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Sample records for human cardiovascular-respiratory model

  1. Using a human cardiovascular-respiratory model to characterize cardiac tamponade and pulsus paradoxus

    PubMed Central

    Ramachandran, Deepa; Luo, Chuan; Ma, Tony S; Clark, John W

    2009-01-01

    Background Cardiac tamponade is a condition whereby fluid accumulation in the pericardial sac surrounding the heart causes elevation and equilibration of pericardial and cardiac chamber pressures, reduced cardiac output, changes in hemodynamics, partial chamber collapse, pulsus paradoxus, and arterio-venous acid-base disparity. Our large-scale model of the human cardiovascular-respiratory system (H-CRS) is employed to study mechanisms underlying cardiac tamponade and pulsus paradoxus. The model integrates hemodynamics, whole-body gas exchange, and autonomic nervous system control to simulate pressure, volume, and blood flow. Methods We integrate a new pericardial model into our previously developed H-CRS model based on a fit to patient pressure data. Virtual experiments are designed to simulate pericardial effusion and study mechanisms of pulsus paradoxus, focusing particularly on the role of the interventricular septum. Model differential equations programmed in C are solved using a 5th-order Runge-Kutta numerical integration scheme. MATLAB is employed for waveform analysis. Results The H-CRS model simulates hemodynamic and respiratory changes associated with tamponade clinically. Our model predicts effects of effusion-generated pericardial constraint on chamber and septal mechanics, such as altered right atrial filling, delayed leftward septal motion, and prolonged left ventricular pre-ejection period, causing atrioventricular interaction and ventricular desynchronization. We demonstrate pericardial constraint to markedly accentuate normal ventricular interactions associated with respiratory effort, which we show to be the distinct mechanisms of pulsus paradoxus, namely, series and parallel ventricular interaction. Series ventricular interaction represents respiratory variation in right ventricular stroke volume carried over to the left ventricle via the pulmonary vasculature, whereas parallel interaction (via the septum and pericardium) is a result of

  2. 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.

  3. 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…

  4. The cardiovascular, respiratory, and metabolic effects of a long duration electronic control device exposure in human volunteers.

    PubMed

    Dawes, Donald M; Ho, Jeffrey D; Reardon, Robert F; Miner, James R

    2010-12-01

    Electronic control devices (ECD) have become popular in law enforcement because they have filled a gap left by other law enforcement devices, tactics, or tools and have been shown to reduce officer and suspect injuries. Civilians are using the same technology for defensive purposes. TASER C2 is the latest generation civilian-marketed device from the manufacturer. Unlike the law enforcement devices, the device discharges for 30 s continuously. This study is the first to look at the cardiovascular, respiratory, and metabolic effects of this device on human subjects. This was a prospective, observational study of human subjects involved in a training course. Subjects were exposed for 30 s on the anterior thorax. Vital signs, ECG, troponin I, pH, lactate, and creatine kinase (CK) were measured before and immediately after the exposure. Troponin I, pH, lactate, and CK were measured again 24 h after the exposure. Continuous spirometry was used to evaluate the respiratory effects. Echocardiography was also performed before, during, and immediately after the exposure to determine heart rate and rhythm. Eleven subjects completed the study. There were no clinically important electrocardiogram changes and no positive troponins. Spirometry showed an increase in minute ventilation during the exposure. There was no important change in CK at 24 h. Lactate was slightly higher and pH was slightly lower after the exposure, but similar to the effects of physical exertion. Echocardiography was performed in 6 subjects. In half of these subjects, the rhythm was determined to be "sinus" and in the other half the rhythm was indeterminant. In our study, the civilian device caused a mild lactic acidosis. No other important physiologic effects were found.

  5. 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

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

    PubMed

    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.

  7. The effect of SK&F 95654, a novel phosphodiesterase inhibitor, on cardiovascular, respiratory and platelet function.

    PubMed Central

    Murray, K. J.; Eden, R. J.; Dolan, J. S.; Grimsditch, D. C.; Stutchbury, C. A.; Patel, B.; Knowles, A.; Worby, A.; Lynham, J. A.; Coates, W. J.

    1992-01-01

    1. SK&F 95654 inhibited the guanosine 3':5'-cyclic monophosphate (cyclic GMP)-inhibited phosphodiesterase (cGI-PDE) with an IC50 value of 0.7 microM. The IC50 values were greater than 100 microM for the other four phosphodiesterase isoenzymes tested. The R-enantiomer of SK&F 95654 (IC50 = 0.35 microM) was a more potent inhibitor of cGI-PDE than was the S-enantiomer (IC50 = 5.3 microM). 2. In the guinea-pig working heart, SK&F 95654 produced a positive inotropic response without altering heart rate. 3. Oral administration of SK&F 95654 to conscious dogs caused dose-dependent increases in left ventricular dp/dtmax in the range 10-50 micrograms kg-1. These positive inotropic responses were maintained for 3 h without simultaneous changes in heart rate or blood pressure. The peak effects on left ventricular dp/dtmax were similar for orally and intravenously administered compound, indicating good oral bioavailability. 4. SK&F 95654 caused a potent inhibition of U46619-induced aggregation in both a human washed platelet suspension (WPS) (IC50 = 70 nM) and in human platelet-rich plasma (PRP) (IC50 = 60 nM), indicating that the compound shows negligible plasma binding. 5. The R-enantiomer of SK&F 95654 was twenty fold more potent as an inhibitor of platelet aggregation than was the S-enantiomer. The similarity of this ratio to that obtained on the cGI-PDE suggests that SK&F 95654 inhibits platelet aggregation via its effects on cGI-PDE. This was also indicated by studies which showed that SK&F 95654 increased adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels and activated cyclic AMP-dependent protein kinase in human platelets.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1422592

  8. 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.

  9. Modelling progressive autonomic failure in MSA: where are we now?

    PubMed

    Stemberger, Sylvia; Wenning, Gregor K

    2011-05-01

    Multiple system atrophy (MSA) is a fatal late-onset α-synucleinopathy that presents with features of ataxia, Parkinsonism, and pyramidal dysfunction in any combination. Over the last decade, efforts have been made to develop preclinical MSA testbeds for novel interventional strategies. The main focus has been on murine analogues of MSA-linked motor features and their underlying brainstem, cerebellar and basal ganglia pathology. Although progressive autonomic failure (AF) is a prominent clinical feature of patients with MSA, reflecting a disruption of both central and peripheral autonomic networks controlling cardiovascular, respiratory, urogenital, gastrointestinal and sudomotor functions, attempts of modelling this aspect of the human disease have been limited. However, emerging evidence suggests that AF-like features may occur in transgenic MSA models reflecting α-synucleinopathy lesions in distributed autonomic networks. Further research is needed to fully characterize both autonomic and motor features in optimized preclinical MSA models.

  10. 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.

  11. Stochastic Models of Human Errors

    NASA Technical Reports Server (NTRS)

    Elshamy, Maged; Elliott, Dawn M. (Technical Monitor)

    2002-01-01

    Humans play an important role in the overall reliability of engineering systems. More often accidents and systems failure are traced to human errors. Therefore, in order to have meaningful system risk analysis, the reliability of the human element must be taken into consideration. Describing the human error process by mathematical models is a key to analyzing contributing factors. Therefore, the objective of this research effort is to establish stochastic models substantiated by sound theoretic foundation to address the occurrence of human errors in the processing of the space shuttle.

  12. 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.

  13. 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.

  14. Human motion analysis and modeling

    NASA Astrophysics Data System (ADS)

    Prussing, Keith; Cathcart, J. Michael; Kocher, Brian

    2011-06-01

    Georgia Tech has investigated methods for the detection and tracking of personnel in a variety of acquisition environments. This research effort focused on a detailed phenomenological analysis of human physiology and signatures with the subsequent identification and characterization of potential observables. As a fundamental part of this research effort, Georgia Tech collected motion capture data on an individual for a variety of walking speeds, carrying loads, and load distributions. These data formed the basis for deriving fundamental properties of the individual's motion and supported the development of a physiologically-based human motion model. Subsequently this model aided the derivation and analysis of motion-based observables, particularly changes in the motion of various body components resulting from load variations. This paper will describe the data acquisition process, development of the human motion model, and use of the model in the observable analysis. Video sequences illustrating the motion data and modeling results will also 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. Rodent models for human diseases.

    PubMed

    Vandamme, Thierry F

    2015-07-15

    One of the factors limiting the translation of knowledge from preclinical studies to the clinic has been the limitations of in vivo diseases models. Except in the case of highly controlled and regulated clinical trials, geneticists and scientists do not use humans for their experimental investigations because of the obvious risk to life. Instead, they use various animal, fungal, bacterial, and plant species as model organisms for their studies. Amongst these model organisms, rodent models are the most used due to the easiness for the experiments and the possibility to modify genetically these model animals. Nevertheless, due to the fact that animal models typically do not contract the same genetic diseases as people, so scientists must alter their genomes to induce human disease states and to know what kind of mutation causes the disease. In this brief review, we will discuss the interests 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.

  17. Human Modeling For Ground Processing Human Factors Engineering Analysis

    NASA Technical Reports Server (NTRS)

    Tran, Donald; Stambolian, Damon; Henderson, Gena; Barth, Tim

    2011-01-01

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

  18. 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

  19. The Shigella human challenge model.

    PubMed

    Porter, C K; Thura, N; Ranallo, R T; Riddle, M S

    2013-02-01

    Shigella is an important bacterial cause of infectious diarrhoea globally. The Shigella human challenge model has been used since 1946 for a variety of objectives including understanding disease pathogenesis, human immune responses and allowing for an early assessment of vaccine efficacy. A systematic review of the literature regarding experimental shigellosis in human subjects was conducted. Summative estimates were calculated by strain and dose. While a total of 19 studies evaluating nine strains at doses ranging from 10 to 1 × 1010 colony-forming units were identified, most studies utilized the S. sonnei strain 53G and the S. flexneri strain 2457T. Inoculum solution and pre-inoculation buffering has varied over time although diarrhoea attack rates do not appear to increase above 75-80%, and dysentery rates remain fairly constant, highlighting the need for additional dose-ranging studies. Expansion of the model to include additional strains from different serotypes will elucidate serotype and strain-specific outcome variability.

  20. Human Operator Control Strategy Model.

    DTIC Science & Technology

    1980-04-01

    control learning control strategy N computer simulation of motor behavior ABSTRACT (Continue on reverese ide If necesery end Identify by block numbe...Frank Vogler has been a continuing resource during testing and analysis phases. Cooperative Plan students Kirk Hoyer , Bob Baltar, and Bob Hummel have...Introduction ....... .................... .. 79 1. Question 1: Do HOPE models match human behavior to an acceptable extent? .... ............ ... 80

  1. Human cardiovascular model and applications.

    PubMed

    Zhu, K Y; Ang, Alvin; Acharya U, Rajendra; Lim, C M

    2011-10-01

    Cardiovascular diseases (CVDs) can be known as a class of diseases which affect different parts of the cardiovascular system such as the heart or blood vessels. Hemodynamic signals are an important tool used by doctors to diagnose the type of CVD occurred in a patient. Diagnosing the correct type of CVD in a patient early will allow the patient to have the suitable medical treatment. Some examples of CVDs include coronary heart disease, cerebrovascular disease and peripheral arterial disease. A human cardiovascular model is developed in order to simulate different hemodynamic signals of the cardiovascular system. The hemodynamic signals include the blood pressures, flow rates and volumes in various part of the cardiovascular system. This paper presents a model which is able to simulate hemodynamic signals and they are able to represent the human arterial blood pressure accurately. Hence this model can also be used to simulate hypertensive patients in order to design control systems for regulation of blood pressure. Signal verification has been performed and the stability of the model is being investigated. Applications of the human cardiovascular model are also presented.

  2. 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

  3. 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.

  4. Modeling of Human Joint Structures.

    DTIC Science & Technology

    1982-09-01

    Radial Lateral " epicondyle Olecranon Radius Ulna Figure 3. Lateral aspect of the right elbow joint. -17- Annular Ligament This strong band encircles... elbow joint, knee joint, human joints, shoulder joint, ankle joint, joint models, hip joint, ligaments. 20. ABSTRACT (Continue on reverse side If...ligaments. -A rather extended discussion of the articulations and anatomical descriptions of the elbow , shoulder, hip, knee and ankle joints are

  5. 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.

  6. 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)

  7. Mouse models of human thalassemia

    SciTech Connect

    Anderson, W.F.; Martinell, J.; Whitney, J.B. III; Popp, R.A.

    1981-01-01

    The group of diseases called the thalassemias is the largest single-gene health problem in the world according the World Health Organization. The thalassemias are lethal hereditary anemias in which the infants cannot make their own blood. Three mouse mutants are shown to be models of the human disease ..cap alpha..-thalassemia. However, since an additional gene is affected, these mutants represent a particularly severe condition in which death occurs in the homozygous embryo even before globin genes are activated. Phenotypic and genotypic characteristics are described. (ACR)

  8. Genetically modified pig models for human diseases.

    PubMed

    Fan, Nana; Lai, Liangxue

    2013-02-20

    Genetically modified animal models are important for understanding the pathogenesis of human disease and developing therapeutic strategies. Although genetically modified mice have been widely used to model human diseases, some of these mouse models do not replicate important disease symptoms or pathology. Pigs are more similar to humans than mice in anatomy, physiology, and genome. Thus, pigs are considered to be better animal models to mimic some human diseases. This review describes genetically modified pigs that have been used to model various diseases including neurological, cardiovascular, and diabetic disorders. We also discuss the development in gene modification technology that can facilitate the generation of transgenic pig models for human diseases.

  9. 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).

  10. 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.

  11. 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.

  12. 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.

  13. Complex Systems and Human Performance Modeling

    DTIC Science & Technology

    2013-12-01

    human communication patterns can be implemented in a task network modeling tool. Although queues are a basic feature in many task network modeling...time. MODELING COMMUNICATIVE BEHAVIOR Barabasi (2010) argues that human communication patterns are “bursty”; that is, the inter-event arrival...Having implemented the methods advocated by Clauset et al. in C3TRACE, we have grown more confident that the human communication data discussed above

  14. Human mammary microenvironment better regulates the biology of human breast cancer in humanized mouse model.

    PubMed

    Zheng, Ming-Jie; Wang, Jue; Xu, Lu; Zha, Xiao-Ming; Zhao, Yi; Ling, Li-Jun; Wang, Shui

    2015-02-01

    During the past decades, many efforts have been made in mimicking the clinical progress of human cancer in mouse models. Previously, we developed a human breast tissue-derived (HB) mouse model. Theoretically, it may mimic the interactions between "species-specific" mammary microenvironment of human origin and human breast cancer cells. However, detailed evidences are absent. The present study (in vivo, cellular, and molecular experiments) was designed to explore the regulatory role of human mammary microenvironment in the progress of human breast cancer cells. Subcutaneous (SUB), mammary fat pad (MFP), and HB mouse models were developed for in vivo comparisons. Then, the orthotopic tumor masses from three different mouse models were collected for primary culture. Finally, the biology of primary cultured human breast cancer cells was compared by cellular and molecular experiments. Results of in vivo mouse models indicated that human breast cancer cells grew better in human mammary microenvironment. Cellular and molecular experiments confirmed that primary cultured human breast cancer cells from HB mouse model showed a better proliferative and anti-apoptotic biology than those from SUB to MFP mouse models. Meanwhile, primary cultured human breast cancer cells from HB mouse model also obtained the migratory and invasive biology for "species-specific" tissue metastasis to human tissues. Comprehensive analyses suggest that "species-specific" mammary microenvironment of human origin better regulates the biology of human breast cancer cells in our humanized mouse model of breast cancer, which is more consistent with the clinical progress of human breast cancer.

  15. 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.

  16. Humanized Mice as Preclinical Models in Transplantation.

    PubMed

    Safinia, N; Becker, P D; Vaikunthanathan, T; Xiao, F; Lechler, R; Lombardi, G

    2016-01-01

    Animal models have been instrumental in our understanding of the mechanisms of rejection and the testing of novel treatment options in the context of transplantation. We have now entered an exciting era with research on humanized mice driving advances in translational studies and in our understanding of the function of human cells in response to pathogens and cancer as well as the recognition of human allogeneic tissues in vivo. In this chapter we provide a historical overview of humanized mouse models of transplantation to date, outlining the distinct strains and share our experiences in the study of human transplantation immunology.

  17. 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.

  18. Parametric identification of human operator models

    NASA Technical Reports Server (NTRS)

    Ninz, N. R.

    1982-01-01

    The accurate and efficient identification of the human operator is still a need in human factors engineering especially concerning multivariable control. Control theoretic identification methods need to be tested with human operator models under realistic boundary conditons. The requirements and criteria for the use of parametric methods, selected models as well as the Maximum Likelihood Method and the Extended Kalman Filter are displayed. The experiments and results are comparatively discussed from the point of practical engineering.

  19. Human Systems Modeling and Simulation

    DTIC Science & Technology

    2005-12-01

    individuals, organizations, and other social forms as systems of practices. A rereading of the propositional and system forms shows that they make no... social inter-dependencies that underwrite human behavior: designing, prototyping, testing and delivering extensions to Synergia’s ACCORD technology for...also and primarily the cognitive and social inter-dependencies that underwrite human behavior. • Develop technology for the computational specification

  20. 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.

  1. Human Exposure Modeling - Databases to Support Exposure Modeling

    EPA Pesticide Factsheets

    Human exposure modeling relates pollutant concentrations in the larger environmental media to pollutant concentrations in the immediate exposure media. The models described here are available on other EPA websites.

  2. A human model for assessing comedogenic substances.

    PubMed

    Mills, O H; Kligman, A M

    1982-11-01

    Substances that are moderately to strongly comedogenic in the rabbit ear model test have been found to be capable of inducing comedones in the human model described in this report. The test substances are applied under occlusion for one month to the upper part of the backs of young adult, black men who have large follicles. The degree of follicular hyperkeratosis is assessed by a noninvasive "follicular biopsy" techniques, employing a fast-setting cyanoacrylate glue to remove the follicular contents. The rabbit model is more sensitive than the human. Substances that are weakly comedogenic in the rabbit are probably safe for human use with the possible exception of acne-prone persons.

  3. Modeling and Mapping of Human Source Data

    DTIC Science & Technology

    2011-03-08

    graduating undergraduates funded by a DoD funded Center of Excellence grant for Education , Research and Engineering: The number of undergraduates funded by...Representations for Military Simulations, Committee on Human Factors, Commission on Behavioral and Social Sciences and Education , ―Representing Human...Commission on Behavioral and Social Sciences and Education , ―Modeling Human and Organizational Behavior: Application to Military Simulations‖, NATIONAL

  4. 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

  5. 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.

  6. [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.

  7. 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

  8. Humanized mouse models of clinical disease

    PubMed Central

    Walsh, Nicole; Kenney, Laurie; Jangalwe, Sonal; Aryee, Ken-Edwin; Greiner, Dale L.; Brehm, Michael A.; Shultz, Leonard D.

    2017-01-01

    Immunodeficient mice engrafted with functional human cells and tissues, i.e., “humanized mice”, have become increasingly important as small pre-clinical animal models for the study of human diseases. Since the description of immunodeficient mice bearing mutations in the IL2 receptor common gamma chain (IL2rgnull) in the early 2000’s, investigators have been able to engraft murine recipients with human hematopoietic stem cells that develop into functional human immune systems. These mice can also be engrafted with human tissues such as islets, liver, skin, and most solid and hematologic cancers. Humanized mice are permitting significant progress in studies of human infectious disease, cancer, regenerative medicine, graft versus host disease, allergies, and immunity. Ultimately, use of humanized mice may lead to the implementation of truly “personalized” medicine in the clinic. This review discusses recent progress in the development and use of humanized mice, and highlights their utility for the study of human diseases. PMID:27959627

  9. 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.

  10. Avian-human influenza epidemic model.

    PubMed

    Iwami, Shingo; Takeuchi, Yasuhiro; Liu, Xianning

    2007-05-01

    A mathematical model is proposed to interpret the spread of avian influenza from the bird world to the human world. Our mathematical model warns that two types of the outbreak of avian influenza may occur if the humans do not prevent the spread of avian influenza. Moreover, it suggests that we cannot feel relieved although the total infected humans are kept at low level. In order to prevent spread of avian influenza in the human world, we must take the measures not only for the birds infected with avian influenza to exterminate but also for the humans infected with mutant avian influenza to quarantine when mutant avian influenza has already occurred. In particular, the latter measure is shown to be important to stop the second pandemic of avian influenza.

  11. Modeling of Embedded Human Systems

    DTIC Science & Technology

    2013-07-01

    reduces to solving an initial value HJ PDE. Let the system dynamics be given by ẋ = f(x, u), where f is bounded and Lipschitz continuous in x. Choose the...Sprinkle, “Synthesizing executable simulations from structural models of component- based systems,” Electronic Communications of the European Association

  12. Cascading Walks Model for Human Mobility Patterns

    PubMed Central

    Han, Xiao-Pu; Wang, Xiang-Wen; Yan, Xiao-Yong; Wang, Bing-Hong

    2015-01-01

    Background Uncovering the mechanism behind the scaling laws and series of anomalies in human trajectories is of fundamental significance in understanding many spatio-temporal phenomena. Recently, several models, e.g. the explorations-returns model (Song et al., 2010) and the radiation model for intercity travels (Simini et al., 2012), have been proposed to study the origin of these anomalies and the prediction of human movements. However, an agent-based model that could reproduce most of empirical observations without priori is still lacking. Methodology/Principal Findings In this paper, considering the empirical findings on the correlations of move-lengths and staying time in human trips, we propose a simple model which is mainly based on the cascading processes to capture the human mobility patterns. In this model, each long-range movement activates series of shorter movements that are organized by the law of localized explorations and preferential returns in prescribed region. Conclusions/Significance Based on the numerical simulations and analytical studies, we show more than five statistical characters that are well consistent with the empirical observations, including several types of scaling anomalies and the ultraslow diffusion properties, implying the cascading processes associated with the localized exploration and preferential returns are indeed a key in the understanding of human mobility activities. Moreover, the model shows both of the diverse individual mobility and aggregated scaling displacements, bridging the micro and macro patterns in human mobility. In summary, our model successfully explains most of empirical findings and provides deeper understandings on the emergence of human mobility patterns. PMID:25860140

  13. [The symmetry approach to the assessment of the functional state of the human body].

    PubMed

    Dmitrieva, N V

    1990-01-01

    A multiparameter description of different functional states of human organism has been accomplished on the basis of clinical and polymetric study of healthy and ill humans. The analysis of multiparameter data has been carried out using symmetry approach, image recognition, and graphic simulation. A harmonic correlation between complex physiological parameters of cardiovascular, respiratory, and vegetative nervous system is characteristic for healthy humans. The harmonic correlation changes by 10-15% in humans under stress and by more than 15% in ill humans. The intersystem interaction of physiological functions has been described.

  14. A Model of the Human Eye

    NASA Astrophysics Data System (ADS)

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

    2008-12-01

    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.

  15. 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.

  16. 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.

  17. 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 ...

  18. 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.

  19. 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.

  20. An Investigation of Human Performance Model Validation

    DTIC Science & Technology

    2005-03-01

    from both models and empirical activities, and the construction of scenarios that will sufficiently exercise model and human participants. 1 Development...Soar to represent peripheral players/platforms in simulation-based exercises that are used to evaluate system design concepts and tactics.) We expect...and operational concepts can best be employed to assist them." As noted above, models used in the JSB exercise must be highly accurate and accredited

  1. 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.

  2. 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.

  3. Human lung ex vivo infection models.

    PubMed

    Hocke, Andreas C; Suttorp, Norbert; Hippenstiel, Stefan

    2017-03-01

    Pneumonia is counted among the leading causes of death worldwide. Viruses, bacteria and pathogen-related molecules interact with cells present in the human alveolus by numerous, yet poorly understood ways. Traditional cell culture models little reflect the cellular composition, matrix complexity and three-dimensional architecture of the human lung. Integrative animal models suffer from species differences, which are of particular importance for the investigation of zoonotic lung diseases. The use of cultured ex vivo infected human lung tissue may overcome some of these limitations and complement traditional models. The present review gives an overview of common bacterial lung infections, such as pneumococcal infection and of widely neglected pathogens modeled in ex vivo infected lung tissue. The role of ex vivo infected lung tissue for the investigation of emerging viral zoonosis including influenza A virus and Middle East respiratory syndrome coronavirus is discussed. Finally, further directions for the elaboration of such models are revealed. Overall, the introduced models represent meaningful and robust methods to investigate principles of pathogen-host interaction in original human lung tissue.

  4. Human Operator Modeling for Aerial Tracking.

    DTIC Science & Technology

    1980-12-01

    HUMAN OPERATOR MODELING FOR AERIAL TRACKING JONA THAN KORN ARTER. EPHRATH DA VLD L. KLEINMAN DBCXMBt 19MDTICSELECTE APR 3 1981.j B Approwd for pVA& u...8217the "Guid 8en th Cart end Use of laboratory Animals, "Inatitate of Laboratory Animl ReaNuWAes, National Rtesarch CouncL The voluntary Infomed consent...Continue. on reverse aide If necessary and identify hc block numbrh) ._Modern Optimal Control techniques are e:iployed to investigate and model human

  5. 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

  6. 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.

  7. 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.

  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. Genetically modified pigs to model human diseases.

    PubMed

    Flisikowska, Tatiana; Kind, Alexander; Schnieke, Angelika

    2014-02-01

    Genetically modified mice are powerful tools to investigate the molecular basis of many human diseases. Mice are, however, of limited value for preclinical studies, because they differ significantly from humans in size, general physiology, anatomy and lifespan. Considerable efforts are, thus, being made to develop alternative animal models for a range of human diseases. These promise powerful new resources that will aid the development of new diagnostics, medicines and medical procedures. Here, we provide a comprehensive review of genetically modified porcine models described in the scientific literature: various cancers, cystic fibrosis, Duchenne muscular dystrophy, autosomal polycystic kidney disease, Huntington’s disease, spinal muscular atrophy, haemophilia A, X-linked severe combined immunodeficiency, retinitis pigmentosa, Stargardt disease, Alzheimer’s disease, various forms of diabetes mellitus and cardiovascular diseases.

  10. 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

  11. 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.

  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. Optical models of the human eye.

    PubMed

    Atchison, David A; Thibos, Larry N

    2016-03-01

    Optical models of the human eye have been used in visual science for purposes such as providing a framework for explaining optical phenomena in vision, for predicting how refraction and aberrations are affected by change in ocular biometry and as computational tools for exploring the limitations imposed on vision by the optical system of the eye. We address the issue of what is understood by optical model eyes, discussing the 'encyclopaedia' and 'toy train' approaches to modelling. An extensive list of purposes of models is provided. We discuss many of the theoretical types of optical models (also schematic eyes) of varying anatomical accuracy, including single, three and four refracting surface variants. We cover the models with lens structure in the form of nested shells and gradient index. Many optical eye models give accurate predictions only for small angles and small fields of view. If aberrations and image quality are important to consider, such 'paraxial' model eyes must be replaced by 'finite model' eyes incorporating features such as aspheric surfaces, tilts and decentrations, wavelength-dependent media and curved retinas. Many optical model eyes are population averages and must become adaptable to account for age, gender, ethnicity, refractive error and accommodation. They can also be customised for the individual when extensive ocular biometry and optical performance data are available. We consider which optical model should be used for a particular purpose, adhering to the principle that the best model is the simplest fit for the task. We provide a glimpse into the future of optical models of the human eye. This review is interwoven with historical developments, highlighting the important people who have contributed so richly to our understanding of visual optics.

  14. A model of the human supervisor

    NASA Technical Reports Server (NTRS)

    Kok, J. J.; Vanwijk, R. A.

    1977-01-01

    A general model of the human supervisor's behavior is given. Submechanisms of the model include: the observer/reconstructor; decision-making; and controller. A set of hypothesis is postulated for the relations between the task variables and the parameters of the different submechanisms of the model. Verification of the model hypotheses is considered using variations in the task variables. An approach is suggested for the identification of the model parameters which makes use of a multidimensional error criterion. Each of the elements of this multidimensional criterion corresponds to a certain aspect of the supervisor's behavior, and is directly related to a particular part of the model and its parameters. This approach offers good possibilities for an efficient parameter adjustment procedure.

  15. Constructing predictive models of human running

    PubMed Central

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

    2015-01-01

    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. PMID:25505131

  16. 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.

  17. Generative models: Human embryonic stem cells and multiple modeling relations.

    PubMed

    Fagan, Melinda Bonnie

    2016-04-01

    Model organisms are at once scientific models and concrete living things. It is widely assumed by philosophers of science that (1) model organisms function much like other kinds of models, and (2) that insofar as their scientific role is distinctive, it is in virtue of representing a wide range of biological species and providing a basis for generalizations about those targets. This paper uses the case of human embryonic stem cells (hESC) to challenge both assumptions. I first argue that hESC can be considered model organisms, analogous to classic examples such as Escherichia coli and Drosophila melanogaster. I then discuss four contrasts between the epistemic role of hESC in practice, and the assumptions about model organisms noted above. These contrasts motivate an alternative view of model organisms as a network of systems related constructively and developmentally to one another. I conclude by relating this result to other accounts of model organisms in recent philosophy of science.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. Benchmarking electrophysiological models of human atrial myocytes

    PubMed Central

    Wilhelms, Mathias; Hettmann, Hanne; Maleckar, Mary M.; Koivumäki, Jussi T.; Dössel, Olaf; Seemann, Gunnar

    2013-01-01

    Mathematical modeling of cardiac electrophysiology is an insightful method to investigate the underlying mechanisms responsible for arrhythmias such as atrial fibrillation (AF). In past years, five models of human atrial electrophysiology with different formulations of ionic currents, and consequently diverging properties, have been published. The aim of this work is to give an overview of strengths and weaknesses of these models depending on the purpose and the general requirements of simulations. Therefore, these models were systematically benchmarked with respect to general mathematical properties and their ability to reproduce certain electrophysiological phenomena, such as action potential (AP) alternans. To assess the models' ability to replicate modified properties of human myocytes and tissue in cardiac disease, electrical remodeling in chronic atrial fibrillation (cAF) was chosen as test case. The healthy and remodeled model variants were compared with experimental results in single-cell, 1D and 2D tissue simulations to investigate AP and restitution properties, as well as the initiation of reentrant circuits. PMID:23316167

  3. Characteristics of human arm based on musculoskeletal model in human-human cooperative task

    NASA Astrophysics Data System (ADS)

    Zhang, Nan; Ikeura, Ryojun; Wang, Yuanxin; Mizutani, Kazuki; Sawai, Hideki

    2007-12-01

    Human characteristics are supposed to be applied to the control systems of the human-friendly robots. Therefore, it is important to know the human characteristics in human-robot cooperative tasks. In this study, we considered a single rotational degree of freedom experimental system as well as a mass-spring-damper-friction dynamic model for the human arm and analyzed the master-slave and the master-semi master cooperative motions. Through the master-slave cooperative motion, we verified the application of the mass-spring-friction dynamic model of the slave's arm, and regarding its parameter we found the damping factor as zero and the stiffness as well as the coulomb friction torque almost individually invariable. Through the master-semi master cooperative motion, we got the torque characteristics and drew a comparison of them with those in the master-slave cooperative motion, and then we found improved torque characteristics, the constant torque characteristics.

  4. Modeling correlated human dynamics with temporal preference

    NASA Astrophysics Data System (ADS)

    Wang, Peng; Zhou, Tao; Han, Xiao-Pu; Wang, Bing-Hong

    2014-03-01

    We empirically study the activity pattern of individual blog-posting and observe the interevent time distributions decay as power-laws at both individual and population level. As different from previous studies, we find significant short-term memory in it. Moreover, the memory coefficient first decays in a power law and then turns to an exponential form. Our findings produce evidence for the strong short-term memory in human dynamics and challenge previous models. Accordingly, we propose a simple model based on temporal preference, which can well reproduce both the heavy-tailed nature and the strong memory effects. This work helps in understanding the temporal regularities of online human behaviors.

  5. A molecular model for sporadic human aneuploidy.

    PubMed

    Warren, William D; Gorringe, Kylie L

    2006-04-01

    Aneuploidy is a leading cause of birth defects and a significant contributor to infertility in humans. Maternal age is the only well-established risk factor for gametic aneuploidy in the general population, with the underlying cause(s) yet to be identified. Here we present an extension of the 'two-hit' model for sporadic human aneuploidy. An important implication of this model is that the genetic makeup of an individual will influence the threshold where recombinationally at-risk oocytes (hit-1 events) become sensitive to the effects of advancing age (hit-2 events). Consequently, the age-related risk of gametic aneuploidy in many individuals is likely to differ significantly from the population average, and single nucleotide polymorphisms (SNPs) associated with altered risk should be identifiable.

  6. 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

  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. Human Factors Engineering Program Review Model

    DTIC Science & Technology

    2004-02-01

    AA NUREG -0711,Rev. 2 Human Factors Engineering Program Review Model 20081009191 I i m To] Bi U.S. Nuclear Regulatory Commission Office of...Material As of November 1999, you may electronically access NUREG -series publications and other NRC records at NRC’s Public Electronic Reading Room at...http://www.nrc.qov/readinq-rm.html. Publicly released records include, to name a few, NUREG -series publications; Federal Register notices; applicant

  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. 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.

  11. 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.

  12. Human embryonic stem cell lines model experimental human cytomegalovirus latency.

    PubMed

    Penkert, Rhiannon R; Kalejta, Robert F

    2013-05-28

    Herpesviruses are highly successful pathogens that persist for the lifetime of their hosts primarily because of their ability to establish and maintain latent infections from which the virus is capable of productively reactivating. Human cytomegalovirus (HCMV), a betaherpesvirus, establishes latency in CD34(+) hematopoietic progenitor cells during natural infections in the body. Experimental infection of CD34(+) cells ex vivo has demonstrated that expression of the viral gene products that drive productive infection is silenced by an intrinsic immune defense mediated by Daxx and histone deacetylases through heterochromatinization of the viral genome during the establishment of latency. Additional mechanistic details about the establishment, let alone maintenance and reactivation, of HCMV latency remain scarce. This is partly due to the technical challenges of CD34(+) cell culture, most notably, the difficulty in preventing spontaneous differentiation that drives reactivation and renders them permissive for productive infection. Here we demonstrate that HCMV can establish, maintain, and reactivate in vitro from experimental latency in cultures of human embryonic stem cells (ESCs), for which spurious differentiation can be prevented or controlled. Furthermore, we show that known molecular aspects of HCMV latency are faithfully recapitulated in these cells. In total, we present ESCs as a novel, tractable model for studies of HCMV latency.

  13. Laboratory animal models for human Taenia solium.

    PubMed

    Avila, Guillermina; Teran, Nancy; Aguilar-Vega, Laura; Maravilla, Pablo; Mata-Miranda, Pilar; Flisser, Ana

    2006-01-01

    Human beings are the only hosts of adult Taenia solium; thus, many aspects of the host-parasite relationship are unknown. The development of successful experimental models of taeniasis allows in-depth investigations of the host-parasite relationship. We established experimental models in hamsters, gerbils and chinchillas. Here we review our findings regarding the characteristics of the tapeworms, their anchoring site and development, as well as the humoral and cellular immune response they elicit. We also used statistics to analyze the data obtained in different infections performed along several years. Furthermore, we compared the size of T. solium rostellum and strobila recovered from hamsters and gerbils to those obtained from humans. Our data indicate that these rodents are adequate experimental models for studying T. solium in its adult stage; that parasites induce immune responses and that hamsters seem to be more permissive hosts than gerbils, since parasites survive for longer times, grow longer and develop more, and the inflammatory response in the intestinal mucosa against T. solium is moderate. Finally, chinchillas are the most successful experimental definitive model for adult T. solium, since tapeworms with gravid proglottids are obtained, and the life cycle can be continued to the intermediate host.

  14. Modeling and simulation of the human eye

    NASA Astrophysics Data System (ADS)

    Duran, R.; Ventura, L.; Nonato, L.; Bruno, O.

    2007-02-01

    The computational modeling of the human eye has been wide studied for different sectors of the scientific and technological community. One of the main reasons for this increasing interest is the possibility to reproduce eye optic properties by means of computational simulations, becoming possible the development of efficient devices to treat and to correct the problems of the vision. This work explores this aspect still little investigated of the modeling of the visual system, considering a computational sketch that make possible the use of real data in the modeling and simulation of the human visual system. This new approach makes possible the individual inquiry of the optic system, assisting in the construction of new techniques used to infer vital data in medical investigations. Using corneal topography to collect real data from patients, a computational model of cornea is constructed and a set of simulations were build to ensure the correctness of the system and to investigate the effect of corneal abnormalities in retinal image formation, such as Plcido Discs, Point Spread Function, Wave front and the projection of a real image and it's visualization on retina.

  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. Zebrafish as a model for human osteosarcoma.

    PubMed

    Mohseny, A B; Hogendoorn, P C W

    2014-01-01

    For various reasons involving biological comparativeness, expansive technological possibilities, accelerated experimental speed, and competitive costs, zebrafish has become a comprehensive model for cancer research. Hence, zebrafish embryos and full-grown fish have been instrumental for studies of leukemia, melanoma, pancreatic cancer, bone tumors, and other malignancies. Although because of its similarities to human osteogenesis zebrafish appears to be an appealing model to investigate osteosarcoma, only a few osteosarcoma specific studies have been accomplished yet. Here, we review interesting related and unrelated reports of which the findings might be extrapolated to osteosarcoma. More importantly, rational but yet unexplored applications of zebrafish are debated to expand the window of opportunities for future establishment of osteosarcoma models. Accordingly technological advances of zebrafish based cancer research, such as robotic high-throughput multicolor injection systems and advanced imaging methods are discussed. Furthermore, various use of zebrafish embryos for screening drug regimens by combinations of chemotherapy, novel drug deliverers, and immune system modulators are suggested. Concerning the etiology, the high degree of genetic similarity between zebrafish and human cancers indicates that affected regions are evolutionarily conserved. Therefore, zebrafish as a swift model system that allows for the investigation of multiple candidate gene-defects is presented.

  17. 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.

  18. 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

  19. 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).

  20. Modeling autism spectrum disorders with human neurons.

    PubMed

    Beltrão-Braga, Patricia C B; Muotri, Alysson R

    2017-02-01

    Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by impaired social communication and interactions and by restricted and repetitive behaviors. Although ASD is suspected to have a heritable or sporadic genetic basis, its underlying etiology and pathogenesis are not well understood. Therefore, viable human neurons and glial cells produced using induced pluripotent stem cells (iPSC) to reprogram cells from individuals affected with ASD provide an unprecedented opportunity to elucidate the pathophysiology of these disorders, providing novel insights regarding ASD and a potential platform to develop and test therapeutic compounds. Herein, we discuss the state of art with regards to ASD modeling, including limitations of this technology, as well as potential future directions. This article is part of a Special Issue entitled SI: Exploiting human neurons.

  1. 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.

  2. 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.

  3. Adaptive human behavior in epidemiological models

    PubMed Central

    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

    2011-01-01

    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. PMID:21444809

  4. 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.

  5. Advancing swine models for human health and diseases.

    PubMed

    Walters, Eric M; Prather, Randall S

    2013-01-01

    Swine models are relatively new kids on the block for modeling human health and diseases when compared to rodents and dogs. Because of the similarity to humans in size, physiology, and genetics, the pig has made significant strides in advancing the understanding of the human condition, and is thus an excellent choice for an animal model. Recent technological advances to genetic engineering of the swine genome enhance the utility of swine as models of human genetic diseases.

  6. 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.

  7. 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.

  8. A Cognitive Architecture for Human Performance Process Model Research

    DTIC Science & Technology

    1992-11-01

    Architecture for Human Performance Process Model C - F33615-91 -D-0009 Research PE - 62205F PR- 1710 6. AUTHOR(S) TA - 00 Michael J. Young WU - 60 7...OF PAGES cognitive architectures human performance process models 4 1 cognitive psychology Implementation architectures 16. PRICE CODE computational...1 Human Performance Process Models ............................................................ 2

  9. A human neurodevelopmental model for Williams syndrome

    PubMed Central

    Chailangkarn, Thanathom; Trujillo, Cleber A.; Freitas, Beatriz C.; Hrvoj-Mihic, Branka; Herai, Roberto H.; Yu, Diana X.; Brown, Timothy T.; Marchetto, Maria C. N.; 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.

    2016-01-01

    Summary Williams syndrome (WS) 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 WS lack precisely the same set of genes, with breakpoints in chromosome band 7q11.231–5. The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioral pathologies in humans, remains largely unexplored. Here, we investigate neural progenitor cells (NPCs) and cortical neurons derived from WS and typically developing (TD) induced pluripotent stem cells (iPSCs). WS NPCs have an increased doubling time and apoptosis compared to TD NPCs. Using an atypical WS subject6, 7, we narrowed this cellular phenotype to a single gene candidate, FZD9. At the neuronal stage, WS-derived layers V/VI cortical neurons were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in WS neurons were validated after Golgi staining of postmortem layers V/VI cortical neurons. This human iPSC model8 fills in the current knowledge gap in WS cellular biology and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain. PMID:27509850

  10. 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.

  11. 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.

  12. A model for learning human reaching movements.

    PubMed

    Karniel, A; Inbar, G F

    1997-09-01

    Reaching movement is a fast movement towards a given target. The main characteristics of such a movement are straight path and a bell-shaped speed profile. In this work a mathematical model for the control of the human arm during ballistic reaching movements is presented. The model of the arm contains a 2 degrees of freedom planar manipulator, and a Hill-type, non-linear mechanical model of six muscles. The arm model is taken from the literature with minor changes. The nervous system is modeled as an adjustable pattern generator that creates the control signals to the muscles. The control signals in this model are rectangular pulses activated at various amplitudes and timings, that are determined according to the given target. These amplitudes and timings are the parameters that should be related to each target and initial conditions in the work-space. The model of the nervous system consists of an artificial neural net that maps any given target to the parameter space of the pattern generator. In order to train this net, the nervous system model includes a sensitivity model that transforms the error from the arm end-point coordinates to the parameter coordinates. The error is assessed only at the termination of the movement from knowledge of the results. The role of the non-linearity in the muscle model and the performance of the learning scheme are analysed, illustrated in simulations and discussed. The results of the present study demonstrate the central nervous system's (CNS) ability to generate typical reaching movements with a simple feedforward controller that controls only the timing and amplitude of rectangular excitation pulses to the muscles and adjusts these parameters based on knowledge of the results. In this scheme, which is based on the adjustment of only a few parameters instead of the whole trajectory, the dimension of the control problem is reduced significantly. It is shown that the non-linear properties of the muscles are essential to achieve

  13. Variable strategy model of the human operator

    NASA Astrophysics Data System (ADS)

    Phillips, John Michael

    Human operators often employ discontinuous or "bang-bang" control strategies when performing large-amplitude acquisition tasks. The current study applies Variable Structure Control (VSC) techniques to model human operator behavior during acquisition tasks. The result is a coupled, multi-input model replicating the discontinuous control strategy. In the VSC formulation, a switching surface is the mathematical representation of the operator's control strategy. The performance of the Variable Strategy Model (VSM) is evaluated by considering several examples, including the longitudinal control of an aircraft during the visual landing task. The aircraft landing task becomes an acquisition maneuver whenever large initial offsets occur. Several different strategies are explored in the VSM formulation for the aircraft landing task. First, a switching surface is constructed from literal interpretations of pilot training literature. This approach yields a mathematical representation of how a pilot is trained to fly a generic aircraft. This switching surface is shown to bound the trajectory response of a group of pilots performing an offset landing task in an aircraft simulator study. Next, front-side and back-side landing strategies are compared. A back-side landing strategy is found to be capable of landing an aircraft flying on either the front side or back side of the power curve. However, the front-side landing strategy is found to be insufficient for landing an aircraft flying on the back side. Finally, a more refined landing strategy is developed that takes into the account the specific aircraft's dynamic characteristics. The refined strategy is translated back into terminology similar to the existing pilot training literature.

  14. 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

  15. A model for humanization in critical care.

    PubMed

    Facioli, Adriano Machado; Amorim, Fábio Ferreira; de Almeida, Karlo Jozefo Quadros

    2012-01-01

    We present a case in which narrative medicine was used to assist a patient with amyotrophic lateral sclerosis who was dependent on mechanical ventilation and prolonged hospitalization. Implementing narrative medicine led to the development of more effective communication that strengthened the therapeutic relationship, enhanced humane care practices, and resulted in greater physical and psychological comfort for the patient. Narrative medicine is a discipline that has been progressively incorporated into medical training to restore a humane and individual physician-patient relationship. The patient is viewed, not merely as a case to diagnose, but as a person with a story that evokes emotions in those who assist him or her. In fact, narrative medicine can be understood as a model of medical practice based on narrative competence, ie, the ability to acknowledge, to absorb, to interpret, and to respond to a person's story. It strengthens empathy, rescues patient individuality, and facilitates solutions to conflicts in complex settings, such as critical care units, where clinicians are constantly exposed to existential issues, both moral and ethical.

  16. Efficiency of a model human image code

    NASA Technical Reports Server (NTRS)

    Watson, Andrew B.

    1987-01-01

    Hypothetical schemes for neural representation of visual information can be expressed as explicit image codes. Here, a code modeled on the simple cells of the primate striate cortex is explored. The Cortex transform maps a digital image into a set of subimages (layers) that are bandpass in spatial frequency and orientation. The layers are sampled so as to minimize the number of samples and still avoid aliasing. Samples are quantized in a manner that exploits the bandpass contrast-masking properties of human vision. The entropy of the samples is computed to provide a lower bound on the code size. Finally, the image is reconstructed from the code. Psychophysical methods are derived for comparing the original and reconstructed images to evaluate the sufficiency of the code. When each resolution is coded at the threshold for detection artifacts, the image-code size is about 1 bit/pixel.

  17. 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

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.…

  6. 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…

  7. 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…

  8. 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.

  9. 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.

  10. Stochastic models for human gene mapping

    SciTech Connect

    Goradia, T.M.

    1992-01-01

    This thesis examines a variety of gene mapping experiments and recommends, on the basis of stochastic and combinatorial analysis, improved experimental designs. Somatic cell hybrid panels can localize genes to particular chromosomes or chromosomal regions. Although the redundancy within randomly generated panels may be beneficial, probability calculations reveal their inefficiency. Equally good panels with far fewer clones can be constructed by choosing clones from pre-existing collection of clones. The method of simulated annealing is suggested for judiciously selecting small, informative panels from larger existing collections of clones. A more difficult exercise is mapping a gene relative to syntenic genes on the basis of genetic distance. Traditional methods of pedigree analysis are able to accomplish this to a great extent. Automatic genotype elimination algorithms for a single locus play a central role in making likelihood computations on human pedigree data feasible. A simple algorithm that is fully efficient in pedigrees without loops is presented. This algorithm can be easily coded and is instrumental in reducing computing times for pedigree analysis. Alternative methods are needed for high-resolution gene mapping. Three-locus sperm typing and its implications for the estimation of recombination fractions and for locus ordering are examined. Comparisons are made among some sequential stopping rules for three-locus order assignment. Poissonization and other stochastic methods are used for approximating the mean stopping times and error probabilities. A trisection strategy for ordering a new locus relative to an existing set of loci is proposed. When used in conjunction with Bayesian methods, this trisection strategy has attractive optimality properties. The genetic distance between the [sup G][gamma] globin locus and the parathyroid hormone locus is verified by a probabilistic model that accounts for the major sources of laboratory error.

  11. Symbolic modeling of human anatomy for visualization and simulation

    NASA Astrophysics Data System (ADS)

    Pommert, Andreas; Schubert, Rainer; Riemer, Martin; Schiemann, Thomas; Tiede, Ulf; Hoehne, Karl H.

    1994-09-01

    Visualization of human anatomy in a 3D atlas requires both spatial and more abstract symbolic knowledge. Within our 'intelligent volume' model which integrates these two levels, we developed and implemented a semantic network model for describing human anatomy. Concepts for structuring (abstraction levels, domains, views, generic and case-specific modeling, inheritance) are introduced. Model, tools for generation and exploration and applications in our 3D anatomical atlas are presented and discussed.

  12. Dynamics of the two process model of human sleep regulation

    NASA Astrophysics Data System (ADS)

    Kenngott, Max; McKay, Cavendish

    2011-04-01

    We examine the dynamics of the two process model of human sleep regulation. In this model, sleep propensity is governed by the interaction between a periodic threshold (process C) and a saturating growth/decay (process S). We find that the parameter space of this model admits sleep cycles with a wide variety of characteristics, many of which are not observed in normal human sleepers. We also examine the effects of phase dependent feedback on this model.

  13. Animal model for study of human hepatitis viruses.

    PubMed

    Chayama, Kazuaki; Hayes, C Nelson; Hiraga, Nobuhiko; Abe, Hiromi; Tsuge, Masataka; Imamura, Michio

    2011-01-01

    Human hepatitis B virus (HBV) and hepatitis C virus (HCV) infect only chimpanzees and humans. Analysis of both viruses has long been hampered by the absence of a small animal model. The recent development of human hepatocyte chimeric mice has enabled us to carry out studies on viral replication and cellular changes induced by replication of human hepatitis viruses. Various therapeutic agents have also been tested using this model. In the present review, we summarize published studies using chimeric mice and discuss the merits and shortcomings of this model.

  14. 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.

  15. Modeling Aggressive Medulloblastoma Using Human-Induced Pluripotent Stem Cells

    DTIC Science & Technology

    2015-07-01

    AWARD NUMBER: W81XWH-14-1-0176 TITLE: Modeling Aggressive Medulloblastoma Using Human-Induced Pluripotent Stem Cells PRINCIPAL INVESTIGATOR...Prescribed by ANSI Std. Z39.18 July 2015 Annual 01-July 2014 -- 30 Jun 2015 Modeling Aggressive Medulloblastoma Using Human-Induced Pluripotent Stem...induced pluripotent stem cells by Atoh1 induction can be efficiently transformed by MYC oncogene to form aggressive brain tumors that recapitulate human

  16. 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.

  17. Humanized mouse model for assessing the human immune response to xenogeneic and allogeneic decellularized biomaterials.

    PubMed

    Wang, Raymond M; Johnson, Todd D; He, Jingjin; Rong, Zhili; Wong, Michelle; Nigam, Vishal; Behfar, Atta; Xu, Yang; Christman, Karen L

    2017-06-01

    Current assessment of biomaterial biocompatibility is typically implemented in wild type rodent models. Unfortunately, different characteristics of the immune systems in rodents versus humans limit the capability of these models to mimic the human immune response to naturally derived biomaterials. Here we investigated the utility of humanized mice as an improved model for testing naturally derived biomaterials. Two injectable hydrogels derived from decellularized porcine or human cadaveric myocardium were compared. Three days and one week after subcutaneous injection, the hydrogels were analyzed for early and mid-phase immune responses, respectively. Immune cells in the humanized mouse model, particularly T-helper cells, responded distinctly between the xenogeneic and allogeneic biomaterials. The allogeneic extracellular matrix derived hydrogels elicited significantly reduced total, human specific, and CD4(+) T-helper cell infiltration in humanized mice compared to xenogeneic extracellular matrix hydrogels, which was not recapitulated in wild type mice. T-helper cells, in response to the allogeneic hydrogel material, were also less polarized towards a pro-remodeling Th2 phenotype compared to xenogeneic extracellular matrix hydrogels in humanized mice. In both models, both biomaterials induced the infiltration of macrophages polarized towards a M2 phenotype and T-helper cells polarized towards a Th2 phenotype. In conclusion, these studies showed the importance of testing naturally derived biomaterials in immune competent animals and the potential of utilizing this humanized mouse model for further studying human immune cell responses to biomaterials in an in vivo environment.

  18. 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...

  19. Mouse Model of Human Hereditary Pancreatitis

    DTIC Science & Technology

    2016-09-01

    cause hereditary pancreatitis in humans. Previous attempts to introduce these mutant forms of human trypsinogen into mice have failed to produce...mutations in mouse trypsinogen isoform T7. Under this aim, we had two major tasks in our SOW: Major Task 1 was the design and construction of mutant forms...of the T7 mouse trypsinogen gene and expression and purification of these mutant enzymes. Major Task 2 was to analyze autoactivation of the T7

  20. 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.

  1. 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.

  2. Fly Models of Human Diseases: Drosophila as a Model for Understanding Human Mitochondrial Mutations and Disease.

    PubMed

    Sen, A; Cox, R T

    2017-01-01

    Mitochondrial diseases are a prevalent, heterogeneous class of diseases caused by defects in oxidative phosphorylation, whose severity depends upon particular genetic mutations. These diseases can be difficult to diagnose, and current therapeutics have limited efficacy, primarily treating only symptoms. Because mitochondria play a pivotal role in numerous cellular functions, especially ATP production, their diminished activity has dramatic physiological consequences. While this in and of itself makes treating mitochondrial disease complex, these organelles contain their own DNA, mtDNA, whose products are required for ATP production, in addition to the hundreds of nucleus-encoded proteins. Drosophila offers a tractable whole-animal model to understand the mechanisms underlying loss of mitochondrial function, the subsequent cellular and tissue damage that results, and how these organelles are inherited. Human and Drosophila mtDNAs encode the same set of products, and the homologous nucleus-encoded genes required for mitochondrial function are conserved. In addition, Drosophila contain sufficiently complex organ systems to effectively recapitulate many basic symptoms of mitochondrial diseases, yet are relatively easy and fast to genetically manipulate. There are several Drosophila models for specific mitochondrial diseases, which have been recently reviewed (Foriel, Willems, Smeitink, Schenck, & Beyrath, 2015). In this review, we highlight the conservation between human and Drosophila mtDNA, the present and future techniques for creating mtDNA mutations for further study, and how Drosophila has contributed to our current understanding of mitochondrial inheritance.

  3. Zebrafish heart as a model for human cardiac electrophysiology.

    PubMed

    Vornanen, Matti; Hassinen, Minna

    2016-01-01

    The zebrafish (Danio rerio) has become a popular model for human cardiac diseases and pharmacology including cardiac arrhythmias and its electrophysiological basis. Notably, the phenotype of zebrafish cardiac action potential is similar to the human cardiac action potential in that both have a long plateau phase. Also the major inward and outward current systems are qualitatively similar in zebrafish and human hearts. However, there are also significant differences in ionic current composition between human and zebrafish hearts, and the molecular basis and pharmacological properties of human and zebrafish cardiac ionic currents differ in several ways. Cardiac ionic currents may be produced by non-orthologous genes in zebrafish and humans, and paralogous gene products of some ion channels are expressed in the zebrafish heart. More research on molecular basis of cardiac ion channels, and regulation and drug sensitivity of the cardiac ionic currents are needed to enable rational use of the zebrafish heart as an electrophysiological model for the human heart.

  4. A novel SCID mouse model for studying spontaneous metastasis of human lung cancer to human tissue.

    PubMed

    Teraoka, S; Kyoizumi, S; Seyama, T; Yamakido, M; Akiyama, M

    1995-05-01

    We established a novel severe combined immunodeficient (SCID) mouse model for the study of human lung cancer metastasis to human lung. Implantation of both human fetal and adult lung tissue into mammary fat pads of SCID mice showed a 100% rate of engraftment, but only fetal lung implants revealed normal morphology of human lung tissue. Using these chimeric mice, we analyzed human lung cancer metastasis to both mouse and human lungs by subcutaneous inoculation of human squamous cell carcinoma and adenocarcinoma cell lines into the mice. In 60 to 70% of SCID mice injected with human-lung squamous-cell carcinoma, RERF-LC-AI, cancer cells were found to have metastasized to both mouse lungs and human fetal lung implants but not to human adult lung implants 80 days after cancer inoculation. Furthermore, human-lung adenocarcinoma cells, RERF-LC-KJ, metastasized to the human lung implants within 90 days in about 40% of SCID mice, whereas there were no metastases to the lungs of the mice. These results demonstrate the potential of this model for the in vivo study of human lung cancer metastasis.

  5. 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?

  6. Human Cancer Models Initiative | Office of Cancer Genomics

    Cancer.gov

    The Human Cancer Models Initiative (HCMI) is an international consortium that is generating novel human tumor-derived culture models, which are annotated with genomic and clinical data. In an effort to advance cancer research and more fully understand how in vitro findings are related to clinical biology, HCMI-developed models and related data will be available as a community resource for cancer research.

  7. A model of human decisionmaking in a fault diagnosis task

    NASA Technical Reports Server (NTRS)

    Rouse, W. B.

    1978-01-01

    Utilizing elementary concepts from the theory of fuzzy sets as well as several nonfuzzy heuristics, a model is presented of human decisionmaking in the task of troubleshooting graphically displayed networks. The performance of the model is compared to the results of two previously reported experimental studies. The ability of the model to represent human decisionmaking as a function of network size, forced-pacing, and computer aiding is considered.

  8. Huntington disease models and human neuropathology: similarities and differences

    PubMed Central

    2009-01-01

    Huntington disease (HD) occurs only in humans. Thus, its natural pathogenesis takes place exclusively within the human brains expressing the causative, mutated protein huntingtin (mhtt). The techniques applicable to postmortem human HD brains are inadequate for investigating the cellular pathogenesis. The creation of genetically engineered animals represents a critical moment in neuroscience. Monitoring the actions of either normal, or abnormal proteins at subcellular levels, and at different time points is now possible thanks to these models. They are the necessary substitutes to investigate the wild type (whtt), or mhtt. The postmortem neuropathologic phenotype of the human HD is well documented. Its pattern and spectrum are highly predictable. From this point of view, the existent models do not exhibit the phenotypic constellation of changes seen in the human HD brains. On one hand, this deficit reflects the limitations of the methods of evaluation used in a clinical setting. On the other hand, it highlights the limitations of the animals. The validity of the models probably should be measured by their capacity of reproducing the cellular dysfunctions of HD rather than the phenotype of the postmortem human brains. Although not perfect, these models are essential for modeling the human disease in cells, which is not feasible with postmortem human HD brains. Nonetheless, their relevance to the patient population remains to be determined. Ultimately needed are means preventing the disease to occur, the discovery of which probably depends on these models. PMID:17978822

  9. 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.

  10. Biofidelic Human Activity Modeling and Simulation with Large Variability

    DTIC Science & Technology

    2014-11-25

    capture data to replicate a human activity in 3D space. Since technologies for simultaneously capturing human motion and dynamic shapes are not yet ready...for practical use, a motion capture system can be used to capture markers on the body during motion and a 3D body scanner can be used to capture the...animation-capable model that can replicate a human activity in 3D space with the true shape and true motion of a human. Using this approach, a model

  11. Humanized in vivo Model for Autoimmune Diabetes

    DTIC Science & Technology

    2010-05-07

    complexes in the thymus. As T cell CD4 avidity interaction with the 2 domain of the MHC class II has been shown to contribute positively to thymic T...mice (DR4) were generated as previously de- scribed [ 2 ]. These C57BL/6 I-Abo/o mice express a human- mouse chimeric class II molecule in which the TcR...transgenic for the type 1 diabetes- associated human MHC class II allele, DRB1*0401. J Clin Invest 1996;98:2597e603. [9] Kim J, Richter W, Aanstoot HJ

  12. 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.

  13. Mouse Model of Human Hereditary Pancreatitis

    DTIC Science & Technology

    2015-09-01

    trypsinogen cause hereditary pancreatitis in humans. Previous attempts to introduce these mutant forms of human trypsinogen into mice have failed to...cationic trypsinogen gene and obtained several new mutant strains. These newly created mouse strains will be characterized with respect to spontaneous...10 8. Special Reporting Requirements……………………………………11 9. Appendices……………………………………………………………11 4  Figure 1. Mutant forms of T7 trypsinogen

  14. 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.

  15. Generation and Analysis of Humanized Mouse Model of EBV Infection.

    PubMed

    Imadome, Ken-Ichi; Fujiwara, Shigeyoshi

    2017-01-01

    The recent development of severely immunodeficient mouse strains enabled the production of new-generation humanized mice, in which major components of the human immune system are reconstituted. These new-generation humanized mice can be infected with human pathogenic viruses that do not infect regular mice and target cells of the hematoimmune system. Here we describe the method for preparing humanized mice, infecting them with EBV, and for their virological and immunological analyses. The results obtained from our own mouse models are briefly described.

  16. Kernel Method Based Human Model for Enhancing Interactive Evolutionary Optimization

    PubMed Central

    Zhao, Qiangfu; Liu, Yong

    2015-01-01

    A fitness landscape presents the relationship between individual and its reproductive success in evolutionary computation (EC). However, discrete and approximate landscape in an original search space may not support enough and accurate information for EC search, especially in interactive EC (IEC). The fitness landscape of human subjective evaluation in IEC is very difficult and impossible to model, even with a hypothesis of what its definition might be. In this paper, we propose a method to establish a human model in projected high dimensional search space by kernel classification for enhancing IEC search. Because bivalent logic is a simplest perceptual paradigm, the human model is established by considering this paradigm principle. In feature space, we design a linear classifier as a human model to obtain user preference knowledge, which cannot be supported linearly in original discrete search space. The human model is established by this method for predicting potential perceptual knowledge of human. With the human model, we design an evolution control method to enhance IEC search. From experimental evaluation results with a pseudo-IEC user, our proposed model and method can enhance IEC search significantly. PMID:25879050

  17. Kernel method based human model for enhancing interactive evolutionary optimization.

    PubMed

    Pei, Yan; Zhao, Qiangfu; Liu, Yong

    2015-01-01

    A fitness landscape presents the relationship between individual and its reproductive success in evolutionary computation (EC). However, discrete and approximate landscape in an original search space may not support enough and accurate information for EC search, especially in interactive EC (IEC). The fitness landscape of human subjective evaluation in IEC is very difficult and impossible to model, even with a hypothesis of what its definition might be. In this paper, we propose a method to establish a human model in projected high dimensional search space by kernel classification for enhancing IEC search. Because bivalent logic is a simplest perceptual paradigm, the human model is established by considering this paradigm principle. In feature space, we design a linear classifier as a human model to obtain user preference knowledge, which cannot be supported linearly in original discrete search space. The human model is established by this method for predicting potential perceptual knowledge of human. With the human model, we design an evolution control method to enhance IEC search. From experimental evaluation results with a pseudo-IEC user, our proposed model and method can enhance IEC search significantly.

  18. A novel mouse model for stable engraftment of a human immune system and human hepatocytes.

    PubMed

    Strick-Marchand, Helene; Dusséaux, Mathilde; Darche, Sylvie; Huntington, Nicholas D; Legrand, Nicolas; Masse-Ranson, Guillemette; Corcuff, Erwan; Ahodantin, James; Weijer, Kees; Spits, Hergen; Kremsdorf, Dina; Di Santo, James P

    2015-01-01

    Hepatic infections by hepatitis B virus (HBV), hepatitis C virus (HCV) and Plasmodium parasites leading to acute or chronic diseases constitute a global health challenge. The species tropism of these hepatotropic pathogens is restricted to chimpanzees and humans, thus model systems to study their pathological mechanisms are severely limited. Although these pathogens infect hepatocytes, disease pathology is intimately related to the degree and quality of the immune response. As a first step to decipher the immune response to infected hepatocytes, we developed an animal model harboring both a human immune system (HIS) and human hepatocytes (HUHEP) in BALB/c Rag2-/- IL-2Rγc-/- NOD.sirpa uPAtg/tg mice. The extent and kinetics of human hepatocyte engraftment were similar between HUHEP and HIS-HUHEP mice. Transplanted human hepatocytes were polarized and mature in vivo, resulting in 20-50% liver chimerism in these models. Human myeloid and lymphoid cell lineages developed at similar frequencies in HIS and HIS-HUHEP mice, and splenic and hepatic compartments were humanized with mature B cells, NK cells and naïve T cells, as well as monocytes and dendritic cells. Taken together, these results demonstrate that HIS-HUHEP mice can be stably (> 5 months) and robustly engrafted with a humanized immune system and chimeric human liver. This novel HIS-HUHEP model provides a platform to investigate human immune responses against hepatotropic pathogens and to test novel drug strategies or vaccine candidates.

  19. 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…

  20. 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…

  1. [A vertical vibration model of human body in supine position].

    PubMed

    Sun, Jing-gong; Niu, Fu; Qi, Jian-cheng; Li, Ruo-xin

    2002-12-01

    Objective. To establish the models of head, abdomen, and chest of supine human body respectively under vertical vibration. Method. The mechanical impedance of 12 healthy volunteers aged 24-56 was measured under vertical white noise stimulus in the frequency range of 2-35 Hz. To explain these findings, the model of head was proposed, the models of abdomen and chest were computed by way of an optimization procedure. Result. The models of abdomen and chest are three-degree-of-freedom and the head is rigid. Conclusion. The mechanical impedance of the supine human body is linear and sole. The established models of head, abdomen and chest of supine human body when subjected to vertical vibration are useful for calculating and evaluating the comfort of supine human body under whole-body vibration.

  2. 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.

  3. 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.

  4. Modeling study of the failing heart and its interaction with an implantable rotary blood pump.

    PubMed

    Ramachandran, Deepa P; Luo, Chuan; Ma, Tony S; Clark, John W

    2011-01-01

    The effectiveness of clinical diagnosis and treatment of heart failure is a direct function of clinical signs that can be measured in a patient within cost and safety constraints. Large-scale mathematical modeling can be a key tool in revealing important, measurable clinical signs of heart failure, furthering medical understanding and development of treatment. In the first part of this study we have created two models of left heart failure--diastolic and systolic, using our human cardiovascular-respiratory system (H-CRS) model, and we present a comparison of the two types with emphasis on novel and differentiating clinical signs, such as tricuspid flow and septal motion. In the event of compromised left ventricular performance, mechanical left ventricular assist devices (LVAD) are often implanted to augment or completely replace the pumping action of the left ventricle (LV). One such type is the implantable rotary blood pump (iRBP). Several design issues related to the iRBP are difficult to study experimentally due to procedure complexity and limitations in animal models of heart failure [2]. Therefore, modeling has become a key tool in iRBP development. In the second part of this study, we have introduced an iRBP model based on [1]-[2] in the systolic failing heart to study the interactions. We consider optimal motor settings for different levels of LV assistance, the effects of the iRBP on the right heart, septum, and pulmonary circulation. Our model results align with those reported in [1]-[2]. Improvement in cardiac output, pulmonary congestion, and heart work are seen with the iRBP. We observe lowered septal assistance to RV and LV ejection with increasing pump speeds, elevating right ventricular (RV) work, reducing LVET, and causing ventricular mechanical dyssynchrony in ejection. These results suggest right heart compromise via the septum's reduced role with the introduction of an iRBP. This work emphasizes the critical role of modeling in heart failure and

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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…

  11. Cyberpsychology: a human-interaction perspective based on cognitive modeling.

    PubMed

    Emond, Bruno; West, Robert L

    2003-10-01

    This paper argues for the relevance of cognitive modeling and cognitive architectures to cyberpsychology. From a human-computer interaction point of view, cognitive modeling can have benefits both for theory and model building, and for the design and evaluation of sociotechnical systems usability. Cognitive modeling research applied to human-computer interaction has two complimentary objectives: (1) to develop theories and computational models of human interactive behavior with information and collaborative technologies, and (2) to use the computational models as building blocks for the design, implementation, and evaluation of interactive technologies. From the perspective of building theories and models, cognitive modeling offers the possibility to anchor cyberpsychology theories and models into cognitive architectures. From the perspective of the design and evaluation of socio-technical systems, cognitive models can provide the basis for simulated users, which can play an important role in usability testing. As an example of application of cognitive modeling to technology design, the paper presents a simulation of interactive behavior with five different adaptive menu algorithms: random, fixed, stacked, frequency based, and activation based. Results of the simulation indicate that fixed menu positions seem to offer the best support for classification like tasks such as filing e-mails. This research is part of the Human-Computer Interaction, and the Broadband Visual Communication research programs at the National Research Council of Canada, in collaboration with the Carleton Cognitive Modeling Lab at Carleton University.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. Human Systems Integration (HSI) Tradeoff Model

    DTIC Science & Technology

    2014-03-01

    while the SURVIAC model development team observed. The users evaluated the functionality and usability of the model in understanding the goal of HSI...Initiated: From scenario initiation 9. Time Completed: Results screen 10. Section 3: Usability /Tasks Walkthrough Please read the instructions...From scenario initiation 19. Time Completed: Results screen 20. Section 3: Usability /Tasks Walkthrough Please read the instructions below

  17. 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.

  18. Computer modeling and simulation of human movement.

    PubMed

    Pandy, M G

    2001-01-01

    Recent interest in using modeling and simulation to study movement is driven by the belief that this approach can provide insight into how the nervous system and muscles interact to produce coordinated motion of the body parts. With the computational resources available today, large-scale models of the body can be used to produce realistic simulations of movement that are an order of magnitude more complex than those produced just 10 years ago. This chapter reviews how the structure of the neuromusculoskeletal system is commonly represented in a multijoint model of movement, how modeling may be combined with optimization theory to simulate the dynamics of a motor task, and how model output can be analyzed to describe and explain muscle function. Some results obtained from simulations of jumping, pedaling, and walking are also reviewed to illustrate the approach.

  19. 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…

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. Development of task network models of human performance in microgravity

    NASA Technical Reports Server (NTRS)

    Diaz, Manuel F.; Adam, Susan

    1992-01-01

    This paper discusses the utility of task-network modeling for quantifying human performance variability in microgravity. The data are gathered for: (1) improving current methodologies for assessing human performance and workload in the operational space environment; (2) developing tools for assessing alternative system designs; and (3) developing an integrated set of methodologies for the evaluation of performance degradation during extended duration spaceflight. The evaluation entailed an analysis of the Remote Manipulator System payload-grapple task performed on many shuttle missions. Task-network modeling can be used as a tool for assessing and enhancing human performance in man-machine systems, particularly for modeling long-duration manned spaceflight. Task-network modeling can be directed toward improving system efficiency by increasing the understanding of basic capabilities of the human component in the system and the factors that influence these capabilities.

  5. Enabling human HUMS with data modeling

    NASA Astrophysics Data System (ADS)

    Jaenisch, Holger M.; Handley, James W.; Jaenisch, Kristina K.; Hicklen, Michael L.

    2006-05-01

    We simulate a notional Navy SEAL rebreather diver on an extended mission using Model Predictive Control (MPC) theory. A mathematical framework for enabling physiological HUMS (Health Usage Management Systems) is shown. A rebreather simulation is used to derive MPC baseline Data Models of diver status by converting the simulation first into differential equations and then into lookup tables (LUT). When abnormal readings are indicated, sensor data from the diver is published to the ad hoc network, enabling intermittent upload. Mission success confidence is updated and determined during the mission. A novel method of converting MPC Data Models into lookup tables worn by the diver is given.

  6. 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

  7. A Review on Human Respiratory Modeling.

    PubMed

    Ghafarian, Pardis; Jamaati, Hamidreza; Hashemian, Seyed Mohammadreza

    2016-01-01

    Input impedance of the respiratory system is measured by forced oscillation technique (FOT). Multiple prior studies have attempted to match the electromechanical models of the respiratory system to impedance data. Since the mechanical behavior of airways and the respiratory system as a whole are similar to an electrical circuit in a combination of series and parallel formats some theories were introduced according to this issue. It should be noted that, the number of elements used in these models might be less than those required due to the complexity of the pulmonary-chest wall anatomy. Various respiratory models have been proposed based on this idea in order to demonstrate and assess the different parts of respiratory system related to children and adults data. With regard to our knowledge, some of famous respiratory models in related to obstructive, restrictive diseases and also Acute Respiratory Distress Syndrome (ARDS) are reviewed in this article.

  8. A Review on Human Respiratory Modeling

    PubMed Central

    Ghafarian, Pardis; Hashemian, Seyed Mohammadreza

    2016-01-01

    Input impedance of the respiratory system is measured by forced oscillation technique (FOT). Multiple prior studies have attempted to match the electromechanical models of the respiratory system to impedance data. Since the mechanical behavior of airways and the respiratory system as a whole are similar to an electrical circuit in a combination of series and parallel formats some theories were introduced according to this issue. It should be noted that, the number of elements used in these models might be less than those required due to the complexity of the pulmonary-chest wall anatomy. Various respiratory models have been proposed based on this idea in order to demonstrate and assess the different parts of respiratory system related to children and adults data. With regard to our knowledge, some of famous respiratory models in related to obstructive, restrictive diseases and also Acute Respiratory Distress Syndrome (ARDS) are reviewed in this article. PMID:27904536

  9. 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.

  10. Inverse Kinematic Analysis of Human Hand Thumb Model

    NASA Astrophysics Data System (ADS)

    Toth-Tascau, Mirela; Pater, Flavius; Stoia, Dan Ioan; Menyhardt, Karoly; Rosu, Serban; Rusu, Lucian; Vigaru, Cosmina

    2011-09-01

    This paper deals with a kinematic model of the thumb of the human hand. The proposed model has 3 degrees of freedom being able to model the movements of the thumb tip with respect to the wrist joint centre. The kinematic equations are derived based on Denavit-Hartenberg Convention and solved in both direct and inverse way. Inverse kinematic analysis of human hand thumb model reveals multiple and connected solutions which are characteristic to nonlinear systems when the number of equations is greater than number of unknowns and correspond to natural movements of the finger.

  11. Evaluating human performance modeling for system assessment: Promise and problems

    NASA Technical Reports Server (NTRS)

    Patterson, Robert W.; Young, Michael J.

    1992-01-01

    The development and evaluation of computational human performance models is examined. An intention is to develop models which can be used to interact with system prototypes and simulations to perform system assessment. Currently LR is working on a set of models emulating cognitive, psychomotor, auditory, and visual activity for multiple operator positions of a command and control simulation system. These models, developed in conjunction with BBN Systems and Technologies, function within the simulation environment and allow for both unmanned system assessment and manned (human-in-loop) assessment of system interface and team interactions. These are relatively generic models with built-in flexibility which allows modification of some model parameters. These models have great potential for improving the efficiency and effectiveness of system design, test, and evaluation. However, the extent of the practical utility of these models is unclear. Initial verification efforts comparing model performance within the simulation to actual human operators on a similar, independent simulation have been performed and current efforts are directed at comparing human and model performance within the same simulation environment.

  12. Modeling human behaviors and reactions under dangerous environment.

    PubMed

    Kang, J; Wright, D K; Qin, S F; Zhao, Y

    2005-01-01

    This paper describes the framework of a real-time simulation system to model human behavior and reactions in dangerous environments. The system utilizes the latest 3D computer animation techniques, combined with artificial intelligence, robotics and psychology, to model human behavior, reactions and decision making under expected/unexpected dangers in real-time in virtual environments. The development of the system includes: classification on the conscious/subconscious behaviors and reactions of different people; capturing different motion postures by the Eagle Digital System; establishing 3D character animation models; establishing 3D models for the scene; planning the scenario and the contents; and programming within Virtools Dev. Programming within Virtools Dev is subdivided into modeling dangerous events, modeling character's perceptions, modeling character's decision making, modeling character's movements, modeling character's interaction with environment and setting up the virtual cameras. The real-time simulation of human reactions in hazardous environments is invaluable in military defense, fire escape, rescue operation planning, traffic safety studies, and safety planning in chemical factories, the design of buildings, airplanes, ships and trains. Currently, human motion modeling can be realized through established technology, whereas to integrate perception and intelligence into virtual human's motion is still a huge undertaking. The challenges here are the synchronization of motion and intelligence, the accurate modeling of human's vision, smell, touch and hearing, the diversity and effects of emotion and personality in decision making. There are three types of software platforms which could be employed to realize the motion and intelligence within one system, and their advantages and disadvantages are discussed.

  13. 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

  14. 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.

  15. 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.

  16. Companion animals symposium: humanized animal models of the microbiome.

    PubMed

    Gootenberg, D B; Turnbaugh, P J

    2011-05-01

    Humans and other mammals are colonized by trillions of microorganisms, most of which reside in the gastrointestinal tract, that provide key metabolic capabilities, such as the biosynthesis of vitamins and AA, the degradation of dietary plant polysaccharides, and the metabolism of orally administered therapeutics. Although much progress has been made by studying the human microbiome directly, comparing the human microbiome with that of other animals, and constructing in vitro models of the human gut, there remains a need to develop in vivo models where host, microbial, and environmental parameters can be manipulated. Here, we discuss some of the initial results from a promising method that enables the direct manipulation of microbial community structure, environmental exposures, host genotype, and other factors: the colonization of germ-free animals with complex microbial communities, including those from humans or other animal donors. Analyses of these resulting "humanized" gut microbiomes have begun to reveal 1) that key microbial activities can be transferred from the donor to the recipient animal (e.g., microbial reduction of cholesterol and production of equol), 2) that dietary shifts can affect the composition, gene abundance, and gene expression of the gut microbiome, 3) the succession of the microbial community in infants and ex-germ-free adult animals, and 4) the biogeography of these microbes across the length of gastrointestinal tract. Continued studies of humanized and other intentionally colonized animal models stand to provide new insight into not only the human microbiome, but also the microbiomes of our animal companions.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. An experimental study of human birth models

    NASA Astrophysics Data System (ADS)

    Baumer, Alexa; Gossmann, Roseanna; Fauci, Lisa J.; Leftwich, Megan C.

    2016-11-01

    The laboring uterus is a complex and dynamic fluid system. Relatively little is known about the fluid properties in this system. However, the two primary fluids of interest, amniotic fluid and vernix caseosa, likely play integral roles in the force transferred to the fetus during the final stages of parturition. This investigation probes the role of fluid in the force transfer during delivery by considering physical models that determine the role of various components of the full system. The first experimental model represents the fetus passing through the birth canal as concentric cylinders with a fluid filled gap. The rigid, inner cylinder moves through the highly flexible outer cylinder at a prescribed velocity. The geometry of the inner cylinder is varied by aspect ratio and length. A total of five different inner geometries are used to fully investigate the parameter space. As the inner cylinder moves through the outer cylinder, strain measurements are taken. These measurements are converted to force measurements as a function of time and position in the outer cylinder. The results of these experiments are compared with numerical results to form a more complete picture of force transfer. This model can be used as the foundation for predicting the force needed to deliver a fetus in the final stages of parturition. Additionally, more complex models, that incorporate uterine contraction forces, are being developed.

  2. Human-Assisted-Manufacturing Model Library

    DTIC Science & Technology

    2012-06-01

    62 3.3.5.3 Design Considerations...Figure 41. Metamodel for META Design models ....................................................................... 72 Figure 42. VME Requirements...supports the MCPML component of the iFAB project which provides for rapid design and configuration of manufacturing capabilities, initially to

  3. 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.

  4. Human pluripotent stem cells: an emerging model in developmental biology.

    PubMed

    Zhu, Zengrong; Huangfu, Danwei

    2013-02-01

    Developmental biology has long benefited from studies of classic model organisms. Recently, human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, have emerged as a new model system that offers unique advantages for developmental studies. Here, we discuss how studies of hPSCs can complement classic approaches using model organisms, and how hPSCs can be used to recapitulate aspects of human embryonic development 'in a dish'. We also summarize some of the recently developed genetic tools that greatly facilitate the interrogation of gene function during hPSC differentiation. With the development of high-throughput screening technologies, hPSCs have the potential to revolutionize gene discovery in mammalian development.

  5. The pathology of comparative animal models of human haemochromatosis.

    PubMed

    Klopfleisch, R; Olias, P

    2012-11-01

    Haemochromatosis is one of the most common human hereditary diseases. It is defined as a pathological condition with normal iron-driven erythropoiesis, but toxic accumulation of iron in vital organs, which is caused by mutations in any gene that encodes a protein involved in limiting the entry of iron into the blood. Iron storage diseases have also been described in several mammalian and avian species and these have been proposed as comparative animal models for human haemochromatosis. Genetically engineered mouse strains with mutations in iron metabolism genes model several aspects of human haemochromatosis and study of these animals has facilitated understanding of the disease. Spontaneously arising iron storage diseases in non-murine species also overlap in some clinicopathological aspects with human haemochromatosis. However, the lack of conclusive information on the molecular biology of theses species-specific diseases and the common impact of dietary iron concentration on disease progression in most species limit their usefulness as comparative models.

  6. Immunology studies in non-human primate models of tuberculosis.

    PubMed

    Flynn, JoAnne L; Gideon, Hannah P; Mattila, Joshua T; Lin, Philana Ling

    2015-03-01

    Non-human primates, primarily macaques, have been used to study tuberculosis for decades. However, in the last 15 years, this model has been refined substantially to allow careful investigations of the immune response and host-pathogen interactions in Mycobacterium tuberculosis infection. Low-dose challenge with fully virulent strains in cynomolgus macaques result in the full clinical spectrum seen in humans, including latent and active infection. Reagents from humans are usually cross-reactive with macaques, further facilitating the use of this model system to study tuberculosis. Finally, macaques develop the spectrum of granuloma types seen in humans, providing a unique opportunity to investigate bacterial and host factors at the local (lung and lymph node) level. Here, we review the past decade of immunology and pathology studies in macaque models of tuberculosis.

  7. 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.

  8. 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.

  9. 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.

  10. The utilization of humanized mouse models for the study of human retroviral infections

    PubMed Central

    Van Duyne, Rachel; Pedati, Caitlin; Guendel, Irene; Carpio, Lawrence; Kehn-Hall, Kylene; Saifuddin, Mohammed; Kashanchi, Fatah

    2009-01-01

    The development of novel techniques and systems to study human infectious diseases in both an in vitro and in vivo settings is always in high demand. Ideally, small animal models are the most efficient method of studying human afflictions. This is especially evident in the study of the human retroviruses, HIV-1 and HTLV-1, in that current simian animal models, though robust, are often expensive and difficult to maintain. Over the past two decades, the construction of humanized animal models through the transplantation and engraftment of human tissues or progenitor cells into immunocompromised mouse strains has allowed for the development of a reconstituted human tissue scaffold in a small animal system. The utilization of small animal models for retroviral studies required expansion of the early CB-17 scid/scid mouse resulting in animals demonstrating improved engraftment efficiency and infectivity. The implantation of uneducated human immune cells and associated tissue provided the basis for the SCID-hu Thy/Liv and hu-PBL-SCID models. Engraftment efficiency of these tissues was further improved through the integration of the non-obese diabetic (NOD) mutation leading to the creation of NODSCID, NOD/Shi-scid IL2rγ-/-, and NOD/SCID β2-microglobulinnull animals. Further efforts at minimizing the response of the innate murine immune system produced the Rag2-/-γc-/- model which marked an important advancement in the use of human CD34+ hematopoietic stem cells. Together, these animal models have revolutionized the investigation of retroviral infections in vivo. PMID:19674458

  11. Non-rotational aspherical models of the human optical system

    NASA Astrophysics Data System (ADS)

    Giovanzana, S.; Kasprzak, H. T.; Pałucki, B.; Ţălu, Ş.

    2013-12-01

    The aim of this work was to define three-dimensional (3D) non-rotational aspherical parametric models for the human cornea and lens using computational geometry and CAD representations. The hyperbolic cosine based function is used for the cornea and a parametric model is used for lens modeling. Data analysis and visualization of 3D non-rotational models were made using the Rhinoceros CAD software and MATLAB software was used for numeric computation. We combined, implemented, and evaluated these models with a 3D ray-tracing in order to fully analyze the human eye model. It was found that 3D non-rotational aspherical models for the human eye could be more accurately modeled and rendered for analysis with finite element method. The objective of this study is to present and analyze mathematical models of the cornea and lens and to highlight the potential of optical applications of the eye models containing astigmatic surfaces, which are more close to the real eye than spherosymmetric eye models.

  12. Humans in Biogeophysical Models: Colonial Period Human-Environment Interactions in the Northeastern United States

    NASA Astrophysics Data System (ADS)

    Parolari, A.; Greco, F.; Green, M.; Lally, M.; Hermans, C.

    2008-12-01

    Earth system models increasingly require representation of human activities and the important role they play in the environment. At the most fundamental level, human decisions are driven by the need to acquire basic resources - nutrients, energy, water, and space - each derived from the biogeophysical setting. Modern theories in Ecological Economics place these basic resources at the base of a consumption hierarchy (from subsistence to luxury resources) on which societies and economies are built. Human decisions at all levels of this hierarchy are driven by dynamic environmental, social, and economic factors. Therefore, models merging socio-economic and biogeophysical dynamics are required to predict the evolving relationship between humans and the hydrologic cycle. To provide an example, our study focuses on changes to the hydrologic cycle during the United States colonial period (1600 to 1800). Both direct, intentional, human water use (e.g. water supply, irrigation, or hydropower) and indirect, unintentional effects resulting from the use of other resources (e.g. deforestation or beaver trapping) are considered. We argue that water was not the limiting resource to either the Native or Colonist population growth. However, food and tobacco production and harvesting of beaver pelts led to indirect interventions and consequent changes in the hydrologic cycle. The analysis presented here suggests the importance of incorporating human decision- making dynamics with existing geophysical models to fully understand trajectories of human-environment interactions. Predictive tools of this type are critical to characterizing the long-term signature of humans on the landscape and hydrologic cycle.

  13. 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.

  14. Modeling Human Behavior at a Large Scale

    DTIC Science & Technology

    2012-01-01

    features (day of week and holiday), our models can handle arbitrary number of additional features, such as season , predicted weather, social and... allergies , that people discuss on Twitter. In a follow-up work (Paul and Dredze, 2011b) begin to consider the geographical patterns in the prevalence...preventative care, focusing specifically on suicide. Twitter has also been used to monitor the seasonal variation in affect around the globe (Golder and Macy

  15. Modelling Human Performance in Maritime Interdiction Operations

    DTIC Science & Technology

    2010-10-01

    high-tempo operations generate heat and therefore clothing needs to reflect the thermoregulatory demands . Currently operators often under-dress for the...influencing the insertion and on-target phases need to be quantified. The initial strategy of evaluation should include, a formal Task Analysis , to assess...initially via formal Task Analysis , so as to assess the potential degradation to performance and operational effectiveness. The ability to model these

  16. 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.

  17. Inverse modeling of human contrast response.

    PubMed

    Katkov, Mikhail; Tsodyks, Misha; Sagi, Dov

    2007-10-01

    Mathematical singularities found in the Signal Detection Theory (SDT) based analysis of the 2-Alternative-Forced-Choice (2AFC) method [Katkov, M., Tsodyks, M., & Sagi, D. (2006a). Analysis of two-alternative force-choice Signal Detection Theory model. Journal of Mathematical Psychology, 50, 411-420; Katkov, M., Tsodyks, M., & Sagi, D. (2006b). Singularities in the inverse modeling of 2AFC contrast discrimination data. Vision Research, 46, 256-266; Katkov, M., Tsodyks, M., & Sagi, D. (2007). Singularities explained: Response to Klein. Vision Research, doi:10.1016/j.visres.2006.10.030] imply that contrast discrimination data obtained with the 2AFC method cannot always be used to reliably estimate the parameters of the underlying model (internal response and noise functions) with a reasonable number of trials. Here we bypass this problem with the Identification Task (IT) where observers identify one of N contrasts. We have found that identification data varies significantly between experimental sessions. Stable estimates using individual session data showed Contrast Response Functions (CRF) with high gain in the low contrast regime and low gain in the high contrast regime. Noise Amplitudes (NA) followed a decreasing function of contrast at low contrast levels, and were practically constant above some contrast level. The transition between these two regimes corresponded approximately to the position of the dipper in the Threshold versus Contrast (TvC) curves that were computed using the estimated parameters and independently measured using 2AFC.

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

    PubMed

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

    2012-05-01

    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.

  19. A Critical Analysis of the Model of Human Occupation.

    ERIC Educational Resources Information Center

    Haglund, Lena; Kjellberg, Anette

    1999-01-01

    Examination of the applicability of the Model of Human Occupation in Swedish occupational therapy concludes that the environment is a central factor in understanding occupational behavior, but the model does not accurately or adequately depict the relationship between individuals and the environment. Volition is also an important factor in…

  20. 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…

  1. 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…

  2. 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 ...

  3. Three Models of Education: Rights, Capabilities and Human Capital

    ERIC Educational Resources Information Center

    Robeyns, Ingrid

    2006-01-01

    This article analyses three normative accounts that can underlie educational policies, with special attention to gender issues. These three models of education are human capital theory, rights discourses and the capability approach. I first outline five different roles that education can play. Then I analyse these three models of educational…

  4. 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…

  5. Combined hand gesture--speech model for human action recognition.

    PubMed

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

    2013-12-12

    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.

  6. 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.

  7. Integrating modelling and smart sensors for environmental and human health.

    PubMed

    Reis, Stefan; Seto, Edmund; Northcross, Amanda; Quinn, Nigel W T; Convertino, Matteo; Jones, Rod L; Maier, Holger R; Schlink, Uwe; Steinle, Susanne; Vieno, Massimo; Wimberly, Michael C

    2015-12-01

    Sensors are becoming ubiquitous in everyday life, generating data at an unprecedented rate and scale. However, models that assess impacts of human activities on environmental and human health, have typically been developed in contexts where data scarcity is the norm. Models are essential tools to understand processes, identify relationships, associations and causality, formalize stakeholder mental models, and to quantify the effects of prevention and interventions. They can help to explain data, as well as inform the deployment and location of sensors by identifying hotspots and areas of interest where data collection may achieve the best results. We identify a paradigm shift in how the integration of models and sensors can contribute to harnessing 'Big Data' and, more importantly, make the vital step from 'Big Data' to 'Big Information'. In this paper, we illustrate current developments and identify key research needs using human and environmental health challenges as an example.

  8. Integrating modelling and smart sensors for environmental and human health

    PubMed Central

    Reis, Stefan; Seto, Edmund; Northcross, Amanda; Quinn, Nigel W.T.; Convertino, Matteo; Jones, Rod L.; Maier, Holger R.; Schlink, Uwe; Steinle, Susanne; Vieno, Massimo; Wimberly, Michael C.

    2015-01-01

    Sensors are becoming ubiquitous in everyday life, generating data at an unprecedented rate and scale. However, models that assess impacts of human activities on environmental and human health, have typically been developed in contexts where data scarcity is the norm. Models are essential tools to understand processes, identify relationships, associations and causality, formalize stakeholder mental models, and to quantify the effects of prevention and interventions. They can help to explain data, as well as inform the deployment and location of sensors by identifying hotspots and areas of interest where data collection may achieve the best results. We identify a paradigm shift in how the integration of models and sensors can contribute to harnessing ‘Big Data’ and, more importantly, make the vital step from ‘Big Data’ to ‘Big Information’. In this paper, we illustrate current developments and identify key research needs using human and environmental health challenges as an example. PMID:26644778

  9. Modeling anesthetic developmental neurotoxicity using human stem cells

    PubMed Central

    Bai, Xiaowen; Twaroski, Danielle; Bosnjak, Zeljko J.

    2013-01-01

    Mounting pre-clinical evidence in rodents and non-human primates has demonstrated that prolonged exposure of developing animals to general anesthetics can induce widespread neuronal cell death followed by long-term memory and learning disabilities. In vitro experimental evidence from cultured neonatal animal neurons confirmed the in vivo findings. However, there is no direct clinical evidence of the detrimental effects of anesthetics in human fetuses, infants, or children. Development of an in vitro neurogenesis system using human stem cells has opened up avenues of research for advancing our understanding of human brain development and the issues relevant to anesthetic-induced developmental toxicity in human neuronal lineages. Recent studies from our group, as well as other groups, showed that isoflurane influences human neural stem cell proliferation and neurogenesis, while ketamine induces neuroapoptosis. Application of this high throughput in vitro stem cell neurogenesis approach is a major stride toward assuring the safety of anesthetic agents in young children. This in vitro human model allows us to (1) screen the toxic effects of various anesthetics under controlled conditions during intense neuronal growth, (2) find the trigger for the anesthetic-induced catastrophic chain of toxic events, and (3) develop prevention strategies to avoid this toxic effect. In this paper, we reviewed the current findings in anesthetic-induced neurotoxicity studies, specifically focusing on the in vitro human stem cell model. PMID:23859832

  10. Discrete time modelization of human pilot behavior

    NASA Technical Reports Server (NTRS)

    Cavalli, D.; Soulatges, D.

    1975-01-01

    This modelization starts from the following hypotheses: pilot's behavior is a time discrete process, he can perform only one task at a time and his operating mode depends on the considered flight subphase. Pilot's behavior was observed using an electro oculometer and a simulator cockpit. A FORTRAN program has been elaborated using two strategies. The first one is a Markovian process in which the successive instrument readings are governed by a matrix of conditional probabilities. In the second one, strategy is an heuristic process and the concepts of mental load and performance are described. The results of the two aspects have been compared with simulation data.

  11. 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.

  12. 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...

  13. Is always high-resolution human model in bioelectromagnetic modeling needed?

    NASA Astrophysics Data System (ADS)

    Dlugosz, Tomasz

    2011-09-01

    The paper presents short profile of analytical and numerical methods used in bioelectromagnetic modeling. Some comparison of different models of human being was made. Author analyzed it in the following points of view: time of calculations and technical specifications

  14. 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.

  15. 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.

  16. Neuropsychiatric SLE: from animal model to human.

    PubMed

    Pikman, R; Kivity, S; Levy, Y; Arango, M-T; Chapman, J; Yonath, H; Shoenfeld, Y; Gofrit, S G

    2017-04-01

    Animal models are a key element in disease research and treatment. In the field of neuropsychiatric lupus research, inbred, transgenic and disease-induced mice provide an opportunity to study the pathogenic routes of this multifactorial illness. In addition to achieving a better understanding of the immune mechanisms underlying the disease onset, supplementary metabolic and endocrine influences have been discovered and investigated. The ever-expanding knowledge about the pathologic events that occur at disease inception enables us to explore new drugs and therapeutic approaches further and to test them using the same animal models. Discovery of the molecular targets that constitute the pathogenic basis of the disease along with scientific advancements allow us to target these molecules with monoclonal antibodies and other specific approaches directly. This novel therapy, termed "targeted biological medication" is a promising endeavor towards producing drugs that are more effective and less toxic. Further work to discover additional molecular targets in lupus' pathogenic mechanism and to produce drugs that neutralize their activity is needed to provide patients with safe and efficient methods of controlling and treating the disease.

  17. 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.

  18. Non-Human Primate Models for AIDS Vaccine Research

    PubMed Central

    Hu, Shiu-Lok

    2006-01-01

    Since the discovery of simian immunodeficiency viruses (SIV) causing AIDS-like diseases in Asian macaques, non-human primates (NHP) have played an important role in AIDS vaccine research. A multitude of vaccines and immunization approaches have been evaluated, including live attenuated viruses, DNA vaccines, viral and bacterial vectors, subunit proteins, and combinations thereof. Depending on the particular vaccine and model used, varying degrees of protection have been achieved, including prevention of infection, reduction of viral load, and amelioration of disease. In a few instances, potential safety concerns and vaccine-enhanced pathogenicity have also been noted. In the past decade, sophisticated methodologies have been developed to define the mechanisms of protective immunity. However, a clear road map for HIV vaccine development has yet to emerge. This is in part because of the intrinsic nature of the surrogate model and in part because of the improbability of any single model to fully capture the complex interactions of natural HIV infection in humans. The lack of standardization, the limited models available, and the incomplete understanding of the immunobiology of NHP contribute to the difficulty to extrapolate findings from such models to HIV vaccine development. Until efficacy data become available from studies of parallel vaccine concepts in humans and macaques, the predictive value of any NHP model remains unknown. Towards this end, greater appreciation of the utility and limitations of the NHP model and further developments to better mimic HIV infection in humans will likely help inform future AIDS vaccine efforts. PMID:15975024

  19. 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

  20. Modeling Human Glaucoma: Lessons from the in vitro Models.

    PubMed

    Aires, Inês Dinis; Ambrósio, António Francisco; Santiago, Ana Raquel

    2017-01-01

    Glaucoma, a leading cause of blindness worldwide, is a degenerative disease characterized by retinal ganglion cell (RGC) loss and optic nerve atrophy. Elevated intraocular pressure (IOP) is a main risk factor for onset and progression of the disease. Since increased IOP is the only modifiable risk factor, relevant models for glaucoma would comprise RGC and optic nerve damage triggered by ocular hypertension. Animal models of glaucoma have greatly contributed to the understanding of the molecular mechanisms of this pathology, and they have also facilitated the development of new pharmacological interventions. Although animal models of glaucoma have provided valuable information about the disease, there is still no ideal model for studying glaucoma due to its complexity. There is a recognized demand for in vitro models that can replace or reduce the need for animal experiments. Several in vitro models have emerged as a great opportunity in the field of glaucoma research, helping to clarify the mechanisms involved in disease progression. Several types of equipment have been developed to expose cells and tissue cultures to elevated pressures. Herein, we discuss the methodology used to increase pressure, the main findings, and the relevance of in vitro models for the study of the pathophysiology of glaucoma.

  1. 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.

  2. Genetically Engineered Humanized Mouse Models for Preclinical Antibody Studies

    PubMed Central

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

    2015-01-01

    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. PMID:24150980

  3. 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.

  4. 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

  5. Knock-in human FGFR3 achondroplasia mutation as a mouse model for human skeletal dysplasia.

    PubMed

    Lee, Yi-Ching; Song, I-Wen; Pai, Ya-Ju; Chen, Sheng-De; Chen, Yuan-Tsong

    2017-02-23

    Achondroplasia (ACH), the most common genetic dwarfism in human, is caused by a gain-of function mutation in fibroblast growth factor receptor 3 (FGFR3). Currently, there is no effective treatment for ACH. The development of an appropriate human-relevant model is important for testing potential therapeutic interventions before human clinical trials. Here, we have generated an ACH mouse model in which the endogenous mouse Fgfr3 gene was replaced with human FGFR3(G380R) (FGFR3(ACH)) cDNA, the most common mutation in human ACH. Heterozygous (FGFR3(ACH/+)) and homozygous (FGFR3(ACH/ACH)) mice expressing human FGFR3(G380R) recapitulate the phenotypes observed in ACH patients, including growth retardation, disproportionate shortening of the limbs, round head, mid-face hypoplasia at birth, and kyphosis progression during postnatal development. We also observed premature fusion of the cranial sutures and low bone density in newborn FGFR3(G380R) mice. The severity of the disease phenotypes corresponds to the copy number of activated FGFR3(G380R), and the phenotypes become more pronounced during postnatal skeletal development. This mouse model offers a tool for assessing potential therapeutic approaches for skeletal dysplasias related to over-activation of human FGFR3, and for further studies of the underlying molecular mechanisms.

  6. Knock-in human FGFR3 achondroplasia mutation as a mouse model for human skeletal dysplasia

    PubMed Central

    Lee, Yi-Ching; Song, I-Wen; Pai, Ya-Ju; Chen, Sheng-De; Chen, Yuan-Tsong

    2017-01-01

    Achondroplasia (ACH), the most common genetic dwarfism in human, is caused by a gain-of function mutation in fibroblast growth factor receptor 3 (FGFR3). Currently, there is no effective treatment for ACH. The development of an appropriate human-relevant model is important for testing potential therapeutic interventions before human clinical trials. Here, we have generated an ACH mouse model in which the endogenous mouse Fgfr3 gene was replaced with human FGFR3G380R (FGFR3ACH) cDNA, the most common mutation in human ACH. Heterozygous (FGFR3ACH/+) and homozygous (FGFR3ACH/ACH) mice expressing human FGFR3G380R recapitulate the phenotypes observed in ACH patients, including growth retardation, disproportionate shortening of the limbs, round head, mid-face hypoplasia at birth, and kyphosis progression during postnatal development. We also observed premature fusion of the cranial sutures and low bone density in newborn FGFR3G380R mice. The severity of the disease phenotypes corresponds to the copy number of activated FGFR3G380R, and the phenotypes become more pronounced during postnatal skeletal development. This mouse model offers a tool for assessing potential therapeutic approaches for skeletal dysplasias related to over-activation of human FGFR3, and for further studies of the underlying molecular mechanisms. PMID:28230213

  7. Avian Models for Human Cognitive Neuroscience: A Proposal.

    PubMed

    Clayton, Nicola S; Emery, Nathan J

    2015-06-17

    Research on avian cognitive neuroscience over the past two decades has revealed the avian brain to be a better model for understanding human cognition than previously thought, despite differences in the neuroarchitecture of avian and mammalian brains. The brain, behavior, and cognition of songbirds have provided an excellent model of human cognition in one domain, namely learning human language and the production of speech. There are other important behavioral candidates of avian cognition, however, notably the capacity of corvids to remember the past and plan for the future, as well as their ability to think about another's perspective, and physical reasoning. We review this work and assess the evidence that the corvid brain can support such a cognitive architecture. We propose potential applications of these behavioral paradigms for cognitive neuroscience, including recent work on single-cell recordings and neuroimaging in corvids. Finally, we discuss their impact on understanding human developmental cognition.

  8. Tracking Human Pose Using Max-Margin Markov Models.

    PubMed

    Zhao, Lin; Gao, Xinbo; Tao, Dacheng; Li, Xuelong

    2015-12-01

    We present a new method for tracking human pose by employing max-margin Markov models. Representing a human body by part-based models, such as pictorial structure, the problem of pose tracking can be modeled by a discrete Markov random field. Considering max-margin Markov networks provide an efficient way to deal with both structured data and strong generalization guarantees, it is thus natural to learn the model parameters using the max-margin technique. Since tracking human pose needs to couple limbs in adjacent frames, the model will introduce loops and will be intractable for learning and inference. Previous work has resorted to pose estimation methods, which discard temporal information by parsing frames individually. Alternatively, approximate inference strategies have been used, which can overfit to statistics of a particular data set. Thus, the performance and generalization of these methods are limited. In this paper, we approximate the full model by introducing an ensemble of two tree-structured sub-models, Markov networks for spatial parsing and Markov chains for temporal parsing. Both models can be trained jointly using the max-margin technique, and an iterative parsing process is proposed to achieve the ensemble inference. We apply our model on three challengeable data sets, which contains highly varied and articulated poses. Comprehensive experimental results demonstrate the superior performance of our method over the state-of-the-art approaches.

  9. 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...

  10. 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

  11. 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.

  12. [Living the birth process in a humanized assistance model].

    PubMed

    da Silva, Larissa Mandarano; Barbieri, Márcia; Fustinoni, Suzete Maria

    2011-01-01

    That was a qualitative study with phenomenological approach that aimed at understanding women's post-partum experiences in a humanized assistance. Data were collected in a hospital from São Paulo, SP, Brazil. Eight women in post-partum period were interviewed. From data analysis two themes were extracted: Bearing the labor and Having the opportunity rescuing autonomy, being disclosed the phenomenon: "Living the ambiguity on the birth process in a humanized assistance model". The reports show feelings like pain, fear and anxiety, however, it allowed a participation and rescuing autonomy. Although the study have been realized in a humanized assistance, the women's experiences reveals that they are far from an effective humanization, according to its principles. This study can be used to guide educative actions target to humanization and to generate managerial changes.

  13. Human granuloma in vitro model, for TB dormancy and resuscitation.

    PubMed

    Kapoor, Nidhi; Pawar, Santosh; Sirakova, Tatiana D; Deb, Chirajyoti; Warren, William L; Kolattukudy, Pappachan E

    2013-01-01

    Tuberculosis (TB) is responsible for death of nearly two million people in the world annually. Upon infection, Mycobacterium tuberculosis (Mtb) causes formation of granuloma where the pathogen goes into dormant state and can live for decades before resuscitation to develop active disease when the immune system of the host is weakened and/or suppressed. In an attempt to better understand host-pathogen interactions, several groups have been developing in vitro models of human tuberculosis granuloma. However, to date, an in vitro granuloma model in which Mtb goes into dormancy and can subsequently resuscitate under conditions that mimic weakening of the immune system has not been reported. We describe the development of a biomimetic in vitro model of human tuberculosis granuloma using human primary leukocytes, in which the Mtb exhibited characteristics of dormant mycobacteria as demonstrated by (1) loss of acid-fastness, (2) accumulation of lipid bodies (3) development of rifampicin-tolerance and (4) gene expression changes. Further, when these micro granulomas were treated with immunosuppressant anti-tumor necrosis factor-alpha monoclonal antibodies (anti-TNFα mAbs), resuscitation of Mtb was observed as has been found in humans. In this human in vitro granuloma model triacylglycerol synthase 1deletion mutant (Δtgs1) with impaired ability to accumulate triacylglycerides (TG), but not the complemented mutant, could not go into dormancy. Deletion mutant of lipY, with compromised ability to mobilize the stored TG, but not the complemented mutant, was unable to come out of dormancy upon treatment with anti-TNFα mAbs. In conclusion, we have developed an in vitro human tuberculosis granuloma model that largely exhibits functional features of dormancy and resuscitation observed in human tuberculosis.

  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.

  15. Zebrafish heart as a model for human cardiac electrophysiology

    PubMed Central

    Vornanen, Matti; Hassinen, Minna

    2016-01-01

    ABSTRACT The zebrafish (Danio rerio) has become a popular model for human cardiac diseases and pharmacology including cardiac arrhythmias and its electrophysiological basis. Notably, the phenotype of zebrafish cardiac action potential is similar to the human cardiac action potential in that both have a long plateau phase. Also the major inward and outward current systems are qualitatively similar in zebrafish and human hearts. However, there are also significant differences in ionic current composition between human and zebrafish hearts, and the molecular basis and pharmacological properties of human and zebrafish cardiac ionic currents differ in several ways. Cardiac ionic currents may be produced by non-orthologous genes in zebrafish and humans, and paralogous gene products of some ion channels are expressed in the zebrafish heart. More research on molecular basis of cardiac ion channels, and regulation and drug sensitivity of the cardiac ionic currents are needed to enable rational use of the zebrafish heart as an electrophysiological model for the human heart. PMID:26671745

  16. Cracking the Egg: Potential of the Developing Chicken as a Model System for Nonclinical Safety Studies of Pharmaceuticals.

    PubMed

    Bjørnstad, Sigrid; Austdal, Lars Peter Engeset; Roald, Borghild; Glover, Joel Clinton; Paulsen, Ragnhild Elisabeth

    2015-12-01

    The advance of perinatal medicine has improved the survival of extremely premature babies, thereby creating a new and heterogeneous patient group with limited information on appropriate treatment regimens. The developing fetus and neonate have traditionally been ignored populations with regard to safety studies of drugs, making medication during pregnancy and in newborns a significant safety concern. Recent initiatives of the Food and Drug Administration and European Medicines Agency have been passed with the objective of expanding the safe pharmacological treatment options in these patients. There is a consensus that neonates should be included in clinical trials. Prior to these trials, drug leads are tested in toxicity and pharmacology studies, as governed by several guidelines summarized in the multidisciplinary International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use M3 (R2). Pharmacology studies must be performed in the major organ systems: cardiovascular, respiratory, and central nervous system. The chicken embryo and fetus have features that make the chicken a convenient animal model for nonclinical safety studies in which effects on all of these organ systems can be tested. The developing chicken is inexpensive, accessible, and nutritionally self-sufficient with a short incubation time and is ideal for drug-screening purposes. Other high-throughput models have been implemented. However, many of these have limitations, including difficulty in mimicking natural tissue architecture and function (human stem cells) and obvious differences from mammals regarding the respiratory organ system and certain aspects of central nervous system development (Caenorhabditis elegans, zebrafish).This minireview outlines the potential and limitations of the developing chicken as an additional model for the early exploratory phase of development of new pharmaceuticals.

  17. 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.

  18. Progress in coupling models of human and coastal landscape change

    NASA Astrophysics Data System (ADS)

    Brad Murray, A.; Gopalakrishnan, Sathya; McNamara, Dylan E.; Smith, Martin D.

    2013-04-01

    Humans are increasingly altering the Earth's surface, and affecting processes that shape and reshape landscapes. In many cases, humans are reacting to landscape-change processes that represent natural hazards. Thus, the landscape is reacting to humans who are reacting to the landscape. When the timescales for landscape change are comparable to those of human dynamics, human and 'natural' components of developed environments are dynamically coupled—necessitating coupling models of human and physical/biological processes to study either environmental change or human responses. Here we focus on a case study coupling models of coastal economics and physical coastline change. In this modeling, coastline change results from patterns of wave-driven sediment transport and sea-level rise, and shoreline stabilization decisions are based on the benefits of wide beaches (capitalized into property values) balanced against the costs of stabilization. This interdisciplinary modeling highlights points that may apply to other coupled human/natural systems. First, climate change, by accelerating the rates of landscape change, tends to strengthen the coupling with human dynamics. In our case study, both increasing sea-level-rise rates and changing storm patterns tend to increase shoreline change rates, which can induce more vigorous shoreline stabilization efforts. However, property values can fall dramatically as erosion rates and stabilization costs rise, which can also lead to the abandonment of expensive stabilization methods as shoreline change rates increase. Second, socio-economic change can also strengthen the human/landscape coupling. Changing costs of shoreline stabilization can alter stabilization decisions, which in turn alters patterns of coastline change. The coupled modeling illuminates the long-range effects of localized shoreline stabilization efforts; communities arrayed along a coastline are unwittingly affecting each other's erosion rates, and therefore each

  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. 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

  1. 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

  2. Pre-clinical Orthotopic Murine Model of Human Prostate Cancer.

    PubMed

    Shahryari, Varahram; Nip, Hannah; Saini, Sharanjot; Dar, Altaf A; Yamamura, Soichiro; Mitsui, Yozo; Colden, Melissa; Bucay, Nathan; Tabatabai, Laura Z; Greene, Kirsten; Deng, Guoren; Tanaka, Yuichiro; Dahiya, Rajvir; Majid, Shahana

    2016-08-29

    To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information about this disease. The human orthotopic prostate cancer xenograft mouse model provides a useful alternative approach for understanding the specific interactions between genetically and molecularly altered tumor cells, their organ microenvironment, and for evaluation of efficacy of therapeutic regimens. This is a well characterized model designed to study the molecular events of primary tumor development and it recapitulates the early events in the metastatic cascade prior to embolism and entry of tumor cells into the circulation. Thus it allows elucidation of molecular mechanisms underlying the initial phase of metastatic disease. In addition, this model can annotate drug targets of clinical relevance and is a valuable tool to study prostate cancer progression. In this manuscript we describe a detailed procedure to establish a human orthotopic prostate cancer xenograft mouse model.

  3. An improved human display model for occupant crash simulation programs

    NASA Technical Reports Server (NTRS)

    Willmert, K. D.; Potter, T. E.

    1975-01-01

    An improved three-dimensional display model of a human being which can be used to display the results of three-dimensional simulation programs that predict the positions of an occupant during impact of a vehicle was presented. The model allows the user to view the occupant from any orientation in any position during the crash. The display model assumes the usual break up of the body into rigid segments which is normal for occupant crash simulation programs, but the shape of the segments in the display model are not necessarily the same as those used in the crash simulation. The display model is proportioned so as to produce a realistic drawing of the human body in any position. Joints connecting the segments are also drawn to improve realism.

  4. 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.

  5. 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.

  6. Modelling of human transplacental transport as performed in Copenhagen, Denmark.

    PubMed

    Mathiesen, Line; Mørck, Thit Aarøe; Zuri, Giuseppina; Andersen, Maria Helena; Pehrson, Caroline; Frederiksen, Marie; Mose, Tina; Rytting, Erik; Poulsen, Marie S; Nielsen, Jeanette K S; Knudsen, Lisbeth E

    2014-07-01

    Placenta perfusion models are very effective when studying the placental mechanisms in order to extrapolate to real-life situations. The models are most often used to investigate the transport of substances between mother and foetus, including the potential metabolism of these. We have studied the relationships between maternal and foetal exposures to various compounds including pollutants such as polychlorinated biphenyls, polybrominated flame retardants, nanoparticles as well as recombinant human antibodies. The compounds have been studied in the human placenta perfusion model and to some extent in vitro with an established human monolayer trophoblast cell culture model. Results from our studies distinguish placental transport of substances by physicochemical properties, adsorption to placental tissue, binding to transport and receptor proteins and metabolism. We have collected data from different classes of chemicals and nanoparticles for comparisons across chemical structures as well as different test systems. Our test systems are based on human material to bypass the extrapolation from animal data. By combining data from our two test systems, we are able to rank and compare the transport of different classes of substances according to their transport ability. Ultimately, human data including measurements in cord blood contribute to the study of placental transport.

  7. Computational modeling of the human atrial anatomy and electrophysiology.

    PubMed

    Dössel, Olaf; Krueger, Martin W; Weber, Frank M; Wilhelms, Mathias; Seemann, Gunnar

    2012-08-01

    This review article gives a comprehensive survey of the progress made in computational modeling of the human atria during the last 10 years. Modeling the anatomy has emerged from simple "peanut"-like structures to very detailed models including atrial wall and fiber direction. Electrophysiological models started with just two cellular models in 1998. Today, five models exist considering e.g. details of intracellular compartments and atrial heterogeneity. On the pathological side, modeling atrial remodeling and fibrotic tissue are the other important aspects. The bridge to data that are measured in the catheter laboratory and on the body surface (ECG) is under construction. Every measurement can be used either for model personalization or for validation. Potential clinical applications are briefly outlined and future research perspectives are suggested.

  8. 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.

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

    PubMed Central

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

    2012-01-01

    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

  10. 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.

  11. 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

  12. 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.

  13. Extracting Feature Points of the Human Body Using the Model of a 3D Human Body

    NASA Astrophysics Data System (ADS)

    Shin, Jeongeun; Ozawa, Shinji

    The purpose of this research is to recognize 3D shape features of a human body automatically using a 3D laser-scanning machine. In order to recognize the 3D shape features, we selected the 23 feature points of a body and modeled its 3D features. The set of 23 feature points consists of the motion axis of a joint, the main point for the bone structure of a human body. For extracting feature points of object model, we made 2.5D templates neighbor for each feature points were extracted according to the feature points of the standard model of human body. And the feature points were extracted by the template matching. The extracted feature points can be applied as body measurement, the 3D virtual fitting system for apparel etc.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. [Development of human embryonic stem cell model for toxicity evaluation].

    PubMed

    Yu, Guang-yan; Cao, Tong; Ouyang, Hong-wei; Peng, Shuang-qing; Deng, Xu-liang; Li, Sheng-lin; Liu, He; Zou, Xiao-hui; Fu, Xin; Peng, Hui; Wang, Xiao-ying; Zhan, Yuan

    2013-02-18

    The current international standard for toxicity screening of biomedical devices and materials recommend the use of immortalized cell lines because of their homogeneous morphologies and infinite proliferation which provide good reproducibility for in vitro cytotoxicity screening. However, most of the widely used immortalized cell lines are derived from animals and may not be representative of normal human cell behavior in vivo, in particular in terms of the cytotoxic and genotoxic response. Therefore, It is vital to develop a model for toxicity evaluation. In our studies, two Chinese human embryonic stem cell (hESC) lines as toxicity model were established. hESC derived tissue/organ cell model for tissue/organ specific toxicity evaluation were developed. The efficiency and accuracy of using hESC model for cytoxicity, embryotoxicity and genotoxicity evaluation were confirmed. The results indicated that hESCs might be good tools for toxicity testing and biosafety evaluation in vitro.

  20. Mechanics, Mechanobiology, and Modeling of Human Abdominal Aorta and Aneurysms

    PubMed Central

    Humphrey, J.D.; Holzapfel, G.A.

    2011-01-01

    Biomechanical factors play fundamental roles in the natural history of abdominal aortic aneurysms (AAAs) and their responses to treatment. Advances during the past two decades have increased our understanding of the mechanics and biology of the human abdominal aorta and AAAs, yet there remains a pressing need for considerable new data and resulting patient-specific computational models that can better describe the current status of a lesion and better predict the evolution of lesion geometry, composition, and material properties and thereby improve interventional planning. In this paper, we briefly review data on the structure and function of the human abdominal aorta and aneurysmal wall, past models of the mechanics, and recent growth and remodeling models. We conclude by identifying open problems that we hope will motivate studies to improve our computational modeling and thus general understanding of AAAs. PMID:22189249

  1. 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

  2. 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

  3. An ideal-observer model of human sound localization.

    PubMed

    Reijniers, J; Vanderelst, D; Jin, C; Carlile, S; Peremans, H

    2014-04-01

    In recent years, a great deal of research within the field of sound localization has been aimed at finding the acoustic cues that human listeners use to localize sounds and understanding the mechanisms by which they process these cues. In this paper, we propose a complementary approach by constructing an ideal-observer model, by which we mean a model that performs optimal information processing within a Bayesian context. The model considers all available spatial information contained within the acoustic signals encoded by each ear. Parameters for the optimal Bayesian model are determined based on psychoacoustic discrimination experiments on interaural time difference and sound intensity. Without regard as to how the human auditory system actually processes information, we examine the best possible localization performance that could be achieved based only on analysis of the input information, given the constraints of the normal auditory system. We show that the model performance is generally in good agreement with the actual human localization performance, as assessed in a meta-analysis of many localization experiments (Best et al. in Principles and applications of spatial hearing, pp 14-23. World Scientific Publishing, Singapore, 2011). We believe this approach can shed new light on the optimality (or otherwise) of human sound localization, especially with regard to the level of uncertainty in the input information. Moreover, the proposed model allows one to study the relative importance of various (combinations of) acoustic cues for spatial localization and enables a prediction of which cues are most informative and therefore likely to be used by humans in various circumstances.

  4. Visual performance modeling in the human operator simulator

    NASA Technical Reports Server (NTRS)

    Strieb, M. I.

    1979-01-01

    A brief description of the history of the development of the human operator simulator (HOS) model is presented. Features of the HOS micromodels that impact on the obtainment of visual performance data are discussed along with preliminary details on a HOS pilot model designed to predict the results of visual performance workload data obtained through oculometer studies on pilots in real and simulated approaches and landings.

  5. 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.

  6. Validation of human physiologically based pharmacokinetic model for vinyl acetate against human nasal dosimetry data.

    PubMed

    Hinderliter, P M; Thrall, K D; Corley, R A; Bloemen, L 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 13C1,13C2 vinyl acetate via inhalation. A probe inserted into the nasopharyngeal region sampled both 13C1,13C2 vinyl acetate and the major metabolite 13C1,13C2 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.

  7. Preclinical humanized mouse model with ectopic ovarian tissues

    PubMed Central

    FU, SHILONG; WANG, JUE; SUN, WU; XU, YI; ZHOU, XIAOYU; CHENG, WENJUN

    2014-01-01

    The aim of the present study was to establish human ovarian stroma within the mouse subcutaneously, in order for the resulting stroma to serve as a useful preclinical tool to study the progression of human ovarian cancer in a humanized ovarian microenvironment. Normal human ovarian tissues were subcutaneously implanted into severe combined immunodeficient (SCID) mice and then the implants were identified by immunohistochemistry. The implants became vascularized and retained their original morphology for about 4 weeks following implantation. Immunohistochemical staining for cytokeratin-7 confirmed the ovarian origin of the epithelial cells. CD34 staining demonstrated human-derived vessels. Positive estrogen receptor and partially-positive progesterone receptor staining indicated the estrogen and progesterone dependence of the implants. Only vascular pericytes expressed α-smooth muscle actin, indicating the normal ovarian origin of the xenografts. Human ovarian tissue successfully survived in SCID mice and retained its original properties. This humanized mouse model may be used as preclinical tool to investigate ovarian cancer. PMID:25120592

  8. 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.

  9. 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.

  10. Perception--action coupling model for human locomotor pointing.

    PubMed

    de Rugy, A; Taga, G; Montagne, G; Buekers, M J; Laurent, M

    2002-08-01

    How do humans achieve the precise positioning of the feet during walking, for example, to reach the first step of a stairway? We addressed this question at the visuomotor integration level. Based on the optical specification of the required adaptation, a dynamical system model of the visuomotor control of human locomotor pointing was devised for the positioning of a foot on a visible target on the floor during walking. Visuomotor integration consists of directly linking optical information to a motor command that specifically modulates step length in accordance with the ongoing dynamics of locomotor pattern generation. The adaptation of locomotion emerges from a perception-action coupling type of control based on temporal information rather than on feedforward planning of movements. The proposed model reproduces experimental results obtained for human locomotor pointing.

  11. 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

  12. Mathematical modelling of carbohydrate degradation by human colonic microbiota.

    PubMed

    Muñoz-Tamayo, Rafael; Laroche, Béatrice; Walter, Eric; Doré, Joël; Leclerc, Marion

    2010-09-07

    The human colon is an anaerobic ecosystem that remains largely unexplored as a result of its limited accessibility and its complexity. Mathematical models can play a central role for a better insight into its dynamics. In this context, this paper presents the development of a mathematical model of carbohydrate degradation. Our aim was to provide an in silico approach to contribute to a better understanding of the fermentation patterns in such an ecosystem. Our mathematical model is knowledge-based, derived by writing down mass-balance equations. It incorporates physiology of the intestine, metabolic reactions and transport phenomena. The model was used to study various nutritional scenarios and to assess the role of the mucus on the system behavior. Model simulations provided an adequate qualitative representation of the human colon. Our model is complementary to experimental studies on human colonic fermentation, which, of course, is not meant to replace. It may be helpful to gain insight on questions that are still difficult to elucidate by experimentation and suggest future experiments.

  13. A biologically plausible model of human radial frequency perception.

    PubMed

    Poirier, Frédéric J A M; Wilson, Hugh R

    2006-07-01

    Several recent studies have used radial frequency patterns to investigate intermediate-level shape perception, a critical precursor to object recognition. Here, we developed the first neural model of RF perception based on known V4 properties that exhibits many of the characteristics of human RF perception. The model is composed of two main parts: (1) recovery of object position using large-scale non-Fourier V4-like concentric units that respond at the center of concentric contour segments across orientations, and (2) curvature detectors that encode local shape information. Each curvature mechanism combines multiplicatively the responses of three oriented filters, the positions and orientation preferences of which determine the curvature mechanism's tuning properties for position, orientation, and degree of curvature. When responding to RF patterns, peak responses occur at points of maximum curvature. Shape is represented as curvature responses as a function of orientation around the object center, and the cross-correlation of that function with a sine wave peaks when the frequency of the sine wave matches the number of peaks in the stimulus. Cross-correlation strength can be used to model human performance. Model and human performance are comparable for detection, identification, and lateral masking tasks. Moreover, the model also shows size invariance of detection performance due to scaling of the curvature mechanisms. The model is then used to make novel predictions.

  14. Modeling heart rate variability in healthy humans: a turbulence analogy.

    PubMed

    Lin, D C; Hughson, R L

    2001-02-19

    Many complex systems share similar statistical characteristics. In this Letter, a turbulence analogy is proposed for the long-term heart rate variability of healthy humans. Based on such an analogy, the equivalence of an inertial range is found and a cascade model, which captures the statistical properties of the heart rate data, is given.

  15. 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…

  16. 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)

  17. Nephrotoxic nephritis and glomerulonephritis: animal model versus human disease.

    PubMed

    Muhammad, S

    2014-01-01

    Glomerulonephritis (GN) encompasses a range of immune-mediated disorders that cause inflammation within the glomerulus of the kidney. The pathogenesis of GN is complex. Intricacy arises from factors such as autoimmunity, cancer and structural abnormalities within the kidney. Studies using animal models have highlighted crucial interaction between inflammatory cells and cells intrinsic to the kidney, both of which are fundamental to the pathogenesis of GN. This review aims to provide insight on a 'suitable' model for nephrotoxic nephritis and glomerulonephritis (NTN GN) and relate its experimental validity to humans. The BALB/c NTN murine model and Wistar Kyoto (WKY) rat have held experimental validity in the study of GN in humans. The chemokine receptor CXCR3 also mediates renal T-cell recruitment and subsequent tissue injury in NTN. It is noteworthy to consider CXCR3 blockade in Th1-mediated renal inflammation as future therapeutic options for patients with GN and subsets thereof. Currently used immunosuppressive therapies for GN are not always uniformly effective and are frequently associated with serious side-effects. Corticosteroids are effective in several types of GN owing to their ability to inhibit the pro-inflammatory effects of cytokines known to promote glomerular inflammation. Differences between experimental and human GN complicate translation of experimental therapies into practice. More research is required to translate animal model research into a better comprehension of human GN disease. However, the complexity of GN research makes findings a challenge to replicate.

  18. 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.

  19. 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.

  20. 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.

  1. A review on otolith models in human perception.

    PubMed

    Asadi, Houshyar; Mohamed, Shady; Lim, Chee Peng; Nahavandi, Saeid

    2016-08-01

    The vestibular system, which consists of semicircular canals and otolith, are the main sensors mammals use to perceive rotational and linear motions. Identifying the most suitable and consistent mathematical model of the vestibular system is important for research related to driving perception. An appropriate vestibular model is essential for implementation of the Motion Cueing Algorithm (MCA) for motion simulation purposes, because the quality of the MCA is directly dependent on the vestibular model used. In this review, the history and development process of otolith models are presented and analyzed. The otolith organs can detect linear acceleration and transmit information about sensed applied specific forces on the human body. The main purpose of this review is to determine the appropriate otolith models that agree with theoretical analyses and experimental results as well as provide reliable estimation for the vestibular system functions. Formulating and selecting the most appropriate mathematical model of the vestibular system is important to ensure successful human perception modelling and simulation when implementing the model into the MCA for motion analysis.

  2. 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.

  3. 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.

  4. Three-dimensional cell culture models for investigating human viruses.

    PubMed

    He, Bing; Chen, Guomin; Zeng, Yi

    2016-10-01

    Three-dimensional (3D) culture models are physiologically relevant, as they provide reproducible results, experimental flexibility and can be adapted for high-throughput experiments. Moreover, these models bridge the gap between traditional two-dimensional (2D) monolayer cultures and animal models. 3D culture systems have significantly advanced basic cell science and tissue engineering, especially in the fields of cell biology and physiology, stem cell research, regenerative medicine, cancer research, drug discovery, and gene and protein expression studies. In addition, 3D models can provide unique insight into bacteriology, virology, parasitology and host-pathogen interactions. This review summarizes and analyzes recent progress in human virological research with 3D cell culture models. We discuss viral growth, replication, proliferation, infection, virus-host interactions and antiviral drugs in 3D culture models.

  5. 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.

  6. 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.

  7. Genome editing of human pluripotent stem cells to generate human cellular disease models.

    PubMed

    Musunuru, Kiran

    2013-07-01

    Disease modeling with human pluripotent stem cells has come into the public spotlight with the awarding of the Nobel Prize in Physiology or Medicine for 2012 to Drs John Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent. This discovery has opened the door for the generation of pluripotent stem cells from individuals with disease and the differentiation of these cells into somatic cell types for the study of disease pathophysiology. The emergence of genome-editing technology over the past few years has made it feasible to generate and investigate human cellular disease models with even greater speed and efficiency. Here, recent technological advances in genome editing, and its utility in human biology and disease studies, are reviewed.

  8. 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.

  9. Tissue-Based Imaging Model of Human Trabecular Meshwork

    PubMed Central

    Chu, Edward R.; Gonzalez, Jose M.

    2014-01-01

    Abstract We have developed a tissue-based model of the human trabecular meshwork (TM) using viable postmortem corneoscleral donor tissue. Two-photon microscopy is used to optically section and image deep in the tissue to analyze cells and extracellular matrix (ECM) within the original three-dimensional (3D) environment of the TM. Multimodal techniques, including autofluorescence (AF), second harmonic generation (SHG), intravital dye fluorescence, and epifluorescence, are combined to provide unique views of the tissue at the cellular and subcellular level. SHG and AF imaging are non-invasive tissue imaging techniques with potential for clinical application, which can be modeled in the system. We describe the following in the tissue-based model: analysis of live cellularity to determine tissue viability; characteristics of live cells based on intravital labeling; features and composition of the TM's structural ECM; localization of specific ECM proteins to regions such as basement membrane; in situ induction and expression of tissue markers characteristic of cultured TM cells relevant to glaucoma; analysis of TM actin and pharmacological effects; in situ visualization of TM, inner wall endothelium, and Schlemm's canal; and application of 3D reconstruction, modeling, and quantitative analysis to the TM. The human model represents a cost-effective use of valuable and scarce yet available human tissue that allows unique cell biology, pharmacology, and translational studies of the TM. PMID:24517246

  10. Thymoma related myasthenia gravis in humans and potential animal models.

    PubMed

    Marx, Alexander; Porubsky, Stefan; Belharazem, Djeda; Saruhan-Direskeneli, Güher; Schalke, Berthold; Ströbel, Philipp; Weis, Cleo-Aron

    2015-08-01

    Thymoma-associated Myasthenia gravis (TAMG) is one of the anti-acetylcholine receptor MG (AChR-MG) subtypes. The clinico-pathological features of TAMG and its pathogenesis are described here in comparison with pathogenetic models suggested for the more common non-thymoma AChR-MG subtypes, early onset MG and late onset MG. Emphasis is put on the role of abnormal intratumorous T cell selection and activation, lack of intratumorous myoid cells and regulatory T cells as well as deficient expression of the autoimmune regulator (AIRE) by neoplastic thymic epithelial cells. We review spontaneous and genetically engineered thymoma models in a spectrum of animals and the extensive clinical and immunological overlap between canine, feline and human TAMG. Finally, limitations and perspectives of the transplantation of human and murine thymoma tissue into nude mice, as potential models for TAMG, are addressed.

  11. 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

  12. Learning from humans: computational modeling of face recognition.

    PubMed

    Wallraven, Christian; Schwaninger, Adrian; Bülthoff, Heinrich H

    2005-12-01

    In this paper, we propose a computational architecture of face recognition based on evidence from cognitive research. Several recent psychophysical experiments have shown that humans process faces by a combination of configural and component information. Using an appearance-based implementation of this architecture based on low-level features and their spatial relations, we were able to model aspects of human performance found in psychophysical studies. Furthermore, results from additional computational recognition experiments show that our framework is able to achieve excellent recognition performance even under large view rotations. Our interdisciplinary study is an example of how results from cognitive research can be used to construct recognition systems with increased performance. Finally, our modeling results also make new experimental predictions that will be tested in further psychophysical studies, thus effectively closing the loop between psychophysical experimentation and computational modeling.

  13. Human Factors Engineering Review Model for advanced nuclear power reactors

    SciTech Connect

    O`Hara, J.; Higgins, J.; Goodman, C.; Galletti, G.: Eckenrode, R.

    1993-05-01

    One of the major issues to emerge from the initial design reviews under the certification process was that detailed human-systems interface (HSI) design information was not available for staff review. To address the lack of design detail issue. The Nuclear Regulatory Commission (NRC) is performing the design certification reviews based on a design process plan which describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification. Since the review of a design process is unprecedented in the nuclear industry. The criteria for review are not addressed by current regulations or guidance documents and. therefore, had to be developed. Thus, an HFE Program Review Model was developed. This paper will describe the model`s rationale, scope, objectives, development, general characteristics. and application.

  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

    2014-11-05

    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. MORPHIN: a web tool for human disease research by projecting model organism biology onto a human integrated gene network.

    PubMed

    Hwang, Sohyun; Kim, Eiru; Yang, Sunmo; Marcotte, Edward M; Lee, Insuk

    2014-07-01

    Despite recent advances in human genetics, model organisms are indispensable for human disease research. Most human disease pathways are evolutionally conserved among other species, where they may phenocopy the human condition or be associated with seemingly unrelated phenotypes. Much of the known gene-to-phenotype association information is distributed across diverse databases, growing rapidly due to new experimental techniques. Accessible bioinformatics tools will therefore facilitate translation of discoveries from model organisms into human disease biology. Here, we present a web-based discovery tool for human disease studies, MORPHIN (model organisms projected on a human integrated gene network), which prioritizes the most relevant human diseases for a given set of model organism genes, potentially highlighting new model systems for human diseases and providing context to model organism studies. Conceptually, MORPHIN investigates human diseases by an orthology-based projection of a set of model organism genes onto a genome-scale human gene network. MORPHIN then prioritizes human diseases by relevance to the projected model organism genes using two distinct methods: a conventional overlap-based gene set enrichment analysis and a network-based measure of closeness between the query and disease gene sets capable of detecting associations undetectable by the conventional overlap-based methods. MORPHIN is freely accessible at http://www.inetbio.org/morphin.

  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

    2016-08-02

    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.

  18. A xenograft animal model of human arteriovenous malformations

    PubMed Central

    2013-01-01

    Background Arteriovenous malformations (AVMs) are a type of high-flow vascular malformations that most commonly occurs in the head and neck. They are present at birth but are usually clinically asymptomatic until later in life. The pathogenesis of AVMs remains unclear and therapeutic approaches to AVMs are unsatisfied. In order to provide a tool for studying the pathogenesis and therapies of this disease, we established and studied a xenograft animal model of human AVMs. Methods Fresh human AVMs specimens harvested from 4 patients were sectioned (5x5x5 mm) and xenografted subcutaneously in 5 immunologically naïve nude mice (Athymic Nude-Foxn1nu). Each mouse had four pieces specimens in four quadrants along the back. The grafts were observed weekly for volume, color and texture. The grafts were harvested at every 30 days intervals for histologic examination. All grafts (n = 20) were sectioned and stained for hematoxylin and eosin (H&E). Comparative pathologic evaluation of the grafts and native AVMs were performed by two blinded pathologists. Immunohistochemical examination of human-specific nuclear antigen, vascular endothelial growth factor receptor-2 (VEGFR-2) and Ki-67 was performed. Results Clinical characteristics and pathologic diagnosis of native human derived AVMs were confirmed. 85% (n = 17) of AVM xenografts survived although the sizes decreased after implantation. Histological examination demonstrated numerous small and medium-size vessels and revealed structural characteristics matching the native AVMs tissue.76.5% (n = 13) of the surviving xenografts were positive for Ki-67 and human-specific nuclear antigen suggesting survival of the human derived tissue, 52.9% (n = 9) were positive for VEGFR-2. Conclusions This preliminary xenograft animal model suggests that AVMs can survive in the nude mouse. The presence of human-specific nuclear antigen, VEGFR-2, and Ki-67 demonstrates the stability of native tissue qualities within the

  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. 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.

  2. Multivariate Models for Prediction of Human Skin Sensitization ...

    EPA Pesticide Factsheets

    One of the lnteragency Coordinating Committee on the Validation of Alternative Method's (ICCVAM) top priorities is the development and evaluation of non-animal approaches to identify potential skin sensitizers. The complexity of biological events necessary to produce skin sensitization suggests that no single alternative method will replace the currently accepted animal tests. ICCVAM is evaluating an integrated approach to testing and assessment based on the adverse outcome pathway for skin sensitization that uses machine learning approaches to predict human skin sensitization hazard. We combined data from three in chemico or in vitro assays - the direct peptide reactivity assay (DPRA), human cell line activation test (h-CLAT) and KeratinoSens TM assay - six physicochemical properties and an in silico read-across prediction of skin sensitization hazard into 12 variable groups. The variable groups were evaluated using two machine learning approaches , logistic regression and support vector machine, to predict human skin sensitization hazard. Models were trained on 72 substances and tested on an external set of 24 substances. The six models (three logistic regression and three support vector machine) with the highest accuracy (92%) used: (1) DPRA, h-CLAT and read-across; (2) DPRA, h-CLAT, read-across and KeratinoSens; or (3) DPRA, h-CLAT, read-across, KeratinoSens and log P. The models performed better at predicting human skin sensitization hazard than the murine

  3. 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.

  4. 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.

  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. 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

  7. Mouse models of human AML accurately predict chemotherapy response.

    PubMed

    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

    2009-04-01

    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.

  8. 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

  9. 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.

  10. 1-D blood flow modelling in a running human body.

    PubMed

    Szabó, Viktor; Halász, Gábor

    2017-04-10

    In this paper an attempt was made to simulate blood flow in a mobile human arterial network, specifically, in a running human subject. In order to simulate the effect of motion, a previously published immobile 1-D model was modified by including an inertial force term into the momentum equation. To calculate inertial force, gait analysis was performed at different levels of speed. Our results show that motion has a significant effect on the amplitudes of the blood pressure and flow rate but the average values are not effected significantly.

  11. 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.

  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. Computational Model for Oxygen Transport and Consumption in Human Vitreous

    PubMed Central

    Filas, Benjamen A.; Shui, Ying-Bo; Beebe, David C.

    2013-01-01

    Purpose. Previous studies that measured liquefaction and oxygen content in human vitreous suggested that exposure of the lens to excess oxygen causes nuclear cataracts. Here, we developed a computational model that reproduced available experimental oxygen distributions for intact and degraded human vitreous in physiologic and environmentally perturbed conditions. After validation, the model was used to estimate how age-related changes in vitreous physiology and structure alter oxygen levels at the lens. Methods. A finite-element model for oxygen transport and consumption in the human vitreous was created. Major inputs included ascorbate-mediated oxygen consumption in the vitreous, consumption at the posterior lens surface, and inflow from the retinal vasculature. Concentration-dependent relations were determined from experimental human data or estimated from animal studies, with the impact of all assumptions explored via parameter studies. Results. The model reproduced experimental data in humans, including oxygen partial pressure (Po2) gradients (≈15 mm Hg) across the anterior-posterior extent of the vitreous body, higher oxygen levels at the pars plana relative to the vitreous core, increases in Po2 near the lens after cataract surgery, and equilibration in the vitreous chamber following vitrectomy. Loss of the antioxidative capacity of ascorbate increases oxygen levels 3-fold at the lens surface. Homogeneous vitreous degeneration (liquefaction), but not partial posterior vitreous detachment, greatly increases oxygen exposure to the lens. Conclusions. Ascorbate content and the structure of the vitreous gel are critical determinants of lens oxygen exposure. Minimally invasive surgery and restoration of vitreous structure warrant further attention as strategies for preventing nuclear cataracts. PMID:24008409

  14. 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

  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. The Contribution of Non-human Primate Models to the Development of Human Vaccines

    PubMed Central

    Rivera-Hernandez, Tania; Carnathan, Diane G.; Moyle, Peter M.; Toth, Istvan; West, Nicholas P.; Young, Paul L.; Silvestri, Guido; Walker, Mark J.

    2015-01-01

    The nonhuman primates (NHPs) model in biomedical research has contributed to the study of human infectious, autoimmune, oncogenic, and neurological diseases. This review focuses on the importance of NHP models in vaccine development for tuberculosis, pertussis, Dengue, group A streptococcus (Streptococcus pyogenes) infection, HIV infection, and certain diseases in the elderly (influenza, for example). From understanding disease pathogenesis and mechanisms of protection, to assessing vaccine safety and efficacy, we discuss selected cases where the importance of the use of NHP models is highlighted. PMID:25549702

  17. 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.

  18. Development of in silico models for human liver microsomal stability

    NASA Astrophysics Data System (ADS)

    Lee, Pil H.; Cucurull-Sanchez, Lourdes; Lu, Jing; Du, Yuhua J.

    2007-12-01

    We developed highly predictive classification models for human liver microsomal (HLM) stability using the apparent intrinsic clearance (CLint, app) as the end point. HLM stability has been shown to be an important factor related to the metabolic clearance of a compound. Robust in silico models that predict metabolic clearance are very useful in early drug discovery stages to optimize the compound structure and to select promising leads to avoid costly drug development failures in later stages. Using Random Forest and Bayesian classification methods with MOE, E-state descriptors, ADME Keys, and ECFP_6 fingerprints, various highly predictive models were developed. The best performance of the models shows 80 and 75% prediction accuracy for the test and validation sets, respectively. A detailed analysis of results will be shown, including an assessment of the prediction confidence, the significant descriptors, and the application of these models to drug discovery projects.

  19. Animal models of human respiratory syncytial virus disease.

    PubMed

    Bem, Reinout A; Domachowske, Joseph B; Rosenberg, Helene F

    2011-08-01

    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.

  20. 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.

  1. A control theory model for human decision making

    NASA Technical Reports Server (NTRS)

    Levison, W. H.

    1972-01-01

    The optimal control model for pilot-vehicle systems has been extended to handle certain types of human decision tasks. The model for decision making incorporates the observation noise, optimal estimation, and prediction concepts that form the basis of the model for control behavior. Experiments are described for the following task situations: (1) single decision tasks; (2) two decision tasks; and (3) simultaneous manual control and decision tasks. Using fixed values for model parameters, single-task and two-task decision performance scores to within an accuracy of 10 percent can be predicted. The experiment on simultaneous control and decision indicates the presence of task interference in this situation, but the results are not adequate to allow a conclusive test of the predictive capability of the model.

  2. 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.

  3. 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).

  4. 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.

  5. 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.

  6. The Non-Human Primate Experimental Glaucoma Model

    PubMed Central

    Burgoyne, Claude F.

    2015-01-01

    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 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. PMID:26070984

  7. 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.

  8. An integrated mathematical model of the human cardiopulmonary system: model development.

    PubMed

    Albanese, Antonio; Cheng, Limei; Ursino, Mauro; Chbat, Nicolas W

    2016-04-01

    Several cardiovascular and pulmonary models have been proposed in the last few decades. However, very few have addressed the interactions between these two systems. Our group has developed an integrated cardiopulmonary model (CP Model) that mathematically describes the interactions between the cardiovascular and respiratory systems, along with their main short-term control mechanisms. The model has been compared with human and animal data taken from published literature. Due to the volume of the work, the paper is divided in two parts. The present paper is on model development and normophysiology, whereas the second is on the model's validation on hypoxic and hypercapnic conditions. The CP Model incorporates cardiovascular circulation, respiratory mechanics, tissue and alveolar gas exchange, as well as short-term neural control mechanisms acting on both the cardiovascular and the respiratory functions. The model is able to simulate physiological variables typically observed in adult humans under normal and pathological conditions and to explain the underlying mechanisms and dynamics.

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. A model for gene therapy of human hereditary lymphedema

    PubMed Central

    Karkkainen, Marika J.; Saaristo, Anne; Jussila, Lotta; Karila, Kaisa A.; Lawrence, Elizabeth C.; Pajusola, Katri; Bueler, Hansruedi; Eichmann, Anne; Kauppinen, Risto; Kettunen, Mikko I.; Ylä-Herttuala, Seppo; Finegold, David N.; Ferrell, Robert E.; Alitalo, Kari

    2001-01-01

    Primary human lymphedema (Milroy's disease), characterized by a chronic and disfiguring swelling of the extremities, is associated with heterozygous inactivating missense mutations of the gene encoding vascular endothelial growth factor C/D receptor (VEGFR-3). Here, we describe a mouse model and a possible treatment for primary lymphedema. Like the human patients, the lymphedema (Chy) mice have an inactivating Vegfr3 mutation in their germ line, and swelling of the limbs because of hypoplastic cutaneous, but not visceral, lymphatic vessels. Neuropilin (NRP)-2 bound VEGF-C and was expressed in the visceral, but not in the cutaneous, lymphatic endothelia, suggesting that it may participate in the pathogenesis of lymphedema. By using virus-mediated VEGF-C gene therapy, we were able to generate functional lymphatic vessels in the lymphedema mice. Our results suggest that growth factor gene therapy is applicable to human lymphedema and provide a paradigm for other diseases associated with mutant receptors. PMID:11592985

  15. 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.

  16. Large animal model for osteoporosis in humans: the ewe.

    PubMed

    Oheim, R; Amling, M; Ignatius, A; Pogoda, P

    2012-11-12

    Osteoporosis is a chronic systemic disease characterised by bone loss and microarchitectural deterioration. Since the underlying regulatory mechanisms are still not fully understood and treatment options are not satisfactorily resolved, massive efforts are underway to further investigate this critical illness. Large animal models are stipulated, e.g. by the Food and Drug Administration, for preclinical prevention and intervention studies related to osteoporosis research; in this context, the ewe has already proven its value for orthopaedic research. Although oestrogen deficiency doubtless influences bone metabolism in sheep, the ovariectomised ewe seems unsuitable as a model for postmenopausal osteoporosis and bone loss induction due to its unreliable impact on bone mass and structure. In contrast, glucocorticoid treatment has a major impact on bone turnover and leads to bone conditions comparable to those found in steroid-treated humans. However, adverse side effects can be dramatic resulting in unacceptable discomfort and illness of the experimental animals. Further improvements are therefore essential to judge this model as ethically appropriate. Additionally, models for osteoporosis induced by surgical interventions of central regulatory mechanisms seem to be attractive, as remarkable bone loss is induced by only one surgical procedure without any further treatment. Taken together, different ewe models for osteoporosis have been successfully established and are invaluable for orthopaedic research. However, the search for a 'perfect' large remodelling animal model - in terms of mimicking the human disease and compatibility of bone loss, and without ethical concerns - is still on-going.

  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. Target discrimination using computational vision human perception models

    NASA Astrophysics Data System (ADS)

    Lindquist, George H.; Witus, Gary; Cook, Thomas H.; Freeling, J. Richard; Gerhart, Grant R.

    1994-07-01

    The current DoD target acquisition models have two primary deficiencies: they use simplistic representations of the vehicle and background signatures, and a highly simplified description of the human observer. The current signature representation often fails for complex signature configurations, yields inaccurate detectability and marginal pay-off predictions for low signature vehicles, is not extensible to false alarms and temporal cues, and precludes vehicle design guidance and diagnosis. The current human observer model is simplified to the same degree as the signature representation, and as such is not extensible to high fidelity signature representations. In answer to the noted deficiencies, we have developed the TARDEC visual model (TVM). We have adopted an alternative approach that is based on emerging academic computational vision models (CVM). Our approach is tailored to visual signatures, though the model is applicable to thermal, SAR as well as other categories of imagery. Color imagery, input to the model, is initially transformed into a 3D color-opponent space comprising luminance, red-green, and yellow- blue axes. Each plane in the color-opponent space is then decomposed by local, oriented spatial frequency analyzers (Gabor or wavelet filters) in keeping with current knowledge of retinal/cortical processing. Signal-to-noise statistics are then calculated on each channel, appropriately aggregated over all channels, and used within the signal detection theory context to predict detection and false alarm probabilities.

  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 Central

    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. A mathematical model of Rift Valley Fever with human host.

    PubMed

    Mpeshe, Saul C; Haario, Heikki; Tchuenche, Jean M

    2011-12-01

    Rift Valley Fever is a vector-borne disease mainly transmitted by mosquito. To gain some quantitative insights into its dynamics, a deterministic model with mosquito, livestock, and human host is formulated as a system of nonlinear ordinary differential equations and analyzed. The disease threshold [Formula: see text] is computed and used to investigate the local stability of the equilibria. A sensitivity analysis is performed and the most sensitive model parameters to the measure of initial disease transmission [Formula: see text] and the endemic equilibrium are determined. Both [Formula: see text] and the disease prevalence in mosquitoes are more sensitive to the natural mosquito death rate, d(m). The disease prevalence in livestock and humans are more sensitive to livestock and human recruitment rates, [Formula: see text] and [Formula: see text], respectively, suggesting isolation of livestock from humans is a viable preventive strategy during an outbreak. Numerical simulations support the analytical results in further exploring theoretically the long-term dynamics of the disease at the population level.

  2. 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.

  3. The Human Model: Changing Focus on Autism Research.

    PubMed

    Muotri, Alysson Renato

    2016-04-15

    The lack of live human brain cells for research has slowed progress toward understanding the mechanisms underlying autism spectrum disorders. A human model using reprogrammed patient somatic cells offers an attractive alternative, as it captures a patient's genome in relevant cell types. Despite the current limitations, the disease-in-a-dish approach allows for progressive time course analyses of target cells, offering a unique opportunity to investigate the cellular and molecular alterations before symptomatic onset. Understanding the current drawbacks of this model is essential for the correct data interpretation and extrapolation of conclusions applicable to the human brain. Innovative strategies for collecting biological material and clinical information from large patient cohorts are important for increasing the statistical power that will allow for the extraction of information from the noise resulting from the variability introduced by reprogramming and differentiation methods. Working with large patient cohorts is also important for understanding how brain cells derived from diverse human genetic backgrounds respond to specific drugs, creating the possibility of personalized medicine for autism spectrum disorders.

  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. 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

  6. Velocity profiles in idealized model of human respiratory tract

    NASA Astrophysics Data System (ADS)

    Elcner, J.; Jedelsky, J.; Lizal, F.; Jicha, M.

    2013-04-01

    This article deals with numerical simulation focused on velocity profiles in idealized model of human upper airways during steady inspiration. Three r gimes of breathing were investigated: Resting condition, Deep breathing and Light activity which correspond to most common regimes used for experiments and simulations. Calculation was validated with experimental data given by Phase Doppler Anemometry performed on the model with same geometry. This comparison was made in multiple points which form one cross-section in trachea near first bifurcation of bronchial tree. Development of velocity profile in trachea during steady inspiration was discussed with respect for common phenomenon formed in trachea and for future research of transport of aerosol particles in human respiratory tract.

  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. 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

  9. Correspondence patterns: mechanisms and models of human dynamics.

    PubMed

    Kentsis, Alex

    2006-05-25

    A stochastic queue model of human behaviour developed on the basis of the distribution of timing of tasks, as studied in a sample of e-mail messages at a university and in the written correspondence of Albert Einstein, may not be as simple as it seems. Although this model reproduces the apparently non-Poisson distribution of correspondence delays, its interpretation is more complicated than suggested by Barabási, who claims that humans execute their tasks based on some perceived priority, setting up queues that generate very uneven waiting-time distributions for different tasks. Such an explanation is intuitively appealing in the context of the queue metaphor, but does not exclude other mechanisms. By attributing delays in the correspondence to task priorities, this explanation ignores two important classes of mechanism that also contribute to the apparent distributions of task timings: the semantic content of an individual's correspondence and the social context in which this correspondence occurs.

  10. Human Factors Engineering Review Model for advanced nuclear power reactors

    SciTech Connect

    O'Hara, J.; Higgins, J. ); Goodman, C.; Galletti, G.: Eckenrode, R. )

    1993-01-01

    One of the major issues to emerge from the initial design reviews under the certification process was that detailed human-systems interface (HSI) design information was not available for staff review. To address the lack of design detail issue. The Nuclear Regulatory Commission (NRC) is performing the design certification reviews based on a design process plan which describes the human factors engineering (HFE) program elements that are necessary and sufficient to develop an acceptable detailed design specification. Since the review of a design process is unprecedented in the nuclear industry. The criteria for review are not addressed by current regulations or guidance documents and. therefore, had to be developed. Thus, an HFE Program Review Model was developed. This paper will describe the model's rationale, scope, objectives, development, general characteristics. and application.

  11. Drosophila as a genetic model for studying pathogenic human viruses.

    PubMed

    Hughes, Tamara T; Allen, Amanda L; Bardin, Joseph E; Christian, Megan N; Daimon, Kansei; Dozier, Kelsey D; Hansen, Caom L; Holcomb, Lisa M; Ahlander, Joseph

    2012-02-05

    Viruses are infectious particles whose viability is dependent on the cells of living organisms, such as bacteria, plants, and animals. It is of great interest to discover how viruses function inside host cells in order to develop therapies to treat virally infected organisms. The fruit fly Drosophila melanogaster is an excellent model system for studying the molecular mechanisms of replication, amplification, and cellular consequences of human viruses. In this review, we describe the advantages of using Drosophila as a model system to study human viruses, and highlight how Drosophila has been used to provide unique insight into the gene function of several pathogenic viruses. We also propose possible directions for future research in this area.

  12. Time-varying priority queuing models for human dynamics

    NASA Astrophysics Data System (ADS)

    Jo, Hang-Hyun; Pan, Raj Kumar; Kaski, Kimmo

    2012-06-01

    Queuing models provide insight into the temporal inhomogeneity of human dynamics, characterized by the broad distribution of waiting times of individuals performing tasks. We theoretically study the queuing model of an agent trying to execute a task of interest, the priority of which may vary with time due to the agent's “state of mind.” However, its execution is disrupted by other tasks of random priorities. By considering the priority of the task of interest either decreasing or increasing algebraically in time, we analytically obtain and numerically confirm the bimodal and unimodal waiting time distributions with power-law decaying tails, respectively. These results are also compared to the updating time distribution of papers in arXiv.org and the processing time distribution of papers in Physical Review journals. Our analysis helps to understand human task execution in a more realistic scenario.

  13. Canine brain tumours: a model for the human disease?

    PubMed

    Hicks, J; Platt, S; Kent, M; Haley, A

    2017-03-01

    Canine brain tumours are becoming established as naturally occurring models of disease to advance diagnostic and therapeutic understanding successfully. The size and structure of the dog's brain, histopathology and molecular characteristics of canine brain tumours, as well as the presence of an intact immune system, all support the potential success of this model. The limited success of current therapeutic regimens such as surgery and radiation for dogs with intracranial tumours means that there can be tremendous mutual benefit from collaboration with our human counterparts resulting in the development of new treatments. The similarities and differences between the canine and human diseases are described in this article, emphasizing both the importance and limitations of canines in brain tumour research. Recent clinical veterinary therapeutic trials are also described to demonstrate the areas of research in which canines have already been utilized and to highlight the important potential benefits of translational research to companion dogs.

  14. 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.

  15. Drosophila as a genetic model for studying pathogenic human viruses

    PubMed Central

    Hughes, Tamara T.; Allen, Amanda L.; Bardin, Joseph E.; Christian, Megan N.; Daimon, Kansei; Dozier, Kelsey D.; Hansen, Caom L.; Holcomb, Lisa M.; Ahlander, Joseph

    2011-01-01

    Viruses are infectious particles whose viability is dependent on the cells of living organisms, such as bacteria, plants, and animals. It is of great interest to discover how viruses function inside host cells in order to develop therapies to treat virally infected organisms. The fruit fly Drosophila melanogaster is an excellent model system for studying the molecular mechanisms of replication, amplification, and cellular consequences of human viruses. In this review, we describe the advantages of using Drosophila as a model system to study human viruses, and highlight how Drosophila has been used to provide unique insight into the gene function of several pathogenic viruses. We also propose possible directions for future research in this area. PMID:22177780

  16. 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.

  17. Modelling human problem solving with data from an online game.

    PubMed

    Rach, Tim; Kirsch, Alexandra

    2016-11-01

    Since the beginning of cognitive science, researchers have tried to understand human strategies in order to develop efficient and adequate computational methods. In the domain of problem solving, the travelling salesperson problem has been used for the investigation and modelling of human solutions. We propose to extend this effort with an online game, in which instances of the travelling salesperson problem have to be solved in the context of a game experience. We report on our effort to design and run such a game, present the data contained in the resulting openly available data set and provide an outlook on the use of games in general for cognitive science research. In addition, we present three geometrical models mapping the starting point preferences in the problems presented in the game as the result of an evaluation of the data set.

  18. Male reproductive toxicology: comparison of the human to animal models.

    PubMed Central

    Working, P K

    1988-01-01

    The human male is of relatively low fertility and thus may be at greater risk from reproductive toxicants than are males of the common laboratory animal model species. Lack of knowledge of the physiological differences that contribute to interspecies variation between man and animals can prevent the effective application of animal data to the assessment of human reproductive risk. Evaluation of spermatogenesis from testicular histology, while uncommon, can provide valuable information about human reproductive risk. The measurement of sperm count or concentration has long been the most feasible approach for human semen evaluation, but may be an insensitive indicator of reproductive function because of high sample-to-sample variability. Interspecies extrapolation factors can be calculated by comparing the reduction in sperm count in humans and test species after exposure to drugs or chemicals. These factors can provide a realistic assessment of relative risk, provided that the sperm are counted at the appropriate time after exposure. However, the degree to which extrapolation factors derived for one agent, and only from sperm counts, can be generalized is not known. Monitoring of sperm motility and morphology parameters is also a common means of evaluating human semen quality, but these techniques are also hampered by the relatively high interindividual and intersample variability. Computer-assisted and morphometric approaches show promise of decreasing the subjective nature of these evaluations and increasing their value in risk assessment procedures. Improvements in predicting human reproductive risk can be expected to come from increased knowledge about reproductive mechanisms in man and animals, together with the utilization of objective measures of cellular indicators of male reproductive function. Images FIGURE 2. PMID:3289906

  19. Human lung morphology models for particle deposition studies.

    PubMed

    Martonen, T B; Schroeter, J D; Hwang, D; Fleming, J S; Conway, J H

    2000-01-01

    Knowledge of human lung morphology is of paramount importance in calculating deposition patterns of inhaled particulate matter (PM) to be used in the definition of ambient air quality standards. Due to the inherently complex nature of the branching structure of the airway network, practical assumptions must be made for modeling purposes. The most commonly used mathematical models reported in the literature that describe PM deposition use Weibel's model A morphology. This assumes the airways of the lung to be a symmetric, dichotomously branching system. However, computer simulations of this model, when compared to scintigraphy images, have shown it to lack physiological realism (Martonen et al., 1994a). Therefore, a more physiologically realistic model of the lung is needed to improve the current PM dosimetry models. Herein, a morphological model is presented that is based on laboratory data from planar gamma camera and single-photon emission computed tomography (SPECT) images. Key elements of this model include: The parenchymal wall of the lung is defined in mathematical terms, the whole lung is divided into distinct left and right components, a set of branching angles is derived from experimental measurements, and the branching network is confined within the discrete left and right components (i.e., there is no overlapping of airways). In future work, this new, more physiologically realistic morphological model can be used to calculate PM deposition patterns for risk assessment protocols.

  20. Of men in mice: the success and promise of humanized mouse models for human malaria parasite infections

    PubMed Central

    Kaushansky, Alexis; Mikolajczak, Sebastian A.; Vignali, Marissa; Kappe, Stefan H.I.

    2014-01-01

    Forty percent of people worldwide are at risk of malaria infection, and despite control efforts it remains the most deadly parasitic disease. Unfortunately, rapid discovery and development of new interventions for malaria are hindered by the lack of small animal models that support the complex life cycles of the main parasite species infecting humans. Such tools must accommodate human parasite tropism for human tissue. Mouse models with human tissue developed to date have already enhanced our knowledge of human parasites, and are useful tools for assessing anti-parasitic interventions. Although these systems are imperfect, their continued refinement will likely broaden their utility. Some of the malaria parasite’s interactions with human hepatocytes and human erythrocytes can already be modeled with available humanized mouse systems. However, interactions with other relevant human tissues such as the skin and immune system, as well as most transitions between life cycle stages in vivo will require refinement of existing humanized mouse models. Here, we review the recent successes achieved in modeling human malaria parasite biology in humanized mice, and discuss how these models have potential to become an valuable part of the toolbox used for understanding the biology of, and development of interventions to, malaria. PMID:24506682

  1. 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.

  2. 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.

  3. Modeling vision: computational science for understanding human visual perception.

    PubMed

    Mrowka, Ralf; Freytag, Alexander; Reuter, Stefanie

    2017-03-25

    Human visual perception system is complex and involves a considerable portion of the brain's cortex. Hence, the wish to understand complex neuronal function is obvious, and the idea to model this by means of artificial neuronal networks might have been born at the time when first computational machines were constructed (Alan Turing, Intelligent machinery, 1948, h t t p: //www.npl.co.uk/about/history/notable-individuals/turing/intelligent-machinery) This article is protected by copyright. All rights reserved.

  4. Modeling human neurological disorders with induced pluripotent stem cells.

    PubMed

    Imaizumi, Yoichi; Okano, Hideyuki

    2014-05-01

    Human induced pluripotent stem (iPS) cells obtained by reprogramming technology are a source of great hope, not only in terms of applications in regenerative medicine, such as cell transplantation therapy, but also for modeling human diseases and new drug development. In particular, the production of iPS cells from the somatic cells of patients with intractable diseases and their subsequent differentiation into cells at affected sites (e.g., neurons, cardiomyocytes, hepatocytes, and myocytes) has permitted the in vitro construction of disease models that contain patient-specific genetic information. For example, disease-specific iPS cells have been established from patients with neuropsychiatric disorders, including schizophrenia and autism, as well as from those with neurodegenerative diseases, including Parkinson's disease and Alzheimer's disease. A multi-omics analysis of neural cells originating from patient-derived iPS cells may thus enable investigators to elucidate the pathogenic mechanisms of neurological diseases that have heretofore been unknown. In addition, large-scale screening of chemical libraries with disease-specific iPS cells is currently underway and is expected to lead to new drug discovery. Accordingly, this review outlines the progress made via the use of patient-derived iPS cells toward the modeling of neurological disorders, the testing of existing drugs, and the discovery of new drugs. The production of human induced pluripotent stem (iPS) cells from the patients' somatic cells and their subsequent differentiation into specific cells have permitted the in vitro construction of disease models that contain patient-specific genetic information. Furthermore, innovations of gene-editing technologies on iPS cells are enabling new approaches for illuminating the pathogenic mechanisms of human diseases. In this review article, we outlined the current status of neurological diseases-specific iPS cell research and described recently obtained

  5. Alzheimer disease models and human neuropathology: similarities and differences.

    PubMed

    Duyckaerts, Charles; Potier, Marie-Claude; Delatour, Benoît

    2008-01-01

    Animal models aim to replicate the symptoms, the lesions or the cause(s) of Alzheimer disease. Numerous mouse transgenic lines have now succeeded in partially reproducing its lesions: the extracellular deposits of Abeta peptide and the intracellular accumulation of tau protein. Mutated human APP transgenes result in the deposition of Abeta peptide, similar but not identical to the Abeta peptide of human senile plaque. Amyloid angiopathy is common. Besides the deposition of Abeta, axon dystrophy and alteration of dendrites have been observed. All of the mutations cause an increase in Abeta 42 levels, except for the Arctic mutation, which alters the Abeta sequence itself. Overexpressing wild-type APP alone (as in the murine models of human trisomy 21) causes no Abeta deposition in most mouse lines. Doubly (APP x mutated PS1) transgenic mice develop the lesions earlier. Transgenic mice in which BACE1 has been knocked out or overexpressed have been produced, as well as lines with altered expression of neprilysin, the main degrading enzyme of Abeta. The APP transgenic mice have raised new questions concerning the mechanisms of neuronal loss, the accumulation of Abeta in the cell body of the neurons, inflammation and gliosis, and the dendritic alterations. They have allowed some insight to be gained into the kinetics of the changes. The connection between the symptoms, the lesions and the increase in Abeta oligomers has been found to be difficult to unravel. Neurofibrillary tangles are only found in mouse lines that overexpress mutated tau or human tau on a murine tau -/- background. A triply transgenic model (mutated APP, PS1 and tau) recapitulates the alterations seen in AD but its physiological relevance may be discussed. A number of modulators of Abeta or of tau accumulation have been tested. A transgenic model may be analyzed at three levels at least (symptoms, lesions, cause of the disease), and a reading key is proposed to summarize this analysis.

  6. A Simulink model for the human circulatory system.

    PubMed

    Wabel, P; Leonhardt, S

    1998-01-01

    This paper presents the mathematical simulation of the human circulatory system. The model is based on the former work of Coleman and co-workers and has been redesigned for simulation with the Matlab toolbox "Simulink". It includes the heart and the peripheral circulation, the respiratory system, the kidneys and the major neural and hormonal control mechanisms, which are necessary for maintaining homeostasis. The model contains more than 30 blocks with over 200 physiological variables, which can be accessed and plotted during the simulation.

  7. Construction vs. development: polarizing models of human gestation.

    PubMed

    Stith, Richard

    2014-12-01

    This essay argues that the polarization of our public debate over embryo-destructive research may be due, to a large extent, not to different valuations of individual human life but to different conceptions of the process of gestation, with one group treating the process as a making or construction and the other treating it as a development. These two incompatible models of reproduction are shown to explain the various positions commonly encountered in this debate over the treatment of embryos, and to a significant degree those encountered in the debate over abortion as well. Finally, the historical, theoretical, and intuitive strengths of each model are examined.

  8. Retention modeling of diesel exhaust particles in rats and humans.

    PubMed

    Yu, C P; Yoon, K J

    1991-05-01

    The objective of this study was to predict the lung burden in rats and humans of diesel exhaust particles from automobile emissions by means of a mathematical model. We previously developed a model to predict the deposition of diesel exhaust particles in the lungs of these species. In this study, the clearance and retention of diesel exhaust particles deposited in the lung are examined. A diesel particle is composed of a carbonaceous core (soot) and adsorbed organics. These materials can be removed from the lung after deposition by two mechanisms: (1) mechanical clearance, provided by mucociliary transport in the ciliated airways as well as macrophage phagocytosis and migration in the nonciliated airways, and (2) clearance by dissolution. To study the clearance of diesel exhaust particles from the lung, we used a compartmental model consisting of four anatomical compartments: nasopharyngeal, tracheobronchial, alveolar, and the lung-associated lymph node compartments. We also assumed a particle model made up of material components according to the characteristics of clearance: (1) a carbonaceous core of about 80 percent of particle mass, (2) slowly cleared organics of about 10 percent of particle mass, and (3) fast-cleared organics accounting for the remaining 10 percent of particle mass. The kinetic equations of the retention model were first developed for Fischer-344 rats. The transport rates of each material component of diesel exhaust particles (soot, slowly cleared organics, and fast-cleared organics) were derived using available experimental data and several mathematical approximations. The lung burden results calculated from the model showed that although the organics were cleared at nearly constant rates, the alveolar clearance rate of diesel soot decreased with increasing lung burden. This is consistent with existing experimental observations. At low lung burdens, the alveolar clearance rate of diesel soot was a constant, equal to the normal clearance rate

  9. 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.

  10. The Human Exposure Model (HEM): A Tool to Support Rapid ...

    EPA Pesticide Factsheets

    The US EPA is developing an open and publically available software program called the Human Exposure Model (HEM) to provide near-field exposure information for Life Cycle Impact Assessments (LCIAs). Historically, LCIAs have often omitted impacts from near-field sources of exposure. The use of consumer products often results in near-field exposures (exposures that occur directly from the use of a product) that are larger than environmentally mediated exposures (i.e. far-field sources)1,2. Failure to consider near-field exposures could result in biases in LCIA-based determinations of the relative sustainability of consumer products. HEM is designed to provide this information.Characterizing near-field sources of chemical exposures present a challenge to LCIA practitioners. Unlike far-field sources, where multimedia mass balance models have been used to determine human exposure, near-field sources require product-specific models of human exposure and considerable information on product use and product composition. Such information is difficult and time-consuming to gather and curate. The HEM software will characterize the distribution of doses and product intake fractions2 across populations of product users and bystanders, allowing for differentiation by various demographic characteristics. The tool incorporates a newly developed database of the composition of more than 17,000 products, data on physical and chemical properties for more than 2,000 chemicals, and mo

  11. Towards a Fast Dynamic Model of the Human Circulatory System

    NASA Astrophysics Data System (ADS)

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

    2011-11-01

    We describe a model for systems-level transport in the human circulatory system that is based on a set of equations for a one-dimensional unsteady elastic pipe flow circuit. The system is 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 drive the fluid, the contractions of a beating heart are modeled as periodic area changes of the elastic vessels. Two different models are compared, both including and neglecting fluid acceleration. Time-resolved distributions of pressure, velocity and area compare reasonably well with reference data. Increasing the rigidity of the vasculature is found to increase peak arterial pressures on the order of ten percent, and including a distributed vascular contraction to model distributed skeletal muscle contractions monotonically increases time-averaged blood flow in the veins, consistent with human physiological response. The circulatory system model presented here simulates the circulatory system on the order of one hundred times faster than real-time; that is, we can compute thousands of heartbeats per minute of CPU time.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. Development of a mathematical model of the human circulatory system.

    PubMed

    Conlon, Martin J; Russell, Donald L; Mussivand, Tofy

    2006-09-01

    A mathematical lumped parameter model of the human circulatory system (HCS) has been developed to complement in vitro testing of ventricular assist devices. Components included in this model represent the major parts of the systemic HCS loop, with all component parameters based on physiological data available in the literature. Two model configurations are presented in this paper, the first featuring elements with purely linear constitutive relations, and the second featuring nonlinear constitutive relations for the larger vessels. Three different aortic compliance functions are presented, and a pressure-dependent venous flow resistance is used to simulate venous collapse. The mathematical model produces reasonable systemic pressure and flow behaviour, and graphs of this data are included.

  19. 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.

  20. 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.

  1. Transgenic animal models of neurodegeneration based on human genetic studies

    PubMed Central

    Richie, Christopher T.; Hoffer, Barry J.; Airavaara, Mikko

    2011-01-01

    The identification of genes linked to neurodegenerative diseases such as Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD) and Parkinson's disease (PD) has led to the development of animal models for studying mechanism and evaluating potential therapies. None of the transgenic models developed based on disease-associated genes have been able to fully recapitulate the behavioral and pathological features of the corresponding disease. However, there has been enormous progress made in identifying potential therapeutic targets and understanding some of the common mechanisms of neurodegeneration. In this review, we will discuss transgenic animal models for AD, ALS, HD and PD that are based on human genetic studies. All of the diseases discussed have active or complete clinical trials for experimental treatments that benefited from transgenic models of the disease. PMID:20931247

  2. 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

  3. 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.

  4. 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.

  5. A Humanized Mouse Model for the Reduced Folate Carrier

    PubMed Central

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

    2008-01-01

    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 5 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 1776 bp 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

  6. Melanocortin MC₁ receptor in human genetics and model systems.

    PubMed

    Beaumont, Kimberley A; Wong, Shu S; Ainger, Stephen A; Liu, Yan Yan; Patel, Mira P; Millhauser, Glenn L; Smith, Jennifer J; Alewood, Paul F; Leonard, J Helen; Sturm, Richard A

    2011-06-11

    The melanocortin MC(1) receptor is a G-protein coupled receptor expressed in the melanocytes of the skin and hair and is known for its key role in the regulation of human pigmentation. Melanocortin MC(1) receptor activation after ultraviolet radiation exposure results in a switch from the red/yellow pheomelanin to the brown/black eumelanin pigment synthesis within cutaneous melanocytes; this pigment is then transferred to the surrounding keratinocytes of the skin. The increase in melanin maturation and uptake results in tanning of the skin, providing a physical protection of skin cells from ultraviolet radiation induced DNA damage. Melanocortin MC(1) receptor polymorphism is widespread within the Caucasian population and some variant alleles are associated with red hair colour, fair skin, poor tanning and increased risk of skin cancer. Here we will discuss the use of mouse coat colour models, human genetic association studies, and in vitro cell culture studies to determine the complex functions of the melanocortin MC(1) receptor and the molecular mechanisms underlying the association between melanocortin MC(1) receptor variant alleles and the red hair colour phenotype. Recent research indicates that melanocortin MC(1) receptor has many non-pigmentary functions, and that the increased risk of skin cancer conferred by melanocortin MC(1) receptor variant alleles is to some extent independent of pigmentation phenotypes. The use of new transgenic mouse models, the study of novel melanocortin MC(1) receptor response genes and the use of more advanced human skin models such as 3D skin reconstruction may provide key elements in understanding the pharmacogenetics of human melanocortin MC(1) receptor polymorphism.

  7. Modeling of the human skull in EEG source analysis.

    PubMed

    Dannhauer, Moritz; Lanfer, Benjamin; Wolters, Carsten H; Knösche, Thomas R

    2011-09-01

    We used computer simulations to investigate finite element models of the layered structure of the human skull in EEG source analysis. Local models, where each skull location was modeled differently, and global models, where the skull was assumed to be homogeneous, were compared to a reference model, in which spongy and compact bone were explicitly accounted for. In both cases, isotropic and anisotropic conductivity assumptions were taken into account. We considered sources in the entire brain and determined errors both in the forward calculation and the reconstructed dipole position. Our results show that accounting for the local variations over the skull surface is important, whereas assuming isotropic or anisotropic skull conductivity has little influence. Moreover, we showed that, if using an isotropic and homogeneous skull model, the ratio between skin/brain and skull conductivities should be considerably lower than the commonly used 80:1. For skull modeling, we recommend (1) Local models: if compact and spongy bone can be identified with sufficient accuracy (e.g., from MRI) and their conductivities can be assumed to be known (e.g., from measurements), one should model these explicitly by assigning each voxel to one of the two conductivities, (2) Global models: if the conditions of (1) are not met, one should model the skull as either homogeneous and isotropic, but with considerably higher skull conductivity than the usual 0.0042 S/m, or as homogeneous and anisotropic, but with higher radial skull conductivity than the usual 0.0042 S/m and a considerably lower radial:tangential conductivity anisotropy than the usual 1:10.

  8. 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

  9. On the use of human mobility proxies for modeling epidemics.

    PubMed

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

    2014-07-01

    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

  10. 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.

  11. Modeling the human body shape in bioimpedance vector measurements.

    PubMed

    Kim, Chul-Hyun; Park, Jae-Hyeon; Kim, Hyeoijin; Chung, Sochung; Park, Seung-Hun

    2010-01-01

    Human body shape, called somatotype, has described physique of humans in health and sports applications, relating anthropometric measurements to fatness, muscularity and linearity in a structured way. Here we propose a new method based on bioelectric impedance vector analysis (BIVA) of R/H and Xc/H to represent the cross-sectional area and the body cell mass in a given surface area (m(2)) respectively. Data from six gymnasts, ten dancers, and five fashion models, groups whose physiques and BMI ranges were distinct from one another, were measured for somatotype and BIVA. The models had highest values of the R/H and gymnasts the lowest. Xc/H was lower in models than in the dancers and gymnasts (p < 0.05). Phase angle was lowest in the models and highest in gymnasts significantly (p < 0.05). Pattern analysis from BIVA corresponded to the calculated anthropometric somatotype supporting the hypothesis that BIA's resistance (R) and reactance (Xc) are meaningful discriminates of body size and function which relate to physique in a purposive way.

  12. 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.

  13. 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

  14. 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

  15. 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.

  16. A numerical investigation of a simplified human birth model

    NASA Astrophysics Data System (ADS)

    Pealatere, Roseanna; Baumer, Alexa; Fauci, Lisa; Leftwich, Megan C.

    2015-11-01

    This work uses simplified models and numerical computations to explore the effects of both the fetal velocity and the viscosity of the surrounding fluid on the forces associated with human birth. The numerical results are compared with the results of an experimental model representing the fetus moving through the birth canal using a rigid cylinder (fetus) that moves at a constant velocity through the center of a passive elastic tube (birth canal). The entire system is immersed in highly viscous fluid. Due to low Reynolds' number, the Stokes equations can be used to describe the relationship between velocity and forces in the system. The mathematical model uses the method of regularized Stokeslets to estimate the pulling force necessary to move the rigid inner cylinder at a constant velocity. The elastic tube through which the rigid cylinder passes is constructed by a discrete network of Hookean springs, with macroscopic elasticity matched to the tube used in the physical experiment. More complex geometries as well as peristaltic activation of the elastic tube can be added to the model to provide more insight into the relationship between force and velocity during human birth.

  17. Modeling cognitive loads for evolving shared mental models in human-agent collaboration.

    PubMed

    Fan, Xiaocong; Yen, John

    2011-04-01

    Recent research on human-centered teamwork highly demands the design of cognitive agents that can model and exploit human partners' cognitive load to enhance team performance. In this paper, we focus on teams composed of human-agent pairs and develop a system called Shared Mental Models for all--SMMall. SMMall implements a hidden Markov model (HMM)-based cognitive load model for an agent to predict its human partner's instantaneous cognitive load status. It also implements a user interface (UI) concept called shared belief map, which offers a synergic representation of team members' information space and allows them to share beliefs. An experiment was conducted to evaluate the HMM-based load models. The results indicate that the HMM-based load models are effective in helping team members develop a shared mental model (SMM), and the benefit of load-based information sharing becomes more significant as communication capacity increases. It also suggests that multiparty communication plays an important role in forming/evolving team SMMs, and when a group of agents can be partitioned into subteams, splitting messages by their load status can be more effective for developing subteam SMMs.

  18. Integrating a human thermoregulatory model with a clothing model to predict core and skin temperatures.

    PubMed

    Yang, Jie; Weng, Wenguo; Wang, Faming; Song, Guowen

    2017-05-01

    This paper aims to integrate a human thermoregulatory model with a clothing model to predict core and skin temperatures. The human thermoregulatory model, consisting of an active system and a passive system, was used to determine the thermoregulation and heat exchanges within the body. The clothing model simulated heat and moisture transfer from the human skin to the environment through the microenvironment and fabric. In this clothing model, the air gap between skin and clothing, as well as clothing properties such as thickness, thermal conductivity, density, porosity, and tortuosity were taken into consideration. The simulated core and mean skin temperatures were compared to the published experimental results of subject tests at three levels of ambient temperatures of 20 °C, 30 °C, and 40 °C. Although lower signal-to-noise-ratio was observed, the developed model demonstrated positive performance at predicting core temperatures with a maximum difference between the simulations and measurements of no more than 0.43 °C. Generally, the current model predicted the mean skin temperatures with reasonable accuracy. It could be applied to predict human physiological responses and assess thermal comfort and heat stress.

  19. Physiologically-based pharmacokinetic (PBPK) models in human exposure assessment

    SciTech Connect

    Krishnan, K.

    1995-12-31

    The potential dose received by an individual during defined exposure situations can be determined using personal dosimeters or estimated by combining information on exposure scenarios with the environmental concentration (C.) of chemicals. With the latter approach, not only the potential dose but also the internal dose (i.e., amount of chemical that has been absorbed and available for interaction with receptors) and biologically-effective dose (i.e., amount of chemical that actually reaches the cellular sites where interaction with macromolecules occur) can be estimated if C. is provided as an input to PBPK models. These models are mathematical representations of the interrelationships among the critical determinants of the absorption, distribution, metabolism and excretion of chemicals in biota. Since the compartments in this model correspond to biologically relevant tissues or tissue groups, the amount of chemical reaching specific target organ(s) can be estimated. Further, the PBPK models permit the use of biological monitoring data such as urinary levels of metabolites, hemoglobin adduct levels, and alveolar air concentrations, to reconstruct the exposure levels and scenarios for specific subgroups of populations. These models are also useful in providing estimates of target tissue dose in humans simultaneously exposed to chemicals in various media (air, water, soil, food) by different routes (oral, dermal, inhalation). Several examples of exposure assessment for volatile organic chemicals using PBPK models for mammals will be presented, and the strategies for development of these models for other classes of chemicals highlighted.

  20. 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.

  1. The Northwestern Abdominoplasty Scar Model: A Novel Human Model for Scar Research and Therapeutics.

    PubMed

    Lanier, Steven T; Liu, Jing; Chavez-Munoz, Claudia; Mustoe, Thomas A; Galiano, Robert D

    2016-09-01

    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.

  2. A modular Human Exposure Model (HEM) framework to ...

    EPA Pesticide Factsheets

    Life Cycle Impact Analysis (LCIA) has proven to be a valuable tool for systematically comparing processes and products, and has been proposed for use in Chemical Alternatives Analysis (CAA). The exposure assessment portion of the human health impact scores of LCIA has historically focused on far-field sources (environmentally mediated exposures) while research has shown that use related exposures, (near-field exposures) typically dominate population exposure. Characterizing the human health impacts of chemicals in consumer products over the life cycle of these products requires an evaluation of both near-field as well far-field sources. Assessing the impacts of the near-field exposures requires bridging the scientific and technical gaps that currently prevent the harmonious use of the best available methods and tools from the fields of LCIA and human health exposure and risk assessment. The U.S. EPA’s Chemical Safety and Sustainability LC-HEM project is developing the Human Exposure Model (HEM) to assess near-field exposures to chemicals that occur to various populations over the life cycle of a commercial product. The HEM will be a publically available, web-based, modular system which will allow for the evaluation of chemical/product impacts in a LCIA framework to support CAA. We present here an overview of the framework for the modular HEM system. The framework includes a data flow diagram of in-progress and future planned modules, the definition of each mod

  3. 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.

  4. Exocytotic dynamics in human chromaffin cells: experiments and modeling.

    PubMed

    Albillos, Almudena; Gil, Amparo; González-Vélez, Virginia; Pérez-Álvarez, Alberto; Segura, Javier; Hernández-Vivanco, Alicia; Caba-González, José Carlos

    2013-02-01

    Chromaffin cells have been widely used to study neurosecretion since they exhibit similar calcium dependence of several exocytotic steps as synaptic terminals do, but having the enormous advantage of being neither as small or fast as neurons, nor as slow as endocrine cells. In the present study, secretion associated to experimental measurements of the exocytotic dynamics in human chromaffin cells of the adrenal gland was simulated by using a model that combines stochastic and deterministic approaches for short and longer depolarizing pulses, respectively. Experimental data were recorded from human chromaffin cells, obtained from healthy organ donors, using the perforated patch configuration of the patch-clamp technique. We have found that in human chromaffin cells, secretion would be mainly managed by small pools of non-equally fusion competent vesicles, slowly refilled over time. Fast secretion evoked by brief pulses can be predicted only when 75% of one of these pools (the "ready releasable pool" of vesicles, abbreviated as RRP) are co-localized to Ca²⁺ channels, indicating an immediately releasable pool in the range reported for isolated cells of bovine and rat (Álvarez and Marengo, J Neurochem 116:155-163, 2011). The need for spatial correlation and close proximity of vesicles to Ca²⁺ channels suggests that in human chromaffin cells there is a tight control of those releasable vesicles available for fast secretion.

  5. Development of a Physiological Model for the Human Spine

    NASA Astrophysics Data System (ADS)

    Kvitnitsky, Michael; Thangam, Siva

    2011-11-01

    The intervertebral disc in a human spine is a complex structure consisting of three distinct parts: the nucleus pulposus, the annulus fibrosus, and the cartilaginous end-plates. The Nucleus Pulposus is centrally located within the disc surrounded by annulus fibrosus. It consists of a loose network of fibers and cells in a proteoglycan gel, which merges indistinctly at its outer margin with the annulus fibrosus. A viscoelastic constitutive model is proposed for the nucleus pulposus of the human spine to facilitate the development of a flexible intervetebral device designed for application in the thoraco-lumbar region of the human spine during surgery. A novel experimental set up was designed to establish application limits of the design concept for different approaches in spinal surgery. Both static and fatigue mechanical tests based on the ASTM standards provided a basis for the comparison with some existing clinically successful spinal implants designed for similar applications. Also, these mechanical tests and in-vitro comparison with normal spine provided the application limits of this design in surgery to maintain physiologic functional performance at the affected spinal level. The model is used to investigate the effect of the various design parameters on the biomechanical environment of the spine segment.

  6. 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

  7. 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

  8. A Non-Human Primate Model of Severe Pneumococcal Pneumonia

    PubMed Central

    Reyes, Luis F.; Restrepo, Marcos I.; Hinojosa, Cecilia A.; Soni, Nilam J.; Shenoy, Anukul T.; Gilley, Ryan P.; Gonzalez-Juarbe, Norberto; Noda, Julio R.; Winter, Vicki T.; de la Garza, Melissa A.; Shade, Robert E.; Coalson, Jacqueline J.; Giavedoni, Luis D.; Anzueto, Antonio; Orihuela, Carlos J.

    2016-01-01

    Rationale Streptococcus pneumoniae is the leading cause of community-acquired pneumonia and infectious death in adults worldwide. A non-human primate model is needed to study the molecular mechanisms that underlie the development of severe pneumonia, identify diagnostic tools, explore potential therapeutic targets, and test clinical interventions during pneumococcal pneumonia. Objective To develop a non-human primate model of pneumococcal pneumonia. Methods Seven adult baboons (Papio cynocephalus) were surgically tethered to a continuous monitoring system that recorded heart rate, temperature, and electrocardiography. Animals were inoculated with 109 colony-forming units of S. pneumoniae using bronchoscopy. Three baboons were rescued with intravenous ampicillin therapy. Pneumonia was diagnosed using lung ultrasonography and ex vivo confirmation by histopathology and immunodetection of pneumococcal capsule. Organ failure, using serum biomarkers and quantification of bacteremia, was assessed daily. Results Challenged animals developed signs and symptoms of pneumonia 4 days after infection. Infection was characterized by the presence of cough, tachypnea, dyspnea, tachycardia and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. A severe inflammatory reaction was detected by elevation of serum cytokines, including Interleukin (IL)1Ra, IL-6, and IL-8, after infection. Lung ultrasonography precisely detected the lobes with pneumonia that were later confirmed by pathological analysis. Lung pathology positively correlated with disease severity. Antimicrobial therapy rapidly reversed symptomology and reduced serum cytokines. Conclusions We have developed a novel animal model for severe pneumococcal pneumonia that mimics the clinical presentation, inflammatory response, and infection kinetics seen in humans. This is a novel model to test vaccines and treatments, measure biomarkers to diagnose pneumonia, and predict outcomes. PMID:27855182

  9. 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.

  10. 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

  11. 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.

  12. Mining and modeling human genetics for autism therapeutics.

    PubMed

    Smith, Daniel G; Ehlers, Michael D

    2012-10-01

    A growing understanding of the genetic origins of autism spectrum disorders (ASDs) and the impact of ASD risk genes on synaptic function presents new opportunities for drug discovery. Large-scale human genetics studies have begun to reveal molecular pathways and potential therapeutic drug targets. Subsequent validation and characterization of ASD risk genes in mouse models holds promise for defining relevant cellular mechanisms and brain circuits associated with the core behavioral symptoms of autism. Here we review recent advances in the molecular therapeutics in ASDs and discuss opportunities and obstacles for converting emerging biology into new medicines. We present emerging concepts on the impact of risk genes during development and adulthood that define points of intervention. We further highlight ongoing clinical trials in patients with syndromic forms of autism. These clinical studies will be an important test of the utility of human genetics as a starting point for drug discovery in ASDs.

  13. Generalized Modeling of the Human Lower Limb Assembly

    NASA Astrophysics Data System (ADS)

    Cofaru, Ioana; Huzu, Iulia

    2014-11-01

    The main reason for creating a generalized assembly of the main bones of the lower human member is to create the premises of realizing a biomechanic assisted study which could be used for the study of the high range of varieties of pathologies that exist at this level. Starting from 3D CAD models of the main bones of the lower human member, which were realized in previous researches, in this study a generalized assembly system was developed, system in which are highlighted both the situation of an healthy subject and the situation of the situation of a subject affected by axial deviations. In order to achieve these purpose reference systems were created, systems that are in accordance with the mechanical axes and the anatomic axes of the lower member, which were later generally assembled in a manner that provides an easy customization option

  14. [Relevance of animal models in the study of human pathologies: a mouse model of Down syndrome].

    PubMed

    Morice, Elise

    2010-01-01

    Animal models provide a simplified representation of biological systems impossible to study directly in the human being. Regarding genetic pathologies, mouse models are the most studied since they enable to reproduce in animals the mutation of the gene or genes responsible for the disease and to study the phenotypic consequences. Down syndrome is a genetic disorder arising from the presence of a third copy of the human chromosome 21 (Hsa21) and is characterized by different degrees of phenotypic alterations including morphological, cardiac, muscular, cerebral, motor and intellectual changes. This high phenotypic heterogeneity involves genetic and environmental effects, which are impossible to dissect out in human beings. Various models in mice have been developed in order to identify the genetic and neurobiological mechanisms responsible for Down syndrome. The Tc1 mouse is the most complete genetic animal model currently available to study Down syndrome, since it carries an almost complete Hsa 21. The behavioural and electrophysiological studies of this model reveal a great similarity between the animal phenotype and the Down syndrome symptomatology, consequently this model represents a powerful genetic tool with a potential to unravel the mechanisms underlying the deficiencies array characteristic of this human condition. In the long term, Tc1 mice will contribute to the development and the screening of new therapeutics, with the goal of improving all the impairments reported in Down syndrome.

  15. Characterization of human ovarian carcinomas in a SCID mouse model.

    PubMed

    Xu, Y; Silver, D F; Yang, N P; Oflazoglu, E; Hempling, R E; Piver, M S; Repasky, E A

    1999-02-01

    This study characterizes a murine model which is promising for the study of the growth and natural history of ovarian cancer and for testing of new therapies for its treatment. Intact portions of 20 different human ovarian cancer surgical specimens were implanted in over 60 severe combined immunodeficient (SCID) mice using techniques previously developed in our laboratory. Growth of xenografts was evaluated by gross examination and histopathologic analysis. Confirmation of the human origin of the tumor outgrowth was obtained using in situ hybridization analysis. By histological evaluation, all of the patients' tumors showed evidence of invasive growth in at least 1 of the mice implanted with portions of each surgical specimen and these tumors remained morphologically similar to the parent tumors for a long period of time. Furthermore, 65% (13/20) of the xenografts grew rapidly enough (i.e., reached a diameter of 1-2 cm within 2-6 months) to allow passage to subsequent SCID mice. Among the passaged xenografts, 3 eventually developed metastases in a distribution pattern similar to that of naturally occurring ovarian cancer and 2 developed ascites without evidence of further metastatic spread. Upon evaluation of sera from tumor-bearing mice, human antibodies presumably derived from immunoglobulin-secreting cells present in the original tumor specimen were identified. In support of this, human B cells and plasma cells could be seen within the tumor xenograft for more than 6 months following implantation. In summary, transplantation of surgical specimens from ovarian cancer patients into SCID mice results in an attractive model for the study of the natural history of ovarian cancer and may also be useful for analysis or new experimental therapeutic approaches for the treatment of this disease.

  16. 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.

  17. 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.

  18. 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

  19. Permeability of the reconstructed human epidermis model Episkin in comparison to various human skin preparations.

    PubMed

    Netzlaff, Frank; Kaca, Monika; Bock, Udo; Haltner-Ukomadu, Eleonore; Meiers, Peter; Lehr, Claus-Michael; Schaefer, Ulrich F

    2007-04-01

    The objective of this work was to compare the barrier function of the small diameter reconstructed human epidermis model Episkin (d=12 mm) to human skin in vitro. For that purpose a modification for the Franz diffusion cell (d=15mm) had to be developed so as to allow direct comparison with the following human skin preparations: Full thickness skin (FTS), split thickness skin (STS), heat-separated epidermis (HSE), and trypsin isolated stratum corneum (TISC). Among the tested preparations, HSE appeared to be the most preferable due to its clear morphological structure and ease of preparation. The lipid profile of HSE and Episkin was analyzed and showed significant differences in terms of cholesterol, ceramides and triglycerides contents, whereas cholesterol esters and fatty acids were not different. Permeation data with HSE and Episkin were then gathered using caffeine and testosterone. Both test compounds permeated much faster through Episkin than through HSE. Moreover, opposed to Episkin, HSE differentiated between the two test compounds. In spite of the remarkable progress in developing RHEs in the past years at this time Episkin can obviously not yet fully replace human skin for in vitro permeability experiments.

  20. Modeling of human artery tissue with probabilistic approach.

    PubMed

    Xiong, Linfei; Chui, Chee-Kong; Fu, Yabo; Teo, Chee-Leong; Li, Yao

    2015-04-01

    Accurate modeling of biological soft tissue properties is vital for realistic medical simulation. Mechanical response of biological soft tissue always exhibits a strong variability due to the complex microstructure and different loading conditions. The inhomogeneity in human artery tissue is modeled with a computational probabilistic approach by assuming that the instantaneous stress at a specific strain varies according to normal distribution. Material parameters of the artery tissue which are modeled with a combined logarithmic and polynomial energy equation are represented by a statistical function with normal distribution. Mean and standard deviation of the material parameters are determined using genetic algorithm (GA) and inverse mean-value first-order second-moment (IMVFOSM) method, respectively. This nondeterministic approach was verified using computer simulation based on the Monte-Carlo (MC) method. Cumulative distribution function (CDF) of the MC simulation corresponds well with that of the experimental stress-strain data and the probabilistic approach is further validated using data from other studies. By taking into account the inhomogeneous mechanical properties of human biological tissue, the proposed method is suitable for realistic virtual simulation as well as an accurate computational approach for medical device validation.

  1. 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.

  2. A recellularized human colon model identifies cancer driver genes

    PubMed Central

    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.

    2016-01-01

    Refined cancer models are needed to bridge the gap 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. 38 candidate invasion driver genes were identified, 17 of which have been previously implicated in colorectal cancer progression, including TCF7L2, TWIST2, MSH2, DCC and EPHB1/2. Six invasion driver genes that to our knowledge have not 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

  3. 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

  4. A numerical investigation of a simplified human birth model

    NASA Astrophysics Data System (ADS)

    Gossmann, Roseanna; Baumer, Alexa; Fauci, Lisa; Leftwich, Megan C.

    2016-11-01

    This work uses a simplified model to explore the forces experienced by the fetus during human birth. Numerical results are compared with the results of a physical model representing the fetus moving through the birth canal using a rigid cylinder (fetus) that moves at a constant velocity through the center of a passive elastic tube (birth canal). The entire system is immersed in a highly viscous fluid. Numerical simulations are run at low and zero Reynolds numbers. In each case, the pulling force necessary to move the rigid inner cylinder at a constant velocity through the tube is measured. The discrete elastic tube through which the rigid cylinder passes has macroscopic elasticity matched to the tube used in the physical experiment. The buckling behavior of the elastic tube is explored by varying velocity, length, and diameter of the rigid cylinder, and length of the elastic tube. More complex geometries as well as peristaltic activation of the elastic tube can be added to the model to provide more insight into the relationship between force and velocity during human birth.

  5. A Three-Dimensional Computational Human Head Model That Captures Live Human Brain Dynamics.

    PubMed

    Ganpule, Shailesh; Daphalapurkar, Nitin P; Ramesh, Kaliat T; Knutsen, Andrew K; Pham, Dzung L; Bayly, Philip V; Prince, Jerry L

    2017-04-10

    Diffuse axonal injury (DAI) is a debilitating consequence of traumatic brain injury (TBI) attributed to abnormal stretching of axons caused by blunt head trauma or acceleration of the head. We developed an anatomically accurate, subject-specific, three-dimensional (3D) computational model of the human brain, and used it to study the dynamic deformations in the substructures of the brain when the head is subjected to rotational accelerations. The computational head models use anatomy and morphology of the white matter fibers obtained using MRI. Subject-specific full-field shearing motions in live human brains obtained through a recently developed tagged MRI imaging technique are then used to validate the models by comparing the measured and predicted heterogeneous dynamic mechanical response of the brain. These results are used to elucidate the dynamics of local shearing deformations in the brain substructures caused by rotational acceleration of the head. Our work demonstrates that the rotational dynamics of the brain has a timescale of ∼100 ms as determined by the shearing wave speeds, and thus the injuries associated with rotational accelerations likely occur over these time scales. After subject-specific validation using the live human subject data, a representative subject-specific head model is used to simulate a real life scenario that resulted in a concussive injury. Results suggest that regions of the brain, in the form of a toroid, encompassing the white matter, the cortical gray matter, and outer parts of the limbic system have a higher susceptibility to injury under axial rotations of the head.

  6. A novel model for evaluating therapies targeting human tumor vasculature and human cancer stem-like cells

    PubMed Central

    Burgos-Ojeda, Daniela; McLean, Karen; Bai, Shoumei; Pulaski, Heather; Gong, Yusong; Silva, Ines; Skorecki, Karl; Tzukerman, Maty; Buckanovich, Ronald J.

    2013-01-01

    Human tumor vessels express tumor vascular markers (TVMs), proteins that are not expressed in normal blood vessels. Antibodies targeting TVMs could act as potent therapeutics. Unfortunately, preclinical in vivo studies testing anti-human TVM therapies have been difficult to perform due to a lack of in vivo models with confirmed expression of human TVMs. We therefore evaluated TVM expression in a human embryonic stem cell derived teratoma (hESCT) tumor model previously shown to have human vessels. We now report that, in the presence of tumor cells, hESCT tumor vessels express human TVMs. The addition of mouse embryonic fibroblasts and human tumor endothelial cells significantly increases the number of human tumor vessels. TVM induction is mostly tumor type specific with ovarian cancer cells inducing primarily ovarian TVMs while breast cancer cells induce breast cancer specific TVMs. We demonstrate the utility of this model to test an anti-human specific TVM immunotherapeutics; anti-human Thy-1 TVM immunotherapy results in central tumor necrosis and a three-fold reduction in human tumor vascular density. Finally, we tested the ability of the hESCT model, with human tumor vascular niche, to enhance the engraftment rate of primary human ovarian cancer stem-like cells (CSC). ALDH+ CSC from patients (n=6) engrafted in hESCT within 4–12 weeks whereas none engrafted in the flank. ALDH- ovarian cancer cells showed no engraftment in the hESCT or flank (n=3). Thus this model represents a useful tool to test anti-human TVM therapy and evaluate in vivo human CSC tumor biology. PMID:23576551

  7. 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.

  8. 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

  9. Norepinephrine metabolism in humans. Kinetic analysis and model

    SciTech Connect

    Linares, O.A.; Jacquez, J.A.; Zech, L.A.; Smith, M.J.; Sanfield, J.A.; Morrow, L.A.; Rosen, S.G.; Halter, J.B.

    1987-11-01

    The present study was undertaken to quantify more precisely and to begin to address the problem of heterogeneity of the kinetics of distribution and metabolism of norepinephrine (NE) in humans, by using compartmental analysis. Steady-state NE specific activity in arterialized plasma during (/sup 3/H)NE infusion and postinfusion plasma disappearance of (/sup 3/H)NE were measured in eight healthy subjects in the supine and upright positions. Two exponentials were clearly identified in the plasma (/sup 3/H)NE disappearance curves of each subject studied in the supine (r = 0.94-1.00, all P less than 0.01) and upright (r = 0.90-0.98, all P less than 0.01) positions. A two-compartment model was the minimal model necessary to simultaneously describe the kinetics of NE in the supine and upright positions. The NE input rate into the extravascular compartment 2, estimated with the minimal model, increased with upright posture (1.87 +/- 0.08 vs. 3.25 +/- 0.2 micrograms/min per m2, P less than 0.001). Upright posture was associated with a fall in the volume of distribution of NE in compartment 1 (7.5 +/- 0.6 vs. 4.7 +/- 0.3 liters, P less than 0.001), and as a result of that, there was a fall in the metabolic clearance rate of NE from compartment 1 (1.80 +/- 0.11 vs. 1.21 +/- 0.08 liters/min per m2, P less than 0.001). We conclude that a two-compartment model is the minimal model that can accurately describe the kinetics of distribution and metabolism of NE in humans.

  10. A mouse model of human repetitive mild traumatic brain injury

    PubMed Central

    Kane, Michael J.; Pérez, Mariana Angoa; Briggs, Denise I.; Viano, David C.; Kreipke, Christian W.; Kuhn, Donald M.

    2011-01-01

    A novel method for the study of repetitive mild traumatic brain injury (rmTBI) that models the most common form of head injury in humans is presented. Existing animal models of TBI impart focal, severe damage unlike that seen in repeated and mild concussive injuries, and few are configured for repetitive application. Our model is a modification of the Marmarou weight drop method and allows repeated head impacts to lightly anesthetized mice. A key facet of this method is the delivery of an impact to the cranium of an unrestrained subject allowing rapid acceleration of the free-moving head and torso, an essential characteristic known to be important for concussive injury in humans, and a factor that is missing from existing animal models of TBI. Our method does not require scalp incision, emplacement of protective skull helmets or surgery and the procedure can be completed in 1-2 minutes. Mice spontaneously recover the righting reflex and show no evidence of seizures, paralysis or impaired behavior. Skull fractures and intracranial bleeding are very rare. Minor deficits in motor coordination and locomotor hyperactivity recover over time. Histological analyses reveal mild astrocytic reactivity (increased expression of GFAP) and increased phospho-tau but a lack of blood-brain-barrier disruption, edema and microglial activation. This new animal model is simple and cost-effective and will facilitate characterization of the neurobiological and behavioral consequences of rmTBI. It is also ideal for high throughput screening of potential new therapies for mild concussive injuries as experienced by athletes and military personnel. PMID:21930157

  11. A mouse model of human repetitive mild traumatic brain injury.

    PubMed

    Kane, Michael J; Angoa-Pérez, Mariana; Briggs, Denise I; Viano, David C; Kreipke, Christian W; Kuhn, Donald M

    2012-01-15

    A novel method for the study of repetitive mild traumatic brain injury (rmTBI) that models the most common form of head injury in humans is presented. Existing animal models of TBI impart focal, severe damage unlike that seen in repeated and mild concussive injuries, and few are configured for repetitive application. Our model is a modification of the Marmarou weight drop method and allows repeated head impacts to lightly anesthetized mice. A key facet of this method is the delivery of an impact to the cranium of an unrestrained subject allowing rapid acceleration of the free-moving head and torso, an essential characteristic known to be important for concussive injury in humans, and a factor that is missing from existing animal models of TBI. Our method does not require scalp incision, emplacement of protective skull helmets or surgery and the procedure can be completed in 1-2 min. Mice spontaneously recover the righting reflex and show no evidence of seizures, paralysis or impaired behavior. Skull fractures and intracranial bleeding are very rare. Minor deficits in motor coordination and locomotor hyperactivity recover over time. Histological analyses reveal mild astrocytic reactivity (increased expression of GFAP) and increased phospho-tau but a lack of blood-brain-barrier disruption, edema and microglial activation. This new animal model is simple and cost-effective and will facilitate characterization of the neurobiological and behavioral consequences of rmTBI. It is also ideal for high throughput screening of potential new therapies for mild concussive injuries as experienced by athletes and military personnel.

  12. Case Report: Successful Sporozoite Challenge Model in Human Volunteers with Plasmodium vivax Strain Derived from Human Donors

    DTIC Science & Technology

    2009-01-01

    Report: Successful Sporozoite Challenge Model in Human Volunteers with Plasmodium vivax Strain Derived from Human Donors Sócrates Herrera...Switzerland Abstract. Successful establishment of a Plasmodium vivax sporozoite challenge model in humans is described. Eighteen healthy adult...among groups (Kruskal-Wallis, P = 0.70). One volunteer exposed to eight mosquito bites did not develop a parasitemia. No dif- ferences in parasite

  13. 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.

  14. 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.

  15. Human body composition: advances in models and methods.

    PubMed

    Heymsfield, S B; Wang, Z; Baumgartner, R N; Ross, R

    1997-01-01

    The field of human body composition research is reaching a mature stage in its development: The three interconnected areas that define body composition research--models and their rules, methodology, and biological effects--are well-defined and are actively investigated by scientists in diverse disciplines from many different nations; and methods are available for measuring all major atomic, molecular, cellular, and tissue-system level body composition components in research, clinical, and epidemiological settings. This review summarizes main body composition research concepts, examines new component-measurement methodologies, and identifies potential areas of future research.

  16. 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.

  17. Screening and analysis of breast cancer genes regulated by the human mammary microenvironment in a humanized mouse model

    PubMed Central

    Zheng, Mingjie; Wang, Jue; Ling, Lijun; Xue, Dandan; Wang, Shui; Zhao, Yi

    2016-01-01

    Tumor microenvironments play critical regulatory roles in tumor growth. Although mouse cancer models have contributed to the understanding of human tumor biology, the effectiveness of mouse cancer models is limited by the inability of the models to accurately present humanized tumor microenvironments. Previously, a humanized breast cancer model in severe combined immunodeficiency mice was established, in which human breast cancer tissue was implanted subcutaneously, followed by injection of human breast cancer cells. It was demonstrated that breast cancer cells showed improved growth in the human mammary microenvironment compared with a conventional subcutaneous mouse model. In the present study, the novel mouse model and microarray technology was used to analyze changes in the expression of genes in breast cancer cells that are regulated by the human mammary microenvironment. Humanized breast and conventional subcutaneous mouse models were established, and orthotopic tumor cells were obtained from orthotopic tumor masses by primary culture. An expression microarray using Illumina HumanHT-12 v4 Expression BeadChip and database analyses were performed to investigate changes in gene expression between tumors from each microenvironment. A total of 94 genes were differentially expressed between the primary cells cultured from the humanized and conventional mouse models. Significant upregulation of genes that promote cell proliferation and metastasis or inhibit apoptosis, such as SH3-domain binding protein 5 (BTK-associated), sodium/chloride cotransporter 3 and periostin, osteoblast specific factor, and genes that promote angiogenesis, such as KIAA1618, was also noted. Other genes that restrain cell proliferation and accelerate cell apoptosis, including tripartite motif containing TRIM36 and NES1, were downregulated. The present results revealed differences in various aspects of tumor growth and metabolism between the two model groups and indicated the functional

  18. Human Xenografts Are Not Rejected in a Naturally Occurring Immunodeficient Porcine Line: A Human Tumor Model in Pigs

    PubMed Central

    Basel, Matthew T.; Balivada, Sivasai; Beck, Amanda P.; Kerrigan, Maureen A.; Pyle, Marla M.; Dekkers, Jack C.M.; Wyatt, Carol R.; Rowland, Robert R.R.; Anderson, David E.; Bossmann, Stefan H.

    2012-01-01

    Abstract Animal models for cancer therapy are invaluable for preclinical testing of potential cancer treatments; however, therapies tested in such models often fail to translate into clinical settings. Therefore, a better preclinical model for cancer treatment testing is needed. Here we demonstrate that an immunodeficient line of pigs can host and support the growth of xenografted human tumors and has the potential to be an effective animal model for cancer therapy. Wild-type and immunodeficient pigs were injected subcutaneously in the left ear with human melanoma cells (A375SM cells) and in the right ear with human pancreatic carcinoma cells (PANC-1). All immunodeficient pigs developed tumors that were verified by histology and immunohistochemistry. Nonaffected littermates did not develop tumors. Immunodeficient pigs, which do not reject xenografted human tumors, have the potential to become an extremely useful animal model for cancer therapy because of their similarity in size, anatomy, and physiology to humans. PMID:23514746

  19. Orientation discrimination in human vision: psychophysics and modeling.

    PubMed

    Beaudot, William H A; Mullen, Kathy T

    2006-01-01

    We evaluated orientation discrimination thresholds using an external noise paradigm. Stimuli were spatiotemporal Gaussian patches of 2D orientation noise band-pass filtered in Fourier domain. Orientation acuity was measured for various combinations of stimulus spatial bandwidth, spatial frequency, and size as a function of orientation bandwidths of the stimuli. Stimulus contrast was matched in multiples of detection threshold. Consistent with the idea that stimulus orientation bandwidth acts as a source of external noise, orientation discrimination thresholds increased monotonically in all conditions with stimulus bandwidth. To interpret these results quantitatively, we first fitted a variance summation model to the data and derived the internal orientation noise, relative sampling efficiency, and orientation tuning of the mechanism underlying orientation discrimination. Due to the equivocal biological nature of these parameters for orientation discrimination, we investigated, with a modeling approach, how neural detectors characterized by a broad orientation tuning may support orientation discrimination. We demonstrated using the ideal-observer theory that while linear models, based on either unimodal filtering or center-surround opponency, predict the monotonic relationship between orientation discrimination threshold and orientation noise, a nonlinear model incorporating a broadband divisive inhibition in the orientation domain is a better candidate due to its contrast invariance. This model, using broad and similar orientation tuning for its excitatory and inhibitory inputs, accounts for the acute orientation acuity of human vision and proves to be robust despite the variance found in natural stimuli.

  20. 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

  1. 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

  2. Reconstruction of genome-scale human metabolic models using omics data.

    PubMed

    Ryu, Jae Yong; Kim, Hyun Uk; Lee, Sang Yup

    2015-08-01

    The impact of genome-scale human metabolic models on human systems biology and medical sciences is becoming greater, thanks to increasing volumes of model building platforms and publicly available omics data. The genome-scale human metabolic models started with Recon 1 in 2007, and have since been used to describe metabolic phenotypes of healthy and diseased human tissues and cells, and to predict therapeutic targets. Here we review recent trends in genome-scale human metabolic modeling, including various generic and tissue/cell type-specific human metabolic models developed to date, and methods, databases and platforms used to construct them. For generic human metabolic models, we pay attention to Recon 2 and HMR 2.0 with emphasis on data sources used to construct them. Draft and high-quality tissue/cell type-specific human metabolic models have been generated using these generic human metabolic models. Integration of tissue/cell type-specific omics data with the generic human metabolic models is the key step, and we discuss omics data and their integration methods to achieve this task. The initial version of the tissue/cell type-specific human metabolic models can further be computationally refined through gap filling, reaction directionality assignment and the subcellular localization of metabolic reactions. We review relevant tools for this model refinement procedure as well. Finally, we suggest the direction of further studies on reconstructing an improved human metabolic model.

  3. ras activation in human tumors and in animal model systems.

    PubMed Central

    Corominas, M; Sloan, S R; Leon, J; Kamino, H; Newcomb, E W; Pellicer, A

    1991-01-01

    Environmental agents such as radiation and chemicals are known to cause genetic damage. Alterations in a limited set of cellular genes called proto-oncogenes lead to unregulated proliferation and differentiation. We have studied the role of the ras gene family in carcinogenesis using two different animal models. In one case, thymic lymphomas were induced in mice by either gamma or neutron radiation, and in the other, keratoacanthomas were induced in rabbit skin with dimethylbezanthracene. Human keratoacanthomas similar to the ones induced in rabbits were also analyzed. We found that different types of radiation such as gamma rays and neutrons, induced different point mutations in ras genes. A novel K-ras mutation in codon 146 has been found in thymic lymphomas induced by neutrons. Keratoacanthomas induced in rabbit skin by dimethylbenzanthracene show a high frequency of H-ras-activated genes carrying a mutation in codon 61. The same is observed in human keratoacanthomas, although mutations are in both the 12th and the 61st codons of the H-ras gene. H-ras activation is less frequent in human squamous cell carcinomas than in keratoacanthomas, suggesting that ras genes could play a role in vivo in differentiation as well as in proliferation. Images FIGURE 1. FIGURE 2. FIGURE 3. FIGURE 4. PMID:1773791

  4. A model of the human M2 muscarinic acetylcholine receptor

    NASA Astrophysics Data System (ADS)

    Jöhren, Kirstin; Höltje, Hans-Dieter

    2002-11-01

    The M2 muscarinic acetylcholine receptor belongs to the family of rhodopsin like G-Protein Coupled Receptors. This subtype of muscarinic receptors is of special interest because it bears, aside from an orthosteric binding site, also an allosteric binding site. Based on the X-ray structure of bovine rhodopsin a complete homology model of the human M2 receptor was developed. For the orthosteric binding site point mutations and binding studies with different agonists and antagonists are available. This knowledge was utilized for an initial verification of the M2 model. Allosteric modulation of activity is mediated by structurally different ligands such as gallamine, caracurine V salts or W84 (a hexamethonium-derivative). Caracurine V derivatives with different affinities to M2 were docked using GRID-fields. Subsequent molecular dynamics simulations yielded different binding energies based on diverse electrostatic and lipophilic interactions. The calculated affinities are in good agreement to experimentally determined affinities.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Using Task Analytic Models and Phenotypes of Erroneous Human Behavior to Discover System Failures Using Model Checking

    PubMed Central

    Bolton, Matthew L.; Bass, Ellen J.

    2011-01-01

    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. PMID:25382961

  11. Development of Animal Models of Human IgA Nephropathy

    PubMed Central

    Suzuki, Hitoshi; Suzuki, Yusuke; Novak, Jan; Tomino, Yasuhiko

    2014-01-01

    IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis in the world. IgAN is characterized by the mesangial accumulation of immune complexes containing IgA1, usually with co-deposits of complement C3 and variable IgG and/or IgM. Although more than 40 years have passed since IgAN was first described, the mechanisms underlying the disease development are not fully understood. Small-animal experimental models of IgAN can be very helpful in studies of IgAN, but development of these models has been hindered by the fact that only humans and hominoid primates have IgA1 subclass. Thus, multiple models have been developed, that may be helpful in studies of some specific aspects of IgAN. These models include a spontaneous animal model of IgAN, the ddY mouse first reported in 1985. These mice show mild proteinuria without hematuria, and glomerular IgA deposits, with a highly variable incidence and degree of glomerular injury, due to the heterogeneous genetic background. To obtain a murine line consistently developing IgAN, we intercrossed an earlyonset group of ddY mice, in which the development of IgAN includes mesangial IgA deposits and glomerular injury. After selective intercrossing for >20 generations, we established a novel 100% early-onset grouped ddY murine model. All grouped ddY mice develop proteinuria within eight weeks of age. The grouped ddY mouse model can be a useful tool for analysis of multiple aspects of the pathogenesis of IgAN and may aid in assessment of some approaches for the treatment of IgAN. PMID:25722731

  12. Human endotoxemia: a model for mechanistic insight and therapeutic targeting.

    PubMed

    Lowry, Stephen F

    2005-12-01

    The diversity of phenotypic manifestations, comorbidities, and therapeutic algorithms in patients with severe inflammation have confounded efforts to translate mechanistic insights from the bench top to the bedside. This dilemma has negatively impacted upon many therapeutic interventions that exhibited seemingly well-reasoned preclinical portfolios. Prudence urges the assessment of potent immunoregulatory therapies, wherever possible, in models that replicate the clinical phenotype absent overt manifestations of genetically or environmentally modified processes. The healthy human model of endotoxin administration (systemic or endobronchial) provides such an opportunity and has been used to great advantage for gaining insight into mechanisms of disease and for determination of therapeutic signal strength. When thoughtfully interpreted, the model may provide proof of principle as well as lessen the unpredictability of clinical responses. Although the broad characteristics of this model are well described in the literature, it is recognized that this model does not fully replicate the magnitude of initial inflammatory stress nor the latent spectrum of inflammation/sepsis-inducible organ system pathologies. Nevertheless, the similarities between the early, transient clinical phenotype, inducible physiochemical change, and biochemical pathway activation of this model to the early hyperdynamic phase of resuscitated injury and infection are striking. Rational testing of a therapeutic mechanism requires a quantifiable and reproducibly altered marker of the hypothetical mechanism. Given the modest nature of endotoxin induced insult, interventions that demonstrate target specific efficacy in conjunction with attenuated phenotype responses are more likely to exhibit efficacy within lower risk patient populations. By contrast, the model cannot predict clinical efficacy among higher risk patients nor in those who have endured extended periods of inflammatory stress.

  13. 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

  14. Surface properties of native human plasma lipoproteins and lipoprotein models.

    PubMed Central

    Massey, J B; Pownall, H J

    1998-01-01

    Plasma lipoprotein surface properties are important but poorly understood determinants of lipoprotein catabolism. To elucidate the relation between surface properties and surface reactivity, the physical properties of surface monolayers of native lipoproteins and lipoprotein models were investigated by fluorescent probes of surface lipid fluidity, surface lateral diffusion, and interfacial polarity, and by their reactivity to Naja melanoleuca phospholipase A2 (PLA2). Native lipoproteins were human very low, low-, and subclass 3 high-density lipoproteins (VLDL, LDL, and HDL3); models were 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) or its ether analog in single-bilayer vesicles, large and small microemulsions of POPC and triolein, and reassembled HDL (apolipoprotein A-I plus phospholipid). Among lipoproteins, surface lipid fluidity increased in the order HDL3 < LDL < VLDL, varying inversely with their (protein + cholesterol)/phospholipid ratios. Models resembled VLDL in fluidity. Both lateral mobility in the surface monolayer and polarity of the interfacial region were lower in native lipoproteins than in models. Among native lipoproteins and models, increased fluidity in the surface monolayer was associated with increased reactivity to PLA2. Addition of cholesterol (up to 20 mol%) to models had little effect on PLA2 activity, whereas the addition of apolipoprotein C-III stimulated it. Single-bilayer vesicles, phospholipid-triolein microemulsions, and VLDL have surface monolayers that are quantitatively similar, and distinct from those of LDL and HDL3. Surface property and enzymatic reactivity differences between lipoproteins and models were associated with differences in surface monolayer protein and cholesterol contents. Thus differences in the surface properties that regulate lipolytic reactivity are a predictable function of surface composition. PMID:9533698

  15. A prototypic mathematical model of the human hair cycle.

    PubMed

    Al-Nuaimi, Yusur; Goodfellow, Marc; Paus, Ralf; Baier, Gerold

    2012-10-07

    The human hair cycle is a complex, dynamic organ-transformation process during which the hair follicle repetitively progresses from a growth phase (anagen) to a rapid apoptosis-driven involution (catagen) and finally a relative quiescent phase (telogen) before returning to anagen. At present no theory satisfactorily explains the origin of the hair cycle rhythm. Based on experimental evidence we propose a prototypic model that focuses on the dynamics of hair matrix keratinocytes. We argue that a plausible feedback-control structure between two key compartments (matrix keratinocytes and dermal papilla) leads to dynamic instabilities in the population dynamics resulting in rhythmic hair growth. The underlying oscillation consists of an autonomous switching between two quasi-steady states. Additional features of the model, namely bistability and excitability, lead to new hypotheses about the impact of interventions on hair growth. We show how in silico testing may facilitate testing of candidate hair growth modulatory agents in human HF organ culture or in clinical trials.

  16. 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.

  17. Human performance models and rear-end collision avoidance algorithms.

    PubMed

    Brown, T L; Lee, J D; McGehee, D V

    2001-01-01

    Collision warning systems offer a promising approach to mitigate rear-end collisions, but substantial uncertainty exists regarding the joint performance of the driver and the collision warning algorithms. A simple deterministic model of driver performance was used to examine kinematics-based and perceptual-based rear-end collision avoidance algorithms over a range of collision situations, algorithm parameters, and assumptions regarding driver performance. The results show that the assumptions concerning driver reaction times have important consequences for algorithm performance, with underestimates dramatically undermining the safety benefit of the warning. Additionally, under some circumstances, when drivers rely on the warning algorithms, larger headways can result in more severe collisions. This reflects the nonlinear interaction among the collision situation, the algorithm, and driver response that should not be attributed to the complexities of driver behavior but to the kinematics of the situation. Comparisons made with experimental data demonstrate that a simple human performance model can capture important elements of system performance and complement expensive human-in-the-loop experiments. Actual or potential applications of this research include selection of an appropriate algorithm, more accurate specification of algorithm parameters, and guidance for future experiments.

  18. Three-dimensional modeling of the human fallopian tube fimbriae

    PubMed Central

    Eddie, Sharon L.; Quartuccio, Suzanne M.; Zhu, Jie; Shepherd, Jessica A.; Kothari, Rajul; Kim, J. Julie; Woodruff, Teresa K.; Burdette, Joanna E.

    2015-01-01

    Objective Ovarian cancer is the most lethal gynecological malignancy that affects women. Recent data suggests the disease may originate in the fallopian fimbriae; however, the anatomical origin of ovarian carcinogenesis remains unclear. This is largely driven by our lack of knowledge regarding the structure and function of normal fimbriae and the relative paucity of models that accurately recapitulate the in vivo fallopian tube. Therefore, a human three-dimensional (3D) culture system was developed to examine the role of the fallopian fimbriae in serous tumorigenesis. Methods Alginate matrix was utilized to support human fallopian fimbriae ex vivo. Fimbriae were cultured with factors hypothesized to contribute to carcinogenesis, namely; H2O2 (1mM) a mimetic of oxidative stress, insulin (5 µg/ml) to stimulate glycolysis, and estradiol (E2, 10nM) which peaks before ovulation. Cultures were evaluated for changes in proliferation and p53 expression, criteria utilized to identify potential precursor lesions. Further, secretory factors were assessed after treatment with E2 to identify if steroid signaling induces a pro-tumorigenic microenvironment. Results 3D fimbriae cultures maintained normal tissue architecture up to 7 days, retaining both epithelial subtypes. Treatment of cultures with H2O2 or insulin significantly induced proliferation. However, p53 stabilization was unaffected by any particular treatment, although was induced by ex vivo culturing. Moreover, E2-alone treatment significantly induced its canonical target PR and expression of IL8, a factor linked to poor outcome. Conclusions 3D alginate cultures of human fallopian fimbriae provide an important microphysicological model, which can be further utilized to investigate serous tumorigenesis originating from the fallopian tube. PMID:25527363

  19. Human natural regulatory T cell development, suppressive function and post-thymic maturation in a humanized mouse model

    PubMed Central

    Onoe, Takashi; Kalscheuer, Hannes; Danzl, Nichole; Chittenden, Meredith; Zhao, Guiling; Yang, Yong-Guang; Sykes, Megan

    2011-01-01

    CD4+ regulatory T (Treg) cells control adaptive immune responses and promote self-tolerance. Various humanized mouse models have been developed in efforts to reproduce and study a human immune system. However, in models that require T cell differentiation in the recipient murine thymus, only low numbers of T cells populate the peripheral immune systems. T cells are positively selected by mouse MHC and therefore do not function well in an HLA-restricted manner. In contrast, cotransplantation of human fetal thymus/liver and i.v. injection of CD34+ cells from the same donor achieves multilineage human lymphohematopoietic reconstitution, including dendritic cells (DCs) and formation of secondary lymphoid organs, in NOD/SCID mice. Strong antigen-specific immune responses and homeostatic expansion of human T cells that is dependent on peripheral human APCs occurs. We now demonstrate that FoxP3+ Helios+ “natural” Tregs develop normally in human fetal thymic grafts and are present in peripheral blood, spleen and lymph nodes of these humanized mice. Humanized mice exhibit normal reversal of CD45 isoform expression in association with thymic egress, post-thymic “naïve” to “activated” phenotypic conversion, and suppressive function. These studies demonstrate the utility of this humanized mouse model for the study of human Treg ontogeny, immunobiology and therapy. PMID:21876039

  20. 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

  1. Computational models can replicate the capacity of human recognition memory.

    PubMed

    Androulidakis, Zacharias; Lulham, Andrew; Bogacz, Rafal; Brown, Malcolm W

    2008-01-01

    The capacity of human recognition memory was investigated by Standing, who presented several groups of participants with different numbers of pictures (from 20 to 10 000), and subsequently tested their ability to distinguish between previously presented and novel pictures. The estimated number of pictures retained in recognition memory by different groups when plotted as a logarithmic function of the number of pictures presented formed a straight line, representing a power-law relationship. Here, we investigate if published models of familiarity discrimination can replicate Standing's results. We first consider a simplified assumption that visual stimuli are represented by uncorrelated patterns of firing of visual neurons providing input to the familiarity discrimination network. We show that for this case three models (Familiarity discrimination based on Energy (FamE), Anti-Hebbian and Info-max) can reproduce the observed power-law relationship when their synaptic weights are appropriately initialized. For more realistic assumptions on neural representation of stimuli, the FamE model is no longer able to reproduce the power-law relationship in simulations, while the Anti-Hebbian and Info-max can reproduce it. Nevertheless, the slopes of the power-law relationships produced by the models in all simulations differ from that observed by Standing. We discuss possible reasons for this difference, including separate contributions of familiarity and recollection processes, and describe experimentally testable predictions based on our analysis.

  2. The Virtual Physiological Human - a European initiative for in silico human modelling -.

    PubMed

    Viceconti, Marco; Clapworthy, Gordon; Van Sint Jan, Serge

    2008-12-01

    The Virtual Physiological Human (VPH) is an initiative, strongly supported by the European Commission (EC), that seeks to develop an integrated model of human physiology at multiple scales from the whole body through the organ, tissue, cell and molecular levels to the genomic level. VPH had its beginnings in 2005 with informal discussions amongst like-minded scientists which led to the STEP project, a Coordination Action funded by the EC that began in early 2006. The STEP project greatly accelerated the progress of the VPH and proved to be a catalyst for wide-ranging discussions within Europe and for outreach activities designed to develop a broad international approach to the huge scientific and technological challenges involved in this area. This paper provides an overview of the VPH and the developments it has engendered in the rapidly expanding worldwide activities associated with the physiome. It then uses one particular project, the Living Human Project, to illustrate the type of advances that are taking place to further the aims of the VPH and similar initiatives worldwide.

  3. 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

  4. Modeling of human factor Va inactivation by activated protein C

    PubMed Central

    2012-01-01

    Background Because understanding of the inventory, connectivity and dynamics of the components characterizing the process of coagulation is relatively mature, it has become an attractive target for physiochemical modeling. Such models can potentially improve the design of therapeutics. The prothrombinase complex (composed of the protease factor (F)Xa and its cofactor FVa) plays a central role in this network as the main producer of thrombin, which catalyses both the activation of platelets and the conversion of fibrinogen to fibrin, the main substances of a clot. A key negative feedback loop that prevents clot propagation beyond the site of injury is the thrombin-dependent generation of activated protein C (APC), an enzyme that inactivates FVa, thus neutralizing the prothrombinase complex. APC inactivation of FVa is complex, involving the production of partially active intermediates and “protection” of FVa from APC by both FXa and prothrombin. An empirically validated mathematical model of this process would be useful in advancing the predictive capacity of comprehensive models of coagulation. Results A model of human APC inactivation of prothrombinase was constructed in a stepwise fashion by analyzing time courses of FVa inactivation in empirical reaction systems with increasing number of interacting components and generating corresponding model constructs of each reaction system. Reaction mechanisms, rate constants and equilibrium constants informing these model constructs were initially derived from various research groups reporting on APC inactivation of FVa in isolation, or in the presence of FXa or prothrombin. Model predictions were assessed against empirical data measuring the appearance and disappearance of multiple FVa degradation intermediates as well as prothrombinase activity changes, with plasma proteins derived from multiple preparations. Our work integrates previously published findings and through the cooperative analysis of in vitro

  5. Effects of mesenchymal stromal cells on human myeloid dendritic cell differentiation and maturation in a humanized mouse model.

    PubMed

    Chen, Ping; Huang, Yanfei; Womer, Karl L

    2015-12-01

    Mesenchymal stromal cells (MSCs) have shown promise as cellular therapy in allogeneic transplantation, although the precise mechanisms underlying their benefit in clinical trials are difficult to study. We previously demonstrated that MSCs exert immunoregulatory effects in mouse bone marrow-derived dendritic cell (DC) culture. Since mouse studies do not reliably reproduce human events, we used a humanized mouse model to study the immunomodulatory effects of human MSCs on human DC immunobiology. Humanized mice were established by injection of cord blood CD34(+) cells into NOD.Cg-Prkdc(scid) Il2rg(tm1Wjl/SzJ) (NOD scid gamma, NSG) mice. Human cells were detected in the mouse bone marrow, blood, and spleen 12weeks after transplantation. Human DCs were differentiated from humanized mouse bone marrow cells during human MSC co-culture. MSCs inhibited DC differentiation and kept DCs in an immature state as demonstrated by phenotype and function. In conclusion, humanized mouse models represent a useful method to study the function of human MSCs on human DC immunobiology.

  6. 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

  7. Bayesian model selection validates a biokinetic model for zirconium processing in humans

    PubMed Central

    2012-01-01

    Background In radiation protection, biokinetic models for zirconium processing are of crucial importance in dose estimation and further risk analysis for humans exposed to this radioactive substance. They provide limiting values of detrimental effects and build the basis for applications in internal dosimetry, the prediction for radioactive zirconium retention in various organs as well as retrospective dosimetry. Multi-compartmental models are the tool of choice for simulating the processing of zirconium. Although easily interpretable, determining the exact compartment structure and interaction mechanisms is generally daunting. In the context of observing the dynamics of multiple compartments, Bayesian methods provide efficient tools for model inference and selection. Results We are the first to apply a Markov chain Monte Carlo approach to compute Bayes factors for the evaluation of two competing models for zirconium processing in the human body after ingestion. Based on in vivo measurements of human plasma and urine levels we were able to show that a recently published model is superior to the standard model of the International Commission on Radiological Protection. The Bayes factors were estimated by means of the numerically stable thermodynamic integration in combination with a recently developed copula-based Metropolis-Hastings sampler. Conclusions In contrast to the standard model the novel model predicts lower accretion of zirconium in bones. This results in lower levels of noxious doses for exposed individuals. Moreover, the Bayesian approach allows for retrospective dose assessment, including credible intervals for the initially ingested zirconium, in a significantly more reliable fashion than previously possible. All methods presented here are readily applicable to many modeling tasks in systems biology. PMID:22863152

  8. 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

  9. A generative sketch model for human hair analysis and synthesis.

    PubMed

    Chen, Hong; Zhu, Song-Chun

    2006-07-01

    In this paper, we present a generative sketch model for human hair analysis and synthesis. We treat hair images as 2D piecewise smooth vector (flow) fields and, thus, our representation is view-based in contrast to the physically-based 3D hair models in graphics. The generative model has three levels. The bottom level is the high-frequency band of the hair image. The middle level is a piecewise smooth vector field for the hair orientation, gradient strength, and growth directions. The top level is an attribute sketch graph for representing the discontinuities in the vector field. A sketch graph typically has a number of sketch curves which are divided into 11 types of directed primitives. Each primitive is a small window (say 5 x 7 pixels) where the orientations and growth directions are defined in parametric forms, for example, hair boundaries, occluding lines between hair strands, dividing lines on top of the hair, etc. In addition to the three level representation, we model the shading effects, i.e., the low-frequency band of the hair image, by a linear superposition of some Gaussian image bases and we encode the hair color by a color map. The inference algorithm is divided into two stages: 1) We compute the undirected orientation field and sketch graph from an input image and 2) we compute the hair growth direction forthe sketch curves and the orientation field using a Swendsen-Wang cut algorithm. Both steps maximize a joint Bayesian posterior probability. The generative model provides a straightforward way for synthesizing realistic hair images and stylistic drawings (rendering) from a sketch graph and a few Gaussian bases. The latter can be either inferred from a real hair image or input (edited) manually using a simple sketching interface. We test our algorithm on a large data set of hair images with diverse hair styles. Analysis, synthesis, and rendering results are reported in the experiments.

  10. Mathematical modelling of the growth of human fetus anatomical structures.

    PubMed

    Dudek, Krzysztof; Kędzia, Wojciech; Kędzia, Emilia; Kędzia, Alicja; Derkowski, Wojciech

    2016-07-08

    The goal of this study was to present a procedure that would enable mathematical analysis of the increase of linear sizes of human anatomical structures, estimate mathematical model parameters and evaluate their adequacy. Section material consisted of 67 foetuses-rectus abdominis muscle and 75 foetuses- biceps femoris muscle. The following methods were incorporated to the study: preparation and anthropologic methods, image digital acquisition, Image J computer system measurements and statistical analysis method. We used an anthropologic method based on age determination with the use of crown-rump length-CRL (V-TUB) by Scammon and Calkins. The choice of mathematical function should be based on a real course of the curve presenting growth of anatomical structure linear size Ύ in subsequent weeks t of pregnancy. Size changes can be described with a segmental-linear model or one-function model with accuracy adequate enough for clinical purposes. The interdependence of size-age is described with many functions. However, the following functions are most often considered: linear, polynomial, spline, logarithmic, power, exponential, power-exponential, log-logistic I and II, Gompertz's I and II and von Bertalanffy's function. With the use of the procedures described above, mathematical models parameters were assessed for V-PL (the total length of body) and CRL body length increases, rectus abdominis total length h, its segments hI, hII, hIII, hIV, as well as biceps femoris length and width of long head (LHL and LHW) and of short head (SHL and SHW). The best adjustments to measurement results were observed in the exponential and Gompertz's models.

  11. 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

  12. Modeling Rett Syndrome Using Human Induced Pluripotent Stem Cells.

    PubMed

    Andoh-Noda, Tomoko; Inouye, Michiko O; Miyake, Kunio; Kubota, Takeo; Okano, Hideyuki; Akamatsu, Wado

    2016-01-01

    Rett syndrome (RTT) is one of a group of neurodevelopmental disorders typically characterized by deficits in the X-linked gene MECP2 (methyl-CpG binding protein 2). The MECP2 gene encodes a multifunctional protein involved in transcriptional repression, transcriptional activation, chromatin remodeling, and RNA splicing. Genetic deletion of Mecp2 in mice revealed neuronal disabilities including RTT-like phenotypes and provided an excellent platform for understanding the pathogenesis of RTT. So far, there are no effective pharmacological treatments for RTT because the role of MECP2 in RTT is incompletely understood. Recently, human induced pluripotent stem cell (hiPSC) technologies have improved our knowledge of neurological and neurodevelopmental diseases including RTT because neurons derived from RTT-hiPSCs can be used for disease modeling to understand RTT phenotypes and to perform high throughput pharmaceutical drug screening. In this review, we provide an overview of RTT, including MeCP2 function and mouse models of RTT. In addition, we introduce recent advances in disease modeling of RTT using hiPSC-derived neural cells.

  13. 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.

  14. Static and Dynamic Human Shape Modeling - Concept Formation and Technology Development

    DTIC Science & Technology

    2011-02-01

    body measurements for product-independent size assignment [6] and were used by Seo et al [7] for human shape synthesizing. Using such a small...model is a base model that provides a complete, fundamental structure for human shape modeling. In order for a template model to be usable for dynamic

  15. 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

  16. 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

  17. A paradigm for human body finite element model integration from a set of regional models.

    PubMed

    Thompson, A B; Gayzik, F S; Moreno, D P; Rhyne, A C; Vavalle, N A; Stitzel, J D

    2012-01-01

    Computational modeling offers versatility, scalability, and cost advantages to researchers in the trauma and injury biomechanics communities. The Global Human Body Models Consortium (GHBMC) is a group of government, industry, and academic researchers developing human body models (HBMs) that aim to become the standard tool to meet this growing research need. The objective of this study is to present the methods used to develop the average seated male occupant model (M50, weight = 78 kg, height = 175 cm) from five separately validated body region models (BRMs). BRMs include the head, neck, thorax, abdomen, and a combined pelvis and lower extremity model. Modeling domains were split at the atlanto-occipital joint, C7-T1 boundary, diaphragm, abdominal cavity (peritoneum/retroperitoneum), and the acetabulum respectively. BRM meshes are based on a custom CAD model of the seated male built from a multi-modality imaging protocol of a volunteer subject found in literature.[1] Various meshing techniques were used to integrate the full body model (FBM) including 1-D beam and discrete element connections (e.g. ligamentous structures), 2D shell nodal connections (e.g. inferior vena cava to right atrium), 3D hexahedral nodal connections (e.g. soft tissue envelope connections between regions), and contact definitions varying from tied (muscle insertions) to sliding (liver and diaphragm contact). The model was developed in a general-purpose finite element code, LS-Dyna (LTSC, Livermore, CA) R4.2.1., and consists of 1.95 million elements and 1.3 million nodes. The element breakdown by type is 41% hexahedral, 33.7% tetrahedral, 19.5% quad shells and 5% tria shell. The integration methodology presented highlights the viability of using a collaborative development paradigm for the construction of HBMs, and will be used as template for expanding the suite of GHBMC models.

  18. 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

  19. 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.

  20. The degradation of curcuminoids in a human faecal fermentation model.