future of neuroscience research. Much of this excitement has centered on the species' reproductive biology and compatibility with gene editing techniques, which together have provided a path for transgenic marmosets to contribute to the study of disease as well as basic brain mechanisms. In step with technical advances is the need to establish experimental paradigms that optimally tap into the marmosets' behavioral and cognitive capacities. While conditioned task performance of a marmoset can compare unfavorably with rhesus monkey performance on conventional testing paradigms, marmosets' social behavior and cognition are more similar to that of humans. For example, marmosets are among only a handful of primates that, like humans, routinely pair bond and care cooperatively for their young. They are also notably pro-social and exhibit social cognitive abilities, such as imitation, that are rare outside of the Apes. In this Primer, we describe key facets of marmoset natural social behavior and demonstrate that emerging behavioral paradigms are well suited to isolate components of marmoset cognition that are highly relevant to humans. These approaches generally embrace natural behavior, which has been rare in conventional primate testing, and thus allow for a new consideration of neural mechanisms underlying primate social cognition and signaling. We anticipate that through parallel technical and paradigmatic advances, marmosets will become an essential model of human social behavior, including its dysfunction in neuropsychiatric disorders. PMID:27100195

  4. Development of biomechanical models for human factors evaluations

    NASA Technical Reports Server (NTRS)

    Woolford, Barbara; Pandya, Abhilash; Maida, James

    1993-01-01

    Computer aided design (CAD) techniques are now well established and have become the norm in many aspects of aerospace engineering. They enable analytical studies, such as finite element analysis, to be performed to measure performance characteristics of the aircraft or spacecraft long before a physical model is built. However, because of the complexity of human performance, CAD systems for human factors are not in widespread use. The purpose of such a program would be to analyze the performance capability of a crew member given a particular environment and task. This requires the design capabilities to describe the environment's geometry and to describe the task's requirements, which may involve motion and strength. This in turn requires extensive data on human physical performance which can be generalized to many different physical configurations. PLAID is developing into such a program. Begun at Johnson Space Center in 1977, it was started to model only the geometry of the environment. The physical appearance of a human body was generated, and the tool took on a new meaning as fit, access, and reach could be checked. Specification of fields-of-view soon followed. This allowed PLAID to be used to predict what the Space Shuttle cameras or crew could see from a given point.

  5. Exploring host–microbiota interactions in animal models and humans

    PubMed Central

    Kostic, Aleksandar D.; Howitt, Michael R.; Garrett, Wendy S.

    2013-01-01

    The animal and bacterial kingdoms have coevolved and coadapted in response to environmental selective pressures over hundreds of millions of years. The meta'omics revolution in both sequencing and its analytic pipelines is fostering an explosion of interest in how the gut microbiome impacts physiology and propensity to disease. Gut microbiome studies are inherently interdisciplinary, drawing on approaches and technical skill sets from the biomedical sciences, ecology, and computational biology. Central to unraveling the complex biology of environment, genetics, and microbiome interaction in human health and disease is a deeper understanding of the symbiosis between animals and bacteria. Experimental model systems, including mice, fish, insects, and the Hawaiian bobtail squid, continue to provide critical insight into how host–microbiota homeostasis is constructed and maintained. Here we consider how model systems are influencing current understanding of host–microbiota interactions and explore recent human microbiome studies. PMID:23592793

  6. Image-based modeling of the human eye.

    PubMed

    François, Guillaume; Gautron, Pascal; Breton, Gaspard; Bouatouch, Kadi

    2009-01-01

    Rendering realistic organic materials is a challenging issue. The human eye is an important part of nonverbal communication which, consequently, requires specific modeling and rendering techniques to enhance the realism of virtual characters. We propose an image-based method for estimating both iris morphology and scattering features in order to generate convincing images of virtual eyes. In this regard, we develop a technique to unrefract iris photographs. We model the morphology of the human iris as an irregular multilayered tissue. We then approximate the scattering features of the captured iris. Finally, we propose a real-time rendering technique based on the subsurface texture mapping representation and introduce a precomputed refraction function as well as a caustic function, which accounts for the light interactions at the corneal interface. PMID:19590107

  7. Zebrafish Models of Human Liver Development and Disease

    PubMed Central

    Wilkins, Benjamin J.; Pack, Michael

    2016-01-01

    The liver performs a large number of essential synthetic and regulatory functions that are acquired during fetal development and persist throughout life. Their disruption underlies a diverse group of heritable and acquired diseases that affect both pediatric and adult patients. Although experimental analyses used to study liver development and disease are typically performed in cell culture models or rodents, the zebrafish is increasingly used to complement discoveries made in these systems. Forward and reverse genetic analyses over the past two decades have shown that the molecular program for liver development is largely conserved between zebrafish and mammals, and that the zebrafish can be used to model heritable human liver disorders. Recent work has demonstrated that zebrafish can also be used to study the mechanistic basis of acquired liver diseases. Here, we provide a comprehensive summary of how the zebrafish has contributed to our understanding of human liver development and disease. PMID:23897685

  8. Modeling of human movement monitoring using Bluetooth Low Energy technology.

    PubMed

    Mokhtari, G; Zhang, Q; Karunanithi, M

    2015-01-01

    Bluetooth Low Energy (BLE) is a wireless communication technology which can be used to monitor human movements. In this monitoring system, a BLE signal scanner scans signal strength of BLE tags carried by people, to thus infer human movement patterns within its monitoring zone. However to the extent of our knowledge one main aspect of this monitoring system which has not yet been thoroughly investigated in literature is how to build a sound theoretical model, based on tunable BLE communication parameters such as scanning time interval and advertising time interval, to enable the study and design of effective and efficient movement monitoring systems. In this paper, we proposed and developed a statistical model based on Monte-Carlo simulation, which can be utilized to assess impacts of BLE technology parameters in terms of latency and efficiency, on a movement monitoring system, and can thus benefit a more efficient system design.

  9. Subject-specific computational modeling of human phonation

    PubMed Central

    Xue, Qian; Zheng, Xudong; Mittal, Rajat; Bielamowicz, Steven

    2014-01-01

    A direct numerical simulation of flow-structure interaction is carried out in a subject-specific larynx model to study human phonation under physiological conditions. The simulation results compare well to the established human data. The resulting glottal flow and waveform are found to be within the normal physiological ranges. The effects of realistic geometry on the vocal fold dynamics and the glottal flow are extensively examined. It is found that the asymmetric anterior-posterior laryngeal configuration produces strong anterior-posterior asymmetries in both vocal fold vibration and glottal flow which has not been captured in the simplified models. It needs to be pointed out that the observations from the current numerical simulation are only valid for the flow conditions investigated. The limitations of the study are also discussed. PMID:24606281

  10. Modeling of human movement monitoring using Bluetooth Low Energy technology.

    PubMed

    Mokhtari, G; Zhang, Q; Karunanithi, M

    2015-01-01

    Bluetooth Low Energy (BLE) is a wireless communication technology which can be used to monitor human movements. In this monitoring system, a BLE signal scanner scans signal strength of BLE tags carried by people, to thus infer human movement patterns within its monitoring zone. However to the extent of our knowledge one main aspect of this monitoring system which has not yet been thoroughly investigated in literature is how to build a sound theoretical model, based on tunable BLE communication parameters such as scanning time interval and advertising time interval, to enable the study and design of effective and efficient movement monitoring systems. In this paper, we proposed and developed a statistical model based on Monte-Carlo simulation, which can be utilized to assess impacts of BLE technology parameters in terms of latency and efficiency, on a movement monitoring system, and can thus benefit a more efficient system design. PMID:26737430

  11. A topological multilayer model of the human body.

    PubMed

    Barbeito, Antonio; Painho, Marco; Cabral, Pedro; O'Neill, João

    2015-11-04

    Geographical information systems deal with spatial databases in which topological models are described with alphanumeric information. Its graphical interfaces implement the multilayer concept and provide powerful interaction tools. In this study, we apply these concepts to the human body creating a representation that would allow an interactive, precise, and detailed anatomical study. A vector surface component of the human body is built using a three-dimensional (3-D) reconstruction methodology. This multilayer concept is implemented by associating raster components with the corresponding vector surfaces, which include neighbourhood topology enabling spatial analysis. A root mean square error of 0.18 mm validated the three-dimensional reconstruction technique of internal anatomical structures. The expansion of the identification and the development of a neighbourhood analysis function are the new tools provided in this model.

  12. A biokinetic model for systemic technetium in adult humans.

    PubMed

    Leggett, R; Giussani, A

    2015-06-01

    This paper reviews biokinetic data for technetium and proposes a biokinetic model for systemic technetium in adult humans. The development of parameter values focuses on data for pertechnetate TcO(-)(4) the most commonly encountered form of technetium and the form expected to be present in body fluids. The model is intended as a default model for occupational or environmental intake of technetium, i.e. applicable in the absence of form- or site-specific information. Tissues depicted explicitly in the model include thyroid, salivary glands, stomach wall, right colon wall, liver, kidneys, and bone. Compared with the ICRP's current biokinetic model for occupational or environmental intake of technetium (ICRP 1993, 1994), the proposed model provides a more detailed and biologically realistic description of the systemic behaviour of technetium and is based on a broader set of experimental and medical data. For acute input of (99m)Tc (T(1/2) = 6.02 h) to blood, the ratios of cumulative (time-integrated) activity predicted by the current ICRP model to that predicted by the proposed model range from 0.4-7 for systemic regions addressed explicitly in both models. For acute input of (99)Tc (T(1/2) = 2.1 × 10(5) year) to blood, the corresponding ratios range from 0.2-30.

  13. A continuous fiber distribution material model for human cervical tissue.

    PubMed

    Myers, Kristin M; Hendon, Christine P; Gan, Yu; Yao, Wang; Yoshida, Kyoko; Fernandez, Michael; Vink, Joy; Wapner, Ronald J

    2015-06-25

    The uterine cervix during pregnancy is the vital mechanical barrier which resists compressive and tensile loads generated from a growing fetus. Premature cervical remodeling and softening is hypothesized to result in the shortening of the cervix, which is known to increase a woman׳s risk of preterm birth. To understand the role of cervical material properties in preventing preterm birth, we derive a cervical material model based on previous mechanical, biochemical and histological experiments conducted on nonpregnant and pregnant human hysterectomy cervical tissue samples. In this study we present a three-dimensional fiber composite model that captures the equilibrium material behavior of the tissue in tension and compression. Cervical tissue is modeled as a fibrous composite material, where a single family of preferentially aligned and continuously distributed collagen fibers are embedded in a compressible neo-Hookean ground substance. The total stress in the collagen solid network is calculated by integrating the fiber stresses. The shape of the fiber distribution is described by an ellipsoid where semi-principal axis lengths are fit to optical coherence tomography measurements. The composite material model is fit to averaged mechanical testing data from uni-axial compression and tension experiments, and averaged material parameters are reported for nonpregnant and term pregnant human cervical tissue. The model is then evaluated by investigating the stress and strain state of a uniform thick-walled cylinder under a compressive stress with collagen fibers preferentially aligned in the circumferential direction. This material modeling framework for the equilibrium behavior of human cervical tissue serves as a basis to determine the role of preferentially-aligned cervical collagen fibers in preventing cervical deformation during pregnancy.

  14. Model systems of human papillomavirus-associated disease.

    PubMed

    Doorbar, John

    2016-01-01

    Human papillomaviruses (HPVs) cause a range of serious diseases, including the vast majority of cervical cancers, most anal cancers and around half of head and neck cancers. They are also responsible for troublesome benign epithelial lesions, including genital warts and laryngeal papillomas, and in some individuals HPVs lead to recurrent respiratory papillomatosis and other difficult-to-manage diseases. As a result, there is a great need for model systems that accurately mimic papillomavirus infections in humans. This is complicated by the diverse variety of HPVs, which now number over 200 types, and the different strategies they have evolved to persist in the population. The most well-developed models involve the culture of HPV-containing keratinocytes in organotypic raft culture, an approach which appears to accurately mimic the life cycle of several of the high-risk cancer-associated HPV types. Included amongst these are HPV16 and 18, which cause the majority of cervical cancers. The low-risk HPV types persist less well in tissue-culture models, and our ability to study the productive life cycle of these viruses is more limited. Although ongoing research is likely to improve this situation, animal models of papillomavirus disease can provide considerable basic information as to how lesions form, regress and can be controlled by the immune system. The best studied are cottontail rabbit papillomavirus, rabbit oral papillomavirus and, more recently, mouse papillomavirus (MmuPV), the last of which is providing exciting new insights into viral tropisms and immune control. In addition, transgenic models of disease have helped us to understand the consequences of persistent viral gene expression and the importance of co-factors such as hormones and UV irradiation in the development of neoplasia and cancer. It is hoped that such disease models will eventually lead us to better understanding and better treatments for human disease. PMID:26456009

  15. Tissue-engineered microenvironment systems for modeling human vasculature.

    PubMed

    Tourovskaia, Anna; Fauver, Mark; Kramer, Gregory; Simonson, Sara; Neumann, Thomas

    2014-09-01

    The high attrition rate of drug candidates late in the development process has led to an increasing demand for test assays that predict clinical outcome better than conventional 2D cell culture systems and animal models. Government agencies, the military, and the pharmaceutical industry have started initiatives for the development of novel in-vitro systems that recapitulate functional units of human tissues and organs. There is growing evidence that 3D cell arrangement, co-culture of different cell types, and physico-chemical cues lead to improved predictive power. A key element of all tissue microenvironments is the vasculature. Beyond transporting blood the microvasculature assumes important organ-specific functions. It is also involved in pathologic conditions, such as inflammation, tumor growth, metastasis, and degenerative diseases. To provide a tool for modeling this important feature of human tissue microenvironments, we developed a microfluidic chip for creating tissue-engineered microenvironment systems (TEMS) composed of tubular cell structures. Our chip design encompasses a small chamber that is filled with an extracellular matrix (ECM) surrounding one or more tubular channels. Endothelial cells (ECs) seeded into the channels adhere to the ECM walls and grow into perfusable tubular tissue structures that are fluidically connected to upstream and downstream fluid channels in the chip. Using these chips we created models of angiogenesis, the blood-brain barrier (BBB), and tumor-cell extravasation. Our angiogenesis model recapitulates true angiogenesis, in which sprouting occurs from a "parent" vessel in response to a gradient of growth factors. Our BBB model is composed of a microvessel generated from brain-specific ECs within an ECM populated with astrocytes and pericytes. Our tumor-cell extravasation model can be utilized to visualize and measure tumor-cell migration through vessel walls into the surrounding matrix. The described technology can be used

  16. Model systems of human papillomavirus-associated disease.

    PubMed

    Doorbar, John

    2016-01-01

    Human papillomaviruses (HPVs) cause a range of serious diseases, including the vast majority of cervical cancers, most anal cancers and around half of head and neck cancers. They are also responsible for troublesome benign epithelial lesions, including genital warts and laryngeal papillomas, and in some individuals HPVs lead to recurrent respiratory papillomatosis and other difficult-to-manage diseases. As a result, there is a great need for model systems that accurately mimic papillomavirus infections in humans. This is complicated by the diverse variety of HPVs, which now number over 200 types, and the different strategies they have evolved to persist in the population. The most well-developed models involve the culture of HPV-containing keratinocytes in organotypic raft culture, an approach which appears to accurately mimic the life cycle of several of the high-risk cancer-associated HPV types. Included amongst these are HPV16 and 18, which cause the majority of cervical cancers. The low-risk HPV types persist less well in tissue-culture models, and our ability to study the productive life cycle of these viruses is more limited. Although ongoing research is likely to improve this situation, animal models of papillomavirus disease can provide considerable basic information as to how lesions form, regress and can be controlled by the immune system. The best studied are cottontail rabbit papillomavirus, rabbit oral papillomavirus and, more recently, mouse papillomavirus (MmuPV), the last of which is providing exciting new insights into viral tropisms and immune control. In addition, transgenic models of disease have helped us to understand the consequences of persistent viral gene expression and the importance of co-factors such as hormones and UV irradiation in the development of neoplasia and cancer. It is hoped that such disease models will eventually lead us to better understanding and better treatments for human disease.

  17. A Revised Model for Dosimetry in the Human Small Intestine

    SciTech Connect

    John Poston; Nasir U. Bhuiyan; R. Alex Redd; Neil Parham; Jennifer Watson

    2005-02-28

    A new model for an adult human gastrointestinal tract (GIT) has been developed for use in internal dose estimations to the wall of the GIT and to the other organs and tissues of the body from radionuclides deposited in the lumenal contents of the five sections of the GIT. These sections were the esophasgus, stomach, small intestine, upper large intestine, and the lower large intestine. The wall of each section was separated from its lumenal contents.

  18. Mechanisms and Genes in Human Strial Presbycusis from Animal Models

    PubMed Central

    Ohlemiller, Kevin K.

    2009-01-01

    Schuknecht proposed a discrete form of presbycusis in which hearing loss results principally from degeneration of cochlear stria vascularis and decline of the endocochlear potential (EP). This form was asserted to be genetically linked, and to arise independently from age-related pathology of either the organ of Corti or cochlear neurons. Although extensive strial degeneration in humans coincides with hearing loss, EPs have never been measured in humans, and age-related EP reduction has never been verified. No human genes that promote strial presbycusis have been identified, nor is its pathophysiology well understood. Effective application of animal models to this issue requires models demonstrating EP decline, and preferably, genetically distinct strains that vary in patterns of EP decline and its cellular correlates. Until recently, only two models, Mongolian gerbils and Tyrp1B-lt mice, were known to undergo age-associated EP reduction. Detailed studies of seven inbred mouse strains have now revealed three strains (C57BL/6J, B6.CAST-Cdh23CAST, CBA/J) showing essentially no EP decline with age, and four strains ranging from modest to severe EP reduction (C57BL/6-Tyrc-2J, BALB/cJ, CBA/CaJ, NOD.NON-H2nbl/LtJ). Collectively, animal models support five basic principles regarding a strial form of presbycusis: 1) Progressive EP decline from initially normal levels as a defining characteristic; 2) Non-universality, not all age-associated hearing loss involves EP decline; 3) A clear genetic basis; 4) Modulation by environment or stochastic events; and 5) Independent strial, organ of Corti, and neural pathology. Shared features between human strial presbycusis, gerbils, and BALB/cJ and C57BL/6-Tyrc-2J mice further suggest this condition frequently begins with strial marginal cell dysfunction and loss. By contrast, NOD.NON-H2nbl mice may model a sequence more closely associated with strial microvascular disease. Additional studies of these and other inbred mouse and rat

  19. Image Watermarking Based on Adaptive Models of Human Visual Perception

    NASA Astrophysics Data System (ADS)

    Khawne, Amnach; Hamamoto, Kazuhiko; Chitsobhuk, Orachat

    This paper proposes a digital image watermarking based on adaptive models of human visual perception. The algorithm exploits the local activities estimated from wavelet coefficients of each subband to adaptively control the luminance masking. The adaptive luminance is thus delicately combined with the contrast masking and edge detection and adopted as a visibility threshold. With the proposed combination of adaptive visual sensitivity parameters, the proposed perceptual model can be more appropriate to the different characteristics of various images. The weighting function is chosen such that the fidelity, imperceptibility and robustness could be preserved without making any perceptual difference to the image quality.

  20. The anisotropic material constitutive models for the human cornea.

    PubMed

    Li, Long-yuan; Tighe, Brian

    2006-03-01

    This paper presents an anisotropic analysis model for the human cornea. The model is based on the assumption that the fibrils in the cornea are organised into lamellae, which may have preferential orientation along the superior-inferior and nasal-temporal directions, while the alignment of lamellae with different orientations is assumed to be random. Hence, the cornea can be regarded as a laminated composite shell. The constitutive equation describing the relationships between membrane forces, bending moments, and membrane strains, bending curvatures are derived. The influences of lamella orientations and the random alignment of lamellae on the stiffness coefficients of the constitutive equation are discussed. PMID:16426861

  1. Experimental performance evaluation of human balance control models.

    PubMed

    Huryn, Thomas P; Blouin, Jean-Sébastien; Croft, Elizabeth A; Koehle, Michael S; Van der Loos, H F Machiel

    2014-11-01

    Two factors commonly differentiate proposed balance control models for quiet human standing: 1) intermittent muscle activation and 2) prediction that overcomes sensorimotor time delays. In this experiment we assessed the viability and performance of intermittent activation and prediction in a balance control loop that included the neuromuscular dynamics of human calf muscles. Muscles were driven by functional electrical stimulation (FES). The performance of the different controllers was compared based on sway patterns and mechanical effort required to balance a human body load on a robotic balance simulator. All evaluated controllers balanced subjects with and without a neural block applied to their common peroneal and tibial nerves, showing that the models can produce stable balance in the absence of natural activation. Intermittent activation required less stimulation energy than continuous control but predisposed the system to increased sway. Relative to intermittent control, continuous control reproduced the sway size of natural standing better. Prediction was not necessary for stable balance control but did improve stability when control was intermittent, suggesting a possible benefit of a predictor for intermittent activation. Further application of intermittent activation and predictive control models may drive prolonged, stable FES-controlled standing that improves quality of life for people with balance impairments. PMID:24771586

  2. A novel in vitro human microglia model: characterization of human monocyte-derived microglia.

    PubMed

    Etemad, Samar; Zamin, Rasheeda Mohd; Ruitenberg, Marc J; Filgueira, Luis

    2012-07-30

    Microglia are the innate immune cells of the central nervous system. They help maintaining physiological homeostasis and contribute significantly to inflammatory responses in the course of infection, injury and degenerative processes. To date, there is no standardized simple model available to investigate the biology of human microglia. The aim of this study was to establish a new human microglia model. For that purpose, human peripheral blood monocytes were cultured in serum free medium in the presence of M-CSF, GM-CSF, NGF and CCL2 to generate monocyte-derived microglia (M-MG). M-MG were clearly different in morphology, phenotype and function from freshly isolated monocytes, cultured monocytes in the absence of the cytokines and monocyte-derived dendritic cells (M-DC) cultured in the presence of GM-CSF and IL-4. M-MG acquired a ramified morphology with primary and secondary processes. M-MG displayed a comparable phenotype to the human microglia cell line HMC3, expressing very low levels of CD45, CD14 and HLA-DR, CD11b and CD11c; and undetectable levels of CD40, CD80 and CD83, and a distinct pattern of chemokine receptors (positive for CCR1, CCR2, CCR4, CCR5, CXCR1, CXCR3, CX3CR1; negative for CCR6 and CCR7). In comparison with M-DC, M-MG displayed lower T-lymphocyte stimulatory capacity, as well as lower phagocytosis activity. The described protocol for the generation of human monocyte-derived microglia is feasible, well standardized and reliable, as it uses well defined culture medium and recombinant cytokines, but no serum or conditioned medium. This protocol will certainly be very helpful for future studies investigating the biology and pathology of human microglia. PMID:22659341

  3. Modeling and percept of transcorneal electrical stimulation in humans.

    PubMed

    Xie, John; Wang, Gene-Jack; Yow, Lindy; J Cela, Carlos; Humayun, Mark S; Weiland, James D; Lazzi, Gianluca; Jadvar, Hossein

    2011-07-01

    Retinal activation via transcorneal electrical stimulation (TcES) in normal humans was investigated by comparing subject perception, model predictions, and brain activation patterns. The preferential location of retinal stimulation was predicted from 3-D admittance modeling. Visual cortex activation was measured using positron emission tomography (PET) and (18)F-fluorodeoxyglucose (FDG). Two different corneal electrodes were investigated: DTL-Plus and ERG-Jet. Modeling results predicted preferential stimulation of the peripheral, inferior, nasal retina during right eye TcES using DTL-Plus, but more extensive activation of peripheral, nasal hemiretina using ERG-Jet. The results from human FDG PET study using both corneal electrodes showed areas of visual cortex activation that consistently corresponded with the reported phosphene percept and modeling predictions. ERG-Jet was able to generate brighter phosphene percept than DTL-Plus and elicited retinotopically mapped primary visual cortex activation. This study demonstrates that admittance modeling and PET imaging consistently predict the perceived location of electrically elicited phosphenes produced during TcES.

  4. Validation of a finite element model of the human metacarpal.

    PubMed

    Barker, D S; Netherway, D J; Krishnan, J; Hearn, T C

    2005-03-01

    Implant loosening and mechanical failure of components are frequently reported following metacarpophalangeal (MCP) joint replacement. Studies of the mechanical environment of the MCP implant-bone construct are rare. The objective of this study was to evaluate the predictive ability of a finite element model of the intact second human metacarpal to provide a validated baseline for further mechanical studies. A right index human metacarpal was subjected to torsion and combined axial/bending loading using strain gauge (SG) and 3D finite element (FE) analysis. Four different representations of bone material properties were considered. Regression analyses were performed comparing maximum and minimum principal surface strains taken from the SG and FE models. Regression slopes close to unity and high correlation coefficients were found when the diaphyseal cortical shell was modelled as anisotropic and cancellous bone properties were derived from quantitative computed tomography. The inclusion of anisotropy for cortical bone was strongly influential in producing high model validity whereas variation in methods of assigning stiffness to cancellous bone had only a minor influence. The validated FE model provides a tool for future investigations of current and novel MCP joint prostheses.

  5. Building a Shared Definitional Model of Long Duration Human Spaceflight

    NASA Technical Reports Server (NTRS)

    Orr, M.; Whitmire, A.; Sandoval, L.; Leveton, L.; Arias, D.

    2011-01-01

    In 1956, on the eve of human space travel Strughold first proposed a simple classification of the present and future stages of manned flight that identified key factors, risks and developmental stages for the evolutionary journey ahead. As we look to optimize the potential of the ISS as a gateway to new destinations, we need a current shared working definitional model of long duration human space flight to help guide our path. Initial search of formal and grey literature augmented by liaison with subject matter experts. Search strategy focused on both the use of term long duration mission and long duration spaceflight, and also broader related current and historical definitions and classification models of spaceflight. The related sea and air travel literature was also subsequently explored with a view to identifying analogous models or classification systems. There are multiple different definitions and classification systems for spaceflight including phase and type of mission, craft and payload and related risk management models. However the frequently used concepts of long duration mission and long duration spaceflight are infrequently operationally defined by authors, and no commonly referenced classical or gold standard definition or model of these terms emerged from the search. The categorization (Cat) system for sailing was found to be of potential analogous utility, with its focus on understanding the need for crew and craft autonomy at various levels of potential adversity and inability to gain outside support or return to a safe location, due to factors of time, distance and location.

  6. An anatomical and functional model of the human tracheobronchial tree.

    PubMed

    Florens, M; Sapoval, B; Filoche, M

    2011-03-01

    The human tracheobronchial tree is a complex branched distribution system in charge of renewing the air inside the acini, which are the gas exchange units. We present here a systematic geometrical model of this system described as a self-similar assembly of rigid pipes. It includes the specific geometry of the upper bronchial tree and a self-similar intermediary tree with a systematic branching asymmetry. It ends by the terminal bronchioles whose generations range from 8 to 22. Unlike classical models, it does not rely on a simple scaling law. With a limited number of parameters, this model reproduces the morphometric data from various sources (Horsfield K, Dart G, Olson DE, Filley GF, Cumming G. J Appl Physiol 31: 207-217, 1971; Weibel ER. Morphometry of the Human Lung. New York: Academic Press, 1963) and the main characteristics of the ventilation. Studying various types of random variations of the airway sizes, we show that strong correlations are needed to reproduce the measured distributions. Moreover, the ventilation performances are observed to be robust against anatomical variability. The same methodology applied to the rat also permits building a geometrical model that reproduces the anatomical and ventilation characteristics of this animal. This simple model can be directly used as a common description of the entire tree in analytical or numerical studies such as the computation of air flow distribution or aerosol transport. PMID:21183626

  7. Development of biomechanical models for human factors evaluations

    NASA Technical Reports Server (NTRS)

    Woolford, Barbara; Pandya, Abhilash; Maida, James

    1991-01-01

    Previewing human capabilities in a computer-aided engineering mode has assisted greatly in planning well-designed systems without the cost and time involved in mockups and engineering models. To date, the computer models have focused on such variables as field of view, accessibility and fit, and reach envelopes. Program outputs have matured from simple static pictures to animations viewable from any eyepoint. However, while kinematics models are available, there are few biomechanical models available for estimating strength and motion patterns. Those, such as Crew Chief, that are available are based on strength measurements taken in specific positions. Johnson Space Center is pursuing a biomechanical model which will use strength data collected on single joints at two or three velocities to attempt to predict compound motions of several joint simultaneously and the resulting force at the end effector. Two lines of research are coming together to produce this result. One is an attempt to use optimal control theory to predict joint motion in complex motions, and another is the development of graphical representation of human capabilities. The progress to date in this research is described.

  8. Head Motion Modeling for Human Behavior Analysis in Dyadic Interaction

    PubMed Central

    Xiao, Bo; Georgiou, Panayiotis; Baucom, Brian; Narayanan, Shrikanth S.

    2015-01-01

    This paper presents a computational study of head motion in human interaction, notably of its role in conveying interlocutors’ behavioral characteristics. Head motion is physically complex and carries rich information; current modeling approaches based on visual signals, however, are still limited in their ability to adequately capture these important properties. Guided by the methodology of kinesics, we propose a data driven approach to identify typical head motion patterns. The approach follows the steps of first segmenting motion events, then parametrically representing the motion by linear predictive features, and finally generalizing the motion types using Gaussian mixture models. The proposed approach is experimentally validated using video recordings of communication sessions from real couples involved in a couples therapy study. In particular we use the head motion model to classify binarized expert judgments of the interactants’ specific behavioral characteristics where entrainment in head motion is hypothesized to play a role: Acceptance, Blame, Positive, and Negative behavior. We achieve accuracies in the range of 60% to 70% for the various experimental settings and conditions. In addition, we describe a measure of motion similarity between the interaction partners based on the proposed model. We show that the relative change of head motion similarity during the interaction significantly correlates with the expert judgments of the interactants’ behavioral characteristics. These findings demonstrate the effectiveness of the proposed head motion model, and underscore the promise of analyzing human behavioral characteristics through signal processing methods. PMID:26557047

  9. Customized Finite Element Modelling of the Human Cornea

    PubMed Central

    Simonini, Irene; Pandolfi, Anna

    2015-01-01

    Aim To construct patient-specific solid models of human cornea from ocular topographer data, to increase the accuracy of the biomechanical and optical estimate of the changes in refractive power and stress caused by photorefractive keratectomy (PRK). Method Corneal elevation maps of five human eyes were taken with a rotating Scheimpflug camera combined with a Placido disk before and after refractive surgery. Patient-specific solid models were created and discretized in finite elements to estimate the corneal strain and stress fields in preoperative and postoperative configurations and derive the refractive parameters of the cornea. Results Patient-specific geometrical models of the cornea allow for the creation of personalized refractive maps at different levels of IOP. Thinned postoperative corneas show a higher stress gradient across the thickness and higher sensitivity of all geometrical and refractive parameters to the fluctuation of the IOP. Conclusion Patient-specific numerical models of the cornea can provide accurate quantitative information on the refractive properties of the cornea under different levels of IOP and describe the change of the stress state of the cornea due to refractive surgery (PRK). Patient-specific models can be used as indicators of feasibility before performing the surgery. PMID:26098104

  10. Human growth and body weight dynamics: an integrative systems model.

    PubMed

    Rahmandad, Hazhir

    2014-01-01

    Quantifying human weight and height dynamics due to growth, aging, and energy balance can inform clinical practice and policy analysis. This paper presents the first mechanism-based model spanning full individual life and capturing changes in body weight, composition and height. Integrating previous empirical and modeling findings and validated against several additional empirical studies, the model replicates key trends in human growth including A) Changes in energy requirements from birth to old ages. B) Short and long-term dynamics of body weight and composition. C) Stunted growth with chronic malnutrition and potential for catch up growth. From obesity policy analysis to treating malnutrition and tracking growth trajectories, the model can address diverse policy questions. For example I find that even without further rise in obesity, the gap between healthy and actual Body Mass Indexes (BMIs) has embedded, for different population groups, a surplus of 14%-24% in energy intake which will be a source of significant inertia in obesity trends. In another analysis, energy deficit percentage needed to reduce BMI by one unit is found to be relatively constant across ages. Accompanying documented and freely available simulation model facilitates diverse applications customized to different sub-populations.

  11. Computational modeling of hypertensive growth in the human carotid artery

    NASA Astrophysics Data System (ADS)

    Sáez, Pablo; Peña, Estefania; Martínez, Miguel Angel; Kuhl, Ellen

    2014-06-01

    Arterial hypertension is a chronic medical condition associated with an elevated blood pressure. Chronic arterial hypertension initiates a series of events, which are known to collectively initiate arterial wall thickening. However, the correlation between macrostructural mechanical loading, microstructural cellular changes, and macrostructural adaptation remains unclear. Here, we present a microstructurally motivated computational model for chronic arterial hypertension through smooth muscle cell growth. To model growth, we adopt a classical concept based on the multiplicative decomposition of the deformation gradient into an elastic part and a growth part. Motivated by clinical observations, we assume that the driving force for growth is the stretch sensed by the smooth muscle cells. We embed our model into a finite element framework, where growth is stored locally as an internal variable. First, to demonstrate the features of our model, we investigate the effects of hypertensive growth in a real human carotid artery. Our results agree nicely with experimental data reported in the literature both qualitatively and quantitatively.

  12. A model of the human observer and decision maker

    NASA Technical Reports Server (NTRS)

    Wewerinke, P. H.

    1981-01-01

    The decision process is described in terms of classical sequential decision theory by considering the hypothesis that an abnormal condition has occurred by means of a generalized likelihood ratio test. For this, a sufficient statistic is provided by the innovation sequence which is the result of the perception an information processing submodel of the human observer. On the basis of only two model parameters, the model predicts the decision speed/accuracy trade-off and various attentional characteristics. A preliminary test of the model for single variable failure detection tasks resulted in a very good fit of the experimental data. In a formal validation program, a variety of multivariable failure detection tasks was investigated and the predictive capability of the model was demonstrated.

  13. Effects of introducing cultured human chondrocytes into a human articular cartilage explant model.

    PubMed

    Secretan, Charles; Bagnall, Keith M; Jomha, Nadr M

    2010-02-01

    Articular cartilage (AC) heals poorly and effective host-tissue integration after reconstruction is a concern. We have investigated the ability of implanted chondrocytes to attach at the site of injury and to be incorporated into the decellularized host matrix adjacent to a defect in an in vitro human explant model. Human osteochondral dowels received a standardized injury, were seeded with passage 3 chondrocytes labelled with PKH 26 and compared with two control groups. All dowels were cultured in vitro, harvested at 0, 7, 14 and 28 days and assessed for chondrocyte adherence and migration into the region of decellularized tissue adjacent to the defects. Additional evaluation included cell viability, general morphology and collagen II production. Seeded chondrocytes adhered to the standardized defect and areas of lamina splendens disruption but did not migrate into the adjacent acellular region. A difference was noted in viable-cell density between the experimental group and one control group. A thin lattice-like network of matrix surrounded the seeded chondrocytes and collagen II was present. The results indicate that cultured human chondrocytes do indeed adhere to regions of AC matrix injury but do not migrate into the host tissue, despite the presence of viable cells. This human explant model is thus an effective tool for studying the interaction of implanted cells and host tissue. PMID:20012649

  14. Incorporating the gut microbiota into models of human and non-human primate ecology and evolution.

    PubMed

    Amato, Katherine R

    2016-01-01

    The mammalian gut is home to a diverse community of microbes. Advances in technology over the past two decades have allowed us to examine this community, the gut microbiota, in more detail, revealing a wide range of influences on host nutrition, health, and behavior. These host-gut microbe interactions appear to shape host plasticity and fitness in a variety of contexts, and therefore represent a key factor missing from existing models of human and non-human primate ecology and evolution. However, current studies of the gut microbiota tend to include limited contextual data or are clinical, making it difficult to directly test broad anthropological hypotheses. Here, I review what is known about the animal gut microbiota and provide examples of how gut microbiota research can be integrated into the study of human and non-human primate ecology and evolution with targeted data collection. Specifically, I examine how the gut microbiota may impact primate diet, energetics, disease resistance, and cognition. While gut microbiota research is proliferating rapidly, especially in the context of humans, there remain important gaps in our understanding of host-gut microbe interactions that will require an anthropological perspective to fill. Likewise, gut microbiota research will be an important tool for filling remaining gaps in anthropological research. PMID:26808106

  15. Incorporating the gut microbiota into models of human and non-human primate ecology and evolution.

    PubMed

    Amato, Katherine R

    2016-01-01

    The mammalian gut is home to a diverse community of microbes. Advances in technology over the past two decades have allowed us to examine this community, the gut microbiota, in more detail, revealing a wide range of influences on host nutrition, health, and behavior. These host-gut microbe interactions appear to shape host plasticity and fitness in a variety of contexts, and therefore represent a key factor missing from existing models of human and non-human primate ecology and evolution. However, current studies of the gut microbiota tend to include limited contextual data or are clinical, making it difficult to directly test broad anthropological hypotheses. Here, I review what is known about the animal gut microbiota and provide examples of how gut microbiota research can be integrated into the study of human and non-human primate ecology and evolution with targeted data collection. Specifically, I examine how the gut microbiota may impact primate diet, energetics, disease resistance, and cognition. While gut microbiota research is proliferating rapidly, especially in the context of humans, there remain important gaps in our understanding of host-gut microbe interactions that will require an anthropological perspective to fill. Likewise, gut microbiota research will be an important tool for filling remaining gaps in anthropological research.

  16. Effects of Instructional Experience in Clay Modeling Skills on Modeled Human Figure Representation in Preschool Children.

    ERIC Educational Resources Information Center

    Grossman, Ellin

    1980-01-01

    After 15 lessons on clay modeling skills, modeled and drawn human figures by 41 nursery school children were compared to those by control children on formal elements, structure, and detail. The instructional experience significantly improved subjects' clay figure work. No significant sex effect or skill transfer to drawing was found. (SJL)

  17. Modeling of interactions of electromagnetic fields with human bodies

    NASA Astrophysics Data System (ADS)

    Caputa, Krzysztof

    Interactions of electromagnetic fields with the human body have been a subject of scientific interest and public concern. In recent years, issues in power line field effects and those of wireless telephones have been in the forefront of research. Engineering research compliments biological investigations by quantifying the induced fields in biological bodies due to exposure to external fields. The research presented in this thesis aims at providing reliable tools, and addressing some of the unresolved issues related to interactions with the human body of power line fields and fields produced by handheld wireless telephones. The research comprises two areas, namely development of versatile models of the human body and their visualisation, and verification and application of numerical codes to solve selected problems of interest. The models of the human body, which are based on the magnetic resonance scans of the body, are unique and differ considerably from other models currently available. With the aid of computer software developed, the models can be arranged to different postures, and medical devices can be accurately placed inside them. A previously developed code for modeling interactions of power line fields with biological bodies has been verified by rigorous, quantitative inter-laboratory comparison for two human body models. This code has been employed to model electromagnetic interference (EMI) of the magnetic field with implanted cardiac pacemakers. In this case, the correct placement and representation of the pacemaker leads are critical, as simplified computations have been shown to result in significant errors. In modeling interactions of wireless communication devices, the finite difference time domain technique (FDTD) has become a de facto standard. The previously developed code has been verified by comparison with the analytical solution for a conductive sphere. While previously researchers limited their verifications to principal axes of the sphere

  18. Model of the Human Eye Based on ABCD Matrix

    NASA Astrophysics Data System (ADS)

    González, G. Díaz; Castillo, M. David Iturbe

    2008-04-01

    At the moment several models of the human eye exist, nevertheless the gradient index models of the human lens (crystalline) have received little attention in optometry and vision sciences, although they consider how the refractive index and the refracting power can change with the accommodation. On the other hand, in study fields like ophthalmology and optometry, exist cases where there is a lack of information about the factors that influence the change of refractive power and therefore the focal length of the eye. By such reason, in this paper we present a model of the human eye based on the ABCD matrix in order to describe the propagation of light rays, that can be understood by professional people in optics, ophthalmology and optometry, and the dispersions of the different ocular mediums are taken into account,. The aim of the model is to obtain data about the refractive power of the eye under different considerations, such as: changes in wavelength, radius of curvature and thicknesses of the ocular mediums. We present results of simulations in Matlab of our model, assuming that the object is punctual and is placed to a certain distance of the eye, and considering at the beginning to the crystalline like a medium with fixed refractive index, and after like a gradient lens. By means of graphs, we show the total refractive power of the eye and its form and type of dependence with respect to variations in radius of curvature and thicknesses of the cornea and crystalline, as well as variations in the thickness of the previous and later cameras.

  19. Further Improvements of the P. falciparum Humanized Mouse Model

    PubMed Central

    Meija, Pedro; Swetman, Claire; Gleeson, James; Pérignon, Jean-Louis; Druilhe, Pierre

    2011-01-01

    Background It has been shown previously that it is possible to obtain growth of Plasmodium falciparum in human erythrocytes grafted in mice lacking adaptive immune responses by controlling, to a certain extent, innate defences with liposomes containing clodronate (clo-lip). However, the reproducibility of those models is limited, with only a proportion of animals supporting longstanding parasitemia, due to strong inflammation induced by P. falciparum. Optimisation of the model is much needed for the study of new anti-malarial drugs, drug combinations, and candidate vaccines. Materials/Methods We investigated the possibility of improving previous models by employing the intravenous route (IV) for delivery of both human erythrocytes (huRBC) and P. falciparum, instead of the intraperitoneal route (IP), by testing various immunosuppressive drugs that might help to control innate mouse defences, and by exploring the potential benefits of using immunodeficient mice with additional genetic defects, such as those with IL-2Rγ deficiency (NSG mice). Results We demonstrate here the role of aging, of inosine and of the IL-2 receptor γ mutation in controlling P. falciparum induced inflammation. IV delivery of huRBC and P. falciparum in clo-lip treated NSG mice led to successful infection in 100% of inoculated mice, rapid rise of parasitemia to high levels (up to 40%), long-lasting parasitemia, and consistent results from mouse-to-mouse. Characteristics were closer to human infection than in previous models, with evidence of synchronisation, partial sequestration, and receptivity to various P. falciparum strains without preliminary adaptation. However, results show that a major IL-12p70 inflammatory response remains prevalent. Conclusion The combination of the NSG mouse, clodronate loaded liposomes, and IV delivery of huRBC has produced a reliable and more relevant model that better meets the needs of Malaria research. PMID:21483851

  20. Regional Intestinal Permeability of Three Model Drugs in Human.

    PubMed

    Dahlgren, David; Roos, Carl; Lundqvist, Anders; Abrahamsson, Bertil; Tannergren, Christer; Hellström, Per M; Sjögren, Erik; Lennernäs, Hans

    2016-09-01

    Currently there are only a limited number of determinations of human Peff in the distal small intestine and none in the large intestine. This has hindered the validation of preclinical models with regard to absorption in the distal parts of the intestinal tract, which can be substantial for BCS class II-IV drugs, and drugs formulated into modified-release (MR) dosage forms. To meet this demand, three model drugs (atenolol, metoprolol, and ketoprofen) were dosed in solution intravenously, and into the jejunum, ileum, and colon of 14 healthy volunteers. The Peff of each model drug was then calculated using a validated deconvolution method. The median Peff of atenolol in the jejunum, ileum, and colon was 0.45, 0.15, and 0.013 × 10(-4) cm/s, respectively. The corresponding values for metoprolol were 1.72, 0.72, and 1.30 × 10(-4) cm/s, and for ketoprofen 8.85, 6.53, and 3.37 × 10(-4) cm/s, respectively. This is the first study where the human Peff of model drugs has been determined in all parts of the human intestinal tract in the same subjects. The jejunal values were similar to directly determined values using intestinal single-pass perfusion, indicating that the deconvolution method is a valid approach for determining regional Peff. The values from this study will be highly useful in the validation of preclinical regional absorption models and in silico tools. PMID:27504798

  1. A humanized mouse model for the reduced folate carrier.

    PubMed

    Patterson, David; Graham, Christine; Cherian, Christina; Matherly, Larry H

    2008-02-01

    The ubiquitously expressed reduced folate carrier (RFC) or SLC19A1 is recognized to be an essential transport system for folates in mammalian cells and tissues. In addition to its generalized role as a folate transporter, RFC provides specialized tissue functions including absorption across intestinal/colonic epithelia, transport across the basolateral membrane of renal proximal tubules, transplacental transport of folates, and folate transport across the blood-brain barrier. The human RFC (hRFC) gene is regulated by five major upstream non-coding regions (designated A1/A2, A, B, C, and D), each transcribed from a unique promoter. Altogether, at least 14 distinct hRFC transcripts can be envisaged in which different 5' untranslated regions (UTRs) are fused to a common splice acceptor region (positions -1 to -49) within the first coding exon with a common 1776bp coding sequence. The 5' non-coding regions are characterized by alternate transcription start sites, multiple splice forms, and selective tissue distributions. Alternate 5' UTRs impact mRNA stabilities and translation efficiencies, and result in synthesis of modified hRFC proteins translated from upstream AUGs. In this report, we describe production and characterization of transgenic mice (TghRFC1) containing a functional hRFC gene and of humanized mice in which the mRFC gene is inactivated and an active hRFC gene has been introduced. The mice appear to be healthy and to breed well. Analysis of tissue specificity of expression in both the TghRFC1 and humanized hRFC mice by real-time RT-PCR demonstrates that the hRFC gene is expressed with a specificity closely resembling that seen in human tissues. For the humanized hRFC mice, levels of B and A1/A2 5' UTRs predominated in all mice/tissues, thus resembling results in normal human tissues. Lower levels of A and C 5' UTRs were also detected. The availability of humanized mouse models for hRFC will permit investigators to address critical unanswered questions

  2. Human Truncated Tau Induces Mature Neurofibrillary Pathology in a Mouse Model of Human Tauopathy.

    PubMed

    Zimova, Ivana; Brezovakova, Veronika; Hromadka, Tomas; Weisova, Petronela; Cubinkova, Veronika; Valachova, Bernadeta; Filipcik, Peter; Jadhav, Santosh; Smolek, Tomas; Novak, Michal; Zilka, Norbert

    2016-09-01

    Alzheimer's disease (AD) represents the most common neurodegenerative disorder. Several animal models have been developed in order to test pathophysiological mechanisms of the disease and to predict effects of pharmacological interventions. Here we examine the molecular and behavioral features of R3m/4 transgenic mice expressing human non-mutated truncated tau protein (3R tau, aa151-391) that were previously used for efficacy testing of passive tau vaccine. The mouse model reliably recapitulated crucial histopathological features of human AD, such as pre-tangles, neurofibrillary tangles, and neuropil threads. The pathology was predominantly located in the brain stem. Transgenic mice developed mature sarkosyl insoluble tau complexes consisting of mouse endogenous and human truncated and hyperphosphorylated forms of tau protein. The histopathological and biochemical features were accompanied by significant sensorimotor impairment and reduced lifespan. The sensorimotor impairment was monitored by a highly sensitive, fully-automated tool that allowed us to assess early deficit in gait and locomotion. We suggest that the novel transgenic mouse model can serve as a valuable tool for analysis of the therapeutic efficacy of tau vaccines for AD therapy. PMID:27567836

  3. A robotic model to investigate human motor control.

    PubMed

    Lenzi, Tommaso; Vitiello, Nicola; McIntyre, Joseph; Roccella, Stefano; Carrozza, Maria Chiara

    2011-07-01

    The role of the mechanical properties of the neuromuscular system in motor control has been investigated for a long time in both human and animal subjects, mainly through the application of mechanical perturbations to the limb during natural movements and the observation of its corrective responses. These methods have provided a wealth of insight into how the central nervous system controls the limb. They suffer, however, from the fact that it is almost impossible to separate the active and passive components of the measured arm stiffness and that the measurement may themselves alter the stiffness characteristic of the arm. As a complement to these analyses, the implementation of a given neuroscientific hypothesis on a real mechanical system could overcome these measurement artifact and provide a tool that is, under full control of the experimenter, able to replicate the relevant functional features of the human arm. In this article, we introduce the NEURARM platform, a robotic arm intended to test hypotheses on the human motor control system. As such, NEURARM satisfies two key requirements. First, its kinematic parameters and inertia are similar to that of the human arm. Second, NEURARM mimics the main physical features of the human actuation system, specifically, the use of tendons to transfer force, the presence of antagonistic muscle pairs, the passive elasticity of muscles in the absence of any neural feedback and the non-linear elastic behaviour. This article presents the design and characterization of the NEURARM actuation system. The resulting mechanical behaviour, which has been tested in joint and Cartesian space under static and dynamic conditions, proves that the NEURARM platform can be exploited as a robotic model of the human arm, and could thus represent a powerful tool for neuroscience investigations.

  4. Xenobiotic metabolizing enzymes in human skin and SkinEthic reconstructed human skin models.

    PubMed

    Eilstein, Joan; Léreaux, Guillaume; Arbey, Eric; Daronnat, Edwige; Wilkinson, Simon; Duché, Daniel

    2015-07-01

    Skin metabolism is becoming a major consideration in the development of new cosmetic ingredients, skin being the first organ exposed to them. In order to replace limited samples of Excised human skin (EHS), in vitro engineered human skins have been developed. 3D models are daily used to develop and evaluate new cosmetic ingredients and have to be characterized and compared with EHS in terms of metabolic capabilities. This work presents the determination of apparent catalytic parameters (apparent Vmax, Km and the ratio Vmax/Km) in 3D models compared with EHS for cytochrome P450 dependent monooxygenase isoforms involved in drug metabolism, esterases, alcohol dehydrogenases, aldehyde dehydrogenases, peroxidases, glutathione S-transferases, N-acetyl transferases, uridinyl diphosphate glucuronyl transferases and sulfotransferases. Results show that all these enzymes involved in the metabolism of xenobiotics are expressed and functional in the EHS and 3D models. Also, the Vmax/Km ratios (estimating the intrinsic metabolic clearances) show that the metabolic abilities are the most often comparable between the skin models and EHS. These results indicate that the 3D models can substitute themselves for EHS to select cosmetic ingredients on the basis of their metabolism, efficacy or/and safety. PMID:25808006

  5. On the Use of Human Mobility Proxies for Modeling Epidemics

    PubMed Central

    Tizzoni, Michele; Bajardi, Paolo; Decuyper, Adeline; Kon Kam King, Guillaume; Schneider, Christian M.; Blondel, Vincent; Smoreda, Zbigniew; González, Marta C.; Colizza, Vittoria

    2014-01-01

    Human mobility is a key component of large-scale spatial-transmission models of infectious diseases. Correctly modeling and quantifying human mobility is critical for improving epidemic control, but may be hindered by data incompleteness or unavailability. Here we explore the opportunity of using proxies for individual mobility to describe commuting flows and predict the diffusion of an influenza-like-illness epidemic. We consider three European countries and the corresponding commuting networks at different resolution scales, obtained from (i) official census surveys, (ii) proxy mobility data extracted from mobile phone call records, and (iii) the radiation model calibrated with census data. Metapopulation models defined on these countries and integrating the different mobility layers are compared in terms of epidemic observables. We show that commuting networks from mobile phone data capture the empirical commuting patterns well, accounting for more than 87% of the total fluxes. The distributions of commuting fluxes per link from mobile phones and census sources are similar and highly correlated, however a systematic overestimation of commuting traffic in the mobile phone data is observed. This leads to epidemics that spread faster than on census commuting networks, once the mobile phone commuting network is considered in the epidemic model, however preserving to a high degree the order of infection of newly affected locations. Proxies' calibration affects the arrival times' agreement across different models, and the observed topological and traffic discrepancies among mobility sources alter the resulting epidemic invasion patterns. Results also suggest that proxies perform differently in approximating commuting patterns for disease spread at different resolution scales, with the radiation model showing higher accuracy than mobile phone data when the seed is central in the network, the opposite being observed for peripheral locations. Proxies should therefore be

  6. Modelling Adaptive Learning Behaviours for Consensus Formation in Human Societies.

    PubMed

    Yu, Chao; Tan, Guozhen; Lv, Hongtao; Wang, Zhen; Meng, Jun; Hao, Jianye; Ren, Fenghui

    2016-01-01

    Learning is an important capability of humans and plays a vital role in human society for forming beliefs and opinions. In this paper, we investigate how learning affects the dynamics of opinion formation in social networks. A novel learning model is proposed, in which agents can dynamically adapt their learning behaviours in order to facilitate the formation of consensus among them, and thus establish a consistent social norm in the whole population more efficiently. In the model, agents adapt their opinions through trail-and-error interactions with others. By exploiting historical interaction experience, a guiding opinion, which is considered to be the most successful opinion in the neighbourhood, can be generated based on the principle of evolutionary game theory. Then, depending on the consistency between its own opinion and the guiding opinion, a focal agent can realize whether its opinion complies with the social norm (i.e., the majority opinion that has been adopted) in the population, and adapt its behaviours accordingly. The highlight of the model lies in that it captures the essential features of people's adaptive learning behaviours during the evolution and formation of opinions. Experimental results show that the proposed model can facilitate the formation of consensus among agents, and some critical factors such as size of opinion space and network topology can have significant influences on opinion dynamics. PMID:27282089

  7. A biokinetic model for systemic technetium in adult humans

    DOE PAGES

    Leggett, Richard Wayne; Giussani, Augusto

    2015-04-10

    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection.more » Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.« less

  8. Modelling Adaptive Learning Behaviours for Consensus Formation in Human Societies

    PubMed Central

    Yu, Chao; Tan, Guozhen; Lv, Hongtao; Wang, Zhen; Meng, Jun; Hao, Jianye; Ren, Fenghui

    2016-01-01

    Learning is an important capability of humans and plays a vital role in human society for forming beliefs and opinions. In this paper, we investigate how learning affects the dynamics of opinion formation in social networks. A novel learning model is proposed, in which agents can dynamically adapt their learning behaviours in order to facilitate the formation of consensus among them, and thus establish a consistent social norm in the whole population more efficiently. In the model, agents adapt their opinions through trail-and-error interactions with others. By exploiting historical interaction experience, a guiding opinion, which is considered to be the most successful opinion in the neighbourhood, can be generated based on the principle of evolutionary game theory. Then, depending on the consistency between its own opinion and the guiding opinion, a focal agent can realize whether its opinion complies with the social norm (i.e., the majority opinion that has been adopted) in the population, and adapt its behaviours accordingly. The highlight of the model lies in that it captures the essential features of people’s adaptive learning behaviours during the evolution and formation of opinions. Experimental results show that the proposed model can facilitate the formation of consensus among agents, and some critical factors such as size of opinion space and network topology can have significant influences on opinion dynamics. PMID:27282089

  9. Modelling Adaptive Learning Behaviours for Consensus Formation in Human Societies

    NASA Astrophysics Data System (ADS)

    Yu, Chao; Tan, Guozhen; Lv, Hongtao; Wang, Zhen; Meng, Jun; Hao, Jianye; Ren, Fenghui

    2016-06-01

    Learning is an important capability of humans and plays a vital role in human society for forming beliefs and opinions. In this paper, we investigate how learning affects the dynamics of opinion formation in social networks. A novel learning model is proposed, in which agents can dynamically adapt their learning behaviours in order to facilitate the formation of consensus among them, and thus establish a consistent social norm in the whole population more efficiently. In the model, agents adapt their opinions through trail-and-error interactions with others. By exploiting historical interaction experience, a guiding opinion, which is considered to be the most successful opinion in the neighbourhood, can be generated based on the principle of evolutionary game theory. Then, depending on the consistency between its own opinion and the guiding opinion, a focal agent can realize whether its opinion complies with the social norm (i.e., the majority opinion that has been adopted) in the population, and adapt its behaviours accordingly. The highlight of the model lies in that it captures the essential features of people’s adaptive learning behaviours during the evolution and formation of opinions. Experimental results show that the proposed model can facilitate the formation of consensus among agents, and some critical factors such as size of opinion space and network topology can have significant influences on opinion dynamics.

  10. Preliminary Exploration of Adaptive State Predictor Based Human Operator Modeling

    NASA Technical Reports Server (NTRS)

    Trujillo, Anna C.; Gregory, Irene M.

    2012-01-01

    Control-theoretic modeling of the human operator dynamic behavior in manual control tasks has a long and rich history. In the last two decades, there has been a renewed interest in modeling the human operator. There has also been significant work on techniques used to identify the pilot model of a given structure. The purpose of this research is to attempt to go beyond pilot identification based on collected experimental data and to develop a predictor of pilot behavior. An experiment was conducted to quantify the effects of changing aircraft dynamics on an operator s ability to track a signal in order to eventually model a pilot adapting to changing aircraft dynamics. A gradient descent estimator and a least squares estimator with exponential forgetting used these data to predict pilot stick input. The results indicate that individual pilot characteristics and vehicle dynamics did not affect the accuracy of either estimator method to estimate pilot stick input. These methods also were able to predict pilot stick input during changing aircraft dynamics and they may have the capability to detect a change in a subject due to workload, engagement, etc., or the effects of changes in vehicle dynamics on the pilot.

  11. A biokinetic model for systemic technetium in adult humans

    SciTech Connect

    Leggett, Richard Wayne; Giussani, Augusto

    2015-04-10

    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection. Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.

  12. Statistical evaluation of alternative models of human evolution

    PubMed Central

    Fagundes, Nelson J. R.; Ray, Nicolas; Beaumont, Mark; Neuenschwander, Samuel; Salzano, Francisco M.; Bonatto, Sandro L.; Excoffier, Laurent

    2007-01-01

    An appropriate model of recent human evolution is not only important to understand our own history, but it is necessary to disentangle the effects of demography and selection on genome diversity. Although most genetic data support the view that our species originated recently in Africa, it is still unclear if it completely replaced former members of the Homo genus, or if some interbreeding occurred during its range expansion. Several scenarios of modern human evolution have been proposed on the basis of molecular and paleontological data, but their likelihood has never been statistically assessed. Using DNA data from 50 nuclear loci sequenced in African, Asian and Native American samples, we show here by extensive simulations that a simple African replacement model with exponential growth has a higher probability (78%) as compared with alternative multiregional evolution or assimilation scenarios. A Bayesian analysis of the data under this best supported model points to an origin of our species ≈141 thousand years ago (Kya), an exit out-of-Africa ≈51 Kya, and a recent colonization of the Americas ≈10.5 Kya. We also find that the African replacement model explains not only the shallow ancestry of mtDNA or Y-chromosomes but also the occurrence of deep lineages at some autosomal loci, which has been formerly interpreted as a sign of interbreeding with Homo erectus. PMID:17978179

  13. Lessons from molecular modeling human α-L-iduronidase.

    PubMed

    Figueiredo, Danieli Forgiarini; Antunes, Dinler A; Rigo, Maurício M; Mendes, Marcus F A; Silva, Jader P; Mayer, Fabiana Q; Matte, Ursula; Giugliani, Roberto; Vieira, Gustavo F; Sinigaglia, Marialva

    2014-11-01

    Human α-L-iduronidase (IDUA) is a member of glycoside hydrolase family and is involved in the catabolism of glycosaminoglycans (GAGs), heparan sulfate (HS) and dermatan sulfate (DS). Mutations in this enzyme are responsible for mucopolysaccharidosis I (MPS I), an inherited lysosomal storage disorder. Despite great interest in determining and studying this enzyme structure, the lack of a high identity to templates and other technical issues have challenged both bioinformaticians and crystallographers, until the recent publication of an IDUA crystal structure (PDB: 4JXP). In the present work, four alternative IDUA models, generated and evaluated prior to crystallographic determination, were compared to the 4JXP structure. A combined analysis using several viability assessment tools and molecular dynamics simulations highlights the strengths and limitations of different comparative modeling protocols, all of which are based on the same low identity template (only 22%). Incorrect alignment between the target and template was confirmed to be a major bottleneck in homology modeling, regardless of the modeling software used. Moreover, secondary structure analysis during a 50ns simulation seems to be useful for indicating alignment errors and structural instabilities. The best model was achieved through the combined use of Phyre 2 and Modeller, suggesting the use of this protocol for the modeling of other proteins that still lack high identity templates.

  14. Low-relief landscape modeling with human activities

    NASA Astrophysics Data System (ADS)

    Yan, Q.; Kumar, P.; Anders, A. M.

    2015-12-01

    Intensively managed landscapes (IMLs) in the Midwestern United States have been shaped by repeated glacial events over geologic time scales followed by rapid human modifications for agriculture and artificial drainage that were overlaid on extremely low gradient stream networks. These landscapes are heavily modified by agriculture, artificial drainage, deforestation, urbanization, and wetland destruction. Channel head extension and periodic dredging for channel straightening not only strongly affected hydrologic and geomorphologic response, but also fundamentally alter the energy consumption in the whole river basin. However, it is unclear how the landscape consumes and responds to the extra energy from human activities. Therefore, we evaluate the present-day dynamics of river network from the perspective of of geomorphic equilibrium, hydrological response, and the rate of energy dissipation. Then, we simulate the landscape evolution to discover the tendency of the system. We find that channel head extension and straightening increases the rate of energy dissipation and pushes the river network further away from equilibrium condition. From our numerical model simulation, extending and maintaining the ditches in the river network can cause large ridge migration, river network redistribution, and enlargement of the drainage basin area. Our research demonstrates how the river basin responds to human activities in glaciated landscape, and how it is likely to behave with artificial modifications on the topography in the future. We attribute the legacy to drainage basin reorganization and theorized that humans can have a lasting impact on the landscape even after active management has ceased.

  15. Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis

    PubMed Central

    Wang, Yunan; Kayoumu, Abudurexiti; Lu, Guotao; Xu, Pengfei; Qiu, Xu; Chen, Liye; Qi, Rong; Huang, Shouxiong; Li, Weiqin; Wang, Yuhui; Liu, George

    2016-01-01

    The hamster has been shown to share a variety of metabolic similarities with humans. To replicate human acute pancreatitis with hamsters, we comparatively studied the efficacy of common methods, such as the peritoneal injections of caerulein, L-arginine, the retrograde infusion of sodium taurocholate, and another novel model with concomitant administration of ethanol and fatty acid. The severity of pancreatitis was evaluated by serum amylase activity, pathological scores, myeloperoxidase activity, and the expression of inflammation factors in pancreas. The results support that the severity of pathological injury is consistent with the pancreatitis induced in mice and rat using the same methods. Specifically, caerulein induced mild edematous pancreatitis accompanied by minimal lung injury, while L-arginine induced extremely severe pancreatic injury including necrosis and neutrophil infiltration. Infusion of Na-taurocholate into the pancreatic duct induced necrotizing pancreatitis in the head of pancreas and lighter inflammation in the distal region. The severity of acute pancreatitis induced by combination of ethanol and fatty acids was between the extent of caerulein and L-arginine induction, with obvious inflammatory cells infiltration. In view of the advantages in lipid metabolism features, hamster models are ideally suited for the studies of pancreatitis associated with altered metabolism in humans. PMID:27302647

  16. Sustainable three-dimensional tissue model of human adipose tissue.

    PubMed

    Bellas, Evangelia; Marra, Kacey G; Kaplan, David L

    2013-10-01

    The need for physiologically relevant sustainable human adipose tissue models is crucial for understanding tissue development, disease progression, in vitro drug development and soft tissue regeneration. The coculture of adipocytes differentiated from human adipose-derived stem cells, with endothelial cells, on porous silk protein matrices for at least 6 months is reported, while maintaining adipose-like outcomes. Cultures were assessed for structure and morphology (Oil Red O content and CD31 expression), metabolic functions (leptin, glycerol production, gene expression for GLUT4, and PPARγ) and cell replication (DNA content). The cocultures maintained size and shape over this extended period in static cultures, while increasing in diameter by 12.5% in spinner flask culture. Spinner flask cultures yielded improved adipose tissue outcomes overall, based on structure and function, when compared to the static cultures. This work establishes a tissue model system that can be applied to the development of chronic metabolic dysfunction systems associated with human adipose tissue, such as obesity and diabetes, due to the long term sustainable functions demonstrated here.

  17. Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis.

    PubMed

    Wang, Yunan; Kayoumu, Abudurexiti; Lu, Guotao; Xu, Pengfei; Qiu, Xu; Chen, Liye; Qi, Rong; Huang, Shouxiong; Li, Weiqin; Wang, Yuhui; Liu, George

    2016-01-01

    The hamster has been shown to share a variety of metabolic similarities with humans. To replicate human acute pancreatitis with hamsters, we comparatively studied the efficacy of common methods, such as the peritoneal injections of caerulein, L-arginine, the retrograde infusion of sodium taurocholate, and another novel model with concomitant administration of ethanol and fatty acid. The severity of pancreatitis was evaluated by serum amylase activity, pathological scores, myeloperoxidase activity, and the expression of inflammation factors in pancreas. The results support that the severity of pathological injury is consistent with the pancreatitis induced in mice and rat using the same methods. Specifically, caerulein induced mild edematous pancreatitis accompanied by minimal lung injury, while L-arginine induced extremely severe pancreatic injury including necrosis and neutrophil infiltration. Infusion of Na-taurocholate into the pancreatic duct induced necrotizing pancreatitis in the head of pancreas and lighter inflammation in the distal region. The severity of acute pancreatitis induced by combination of ethanol and fatty acids was between the extent of caerulein and L-arginine induction, with obvious inflammatory cells infiltration. In view of the advantages in lipid metabolism features, hamster models are ideally suited for the studies of pancreatitis associated with altered metabolism in humans. PMID:27302647

  18. Simplification of the kinematic model of human movement

    NASA Astrophysics Data System (ADS)

    Dusza, Jacek J.; Wawrzyniak, Zbigniew M.; del Prado Martinez, David

    2013-10-01

    The paper presents a methods of simplification of the human gait model. The experimental data were obtained in the laboratory of the group SATI in the Electronics Engineering Department of the University of Valencia. As a result of the Mean Double Step (MDS) procedure, the human motion were described by a matrix containing the Cartesian coordinates of 26 markers placed on the human body recorded in the 100 time points. With these data it has been possible to develop an software application which performs a wide diversity of tasks like array simplification, mask calculation for the simplification, error calculation as well as tools for signals comparison and movement animation of the markers. Simplifications were made by the spectral analysis of signals and calculating the standard deviation of the differences between the signal and its approximation. Using this method the signals of displacement could be written as the time series limited to a small number of harmonic signals. This approach allows us for a high degree of data compression. The model presented in this work can be applied into the context of medical diagnostics or rehabilitation because for a given approximation error and a large number of harmonics may demonstrate some abnormalities (of orthopaedic symptoms) in the gait cycle analysis.

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

    NASA Technical Reports Server (NTRS)

    Ancel, Ersin; Shih, Ann T.

    2015-01-01

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

  20. A Big Bang model of human colorectal tumor growth.

    PubMed

    Sottoriva, Andrea; Kang, Haeyoun; Ma, Zhicheng; Graham, Trevor A; Salomon, Matthew P; Zhao, Junsong; Marjoram, Paul; Siegmund, Kimberly; Press, Michael F; Shibata, Darryl; Curtis, Christina

    2015-03-01

    What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion producing numerous intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear 'born to be bad', with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH, with important clinical implications.

  1. A Big Bang model of human colorectal tumor growth.

    PubMed

    Sottoriva, Andrea; Kang, Haeyoun; Ma, Zhicheng; Graham, Trevor A; Salomon, Matthew P; Zhao, Junsong; Marjoram, Paul; Siegmund, Kimberly; Press, Michael F; Shibata, Darryl; Curtis, Christina

    2015-03-01

    What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion producing numerous intermixed subclones that are not subject to stringent selection and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors showed an absence of selective sweeps, uniformly high intratumoral heterogeneity (ITH) and subclone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear 'born to be bad', with subclone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH, with important clinical implications. PMID:25665006

  2. An Embodied Brain Model of the Human Foetus

    PubMed Central

    Yamada, Yasunori; Kanazawa, Hoshinori; Iwasaki, Sho; Tsukahara, Yuki; Iwata, Osuke; Yamada, Shigehito; Kuniyoshi, Yasuo

    2016-01-01

    Cortical learning via sensorimotor experiences evoked by bodily movements begins as early as the foetal period. However, the learning mechanisms by which sensorimotor experiences guide cortical learning remain unknown owing to technical and ethical difficulties. To bridge this gap, we present an embodied brain model of a human foetus as a coupled brain-body-environment system by integrating anatomical/physiological data. Using this model, we show how intrauterine sensorimotor experiences related to bodily movements induce specific statistical regularities in somatosensory feedback that facilitate cortical learning of body representations and subsequent visual-somatosensory integration. We also show how extrauterine sensorimotor experiences affect these processes. Our embodied brain model can provide a novel computational approach to the mechanistic understanding of cortical learning based on sensorimotor experiences mediated by complex interactions between the body, environment and nervous system. PMID:27302194

  3. Modeling HIV-1 Mucosal Transmission and Prevention in Humanized Mice.

    PubMed

    Veselinovic, Milena; Charlins, Paige; Akkina, Ramesh

    2016-01-01

    The new generation humanized mice (hu-mice) that permit continuous de novo generation of human hematopoietic cells have led to novel strategies in studying HIV-1 pathogenesis, prevention and therapies. HIV-1 infection of hu-mice results in chronic viremia and CD4+ T cell loss, thus mimicking key aspects of the disease progression. In addition, the new generation hu-mice are permissive for HIV-1 sexual transmission by vaginal and rectal routes thus allowing in vivo efficacy testing of new anti-HIV-1 drugs for prevention. Two leading models are currently being used, namely the hu-HSC mice and the BLT mice. Here we describe the methodology for generating both hu-HSC and BLT mice and their use in the study of HIV-1 transmission and prevention of infection by topical and oral administration of anti-retroviral drugs. Practical aspects of the methodologies are emphasized.

  4. Adapting GOMS to Model Human-Robot Interaction

    SciTech Connect

    Drury, Jill; Scholtz, Jean; Kieras, David

    2007-03-09

    Human-robot interaction (HRI) has been maturing in tandem with robots’ commercial success. In the last few years HRI researchers have been adopting—and sometimes adapting—human-computer interaction (HCI) evaluation techniques to assess the efficiency and intuitiveness of HRI designs. For example, Adams (2005) used Goal Directed Task Analysis to determine the interaction needs of officers from the Nashville Metro Police Bomb Squad. Scholtz et al. (2004) used Endsley’s (1988) Situation Awareness Global Assessment Technique to determine robotic vehicle supervisors’ awareness of when vehicles were in trouble and thus required closer monitoring or intervention. Yanco and Drury (2004) employed usability testing to determine (among other things) how well a search-andrescue interface supported use by first responders. One set of HCI tools that has so far seen little exploration in the HRI domain, however, is the class of modeling and evaluation techniques known as formal methods.

  5. Modeling human nonalcoholic steatohepatitis-associated changes in drug transporter expression using experimental rodent models.

    PubMed

    Canet, Mark J; Hardwick, Rhiannon N; Lake, April D; Dzierlenga, Anika L; Clarke, John D; Cherrington, Nathan J

    2014-04-01

    Nonalcoholic fatty liver disease is a prevalent form of chronic liver disease that can progress to the more advanced stage of nonalcoholic steatohepatitis (NASH). NASH has been shown to alter drug transporter regulation and may have implications in the development of adverse drug reactions. Several experimental rodent models have been proposed for the study of NASH, but no single model fully recapitulates all aspects of the human disease. The purpose of the current study was to determine which experimental NASH model best reflects the known alterations in human drug transporter expression to enable more accurate drug disposition predictions in NASH. Both rat and mouse NASH models were used in this investigation and include the methionine and choline deficient (MCD) diet model, atherogenic diet model, ob/ob and db/db mice, and fa/fa rats. Pathologic scoring evaluations demonstrated that MCD and atherogenic rats, as well as ob/ob and db/db mice, developed NASH. Liver mRNA and protein expression analyses of drug transporters showed that in general, efflux transporters were induced and uptake transporters were repressed in the rat MCD and the mouse ob/ob and db/db models. Lastly, concordance analyses suggest that both the mouse and rat MCD models as well as mouse ob/ob and db/db NASH models show the most similarity to human transporter mRNA and protein expression. These results suggest that the MCD rat and mouse model, as well as the ob/ob and db/db mouse models, may be useful for predicting altered disposition of drugs with similar kinetics across humans and rodents.

  6. [A study on three dimensional modeling of human body in man-machine system simulation].

    PubMed

    Wei, B; Yuan, X

    1997-12-01

    Modeling of the human body is a basic problem in human-machine system simulation. In this study a B-spline surface model of the human body was established. In the modeling, human body is split into several segments and each segment is a cubic B-spline surface. A blend surface was used to link two jointed segments. It is easy to simulate the motion of the human body by using the algorithm of axial deformation. PMID:11540444

  7. Computational Human Performance Modeling For Alarm System Design

    SciTech Connect

    Jacques Hugo

    2012-07-01

    The introduction of new technologies like adaptive automation systems and advanced alarms processing and presentation techniques in nuclear power plants is already having an impact on the safety and effectiveness of plant operations and also the role of the control room operator. This impact is expected to escalate dramatically as more and more nuclear power utilities embark on upgrade projects in order to extend the lifetime of their plants. One of the most visible impacts in control rooms will be the need to replace aging alarm systems. Because most of these alarm systems use obsolete technologies, the methods, techniques and tools that were used to design the previous generation of alarm system designs are no longer effective and need to be updated. The same applies to the need to analyze and redefine operators’ alarm handling tasks. In the past, methods for analyzing human tasks and workload have relied on crude, paper-based methods that often lacked traceability. New approaches are needed to allow analysts to model and represent the new concepts of alarm operation and human-system interaction. State-of-the-art task simulation tools are now available that offer a cost-effective and efficient method for examining the effect of operator performance in different conditions and operational scenarios. A discrete event simulation system was used by human factors researchers at the Idaho National Laboratory to develop a generic alarm handling model to examine the effect of operator performance with simulated modern alarm system. It allowed analysts to evaluate alarm generation patterns as well as critical task times and human workload predicted by the system.

  8. Drosophila as an In Vivo Model for Human Neurodegenerative Disease

    PubMed Central

    McGurk, Leeanne; Berson, Amit; Bonini, Nancy M.

    2015-01-01

    With the increase in the ageing population, neurodegenerative disease is devastating to families and poses a huge burden on society. The brain and spinal cord are extraordinarily complex: they consist of a highly organized network of neuronal and support cells that communicate in a highly specialized manner. One approach to tackling problems of such complexity is to address the scientific questions in simpler, yet analogous, systems. The fruit fly, Drosophila melanogaster, has been proven tremendously valuable as a model organism, enabling many major discoveries in neuroscientific disease research. The plethora of genetic tools available in Drosophila allows for exquisite targeted manipulation of the genome. Due to its relatively short lifespan, complex questions of brain function can be addressed more rapidly than in other model organisms, such as the mouse. Here we discuss features of the fly as a model for human neurodegenerative disease. There are many distinct fly models for a range of neurodegenerative diseases; we focus on select studies from models of polyglutamine disease and amyotrophic lateral sclerosis that illustrate the type and range of insights that can be gleaned. In discussion of these models, we underscore strengths of the fly in providing understanding into mechanisms and pathways, as a foundation for translational and therapeutic research. PMID:26447127

  9. Use of rodents as models of human diseases

    PubMed Central

    Vandamme, Thierry F.

    2014-01-01

    Advances in molecular biology have significantly increased the understanding of the biology of different diseases. However, these discoveries have not yet been fully translated into improved treatments for patients with diseases such as cancers. One of the factors limiting the translation of knowledge from preclinical studies to the clinic has been the limitations of in vivo diseases models. In this brief review, we will discuss the advantages and disadvantages of rodent models that have been developed to simulate human pathologies, focusing in models that employ xenografts and genetic modification. Within the framework of genetically engineered mouse (GEM) models, we will review some of the current genetic strategies for modeling diseases in the mouse and the preclinical studies that have already been undertaken. We will also discuss how recent improvements in imaging technologies may increase the information derived from using these GEMs during early assessments of potential therapeutic pathways. Furthermore, it is interesting to note that one of the values of using a mouse model is the very rapid turnover rate of the animal, going through the process of birth to death in a very short timeframe relative to that of larger mammalian species. PMID:24459397

  10. Development of a human eye model for visual performance assessment

    NASA Astrophysics Data System (ADS)

    Jiang, Chong-Jhih; Chen, Yi-Chun; Yang, Tsung-Hsun; Sun, Ching-Cherng

    2009-08-01

    A biometry-based human eye model was developed by using the empirical anatomic and optical data of ocular parameters. The gradient refractive index of the crystalline lens was modeled by concentric conicoid isoindical surfaces and was adaptive to accommodation and age. The chromatic dispersion of homogeneous ocular media was described by Cauchy equations. The gradient equations for the refractive index of crystalline lens were modified at particular wavelengths according to the same dispersion model. Mie scattering was introduced to simulate volumetric light scattering in the crystalline lens. The optical performance of the eye model was evaluated in CodeV and ASAP and presented by the modulation transfer function (MTF) at single and multiple wavelengths. The chromatic optical powers obtained from this model matched that of physiological eyes. The scattering property was assessed by means of glare veiling luminance and compared with CIE general disability glare equation. This model is highly potential for investigating visual performance in ordinary lighting and display conditions and under the influence of glare sources.

  11. A recellularized human colon model identifies cancer driver genes.

    PubMed

    Chen, Huanhuan Joyce; Wei, Zhubo; Sun, Jian; Bhattacharya, Asmita; Savage, David J; Serda, Rita; Mackeyev, Yuri; Curley, Steven A; Bu, Pengcheng; Wang, Lihua; Chen, Shuibing; Cohen-Gould, Leona; Huang, Emina; Shen, Xiling; Lipkin, Steven M; Copeland, Neal G; Jenkins, Nancy A; Shuler, Michael L

    2016-08-01

    Refined cancer models are needed to bridge the gaps between cell line, animal and clinical research. Here we describe the engineering of an organotypic colon cancer model by recellularization of a native human matrix that contains cell-populated mucosa and an intact muscularis mucosa layer. This ex vivo system recapitulates the pathophysiological progression from APC-mutant neoplasia to submucosal invasive tumor. We used it to perform a Sleeping Beauty transposon mutagenesis screen to identify genes that cooperate with mutant APC in driving invasive neoplasia. We identified 38 candidate invasion-driver genes, 17 of which, including TCF7L2, TWIST2, MSH2, DCC, EPHB1 and EPHB2 have been previously implicated in colorectal cancer progression. Six invasion-driver genes that have not, to our knowledge, been previously described were validated in vitro using cell proliferation, migration and invasion assays and ex vivo using recellularized human colon. These results demonstrate the utility of our organoid model for studying cancer biology. PMID:27398792

  12. A Dynamic Approach to Modeling Dependence Between Human Failure Events

    SciTech Connect

    Boring, Ronald Laurids

    2015-09-01

    In practice, most HRA methods use direct dependence from THERP—the notion that error be- gets error, and one human failure event (HFE) may increase the likelihood of subsequent HFEs. In this paper, we approach dependence from a simulation perspective in which the effects of human errors are dynamically modeled. There are three key concepts that play into this modeling: (1) Errors are driven by performance shaping factors (PSFs). In this context, the error propagation is not a result of the presence of an HFE yielding overall increases in subsequent HFEs. Rather, it is shared PSFs that cause dependence. (2) PSFs have qualities of lag and latency. These two qualities are not currently considered in HRA methods that use PSFs. Yet, to model the effects of PSFs, it is not simply a matter of identifying the discrete effects of a particular PSF on performance. The effects of PSFs must be considered temporally, as the PSFs will have a range of effects across the event sequence. (3) Finally, there is the concept of error spilling. When PSFs are activated, they not only have temporal effects but also lateral effects on other PSFs, leading to emergent errors. This paper presents the framework for tying together these dynamic dependence concepts.

  13. Zebrafish as a disease model for studying human hepatocellular carcinoma

    PubMed Central

    Lu, Jeng-Wei; Ho, Yi-Jung; Yang, Yi-Ju; Liao, Heng-An; Ciou, Shih-Ci; Lin, Liang-In; Ou, Da-Liang

    2015-01-01

    Liver cancer is one of the world’s most common cancers and the second leading cause of cancer deaths. Hepatocellular carcinoma (HCC), a primary hepatic cancer, accounts for 90%-95% of liver cancer cases. The pathogenesis of HCC consists of a stepwise process of liver damage that extends over decades, due to hepatitis, fatty liver, fibrosis, and cirrhosis before developing fully into HCC. Multiple risk factors are highly correlated with HCC, including infection with the hepatitis B or C viruses, alcohol abuse, aflatoxin exposure, and metabolic diseases. Over the last decade, genetic alterations, which include the regulation of multiple oncogenes or tumor suppressor genes and the activation of tumorigenesis-related pathways, have also been identified as important factors in HCC. Recently, zebrafish have become an important living vertebrate model organism, especially for translational medical research. In studies focusing on the biology of cancer, carcinogen induced tumors in zebrafish were found to have many similarities to human tumors. Several zebrafish models have therefore been developed to provide insight into the pathogenesis of liver cancer and the related drug discovery and toxicology, and to enable the evaluation of novel small-molecule inhibitors. This review will focus on illustrative examples involving the application of zebrafish models to the study of human liver disease and HCC, through transgenesis, genome editing technology, xenografts, drug discovery, and drug-induced toxic liver injury. PMID:26576090

  14. The Northwestern Abdominoplasty Scar Model: A Novel Human Model for Scar Research and Therapeutics

    PubMed Central

    Lanier, Steven T.; Liu, Jing; Chavez-Munoz, Claudia; Mustoe, Thomas A.

    2016-01-01

    Summary: There is a growing interest in the development and evaluation of therapeutic agents that improve the cosmetic appearance of scars. Existing nonhuman animal models to study scarring, while valuable, have well-acknowledged limitations, as it is accepted that the biology of human scarring differs significantly from scarring in other species. Moreover, human clinical trials of scarring require large numbers of subjects to achieve statistical power and are plagued by inherent intersubject variability because of the complex nature of wound healing in human beings. As a better alternative, we have developed the Northwestern Abdominoplasty Scar Model—a novel human clinical model that permits analysis of up to 20 cutaneous scars in a single subject and allows for not only visual scar comparison, but also histologic and molecular analyses of factors involved in scarring and wound healing. We have utilized this model in 5 early phase clinical trials designed to test the safety and efficacy of a variety of scar therapeutics without any complications to date. The model not only is applicable to scar therapeutics, but also can be utilized for other applications, such as the testing of implantable biomaterials, injectable products, therapies such as lasers, or even for in vivo study of wound healing processes in humans. PMID:27757332

  15. Zebrafish models of human motor neuron diseases: advantages and limitations.

    PubMed

    Babin, Patrick J; Goizet, Cyril; Raldúa, Demetrio

    2014-07-01

    Motor neuron diseases (MNDs) are an etiologically heterogeneous group of disorders of neurodegenerative origin, which result in degeneration of lower (LMNs) and/or upper motor neurons (UMNs). Neurodegenerative MNDs include pure hereditary spastic paraplegia (HSP), which involves specific degeneration of UMNs, leading to progressive spasticity of the lower limbs. In contrast, spinal muscular atrophy (SMA) involves the specific degeneration of LMNs, with symmetrical muscle weakness and atrophy. Amyotrophic lateral sclerosis (ALS), the most common adult-onset MND, is characterized by the degeneration of both UMNs and LMNs, leading to progressive muscle weakness, atrophy, and spasticity. A review of the comparative neuroanatomy of the human and zebrafish motor systems showed that, while the zebrafish was a homologous model for LMN disorders, such as SMA, it was only partially relevant in the case of UMN disorders, due to the absence of corticospinal and rubrospinal tracts in its central nervous system. Even considering the limitation of this model to fully reproduce the human UMN disorders, zebrafish offer an excellent alternative vertebrate model for the molecular and genetic dissection of MND mechanisms. Its advantages include the conservation of genome and physiological processes and applicable in vivo tools, including easy imaging, loss or gain of function methods, behavioral tests to examine changes in motor activity, and the ease of simultaneous chemical/drug testing on large numbers of animals. This facilitates the assessment of the environmental origin of MNDs, alone or in combination with genetic traits and putative modifier genes. Positive hits obtained by phenotype-based small-molecule screening using zebrafish may potentially be effective drugs for treatment of human MNDs.

  16. Zebrafish models of human motor neuron diseases: advantages and limitations.

    PubMed

    Babin, Patrick J; Goizet, Cyril; Raldúa, Demetrio

    2014-07-01

    Motor neuron diseases (MNDs) are an etiologically heterogeneous group of disorders of neurodegenerative origin, which result in degeneration of lower (LMNs) and/or upper motor neurons (UMNs). Neurodegenerative MNDs include pure hereditary spastic paraplegia (HSP), which involves specific degeneration of UMNs, leading to progressive spasticity of the lower limbs. In contrast, spinal muscular atrophy (SMA) involves the specific degeneration of LMNs, with symmetrical muscle weakness and atrophy. Amyotrophic lateral sclerosis (ALS), the most common adult-onset MND, is characterized by the degeneration of both UMNs and LMNs, leading to progressive muscle weakness, atrophy, and spasticity. A review of the comparative neuroanatomy of the human and zebrafish motor systems showed that, while the zebrafish was a homologous model for LMN disorders, such as SMA, it was only partially relevant in the case of UMN disorders, due to the absence of corticospinal and rubrospinal tracts in its central nervous system. Even considering the limitation of this model to fully reproduce the human UMN disorders, zebrafish offer an excellent alternative vertebrate model for the molecular and genetic dissection of MND mechanisms. Its advantages include the conservation of genome and physiological processes and applicable in vivo tools, including easy imaging, loss or gain of function methods, behavioral tests to examine changes in motor activity, and the ease of simultaneous chemical/drug testing on large numbers of animals. This facilitates the assessment of the environmental origin of MNDs, alone or in combination with genetic traits and putative modifier genes. Positive hits obtained by phenotype-based small-molecule screening using zebrafish may potentially be effective drugs for treatment of human MNDs. PMID:24705136

  17. Modeling of the Nitric Oxide Transport in the Human Lungs

    PubMed Central

    Karamaoun, Cyril; Van Muylem, Alain; Haut, Benoît

    2016-01-01

    In the human lungs, nitric oxide (NO) acts as a bronchodilatator, by relaxing the bronchial smooth muscles and is closely linked to the inflammatory status of the lungs, owing to its antimicrobial activity. Furthermore, the molar fraction of NO in the exhaled air has been shown to be higher for asthmatic patients than for healthy patients. Multiple models have been developed in order to characterize the NO dynamics in the lungs, owing to their complex structure. Indeed, direct measurements in the lungs are difficult and, therefore, these models are valuable tools to interpret experimental data. In this work, a new model of the NO transport in the human lungs is proposed. It belongs to the family of the morphological models and is based on the morphometric model of Weibel (1963). When compared to models published previously, its main new features are the layered representation of the wall of the airways and the possibility to simulate the influence of bronchoconstriction (BC) and of the presence of mucus on the NO transport in lungs. The model is based on a geometrical description of the lungs, at rest and during a respiratory cycle, coupled with transport equations, written in the layers composing an airway wall and in the lumen of the airways. First, it is checked that the model is able to reproduce experimental information available in the literature. Second, the model is used to discuss some features of the NO transport in healthy and unhealthy lungs. The simulation results are analyzed, especially when BC has occurred in the lungs. For instance, it is shown that BC can have a significant influence on the NO transport in the tissues composing an airway wall. It is also shown that the relation between BC and the molar fraction of NO in the exhaled air is complex. Indeed, BC might lead to an increase or to a decrease of this molar fraction, depending on the extent of the BC and on the possible presence of mucus. This should be confirmed experimentally and might

  18. A human performance modelling approach to intelligent decision support systems

    NASA Technical Reports Server (NTRS)

    Mccoy, Michael S.; Boys, Randy M.

    1987-01-01

    Manned space operations require that the many automated subsystems of a space platform be controllable by a limited number of personnel. To minimize the interaction required of these operators, artificial intelligence techniques may be applied to embed a human performance model within the automated, or semi-automated, systems, thereby allowing the derivation of operator intent. A similar application has previously been proposed in the domain of fighter piloting, where the demand for pilot intent derivation is primarily a function of limited time and high workload rather than limited operators. The derivation and propagation of pilot intent is presented as it might be applied to some programs.

  19. An object oriented implementation of the Yeadon human inertia model

    PubMed Central

    Dembia, Christopher; Moore, Jason K.; Hubbard, Mont

    2015-01-01

    We present an open source software implementation of a popular mathematical method developed by M.R. Yeadon for calculating the body and segment inertia parameters of a human body. The software is written in a high level open source language and provides three interfaces for manipulating the data and the model: a Python API, a command-line user interface, and a graphical user interface. Thus the software can fit into various data processing pipelines and requires only simple geometrical measures as input. PMID:25717365

  20. Mouse and Cotton Rat Models of Human Respiratory Syncytial Virus.

    PubMed

    Rudd, Penny A; Chen, Weiqiang; Mahalingam, Suresh

    2016-01-01

    Human respiratory syncytial virus (hRSV) is a common respiratory virus that is usually no cause for alarm. Symptoms of hRSV usually resemble those of the common cold and can go undiagnosed. However, infants as well as the elderly are at risk for developing severe cases, which can lead to high morbidity and mortality rates especially if there are underlying health issues. Despite many years of effort, no vaccine or specific treatments exist and RSV is still the leading cause of infant hospitalizations worldwide. Here, we describe methods to infect two widely used small animal models: laboratory mice and cotton rats. PMID:27464697

  1. Air pollution dispersion models for human exposure predictions in London.

    PubMed

    Beevers, Sean D; Kitwiroon, Nutthida; Williams, Martin L; Kelly, Frank J; Ross Anderson, H; Carslaw, David C

    2013-01-01

    The London household survey has shown that people travel and are exposed to air pollutants differently. This argues for human exposure to be based upon space-time-activity data and spatio-temporal air quality predictions. For the latter, we have demonstrated the role that dispersion models can play by using two complimentary models, KCLurban, which gives source apportionment information, and Community Multi-scale Air Quality Model (CMAQ)-urban, which predicts hourly air quality. The KCLurban model is in close agreement with observations of NO(X), NO(2) and particulate matter (PM)(10/2.5), having a small normalised mean bias (-6% to 4%) and a large Index of Agreement (0.71-0.88). The temporal trends of NO(X) from the CMAQ-urban model are also in reasonable agreement with observations. Spatially, NO(2) predictions show that within 10's of metres of major roads, concentrations can range from approximately 10-20 p.p.b. up to 70 p.p.b. and that for PM(10/2.5) central London roadside concentrations are approximately double the suburban background concentrations. Exposure to different PM sources is important and we predict that brake wear-related PM(10) concentrations are approximately eight times greater near major roads than at suburban background locations. Temporally, we have shown that average NO(X) concentrations close to roads can range by a factor of approximately six between the early morning minimum and morning rush hour maximum periods. These results present strong arguments for the hybrid exposure model under development at King's and, in future, for in-building models and a model for the London Underground.

  2. The stability of the three transmembrane and the four transmembrane human vitamin K epoxide reductase models

    NASA Astrophysics Data System (ADS)

    Wu, Sangwook

    2016-04-01

    The three transmembrane and the four transmembrane helix models are suggested for human vitamin K epoxide reductase (VKOR). In this study, we investigate the stability of the human three transmembrane/four transmembrane VKOR models by employing a coarse-grained normal mode analysis and molecular dynamics simulation. Based on the analysis of the mobility of each transmembrane domain, we suggest that the three transmembrane human VKOR model is more stable than the four transmembrane human VKOR model.

  3. Acetaminophen-induced Liver Injury: from Animal Models to Humans.

    PubMed

    Jaeschke, Hartmut; Xie, Yuchao; McGill, Mitchell R

    2014-09-01

    Drug-induced liver injury is an important clinical problem and a challenge for drug development. Whereas progress in understanding rare and unpredictable (idiosyncratic) drug hepatotoxicity is severely hampered by the lack of relevant animal models, enormous insight has been gained in the area of predictable hepatotoxins, in particular acetaminophen-induced liver injury, from a broad range of experimental models. Importantly, mechanisms of toxicity obtained with certain experimental systems, such as in vivo mouse models, primary mouse hepatocytes, and metabolically competent cell lines, are being confirmed in translational studies in patients and in primary human hepatocytes. Despite this progress, suboptimal models are still being used and experimental data can be confusing, leading to controversial conclusions. Therefore, this review attempts to discuss mechanisms of drug hepatotoxicity using the most studied drug acetaminophen as an example. We compare the various experimental models that are used to investigate mechanisms of acetaminophen hepatotoxicity, discuss controversial topics in the mechanisms, and assess how these experimental findings can be translated to the clinic. The success with acetaminophen in demonstrating the clinical relevance of experimental findings could serve as an example for the study of other drug toxicities. PMID:26355817

  4. Dynamic viscoelastic models of human skin using optical elastography

    PubMed Central

    Kearney, Steven P.; Khan, Altaf; Dai, Zoujun; Royston, Thomas J.

    2015-01-01

    A novel technique for measuring in vivo human skin viscoelastic properties using optical elastography has been developed. The technique uses geometrically focused surface (GFS) waves that allow for wide bandwidth measurements of the wave field. An analytical solution for the case of a radiating annular disk surface source was fit to experimentally measured GFS waves, enabling an estimate of the frequency-dependent surface wavenumber, which can then be related to the dynamic shear modulus. Several viscoelastic models were then fit to the dynamic shear modulus dispersion curve. Viscoelastic models were evaluated based on their overall quality of fit and variability amongst healthy volunteers. An Ecoflex phantom was used to validate the procedure and results by comparison to similar studies using the same type of phantom. For skin results, it was found that the “α” parameters from the fractional models had the least variability, with coefficients of variability of 0.15, and 0.16. The best fitting models were the standard linear solid, and the fractional Voigt, with a mean fit correlation coefficient, R2, of 0.93, 0.89, respectively. This study has demonstrated the efficacy of this new method, and with larger studies the viscoelastic skin models could be used to identify various skin diseases and their response to treatment. PMID:26305137

  5. An Orthotopic Murine Model of Human Prostate Cancer Metastasis

    PubMed Central

    Pavese, Janet; Ogden, Irene M.; Bergan, Raymond C.

    2013-01-01

    Our laboratory has developed a novel orthotopic implantation model of human prostate cancer (PCa). As PCa death is not due to the primary tumor, but rather the formation of distinct metastasis, the ability to effectively model this progression pre-clinically is of high value. In this model, cells are directly implanted into the ventral lobe of the prostate in Balb/c athymic mice, and allowed to progress for 4-6 weeks. At experiment termination, several distinct endpoints can be measured, such as size and molecular characterization of the primary tumor, the presence and quantification of circulating tumor cells in the blood and bone marrow, and formation of metastasis to the lung. In addition to a variety of endpoints, this model provides a picture of a cells ability to invade and escape the primary organ, enter and survive in the circulatory system, and implant and grow in a secondary site. This model has been used effectively to measure metastatic response to both changes in protein expression as well as to response to small molecule therapeutics, in a short turnaround time. PMID:24084571

  6. Beyond the zebrafish: diverse fish species for modeling human disease

    PubMed Central

    Schartl, Manfred

    2014-01-01

    ABSTRACT In recent years, zebrafish, and to a lesser extent medaka, have become widely used small animal models for human diseases. These organisms have convincingly demonstrated the usefulness of fish for improving our understanding of the molecular and cellular mechanisms leading to pathological conditions, and for the development of new diagnostic and therapeutic tools. Despite the usefulness of zebrafish and medaka in the investigation of a wide spectrum of traits, there is evidence to suggest that other fish species could be better suited for more targeted questions. With the emergence of new, improved sequencing technologies that enable genomic resources to be generated with increasing efficiency and speed, the potential of non-mainstream fish species as disease models can now be explored. A key feature of these fish species is that the pathological condition that they model is often related to specific evolutionary adaptations. By exploring these adaptations, new disease-causing and disease-modifier genes might be identified; thus, diverse fish species could be exploited to better understand the complexity of disease processes. In addition, non-mainstream fish models could allow us to study the impact of environmental factors, as well as genetic variation, on complex disease phenotypes. This Review will discuss the opportunities that such fish models offer for current and future biomedical research. PMID:24271780

  7. Dynamic viscoelastic models of human skin using optical elastography.

    PubMed

    Kearney, Steven P; Khan, Altaf; Dai, Zoujun; Royston, Thomas J

    2015-09-01

    A novel technique for measuring in vivo human skin viscoelastic properties using optical elastography has been developed. The technique uses geometrically focused surface (GFS) waves that allow for wide bandwidth measurements of the wave field. An analytical solution for the case of a radiating annular disk surface source was fit to experimentally measured GFS waves, enabling an estimate of the frequency-dependent surface wavenumber, which can then be related to the dynamic shear modulus. Several viscoelastic models were then fit to the dynamic shear modulus dispersion curve. Viscoelastic models were evaluated based on their overall quality of fit and variability amongst healthy volunteers. An Ecoflex phantom was used to validate the procedure and results by comparison to similar studies using the same type of phantom. For skin results, it was found that the 'α' parameters from the fractional models had the least variability, with coefficients of variability of 0.15, and 0.16. The best fitting models were the standard linear solid, and the fractional Voigt, with a mean fit correlation coefficient, R(2), of 0.93, 0.89, respectively. This study has demonstrated the efficacy of this new method, and with larger studies the viscoelastic skin models could be used to identify various skin diseases and their response to treatment. PMID:26305137

  8. Crazy like a fox. Validity and ethics of animal models of human psychiatric disease.

    PubMed

    Rollin, Michael D H; Rollin, Bernard E

    2014-04-01

    Animal models of human disease play a central role in modern biomedical science. Developing animal models for human mental illness presents unique practical and philosophical challenges. In this article we argue that (1) existing animal models of psychiatric disease are not valid, (2) attempts to model syndromes are undermined by current nosology, (3) models of symptoms are rife with circular logic and anthropomorphism, (4) any model must make unjustified assumptions about subjective experience, and (5) any model deemed valid would be inherently unethical, for if an animal adequately models human subjective experience, then there is no morally relevant difference between that animal and a human.

  9. Acrylamide induces accelerated endothelial aging in a human cell model.

    PubMed

    Sellier, Cyril; Boulanger, Eric; Maladry, François; Tessier, Frédéric J; Lorenzi, Rodrigo; Nevière, Rémi; Desreumaux, Pierre; Beuscart, Jean-Baptiste; Puisieux, François; Grossin, Nicolas

    2015-09-01

    Acrylamide (AAM) has been recently discovered in food as a Maillard reaction product. AAM and glycidamide (GA), its metabolite, have been described as probably carcinogenic to humans. It is widely established that senescence and carcinogenicity are closely related. In vitro, endothelial aging is characterized by replicative senescence in which primary cells in culture lose their ability to divide. Our objective was to assess the effects of AAM and GA on human endothelial cell senescence. Human umbilical vein endothelial cells (HUVECs) cultured in vitro were used as model. HUVECs were cultured over 3 months with AAM or GA (1, 10 or 100 μM) until growth arrest. To analyze senescence, β-galactosidase activity and telomere length of HUVECs were measured by cytometry and semi-quantitative PCR, respectively. At all tested concentrations, AAM or GA reduced cell population doubling compared to the control condition (p < 0.001). β-galactosidase activity in endothelial cells was increased when exposed to AAM (≥10 μM) or GA (≥1 μM) (p < 0.05). AAM (≥10 μM) or GA (100 μM) accelerated telomere shortening in HUVECs (p < 0.05). In conclusion, in vitro chronic exposure to AAM or GA at low concentrations induces accelerated senescence. This result suggests that an exposure to AAM might contribute to endothelial aging.

  10. Labor of love. A model for planning human resource needs.

    PubMed

    Brady, F J

    1989-01-01

    Typically, the annual budgeting process is the hospital's only attempt to forecast human resource requirements. In times of rapid change, this traditional ad hoc approach is incapable of satisfying either the Catholic hospital's ethical obligations as an employer or its responsibilities to provide healthcare to the poor and suffering. Assumptions about future activity, including volume projections on admissions, patient days, and other services, influence the budgeting process to a large degree. Because the amount of work to be done and the number of employees required to do it are related, changes in demand for service immediately and directly affect staffing requirements. A hospital cannot achieve ethical human resource management or provide high-quality healthcare if inadequate planning forces management into a cycle of crisis-coping--reacting to this year's nursing shortage with a major recruiting effort and next year's financial crunch with a traumatic reduction in force. The human resource planning approach outlined here helps the hospital meet legitimate business needs while satisfying its ethical obligations. The model has four phases and covers a charge to the planning committee; committee appointments; announcements; the establishment of ground rules, focus, and task forces; and the work of each task force.

  11. Human Liver Transplantation As A Model To Study HCV Pathogenesis

    PubMed Central

    Hughes, Michael G.; Rosen, Hugo R.

    2010-01-01

    Hepatitis C is a leading etiology of liver cancer and cause for liver transplantation. Although new therapies have improved the rates of sustained response, a large proportion of patients (~50%) fail to respond to antiviral treatment, thus remaining at risk for disease progression. While chimpanzees have been used to study HCV biology and treatments, their cost is quite high and their use is strictly regulated; indeed, the NIH no longer supports the breeding of chimpanzees for study. The development of HCV therapies has been hindered by the relative paucity of small animal models to study HCV pathogenesis. This review presents the strengths of the human liver transplant, highlighting the advances derived from this model, including insights into viral kinetics and quasispecies, viral receptor binding and entry, innate and adaptive immunity. Moreover, consideration is made of current and emerging antiviral therapeutic approaches based on translational research results. PMID:19877210

  12. Developing a computational model of human hand kinetics using AVS

    SciTech Connect

    Abramowitz, Mark S.

    1996-05-01

    As part of an ongoing effort to develop a finite element model of the human hand at the Institute for Scientific Computing Research (ISCR), this project extended existing computational tools for analyzing and visualizing hand kinetics. These tools employ a commercial, scientific visualization package called AVS. FORTRAN and C code, originally written by David Giurintano of the Gillis W. Long Hansen`s Disease Center, was ported to a different computing platform, debugged, and documented. Usability features were added and the code was made more modular and readable. When the code is used to visualize bone movement and tendon paths for the thumb, graphical output is consistent with expected results. However, numerical values for forces and moments at the thumb joints do not yet appear to be accurate enough to be included in ISCR`s finite element model. Future work includes debugging the parts of the code that calculate forces and moments and verifying the correctness of these values.

  13. Mathematical modelling of flow distribution in the human cardiovascular system

    NASA Technical Reports Server (NTRS)

    Sud, V. K.; Srinivasan, R. S.; Charles, J. B.; Bungo, M. W.

    1992-01-01

    The paper presents a detailed model of the entire human cardiovascular system which aims to study the changes in flow distribution caused by external stimuli, changes in internal parameters, or other factors. The arterial-venous network is represented by 325 interconnected elastic segments. The mathematical description of each segment is based on equations of hydrodynamics and those of stress/strain relationships in elastic materials. Appropriate input functions provide for the pumping of blood by the heart through the system. The analysis employs the finite-element technique which can accommodate any prescribed boundary conditions. Values of model parameters are from available data on physical and rheological properties of blood and blood vessels. As a representative example, simulation results on changes in flow distribution with changes in the elastic properties of blood vessels are discussed. They indicate that the errors in the calculated overall flow rates are not significant even in the extreme case of arteries and veins behaving as rigid tubes.

  14. Physical model of human eye with implantable intraocular lenses

    NASA Astrophysics Data System (ADS)

    Barcik, Agnieszka; Nowak, Jerzy; Siedlecki, Damian; Zając, Marek; Zarówny, Józef

    2008-12-01

    An optomechanical model of human eye containing artificial cornea and a cuvette with immersion liquid is developed. An artificial implantable intraoculer lens (IOL) inserted into the cuvette stands for the eye crystalline lens. A special mechanical handle holding the IOL enables to move and rotate it thus simulationg possible errors during lens implantation procedure. The "retinal" image is recorded with the high resolution CCD camera. The image of Siemens star serves as qualitative measure of "retinal" image, while more quantitatively data come from Modulation Transfer Function obtained by the analysis of the images of sinusoidal tests generated on the computer screen. The whole eye model can be used for investigation of the impact of type and location of the IOL on the optical performance.

  15. AADC deficiency: occurring in humans, modeled in rodents.

    PubMed

    Hwu, Wuh-Liang; Lee, Ni-Chung; Chien, Yin-Hsiu; Muramatsu, Shin-ichi; Ichinose, Hiroshi

    2013-01-01

    Aromatic l-amino acid decarboxylase (AADC) is a homodimeric pyridoxal phosphate-dependent enzyme responsible for the syntheses of dopamine and serotonin. Defects in the AADC gene result in neurotransmitter deficiencies. Patients with AADC deficiency have severe motor and autonomic dysfunctions. A mouse model of AADC deficiency was recently established. These mice grow poorly and move awkwardly during infancy. They also show high anxiety when they grow up. Because drug therapy provides little or no benefit for many patients with AADC deficiency, a gene therapy has been attempted. The gene therapy employed an adeno-associated virus viral vector that can express the human AADC protein. The vector was injected to the brain of several children with AADC deficiency. The therapy was well tolerated, and all treated patients showed improvement. In the future, the mouse model will also help the development of treatments for AADC deficiency.

  16. On the dynamics of a human body model.

    NASA Technical Reports Server (NTRS)

    Huston, R. L.; Passerello, C. E.

    1971-01-01

    Equations of motion for a model of the human body are developed. Basically, the model consists of an elliptical cylinder representing the torso, together with a system of frustrums of elliptical cones representing the limbs. They are connected to the main body and each other by hinges and ball and socket joints. Vector, tensor, and matrix methods provide a systematic organization of the geometry. The equations of motion are developed from the principles of classical mechanics. The solution of these equations then provide the displacement and rotation of the main body when the external forces and relative limb motions are specified. Three simple example motions are studied to illustrate the method. The first is an analysis and comparison of simple lifting on the earth and the moon. The second is an elementary approach to underwater swimming, including both viscous and inertia effects. The third is an analysis of kicking motion and its effect upon a vertically suspended man such as a parachutist.

  17. Treatment model of dengue hemorrhagic fever infection in human body

    NASA Astrophysics Data System (ADS)

    Handayani, D.; Nuraini, N.; Primasari, N.; Wijaya, K. P.

    2014-03-01

    The treatment model of DHF presented in this paper involves the dynamic of five time-dependent compartments, i.e. susceptible, infected, free virus particle, immune cell, and haematocrit level. The treatment model is investigated based on normalization of haematocrit level, which is expressed as intravenous fluid infusion control. We analyze the stability of the disease free equilibrium and the endemic equilibrium. The numerical simulations will explain the dynamic of each compartment in human body. These results show particularly that infected compartment and free virus particle compartment are tend to be vanished in two weeks after the onset of dengue virus. However, these simulation results also show that without the treatment, the haematocrit level will decrease even though not up to the normal level. Therefore the effective haematocrit normalization should be done with the treatment control.

  18. [Human resources planning: the use of demographic-economic models].

    PubMed

    Daubon, R E

    1980-01-01

    This article provides an overview of the evolution of employment at different stages of economic development and describes the employment situation in developing countries, suggesting future trends and means of improvement. The lack of authentic development is reflected in the problem of employment of both natural and human resources in Third World countries. Their occupational structures may be examined in 2 periods, 1 in which a certain pretransitional equilibrium was still observed, and the other following the beginning of industrialization. With increased population growth and the application of development strategies favoring urban areas and manufacturing, a series of imbalances were introduced which had as 1 consequence an ever widening income gap between rural areas, cities, and developed countries. Rural stagnation and population pressure ultimately led to massive urban migration in many areas, swelling the cities and creating an "informal sector" of underemployed persons in marginal activities of low productivity. By 2050, the world labor force will have increased from its present 1.7 billion workers to 3.8 billion, of which only 660 million will be in presently developed countries. Each country must plan the best use of its human resources, and must include employment planning in overall development planning. The development of economic-demographic models, adapted to the context of each country, can be a valuable tool in planning. Various types of economic-demographic models and their uses are described and differentiated. Economic-demographic models of employment have 3 main parts, demography, economy, and training. Their use in the analysis of the impact of specific variables on employment, of policies, and of general strategies is described. Finally, the characteristics and uses of MODEMP, an economic-demographic model created for analysis of labor force and employment problems in Peru, are described. PMID:12265325

  19. ALIGNING MOUSE MODELS OF ASTHMA TO HUMAN ENDOTYPES OF DISEASE

    PubMed Central

    Martin, Rebecca A; Hodgkins, Samantha R; Dixon, Anne E; Poynter, Matthew E

    2014-01-01

    Substantial gains in understanding the pathophysiologic mechanisms underlying asthma have been made using preclinical mouse models. However, because asthma is a complex, heterogeneous syndrome that is rarely due to a single allergen and that often presents in the absence of atopy, few of the promising therapeutics that demonstrated effectiveness in mouse models have translated into new treatments for patients. This has resulted in an urgent need to characterize Th2-low, noneosinophilic subsets of asthma, to study models that are resistant to conventional treatments such as corticosteroids, and to develop therapies targeting patients with severe disease. Classifying asthma based on underlying pathophysiologic mechanisms, known as endotyping, offers a stratified approach for the development of new therapies for asthma. In preclinical research, new models of asthma are being utilized that more closely resemble the clinical features of different asthma endotypes, including the presence of IL-17 and a Th17 response, a biomarker of severe disease. These models utilize more physiologically relevant sensitizing agents, exacerbating factors, and allergens, as well as incorporate time points that better reflect the natural history and chronicity of clinical asthma. Importantly, some models better represent nonclassical asthma endotypes that facilitate the study of non-Th2 driven pathology and resemble the complex nature of clinical asthma, including corticosteroid resistance. Placing mouse asthma models into the context of human asthma endotypes will afford a more relevant approach to the understanding of pathophysiological mechanisms of disease that will afford the development of new therapies for those asthmatics that remain difficult to treat. PMID:24811131

  20. Machine vision algorithm generation using human visual models

    NASA Astrophysics Data System (ADS)

    Daley, Wayne D.; Doll, Theodore J.; McWhorter, Shane W.; Wasilewski, Anthony A.

    1999-01-01

    The design of robust machine vision algorithms is one of the most difficult parts of developing and integrating automated systems. Historically, most of the techniques have been developed using ad hoc methodologies. This problem is more severe in the area of natural/biological products. In this arena, it has been difficult to capture and model the natural variability to be expected in the products. This present difficulty in performing quality and process control in the meat, fruit and vegetable industries. While some systems have been introduced, they do not adequately address the wide range of needs. This paper will propose an algorithm development technique that utilizes modes of the human visual system. It will address that subset of problems that humans perform well, but have proven difficult to automate with the standard machine vision techniques. The basis of the technique evaluation will be the Georgia Tech Vision model. This approach demonstrates a high level of accuracy in its ability to solve difficult problems. This paper will present the approach, the result, and possibilities for implementation.

  1. Modelling and monitoring of passive control structures in human movement

    NASA Astrophysics Data System (ADS)

    Hemami, Hooshang; Hemami, Mahmoud

    2014-09-01

    Passive tissues, ligaments and cartilage are vital to human movement. Their contribution to stability, joint function and joint integrity is essential. The articulation of their functions and quantitative assessment of what they do in a healthy or injured state are important in athletics, orthopaedics, medicine and health. In this paper, the role of cartilage and ligaments in stability of natural contacts, connections and joints is articulated by including them in two very simple skeletal systems: one- and three-link rigid body systems. Based on the Newton-Euler equations, a state space presentation of the dynamics is discussed that allows inclusion of ligament and cartilage structures in the model, and allows for Lyapunov stability studies for the original and reduced systems. The connection constraints may be holonomic and non-holonomic depending on the structure of the passive elements. The development is pertinent to the eventual design of a computational framework for the study of human movement that involves computer models of all the relevant skeletal, neural and physiological elements of the central nervous system (CNS). Such a structure also permits testing of different hypotheses about the functional neuroanatomy of the CNS, and the study of the effects and dynamics of disease, deterioration, aging and injuries. The formulation here is applied to one- and three-link systems. Digital computer simulations of a two rigid body system are presented to demonstrate the feasibility and effectiveness of the approach and the methods.

  2. Visual model of human blur perception for scene adaptive capturing

    NASA Astrophysics Data System (ADS)

    Kim, Sung-Su; Chung, DaeSu; Park, Byung-Kwan; Kim, Jung-Bae; Lee, Seong-Deok

    2009-01-01

    Despite fast spreading of digital cameras, many people cannot take pictures of high quality, they want, due to lack of photography. To help users under the unfavorable capturing environments, e.g. 'Night', 'Backlighting', 'Indoor', or 'Portrait', the automatic mode of cameras provides parameter sets by manufactures. Unfortunately, this automatic functionality does not give pleasing image quality in general. Especially, length of exposure (shutter speed) is critical factor in taking high quality pictures in the night. One of key factors causing this bad quality in the night is the image blur, which mainly comes from hand-shaking in long capturing. In this study, to circumvent this problem and to enhance image quality of automatic cameras, we propose an intelligent camera processing core having BASE (Scene Adaptive Blur Estimation) and VisBLE (Visual Blur Limitation Estimation). SABE analyzes the high frequency component in the DCT (Discrete Cosine Transform) domain. VisBLE determines acceptable blur level on the basis of human visual tolerance and Gaussian model. This visual tolerance model is developed on the basis of human perception physiological mechanism. In the experiments proposed method outperforms existing imaging systems by general users and photographers, as well.

  3. Immunology of membranous nephropathy: from animal models to humans.

    PubMed

    Sinico, R A; Mezzina, N; Trezzi, B; Ghiggeri, G M; Radice, A

    2016-02-01

    Membranous nephropathy (MN), the leading cause of nephrotic syndrome in adults, is characterized by the deposition of subepithelial immune deposits that consist mainly of immunoglobulin (Ig)G and complement. Most of the cases are primary or idiopathic (iMN), while only approximately 25% of the cases are secondary to some known disease such as systemic lupus erythematosus, hepatitis B, drugs and malignancies. Most of our knowledge on the pathogenesis of iMN has relied upon old experimental models (i.e. Heymann nephritis) that have shown that immune deposits are formed in situ by the reaction of autoantibodies against the respective podocyte antigen. Recent findings indicate that podocyte proteins also act as an autoantigen in human iMN. The M-type phospholipase A2 receptor (PLA2R) has been identified as the main target antigen, as it can be found in approximately 70% of iMN patients but only rarely in other glomerulonephritides. Podocytes damage in the experimental model of Heymann nephritis is complement-mediated. In humans, the presence of complement within the subepithelial deposits is well established, but IgG4, which does not activate complement by classical or alternative pathways, represents the predominant subclass of IgG anti-PLA2R. Some evidence suggests that IgG4 anti-PLA2R autoantibodies can bind mannan-binding lectin (MBL) and activate the lectin complement pathway. A genetic background for iMN has been demonstrated by genome-wide association studies that have shown highly significant associations of the PLA2R1 and the human leucocyte antigen (HLA)-DQA1 loci with iMN. In addition to their diagnostic value, anti-PLA2R antibodies may be useful to monitor disease activity and predict response to treatment. PMID:26459770

  4. A Golden Hamster Model for Human Acute Nipah Virus Infection

    PubMed Central

    Wong, K. Thong; Grosjean, Isabelle; Brisson, Christine; Blanquier, Barissa; Fevre-Montange, Michelle; Bernard, Arlette; Loth, Philippe; Georges-Courbot, Marie-Claude; Chevallier, Michelle; Akaoka, Hideo; Marianneau, Philippe; Lam, Sai Kit; Wild, T. Fabian; Deubel, Vincent

    2003-01-01

    A predominantly pig-to-human zoonotic infection caused by the novel Nipah virus emerged recently to cause severe morbidity and mortality in both animals and man. Human autopsy studies showed the pathogenesis to be related to systemic vasculitis that led to widespread thrombotic occlusion and microinfarction in most major organs especially in the central nervous system. There was also evidence of extravascular parenchymal infection, particularly near damaged vessels (Wong KT, Shieh WJ, Kumar S, Norain K, Abdullah W, Guarner J, Goldsmith CS, Chua KB, Lam SK, Tan CT, Goh KJ, Chong HT, Jusoh R, Rollin PE, Ksiazek TG, Zaki SR, Nipah Virus Pathology Working Group: Nipah virus infection: Pathology and pathogenesis of an emerging paramyxoviral zoonosis. Am J Pathol 2002, 161:2153–2167). We describe here a golden hamster (Mesocricetus auratus) model that appears to reproduce the pathology and pathogenesis of acute human Nipah infection. Hamsters infected by intranasal or intraperitoneal routes died within 9 to 29 days or 5 to 9 days, respectively. Pathological lesions were most severe and extensive in the hamster brain. Vasculitis, thrombosis, and more rarely, multinucleated endothelial syncytia, were found in blood vessels of multiple organs. Viral antigen and RNA were localized in both vascular and extravascular tissues including neurons, lung, kidney, and spleen, as demonstrated by immunohistochemistry and in situ hybridization, respectively. Paramyxoviral-type nucleocapsids were identified in neurons and in vessel walls. At the terminal stage of infection, virus and/or viral RNA could be recovered from most solid organs and urine, but not from serum. The golden hamster is proposed as a suitable model for further studies including pathogenesis studies, anti-viral drug testing, and vaccine development against acute Nipah infection. PMID:14578210

  5. Immunology of membranous nephropathy: from animal models to humans.

    PubMed

    Sinico, R A; Mezzina, N; Trezzi, B; Ghiggeri, G M; Radice, A

    2016-02-01

    Membranous nephropathy (MN), the leading cause of nephrotic syndrome in adults, is characterized by the deposition of subepithelial immune deposits that consist mainly of immunoglobulin (Ig)G and complement. Most of the cases are primary or idiopathic (iMN), while only approximately 25% of the cases are secondary to some known disease such as systemic lupus erythematosus, hepatitis B, drugs and malignancies. Most of our knowledge on the pathogenesis of iMN has relied upon old experimental models (i.e. Heymann nephritis) that have shown that immune deposits are formed in situ by the reaction of autoantibodies against the respective podocyte antigen. Recent findings indicate that podocyte proteins also act as an autoantigen in human iMN. The M-type phospholipase A2 receptor (PLA2R) has been identified as the main target antigen, as it can be found in approximately 70% of iMN patients but only rarely in other glomerulonephritides. Podocytes damage in the experimental model of Heymann nephritis is complement-mediated. In humans, the presence of complement within the subepithelial deposits is well established, but IgG4, which does not activate complement by classical or alternative pathways, represents the predominant subclass of IgG anti-PLA2R. Some evidence suggests that IgG4 anti-PLA2R autoantibodies can bind mannan-binding lectin (MBL) and activate the lectin complement pathway. A genetic background for iMN has been demonstrated by genome-wide association studies that have shown highly significant associations of the PLA2R1 and the human leucocyte antigen (HLA)-DQA1 loci with iMN. In addition to their diagnostic value, anti-PLA2R antibodies may be useful to monitor disease activity and predict response to treatment.

  6. Using Task Analytic Models and Phenotypes of Erroneous Human Behavior to Discover System Failures Using Model Checking.

    PubMed

    Bolton, Matthew L; Bass, Ellen J

    2010-09-01

    Breakdowns in complex systems often occur as a result of system elements interacting in ways unanticipated by analysts or designers. In systems with human operators, human-automation interaction associated with both normative and erroneous human behavior can contribute to such failures. This paper presents a method for automatically generating task analytic models encompassing both erroneous and normative human behavior from normative task models. The resulting model can be integrated into a formal system model so that system safety properties can be formally verified with a model checker. This allows analysts to prove that a human automation-interactive system (as represented by the model) will or will not satisfy safety properties with both normative and generated erroneous human behavior. This method is illustrated with a case study: the operation of a radiation therapy machine. In this example, a problem resulting from a generated erroneous human action is discovered. Future extensions of our method are discussed.

  7. Modeling left ventricular diastolic dysfunction: classification and key indicators

    PubMed Central

    2011-01-01

    Background Mathematical modeling can be employed to overcome the practical difficulty of isolating the mechanisms responsible for clinical heart failure in the setting of normal left ventricular ejection fraction (HFNEF). In a human cardiovascular respiratory system (H-CRS) model we introduce three cases of left ventricular diastolic dysfunction (LVDD): (1) impaired left ventricular active relaxation (IR-type); (2) increased passive stiffness (restrictive or R-type); and (3) the combination of both (pseudo-normal or PN-type), to produce HFNEF. The effects of increasing systolic contractility are also considered. Model results showing ensuing heart failure and mechanisms involved are reported. Methods We employ our previously described H-CRS model with modified pulmonary compliances to better mimic normal pulmonary blood distribution. IR-type is modeled by changing the activation function of the left ventricle (LV), and R-type by increasing diastolic stiffness of the LV wall and septum. A 5th-order Cash-Karp Runge-Kutta numerical integration method solves the model differential equations. Results IR-type and R-type decrease LV stroke volume, cardiac output, ejection fraction (EF), and mean systemic arterial pressure. Heart rate, pulmonary pressures, pulmonary volumes, and pulmonary and systemic arterial-venous O2 and CO2 differences increase. IR-type decreases, but R-type increases the mitral E/A ratio. PN-type produces the well-described, pseudo-normal mitral inflow pattern. All three types of LVDD reduce right ventricular (RV) and LV EF, but the latter remains normal or near normal. Simulations show reduced EF is partly restored by an accompanying increase in systolic stiffness, a compensatory mechanism that may lead clinicians to miss the presence of HF if they only consider LVEF and other indices of LV function. Simulations using the H-CRS model indicate that changes in RV function might well be diagnostic. This study also highlights the importance of septal

  8. [A planar nonlinear model of the human spine].

    PubMed

    Nolte, L P; Pingel, T H

    1991-12-01

    In this study the derivation of a two-dimensional mathematical model of the human lumbar spine and its approximate solution using the method of finite elements is described. The computer model LUSP (Lumbar Spine) serves as a basis for studying the kinematic and load-bearing behaviour of the lumbar spine. The underlying working hypothesis is that the smallest spinal unit, the so called functional spinal unit (Junghanns, reflects the basic characteristic behaviour of the musclefree spine. On the basis of Lagrange's virtual work principle the nonlinear static and dynamic equations of motion for a sagitally symmetrical spine model of comprising rigid bodies, springs, beams and dampers are derived. The finite element method is used as an appropriate approximation scheme. Intensive research was conducted to provide the necessary geometrical and material input data. Special attention was paid to achieving a realistic description of the nonlinear stress-strain relationships for the soft tissue involved. A database-type preprocessor and a graphics-oriented postprocessor are made for convenient handling of the input and output data. The efficiency of the present computer model is demonstrated by means of an orthopaedic-biomechanical study on degenerative phenomena in so-called juxta-fused lumbosacral motion segments.

  9. High-resolution Doppler model of the human gait

    NASA Astrophysics Data System (ADS)

    Geisheimer, Jonathan L.; Greneker, Eugene F., III; Marshall, William S.

    2002-07-01

    A high resolution Doppler model of the walking human was developed for analyzing the continuous wave (CW) radar gait signature. Data for twenty subjects were collected simultaneously using an infrared motion capture system along with a two channel 10.525 GHz CW radar. The motion capture system recorded three-dimensional coordinates of infrared markers placed on the body. These body marker coordinates were used as inputs to create the theoretical Doppler output using a model constructed in MATLAB. The outputs of the model are the simulated Doppler signals due to each of the major limbs and the thorax. An estimated radar cross section for each part of the body was assigned using the Lund & Browder chart of estimated body surface area. The resultant Doppler model was then compared with the actual recorded Doppler gait signature in the frequency domain using the spectrogram. Comparison of the two sets of data has revealed several identifiable biomechanical features in the radar gait signature due to leg and body motion. The result of the research shows that a wealth of information can be unlocked from the radar gait signature, which may be useful in security and biometric applications.

  10. Computational modeling of hypertensive growth in the human carotid artery

    PubMed Central

    Sáez, Pablo; Peña, Estefania; Martínez, Miguel Angel; Kuhl, Ellen

    2014-01-01

    Arterial hypertension is a chronic medical condition associated with an elevated blood pressure. Chronic arterial hypertension initiates a series of events, which are known to collectively initiate arterial wall thickening. However, the correlation between macrostructural mechanical loading, microstructural cellular changes, and macrostructural adaptation remains unclear. Here, we present a microstructurally motivated computational model for chronic arterial hypertension through smooth muscle cell growth. To model growth, we adopt a classical concept based on the multiplicative decomposition of the deformation gradient into an elastic part and a growth part. Motivated by clinical observations, we assume that the driving force for growth is the stretch sensed by the smooth muscle cells. We embed our model into a finite element framework, where growth is stored locally as an internal variable. First, to demonstrate the features of our model, we investigate the effects of hypertensive growth in a real human carotid artery. Our results agree nicely with experimental data reported in the literature both qualitatively and quantitatively. PMID:25342868

  11. Integrated modeling of natural and human systems - problems and initiatives

    NASA Astrophysics Data System (ADS)

    Kessler, H.; Giles, J.; Gunnink, J.; Hughes, A.; Moore, R. V.; Peach, D.

    2009-12-01

    Governments and their executive agencies across the world are facing increasing pressure to make decisions about the management of resources in light of population growth and environmental change. In the UK and the Netherlands, for example, groundwater is becoming a scarce resource for large parts of its most densely populated areas. At the same time river and groundwater flooding resulting from high rainfall events are increasing in scale and frequency and sea level rise is threatening the defences of coastal cities. There is also a need for affordable housing, improved transport infrastructure and waste disposal as well as sources of renewable energy and sustainable food production. These challenges can only be resolved if solutions are based on sound scientific evidence. Although we have knowledge and understanding of many individual processes in the natural sciences it is clear that a single science discipline is unable to answer the questions and their inter-relationships. Modern science increasingly employs computer models to simulate the natural, economic and human system. Management and planning requires scenario modelling, forecasts and “predictions”. Although the outputs are often impressive in terms of apparent accuracy and visualisation, they are inherently not suited to simulate the response to feedbacks from other models of the earth system, such as the impact of human actions. Geological Survey Organisations (GSO) are increasingly employing advances in Information Technology to visualise and improve their understanding of geological systems. Instead of 2 dimensional paper maps and reports many GSOs now produce 3 dimensional geological framework models and groundwater flow models as their standard output. Additionally the British Geological Survey and the Geological Survey of the Netherlands have developed standard routines to link geological data to groundwater models, but these models are only aimed at solving one specific part of the earth

  12. Numerical human models for accident research and safety - potentials and limitations.

    PubMed

    Praxl, Norbert; Adamec, Jiri; Muggenthaler, Holger; von Merten, Katja

    2008-01-01

    The method of numerical simulation is frequently used in the area of automotive safety. Recently, numerical models of the human body have been developed for the numerical simulation of occupants. Different approaches in modelling the human body have been used: the finite-element and the multibody technique. Numerical human models representing the two modelling approaches are introduced and the potentials and limitations of these models are discussed.

  13. An Optimised Human Cell Culture Model for Alveolar Epithelial Transport

    PubMed Central

    Birch, Nigel P.; Suresh, Vinod

    2016-01-01

    Robust and reproducible in vitro models are required for investigating the pathways involved in fluid homeostasis in the human alveolar epithelium. We performed functional and phenotypic characterisation of ion transport in the human pulmonary epithelial cell lines NCI-H441 and A549 to determine their similarity to primary human alveolar type II cells. NCI-H441 cells exhibited high expression of junctional proteins ZO-1, and E-cadherin, seal-forming claudin-3, -4, -5 and Na+-K+-ATPase while A549 cells exhibited high expression of pore-forming claudin-2. Consistent with this phenotype NCI-H441, but not A549, cells formed a functional barrier with active ion transport characterised by higher electrical resistance (529 ± 178 Ω cm2 vs 28 ± 4 Ω cm2), lower paracellular permeability ((176 ± 42) ×10−8 cm/s vs (738 ± 190) ×10−8 cm/s) and higher transepithelial potential difference (11.9 ± 4 mV vs 0 mV). Phenotypic and functional properties of NCI-H441 cells were tuned by varying cell seeding density and supplement concentrations. The cells formed a polarised monolayer typical of in vivo epithelium at seeding densities of 100,000 cells per 12-well insert while higher densities resulted in multiple cell layers. Dexamethasone and insulin-transferrin-selenium supplements were required for the development of high levels of electrical resistance, potential difference and expression of claudin-3 and Na+-K+-ATPase. Treatment of NCI-H441 cells with inhibitors and agonists of sodium and chloride channels indicated sodium absorption through ENaC under baseline and forskolin-stimulated conditions. Chloride transport was not sensitive to inhibitors of the cystic fibrosis transmembrane conductance regulator (CFTR) under either condition. Channels inhibited by 5-nitro-1-(3-phenylpropylamino) benzoic acid (NPPB) contributed to chloride secretion following forskolin stimulation, but not at baseline. These data precisely define experimental conditions for the application of NCI

  14. A theoretical microbial contamination model for a human Mars mission

    NASA Astrophysics Data System (ADS)

    Lupisella, Mark Lewis

    Contamination from a human presence on Mars could significantly compromise the search for extraterrestrial life. In particular, the difficulties in controlling microbial contamination, the potential for terrestrial microbes to grow, evolve, compete, and modify the Martian environment, and the likely microbial nature of putative Martian life, make microbial contamination worthy of focus as we begin to plan for a human mission to Mars. This dissertation describes a relatively simple theoretical model that can be used to explore how microbial contamination from a human Mars mission might survive and grow in the Martian soil environment surrounding a habitat. A user interface has been developed to allow a general practitioner to choose values and functions for almost all parameters ranging from the number of astronauts to the half-saturation constants for microbial growth. Systematic deviations from a baseline set of parameter values are explored as potential plausible scenarios for the first human Mars missions. The total viable population and population density are the primary state variables of interest, but other variables such as the total number of births and total dead and viable microbes are also tracked. The general approach was to find the most plausible parameter value combinations that produced a population density of 1 microbe/cm3 or greater, a threshold that was used to categorize the more noteworthy populations for subsequent analysis. Preliminary assessments indicate that terrestrial microbial contamination resulting from leakage from a limited human mission (perhaps lasting up to 5 months) will not likely become a problematic population in the near-term as long as reasonable contamination control measures are implemented (for example, a habitat leak rate no greater than 1% per hour). However, there appear to be plausible, albeit unlikely, scenarios that could cause problematic populations, depending in part on (a) the initial survival fraction and

  15. A Mouse Model for Imprinting of the Human Retinoblastoma Gene

    PubMed Central

    Tasiou, Vasiliki; Hiber, Michaela; Steenpass, Laura

    2015-01-01

    The human RB1 gene is imprinted due to integration of the PPP1R26P1 pseudogene into intron 2. PPP1R26P1 harbors the gametic differentially methylated region of the RB1 gene, CpG85, which is methylated in the female germ line. The paternally unmethylated CpG85 acts as promoter for the alternative transcript 2B of RB1, which interferes with expression of full-length RB1 in cis. In mice, PPP1R26P1 is not present in the Rb1 gene and Rb1 is not imprinted. Assuming that the mechanisms responsible for genomic imprinting are conserved, we investigated if imprinting of mouse Rb1 can be induced by transferring human PPP1R26P1 into mouse Rb1. We generated humanized Rb1_PPP1R26P1 knock-in mice that pass human PPP1R26P1 through the mouse germ line. We found that the function of unmethylated CpG85 as promoter for an alternative Rb1 transcript and as cis-repressor of the main Rb1 transcript is maintained in mouse tissues. However, CpG85 is not recognized as a gametic differentially methylated region in the mouse germ line. DNA methylation at CpG85 is acquired only in tissues of neuroectodermal origin, independent of parental transmission of PPP1R26P1. Absence of CpG85 methylation in oocytes and sperm implies a failure of imprint methylation establishment in the germ line. Our results indicate that site-specific integration of a proven human gametic differentially methylated region is not sufficient for acquisition of DNA methylation in the mouse germ line, even if promoter function of the element is maintained. This suggests a considerable dependency of DNA methylation induction on the surrounding sequence. However, our model is suited to determine the cellular function of the alternative Rb1 transcript. PMID:26275142

  16. HeMoLab--Hemodynamics Modelling Laboratory: an application for modelling the human cardiovascular system.

    PubMed

    Larrabide, I; Blanco, P J; Urquiza, S A; Dari, E A; Vénere, M J; de Souza e Silva, N A; Feijóo, R A

    2012-10-01

    In this work we present HeMoLab (Hemodynamics Modeling Laboratory), a computational environment for modeling the Human Cardiovascular System. Its integrates novel computational tools, running from medical image processing to numerical simulation and visualization. As a simulation tool, it allows to accommodate complex physiological and/or pathophysiological (virtual) scenarios aimed to retrieve detailed information from the numerical computations. Such application makes possible to speed up research in the study and analysis of the cardiovascular system and, to provide a virtual laboratory for medical training and education, and specialized Human Resources development. In order to demonstrate the modeling and simulation capabilities of HeMoLab some cases of use are presented.

  17. The Human Auditory System Modeled as AN Autocorrelator.

    NASA Astrophysics Data System (ADS)

    Martin, Mark Aaron

    This thesis is intended to investigate a new strategy for interpreting the human auditory physiology and assess the impact this knowledge might have on engineering applications such as speech encoding, word recognition, and speaker verification. The new interpretation is based around the signal processing properties associated with the autocorrelation function and has been developed from a strong foundation of literature that has been compiled over the last 50 years. A distilation of the pertinent literature includes the phylogenetic development of audition, a detailed description of the anatomy of the inner ear, and the well-recognized inconsistencies involved with traditional interpretations of physiology and psychoacoustic experiments. These issues are discussed and reinterpreted to support a new philosophy on the signal processing functionality of the inner ear. From this conceptual model, a mathematical description and a partly phenomenological computer model are developed. The responses of the new model to test stimuli show qualitative similarity to the results of important psychoacoustic experiments, demonstrating that the new philosophy represents a more unified theory on audition than any proposed so far. In particular the new model predicts the effects known as "pitch", "the second filter", and some other phenomena that are not specifically recognized in the literature. The knowledge gained in this effort is applied to techniques for speech encoding by real zeros, specifically, the reconstruction of signals that have been infinitely clipped. Finally, the concept is extended to include speculation on neural processes at the level of the cochlear nucleus in the brain. At this level an investigation is made to explore the power with which the new model can characterize phoneme signals generated by several different speakers. The results are shown to possess the historically accepted techniques for phoneme characterization as a subset of a dimensionally

  18. Agent Based Modeling of Human Gut Microbiome Interactions and Perturbations

    PubMed Central

    Shashkova, Tatiana; Popenko, Anna; Tyakht, Alexander; Peskov, Kirill; Kosinsky, Yuri; Bogolubsky, Lev; Raigorodskii, Andrei; Ischenko, Dmitry; Alexeev, Dmitry; Govorun, Vadim

    2016-01-01

    Background Intestinal microbiota plays an important role in the human health. It is involved in the digestion and protects the host against external pathogens. Examination of the intestinal microbiome interactions is required for understanding of the community influence on host health. Studies of the microbiome can provide insight on methods of improving health, including specific clinical procedures for individual microbial community composition modification and microbiota correction by colonizing with new bacterial species or dietary changes. Methodology/Principal Findings In this work we report an agent-based model of interactions between two bacterial species and between species and the gut. The model is based on reactions describing bacterial fermentation of polysaccharides to acetate and propionate and fermentation of acetate to butyrate. Antibiotic treatment was chosen as disturbance factor and used to investigate stability of the system. System recovery after antibiotic treatment was analyzed as dependence on quantity of feedback interactions inside the community, therapy duration and amount of antibiotics. Bacterial species are known to mutate and acquire resistance to the antibiotics. The ability to mutate was considered to be a stochastic process, under this suggestion ratio of sensitive to resistant bacteria was calculated during antibiotic therapy and recovery. Conclusion/Significance The model confirms a hypothesis of feedbacks mechanisms necessity for providing functionality and stability of the system after disturbance. High fraction of bacterial community was shown to mutate during antibiotic treatment, though sensitive strains could become dominating after recovery. The recovery of sensitive strains is explained by fitness cost of the resistance. The model demonstrates not only quantitative dynamics of bacterial species, but also gives an ability to observe the emergent spatial structure and its alteration, depending on various feedback mechanisms

  19. A Big Bang model of human colorectal tumor growth

    PubMed Central

    Sottoriva, Andrea; Kang, Haeyoun; Ma, Zhicheng; Graham, Trevor A.; Salomon, Matthew P.; Zhao, Junsong; Marjoram, Paul; Siegmund, Kimberly; Press, Michael F.; Shibata, Darryl; Curtis, Christina

    2015-01-01

    What happens in the early, still undetectable human malignancy is unknown because direct observations are impractical. Here we present and validate a “Big Bang” model, whereby tumors grow predominantly as a single expansion producing numerous intermixed sub-clones that are not subject to stringent selection, and where both public (clonal) and most detectable private (subclonal) alterations arise early during growth. Genomic profiling of 349 individual glands from 15 colorectal tumors revealed the absence of selective sweeps, uniformly high intra-tumor heterogeneity (ITH), and sub-clone mixing in distant regions, as postulated by our model. We also verified the prediction that most detectable ITH originates from early private alterations, and not from later clonal expansions, thus exposing the profile of the primordial tumor. Moreover, some tumors appear born-to-be-bad, with sub-clone mixing indicative of early malignant potential. This new model provides a quantitative framework to interpret tumor growth dynamics and the origins of ITH with significant clinical implications. PMID:25665006

  20. Three-dimensional model of cytochrome P450 human aromatase.

    PubMed

    Loge, Cedric; Le Borgne, Marc; Marchand, Pascal; Robert, Jean-Michel; Le Baut, Guillaume; Palzer, Martina; Hartmann, Rolf W

    2005-12-01

    A three-dimensional (3-D) structure of human aromatase (CYP 19) was modeled on the basis of the crystal structure of rabbit CYP2C5, the first solved X-ray structure of an eukaryotic cytochrome P450 and was evaluated by docking S-fadrozole and the steroidal competitive inhibitor (19R)-10-thiiranylestr-4-ene-3,17-dione, into the enzyme active site. According to a previous pharmacophoric hypothesis described in the literature, the cyano group of S-fadrozole partially mimics the steroid backbone C(17) carbonyl group of (19R)-10-thiiranylestr-4-ene-3,17-dione, and was oriented in a favorable position for H-bonding with the newly identified positively charged residues Lys 119 and Arg435. In addition, this model is consistent with the recent combined mutagenesis/modeling studies already published concerning the roles ofAsp309 and His480 in the aromatization of the steroid A ring. PMID:16408794

  1. Transplantation of human skin microbiota in models of atopic dermatitis

    PubMed Central

    Myles, Ian A.; Williams, Kelli W.; Reckhow, Jensen D.; Jammeh, Momodou L.; Pincus, Nathan B.; Sastalla, Inka; Saleem, Danial; Stone, Kelly D.; Datta, Sandip K.

    2016-01-01

    Atopic dermatitis (AD) is characterized by reduced barrier function, reduced innate immune activation, and susceptibility to Staphylococcus aureus. Host susceptibility factors are suggested by monogenic disorders associated with AD-like phenotypes and can be medically modulated. S. aureus contributes to AD pathogenesis and can be mitigated by antibiotics and bleach baths. Recent work has revealed that the skin microbiome differs significantly between healthy controls and patients with AD, including decreased Gram-negative bacteria in AD. However, little is known about the potential therapeutic benefit of microbiome modulation. To evaluate whether parameters of AD pathogenesis are altered after exposure to different culturable Gram-negative bacteria (CGN) collected from human skin, CGN were collected from healthy controls and patients with AD. Then, effects on cellular and culture-based models of immune, epithelial, and bacterial function were evaluated. Representative strains were evaluated in the MC903 mouse model of AD. We found that CGN taken from healthy volunteers but not from patients with AD were associated with enhanced barrier function, innate immunity activation, and control of S. aureus. Treatment with CGN from healthy controls improved outcomes in a mouse model of AD. These findings suggest that a live-biotherapeutic approach may hold promise for treatment of patients with AD. PMID:27478874

  2. Modeling and analysis of cosmetic treatment effects on human skin

    NASA Astrophysics Data System (ADS)

    Lunderstaedt, Reinhart A.; Hopermann, Hermann; Hillemann, Thomas

    2000-10-01

    In view of treatment effects of cosmetics, quality management becomes more and more important. Due to the efficiency reasons it is desirable to quantify these effects and predict them as a function of time. For this, a mathematical model of the skin's surface (epidermis) is needed. Such a model cannot be worked out purely analytically. It can only be derived with the help of measurement data. The signals of interest as output of different measurement devices consist of two parts: noise of high (spatial) frequencies (stochastic signal) and periodic functions (deterministic signal) of low (spatial) frequencies. Both parts can be separated by correlation analysis. The paper introduces in addition to the Fourier Transform (FT) with the Wavelet Transform (WT), a brand new, highly sophisticated method with excellent properties for both modeling the skin's surface as well as evaluating treatment effects. Its main physical advantage is (in comparison to the FT) that local irregularities in the measurement signal (e.g. by scars) remain at their place and are not represented as mean square values as it is the case when applying the FT. The method has just now been installed in industry and will there be used in connection with a new in vivo measurement device for quality control of cosmetic products. As texture parameter for an integral description of the human skin the fractal dimension D is used which is appropriate for classification of different skin regions and treatment effects as well.

  3. Computational Flow Modeling of Human Upper Airway Breathing

    NASA Astrophysics Data System (ADS)

    Mylavarapu, Goutham

    Computational modeling of biological systems have gained a lot of interest in biomedical research, in the recent past. This thesis focuses on the application of computational simulations to study airflow dynamics in human upper respiratory tract. With advancements in medical imaging, patient specific geometries of anatomically accurate respiratory tracts can now be reconstructed from Magnetic Resonance Images (MRI) or Computed Tomography (CT) scans, with better and accurate details than traditional cadaver cast models. Computational studies using these individualized geometrical models have advantages of non-invasiveness, ease, minimum patient interaction, improved accuracy over experimental and clinical studies. Numerical simulations can provide detailed flow fields including velocities, flow rates, airway wall pressure, shear stresses, turbulence in an airway. Interpretation of these physical quantities will enable to develop efficient treatment procedures, medical devices, targeted drug delivery etc. The hypothesis for this research is that computational modeling can predict the outcomes of a surgical intervention or a treatment plan prior to its application and will guide the physician in providing better treatment to the patients. In the current work, three different computational approaches Computational Fluid Dynamics (CFD), Flow-Structure Interaction (FSI) and Particle Flow simulations were used to investigate flow in airway geometries. CFD approach assumes airway wall as rigid, and relatively easy to simulate, compared to the more challenging FSI approach, where interactions of airway wall deformations with flow are also accounted. The CFD methodology using different turbulence models is validated against experimental measurements in an airway phantom. Two case-studies using CFD, to quantify a pre and post-operative airway and another, to perform virtual surgery to determine the best possible surgery in a constricted airway is demonstrated. The unsteady

  4. Predictive models of procedural human supervisory control behavior

    NASA Astrophysics Data System (ADS)

    Boussemart, Yves

    Human supervisory control systems are characterized by the computer-mediated nature of the interactions between one or more operators and a given task. Nuclear power plants, air traffic management and unmanned vehicles operations are examples of such systems. In this context, the role of the operators is typically highly proceduralized due to the time and mission-critical nature of the tasks. Therefore, the ability to continuously monitor operator behavior so as to detect and predict anomalous situations is a critical safeguard for proper system operation. In particular, such models can help support the decision J]l8king process of a supervisor of a team of operators by providing alerts when likely anomalous behaviors are detected By exploiting the operator behavioral patterns which are typically reinforced through standard operating procedures, this thesis proposes a methodology that uses statistical learning techniques in order to detect and predict anomalous operator conditions. More specifically, the proposed methodology relies on hidden Markov models (HMMs) and hidden semi-Markov models (HSMMs) to generate predictive models of unmanned vehicle systems operators. Through the exploration of the resulting HMMs in two distinct single operator scenarios, the methodology presented in this thesis is validated and shown to provide models capable of reliably predicting operator behavior. In addition, the use of HSMMs on the same data scenarios provides the temporal component of the predictions missing from the HMMs. The final step of this work is to examine how the proposed methodology scales to more complex scenarios involving teams of operators. Adopting a holistic team modeling approach, both HMMs and HSMMs are learned based on two team-based data sets. The results show that the HSMMs can provide valuable timing information in the single operator case, whereas HMMs tend to be more robust to increased team complexity. In addition, this thesis discusses the

  5. Fiber deposition in human upper airway model. Final report

    SciTech Connect

    Swift, D.L.

    1986-01-01

    The possibility that airborne fibers may behave differently than spherical particles in their deposition in the upper airways was examined. Deposition measurements were taken in a replicate model of the upper human airways above the larynx with well-characterized glass-fiber aerosols typical of glass fibers in normal use. The overall deposition of the aerosols in the nasal airways ranged from 10 to 90 percent. The deposition increased with flow rate and was somewhat higher with nasal-hair stimulant in the anterior vestibule. There was no dependency between the effect of fiber diameter and inertial theory, suggesting that interception is an important factor. Deposition occurred mainly anterior to the nasopharynx, equally divided between the vestibule and the turbinate region. The establishment of the anterior nasal region as the prime site for interception deposition was verified by the lack of significant deposition in the nasopharynx and larynx during nasal breathing. The authors conclude that the human nasal passage is able to remove a significant fraction of inhaled fibers, most of which will be physically cleared and others of which will be cleared to the gastro-intestinal tract. No long-term effect is expected from fibers deposited in the nasal region and cleared physically.

  6. Canine degenerative myelopathy: a model of human amyotrophic lateral sclerosis.

    PubMed

    Nardone, Raffaele; Höller, Yvonne; Taylor, Alexandra C; Lochner, Piergiorgio; Tezzon, Frediano; Golaszewski, Stefan; Brigo, Francesco; Trinka, Eugen

    2016-02-01

    Canine degenerative myelopathy (CDM) represents a unique naturally occurring animal model for human amyotrophic lateral sclerosis (ALS) because of similar clinical signs, neuropathologic findings, and involvement of the superoxide dismutase 1 (SOD1) mutation. A definitive diagnosis can only be made postmortem through microscopic detection of axonal degeneration, demyelination and astroglial proliferation, which is more severe in the dorsal columns of the thoracic spinal cord and in the dorsal portion of the lateral funiculus. Interestingly, the muscle acetylcholine receptor complexes are intact in CDM prior to functional impairment, thus suggesting that muscle atrophy in CDM does not result from physical denervation. Moreover, since sensory involvement seems to play an important role in CDM progression, a more careful investigation of the sensory pathology in ALS is also warranted. The importance of SOD1 expression remains unclear, while oxidative stress and denatured ubiquinated proteins appear to play a crucial role in the pathogenesis of CDM. In this updated narrative review we performed a systematic search of the published studies on CDM that may shed light on the pathophysiological mechanisms of human ALS. A better understanding of the factors that determine the disease progression in CDM may be beneficial for the development of effective treatments for ALS.

  7. Human operator identification model and related computer programs

    NASA Technical Reports Server (NTRS)

    Kessler, K. M.; Mohr, J. N.

    1978-01-01

    Four computer programs which provide computational assistance in the analysis of man/machine systems are reported. The programs are: (1) Modified Transfer Function Program (TF); (2) Time Varying Response Program (TVSR); (3) Optimal Simulation Program (TVOPT); and (4) Linear Identification Program (SCIDNT). The TV program converts the time domain state variable system representative to frequency domain transfer function system representation. The TVSR program computes time histories of the input/output responses of the human operator model. The TVOPT program is an optimal simulation program and is similar to TVSR in that it produces time histories of system states associated with an operator in the loop system. The differences between the two programs are presented. The SCIDNT program is an open loop identification code which operates on the simulated data from TVOPT (or TVSR) or real operator data from motion simulators.

  8. Incorporating affective bias in models of human decision making

    NASA Technical Reports Server (NTRS)

    Nygren, Thomas E.

    1991-01-01

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

  9. Modeling mouse and human development using organoid cultures.

    PubMed

    Huch, Meritxell; Koo, Bon-Kyoung

    2015-09-15

    In vitro three-dimensional (3D) cultures are emerging as novel systems with which to study tissue development, organogenesis and stem cell behavior ex vivo. When grown in a 3D environment, embryonic stem cells (ESCs) self-organize into organoids and acquire the right tissue patterning to develop into several endoderm- and ectoderm-derived tissues, mimicking their in vivo counterparts. Tissue-resident adult stem cells (AdSCs) also form organoids when grown in 3D and can be propagated in vitro for long periods of time. In this Review, we discuss recent advances in the generation of pluripotent stem cell- and AdSC-derived organoids, highlighting their potential for enhancing our understanding of human development. We will also explore how this new culture system allows disease modeling and gene repair for a personalized regenerative medicine approach. PMID:26395140

  10. Differentiation and Genomic Instability in a Human Mammary Cell Model

    NASA Technical Reports Server (NTRS)

    Richmond, R.; Kale, R.; Pettengill, O.; Rose, M. Franklin (Technical Monitor)

    2001-01-01

    Harvest of prophylactic mastectomy specimens from an obligate heterozygote for ataxia-telangiectasia provided autologous fibroblasts as well epithelial cells (HMEC). The routine availability of these autologous cells has provided an opportunity to study cell-cell interactions in coculture and monoculture, and in 3-dimensional cultures grown in the NASA rotating bioreactor. HMEC and stromal fibroblasts grown in 2-dimensional monoculture were both observed to produce extracellular matrix. Similar matrix was encountered in 3-dimensional cultures containing HMEC. Metaphases were analyzed. For stromal fibroblasts, genomic aberrations were found in 18% of metaphase spreads. For HMEC, aberrations were greater such that a majority were found to be abnormal. The level of genomic instability determined for these noncancerous cells in 2-dimensional monoculture should be useful for generating a human cell model that can correlate the effects of differentiation in 3-dimensional coculture on the level of genomic instability.

  11. Multiscale analysis of the murine intestine for modeling human diseases

    PubMed Central

    Lyons, Jesse; Herring, Charles A.; Banerjee, Amrita; Simmons, Alan J.

    2015-01-01

    When functioning properly, the intestine is one of the key interfaces between the human body and its environment. It is responsible for extracting nutrients from our food and excreting our waste products. It provides an environment for a host of healthful microbes and serves as a first defense against pathogenic ones. These processes require tight homeostatic controls, which are provided by the interactions of a complex mix of epithelial, stromal, neural and immune cells, as well as the resident microflora. This homeostasis can be disrupted by invasive microbes, genetic lesions, and carcinogens, resulting in diseases such Clostridium difficile infection, inflammatory bowel disease (IBD) and cancer. Enormous strides have been made in understanding how this important organ functions in health and disease using everything from cell culture systems to animal models to human tissue samples. This has resulted in better therapies for all of these diseases, but there is still significant room for improvement. In the United States alone, 14000 people per year die of C. difficile, up to 1.6 million people suffer from IBD, and more than 50000 people die every year from colon cancer. Because these and other intestinal diseases arise from complex interactions between the different components of the gut ecosystem, we propose that systems approaches that address this complexity in an integrative manner may eventually lead to improved therapeutics that deliver lasting cures. This review will discuss the use of systems biology for studying intestinal diseases in vivo with particular emphasis on mouse models. Additionally, it will focus on established experimental techniques that have been used to drive this systems-level analysis, and emerging techniques that will push this field forward in the future. PMID:26040649

  12. New Safety Model for the Commercial Human Spaceflight Industry

    NASA Astrophysics Data System (ADS)

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

    2012-01-01

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

  13. Mouse models rarely mimic the transcriptome of human neurodegenerative diseases: A systematic bioinformatics-based critique of preclinical models.

    PubMed

    Burns, Terry C; Li, Matthew D; Mehta, Swapnil; Awad, Ahmed J; Morgan, Alexander A

    2015-07-15

    Translational research for neurodegenerative disease depends intimately upon animal models. Unfortunately, promising therapies developed using mouse models mostly fail in clinical trials, highlighting uncertainty about how well mouse models mimic human neurodegenerative disease at the molecular level. We compared the transcriptional signature of neurodegeneration in mouse models of Alzheimer׳s disease (AD), Parkinson׳s disease (PD), Huntington׳s disease (HD) and amyotrophic lateral sclerosis (ALS) to human disease. In contrast to aging, which demonstrated a conserved transcriptome between humans and mice, only 3 of 19 animal models showed significant enrichment for gene sets comprising the most dysregulated up- and down-regulated human genes. Spearman׳s correlation analysis revealed even healthy human aging to be more closely related to human neurodegeneration than any mouse model of AD, PD, ALS or HD. Remarkably, mouse models frequently upregulated stress response genes that were consistently downregulated in human diseases. Among potential alternate models of neurodegeneration, mouse prion disease outperformed all other disease-specific models. Even among the best available animal models, conserved differences between mouse and human transcriptomes were found across multiple animal model versus human disease comparisons, surprisingly, even including aging. Relative to mouse models, mouse disease signatures demonstrated consistent trends toward preserved mitochondrial function protein catabolism, DNA repair responses, and chromatin maintenance. These findings suggest a more complex and multifactorial pathophysiology in human neurodegeneration than is captured through standard animal models, and suggest that even among conserved physiological processes such as aging, mice are less prone to exhibit neurodegeneration-like changes. This work may help explain the poor track record of mouse-based translational therapies for neurodegeneration and provides a path

  14. A Simplified Model of Human Alcohol Metabolism That Integrates Biotechnology and Human Health into a Mass Balance Team Project

    ERIC Educational Resources Information Center

    Yang, Allen H. J.; Dimiduk, Kathryn; Daniel, Susan

    2011-01-01

    We present a simplified human alcohol metabolism model for a mass balance team project. Students explore aspects of engineering in biotechnology: designing/modeling biological systems, testing the design/model, evaluating new conditions, and exploring cutting-edge "lab-on-a-chip" research. This project highlights chemical engineering's impact on…

  15. Teaching Qualitative Research for Human Services Students: A Three-Phase Model

    ERIC Educational Resources Information Center

    Goussinsky, Ruhama; Reshef, Arie; Yanay-Ventura, Galit; Yassour-Borochowitz, Dalit

    2011-01-01

    Qualitative research is an inherent part of the human services profession, since it emphasizes the great and multifaceted complexity characterizing human experience and the sociocultural context in which humans act. In the department of human services at Emek Yezreel College, Israel, we have developed a three-phase model to ensure a relatively…

  16. Computational modeling and analysis of the hydrodynamics of human swimming

    NASA Astrophysics Data System (ADS)

    von Loebbecke, Alfred

    Computational modeling and simulations are used to investigate the hydrodynamics of competitive human swimming. The simulations employ an immersed boundary (IB) solver that allows us to simulate viscous, incompressible, unsteady flow past complex, moving/deforming three-dimensional bodies on stationary Cartesian grids. This study focuses on the hydrodynamics of the "dolphin kick". Three female and two male Olympic level swimmers are used to develop kinematically accurate models of this stroke for the simulations. A simulation of a dolphin undergoing its natural swimming motion is also presented for comparison. CFD enables the calculation of flow variables throughout the domain and over the swimmer's body surface during the entire kick cycle. The feet are responsible for all thrust generation in the dolphin kick. Moreover, it is found that the down-kick (ventral position) produces more thrust than the up-kick. A quantity of interest to the swimming community is the drag of a swimmer in motion (active drag). Accurate estimates of this quantity have been difficult to obtain in experiments but are easily calculated with CFD simulations. Propulsive efficiencies of the human swimmers are found to be in the range of 11% to 30%. The dolphin simulation case has a much higher efficiency of 55%. Investigation of vortex structures in the wake indicate that the down-kick can produce a vortex ring with a jet of accelerated fluid flowing through its center. This vortex ring and the accompanying jet are the primary thrust generating mechanisms in the human dolphin kick. In an attempt to understand the propulsive mechanisms of surface strokes, we have also conducted a computational analysis of two different styles of arm-pulls in the backstroke and the front crawl. These simulations involve only the arm and no air-water interface is included. Two of the four strokes are specifically designed to take advantage of lift-based propulsion by undergoing lateral motions of the hand

  17. A Simple Model for Human and Nature Interaction

    NASA Astrophysics Data System (ADS)

    Motesharrei, S.; Rivas, J.; Kalnay, E.

    2012-12-01

    There are widespread concerns that current trends in population and resource-use are unsustainable, but the possibilities of an overshoot and collapse remain unclear and controversial. Collapses of civilizations have occurred many times in the past 5000 years, often followed by centuries of economic, intellectual, and population decline. Many different natural and social phenomena have been invoked to explain specific collapses, but a general explanation remains elusive. Two important features seem to appear across societies that have collapsed: Ecological Strain and Economic Stratification. Our new model (Human And Nature DYnamics, HANDY) has just four equations that describe the evolution of Elites, Commoners, Nature, and Wealth. Mechanisms leading to collapse are discussed and the measure "Carrying Capacity" is developed and defined. The model shows that societal collapse can happen due to either one of two independent factors: (1) over-consumption of natural resources, and/or (2) deep inequity between Elites and Commoners. The model also portrays two distinct types of collapse: (i) collapse followed by recovery of nature, and (ii) full collapse. The model suggests that the estimation of Carrying Capacity is a practical means for early detection of a collapse. Collapse can be avoided, and population can reach a sustainable equilibrium, if the rate of depletion of nature is reduced to a sustainable level, and if resources are distributed in a reasonably equitable fashion.; A type-ii (full) collapse is shown in this figure. With high inequality and high depletion, societies are doomed to collapse. Wealth starts to decrease when population rises above the carrying capacity. The large gap between carrying capacity and its maximum is a result of depletion factor being much larger than the sustainable limit. ; It is possible to overshoot, oscillate, and eventually converge to an equilibrium, even in an inequitable society. However, it requires policies that control

  18. In vitro model for decontamination of human skin: formaldehyde.

    PubMed

    Zhai, H; Barbadillo, S; Hui, X; Maibach, H I

    2007-04-01

    Decontamination of a chemical from skin is often an emergency measure. This study utilized an in vitro model to compare the decontamination capacity of three model decontaminant solutions (tap water, isotonic saline, and hypertonic saline). Human cadaver skin was dosed (approximately 0.25 microg on 3 cm(2) per skin) with radio-labeled [(14)C]-formaldehyde. After a defined exposure time (1, 3, and 30 min post-dosing, respectively), the surface skin was washed three times (4ml per time) with each solution. After washing, the skin was stripped with tape discs twice. Lastly, the wash solutions, strippings, receptor fluid, and remainder of skin were liquid scintillation analyzer counted to determine the amounts of formaldehyde. Additionally, an evaporation test at different exposure times (1min, 3min, 15min, 30min, and 60min, respectively) was conducted to monitor formaldehyde % evaporation. There were no statistical differences among these groups except isotonic saline, at 3min post-exposure (in wash solutions), showed a significantly difference (p<0.05) when compared to tap water. Formaldehyde % evaporation increased linearly with extending application times, and were 7.7%, 13.6%, 19.7%, 24.4%, and 35.9% (1min, 3min, 15min, 30min, and 60min, respectively). This data suggests that isotonic saline may be effective in removing formaldehyde from skin. However, results from this model need validation in vivo. The model may provide a facile and robust method of accelerating knowledge of decontamination mechanism and lead to enhanced efficacy. PMID:17123683

  19. Modelling soft tissue for kinematic analysis of multi-segment human body models.

    PubMed

    Benham, M P; Wright, D K; Bibb, R

    2001-01-01

    Traditionally biomechanical models represent the musculoskeletal system by a series of rigid links connected by rigidly defined rotational joints. More recently though the mechanics of joints and the action of soft tissues has come under closer scrutiny: biomechanical models might now include a full range of physiological structures. However, soft tissue representation, within multi-segment human body models, presents significant problems; not least in computational speed. We present a method for representing soft tissue physiology which provides for soft tissue wrapping around multiple bony objects; while showing forces at the insertion points, as well as normal reactions due to contact between the soft and bony tissues. These soft tissue representations may therefore be used to constrain the joint, as ligaments would, or to generate motion, like a muscle, so that joints may be modelled which more accurately simulate musculoskeletal motion in all degrees of freedom--rotational and translational. This method produces soft tissues that do not need to be tied to a certain path or route between the bony structures, but may move with the motion of the model; demonstrating a more realistic analysis of soft tissue activity in the musculoskeletal system. The combination of solid geometry models of the skeletal structure, and these novel soft tissue representations, may also provide a useful approach to synthesised human motion.

  20. A stochastic model of randomly accelerated walkers for human mobility

    NASA Astrophysics Data System (ADS)

    Gallotti, Riccardo; Bazzani, Armando; Rambaldi, Sandro; Barthelemy, Marc

    2016-08-01

    Recent studies of human mobility largely focus on displacements patterns and power law fits of empirical long-tailed distributions of distances are usually associated to scale-free superdiffusive random walks called Lévy flights. However, drawing conclusions about a complex system from a fit, without any further knowledge of the underlying dynamics, might lead to erroneous interpretations. Here we show, on the basis of a data set describing the trajectories of 780,000 private vehicles in Italy, that the Lévy flight model cannot explain the behaviour of travel times and speeds. We therefore introduce a class of accelerated random walks, validated by empirical observations, where the velocity changes due to acceleration kicks at random times. Combining this mechanism with an exponentially decaying distribution of travel times leads to a short-tailed distribution of distances which could indeed be mistaken with a truncated power law. These results illustrate the limits of purely descriptive models and provide a mechanistic view of mobility.